.I 200405
.U
90000002
.S
Alcohol Alcohol 9001; 24(4):281-9
.T
Covalent interactions of acetaldehyde with the actin/microfilament system.
.P
JOURNAL ARTICLE.
.W
The covalent binding of [14C]acetaldehyde to purified rabbit skeletal muscle actin was characterized. As we have found for other cytoskeletal proteins, actin formed stable covalent adducts under reductive and non-reductive conditions. Under non-reductive conditions, individual and competition binding studies versus albumin both showed that the G-form of actin is more reactive toward acetaldehyde than the F-form. When proteins were compared on an 'equi-lysine' basis under non-reducing conditions, G-actin was found to preferentially compete with albumin for binding to acetaldehyde. Time-course dialysis studies indicated that acetaldehyde-actin adducts become more stable with prolonged incubation at 37 degrees C. These data raise the possibility that actin could be a preferential target for adduct formation in cellular systems and will serve as the basis for ongoing studies aimed at defining the role of acetaldehyde-protein adducts in ethanol-induced cell injury.
.A
Xu DS; Jennett RB; Smith SL; Sorrell MF; Tuma DJ.
.I 200406
.U
90000005
.S
Alcohol Alcohol 9001; 24(4):311-8
.T
An investigation into the effects of chronic ethanol feeding on hepatic mixed protein synthesis in immature and mature rats.
.P
JOURNAL ARTICLE.
.W
1. The response of the liver to chronic ethanol feeding was investigated in sexually immature (85 g) and sexually mature (280 g) male Wistar rats. Rats received a nutritionally adequate liquid diet ad libitum, in which ethanol comprised 36% of total calories, for up to 6 weeks. Controls were pair-fed the same liquid diet in which ethanol was substituted by isocaloric glucose. 2. In immature rats, total hepatic protein, RNA and DNA contents were reduced by 12-23%. The amount of RNA, relative to protein or DNA, was also decreased by 11-12%, though the amount of protein relative to DNA was unaltered. In mature rats, no change in total hepatic protein and DNA contents were observed, though total RNA, RNA/protein ratio, RNA/DNA ratio and the amount of protein relative to DNA was reduced by 7-18%. 3. Rates of protein synthesis were measured with a flooding dose of L[4-3H]-phenylalanine without anaesthesia or surgical stress. In both immature and mature rats the fractional and absolute rates of hepatic protein synthesis and protein synthesis relative to DNA were reduced by approx 25%.
.A
Preedy VR; Peters TJ.
.I 200407
.U
90000007
.S
Alcohol Alcohol 9001; 24(4):331-7
.T
Alcoholic housewives and role satisfaction.
.P
JOURNAL ARTICLE.
.W
Three groups of housewives adhering to strict inclusion criteria were compared along several variables. The groups were patients with non-alcoholic liver disease (N = 19), alcoholic liver disease (N = 15) and alcoholics attending a community treatment centre (N = 13). The study confirms the differences between alcoholics who develop liver disease from those who do not. There was a strong relationship between dissatisfaction with the role of housewife and severity of alcoholism.
.A
Farid B; Elsherbini M; Ogden M; Lucas G; Williams R.
.I 200416
.U
90000159
.S
Acad Med 9001; 64(10):588-94
.T
Likelihood of contact with AIDS patients as a factor in medical students' residency selections.
.P
JOURNAL ARTICLE.
.W
Results from the National Resident Matching Program for the years 1980, 1983, and 1987 were used to examine changes over time in the matches of U.S. medical students to residencies in cities with high concentrations of patients with acquired immunodeficiency syndrome (AIDS) and to specialties in which the care of AIDS patients was most concentrated. Medical students seeking postgraduate training in categorical surgery residency programs were less likely to be matched with programs located in areas where the numbers of reported AIDS cases were high in 1987 as compared with the "pre-AIDS" years of 1980 or 1983. This trend was more pronounced for students from medical schools located in cities with high numbers of AIDS cases. There was a decline in matches to residencies in categorical internal medicine nationally, regardless of location; this decline was also greater among the students coming from medical schools in cities with high numbers of AIDS cases. The authors discuss the implications for medical educators of declines in matches to specialties in which the care of AIDS patients is most concentrated. The imperfect nature of available measures of students' exposure to AIDS patients makes the data of this study preliminary, and further studies are being undertaken. However, the finding of significant effects in spite of the imprecision of some measures suggests that future work will confirm the results of this study.
.A
Ness R; Killian CD; Ness DE; Frost JB; McMahon D.
.I 200417
.U
90000160
.S
Acad Med 9001; 64(10):595-9
.T
Racial-ethnic background and specialty choice: a study of U.S. medical school graduates in 1987.
.P
JOURNAL ARTICLE.
.W
This study used two Association of American Medical Colleges' questionnaires to determine whether there was a relationship between the racial-ethnic backgrounds and the specialty choices of a 1987 cohort of 11,136 U.S. medical school seniors, both prior to entering medical school and as they prepared for residency training. Their specialty preferences as premedical students were shown by their responses to the Premedical Student Questionnaire, administered when they registered for the Medical College Admission Test; their specialty choices at the end of their medical school training were shown by their responses to the Medical Student Graduation Questionnaire, which they completed shortly before graduation. Racial-ethnic backgrounds, self-recorded, were classified into black, other underrepresented minorities, Asian, other non-underrepresented minorities, and white. Specialties were clustered into primary care, medical specialties, surgical specialties, and supporting services. Before entering medical school, the students had similar specialty preferences regardless of background. As seniors in medical school, there was even greater convergence of specialty choices among the students of all backgrounds. Racial-ethnic background in itself appears not to have been a major factor influencing the senior medical students' specialty choices.
.A
Babbott D; Baldwin DC Jr; Killian CD; Weaver SO.
.I 200418
.U
90000161
.S
Acad Med 9001; 64(10):600-5
.T
Early and final preferences for pediatrics as a specialty: a study of U.S. medical school graduates in 1983.
.P
JOURNAL ARTICLE.
.W
The early and final specialty preferences for pediatrics made by 10,321 U.S. medical school graduates in 1983 were obtained from the students' responses to the Premedical Student Questionnaire, which accompanied their Medical College Admissions Test, and to the Medical Student Graduation Questionnaire, filled out not long before they graduated from medical school. A total of 11.5% of the women and 5.9% of the men expressed a preference for pediatrics on the earlier questionnaire, when they were premedical students; 13.5% of the women and 4.8% of the men actually chose pediatrics when they were senior medical students, as reflected on the later questionnaire. On both questionnaires, 31.3% of the women's preferences and 14.6% of the men's preferences for pediatrics did not change. More than 70% of all the graduating students choosing pediatrics had expressed a premedical preference for a primary care specialty. Fifty-one percent of the women and 42% of the men who abandoned their early preferences for pediatrics chose another specialty within primary care. More students of both genders shifted from a premedical preference for family practice into pediatrics than kept their early preference for pediatrics. If the direction of change noted in this study and others continues, pediatrics will increasingly become a specialty chosen by women.
.A
Coffin SE; Babbott D.
.I 200419
.U
90000162
.S
Acad Med 9001; 64(10):606-9
.T
Controllable lifestyle: a new factor in career choice by medical students.
.P
JOURNAL ARTICLE.
.W
To determine whether control of work hours (controllable lifestyle) was becoming an increasingly important factor in choices of specialties by medical students, data from three medical schools over the past ten, ten, and six years, respectively, were reviewed for the types of specialty training entered by students in the top 15% of their classes. Since students in the upper 15% of the class are likely to obtain the specialties of their choice, any change in the pattern of their specialty preferences probably reflects a general trend. Specialties that feature a controllable lifestyle (CL) were defined as anesthesiology, dermatology, emergency medicine, neurology, ophthalmology, otolaryngology, pathology, psychiatry, and radiology. Non-CL specialties were surgery, medicine, family practice, pediatrics, and obstetrics-gynecology. The results showed that the percentages of students entering CL specialties increased significantly at all three schools, the percentages of students entering non-CL specialties decreased significantly at all three schools, and there was no significant change in the percentage of students entering surgical specialties.
.A
Schwartz RW; Jarecky RK; Strodel WE; Haley JV; Young B; Griffen WO Jr.
.I 200420
.U
90000163
.S
Acad Med 9001; 64(10):610-5
.T
Characteristics of medical schools related to the choice of family medicine as a specialty.
.P
JOURNAL ARTICLE.
.W
Previous research has identified five characteristics of medical schools that are related to the choice of family medicine as a specialty: (1) the amount of time devoted to required training in family medicine, (2) the timing of the required family medicine training, (3) the type of ownership of the school (public or private), (4) the geographic location of the school, and (5) the administrative structure of family medicine within the school. These five characteristics of U.S. medical schools during the mid-1980s, together with the school tuition levels, were examined with both univariate and multivariate analysis to observe their relationships to the percentage of U.S. medical graduates entering family medicine between July 1986 and December 1987. With univariate analysis, each characteristic was significantly related to the percentage of graduates entering family medicine. Using multivariate analysis, only the number of weeks required and the type of ownership of the school were significantly related to the percentage of graduates entering family medicine, with the higher percentages related to greater numbers of required weeks of family medicine training and to public ownership of the school.
.A
Campos-Outcalt D; Senf JH.
.I 200421
.U
90000164
.S
Acad Med 9001; 64(10):616-21
.T
Initial career choices of medical school honors graduates in the early 1970s and 1980s.
.P
JOURNAL ARTICLE.
.W
To investigate the changes over time in the attractiveness of a number of medical specialties as careers, the author analyzed the initial career pathways of students who graduated with honors in 1972, 1973, 1982, and 1983 from nine of the most prestigious American medical schools. The data were analyzed to discern career selection differences among the total population studied, between the men and women, and between the graduates of public and private institutions. Internal medicine showed statistically significant declines in its attractiveness to the students in all the categories but remained overrepresented as a career choice by honors students compared with its attractiveness to medical students in general for the years studied. Radiology was chosen by an increasing percentage of the honors students in the 1980s, but mostly by students from private medical schools. The men who were honors graduates in the 1980s chose surgery fields more often, while women honors graduates tended to enter pediatrics and obstetrics-gynecology. These data indicate that the career choices of honors graduates in the early 1980s more closely mirrored the career choices of all students entering medical specialty fields and do not reveal gross imbalances. Of the primary care disciplines, only internal medicine attracted fewer honors graduates in the 1980s.
.A
Golden WE.
.I 200422
.U
90000165
.S
Acad Med 9001; 64(10):622-9
.T
Specialty choices at one medical school: recent trends and analysis of predictive factors.
.P
JOURNAL ARTICLE.
.W
Recent reports have raised the concern that personal care specialties, especially primary care specialties, are attracting fewer medical school graduates. In the present study, the authors evaluated the proportions of University of California, San Francisco (UCSF), medical school graduates entering personal care specialties and technology-oriented specialties from 1982 through 1988 and found no significant trend away from personal care specialties such as internal medicine, family practice, pediatrics, and psychiatry during these years. For the graduating class of 1988, admissions and questionnaire data were used to evaluate the importance of pre-admission, medical school, and postgraduate factors as determinants of specialty choice. The group entering personal care specialties (66% of all 1988 graduates) was significantly older and included more women and fewer minority students than the group entering technology-oriented specialties. Students rated income and lifestyle factors as being less important determinants of specialty choice than are medical school experiences and intrinsic qualities of the chosen specialties. However, compared with the students who entered personal care specialties, those who chose technology-oriented specialties over an alternate choice in personal care rated as significantly more important the opportunity to do procedures (p less than .001), income (p less than .005), the lesser degree of diagnostic uncertainty (p less than .005), and the rejected specialty's allowing less time for family (p less than .005) and for other interests (p less than .008). Exposure to acquired immunodeficiency syndrome and loan indebtedness were rated the least significant influences on specialty choice.(ABSTRACT TRUNCATED AT 250 WORDS)
.A
Lieu TA; Schroeder SA; Altman DF.
.I 200424
.U
90000167
.S
Acad Med 9001; 64(10 Suppl):S1-4
.T
A study of ambulatory care education in medical schools and U.S. Department of Veterans Affairs health care facilities.
.P
JOURNAL ARTICLE.
.W
A study of ambulatory care and education was conducted by sending questionnaires to U.S. Department of Veterans Affairs hospitals (75) and medical schools (65) prior to the Conference on Ambulatory Care and Education. Responses from 48% of medical schools indicated that there was little required clinical time in ambulatory care (15-20%), as well as faculty resistance and lack of medical school commitment to ambulatory care education. VA respondents (35% sample) also documented relatively little training in ambulatory care at the undergraduate and graduate levels. Numerous barriers to ambulatory care education are mentioned and strategies for overcoming the problems found are discussed.
.A
Robbins AS; Lussier RR; Koser K.
.I 200426
.U
90000169
.S
Acad Med 9001; 64(10 Suppl):S16-21
.T
Graduate medical education in ambulatory care.
.P
JOURNAL ARTICLE.
.W
Graduate medical education is currently in transition, with educators being asked to re-examine the extent to which hospital-based teaching models still provide adequate comprehensive training. To educate future physicians adequately, the Department of Veterans Affairs (VA) will have to change its system for delivering ambulatory care services and for teaching in ambulatory care settings. Workshop discussions focused on five major areas regarding educating residents in the ambulatory setting: educational goals and objectives, clinical experiences, curriculum development and evaluation, faculty issues, and fellowship opportunities. Recommendations include the need for residency programs to develop explicit educational goals and objectives for resident training, the identification of transdepartmental needs and coordinated planning, the support of academic clinical faculty, research and development of educational programs, and further development of fellowship training in ambulatory care. Further integration of ambulatory care activities in graduate training will require significant effort, a shift in manpower and resources and, more fundamentally, a shift in attitude and commitment at all levels of the VA and medical schools.
.A
Hayashi SA; Hayden BB; Yager J; Guze PA.
.I 200427
.U
90000171
.S
Acad Med 9001; 64(10 Suppl):S28-34
.T
Administration in ambulatory care.
.P
JOURNAL ARTICLE.
.W
Deficiencies in management of U.S. Department of Veterans Affairs (USDVA) ambulatory care programs have been documented in the literature and were reaffirmed by conference participants. These represent significant barriers to developing an effective and efficient system of outpatient health care delivery for veterans and to expanding educational opportunities for trainees. Based on impact and feasibility rankings from the symposium, review of the literature, and the personal experiences of USDVA ambulatory care managers, several recommendations emerged: (1) implement a system of matrix management; (2) invest in a leader; (3) develop "user-friendly" management information systems; (4) utilize existing resources efficiently; (5) embrace quality assurance; and (6) improve support from clerical and diagnostic services, nursing, and pharmacy personnel. Although intervention from leadership at the level of the USDVA Central Office will be necessary, many of these recommendations can be adopted by managers at the local facilities. The biggest challenge is to change the attitudes of clinical and support staff whose responsibilities have traditionally been inpatient-oriented.
.A
Nardone DA; Webb DW.
.I 200428
.U
90000172
.S
Acad Med 9001; 64(10 Suppl):S35-43
.T
Ambulatory care research in the VA: present status and recommendations for the future.
.P
JOURNAL ARTICLE.
.W
The growth of ambulatory care delivery in the Department of Veterans Affairs (VA) has been accompanied by increasing interest in and need for ambulatory care research. Results from a national survey of academic general internal medicine units suggest that those that share VA and university affiliation tend to be more successful than those that are unaffiliated. The VA must strive to improve the environment for ambulatory care research. Among other things, this will entail providing adequate protected time to ambulatory care faculty and developing a uniform ambulatory care database to facilitate longitudinal, population-based research. Extended fellowships in ambulatory care and faculty development programs for existing staff will be required to create a core of competent investigators. The VA must also provide increased funding to the Health Services Research and Development and Cooperative Studies programs. Special funding programs targeted to key areas such as quality assurance, medical education, and direct patient care should be established. In addition, the VA should seek to develop joint ventures with other funding agencies for innovative ambulatory care initiatives.
.A
Fihn SD; Larson EB; Friedman RH; Moskowitz MA.
.I 200429
.U
90000174
.S
Acad Med 9001; 64(10 Suppl):S44-50
.T
Costs associated with ambulatory care and education.
.P
JOURNAL ARTICLE.
.W
The adoption of an ambulatory care classification system by the Health Care Financing Administration in 1991 may have significant implications for medical education programs in the Department of Veterans Affairs (VA) ambulatory care setting. Presently there is not adequate methodology in the VA to determine costs in ambulatory care and education. (Experience with the VA allocation model suggests that selected characteristics of reimbursement systems are incompatible with educational goals.) Barriers that inhibit the cost-effective delivery of ambulatory care in many VA hospitals must be eliminated so that effective patient care and training care can take place. These barriers include inadequacies of information systems, physical layouts, and staffing. Despite the perception that outpatient care is less costly than inpatient care, the transition from an inpatient-based education model to an ambulatory care model will require an infusion of resources to improve the ambulatory care environment in the VA.
.A
Lee D; Nugent G.
.I 200434
.U
90000180
.S
Acad Med 9001; 64(10 Suppl):S9-15
.T
Medical student education in ambulatory care.
.P
JOURNAL ARTICLE.
.W
New forms of health care delivery and reimbursement trends have increased interest in the ambulatory care setting as a site for medical student education. It is estimated that from 50% to 60% of all medical students receive some portion of their medical training in a Department of Veterans Affairs (VA) facility. However, only about 5% of the total student ambulatory care educational experience is taking place at VA facilities. The problems in implementing and maintaining ambulatory care teaching programs for medical students encompass a variety of areas, such as lack of faculty incentive, time, expertise, and commitment; student resistance to training in this less attractive arena, and economic obstacles. Medical schools and VA medical centers will have to work in a mutually supportive relationship to develop joint goals and objectives for medical student teaching. Commitment of resources is essential, as is the need to reward ambulatory teaching through academic advancement and salary incentives. Faculty recruitment and development will be necessary, and research to identify the most successful of the VA ambulatory care teaching settings should be undertaken. The time has come for improved medical student education in VA ambulatory care settings, and there is now a need for collaborative planning between the medical schools and the VA.
.A
Abbott AV; Lee PV.
.I 200436
.U
90000775
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1181-5
.T
Lower trapezius myocutaneous island flap.
.P
JOURNAL ARTICLE.
.W
Resurfacing of the floor of the mouth and buccal region of the oral cavity and the tonsillar region of the oropharynx may be accomplished with many variations of regional and distant vascularized flaps. Our experiences in the use of 14 lower trapezius myocutaneous island flaps are described with respect to the unique application and suitability of this flap to resurface defects in these areas, as well as the contraindications, both relative and absolute, to the use of this particular method of resurfacing. In addition, the intraoperative technique and attendant problems, as well as postoperative complications, are presented. The overall advantages and disadvantages of this flap as compared with the more traditional pectoralis myocutaneous flap are outlined. It is our belief that because of the distinct qualities of this flap, including extended scope and flap thinness, this method of reconstruction merits consideration in the preoperative planning process.
.A
Cummings CW; Eisele DW; Coltrera MD.
.I 200437
.U
90000776
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1186-9
.T
Carcinoma of the tonsillar fossa. An update.
.P
JOURNAL ARTICLE.
.W
A retrospective analysis of 162 patients with carcinoma of the tonsillar fossa treated between 1969 and 1983 was undertaken. Of these patients, 117 were previously untreated; 11 had stage I, carcinoma, 24 had stage II, 40 had stage III, and 42 had stage IV. Combination therapy was utilized in 29% of patients with stage II disease, 40% of patients with stage III disease, and 67% of patients with stage IV disease. The three-year determinate "cure" rates were 89%, 83%, 58%, and 49% for stages I through IV, respectively. Only 22% of the previously treated patients were salvaged. Complications occurred in 36% of the previously treated patients and 18% of the previously untreated patients. Since our previous report, survival has improved, whereas operative mortality has decreased. We are unable to demonstrate a significant survival advantage when surgery and radiotherapy were used in combination.
.A
Spiro JD; Spiro RH.
.I 200438
.U
90000777
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1190-2
.T
Nonrigid reconstruction of the mandible.
.P
JOURNAL ARTICLE.
.W
Immediate rigid reconstruction of sacrificed portions of the mandible is desirable, but experience has shown that as many as 50% of bony or alloplastic implants are ultimately rejected or removed within the first few months after reconstruction. Functional and cosmetic reconstruction of the mandible, floor of the mouth, and, where necessary, skin of the lower lip and chin can be achieved with various local and myocutaneous flaps, to be followed after approximately 1 year by secondary bony reconstruction with a significantly lower complication rate. We describe the results in 43 patients treated by this approach.
.A
Tucker HM.
.I 200439
.U
90000778
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1193-6
.T
Five-year results of functional neck dissection for cancer of the larynx.
.P
JOURNAL ARTICLE.
.W
Two hundred forty-two patients with a diagnosis of epidermoid carcinoma of the larynx were studied. All of them underwent surgery. One hundred sixty-one patients underwent functional neck dissection, with a total of 206 performed. Thirty-three patients underwent classic radical neck dissection, with a total of 35 performed. The overall 5-year neck tumor recurrence rate in the necks with functional neck dissection was 3.4%. Recurrences developed in 5.7% of fields protected by radical neck dissection. The overall recurrence rate in the surgically unprotected necks was 6.2%. Our results confirm that functional neck dissection is the procedure of choice in cases with NO disease and in cases with mobile nodes. From the oncologic viewpoint, functional neck dissection is a safe technique to treat the cervical spread from cancer of the larynx as long as its indications and technical characteristics are carefully observed.
.A
Gavilan C; Gavilan J.
.I 200440
.U
90000780
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1203-5
.T
Alternatives to packing in septorhinoplasty.
.P
JOURNAL ARTICLE.
.W
Nasal packing is considered routine by most physicians and patients at the completion of nasal and septal surgery. Yet the rationale for this maneuver is not clearly defined by reported investigation or logical analysis. We discuss 75 consecutive nasal surgical procedures completed without packing. There were two postoperative episodes of bleeding, both from pyriform aperture incisions for lateral osteotomy and both managed in the recovery room with an absorbable gelatin sponge. Technical refinements such as scrupulous preoperative history taking, through-and-through suturing of the entire septal flaps, small-caliber osteotomy, meticulous closure of all intranasal incisions, and proper application of a conforming dressing are essential for hemostasis. We offer specific procedural guidance to minimize the risk of postoperative nasal bleeding.
.A
Reiter D; Alford E; Jabourian Z.
.I 200441
.U
90000781
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1206-12
.T
Advances in nasal tip surgery. The lateral crural steal.
.P
JOURNAL ARTICLE.
.W
Increasing nasal tip projection, rotation, and definition have classically been attempted through a variety of lobular cartilage incising or excising techniques. Resultant long-term complications, including bossing, alar notching, pinched tips, and alar collapse, have occasionally resulted from the use of these techniques. The majority of these complications have arisen secondary to a loss of structural support following the interruption of the lower lateral cartilages. This article describes the "lateral crural steal," a method of increasing nasal tip projection and nasal tip rotation while preserving the integrity of the lobular cartilage complex. The procedure uses the external rhinoplasty approach for exposure. By elevating both the dorsal and the vestibular skin from the domes of the lobular cartilages, the lateral crura may be advanced onto the medial crura to further project the nasal tip and to reorient the tip upward. This technique along with its philosophy and long-term follow-up results are presented.
.A
Kridel RW; Konior RJ; Shumrick KA; Wright WK.
.I 200442
.U
90000783
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1217-24
.T
Myringotomy with and without tympanostomy tubes for chronic otitis media with effusion.
.P
JOURNAL ARTICLE.
.W
We studied 109 children with otitis media with effusion of 2 months' duration or longer that was unresponsive to medical management. Eighty-six subjects who had neither "significant" hearing loss nor defined symptoms were randomly assigned to receive myringotomy, myringotomy with tympanostomy tube insertion, or no surgery, and 23 subjects with significant hearing loss, defined symptoms, or both were randomly assigned to receive either myringotomy or myringotomy with tube insertion. Myringotomy with tube insertion provided more disease-free time and better hearing than either myringotomy alone or no surgery; however, some subjects who underwent myringotomy with tube insertion developed otorrhea or persistent perforation of the tympanic membrane. Myringotomy offered no advantage over no surgery regarding percent of time with middle-ear effusion, number of acute otitis media episodes, and number of subsequent surgical procedures. These results may not properly be extrapolated to less severely affected children.
.A
Mandel EM; Rockette HE; Bluestone CD; Paradise JL; Nozza RJ.
.I 200443
.U
90000784
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1225-6
.T
Bacteriology of otorrhea from tympanostomy tubes.
.P
JOURNAL ARTICLE.
.W
Culture results from 100 consecutive cases of otorrhea from tympanostomy tubes are presented. In children younger than 3 years, the culture results are very similar to those seen in patients with acute otitis media who do not have tubes. In children older than 3 years, the flora resembles that of external otitis. Suggestions for treatment are made.
.A
Schneider ML.
.I 200444
.U
90000785
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1227-30
.T
Blood viscosity and hearing levels in the Caerphilly Collaborative Heart Disease Study.
.P
JOURNAL ARTICLE.
.W
Data from 342 men who are participants in the Caerphilly Collaborative Heart Disease Study were used to replicate a previous report of a significant relationship between measures of whole-blood viscosity and hearing levels in persons with sensorineural hearing impairment. In the unselected data, there were significant relationships between measures of whole-blood viscosity at high shear rates and hearing threshold levels at 2000 and 4000 Hz, even after accounting for the effects of age and socioeconomic group. In a subset of the data containing 124 persons selected on the basis of likely sensorineural hearing impairment, there were significant relationships between whole-blood viscosity and hearing level at all frequencies, with stronger effects at the higher frequencies. The data support the contention of a potentially important relationship between whole-blood viscosity and sensorineural hearing impairment.
.A
Gatehouse S; Gallacher JE; Lowe GD; Yarnell JW; Hutton RD; Ising I.
.I 200445
.U
90000786
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1231-3
.T
Comparison of computed tomography and magnetic resonance imaging in chronic otitis media with cholesteatoma.
.P
JOURNAL ARTICLE.
.W
We prospectively studied 10 patients with chronic otitis media suspected of having cholesteatoma with computed tomography and magnetic resonance imaging to assess which imaging modality would be most specific in predicting the presence of cholesteatoma. The interpretation of images was then correlated with the operative findings. In 9 of the 10 cases, computed tomography accurately predicted the extent and destructiveness of the disease but did not consistently differentiate between cholesteatoma and associated granulation tissue. In 2 of the 10 cases, the T1-weighted magnetic resonance imaging demonstrated high signal, suggestive of cholesteatoma. In one case, magnetic resonance imaging predicted cholesteatoma on the basis of bony destruction. However, in 7 of 10 cases the scan was nonspecific for cholesteatoma. We conclude that high-resolution computed tomography remains the primary imaging modality for chronic otitis media.
.A
Koltai PJ; Eames FA; Parnes SM; Wood GW; Bie B.
.I 200446
.U
90000789
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1244-7
.T
Gadolinium. The new gold standard for diagnosing cerebellopontine angle tumors.
.P
JOURNAL ARTICLE.
.W
All physicians involved with the diagnosis and management of patients with tumors in the temporal bone and cerebellopontine angle are faced with the challenge removing these tumors while preserving hearing. Part of the challenge is to make the diagnosis while the tumor is still small enough to attempt a hearing-conservation surgical approach. Air-contrast (air cisternography) computed tomography is the "gold standard" by which all techniques of diagnosis are compared. Most physicians, however, are reluctant to use this test as a screen for tumors because of the associated morbidity, time, and expense. We present three case reports of contrast-enhanced magnetic resonance imaging for the detection of small intracanalicular or cerebellopontine angle tumors, and review the literature of this new and exciting technology. We feel that gadolinium-enhanced magnetic resonance imaging is now the procedure of choice for evaluating patients with suspected temporal bone tumors.
.A
Sidman JD; Carrasco VN; Whaley RA; Pillsbury HC 3d.
.I 200447
.U
90000790
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1248-9
.T
Secondary intention healing. The primary approach for management of selected wounds.
.P
JOURNAL ARTICLE.
.W
Secondary intention healing is an ancient and well-established method of wound management. Since the advent of various reconstructive techniques, it is often forgotten as a valuable alternative to immediate surgical reconstruction of wounds. In certain situations the cosmetic and functional results of secondary intention healing are equal to the results of more complex reconstructive surgery. We describe a case in which remarkable results were obtained from spontaneous healing of a facial wound.
.A
Diwan R; Tromovitch TA; Glogau RG; Stegman SJ.
.I 200448
.U
90000791
.S
Arch Otolaryngol Head Neck Surg 9001; 115(10):1250-2
.T
Fibrosarcoma of the mandible following supravoltage irradiation. Report of a case.
.P
JOURNAL ARTICLE.
.W
Supravoltage irradiation is commonly thought not to be carcinogenic. Several recent studies question this concept, as does our case report. A 50-year-old woman with stage 1 squamous carcinoma of the left side of the tongue was treated in 1973 with 73 Gy of supravoltage irradiation. Twelve years later a painful, ulcerated lesion that eventually was shown to be fibrosarcoma developed in the contralateral mandible. The fibrosarcoma in this case fulfills all criteria for diagnosing radiation-induced neoplasia and demonstrates that supravoltage irradiation, like other forms of irradiation, can cause malignancy. The occasional occurrence of sarcoma should be recalled during follow-up of patients treated with supravoltage radiation. Similarly, the possibility of radiation-induced tumors should be considered in planning treatment for younger patients with tumors that can be treated equally well by surgery or irradiation.
.A
Moloy PJ; Kowal KA; Siegel WM..
.I 200453
.U
90000980
.S
Br Heart J 9001; 62(3):165-70
.T
Cardiac parasympathetic activity during the early hours of acute myocardial infarction.
.P
JOURNAL ARTICLE.
.W
Cardiac parasympathetic activity was assessed in 21 patients during the first 24 hours of acute myocardial infarction by measuring abrupt beat by beat changes in RR interval, which are expressed as "RR counts". Eleven patients had inferior wall infarction and 10 had anterior wall myocardial infarction. The whole recording period was analysed in 11 patients (five inferior and six anterior), and intermittent hourly periods were analysed in all 21 subjects. Mean RR counts were significantly lower in patients with anterior than inferior infarction, and below the normal range. Although mean heart rates were faster in the group with anterior infarction, there was a dissociation between RR counts and mean heart rate that was consistent with RR interval variability being an independent measure of parasympathetic activity. This study indicates that cardiac parasympathetic activity during acute myocardial infarction can be simply and reliably assessed from continuous electrocardiographic recordings, and it showed significantly lower cardiac parasympathetic activity in patients with anterior infarction.
.A
McAreavey D; Neilson JM; Ewing DJ; Russell DC.
.I 200454
.U
90000981
.S
Br Heart J 9001; 62(3):171-6
.T
Aortic regurgitation associated with hypertrophic cardiomyopathy: a colour Doppler echocardiographic study.
.P
JOURNAL ARTICLE.
.W
The frequency, severity, and cause of aortic regurgitation were assessed by colour Doppler and cross sectional echocardiography in 87 patients (mean SD) age 57 (12) years) with hypertrophic cardiomyopathy, and 48 age matched controls (57 (8) years). Aortic regurgitant murmurs were recorded in only three of 87 patients and in none of the controls. Colour Doppler echocardiography showed an aortic regurgitant signal in 20 (23%) of the patients and three (6%) of the 48 controls. The colour Doppler signals typical of aortic regurgitation were limited to the left ventricular outflow tract. There were no significant differences between patients with hypertrophic cardiomyopathy with and without aortic regurgitation in terms of age (59 years v 56 years), blood pressure (140/84 mm Hg v 136/80 mm Hg), aortic diameter (34 mm v 33 mm), or frequency of calcification of the aortic valve (15% v 10%) and of systolic anterior motion of the mitral valve with mitral-septal contact (25% v 16%). On cross sectional echocardiograms, the degree of septal protrusion into the left ventricular outflow tract during systole was significantly more prominent (15 v 10 mm), and the portion of the basal septum that protruded most deeply into the left ventricular outflow tract was significantly closer to the aortic annulus in patients with aortic regurgitation than in those without it (11 v 14 mm). Mild aortic regurgitation was found in almost a quarter of patients with hypertrophic cardiomyopathy. The regurgitation was related to the morphological abnormality of the left ventricular outflow tract.
.A
Shiota T; Sakamoto T; Takenaka K; Amano K; Hada Y; Hasegawa I; Suzuki J; Takahashi H; Sugimoto T.
.I 200455
.U
90000982
.S
Br Heart J 9001; 62(3):177-84
.T
Cross sectional early mitral flow velocity profiles from colour Doppler.
.P
JOURNAL ARTICLE.
.W
Instantaneous cross sectional flow velocity profiles from early mitral flow in 10 healthy men were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital Doppler ultrasound maps. This interpolation allows correction of the artificially produced skewness of velocities across the flow sector caused by the time taken to scan the flow sector for velocity recording of pulsatile blood flow. These results suggested that early mitral flow studied in an apical four chamber view is variably skewed both at the leaflet tips and at the annulus. The maximum flow velocity overestimated the cross sectional mean velocity at the same time by a factor of 1.2-2.2. Also the maximum time velocity integral overestimated the cross sectional mean time velocity integral to the same extent. This cross sectional skew must be taken into account when calculation of blood flow is based on recordings with pulsed wave Doppler ultrasound from a single sample volume.
.A
Samstad SO; Torp HG; Linker DT; Rossvoll O; Skjaerpe T; Johansen E; Kristoffersen K; Angelsen BA; Hatle L.
.I 200456
.U
90000983
.S
Br Heart J 9001; 62(3):185-94
.T
Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle [see comments]
.P
JOURNAL ARTICLE.
.W
Acromegaly is associated with an increased cardiac morbidity and mortality, but it is not clear whether this is the result of increased incidence of hypertension and coronary heart disease or of a specific disease of heart muscle. Thirty four acromegalic patients were studied by non-invasive techniques. Seven of these patients had raised plasma concentrations of growth hormone at the time of study; three were newly diagnosed and had not received any treatment. Hypertension was present in nine (26%) but only three (9%) had electrocardiographic left ventricular hypertrophy. Echocardiography showed ventricular hypertrophy in 12 (48%) and increased left ventricular mass in 17 (68%) patients. Holter monitoring detected important ventricular arrhythmias in 14 patients. Thallium-201 scanning showed evidence for coronary heart disease in eight patients. Systolic time intervals were normal except when there was coexistent ischaemic heart disease. A comparison between 19 acromegalic patients with no other detectable cause of heart disease and 22 age matched controls showed appreciably abnormal left ventricular diastolic function in the group with acromegaly. The abnormalities shown did not correlate with left ventricular mass or wall thickness. There was no difference in diastolic function between patients with active acromegaly and those with treated acromegaly. Hypertensive acromegalic patients had worse diastolic function than hypertensive controls, suggesting that hypertension may further impair the left ventricular diastolic abnormality in acromegaly. This is the first study to find evidence of subclinical cardiac diastolic dysfunction in acromegaly and it supports the suggestion that there is a specific disease of heart muscle in acromegaly.
.A
Rodrigues EA; Caruana MP; Lahiri A; Nabarro JD; Jacobs HS; Raftery EB.
.I 200457
.U
90000984
.S
Br Heart J 9001; 62(3):195-203
.T
Value and limitations of adenosine in the diagnosis and treatment of narrow and broad complex tachycardias.
.P
JOURNAL ARTICLE.
.W
The diagnostic and therapeutic potential of intravenous adenosine was studied in 64 patients during 92 episodes of regular sustained tachycardia. In 40 patients who had narrow complex tachycardias (QRS less than 0.12 s) adenosine (2.5-25 mg) restored sinus rhythm in 25 with junctional tachycardias (46 of 48 episodes) and produced atrioventricular block to reveal atrial or sinus tachycardia in 15. In 24 patients with broad complex tachycardias (QRS greater than or equal to 0.12 s) adenosine terminated the tachycardias in six patients and revealed atrial or sinus arrhythmias in four. The tachycardias persisted in 14 patients despite doses up to 20 mg, but adenosine allowed the diagnosis of ventricular tachycardia with retrograde atrial activation in two patients by producing transient ventriculoatrial dissociation. Diagnosis based on adenosine induced atrioventricular nodal block was correct in all patients with narrow complex tachycardias and in 92% of those with broad complex tachycardias, compared with correct electrocardiographic diagnoses in 90% and 75% respectively. Adenosine gave diagnostic information additional to the electrocardiogram in 25%. The response to adenosine in broad complex tachycardias identified those of supraventricular origin with 90% sensitivity, 93% specificity, and 92% predictive accuracy. Adenosine restored sinus rhythm in all patients with junctional reentrant tachycardias, but in 10 (35%) the arrhythmias recurred within two minutes. Symptomatic side effects (dyspnoea, chest pain, flushing, headache) were reported by 40 (63%) patients and, although transient, were severe in 23 (36%). There were ventricular pauses of over 2 s in 16% of patients, the longest pause being 6.1 s.(ABSTRACT TRUNCATED AT 250 WORDS)
.A
Rankin AC; Oldroyd KG; Chong E; Rae AP; Cobbe SM.
.I 200458
.U
90000985
.S
Br Heart J 9001; 62(3):204-11
.T
Efficacy and safety of adenosine in the treatment of supraventricular tachycardia in infants and children.
.P
JOURNAL ARTICLE.
.W
One hundred and seventeen episodes of supraventricular tachycardia in 50 children, including 28 infants, were treated with intravenous adenosine. Adenosine was prepared in a sterile solution of 0.9% saline (1 mg/ml) and given in incremental doses of 0.05 mg/kg every two minutes to a maximum of 0.25 mg/kg. Ninety of the 117 episodes were terminated. This included 88 of the 102 episodes of junctional tachycardia (79 of the 92 episodes of atrioventricular reentry tachycardia, seven of the eight episodes of atrioventricular nodal reentry tachycardia, and both of the episodes of long R-P' tachycardia). Only one of four episodes of His bundle tachycardia and one of the eight episodes of ectopic atrial tachycardia were terminated. None of the three episodes of atrial flutter were terminated. Side effects were frequent but mild and included transient complete atrioventricular block (less than 6 s), sinus bradycardia (less than 40 s), ventricular extrasystoles, flushing, nausea, headache, and respiratory disturbance. Reinitiation (within 5 s) of supraventricular tachycardia occurred in 13 of the terminated episodes. Although reinitiation limited its clinical efficacy in some patients, intravenous adenosine offered a safe and efficient method of rapid termination of most episodes of supraventricular tachycardia and in some cases facilitated diagnosis of the mechanism.
.A
Till J; Shinebourne EA; Rigby ML; Clarke B; Ward DE; Rowland E.
.I 200459
.U
90000986
.S
Br Heart J 9001; 62(3):212-6
.T
Variability of the Doppler gradient in pulmonary valve stenosis before and after balloon dilatation.
.P
JOURNAL ARTICLE.
.W
The variability of the valve gradient measured by Doppler in pulmonary stenosis was compared with the variability of the gradient measured at catheterisation in 42 infants and children undergoing catheterisation with a view to balloon dilatation of the pulmonary valve. The maximum value measured by Doppler when the patient was unsedated was significantly higher than that measured when the patient was sedated for catheterisation, and the maximum gradient was significantly higher shortly after than several days later. In a patient with pronounced infundibular obstruction after dilatation the Doppler signal clearly showed that the obstruction was dynamic, with a superimposed lower fixed signal that correctly predicted the final low gradient. The Doppler gradient in an alert and unsedated patient may be a better measure of the true physiological value. The highest Doppler value so obtained is a more appropriate indicator of the need for balloon dilatation than a single catheter measurement. The result of dilatation is best assessed by Doppler measurement at least a day after the procedure.
.A
Lim MK; Houston AB; Doig WB; Lilley S; Murtagh EP.
.I 200460
.U
90000987
.S
Br Heart J 9001; 62(3):217-9
.T
Use of streptokinase to aid in drainage of postoperative pericardial effusion.
.P
JOURNAL ARTICLE.
.W
A case of cardiac tamponade secondary to a late, loculated pericardial effusion after open pulmonary valvotomy is described. Percutaneous drainage of the effusion was aided by the infusion of intrapericardial streptokinase.
.A
Cross JH; De Giovanni JV; Silove ED.
.I 200461
.U
90000988
.S
Br Heart J 9001; 62(3):220-1
.T
Development of multiform ventricular tachycardia during atrioventricular nodal reentrant tachycardia.
.P
JOURNAL ARTICLE.
.W
A woman of 18 presented with a supraventricular tachycardia, subsequently shown to be caused by atrioventricular nodal reentry, which abruptly deteriorated to a multiform ventricular tachycardia. She had not received any antiarrhythmic drugs nor did she have any of the disorders that are usually associated with this atypical ventricular tachycardia.
.A
Bennett DH; Coyle C.
.I 200462
.U
90000989
.S
Br Heart J 9001; 62(3):222-4
.T
Straddling tricuspid valve without a ventricular septal defect.
.P
JOURNAL ARTICLE.
.W
A four year old girl with pulmonary atresia had a straddling tricuspid valve without an interventricular communication. The overriding tricuspid valve had two orifices, which connected with the right and the left ventricles. Valve tissue separated both orifices and was firmly connected to the crest of the ventricular septum, thus sealing off the expected interventricular communication. Surgical correction was performed and the outcome was satisfactory.
.A
Isomatsu Y; Kurosawa H; Imai Y.
.I 200463
.U
90000990
.S
Br Heart J 9001; 62(3):225-7
.T
Subacute rupture of a pseudoaneurysm formed by late rupture of a true left ventricular aneurysm.
.P
JOURNAL ARTICLE.
.W
A man aged 34 in whom rupture of a true aneurysm at least four weeks after acute myocardial infarction led to the development of a pseudoaneurysm is described. Because the pseudoaneurysm ruptured subacutely and the haemodynamic, clinical, and echocardiographic signs were not consistent, diagnosis of the cardiac rupture was delayed. Operative repair was successful, but the patient died.
.A
Goudevenos J; Parry G; Morritt GN.
.I 200464
.U
90000991
.S
Br Heart J 9001; 62(3):228-9
.T
Balloon dilatation of a stenosed modified (polytetrafluoroethylene) Blalock-Taussig shunt.
.P
JOURNAL ARTICLE.
.W
A 17 month old girl with tricuspid atresia, ventricular septal defect, subvalvar and valvar pulmonary stenosis, and increasing cyanosis had angiographic evidence of proximal stenosis of a right modified (5 mm diameter) Blalock-Taussig shunt. She underwent palliative balloon angioplasty with a 6 mm Schneider balloon catheter. Successful dilatation was achieved without complication. Four months later there was subjective clinical improvement with a rise in systemic arterial saturation. Repeat angiography showed patency of the shunt without restenosis or formation of an aneurysm.
.A
Parsons JM; Ladusans EJ; Qureshi SA.
.I 200466
.U
90001523
.S
Blood 9001; 74(5):1477-80
.T
Antibody-mediated marrow failure after allogeneic bone marrow transplantation.
.P
JOURNAL ARTICLE.
.W
Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft failure, either by antibody-dependent cell-mediated cytotoxicity (ADCC), or complement-mediated cytotoxicity. In the case of HLA Class I disparity, where all donor cells express the target antigen, the presence of alpha-donor antibody was associated with complete graft failure and death. In the case of ABO blood group antigen disparity, the presence of alpha-donor antibody resulted in erythroid hypoplasia. The latter cases proved informative insofar as they established that host antibodies could persist for more than 18 months after chemoradiotherapy and impair marrow function.
.A
Barge AJ; Johnson G; Witherspoon R; Torok-Storb B.
.I 200467
.U
90001524
.S
Blood 9001; 74(5):1481-5
.T
Enrichment of two glycosyl-phosphatidylinositol-anchored proteins, acetylcholinesterase and decay accelerating factor, in vesicles released from human red blood cells.
.P
JOURNAL ARTICLE.
.W
Several proteins are attached to the cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. In this report, we show that during vesiculation of human RBCs in vitro, two of these proteins, acetylcholinesterase and decay accelerating factor, redistribute on the cell surface and become enriched in the released vesicles. As a result, the remnant cells are depleted of these proteins. We suggest that alterations in the architecture of the RBC membrane that precede vesiculation lead to selective polarization of GPI-anchored proteins within the domain of the membrane destined to become a vesicle. Since vesiculation occurs in many cell types, and if the loss of GPI-anchored proteins accompanies this process, it may have important biologic significance.
.A
Butikofer P; Kuypers FA; Xu CM; Chiu DT; Lubin B.
.I 200468
.U
90001525
.S
Blood 9001; 74(5):1486-90
.T
Molecular characterization of human factor XSan Antonio.
.P
JOURNAL ARTICLE.
.W
Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio.
.A
Reddy SV; Zhou ZQ; Rao KJ; Scott JP; Watzke H; High KA; Jagadeeswaran P.
.I 200469
.U
90001528
.S
Blood 9001; 74(5):1507-16
.T
Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]
.P
JOURNAL ARTICLE.
.W
The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).
.A
Beelen DW; Quabeck K; Graeven U; Sayer HG; Mahmoud HK; Schaefer UW.
.I 200470
.U
90001532
.S
Blood 9001; 74(5):1537-44
.T
Use of scid mice to identify and quantitate lymphoid-restricted stem cells in long-term bone marrow cultures.
.P
JOURNAL ARTICLE.
.W
Mice homozygous for an autosomal recessive scid (severe combined immune deficiency) mutation on chromosome 16 exhibit a defect that specifically impairs lymphoid differentiation but not myelopoiesis. Consequently such mice are deficient in both humoral and cell-mediated immune functions. Despite their defect, scid mice survive under pathogen-free conditions and are fertile. The mutation does not impair the hematopoietic microenvironment necessary for lymphoid differentiation, since these mice can be cured with grafts of normal bone marrow (BM) or cells from long-term BM cultures (LTBMC); however, reconstitution requires sublethal (400 cGy) irradiation of recipients. Engraftment with cells from LTBMC gave near-normal levels of colony-forming B cells (CFU-B) in spleen and BM of the recipients by 6 weeks postgrafting. Since LTBMC are devoid of all mature B and pre-B cells but contain stem cells that restore lymphoid function in scid mice, we used a limiting-dilution assay to characterize and enumerate the number of stem cells in LTBMC capable of restoring lymphoid function. Curing was determined by the CFU-B-cell assay, since CFU-B are not detectable in normal scid mice. The results indicate that fewer cells from LTBMC than from fresh BM are required to obtain lymphoid reconstitution. As few as 10(3) LTBMC cells can repopulate significant B- and T-cell function in scid recipients. From these results we conclude that scid mice can be used as recipients to quantify lymphoid-restricted stem cells and that there is a functional separation of lymphoid- and myeloid-restricted stem cells in LTBMC with an enrichment for lymphoid-restricted stem cells in these cultures.
.A
Fulop GM; Phillips RA.
.I 200471
.U
90001533
.S
Blood 9001; 74(5):1545-51
.T
Regulation of megakaryocyte development by interleukin-6.
.P
JOURNAL ARTICLE.
.W
Megakaryocytes develop in densely seeded normal mouse bone marrow (BM) cells cultured in agar or in liquid medium. This formation of megakaryocytes is enhanced by the myeloid differentiation-inducing protein MGI-2, which we have shown to be interleukin-6 (IL-6). Monoclonal antibody (MoAb) that specifically neutralizes mouse IL-6 but not human IL-6 inhibited megakaryocyte development in cells cultured either with or without the addition of mouse IL-6 but did not inhibit megakaryocyte development induced by human IL-6. This MoAb to mouse IL-6 that does not neutralize mouse IL-3 also inhibited mouse IL-3-induced megakaryocyte development. Antibody to mouse GM-CSF did not inhibit the formation of megakaryocytes. The results show that the induction of megakaryocyte development by IL-3 is due to the production of IL-6 in the BM cultures. The present experiments demonstrate a new property of IL-6 and indicate that IL-6 is a regulatory protein of normal megakaryocyte development.
.A
Lotem J; Shabo Y; Sachs L.
.I 200472
.U
90001534
.S
Blood 9001; 74(5):1552-6
.T
Different repopulation profile between erythroid and nonerythroid progenitor cells in genetically anemic W/Wv mice after bone marrow transplantation.
.P
JOURNAL ARTICLE.
.W
Repopulation kinetics of erythrocytes and neutrophils and replacement of hematopoietic progenitors were studied in genetically anemic (WB x C57BL/6)F1-W/Wv (WBB6F1-W/Wv) hosts after bone marrow transplantation from C57BL/6-bgJ/bgJ or C57BL/6-bgJ/bgJ;Pgk-1a/Y mice. Electrophoretic pattern of hemoglobin was used as a marker of donor-type erythrocytes, giant granules of bgJ/bgJ mice as a marker of donor-type neutrophils, and A-type phosphoglycerate kinase-1 (PGK-1) as a marker of hematopoietic colonies produced by donor-derived progenitor cells. Repopulation of donor-type erythrocytes was significantly faster than that of donor-type neutrophils. Moreover, the extent of replacement was greater for erythroid progenitor cells than for nonerythroid progenitor cells. When nonirradiated WBB6F1-W/Wv mice with B-type PGK-1 received 10(5) bone marrow cells from C57BL/6-bgJ/bgJ;Pgk-1a donors, only approximately 20% replacement of erythroid progenitor cells gave rise to total reconstitution of erythrocytes. The present result suggests that normal multipotential stem cells may preferentially differentiate into erythroid lineage cells in anemic WBB6F1-W/Wv hosts and that normal erythroid progenitor cells may suppress the differentiation of erythroid progenitors of WBB6F1-W/Wv hosts.
.A
Nakano T; Waki N; Asai H; Kitamura Y.
.I 200473
.U
90001535
.S
Blood 9001; 74(5):1557-62
.T
Suppressive effect of Sl/Sld mouse embryo-derived fibroblast cell lines on diffusible factor-dependent proliferation of mast cells.
.P
JOURNAL ARTICLE.
.W
Two modes of mast cell growth are present, one dependent on diffusible growth factors (interleukins [IL] 3 and 4) and another dependent on contact with fibroblasts. The 3T3 fibroblast cell lines derived from WCB6F1-+/+ mouse embryos supported the proliferation of cultured mast cells (CMC), whereas the 3T3 fibroblast cell lines from WCB6F1-Sl/Sld mouse embryos did not. To investigate the relationship between growth factor-dependent and fibroblast-dependent growths of mast cells, we cocultured CMC and 3T3 fibroblasts in the presence of diffusible growth factors. WCB6F1-+/+ mouse embryo-derived 3T3 cells did not affect the growth factor-dependent proliferation of CMC, but WCB6F1-Sl/Sld mouse embryo-derived 3T3 cells significantly suppressed the proliferation. Close cell-to-cell contact was necessary for the suppression. The NWS1 fibroblast cell line was established from the spleen cells of an adult WBB6F1-+/+ mouse. Although the NWS1 cell line had no supporting effect on the proliferation of CMC in the absence of diffusible growth factors, it did not suppress the proliferation of CMC induced by the growth factors. The present result suggests that a product of mutant Sl genes may be involved in the suppressive activity of WCB6F1-Sl/Sld mouse embryo-derived 3T3 cells.
.A
Onoue H; Ebi Y; Nakayama H; Ru XM; Kitamura Y; Fujita J.
.I 200474
.U
90001536
.S
Blood 9001; 74(5):1563-70
.T
Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro.
.P
JOURNAL ARTICLE.
.W
To develop a purification strategy for isolating the most primitive hematopoietic stem cells present in normal human marrow we have combined cell separation techniques with an assay for cells that initiate sustained hematopoiesis in vitro in the presence of irradiated human marrow adherent cells. These "feeders" were established by subculturing 2- to 6-week-old primary long-term marrow culture adherent layers at a density of 3 x 10(4) irradiated cells per square centimeter. Test "long-term culture (LTC)-initiating cells" were plated on top of the feeders and the cocultures then maintained as standard long-term marrow cultures with half-media changes and removal of half of the nonadherent cells each week. The total number of myeloid, erythroid, and multilineage clonogenic progenitors present after 5 weeks was used to provide a quantitative assessment of the number of LTC-initiating cells originally added. Using this assay, the density, light scatter, and two cell surface antigen properties of LTC-initiating cells have been defined and compared with cells capable of directly forming colonies in methylcellulose. While the majority of the clonogenic cells were found in the high forward light scatter (FLS) "blast" window, LTC-initiating cells had significantly lower FLS properties and in this respect were more similar to lymphocytes. LTC-initiating cells also expressed less HLA-DR antigen than clonogenic cells. The majority of LTC-initiating cells were found in the top 2% of the CD34 (My10) fluorescence profile, whereas clonogenic cells were found throughout the top 5% of the CD34 fluorescence profile. By combining low FLS, low orthogonal light scatter (OLS), low HLA-DR expression, and high CD34 expression, a population could be obtained that was enriched for LTC-initiating cells approximately 800-fold over unseparated marrow. This population contains only 0.06% of the marrow cells and 2% of the total clonogenic cells, but retains 50% to 60% of the LTC-initiating cells present in the original marrow. The ability to purify these two populations independently shows that the LTC and clonogenic assays identify distinct, although not necessarily nonoverlapping cell types in human marrow. Since clonogenic cells are derived from LTC-initiating cells, the LTC assay clearly detects a more primitive population. The availability of a simple approach that allows the purification of such cells by three orders of magnitude in high yield should be useful for the investigation of early events in hematopoiesis as well as for the definitive isolation of human hematopoietic stem cells with long-term in vivo repopulating potential.
.A
Sutherland HJ; Eaves CJ; Eaves AC; Dragowska W; Lansdorp PM.
.I 200475
.U
90001537
.S
Blood 9001; 74(5):1571-6
.T
Effects of interleukin-3 and erythropoietin on in vivo erythropoiesis and F-cell formation in primates.
.P
JOURNAL ARTICLE.
.W
To test the in vivo cooperativity between interleukin-3 (IL-3) and erythropoietin (Epo) in stimulating erythropoiesis and hemoglobin F (HbF) production in primates, we administered recombinant human IL-3 and recombinant human Epo to baboons and macaques. The effect of these treatments was assessed by serial bone marrow cultures and by measuring HbF production in the progeny of bone marrow progenitors and in peripheral-blood reticulocytes. Administration of IL-3 alone to hematologically normal or anemic baboons produced an early increase in erythroid colony-forming units (CFUe) and erythroid clusters (e-clusters) with an increase in reticulocyte counts and a late increment in the relative frequency of erythroid burst-forming units (BFUe). In parallel to the increase in peripheral-blood reticulocytes, IL-3 increased the frequency of F reticulocytes in the normal and anemic animals. When administration of IL-3 was followed by administration of Epo, expansion in all classes of erythroid progenitors and increase in reticulocytes occurred, beyond the levels observed when the animals were treated with Epo alone. The combination of IL-3 and Epo, however, did not increase consistently the rate of F reticulocytes beyond the level induced by Epo alone. These results suggest that IL-3 enhances the effect of Epo on erythropoiesis, but the combination of the two growth factors does not lead to a preferential and significant enhancement of HbF production.
.A
Umemura T; al-Khatti A; Donahue RE; Papayannopoulou T; Stamatoyannopoulos G.
.I 200476
.U
90001538
.S
Blood 9001; 74(5):1577-82
.T
Pharmacodynamics and pharmacokinetics of dermatan sulfate in humans.
.P
JOURNAL ARTICLE.
.W
Dermatan sulfate (DS), a catalyst of the thrombin-heparin cofactor II interaction, has antithrombotic activity and is devoid of significant hemorrhagic risk in several animal models. We investigated the pharmacodynamic and pharmacokinetic properties of DS in humans. DS was injected in single bolus intravenous injections of four increasing doses (0.5, 1, 1.5, 2 mg/kg) to six healthy volunteers. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT). There were dose-dependent prolongations of the APTT and TCT, and the anticoagulant activities disappeared in less than three hours. The pharmacokinetic parameters were calculated from the plasma concentrations of DS measured with a new chromogenic assay. The volume of distribution was approximately 1.8 times greater than the theoretical plasma volume and was independent of dose. In contrast, the clearance decreased with dose and the terminal half-life ranged from 0.45 +/- 0.08 hours at 0.5 mg/kg to 0.72 +/- 0.11 hours (mean +/- SD) at 2 mg/kg. The bioavailabilities of subcutaneous (SC) and intramuscular (IM) administration relative to those of intravenous administration were determined in 12 other volunteers. The respective bioavailabilities were 24.7% +/- 12.9% and 12.4% +/- 9.2% for SC and IM administration. There was no detectable change in the APTT and the TCT when the volunteers were injected with 1.5 mg/kg SC or IM. In addition, the pharmacokinetic parameters derived from plasma concentrations of DS showed considerable interindividual variations by the two later routes of administration. Peak concentrations were noted 2.7 +/- 1.3 hours after SC injection and 4.3 +/- 4.9 hours after IM injection. The average peak concentrations were 0.7 +/- 0.3 and 0.4 +/- 0.2 mg/L after SC and IM injections, respectively. The half-lives of DS were 7.9 +/- 6.5 hours (SC) and 6.3 +/- 7.4 hours (IM). No adverse reaction to DS was recorded during this study.
.A
Dol F; Houin G; Rostin M; Montastruc JL; Dupouy D; Gianese F; Sie P; Boneu B.
.I 200477
.U
90001539
.S
Blood 9001; 74(5):1583-90
.T
Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study.
.P
JOURNAL ARTICLE.
.W
We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.
.A
McGee MP; Wallin R; Wheeler FB; Rothberger H.
.I 200478
.U
90001541
.S
Blood 9001; 74(5):1600-2
.T
Autoantibodies against platelet membrane glycoproteins in children with acute and chronic immune thrombocytopenic purpura.
.P
JOURNAL ARTICLE.
.W
The autoimmune nature of chronic immune thrombocytopenic purpura (ITP) in adults is widely accepted. In contrast, the pathogenetic mechanism in acute and chronic ITP in children is not known. In this report, we studied 39 children with destructive thrombocytopenia, 15 patients with acute ITP and 24 patients with chronic ITP. Platelet autoantibodies to platelet glycoprotein IIb/IIIa were detected in 14 of 24 patients (58.3%) in the chronic ITP group and in four of 15 (26.7%) with acute ITP. Binding ratios (+/- SD) of positive patients were significantly greater (P = .01) in chronic ITP (8.0 +/- 9.1) when compared with those of acute ITP where the binding ratios were only slightly above the normal range (1.9 +/- 0.4). The results show that autoantibodies against platelet glycoproteins are present in the majority of children with chronic ITP confirming the autoimmune nature of this disorder. The minimal elevation seen in the positive children with acute ITP suggests a different pathogenetic mechanism. These data suggest that this approach may be useful in differentiating acute from chronic ITP patients.
.A
Berchtold P; McMillan R; Tani P; Sommerville-Nielsen S; Blanchette VS.
.I 200479
.U
90001547
.S
Blood 9001; 74(5):1644-50
.T
Differential regulation of tissue factor and plasminogen activator inhibitor by human mononuclear cells.
.P
JOURNAL ARTICLE.
.W
Fibrin is a hallmark of immune-mediated tissue lesions. The presence of fibrin in such lesions implies both the formation of fibrin via coagulation and the accompanying restriction of fibrinolysis, allowing fibrin to persist. Previous work has shown that human monocytes exposed to an inflammatory stimulus such as lipopolysaccharide (LPS) produce both tissue factor (TF) and plasminogen activator inhibitor--type 2 (PAI-2). These two proteins favor fibrin deposition, and evidence implies that cellular production of these two molecules may be linked. Another proinflammatory process pertinent to immune-mediated tissue damage and fibrin deposition is the response to alloantigen. Peripheral-blood mononuclear cells (PBM), consisting of lymphocytes and monocytes together, responded to alloantigen stimulation with differential expression of TF and PAI-2. PBM exposed to alloantigen developed high levels of TF activity, with no concomitant increase in PAI-2 activity or antigen. Alloantigen-stimulated PBM did not accumulate intracellular PAI-2, nor did they degrade PAI-2 added to cultures. This lack of PAI-2 production was not due to inadequate stimulation, as tritiated thymidine uptake and TF production demonstrated recognition of, and a vigorous reaction to, alloantigen. The divergent TF and PAI-2 responses of PBM exposed to alloantigen was maintained over 5 days and was reflected by mRNA profiles. These results imply that under specific physiologically relevant conditions, the procoagulant and antifibrinolytic effectors of inflammatory mononuclear cells can be independently regulated. This would imply more flexibility to monocyte mechanisms that favor fibrin deposition than previously thought.
.A
Schwartz BS; Bradshaw JD.
.I 200480
.U
90001548
.S
Blood 9001; 74(5):1651-7
.T
Proliferative pathways in CD1- CD3+ CD4+ CD8+ T-prolymphocytic leukemic cells: analysis with monoclonal antibodies and cytokines.
.P
JOURNAL ARTICLE.
.W
The antigenic profile and the proliferative pathways in leukemic cells from the patient TRT with T-prolymphocytic leukemia (T-PLL) were analyzed using monoclonal antibodies (MoAbs) and cytokines. T-PLL cells expressed the phenotype CD1- CD3+ CD4+ CD8+. Incubation with the differentiating agent phorbol-12-myristate-13-acetate markedly increased the percentage of cells with the CD4- CD8+ phenotype, suggesting that leukemic cells were already committed towards a differentiated element with the CD4- CD8+ phenotype. T-PLL cells were induced to proliferate by anti-CD2 MoAb 9-1 + 9.6 and by anti-CD3 MoAb OKT3. The two pathways exhibited normal functional interactions and were susceptible to modulation by anti-HLA class I MoAbs. These results indicate that regulation of cell proliferation was preserved to a significant extent in the T-PLL cells analyzed. At variance with normal resting T cells that require previous activation to proliferate when incubated with interleukin-1 (IL-1) or interleukin-2 (IL-2), T-PLL cells proliferated vigorously when incubated with either interleukin. Furthermore, T-PLL cells proliferated when incubated with immune interferon (IFN-gamma). The latter finding parallels the enhancement by IFN-gamma of the proliferative response of lectin-activated murine T lymphocytes. These results suggest that T-PLL cells, which express a high constitutive level of c-myc mRNA, may be in an activated state. The antigenic phenotype and the characteristics of the proliferative pathways of T-PLL cells from the patient TRT are compatible with the possibility that they may be derived from an intermediate thymocyte.
.A
Turco MC; De Felice M; Alfinito F; Lamberti A; Costanzo F; Giordano M; Martinelli V; Rotoli B; Ferrone S; Venuta S.
.I 200481
.U
90001549
.S
Blood 9001; 74(5):1658-64
.T
Prevalence of human T-cell leukemia/lymphoma virus (HTLV) type II infection among high-risk individuals: type-specific identification of HTLVs by polymerase chain reaction.
.P
JOURNAL ARTICLE.
.W
The extent of human T-cell leukemia/lymphoma virus type II (HTLV-II) infection and its rate of spread have been difficult to determine owing to the serological cross-reactivity between HTLV-I and HTLV-II. The present study overcame this problem by directly detecting type-specific proviral sequences by means of the polymerase chain reaction (PCR) and liquid hybridization. Screening was performed on a cohort of primarily white intravenous drug abusers (IVDAs), and individuals of other behaviorally defined risk groups from the New York City area. Eleven percent (19 of 169) of the individuals in these high-risk groups were determined by PCR to have HTLV-II proviral infections. One of these patients displayed an exfoliative erythrodermatitis. Thirteen of the 19 subjects were positive in an HTLV-II enzyme-linked immunosorbent assay (ELISA). The remaining six individuals, although negative in the HTLV-II ELISA, were confirmed as HTLV-II positive by analyzing their DNA with a second HTLV-II-specific primer detector system. Four additional individuals were reactive in the HTLV-II ELISA but were PCR-negative for HTLV-II. PCR analysis for HTLV-I revealed that all four were positive for that virus. Thirty-seven percent (seven of 19) of the HTLV-II PCR-positive subjects were also PCR-positive for HTLV-I, and 84% (16 of 19) of the HTLV-II positive individuals were infected with human immunodeficiency virus (HIV-1). Six individuals were triply infected with HTLV-I, HTLV-II, and HIV-1.
.A
Ehrlich GD; Glaser JB; LaVigne K; Quan D; Mildvan D; Sninsky JJ; Kwok S; Papsidero L; Poiesz BJ.
.I 200482
.U
90001553
.S
Blood 9001; 74(5):1690-7
.T
Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission.
.P
JOURNAL ARTICLE.
.W
Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.
.A
Adler A; Albo V; Blatt J; Whiteside TL; Herberman RB.
.I 200483
.U
90001555
.S
Blood 9001; 74(5):1704-10
.T
Increased plasma levels of interleukin-6 in sepsis [see comments]
.P
JOURNAL ARTICLE.
.W
Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response. We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome. In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level. The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001). In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002). Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed. IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001). All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died. These data provide evidence for a role of IL-6 in the pathophysiology of septic shock. Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an "alarm hormone" that reflects endothelial cell injury probably mediated by the anaphylatoxines.
.A
Hack CE; De Groot ER; Felt-Bersma RJ; Nuijens JH; Strack Van Schijndel RJ; Eerenberg-Belmer AJ; Thijs LG; Aarden LA.
.I 200484
.U
90001556
.S
Blood 9001; 74(5):1711-7
.T
Differential effects of TGF-beta 1 on lymphohemopoiesis in long-term bone marrow cultures.
.P
JOURNAL ARTICLE.
.W
Latent transforming growth factors beta (TGF-beta) are easily detectable in embryonic and adult hematopoietic tissues and in vitro studies show that they are potent antagonists of lymphopoiesis and myelopoiesis when converted to biologically active form. To learn more about possible roles in hematopoiesis, active TGF-beta 1 was added to cultures prepared to support myeloid cells (Dexter conditions) or B lineage lymphocytes (Whitlock-Witte conditions) and studied in detail. Hematopoiesis was permanently arrested in Dexter cultures treated with 40 pmol/L (1 ng/mL) of active TGF-beta from initiation. In addition, adipogenesis was inhibited in a dose-dependent manner, and adherent layers from treated cultures were defective when recharged with fresh bone marrow cells. Ongoing neutrophil production was terminated in established cultures when addition of the factor was delayed for 8 weeks. In contrast, in experiments with Whitlock-Witte cultures, some of the flasks produced lymphocytes in the continuous presence of TGF-beta 1 (40 pmol/L). Lymphopoiesis was completely arrested by ten-fold higher concentrations, and this was most effective when added at the beginning of culture. Precursors of lymphocytes as well as the microenvironmental elements necessary for supporting their growth survived 2 weeks of cytokine treatment (400 pmol/L) in Dexter cultures. Normal outgrowth of lymphocytes occurred when the cultures were switched to Whitlock-Witte conditions. Surface marker expression on lymphocytes growing in TGF-beta resistant or previously treated cultures was not unusual. These studies demonstrate that TGF-beta is a negative regulator of hematopoiesis in long-term cultures and show that this includes effects on microenvironmental elements. At low concentrations, production of myeloid cells was preferentially affected.
.A
Hayashi S; Gimble JM; Henley A; Ellingsworth LR; Kincade PW.
.I 200485
.U
90001557
.S
Blood 9001; 74(5):1718-22
.T
Sensitive inhibitory effect of interferon-alpha on M-protein secretion of human myeloma cells.
.P
JOURNAL ARTICLE.
.W
The effects of interferon-alpha (IFN alpha) on in vitro proliferation and M-protein secretion in human myeloma cells were investigated. Human myeloma cells were purified from bone marrow aspirates in 12 multiple myeloma patients. Purified myeloma cells were cultured for 48 hours with IFN alpha at its lower concentrations (0.1 to 100 U/mL). The cells were then pulsed with 3H-TdR for the last 12 hours and 3H-TdR uptake was measured (in vitro proliferation). After 48-hour culture, supernatants were harvested and the amount of M-protein in these fluids were measured by enzyme-linked immunosorbent assay (ELISA) (in vitro M-protein secretion). In vitro M-protein secretions of myeloma cells were significantly suppressed even at 0.1 U/mL of IFN alpha, while 3H-TdR uptakes were not so suppressed until 10 or 100 U/mL of IFN alpha were added. The expressions of secretory immunoglobulin (Ig) mRNA of these myeloma cells were also selectively suppressed by IFN alpha. Furthermore, after IFN alpha had been administered intramuscularly, 3 to 6 x 10(6) U/d for at least 1 month, in vitro M-protein secretions of these myeloma cells were decreased compared with those before IFN alpha administration. Therefore, these results suggest that IFN alpha has more sensitive inhibitory effect on M-protein secretion of human myeloma cells rather than on myeloma cell proliferation.
.A
Tanaka H; Tanabe O; Iwato K; Asaoku H; Ishikawa H; Nobuyoshi M; Kawano M; Kuramoto A.
.I 200486
.U
90001558
.S
Blood 9001; 74(5):1723-7
.T
Effects of tumor necrosis factor on sensitive and multidrug resistant human leukemia and myeloma cell lines.
.P
JOURNAL ARTICLE.
.W
Two human tumor cell lines exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (GP-170) were tested for their sensitivity to human recombinant tumor necrosis factor (rTNF). The drug resistant mutant lines (CEM/V, a T-cell leukemia line resistant to vinblastine, and 8226/D, a multiple myeloma line resistant to doxorubicin), were markedly more sensitive to rTNF in clonogenic assay than were their drug-sensitive parental lines (CEM, 8226). As determined by radioreceptor assay, the number of cell surface receptors for rTNF did not differ on the parental and drug-resistant lines. During the first 24 hours after addition of rTNF, there was a decrease in intracellular ATP content in the CEM/V line but not in the CEM line. No differential effect of rTNF on ATP content was observed between 8226 and 8226/D. As determined by RNA dot-blot analysis, total cellular RNA for GP-170 was increased in the 8226/D cells. After rTNF exposure, expression of total cellular RNA for GP-170 was not altered. Accumulation of radiolabeled doxorubicin by 8226/D cells was not altered by previous or coincubation with rTNF. These findings suggest that the effects of rTNF on MDR cells is not related to TNF receptor number and is mediated at a step subsequent to rTNF binding and not by either inhibition of synthesis of GP-170 or by alteration in the function of the GP-170 efflux pump.
.A
Salmon SE; Soehnlen B; Dalton WS; Meltzer P; Scuderi P.
.I 200487
.U
90001559
.S
Blood 9001; 74(5):1728-37
.T
Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin.
.P
JOURNAL ARTICLE.
.W
Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N-formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL.
.A
Nichols KE; Chitneni SR; Moore JO; Weinberg JB.
.I 200488
.U
90001560
.S
Blood 9001; 74(5):1738-46
.T
Molecular analysis of acute undifferentiated leukemia: two distinct subgroups at the DNA and RNA levels.
.P
JOURNAL ARTICLE.
.W
On the basis of negativity for myeloperoxidase (MPO) and absence of lineage-associated antigens on the cell surface, 11 children were diagnosed as having acute undifferentiated leukemia. To analyze the molecular events associated with hematopoietic cell differentiation, we analyzed the configuration of the immunoglobulin (Ig) and T-cell receptor (TCR) delta, alpha, gamma, and beta genes in these patients. In parallel, transcription of the genes for MPO, terminal deoxynucleotidyltransferase (TdT), CD3-gamma, Ig-mu, TCR-gamma, and beta was also examined. Six patients showed rearrangements of both the Ig heavy (H) and TCR-delta genes, frequently accompanied with Ig-kappa, TCR-alpha, gamma, and beta gene rearrangements. These findings indicated that the leukemic cells from the six patients had been committed to the lymphoid lineage. This concept was supported by the presence of TdT transcripts in three analyzed specimens from these patients. In contrast, the remaining five patients did not display rearrangements of the Ig or TCR genes, and TdT transcripts were undetectable in two patients tested. MPO transcripts were not detected in four patients analyzed, thus providing no evidence of myeloid differentiation. After hybridization with the CD3-gamma gene, three of six patients showed transcription of the CD3-gamma gene. In addition to CD3-gamma transcripts, one patient with rearrangements of the Ig-H, TCR-delta, alpha, gamma, and beta genes also had full-length TCR-beta and gamma transcripts, indicating a T-precursor-cell origin of the leukemic cells from this patient. The Ig and TCR genes were in the germline configuration in the other two patients with CD3-gamma transcripts. One of them did not express the CD7 antigen but did express the CD33 antigen on the cell surface, suggesting that CD3-gamma transcription may not always be an event restricted to cells differentiating along the T-cell lineage.
.A
Hara J; Yumura-Yagi K; Tawa A; Ishihara S; Murata M; Terada N; Izumi Y; Champagne E; Takihara Y; Mak TW; et al.
.I 200489
.U
90001562
.S
Blood 9001; 74(5):1758-61
.T
Peripheral acute leukemia: high peripheral but low-marrow blast count.
.P
JOURNAL ARTICLE.
.W
We report five patients who had greater than 30% peripheral blasts and less than 30% marrow blasts. By the current standards these cases would be classified as myelodysplastic syndrome. Four of five patients progressed to acute leukemia within approximately 1 1/2 months of developing greater than 30% peripheral blasts. Two of these four patients had evidence of acute leukemia by criteria other than marrow involvement at the time of presentation: one patient had evidence of multifocal dermal involvement; and the other patient had a cytogenetic abnormality, t(8;21), found predominantly in acute leukemia. The fifth patient developed acute leukemia 2 years after initial presentation with greater than 30% peripheral blasts. Although our series of patients is small, it does suggest that patients who have greater than 30% peripheral blasts should be considered an acute leukemia, even with less than 30% marrow blasts.
.A
Cason JD; Trujillo JM; Estey EH; Huh YO; Freireich EJ; Stass SA.
.I 200490
.U
90001565
.S
Blood 9001; 74(5):1774-80
.T
Prognostic variables and clinical staging in multiple myeloma.
.P
JOURNAL ARTICLE.
.W
To evaluate the most important factors in the prognosis and staging of multiple myeloma (MM), the presenting clinical features of 163 previously untreated patients with MM were correlated with survival duration using univariate and multivariate regression analyses. The univariate proportional hazard analysis ranked the parameters in the following order of importance: platelet count, hemoglobin level (Hb), tumor cell mass stage, lytic bone lesions, creatinine, and age. When the individual contribution of each variable was assessed by multivariate regression analysis, platelet count was confirmed to be the dominant feature for prognosis and clinical stage provided additional information. The introduction of platelet count could then be used to improve the reliability of the Durie and Salmon staging, by allowing to separate the high-risk group (stages II and III) into a smaller subgroup (22%) of thrombocytopenic patients (less than 150 x 10(9) platelets/L) whose risk of death was actually very high (median survival, 9 months) and a larger subgroup (46%) of patients with normal platelet count and intermediate or standard risk (median survival, 48 months). This simple change in the prognostic system gave rise to markedly different survival curves also after the exclusion of patients with renal failure and applied successfully to both old and young patients (greater than and less than 50 years, respectively). Finally, platelet count, Hb, and lytic bone lesions could be combined simply to stratify patients with normal renal function into three risk groups: (1) low (39% of cases; median survival, 79 months), (2) intermediate (53% of cases; median survival, 48 months), and (3) high (8% of cases; median survival, 19 months).
.A
Cavo M; Galieni P; Zuffa E; Baccarani M; Gobbi M; Tura S.
.I 200491
.U
90001566
.S
Blood 9001; 74(5):1781-90
.T
Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients.
.P
JOURNAL ARTICLE.
.W
Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlymphocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evaluable patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed -7/7q- and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13 or 14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of -7/7q- and -5/5q- in ANLL-M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells.
.A
Cuneo A; Mecucci C; Kerim S; Vandenberghe E; Dal Cin P; Van Orshoven A; Rodhain J; Bosly A; Michaux JL; Martiat P; et al.
.I 200492
.U
90001569
.S
Blood 9001; 74(5):1801-6
.T
An additional breakpoint region in the BCL-1 locus associated with the t(11;14)(q13;q32) translocation of B-lymphocytic malignancy.
.P
JOURNAL ARTICLE.
.W
The t(11;14)(q13;q32) translocation is associated with human B-lymphocytic malignancy. This translocation divides the IgH locus on chromosome 14q32 and may activate a postulated proto-oncogene, bcl-1, located on chromosome 11q13. Two samples of chronic lymphocytic leukemia with the t(11;14)(q32;q13) translocation were studied. The break in one sample was shown to join Jh sequences with the previously described bcl-1 major translocation cluster. DNA blots of the second sample suggested that Jh sequences were joined to a different breakpoint region on chromosome 11. This translocation was cloned and found to link the human Jh3 region and a new breakpoint region 63 kb telomeric of the major translocation cluster. This translocation occurred in part as the result of an aberrant D-J recombination. Recurrent translocations human B-lymphocytic malignancy. The definition of a new breakpoint region may aid the identification of the postulated bcl-1 gene.
.A
Meeker TC; Grimaldi JC; O'Rourke R; Louie E; Juliusson G; Einhorn S.
.I 200493
.U
90001570
.S
Blood 9001; 74(5):1807-10
.T
Loss of copper-zinc superoxide dismutase gene expression in differentiated cells of myelo-monocytic origin.
.P
JOURNAL ARTICLE.
.W
Changes in the production of reactive oxygen species and total superoxide dismutase activity have been observed during differentiation of some hematopoietic cells. We therefore investigated whether the steady-state level and rate of transcription of superoxide dismutase-1 (SOD-1) mRNA change during terminal differentiation of the human leukemia cell lines THP-1, HEL, and HL-60 into macrophages and/or granulocytes, respectively. Macrophage differentiation is accompanied by a gradual decrease in both the transcription rate (10x) and the steady-state level (6x) of SOD-1 mRNA. No decrease was observed after treatment with the diacylglycerol analog 1,2 dioctanol-rac-glycerol (di-C8), which like phorbol 12-myristate 13-acetate also activates protein kinase C but does not induce differentiation at the concentration used. The same decrease in SOD-1 mRNA level was observed when HL-60 cells were induced to differentiate into granulocytes by treatment with dimethylsulfoxide. These data suggest that a decrease in SOD-1 mRNA to almost undetectable levels accompanies differentiation of macrophages and granulocytes.
.A
Auwerx JH; Chait A; Wolfbauer G; Deeb SS.
.I 200494
.U
90001572
.S
Blood 9001; 74(5):1817-22
.T
Beta+-thalassemia in cis of a sickle cell gene: occurrence of a promoter mutation on a beta s chromosome.
.P
JOURNAL ARTICLE.
.W
An atypical sickle cell trait with a very low level of hemoglobin S and features of heterozygous beta-thalassemia was recently described. In vitro globin chain synthesis strongly suggested the presence of the two abnormalities on the same chromosome. We report the corresponding beta S-thal gene. DNA sequence revealed a C----T base substitution in the distal promoter element CACCC, at position-88 from the cap site, in addition to the expected GAG----GTG mutation responsible for the structural variant (beta 6 Glu----Val). Reticulocyte mRNA titration and transient assay of the mutant gene in COS cells showed a defect in beta-mRNA production. Restriction haplotype and DNA sequence analyses revealed that the doubly mutated gene is associated with haplotype 19 (or Benin/Algeria haplotype). In particular, we found the (AT)9(T)4 repeated sequences specifically encountered 5' to the beta S gene of Benin Algeria type. These results support the view that the beta S-thal gene resulted from an independent thalassemic mutation having occurred on a beta S chromosome rather than (a) from a beta S mutation having altered a beta-thalassemic gene or (b) from a recombination event between two chromosomes, each carrying one of the mutations.
.A
Baklouti F; Ouazana R; Gonnet C; Lapillonne A; Delaunay J; Godet J.
.I 200495
.U
90001573
.S
Blood 9001; 74(5):1823-5
.T
Acceleration of hemoglobin C crystallization by hemoglobin S.
.P
JOURNAL ARTICLE.
.W
We previously reported that circulating hemoglobin (Hb) CC erythrocytes contain oxygenated HbC crystals with little or no HbF and that HbF inhibits in vitro crystallization of HbC. We now report that HbS accelerates in vitro crystallization of HbC. Crystals were formed in 1.8 mol/L potassium phosphate buffer, pH 7.4, at 30 degrees C and were counted in several time intervals with a hematocytometer. The hemoglobin composition of Millipore-isolated crystals and supernatant were also analyzed. Under the conditions selected, 100% HbS formed needle-shaped crystals only after two hours. Pure HbC does not form crystals within 15 minutes, whereas a ratio of 10% HbS:90% HbC forms 1,100 crystals/mm3, 20% HbS:80% HbC forms 370 crystals/mm3, and 30% HbS:70% HbC forms 5 crystals/mm3. Crystals formed in the presence of HbS are tetragonal, as are pure HbC crystals. As compared with 100% HbC, HbA or albumin mixed with HbC showed a decreased number of crystals as a result of dilution. Analysis of the Hb content of isolated crystals by citrate agar gel electrophoresis showed that HbS was rapidly incorporated into the crystal in the same ratio over time. These results demonstrate that HbS accelerates crystallization of HbC with respect to the rates of crystallization of any of these two Hbs separately, through a mechanism that involves cocrystallization. These results may be significant in understanding SC disease.
.A
Lin MJ; Nagel RL; Hirsch RE.
.I 200496
.U
90001574
.S
Blood 9001; 74(5):1826-35
.T
Effect of phosphatidylserine on the shape of McLeod red cell acanthocytes.
.P
JOURNAL ARTICLE.
.W
The rare McLeod blood group phenotype is characterized by weak Kell antigens, lack of the common Kx antigen, and acanthocytic morphology. Previous studies that did not detect membrane or cytoskeletal protein abnormalities suggested a lipid disturbance. In normal red cells, dimyristoyl phosphatidylserine (DMPS) is transported across the membrane by an enzymatic process and accumulates in the inner leaflet of the membrane bilayer causing discocyte to stomatocyte shape changes. Scanning electron microscopy of McLeod red cells shows a mixture comprised of 15% discocytes, 51% with irregular surfaces, and 34% acanthocytes. On incubation with various concentrations of DMPS at 37 degrees C for periods up to two hours, McLeod red cells transported DMPS across the membrane and caused irregularly shaped and acanthocytic McLeod red cells to attain normal discocyte shape and later to become stomatocytes. Chlorpromazine, which at 0 degrees C preferentially partitions into the inner monolayer of the membrane, had a similar effect on the shape of McLeod red cells. This suggests that in McLeod cells acanthocytosis is due to a lack of lipid in the inner leaflet of the membrane bilayer but that the imbalance is not caused by defective transport of phosphatidylserine across the membrane.
.A
Redman CM; Huima T; Robbins E; Lee S; Marsh WL.
.I 200497
.U
90001576
.S
Blood 9001; 74(5):1844-51
.T
Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions.
.P
JOURNAL ARTICLE.
.W
Vesicles (exosomes) released during sheep reticulocyte maturation contain a number of plasma membrane functions. Using an antibody coated, magnetic core bead, it has been shown unequivocally that vesicles that contain the transferrin receptor also contain other plasma membrane activities, such as the nucleoside transporter and acetylcholinesterase. Lysosomal activities, normally found in the same pellet, are excluded from the transferrin receptor-containing exosomes, suggesting that there is a common mechanism to segregate and externalize specific plasma membrane proteins. In addition to the sheep, electron micrographic studies show that exosomes can be retrieved from the circulation of anemic pigs, rats, and rabbits.
.A
Johnstone RM; Bianchini A; Teng K.
.I 200498
.U
90001577
.S
Blood 9001; 74(5):1852-7
.T
Bone marrow transplantation for children with severe aplastic anemia: use of donors other than HLA-identical siblings.
.P
JOURNAL ARTICLE.
.W
Eighty-five percent of untransfused and 70% of transfused patients with severe aplastic anemia (SAA) are cured with bone marrow transplants from histocompatible sibling donors. Use of partially matched family donors or unrelated donors has been relatively unsuccessful because of high incidences of graft rejection and graft-versus-host disease (GVHD). Thirteen children with SAA received marrow grafts from alternative donors (sibling 4, parent 5, unrelated 4). The first three patients were pretreated with cyclophosphamide (CYCLO) +/- irradiation and received methotrexate for GVHD prophylaxis. Subsequent children were pretreated with CYCLO + high-dose cytosine arabinoside + methylprednisolone + total body irradiation, had monoclonal antibody T-cell depletion of the donor marrow, and received cyclosporine for GVHD prophylaxis. Three heavily transfused patients with haploidentical-related donors failed to engraft and died. All 10 patients with more closely matched donors engrafted. Acute GVHD was grade II in only one patient (non-T-depleted); this patient is the only one with severe chronic GVHD. Three engrafted patients died (Pneumocystis pneumonia, systemic parainfluenza, venocclusive disease). Seven children are alive 33+ to 2,692+ days. Donors for the survivors were siblings 3, parent 1, unrelated 3. These data suggest that bone marrow transplantation from closely matched donors other than histocompatible siblings can be effective therapy for SAA if an intensive conditioning regimen is used. These results must be confirmed with larger numbers and longer follow-up.
.A
Camitta B; Ash R; Menitove J; Murray K; Lawton C; Hunter J; Casper J.
.I 200505
.U
90002057
.S
Br J Rheumatol 9001; 28(5):374-8
.T
HLA-DO-related restriction fragment length polymorphisms in rheumatoid arthritis: evidence for a link with disease expression.
.P
JOURNAL ARTICLE.
.W
Eighty-three patients with rheumatoid arthritis (RA) were investigated for HLA-DQ and DR locus restriction fragment length polymorphisms (RFLP). Of the 83 patients, 61 (73%) possessed the DR4 allele and within this group we have investigated the relative frequencies of two DQ beta gene variants of DQw3, DQw7 and DQw8, one of which we had previously found to be raised in Felty's syndrome. This analysis revealed a significantly higher frequency of DQw7 containing haplotypes in DR4 positive rheumatoid patients (64%) than in DR-matched healthy controls (42%). Furthermore, the distribution of DQw7 was biased towards those patients with greater disability indicated by the HAQ score, more systemic disease and higher titres of rheumatoid factor, suggesting that DQw7 may contribute to disease expression.
.A
Sansom DM; Amin SN; Bidwell JL; Klouda PT; Bradley BA; Evison G; Goulding NJ; Hall ND; Maddison PJ.
.I 200506
.U
90002058
.S
Br J Rheumatol 9001; 28(5):379-82
.T
The relationship of anticardiolipin antibodies to disease activity in systemic lupus erythematosus.
.P
JOURNAL ARTICLE.
.W
Sera from 124 blood donors, 60 rheumatoid arthritis (RA) and 57 SLE patients were measured for anticardiolipin antibodies by ELISA. Significantly raised IgG (aCLG) and IgM (aCLM) anticardiolipin antibody levels were found in RA and SLE (p less than 0.0005). However, in SLE both aCLG and aCLM levels were significantly higher than in RA (p less than 0.0025). We then conducted a transectional study to evaluate aCL levels and disease activity in SLE. There was a good positive predictive value (70%) between aCL and overall disease activity, but not for individual systems. A strong association between aCL and renal involvement irrespective of activity was also found (80%). Nine SLE patients fulfilled both the clinical and serological criteria for the antiphospholipid syndrome (APS) and a further 18 patients fulfilled the serological criteria for APS. Results indicate that aCL levels are of value in predicting overall disease activity in SLE and in monitoring those patients who fulfil or partially fulfil the criteria for APS.
.A
Cooper RC; Klemp P; Stipp CJ; Brink S.
.I 200508
.U
90002060
.S
Br J Rheumatol 9001; 28(5):383-5
.T
Sialochemistry in juvenile chronic arthritis.
.P
JOURNAL ARTICLE.
.W
Stimulated parotid gland secretions collected from 16 patients with juvenile chronic arthritis (JCA) were analysed and the results compared with those obtained from 83 healthy sex-, age-, and socioeconomic status-matched children. Parotid salivary flow rate was measured and the saliva samples were assayed for calcium, phosphorus, potassium, chloride, sodium, urea, lysozyme, amylase and immunoglobulin levels (IgA, Ig, IgM). Our results showed that parotid flow rate (PFR) values in JCA patients were not statistically different from those in healthy controls. However, the mean salivary concentrations of calcium, phosphorus, potassium, lysozyme and IgA were significantly lower in the patients. These data could provide an explanation for the increased incidence of caries and gingivitis observed in JCA.
.A
Siamopoulou A; Mavridis AK; Vasakos S; Benecos P; Tzioufas AG; Andonopoulos AP.
.I 200509
.U
90002062
.S
Br J Rheumatol 9001; 28(5):393-8
.T
Serum and synovial fluid osteocalcin (bone gla protein) levels in joint disease [see comments]
.P
JOURNAL ARTICLE.
.W
Osteocalcin (bone gla protein) is a sensitive marker of bone turnover in metabolic disease. Using a well characterized antiserum (R 102M) we have assayed serum and synovial fluid samples from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and related levels to serological and radiological markers of disease. There were 21 patients with RA (mean age 58.2 years, 15 F) and 33 with OA (mean age 69.2, 28 F). Paired serum and synovial fluids (SF) were available in 19 RA patients and 30 OA patients. Serum osteocalcin levels were related to age-/sex-matched normals and to a small group of elderly disease controls. Serum levels tended to be lower in RA than controls, but not significantly so: RA 5.56 (3.67); control 6.09 (2.54) ng/ml; expressed as mean (SD) and the mean serum/SF ratio was 0.88 (0.86). The results were much more variable in OA (mean serum osteocalcin 6.1 (3.9]. Elevated levels were mainly due to a small number of patients with a destructive form of OA and were higher than those with non-destructive OA (10.3 (3.5), n = 20, versus 3.83 (1.6), n = 10). Patients with non-destructive OA had a lower serum osteocalcin than age-/sex-matched normals. In this study, synovial fluid levels were usually less than serum concentrations, but in two RA and four OA patients the ratio was reversed, suggesting local production. Osteocalcin may be an important marker of bone activity in OA.
.A
Campion GV; Delmas PD; Dieppe PA.
.I 200510
.U
90002063
.S
Br J Rheumatol 9001; 28(5):399-403
.T
Reflex sympathetic dystrophy (algoneurodystrophy): temperature studies in the upper limb.
.P
JOURNAL ARTICLE.
.W
The temperature response of the hands to mild cold stress (20 degrees C for one minute) has been measured in 20 normal subjects, 20 patients with reflex sympathetic dystrophy (RSD) and 10 patients with chronic upper limb pain (CULP) of uncertain origin. The results of RSD and CULP groups were significantly (p less than 0.05) different from normal but were indistinguishable. For each patient, 11 variables obtained from the thermal stress test were compared with the normal range. Ten of the RSD group and seven of the CULP group had four or more abnormal variables and were considered to have a thermoregulatory abnormality. The thermal stress test is useful in the objective assessment of RSD. It is non-invasive, patient acceptable and reproducible.
.A
Cooke ED; Glick EN; Bowcock SA; Smith RE; Ward C; Almond NE; Beacham JA.
.I 200511
.U
90002064
.S
Br J Rheumatol 9001; 28(5):404-9
.T
The use of dolorimetry in the assessment of post-traumatic algodystrophy of the hand.
.P
JOURNAL ARTICLE.
.W
We have investigated the use of dolorimetry in the assessment of algodystrophy of the hand. Findings in 12 affected patients following Colles' fracture were compared with age- and sex-matched normal controls. Algodystrophy was associated with a significant increase in tenderness of both the finger joints and bones. Tenderness of the whole hand was quantified by summing the dolorimetry readings at each site within the hand and the ratio of the summed readings for the two hands was defined as the dolorimetry ratio. This ratio was highly reproducible and independent of external variables. It was significantly lower in patients with algodystrophy than in controls and may provide a method for the diagnosis and serial assessment of the disorder.
.A
Atkins RM; Kanis JA.
.I 200513
.U
90002066
.S
Br J Rheumatol 9001; 28(5):410-3
.T
Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin.
.P
JOURNAL ARTICLE.
.W
Serum levels of immunoglobulin A (IgA) and the complex immunoglobulin A-alpha 1 antitrypsin (IgA-alpha 1AT) were measured at the commencement and after 3 months of a double-blind, placebo-controlled trial of sulphasalazine (SAS) in patients with active ankylosing spondylitis (AS). Twenty-eight patients were evaluated, 15 on sulphasalazine, 13 on placebo. Significant falls were seen in both IgA (p less than 0.01) and IgA-alpha 1AT (p less than 0.001) in the actively treated patients. In addition, significant improvement in clinical and laboratory measures of disease were observed. It is concluded that SAS is effective in AS and modulates the immune response.
.A
Davis MJ; Dawes PT; Beswick E; Lewin IV; Stanworth DR.
.I 200514
.U
90002067
.S
Br J Rheumatol 9001; 28(5):414-7
.T
Haematological side-effects of sulphasalazine in inflammatory arthritis.
.P
JOURNAL ARTICLE.
.W
The nature and incidence of haematological side-effects of sulphasalazine was sought in a retrospective study of 130 sulphasalazine-treated patients with chronic inflammatory arthritis. Macrocytosis was seen to occur in 27 patients (20.8%) and four patients (3%) developed a macrocytic anaemia. Only eight of 23 macrocytic patients had low red cell folate levels, three of whom were anaemic. An increased risk of developing macrocytosis was seen with doses of sulphasalazine greater than 2 g per day. In most patients the macrocytosis was noted during the first 6 months but did occur in the second and third 6-month period of treatment. Only one patient (0.8%) developed neutropenia and no cases of thrombocytopenia were observed. Regular blood counts should be performed while patients remain on treatment but haematological side-effects are seldom the reason for withdrawal of sulphasalazine.
.A
Hopkinson ND; Saiz Garcia F; Gumpel JM.
.I 200515
.U
90002068
.S
Br J Rheumatol 9001; 28(5):418-21
.T
The effect of CPH 82 on the growth of human lymphocytes in vitro. Definition of cytobiological action.
.P
JOURNAL ARTICLE.
.W
A drug composed of two semisynthetic podophylline derivatives, CPH 82, has recently been launched for the treatment of severe rheumatoid arthritis. The present in vitro study of PHA-stimulated human T-lymphocytes showed that CPH 82 arrested cell division in a metaphase-like configuration. The cell cycle effects of CPH 82 were indistinguishable from the cell cycle effects of the classical microtubule depolymerizers, Colcemid (a colchicine derivative) and podophyllotoxin. A CPH 82 concentration of 1 microgram/ml, which is close to therapeutic serum concentrations, had an almost maximal effect on cell division. It is suggested that at least part of the anti-inflammatory effect of CPH 82 is due to a colchicine-like activity on, for example, proliferating lymphocytes.
.A
Rantapaa Dahlqvist S; Norberg B; Sondell K; Nordenson I; Holmgren G.
.I 200517
.U
90002070
.S
Br J Rheumatol 9001; 28(5):422-3
.T
Synovial and serum levels of methotrexate during methotrexate therapy of rheumatoid arthritis.
.P
JOURNAL ARTICLE.
.W
Methotrexate (MTX) levels were studied following intravenous MTX in both serum and synovial fluid (SF) of rheumatoid arthritis patients. Two hours after injection serum MTX levels were higher than those of SF. At 24 hours SF levels of MTX exceeded those of the serum, while at 72 hours both blood and SF concentrations were undetectable. The localization of parenteral MTX in the SF may have importance in the understanding of its mechanism and site of action in rheumatoid arthritis.
.A
Tishler M; Caspi D; Graff E; Segal R; Peretz H; Yaron M.
.I 200518
.U
90002071
.S
Br J Rheumatol 9001; 28(5):424-7
.T
Correlation between clinical and laboratory findings when the whole blood filterability rate is modified by ticlopidine in the treatment of rheumatoid arthritis.
.P
JOURNAL ARTICLE.
.W
This double-blind study assessed the effects of oral ticlopidine versus placebo on whole blood filterability in two homogenous groups of 20 rheumatoid arthritis patients taking one NSAID. The patients' clinical progress was monitored to see if modifications in the whole blood filterability rate could be correlated with any improvement in the clinical picture. Our results showed treatment with ticlopidine significantly (p less than 0.01) improved both the ESR (-28%) and the whole blood filterability rate (-15%), pain (-24%), and morning stiffness (-28%). These clinical benefits correlated with improvement in the whole blood filterability rate. Clinical benefits may have resulted from improved perfusion and transport of NSAID to target tissues.
.A
Ciuffetti G; Ciacca A; Mercuri M; Lombardini R; Maragoni G; Scarponi AM.
.I 200520
.U
90002073
.S
Br J Rheumatol 9001; 28(5):440-2
.T
A case of systemic lupus erythematosus presenting as Guillain-Barre syndrome.
.P
JOURNAL ARTICLE.
.W
Acute demyelinating polyneuropathy has been reported only twice as a presenting feature of systemic lupus erythematosus (SLE) in female patients. We report a male presenting with an acute demyelinating polyneuropathy who subsequently was found to have SLE.
.A
Chaudhuri KR; Taylor IK; Niven RM; Abbott RJ.
.I 200521
.U
90002074
.S
Br J Rheumatol 9001; 28(5):443-5
.T
Myositis ossificans non-progressiva--reversible muscle calcification in polymyositis [see comments]
.P
JOURNAL ARTICLE.
.W
We report a case of muscle calcification, a rare complication of polymyositis, documented on muscle biopsy and computerized tomography scanning. As the calcification resolved radiologically, marked hypercalcaemia developed requiring forced diuresis.
.A
Coakley JH; Smith PE; Jackson MJ; Edwards RH; Carty AT.
.I 200530
.U
90002088
.S
Br J Radiol 9001; 62(741):785-9
.T
Treatment of tumours of the parotid gland and middle ear using obliquely reconstructed computed tomographic images.
.P
JOURNAL ARTICLE.
.W
Conventional planning of radiotherapy of tumours of the parotid, middle ear and other tumours in the head and neck often requires the treatment plane to be non-transverse. This produces major problems in delineating the tumour as well as verifying that vital structures such as the spinal cord are not included in the target volume. The use of computed tomography (CT) generally overcomes some of these problems and we have developed an algorithm to reconstruct transverse CT images into the appropriate oblique plane. Software has been written on the Picker Independent Treatment Planning System (ITPS) to allow planning on central axis and off-axis oblique planes. In addition we have used a beam's eye view facility to aid in the verification process.
.A
Sims C; Manifold IH; Conway J.
.I 200531
.U
90002089
.S
Br J Radiol 9001; 62(741):790-5
.T
Bone marrow scintigraphy in the diagnosis of post-traumatic avascular necrosis of bone.
.P
JOURNAL ARTICLE.
.W
A series of 19 patients, who were clinically suspected of developing avascular necrosis of bone following fracture, were entered into a pilot study comparing the use of bone marrow scintigraphy with conventional skeletal scintigraphy. Two-phase bone scintigraphy, using 600 MBq of 99Tcm-HMDP, and perfusion and late-phase nanocolloid scintigraphy, using 370 MBq of 99Tcm-nanocolloid, were performed on each patient. In both methods, photon deficiency at the site of interest was taken to indicate avascularity. The perfusion phase of both methods was found to be unhelpful. Agreement between methods was obtained in 18 patients (95%). Six patients had abnormal nanocolloid scans, one of which was normal on the conventional bone scintigram. The remaining 13 patients had no evidence to suggest avascularity in either method. Three of the patients with abnormal scans have had hip replacement surgery following which avascularity of the femoral head was confirmed. 99Tcm-nanocolloid scintigraphy is thus shown to be a very sensitive method of demonstrating avascularity of bone following trauma.
.A
Tawn DJ; Watt I.
.I 200532
.U
90002092
.S
Br J Radiol 9001; 62(741):807-12
.T
Late radiation injury of the rectum and sigmoid colon: barium enema findings in 92 patients.
.P
JOURNAL ARTICLE.
.W
We reviewed the findings on 169 contrast enema examinations in 92 patients with late radiation injury of the rectum and sigmoid colon, encountered over an 11-year period. The diagnosis was made by rectosigmoidoscopy in all patients. The limitations and pitfalls of both examinations were studied. The mean interval between radiotherapy and diagnosis was 1.7 years and the mean follow-up period was 3.5 years. The main radiological features varied from normal findings (15% of the initial examinations) to decreased distensibility of the bowel wall, intestinal fixation, mucosal and contour abnormalities, ulceration, stenoses and fistula formation. During follow-up, the number of all pathological findings increased. Pre-stenotic dilatation of the descending colon was always absent. The contrast enema examinations and endoscopies were found to be complementary. The barium enema showed the extent of the disease and accurately identified stenoses and fistulas, but underdiagnosed ulceration and overdiagnosed malignancy. Endoscopy allowed unequivocal detection of mucosal damage, especially ulceration, and was accurate in showing stenoses but sometimes failed to demonstrate fistulas. Moreover, in 25% of examinations it was impossible to examine the entire abnormal area.
.A
den Hartog Jager FC; Cohen P; van Haastert M.
.I 200533
.U
90002093
.S
Br J Radiol 9001; 62(741):813-6
.T
Relative safety of intravenous digital subtraction angiography over other methods of carotid angiography and impact on clinical management of cerebrovascular disease.
.P
JOURNAL ARTICLE.
.W
Data from a multicentre survey based on three London teaching hospitals on the relative safety and clinical utility of intravenous carotid digital subtraction angiography (DSA) over intra-arterial DSA and conventional carotid angiography are presented. The incidence of stroke during intra-arterial DSA was 0.7% (n = 538) and during conventional angiography was 0.8% (n = 780). The incidence of stroke during intravenous DSA was zero (n = 3710). When it constituted the initial investigation, intravenous DSA achieved a 93.8% replacement value over intra-arterial studies as a whole (n = 474) and 89% replacement value for patients having carotid endarterectomy (n = 99). It was also noted that the installation of DSA equipment at one unit coincided with a sixfold increase in the number of carotid angiographic examinations and an almost threefold increase in carotid endarterectomies.
.A
Stevens JM; Barter S; Kerslake R; Schneidau A; Barber C; Thomas DJ.
.I 200534
.U
90002094
.S
Br J Radiol 9001; 62(741):817-23
.T
Assessment of feature size abnormalities using receiver operating characteristic analysis.
.P
JOURNAL ARTICLE.
.W
The ability of an observer to detect variations in size of a geometrical image feature have been investigated using receiver operating characteristic (ROC) analysis. Three types of image were constructed using computer graphics: disc-shaped targets of variable radius, model chest radiographs showing a variable heart diameter and model arterial angiograms with variable vessel width. Five factors were investigated: observer experience, variation of detectability with theoretical signal-to-noise ratio, the prior probability of the presence of an abnormality, viewing distance, and uncertainty in the location of an abnormality. In all but one experiment, excellent agreement was found between measured detectabilities and the predictions of signal detection theory, providing an initial practice session was included for each observer. No significant variation in detectability was found using six different prior probabilities and two different viewing distances, and the reduction in detectability for a four-alternative location task was in good agreement with theoretical predictions. The high statistical efficiencies found for the detection of geometrical signals suggest that the levels of observer "internal" noise arising from decision-making processes during an ROC experiment are very low.
.A
Warren RC; Darwin CJ.
.I 200535
.U
90002096
.S
Br J Radiol 9001; 62(741):830-7
.T
The effects of single doses of X rays on the mechanical properties of pig skin in vivo.
.P
JOURNAL ARTICLE.
.W
Changes in the mechanical properties of pig skin have been studied in vivo, using a dermal extensometer, after irradiation with a single dose of 18 Gy of X rays. There was no significant change in the stiffness of irradiated skin, when compared with unirradiated skin, until 9 weeks after irradiation when the irradiated skin was significantly stiffer. This effect was also found at 12 and 15 weeks after irradiation. When the increase in skin thickness, as a consequence of oedema, was taken into account a significant increase in the unrelaxed elastic modulus of irradiated skin was only seen at 12 and 15 weeks after irradiation. There were no significant changes in force relaxation, after extension of the skin, over this time period. After the resolution of oedema, which was associated with a significant 20% reduction in the thickness of irradiated skin relative to unirradiated skin, the mechanical properties of irradiated skin were not markedly different from those of unirradiated skin. However, between 30 and 39 weeks after irradiation there was a further wave of dermal thinning, resulting in a total reduction in the thickness of irradiated skin relative to unirradiated skin of 26%. This was associated with a rapid rise in the skin stiffness and unrelaxed elastic modulus by approximately 65 and approximately 140%, respectively. It was only at these late times after irradiation that the force relaxation of the skin was modified significantly. At 9 and 12 weeks after irradiation the reduction in skin stiffness and the unrelaxed elastic modulus were dose related. Based on the percentage of fields showing a significant reduction in these biomechanical parameters, ED50 values of between 12 and 14.5 Gy were established. This would appear to be a sensitive method for assessing radiation-induced dermal changes since few gross changes are observed in this dose range.
.A
Baker MR; Bader D; Hopewell JW.
.I 200536
.U
90002097
.S
Br J Radiol 9001; 62(741):838-42
.T
Organ doses from cardiac and carotid digital subtraction angiography.
.P
JOURNAL ARTICLE.
.W
Estimates of mean organ doses from cardiac and carotid digital subtraction angiography (DSA) are obtained from measurements done using a Rando-Alderson tissue-equivalent phantom. Thermoluminescent dosemeter chips and discs were calibrated and used for all measurements in the primary and scattered radiation fields. Skin doses as well as mean doses received by the thyroid, lung, lens of the eye, breast, uterus and the ovaries were measured. A 30 degree right anterior oblique (RAO) cardiac DSA study produces a beam entrance dose of about 121 mGy at a rate of 0.48 mGy/frame. The highest mean organ dose from cardiac DSA was to the lung with a value of 14.4 mGy. The rest of the organs received doses below 1 mGy. In carotid DSA, the mean entrance doses resulted from the RAO, left anterior oblique, and the Towne's view projections give an average of 168 mGy at a rate of 8.4 mGy/frame. The highest mean organ dose from the three projections, 21 mGy, was received by the thyroid. The uterus and ovaries received the lowest doses from both procedures with values below 0.04 mGy. Patient and phantom surface exposures were compared using an exposure area product system. Hence, exposure conditions used for measuring organ doses on the phantom were adjusted to resemble those used for patients.
.A
Mustafa AA; Janeczek J.
.I 200537
.U
90002098
.S
Br J Radiol 9001; 62(741):843-8
.T
Soft-tissue effects of biliary extracorporeal shockwave lithotripsy in swine.
.P
JOURNAL ARTICLE.
.W
This study investigates the soft-tissue effects of biliary extracorporeal shockwave lithotripsy (BESWL) using a recently developed lithotripter, which consists of an electromagnetic shockwave generator and an integrated ultrasonic targeting system. Sixteen swine, evenly divided into four groups, underwent BESWL. One group had one BESWL session targeted on the gallbladder and another group had two BESWL sessions targeted on the gallbladder. The third group had one BESWL session targeted on implanted gallbladder stones and the fourth group had one BESWL session targeted on the region of the common bile duct (CBD). Half of each group were sacrificed on the day of lithotripsy and half 1 week later. Post-mortem examinations were performed. Each implanted gallstone had fragmented. There were no findings attributable to BESWL in 11 animals. Three animals had pulmonary haemorrhagic spots (the largest was 10 mm in diameter) and one had a submucosal CBD petechia; these findings were attributable to BESWL. In two animals, microscopic haemorrhage associated with bronchopneumonia (usually present in our pig population) was more prominent than usual. This was possibly attributable to BESWL. The swine's deep posterior costophrenic sulcus makes it difficult to avoid the lung base during BESWL in swine. We conclude that this BESWL device can fragment gallstones without causing clinically significant soft-tissue damage.
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Malone DE; Becker CD; Reich D; Quenville NF; Burhenne HJ.
.I 200538
.U
90002099
.S
Br J Radiol 9001; 62(741):849-53
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Squamous cell carcinoma of the base of the tongue: results of treatment in 115 cases.
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JOURNAL ARTICLE.
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Between 1976 and 1986, we treated 115 patients (mean age 53.8 years) with base of tongue carcinomas. The staging system used was the UICC TNM classification of 1979. Seventy per cent of the tumours were T3 or T4 and 42% had N2 or N3 lymph node. Locoregional treatment was irradiation alone (98/115) or surgery and post-operative radiotherapy (17/115). Sixty-seven patients received induction chemotherapy. Actuarial survival of the entire group at 3 and 5 years was 25 and 23%, respectively, and 3-year actuarial survival rates for T1, T2, T3 and T4 lesions were 42, 48, 20 and 17%, respectively. The local control rate at the primary site was 55% and 78% in the neck. Distant metastases occurred in 10% of patients and 8% had a second primary. Nodal status was the only other prognostic factor. The local control rate obtained with irradiation alone was not good. For limited T1 and T2 tumours, interstitial therapy or surgery should improve the local control rate.
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Calais G; Reynaud-Bougnoux A; Bougnoux P; Le Floch O.
.I 200560
.U
90002641
.S
Can Med Assoc J 9001; 141(7):673-6
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The specialty match: a necessity in the equitable resident selection process.
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JOURNAL ARTICLE.
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For many years directors of Canadian postgraduate specialty programs have selected candidates in an uncontrolled and haphazard way. Candidates and programs alike have therefore been unfairly treated. Since 1986 the Canadian Intern and Resident Matching Service has offered a centrally coordinated matching program to allow candidates to select specialty programs at centres of their choice and program directors to rate candidates. The result has been an effective method to achieve fairness in the selection of postgraduate trainees for participating Canadian specialty programs.
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Taylor B; Banner SR.
.I 200561
.U
90002642
.S
Can Med Assoc J 9001; 141(7):677-82
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Mortality rates among patients with end-stage renal disease in Canada, 1981-86.
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JOURNAL ARTICLE.
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We assessed the mortality rates by age, sex, race, blood type, primary diagnosis, treatment and transplantation history of 8432 patients in Canada for whom end-stage renal disease (ESRD) was diagnosed between 1981 and 1986. Significant differences in the probability of dying were found between those with and without diabetes mellitus, between those who had received a renal transplant and those who had not, between white and nonwhite patients and between various age groups. The mortality rates of the ESRD patients were at least three times higher than those of the general Canadian population. Primary diagnosis and treatment were significantly associated with the risk of dying among the ESRD patients. For those who had received a transplant, the length of time spent waiting for a transplant was positively associated with the risk of death from ESRD. Patients who had received peritoneal dialysis before transplantation had a higher risk of death than those who had received either hemodialysis (risk ratio 1.3) or transplantation (risk ratio 3.2) as the first treatment. No significant differences were found in the cause of death between those who had received peritoneal dialysis and those who had received hemodialysis. Almost half of the deaths among women without diabetes who had received a transplant were due to infection.
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Silins J; Fortier L; Mao Y; Posen G; Ugnat AM; Brancker A; Gaudette L; Wigle D.
.I 200562
.U
90002643
.S
Can Med Assoc J 9001; 141(7):685-91
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Chronic exposure to sour gas emissions: meeting a community concern with epidemiologic evidence.
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JOURNAL ARTICLE.
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For 25 years residents of a rural area in southwestern Alberta have complained of health problems attributed to sour gas emissions from nearby natural gas refineries. We undertook a large epidemiologic study of the current health status and the selected morbidity rates among 2152 people in the exposed area. We established two comparison groups: one was a demographically similar unexposed population and the other a demographically different group also exposed to sour gas emissions in another region. The methods included a cross-sectional survey of current residents and separate historical cohort studies involving registry linkage to investigate cancer incidence and all-cause mortality. The cross-sectional survey involved a comprehensive health questionnaire, standardized clinical examinations by physicians blinded to the subjects' symptoms and concerns, and several laboratory tests. We were able to contact just under 60% of the people who we knew had moved from each area since 1958 and found no evidence of selective migration for health reasons. Although the residents of the exposed area reported an excess number of symptoms and health problems there were no significant differences in the mortality rate, incidence of cancer, reproductive problems, major ailments, hair levels of arsenic and certain metals or respiratory function between the groups.
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Spitzer WO; Dales RE; Schechter MT; Suissa S; Tousignant P; Steinmetz N; Hutcheon ME.
.I 200563
.U
90002644
.S
Can Med Assoc J 9001; 141(7):693-7
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Management of Ontario children with acute lymphoblastic leukemia by the Dana-Farber Cancer Institute protocols.
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JOURNAL ARTICLE.
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There is ample evidence of the value of intensive therapeutic strategies in the management of acute lymphoblastic leukemia (ALL), the commonest form of malignant disease in children. Such a program, devised at the Dana-Farber Cancer Institute (DFCI), Boston, and incorporating high-dose L-asparaginase, was adopted in 1984 by the Children's Hospital at Chedoke-McMaster, Hamilton, Ont., and the Children's Hospital of Western Ontario, London. We describe the experience of these institutions in the treatment of 82 children with ALL, 19 of whom were switched to the DFCI protocols while in continuing first remission with other treatment programs to complete a minimum of 2 years of maintenance therapy; the remaining 63 children, who had recently diagnosed disease, were consecutively enrolled in the DFCI protocols. Each child was assigned at diagnosis to a category of risk for relapse and treated accordingly. There were no remission induction failures or deaths due to induction therapy among the patients with newly diagnosed disease. There were no differences in total or event-free survival rates between the patients in Hamilton and those in London or between those whose protocols were switched and those who were treated from the beginning with the DFCI protocols. With a median follow-up interval of 144 weeks the total survival rate was 95% and the event-free survival rate 88%. For patients at standard risk of relapse the event-free survival rate was 100%, for those at high risk the rate was 82%, and for those at very high risk the rate was 67%. If infants (all of whom suffered a relapse) are excluded from the last category the rate was 89%. These results were achieved with moderate toxic effects (except for two deaths, one of which was due to a therapeutic misadventure) and suggest that the prospect for cure in children with ALL. may now approximate 80%, a degree of success that demands that consideration be given to reducing total therapy, at least for children with standard-risk disease. Further follow-up will determine whether these high event-free survival rates will stabilize and meet the criteria for cure.
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Desai SJ; Barr RD; Andrew M; deVeber LL; Pai MK.