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Biomedical subjects

S Lester

Publications and source records attributed to S Lester.

At least 55 records · Page 3Linked to original sources

Evolution in HLA-DRB1 and major histocompatibility complex class II haplotypes of Australian aborigines. Definition of a new DRB1 allele and distribution of DRB1 gene frequencies.

The distribution of HLA-DRB1 alleles was studied in Australian aborigines from different parts of Australia. There were significant differences in the frequencies of DRB1*0412, 1409, and 1410 between the Central Desert and Yuendumu populations and the previously reported Cape York and Kimberley aboriginal populations. A new DRB1 allele, DRB1*1414, present at low frequency in the Central Desert population, was identified. DRB1*1414 appears to be closely related to DRB1*1407 and is proposed to have arisen by intragenic recombination. A novel DR-DQ haplotype, DRB1*1402-DRB3*0101-DQA1*0501-DQB1*0402, was also identified. This haplotype may be ancestral to the DRB1*1409-DQB1*0402 haplotype present in these populations. The presence of alleles and haplotypes apparently confined to Australian aboriginal populations and differences in the distribution of these alleles in different populations suggests that evolution has occurred in the class II region in the period since colonization of Australia, an estimated 50,000 years ago.

Amino Acid Sequence↗

Iododeoxyuridine (IUdR) combined with radiation in the treatment of malignant glioma: a comparison of short versus long intravenous dose schedules (RTOG 86-12).

PURPOSE: To evaluate the toxicity and tumor efficacy of the halopyrimidine IUdR (NSC #39661, IND 22475) as a chemical modifier of radiation response when used in a high dose short time infusion versus the acceptable 4 day infusion. METHODS AND MATERIALS: In August 1987 we initiated a prospective study in patients with newly diagnosed anaplastic astrocytoma and glioblastoma. The study was designed to have a fixed dose of radiation (60.16 Gy = 1.88 Gy in 32 fractions in 6.5 weeks) but varying the dose schedule of IUdR, keeping the total dose between 21 and 24 g/m2. IUdR was delivered in a 96, 48, or 24 hr continuous intravenous infusion per week for 6.5 weeks during radiation treatment. RESULTS: The study was closed for patient accrual on October 1, 1991. Twenty-two patients were treated on the 96 hrs, 32 on the 48 hr and 25 on the 24 hr schedules. The incidence of glioblastoma ranged between 68 and 75% in the three arms. Seventy percent of the patients had a Karnofsky of 80-90% at the onset of treatment. Over 50% of the patient population were under age 55. Drug tolerance was related to the duration of the IUdR infusion. Toxicities were most pronounced in the 96 hr IUdR infusion schedule where 27.4% of the patients reported a grade 3 drug toxicity. No fatal or grade 4 toxicities were observed. More patients on the 24 and 48 hr schedule received at least 80% of the IUdR dose specified per protocol. We did not observe a trend in acute normal tissue radiation reactions in any of the three arms. The median survivals calculated from the Kaplan-Meier plot are 13.4, 10.5, and 11 months, respectively, for the 96, 48, and 24 hr infusions. The Cox Proportional Hazards model showed that any difference in survival can be attributed to histological grade, type of previous surgery and, to some extent, age of the patient. Dose schedule was not a significant predictor of survival, although statistically nonsignificant trend toward longer survival is seen in those patients with glioblastoma treated in the "long" 4 day schedule. CONCLUSION: Overall, our treatment combination, particularly for patients with glioblastoma, has not shown convincing evidence of an improvement in survival. Of interest, however, it is the 2 year survival rate of 68% for patients with anaplastic astrocytoma. In our experience, the administration of IUdR is laborious, time consuming and with bothersome acute gastrointestinal and hematological toxicities.

Adolescent↗

Musculoskeletal manifestations in beta 2-microglobulin amyloidosis. Case discussion.

The cases presented illustrate some of the typical (case 1) and less common (case 2) clinical features of beta 2m amyloidosis. The accumulation of beta 2m amyloid in tissues is a potentially severe complication of dialysis-treated chronic renal failure. Beta 2m amyloidosis has been shown to have distinct clinical, radiologic, and pathologic features. The pathogenesis of this condition is not yet clearly understood, and recommendations for the clinical management of these patients at present are limited to recognition of the disease and symptomatic treatment. Further insights into the biology of this disease should lead to new strategies for prevention and treatment.

Aged↗

Utility of high-resolution ultrasound for the diagnosis of dialysis-related amyloidosis.

OBJECTIVE: To evaluate the utility of real-time, high-resolution ultrasound of the shoulder in the diagnosis of dialysis-related amyloidosis. METHODS: We performed a case series study of 2 groups of patients seen at a referral-based clinic in a tertiary care hospital. The shoulders of 13 patients with normal renal function and of 38 patients receiving long-term hemodialysis were studied by real-time, high-resolution ultrasound. All hemodialysis patients were evaluated clinically for the presence of dialysis-related amyloidosis. Surgical specimens of joints were available for all 13 patients with normal renal function and for 17 of the 38 hemodialysis patients. These specimens were evaluated for the presence of beta 2-microglobulin (beta 2m) amyloid by Congo red and immunohistochemical staining. RESULTS: Two ultrasonographic findings were selectively observed in the dialysis patients with clinical and histologic evidence of beta 2m amyloid in comparison with patients with normal renal function and no evidence of amyloid: rotator cuffs greater than 8 mm in thickness and echogenic pads between muscle groups of the rotator cuff. The presence of at least 1 of these 2 findings corresponded to the presence of clinically and histologically evident beta 2m amyloid with a sensitivity of 79% and a specificity of 100%. When additional patients without surgical specimens for histologic confirmation of amyloidosis were included, the sensitivity of these 2 sonographic findings was 72% and the specificity was 97%. CONCLUSION: Real-time, high-resolution ultrasound is a relatively sensitive and highly specific noninvasive adjunct to the clinical diagnosis of beta 2m amyloidosis in patients receiving long-term hemodialysis.

Adult↗

Multimodality imaging and intracranial EEG display for stereotactic surgery planning in epilepsy.

We describe a computer program for stereotactic surgery planning based on multimodality imaging and the display of intracranial EEG data in relation to anatomical data. The program is primarily designed to be used by surgeons to assist them in localizing brain structures and plan the safe and accurate insertion of surgical tools and depth electrodes. The mathematics underlying these concepts are briefly described. Estimates of the accuracy of the procedures are calculated and made available to the user. An extension of the program was developed to integrate intracranial EEG data with conventional images in order to help the neurologist and neurosurgeon in visualizing the EEG data in relation to the anatomy. It can be used to visualize the measured EEG voltages, or processed signals such as the application of the tetrahedral field calculation, which provides an extension of conventional bipolar EEG to 3 dimensions.

Brain↗

Nosocomial spread of an amikacin resistance gene on both a mobilized, nonconjugative plasmid and a conjugative plasmid.

Resistance to amikacin among members of the family Enterobacteriaceae at a hospital in Venezuela rose from 2% in 1979 to 5% in 1984 and 10% in 1985 as amikacin usage rose 20-fold to exceed gentamicin usage. Resistance to gentamicin remained at 25 to 27%. We examined the plasmids from 21 isolates obtained in 1984 and 1985. Nine of eleven in 1984 and three of ten in 1985 carried aacA and sul on a 3.8-kb BamHI fragment of pBWH300, a 10.4-kb nonconjugative plasmid that had been mobilized into strains of six species by at least two different coresident conjugative plasmids. Six 1985 isolates of two species carried these genes on a similar BamHI fragment of the 104-kb conjugative plasmid pBWH303. One isolate in 1984 and one in 1985 carried the 69-kb conjugative plasmid pBWH301, which had aacA as the promoter-proximal gene of an operon that also encompassed the cat and aadB resistance genes. Another conjugative plasmid, pBWH302, was found in a single isolate. It carried a different aacA allele on the functional transposon Tn654, which appeared to be closely related to Tn1331, a transposon previously isolated in Argentina and Chile. Increased selection may thus have led to dissemination of an endemic aacA allele on two endemic plasmids, one spread by mobilization, with occasional intrusion of additional aacA alleles from outside.

Alleles↗

Mixed lymphocyte reaction and graft survival in forty cadaveric renal transplants.

The value of the MLR in predicting graft outcome was evaluated in forty cadaveric grafts. The MLR was assessed by the one and two way stimulation index (SI), the relative response (RR), and the stabilized relative response (SRR). Graft function was assessed by function at 3 and 6 months after transplantation, and a rejection grading based on the number and severity of rejection episodes during the first 3 months after transplantation. No correlation was found between the MLR and graft outcome in these patients.

Cadaver↗

Clinical and pathologic features of breast cancers in women treated for Hodgkin's disease: a case-control study.

The goal of this study was to assess whether there are clinical or pathologic differences between radiation-associated breast cancers developing after treatment for Hodgkin's disease and spontaneously arising breast cancers. Clinical and pathologic data were reviewed for 26 Hodgkin's disease patients who received irradiation and subsequently developed breast cancer (cases) and 26 age- and stage-matched patients with sporadic breast cancers (controls). The median age at diagnosis of Hodgkin's disease was 21 years (range 11-40 years), and the median interval between Hodgkin's disease and breast cancer diagnosis was 15 years (range 4-27 years). There were no differences between cases and controls with regard to clinical factors. Cases had a lower frequency of histologic grade III tumors (38% versus 65%, p = 0.09) and moderate to marked mononuclear inflammatory cell reaction (11% versus 35%, p = 0.03). When these covariates were combined, grade III tumors in conjunction with mononuclear inflammatory cell reaction were also seen less frequently in the case group than in the control group (11% versus 31%, p = 0.06). Seven cases developed additional cancers, but no additional cancers developed in the control group (p = 0.01). Patients who developed breast cancers after Hodgkin's disease did not differ from patients with spontaneous breast cancers, with regard to clinical factors. However, the lower frequency of high-grade tumors and moderate to marked mononuclear inflammatory cell reaction among the cases suggests that radiation-associated breast cancers may differ from spontaneously arising cancers in their pathogenesis. Cases appeared to be at increased risk of developing additional cancers, but we cannot exclude surveillance as a possible contributing factor.

Adolescent↗

Vaccine site-associated sarcomas in cats: clinical experience and a laboratory review (1982-1993).

Recent information regarding vaccine site-associated sarcomas in cats suggest a relationship to either feline leukemia virus or rabies vaccines. The authors' initial case was in a cat that had received neither of these vaccines. Review of the available hospital records revealed an increasing number of vaccine site-associated sarcomas, none of which were related to feline leukemia virus vaccines. Only one was related to the use of a rabies vaccine, and this tumor occurred in the thigh as opposed to between the shoulder blades. The laboratory data supported an increasing incidence of vaccine site-associated sarcomas, the majority of which occurred in the interscapular area and were associated with routine prophylactic vaccinations.

Animals↗