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Biomedical subjects

F Williams

Publications and source records attributed to F Williams.

At least 55 records · Page 3Linked to original sources

HLA class I DNA typing of 215 "HLA-A, -B, -DR zero mismatched" kidney transplants.

DNA typing for HLA class II improves the typing quality and this was shown previously to be relevant for kidney graft survival. In this project we addressed the question whether molecular typing for HLA class I also increases the efficacy of HLA matching in kidney transplantation. 215 HLA-A,-B,-DR zero-mismatched donor/recipient pairs as defined by serological typing were selected. Retrospective HLA-A and HLA-B typing was performed both by the PCR-SSP and the PCR-SSOP method. DNA typing for HLA-A revealed discrepant results to serology in 5.7% of the donors and 2.8% of the recipients. HLA-B typing discrepancies were found in 6.6% of the donors and 5.6% of the recipients. 10.4% of the donors and 6.5% of the recipients showed either an HLA-A or an HLA-B discrepancy Nearly one-third of the HLA-A discrepancies affected A19 splits. The most common reason for HLA-A discrepancies was the erroneous assignment of serological blanks, whereas HLA-B errors were caused mainly by the assignment of incorrect specificities. DNA typing allowed the definition of HLA-A and -B split specificities in all 118 "splitable" cases for which only broad specificities were reported based on serological typing. A total of 183 DNA class I compatible transplants had a 15% higher one-year graft survival rate than 32 transplants for which DNA typing revealed a class I incompatibility

DNA Probes, HLA↗

Molecular typing of HLA class I and class II antigens in Indian kala-azar patients.

HLA has been shown to be associated with many diseases. To find out whether host genetic factors like the HLA are involved in susceptibility to kala-azar (visceral leishmaniasis) in India, we formulated an association study with genetically related controls. All samples were typed by PCR SSOP (sequence specific oligonucleotide probes) for HLA class I (A and B) and class II (DR) antigens. The test of association we used was the transmission disequilibrium test (TDT). No significant evidence for association with any of the three HLA loci was obtained.

Disease Susceptibility↗

Defendants are clueless--the 30-day psychiatric observation.

OBJECTIVE: To investigate the understanding and expectations of defendants referred to Valkenberg Hospital for 30-day observation. DESIGN: Defendants referred for 30 days of psychiatric assessment were surveyed by means of a semi-structured interview within 3 days of admission. PARTICIPANTS: One hundred consecutive referrals from the Western, Northern and Eastern Cape were considered; 88 were eventually entered into the study. RESULTS: All defendants were generally ignorant of the reasons for referral, but had a good understanding of court procedure and wrongfulness. Mentally ill subjects differed only in their not being able to distinguish between a guilty/not guilty plea. Most did not have legal representation, did not personally request the assessment and denied guilt of the alleged offence. CONCLUSIONS: Mental illness affects triability but not necessarily criminal responsibility. Disturbingly, most defendants were without legal representation and were unaware of the purpose, implications and possible outcomes of psychiatric observation. It is imperative that the legislation governing these aspects be reviewed.

Adolescent↗

Long-range PCR amplification as an alternative strategy for characterizing novel HLA-B alleles.

We have developed a simple, rapid and reliable method for specifically amplifying and cloning full-length HLA-B genes from genomic DNA. Using this methodology we characterized three alleles of interest at the molecular level. Two of the alleles appeared in our routine class I PCR-SSOP typing system, a variant of B*5801 found in the Daudi cell line and RCE 56 and a variant of B*4101 found in a number of volunteer donors on our Bone Marrow Donor Registry. The third, a variant B35 allele found in RCE 80, was first identified as unusual by serology. Our sequencing analysis of exon 2 and exon 3 identified two of these alleles as the recently reported novel HLA-B*5802 and HLA-B*4102 alleles, while the third represents a new B35 allele officially designated B*3513.

Alleles↗

The diffuse infiltrative lymphocytosis syndrome. Clinical and immunogenetic features in 35 patients.

OBJECTIVE: To study the epidemiological, clinical, serological and immunogenetic features of the diffuse infiltrative lymphocytosis syndrome (DILS). DESIGN: Consecutive series of 35 patients with DILS diagnosed from 1992 to 1995 in a cohort of 4100 outpatients infected with HIV-1. METHODS: Thirty-five individuals with DILS were ascertained from this cohort and followed for 720 patient-months. Clinical, serological and immunogenetic features of these patients were studied and their demographics were compared with the rest of the outpatient population. RESULTS: DILS was found to be more prevalent in African Americans (60%) than in Caucasians (26%) or Mexican Americans (14%) [odds ratio (OR), 2.32; 95% confidence interval (CI), 1-12-4.81; P = 0.02] and in persons with male-to-male transmission of HIV-1 (71%) (OR, 2.82; 95% CI, 1.29-6.29; P = 0.007). All patients had bilateral parotid gland enlargement. The majority had sicca symptoms. The most common extraglandular sites of disease were lung (31%), muscle (26%), and liver (23%). Four patients had biopsy-proven polymyositis. Thirteen patients met the 1993 Centers for Disease Control and Prevention case definition of AIDS. Sixteen (52%) patients expressed human leukocyte antigen (HLA)-DRS (DRB1*1102), DR6 (DRB1*1301, *1302), or DR7, and 11 (36%) expressed HLA-DR2. CONCLUSIONS: DILS is more common in African Americans and in persons with male-to-male transmission of HIV-1. HIV-associated polymyositis appears to occur in the setting of DILS.

Adult↗

Modification of an HLA-B PCR-SSOP typing system leading to improved allele determination.

Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type.

Alleles↗

Cardiovascular risk reduction: a randomized trial of two health promotion strategies for lowering risk in a community with low socioeconomic status.

AIM: To compare the effects of information pamphlets with those of group counselling on cardiovascular risk among individuals from a community with low socioeconomic status. METHODS: Risk factors for coronary heart disease were assessed in 1131 men and women from a community with low socioeconomic status in suburban Melbourne. Individuals deemed to be at moderate risk, on the basis of an integrated risk score greater than 65, were asked to participate in a randomized trial comparing two simple interventions designed to reduce cardiovascular risk. One hundred and sixty-four individuals were randomly assigned to group A (n = 85) and participated in a single group counselling session lasting between 1.5 and 2.0 h. Group B (n = 79) received a specially prepared pamphlet that provided brief written information concerning risk-factor modification. Both groups were asked to attend a follow-up assessment of risk factors 3 and 6 months after entry. RESULTS: There were no significant difference in the change in risk-factor levels between those receiving information pamphlets and those attending the group counselling session after 3 or 6 months of follow-up. Small but significant decreases (P<0.05) were seen in systolic and diastolic blood pressures (-5/4 mmHg for group A, -5/3 mmHg for group B), total plasma cholesterol level (-0.30 mmol/l for groups A and B) and overall coronary risk score (-14.4 and -13.9 for groups A and B, respectively). Body weight remained unchanged during the study period in both groups. CONCLUSION: Screening together with 1.5-2h group counselling had no more influence on cardiovascular risk factors than screening together with provision of information pamphlets in a population with low socioeconomic status.

Adolescent↗

Physiological responses during shipboard firefighting.

This study determined the level of heat strain experienced by U.S. Navy personnel while combating fires aboard a damage control research ship. Male volunteers (n = 9), wearing the standard Navy firefighting ensemble, were recorded for core temperature (Tre), skin temperatures (weighted mean, Tmsk), and heart rate (HR) during three fire test days. During the tests, air temperatures in the compartment containing the fire to be extinguished averaged 470 +/- 170 degrees C, while air temperatures in the compartment from which the fire was fought ranged from 40 to 125 degrees C. Dressing in the ensemble and execution of preliminary firefighting activities led to a gradual increase in Tre, Tmsk, and HR; while during active firefighting, Tre, Tmsk, and HR increased rapidly. For all tests, the rate of Tmsk rise (8.73 degrees C.h-1) exceeded the rate of Tre rise (2.95 degrees C.h-1), leading to convergence of these values. Average peak values for all tests were: Tre, 39.2 +/- 1.0 degrees C; Tmsk, 39.5 +/- 0.9 degrees C; body heat storage (HS), 2.02 +/- 0.77 kcal.kg-1; rate of HS during firefighting, 170 +/- 92 kcal.m-2.h-1; HR, 186 +/- 13 bpm. Our findings quantify the limits of tolerance of heat strain encountered during shipboard firefighting.

Adult↗

Combination chemotherapy in refractory immune thrombocytopenic purpura.

BACKGROUND: Chronic idiopathic thrombocytopenic purpura is a destructive thrombocytopenia caused by an autoantibody. About 80 percent of patients with chronic idiopathic thrombocytopenic purpura have remissions after either corticosteroid therapy or splenectomy. Some patients with resistant disease respond to other agents, but a substantial group are refractory to therapy. METHODS: We used combination chemotherapy to treat 10 patients with refractory immune thrombocytopenia. An average of 6.8 (range, 3 to 10) previous therapies, including corticosteroids and splenectomy, had been unsuccessful in these patients. The patients received from three to eight cycles of therapy consisting of cyclophosphamide and prednisone combined with either vincristine (one patient), vincristine and procarbazine (four patients), or etoposide (six patients, including one patient who received four cycles each containing procarbazine and etoposide). RESULTS: Among the 10 patients, 6 had complete responses (platelet count, > 180,000 per cubic millimeter); of these, 4 patients had responses that persisted for more than 11, 30, 54, or 126 months, 1 had a relapse 9 months after therapy but had a remission with further therapy and remained in remission for 48 months before dying of an unrelated illness, and another relapsed just before her fifth course of therapy. Two patients had partial responses (platelet count, > 50,000 per cubic millimeter); the platelet counts in one remained stable for more than nine months after the end of therapy, and the other patient relapsed. The remaining two patients had no response. Complete responses were associated with a disappearance or marked decrease in the level of platelet-associated autoantibody. CONCLUSIONS: Combination chemotherapy is beneficial in some patients in whom immune thrombocytopenia is refractory to corticosteroids and splenectomy.

Adult↗

Evaluation of shipboard formation of a neurotoxicant (trimethylolpropane phosphate) from thermal decomposition of synthetic aircraft engine lubricant.

MIL-L-23699 lubricants that are composed principally of trimethylolpropane triheptanoate (TMP) and tricresyl phosphate (TCP) have been shown to form a neurotoxicant, trimethylolpropane phosphate (TMPP), during pyrolysis and/or combustion. Mechanistically, TMPP is thought to irreversibly inhibit the GABA-mediated inhibitory response and thereby produce epileptiform clonic/tonic seizures with convulsions followed by death. Thermal decomposition of MIL-L-23699 lubricant produces TMPP under laboratory conditions, but this product has not been detected in the workplace following actual fires. This study has examined whether TMPP is produced during an actual shipboard fire by placing the synthetic lubricant in a fire environment aboard the ex-U.S.S. Shadwell, Mobile, Alabama. Both biological and chemical analyses were performed on the thermally decomposed lubricant to ensure detection of the neurotoxic material. Under the conditions of this study, the formation of TMPP during a shipboard fire was confirmed. The implications of this finding for safe management of post-fire cleanup are discussed.

Bridged Bicyclo Compounds, Heterocyclic↗