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F Williams

Publications and source records attributed to F Williams.

At least 19 recordsLinked to original sources

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

Development of a bioartificial liver: properties and function of a hollow-fiber module inoculated with liver cells.

We have developed a bioartificial liver support system utilizing hollow-fiber bioreactor, plasmapheresis and microcarrier cell culture technologies. Liver cells were obtained through portal vein perfusion with ethylenediaminetetraacetate or ethylenediaminetetraacetate/collagenase. A mathematical model of mass transport in a hollow-fiber module, at various plasma flow velocities and system configurations, was developed. The bioartificial liver's ability to carry out specific differentiated metabolic liver functions was tested in vitro and in vivo. A reproducible large-animal model of acute ischemic liver failure was developed. Most major first-generation cyclosporine and 19-norterstosterone metabolites were isolated after substrate addition to the bioartificial liver in vitro. After bioartificial liver treatment for 6 hr (with dog or pig liver cells), dogs with acute liver failure had significantly lower serum ammonia and lactate levels and significantly higher serum glucose levels than did control animals treated with a bioartificial liver system inoculated with microcarriers alone. In addition, bioartificial liver-treated animals had significantly higher mean systolic blood pressures than did controls. Liver cell viability at the end of the 6-hr in vivo experiment was greater than 90%.

Animals

The failure of conventional methods to promote spontaneous transpyloric feeding tube passage and the safety of intragastric feeding in the critically ill ventilated patient.

Nasoenteral tube feedings are often recommended in critically ill patients when gastrointestinal tract function is intact. Conventional methods of placement include turning the patient on the right side and the use of drugs that stimulate peristalsis to promote transpyloric passage. A prospective study was initially performed to assess the success of conventional methods used to promote transpyloric feeding tube placement in patients requiring assisted ventilation admitted to the Surgical Intensive Care Unit (SICU) (Part I of the study). In 68 critically ill ventilated patients, placement of nasoduodenal feeding tubes was attempted. Successful transpyloric placement was achieved in only ten patients. There was no correlation between age, gender, admitting diagnosis, time of tube placement and successful placement. The second part of the study was initiated to assess the safety of nasogastric feeding in critically ill ventilated patients. Forty-two patients admitted to the SICU were considered candidates for gastrointestinal tract feeding and were fed through the gastric route. Twenty-five patients reached enteral feeding goal rate within 72 hours, while 34 patients achieved goal rate by five days. Eight patients required total parenteral nutrition to meet nutritional needs because of an inability to achieve adequate nutritional support enterally. There were 11 complications noted in ten patients, including one episode of aspiration pneumonia. The presence of complications was not related to age, gender, admitting diagnosis, infusion method or type of formula used. Duodenal intubation using conventional methods in critically ill ventilated patients is unsuccessful in most patients. Nasogastric feeding in this group of patients can be safely administered in selected instances.

Critical Illness

Parasympathetic nuclei.

A series of experiments in monkeys using the fluorescent tracer substances Fast Blue and Nuclear yellow as well as wheat germ agglutinin-horseradish peroxidase injected into the ciliary ganglion has demonstrated labeling in 3 distinct regions of the mesencephalon: (1) anterior median nucleus; (2) Edinger-Westphal nucleus; and (3) the nucleus of Perlia. Further it was shown that the caudal extent of the Edinger-Westphal nucleus reaches the level of the central caudal nucleus of the somatic complex and that the lateral visceral column divided into a major and accessory column at the junction of the middle and posterior one-third of the somatic complex.

Amidines

Incidental lesions noted on magnetic resonance imaging of the brain: prevalence and clinical significance in various age groups.

With the advent of magnetic resonance imaging (MRI) of the brain, a large number of incidental lesions (ILs) are being identified. The prevalence and clinical significance of these ILs are not known. The MRI and clinical records of 86 consecutive patients who underwent technically satisfactory brain imaging at a large urban referral center were reviewed. Patients with definite or probably demyelinating disease were excluded. Incidental lesions were defined as parenchymal areas of increased signal intensity on T2-weighted imaging, which could not be directly explained by the patient's current clinical diagnosis, neurological status, or computed tomographic (CT) scan. The ILs were noted and graded according to size, multiplicity, and location and were correlated with age, clinical presentation, CT scan findings, and risk factors for cerebrovascular disease. One or more IL were identified in 22% of patients under 40 years of age, in 57% of patients 41 to 60 years of age, and in 90% of patients over 60 years of age. Large patches of confluent ILs were not encountered in any patient less than 40 years of age; they were present in 10% of patients 41 to 60 years of age, and in 30% of patients over 60 years of age. The incidence of severity of ILs correlated significantly with age (P less than 0.0005) and with risk factors for cerebrovascular disease (P less than 0.02). Patients with most severe ILs also had areas of vague periventricular leukomalacia on the CT scan. The clinical significance of incidental MRI lesions in various age groups is discussed in detail.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent