Biomedical subjects
Publications and source records attributed to D W Thomas.
The formation of hypertrophic and keloid scars after cutaneous wounding is of particular relevance to the practice of maxillofacial surgery. This paper reviews current knowledge of the local and systemic factors underlying the formation of these scars and outlines the current and potential treatment modalities for these lesions.
Measurement of total-body calcium (TBCa) is important in the study of several medical conditions. Neutron activation analysis (NAA) is sufficiently precise for serial measurements, but in order to provide single, absolute determinations of TBCa, it requires a correction for body habitus. A method is described for the absolute determination of TBCa by comparing the total-body chlorine, obtained by NAA, with that obtained by stable bromine dilution. The method is applied to a group of thirty patients who had been treated for chronic renal failure, and significant differences are found between measured values of TBCa and those predicted for 'normal' healthy subjects. The overall experimental error in the absolute determination of TBCa is estimated to be 8%, for a dose equivalent of 3.1 mSv (based on skin dose, and a quality factor of 10 for neutrons).
Recent advances have been made in understanding the aetiology, diagnosis and treatment of Paget's disease of bone (osteitis deformans). The role of viruses in the pathogenesis of the disease has been extensively investigated, although no causative link has yet been demonstrated between infective agents and Paget's disease. Recent advances in the diagnosis of the disease have been made with increasing usage of radionucleotide imaging to determine the extent and distribution of the lesions. Treatment options have been extended with the emergence of the biphosphonates as potential main line therapeutic agents.
Paget's disease (osteitis deformans) and osteoporosis represent the commonest systemic bone disorders. Clinically Paget's disease may be mono-, or polyostotic, and is characterized by excessive and disorganized formation and resorption of bone. It may affect any of the facial bones, most notably the skull and the jaws. A case is described in which the only symptomatic manifestation of Paget's disease was mandibular prognathism. The pathogenesis, aetiology, and management are discussed.
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The purpose of this study was to see whether artificial acclimatization to cold would reduce the pressor response to noradrenaline (NA) as natural acclimatization has been shown to do, and whether it would induce nonshivering thermogenesis. Three white men were infused with NA at four dosage levels between 0.038 and 0.300 microgram.kg-1.min-1 (2-23 micrograms.min-1), before and after artificial acclimatization to cold and again 4 months later when acclimatization had decayed. Acclimatization was induced by ten daily cold (15 degrees C) baths of 30-60 min followed by rapid rewarming in hot (38-42 degrees C) water, and was confirmed by tests of the subjects' responses to whole-body cooling in air. Three control subjects also underwent the first and third tests. Acclimatization substantially reduced the pressor response to NA at 0.150 and 0.300 micrograms.kg-1.min-1, confirming earlier findings by the same technique in naturally acclimatized men, and its decay increased this response to beyond its initial levels (P < 0.05 for both changes). Acclimatization did not change the response to NA of heart rate, subjective impressions, skin temperature of finger and toe, pulmonary ventilation, or plasma free fatty acids and ketone bodies. At no time did NA increase oxygen consumption, or increase skin temperature or heat flow over reported sites of brown fat. These findings would seem to show that acclimatization to cold reduces sensitivity to the pressor effect of NA but does not induce nonshivering thermogenesis, and that the reduced sensitivity is replaced by a hypersensitivity to NA when acclimatization decays.
The in vivo expression and regulation of the LDL receptor of circulating mononuclear cells was studied using a sensitive spectrophotometric assay with low density lipoproteins conjugated to colloidal gold (LDL-gold). The high plasma cholesterol of familial hypercholesterolemic subjects was shown to be related to a low in vivo LDL receptor activity; cells from a homozygote had virtually no activity and those from 24 heterozygotes expressed 45% of the activity of cells from 35 normals. The average receptor activity of cells from 18 polygenic hypercholesterolemic (PH) subjects was not significantly different from normal but a low expression may have been a factor in six of these subjects. Simvastatin increased the LDL receptor activity of cells from the PH subjects by 70% while lowering their plasma cholesterol by 26%, but reducing the fat intake from 38% to 20% of energy and cholesterol from 239 to 96 mg/day had no effect on the receptor despite a 10% reduction in plasma cholesterol. Upregulation of the LDL receptor may therefore have been involved in the lowering of plasma cholesterol by simvastatin but not by the reduction in dietary fat and cholesterol.
A case is described of squamous cell carcinoma (SCC) of the lower lip in a patient receiving systemic immunosuppression. Contemporary theories on the aetiology of malignancy in such systemically immuno-compromised patients are discussed.
The aim was to assess relationships between increased aerobic fitness sustained over 4 years, and changes in blood pressure (SBP and DBP) and lipids. Measurements were made of BP, lipids, weight, and fitness in 1000 middle-aged men and women entering a fitness programme, and were repeated 2 and 4 years later. The 342 men and women selected for this 4-year follow-up were either consistent fitness "gainers" (improved by > 5%) or "non-gainers" (improved by < or = 5%) at 2 and 4 year stages. For men, comparisons of these groups and multiple regression analyses failed to show significant relationships between changes in fitness and risk factors over the 4 year period. For women, "gainers" improved more than "non-gainers" in SBP (by 4 mmHg, p < 0.03), HDL/cholesterol ratio (by 0.01 mmol l-1, p < 0.0001), and triglycerides (by 0.02 mmol l-1, p < 0.05); regression analyses resulted in a significant relationship between changes in fitness and SBP (B = 0.012, p < 0.05). The study gave weak support to the existence of causal relationships between aerobic fitness and CHD risk factors for women, and no support for men.
OBJECTIVE: To assess the contribution of protein-losing enteropathy to AIDS-associated hypoalbuminemia. DESIGN: Prospective assessment of patients with AIDS. SETTING: An urban county hospital (Los Angeles & University of Southern California Medical Center. USA). PATIENTS: Four groups of patients with AIDS were studied: (1) patients with normal serum albumin (> or = 3.9 g/dl) and normal bowel habits; (2) patients with normal serum albumin and diarrhea (> or = four loose or watery stools per day for > or = 2 weeks); (3) patients with hypoalbuminemia (< or = 3.0 g/dl) and normal bowel habits; and (4) patients with hypoalbuminemia and diarrhea. MAIN OUTCOME MEASURE: Fecal alpha 1-antitrypsin concentration was used as a measure of protein loss in the gut. RESULTS: Patients with hypoalbuminemia had a significantly higher mean fecal alpha 1-antitrypsin concentration than those with normal albumin (10.8 +/- 3.0 mg/g dry stool versus 2.4 +/- 0.4 mg/g dry stool; P < or = 0.001). Although mean fecal alpha 1-antitrypsin concentrations were similar in patients with and without diarrhea in the normal albumin group, patients with hypoalbuminemia and diarrhea had significantly higher levels of fecal alpha 1-antitrypsin than those with hypoalbuminemia and normal bowel habits (17.3 +/- 5.8 mg/g dry stool versus 4.6 +/- 1.0 mg/g dry stool; P = 0.009). Twelve out of 36 (33%) patients with normal albumin had elevation of fecal alpha 1-antitrypsin compared with 33 (70%) of 47 patients with hypoalbuminemia (P < or = 0.001). Linear regression analysis showed a significant negative correlation between serum albumin and fecal alpha 1-antitrypsin concentration (r = -0.38; P < or = 0.001). Fecal alpha 1-antitrypsin was significantly higher in patients with mucosal disease visualized at upper endoscopy or flexible sigmoidoscopy than in those without gross abnormalities (13.5 +/- 5.8 mg/g dry stool versus 2.4 +/- 0.7 mg/g dry stool; P = 0.005). CONCLUSION: Protein-losing enteropathy is common in patients with AIDS and may contribute to the development of hypoalbuminemia in these patients.
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Dietary protein-induced colitis is a frequent cause of rectal bleeding in infants. The exact pathogenic mechanism is unknown but the disorder has been thought to be due to an allergic response. Rectal mucosal edema and eosinophilia are typically found but there are no specific markers currently available. Because eosinophil degranulation, as evidenced by the release of major basic protein, has been implicated in hypersensitivity disorders, we aimed to assess major basic protein deposition as a marker of dietary protein-induced colitis occurring in young infants. Suction rectal biopsies from five infants aged 1 to 7 months with findings consistent with dietary protein-induced colitis were compared histologically with five age matched controls who underwent rectal biopsies to rule out Hirschsprung's disease. An established indirect immunofluorescent staining method was used to identify tissue major basic protein. Comparable rectal deposition of major basic protein was found for the controls and colitic patients. Mucosal eosinophilia but not mast cell content was more prominent in the colitic patients (P < .05) than in the controls. Some of the colitic infants had elevated serum IgE levels (1 of 5), positive RAST for milk (2 of 5), and peripheral blood eosinophilia (1 of 5). Our findings do not support the concept that dietary protein-induced colitis of infancy is due solely to an immediate hypersensitivity response. The results also indicate that major basic protein is probably not a marker or likely primary mediator of this disorder.
An improved gas chromatography-mass spectrometry method has been applied to the quantitation of both in vitro and in vivo products of lipid peroxidation in rat liver stimulated with carbon tetrachloride. The method avoids problems of autoxidation of unsaturated fatty acids during sample preparation, and the sensitivity permits assays on as little as 1 mg of tissue. This permits small samples of tissue to be obtained by biopsy from the same organ, thus making it possible to perform in vivo time studies on a single animal. Lipids from whole tissue or cell preparations are simultaneously extracted and reduced by catalytic hydrogenation and then saponified and derivatized to their pentafluorobenzyl esters and trimethylsilyl ethers. Quantitation is accomplished by negative ion chemical ionization gas chromatography-mass spectrometry, using either deuterated compounds or naturally occurring fatty acid metabolites as internal standards. Hydroxy fatty acids which result from reduction of the hydroperoxides of arachidonic and docosapentaenoic acids are found to increase within 20 min after exposure of liver or hepatocyte suspensions to carbon tetrachloride.
HIV use the CD4 molecule as their primary cellular receptor. Residues in the N-terminal domain (D1) of CD4 are crucial to HIV attachment through the gp120 envelope component. However, other regions of CD4 appear to be required subsequently for virus- and cell-cell fusion. Little is understood of the post-binding steps which may differ between HIV variants. We report a novel anti-CD4 mAb that does not block CD4/gp120 binding, but that does efficiently block both viral infection and cell-cell syncytia formation, and define its contact site as residues in CD4 D2 using both mouse/human CD4 chimeras and CD4 substitution mutants. We also investigated the basis for its antiviral effect. Using the CD4 D2 specific mAb, we identify another conserved step in HIV infection, as evidenced by its ability to neutralize a broad range of primary isolates and T cell-line passaged strains. Monovalent forms of the mAb were used to determine if its activity was due to masking of the D2 epitope, to steric inhibition, or bivalency. Our data indicate that both binding site and bivalency of the mAb underlie its potency. The need for bivalency is not simply explained by affinity, because monovalent forms can displace the intact mAb and reverse its protective effect. These results provide evidence that binding of the D2-specific mAb prevents structural alterations necessary for membrane fusion.
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We have compared the lipid and apolipoprotein values and the frequency of DNA polymorphisms of the apolipoprotein B gene detected with the restriction enzymes, Xba I and Eco RI in 122 patients with coronary heart disease (CHD) and 80 control subjects. The patients with coronary heart disease (CHD) were defined by > 70% stenosis in at least one major coronary artery whereas the controls showed no signs of coronary artery narrowing at angiography. When males and females were considered separately, differences in triglyceride, total cholesterol and high density lipoprotein-cholesterol (HDL-cholesterol) between CHD and control subjects were significant only for females. The polymorphism studies showed no significant differences between the control and CHD subjects except for a difference in the frequency in the females of the Xba I polymorphism (p < 0.05). The X1 allele (absence of the restriction enzyme cutting site) occurred significantly more often in the patient group than in the controls. Individuals with the X1X2 genotype had the highest serum total cholesterol whereas those with the X1X1 genotype had the lowest HDL-cholesterol value. Generally, the associations between the Xba I and Eco RI alleles and serum lipid levels were weak and inconsistent. Furthermore, even after careful selection of disease and control groups, a useful role for restriction fragment length polymorphism studies in assessing CHD risk in individual patients was not demonstrated.