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Biomedical subjects

D M Thomas

Publications and source records attributed to D M Thomas.

At least 73 records · Page 4Linked to original sources

Peripheral nerve sheath differentiation in malignant soft tissue tumours: an ultrastructural and immunohistochemical study.

Thirteen soft tissue sarcomas with ultrastructural evidence of nerve sheath differentiation were investigated by immunohistochemistry. Three arose in a major nerve or nerve trunk and four patients had von Recklinghausen's neurofibromatosis. Ultrastructurally, 10 cases showed variable differentiation towards Schwann cells, two resembled perineurial cells and one tumour had features suggestive of both cell types. Immunostaining for S-100 protein was positive in eight Schwann cell tumours, negative in the other two Schwann cell tumours and negative in those with perineurial-like cells. No cases demonstrated epithelial membrane antigen, so that the existence of perineurial cells in malignant nerve sheath tumours remains immunohistochemically unsubstantiated; it may be that the perineurial-like cells are merely incompletely differentiated Schwann cells, with nerve sheath differentiation manifesting a continuous spectrum. Leu 7 was detected in four Schwann cell tumours, three of which were ultrastructurally well differentiated. Cytokeratin and desmin were demonstrated only in an undifferentiated pleomorphic area of one Schwann cell tumour. Electronmicroscopy can aid diagnosis by revealing nerve sheath differentiation in malignant soft tissue tumours without demonstrable S-100 protein.

Adolescent↗

Transforming growth factor alpha expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric carcinoma--an immunohistochemical study.

Using a monoclonal antibody (GF10) and a standard immunohistochemical technique, immuno-expression of transforming growth factor alpha (TGF-alpha) was found consistently within the differentiated compartment of normal adult human gastric mucosa. In 70% of mucosal samples exhibiting intestinal metaplasia there was more or less uniform TGF-alpha immunoreactivity throughout the intestinalized mucosa. Similarly, 60% of cases of dysplasia and 60% of gastric carcinomas showed strong immunoreactivity in most of the cells. However, whereas 93% of intestinal-type cancers showed strong immunoreactivity only 30% of the diffuse type were stained and then only weakly. Transforming growth factor alpha expression is thus a fairly regular feature of several types of differentiated gastric epithelia (normal, metaplastic, dysplastic and intestinal-type carcinoma), while its relative absence may be a factor in the histogenesis of the diffuse type of gastric carcinoma.

Gastric Mucosa↗

Intestinal lymphangiectasia associated with angiofollicular lymph node hyperplasia (Castleman's disease).

A patient presenting with predominantly gastrointestinal symptoms and a history of myocardial infarction was found to have ascites, hepatosplenomegaly, para-aortic lymphadenopathy, thrombocytosis, and a paraproteinaemia. A jejunal biopsy specimen showed lymphangiectasia and histology of the spleen and lymph nodes showed angiofollicular hyperplasia or Castleman's disease of the hyaline vascular type. This association has not previously been described and, moreover, systemic symptoms are unusual in this variant of Castleman's disease.

Castleman Disease↗

Immunoreactivity of transforming growth factor alpha in the normal adult gastrointestinal tract.

The immunolocalisation of transforming growth factor alpha (TGF alpha) in the normal human oesophagus and the gastrointestinal tract was elucidated using two different antibodies - Ab2, a monoclonal antibody reacting with part of the human TGF alpha molecule, and 26T a rabbit affinity purified polyclonal antibody raised against part of the rat TGF alpha peptide. There have been conflicting reports on the distribution of this growth factor in the gut. The results clearly showed that this peptide regulatory factor is confined to the luminal surface and foveolae in the stomach, restricted to the villous epithelium in the small intestine, and in the colon was seen in the upper one third of the crypt. This pattern indicates that the distribution of this peptide regulatory factor is within the differentiated compartment and indicates a role in differentiation besides its well known proliferative effects.

Adult↗

An electron microscopic and nuclear magnetic resonance spectroscopic evaluation of rabbit corneal epithelial wound healing.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy is a powerful method that can be used to measure levels of phosphorus metabolites in living tissue. To determine whether NMR measurements adequately describe and quantify the wound-healing process in corneal epithelium, 31P NMR spectroscopic and electron microscopic results were correlated. Dutch belted rabbit corneal epithelium was removed with a limbus-to-limbus scrape wound and sampled from 0-30 days postwounding. Four corneas were pooled for each NMR determination of corneal adenosine triphosphate (ATP). A minimum of three animals from each time point were processed for transmission and scanning electron microscopy (EM). Similar to previous studies, migrating cells completely closed the defect by 4 days postwounding. The epithelium continued to increase in thickness and hemidesmosome density was similar qualitatively to that in control animals by 10 days postwounding. The 31P NMR ATP values showed an increase toward control values after an initial 70-75% decrease, returned to within 90-95% of nonwounded values by 10 days, and returned to control values by 30 days. After these experimental values were obtained, the predictive value of the model was tested using platelet-derived growth factor (PDGF)-treated corneas. The PDGF-treated corneas showed NMR and EM results similar to day-10 untreated corneas by 5 days after wounding. These results demonstrated the feasibility of using 31P NMR spectroscopic measurements of ATP levels as a nondestructive technique for quantifying corneal epithelial wound healing.

Adenosine Triphosphate↗

Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique.

By using a modified polymerase chain reaction strategy, we have devised an approach to detect a K-ras oncogene mutated at codon 12 in the presence of 1000 normal alleles. This is a considerable improvement in sensitivity on previous assays. Application of this assay to 15 cholangiocarcinomas showed that all contained a K-ras mutation to codon 12 and that nine of the tumors contained two or more mutations. In 11 cases, mutations were present in less than 10% of the cells in the sample. In common with pancreatic adenocarcinomas, in which 75 to 95% of cases contain a mutation in K-ras, cholangiocarcinomas show a very high frequency of ras gene mutation, but within a tumor only a fraction of cells contain a ras mutation. The presence of multiple mutations and the low frequency of mutant alleles in the samples argue against K-ras mutations being the initiating genetic lesion in this tumor, but suggest that ras gene mutation is involved in the stepwise progression of neoplastic cells to full malignancy.

Adenoma, Bile Duct↗

Enalapril can treat the proteinuria of membranous glomerulonephritis without detriment to systemic or renal hemodynamics.

The effect of enalapril on renal hemodynamics and glomerular permselectivity was studied in eight patients with nephrotic syndrome secondary to biopsy-proven membranous glomerulonephritis. The patients received the drug in incremental doses (median, 5 mg) until 24-hour urinary protein excretion had decreased persistently by 30%. Median treatment duration was 6 weeks. Patients were studied three times: (I) after a 4-week run-in period, (II) on the final day of treatment, and (III) after a 4-week wash-out. Median 24-hour urinary protein excretion decreased on treatment from 10.45 g/d to 5.25 g/d and increased to pretreatment levels after the drug was stopped (P less than 0.05 for both changes). Fractional clearance of dextrans greater than 4.1 nm decreased on treatment, indicating both a reduction of macromolecules passing through the shunt pathway of the glomerular basement membrane (GBM) and a possible decrease in ultrafiltration coefficient. There were no significant changes in glomerular filtration rate (GFR), effective renal plasma flow (ERPF), or mean arterial blood pressure (MAP) throughout the study. The effect of enalapril in treating proteinuria appears therefore to be due to a specific intraglomerular action.

Adult↗

Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man.

1. The effects of the subcutaneous administration of a long-acting somatostatin analogue (octreotide) or of placebo on the splanchnic blood flow response to a mixed solid meal has been examined in eight normal subjects by using a transcutaneous Doppler ultrasound technique. Each subject was studied on two occasions more than 1 week apart. 2. On the control day, feeding had a pronounced effect on both superior mesenteric artery and portal venous blood flows, causing a peak rise of 82% in superior mesenteric artery blood flow at 15 min and of 75% in portal venous blood flow at 30 min post-prandially (P less than 0.001). Blood flows remained elevated 2 h after the meal. Pulse and blood pressure showed no significant changes from baseline. 3. Octreotide reduced fasting superior mesenteric artery blood flow by 59% (P less than 0.05) and portal venous blood flow by 49% (P less than 0.01) and blunted the normal post-prandial rise. Pulse and blood pressure did not change in response to either the injection or the ingestion of the meal. 4. Octreotide suppressed the release of insulin, glucagon and pancreatic polypeptide in response to feeding and resulted in post-prandial hyperglycaemia. 5. The mechanism of action of octreotide on splanchnic blood flow is uncertain. It may be mediated via a direct vascular effect or it may act via suppression of vasoactive intestinal hormones.

Adult↗

Experience with a new method for percutaneous renal biopsy.

Between January 1989 and August 1990 a new technique for percutaneous renal biopsy was evaluated in all patients undergoing native kidney biopsy in our hospital. The method combines the use of an automated biopsy device, disposable biopsy needles, and a needle guide attached to an ultrasound probe. This allows real-time ultrasound scanning throughout the procedure. All biopsies were performed by trainee nephrologists. The success of the technique was evaluated by analysis of histopathological data, and the complications of the procedure from case-notes and nursing records. During the study 192 biopsies were attempted, of which 188 (97.8%) were successful. For each biopsy a mean of 2.8 needle passes were required and 75% of these obtained cores of tissue. An average of 25 glomeruli (range 1-90) were seen per biopsy. Although microscopic haematuria was almost invariable, there were no episodes of frank haematuria and no blood transfusion or surgical intervention was required. The new method is simple, providing accurate localisation of the kidney coupled with direct visualisation of the biopsy, and results in a very high success rate. Intrarenal needle dwell time is kept to a minimum and there were only minor complications. This technique deserves more widespread use.

Adult↗

Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability?

OBJECTIVE: To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. DESIGN: Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. SETTING: Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. PATIENTS: 50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. MAIN OUTCOME MEASURES: Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. RESULTS: Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. CONCLUSIONS: The findings suggest that in the presence of atrial fibrillation physicians' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem.

Aged↗

Phosphorus-31 NMR study of the effects of hydrogen peroxide on young and old rat lenses.

31P-NMR spectroscopy was used to study the dynamic changes in young and old rat lenses under oxidative stress with hydrogen peroxide. Control spectra were recorded for young and old rat lenses using normal media. Oxidative stress spectra were recorded under the same conditions, except that the normal media also contained hydrogen peroxide at four different concentrations. With increasing H2O2 concentration in the perfusion media there was a corresponding decrease in the observed phosphorus metabolites, phosphorylcholine and ATP. There was significant difference in the rate of depletion of metabolites between the young and old rat lenses; old rat lens showed an ATP decrease almost double that for young rat lenses. Also, the 31P control spectrum of the old rat lens was different from that of the young lens. The NMR results showed the importance of comparison of old and young rat lenses under oxidative stress as a model for senile cataractogenesis.

Adenosine Triphosphate↗

Economic impact of motor vehicle restraints in Kentucky: a trauma center's experience.

Motor vehicle seat belts save lives and decrease the cost of care. Victims involved in motor vehicular accidents requiring ED evaluation and in-patient care were evaluated for seat belt usage. In addition to outcome parameters, the economic impact was assessed. During the five month study period, 38 (14%) restrained drivers and 238 (86%) unrestrained drivers were entered. Unrestrained drivers were more likely to be killed or disabled. The average cost of medical care for unrestrained drivers ($18,165) was significantly higher than that for restrained drivers ($7,634) (p less than .02). Twenty-eight percent of the unrestrained drivers' bills were paid with public funds. Assuming mandatory seat belt legislation would alter usage patterns as demonstrated in other states, the Commonwealth of Kentucky could save not only lives but millions of tax dollars.

Accidents, Traffic↗

The effect of an aldose reductase inhibitor on lens phosphorylcholine under hyperglycemic conditions: biochemical and NMR studies.

Phosphorylcholine (P-choline) is a precursor of the phospholipids in the lens membrane. A human lens normally contains approx. 1 mM P-choline but this is significantly lowered in some cataractous lenses. A normal rat lens contains a very high concentration (11 mM). We found that rat lens P-choline was depleted drastically when the lenses were exposed to hyperglycemic conditions either in culture, with galactose or xylose, or in vivo by streptozotocin-induced diabetes. The lens P-choline level was measured by fractionating the organic phosphates in the lens homogenate using an ion exchange column, or by quantitating the P-choline 31P NMR intensity in intact lenses. The results of both the chemical method and the noninvasive method agreed remarkably well. Besides the change in P-choline, the choline influx was also drastically reduced both in lenses from diabetic rats and in lenses incubated with 30 mM xylose. In addition, the ATP concentration was greatly diminished under similar conditions. The changes in P-choline, choline, and ATP could all be prevented in the presence of an aldose reductase inhibitor (ARI). It is thus concluded that these changes in phospholipid precursors may result from lenticular membrane defects caused by hyperglycemic stress. The effect of the lowered precursors on lipid biosynthesis was observed, and surprisingly showed a more rapid phospholipid-biosynthesis in the 2-week diabetic rat lens than in the 3-day diabetic rat lens.

Adenosine Triphosphate↗

Short-term effect of captopril on renal haemodynamics in chronic renal failure.

Glomerular filtration rate (GFR), effective renal plasma flow, and creatinine clearance were measured in ten patients with stable chronic renal failure (GFR less than 50 ml/min) before, during and after 1 month's treatment with captopril. Plasma angiotensin II decreased significantly during treatment (P less than 0.05) and increased after the drug was stopped. Renin concentration increased with captopril (P less than 0.02) and urine protein excretion decreased (P less than 0.05). Blood pressure did not change in any individual. There was no alteration in baseline GFR, effective renal plasma flow, or creatinine clearance, with or without captopril. Following a high-protein meal there was no increase in any of the measured renal haemodynamic parameters before, during, or after taking the drug. There was a significant increase in plasma creatinine while taking captopril (P less than 0.02) which reversed on cessation of the drug. These results suggest that in stable chronic renal failure the human renal microvasculature is unresponsive to inhibitors of angiotensin-converting enzyme.

Adult↗