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Biomedical subjects

D J Thomas

Publications and source records attributed to D J Thomas.

At least 163 records · Page 9Linked to original sources
PubMed1989

Stabilisation of cathepsin E by ATP.

The hydrolysis of 3 distinct substrates by cathepsin E from human red blood cells and gastric mucosa was measured in the presence and absence of physiologically relevant concentrations of ATP. At pH values below about 5.0, the nucleotide was without effect. However, at pH 5.8, whereas cathepsin E was virtually inactive by itself, it was restored to full activity (kcat) by ATP and the non-hydrolysable methylene-ATP analogue. At still higher pH values, kcat progressively diminished but significant levels of cathepsin E activity were readily detectable at pH 7.0. The specificity of this stabilisation effect was examined.

Adenosine Triphosphate↗
PubMed1989

Influence of age upon the metabolism of zinc in livers of C57BL/6J mice.

The kinetics of accumulation and loss of zinc from the liver following subcutaneous administration of 10 mg of zinc per kg were examined in young adult (6 months old) and old (24 months old) male C57BL/6J mice. After zinc treatment, total liver zinc concentrations rose equally in both groups and returned to basal levels at 96 h post treatment. However, differences were found in the subcellular distribution of zinc in these two age groups. The concentration of zinc in the cytosolic fraction (104,000 g supernate) prepared from the livers of old mice attained its maximum at 24 h post treatment. In contrast, the concentration of zinc in the cytosolic fraction of liver from young adult mice peaked at 48 h post treatment. This difference in accumulation of zinc in the cytosol was reflected by differences in the binding of zinc to metallothionein, a cytosolic transition metal binding protein. In old mice the highest amounts of zinc bound to metallothionein were found at 24 h post treatment: in young adults the maximal zinc binding to this protein occurred at 48 h post treatment. Examination of the relationship between cytosolic zinc contents and the binding of zinc to metallothionein in young adult and old mice suggested similar regulatory processes in the two age groups. Thus, age-dependent differences in accumulation and loss of zinc from the cytosolic fraction of liver probably reflect factors other than differences in regulation of the synthesis of metallothionein by this essential metal.

Age Factors↗
PubMed1989

Brain dehydration and neurologic deterioration after rapid correction of hyponatremia.

We made rats severely hyponatremic, varying the rate of onset and duration of the disturbance, and then compared rapid correction to slow correction. An acute fall in the plasma Na to 106 mEq/liter within seven hours caused seizures and coma, but these findings resolved and survival was 100% after either rapid or slow correction. A more gradual fall in plasma Na to 95 mEq/liter in three days caused neither seizures nor coma. Measurements of brain water and electrolytes showed that adaptive losses of brain Na and K (maximally depleted within seven hours) and slower losses of non-electrolyte solutes progressively reduced brain edema. After three days of hyponatremia, rapid correction to 119 mEq/liter with 1 M NaCl or to 129 mEq/liter by withdrawing DDAVP caused brain dehydration because lost brain K and non-electrolyte solutes were recovered slowly. This treatment was followed by a delayed onset of severe neurologic findings, demyelinating brain lesions and a mortality rate of over 40%. Slow correction (0.3 mEq/liter/hr) avoided these complications and permitted 100% survival. We conclude that the rat adapts quickly to hyponatremia and can survive with extremely low plasma sodium concentrations for prolonged periods. Although rapid correction is well tolerated when hyponatremia is of brief duration, it may cause brain damage in animals that have had time to more fully adapt to the disturbance.

Animals↗
PubMed1989

Neonatal nosocomial infections.

Prevention of infection in the high-risk infant presents a challenge for all members of the health care team. The infant's condition must be constantly assessed for risk factors, and a plan of care must be developed to reduce that risk. That plan requires a thorough understanding of the multiple factors (the infant host, potential pathogens, and therapeutic procedures) involved in neonatal infections and strict adherence to infection control procedures.

Critical Care↗
PubMed1989

Inhibition of enoxacin absorption by antacids or ranitidine.

Ten normal volunteers participated in a randomized, five-way crossover study to determine the effect of concurrent enoxacin and antacid or ranitidine administration on enoxacin absorption. The bioavailability of a single oral 400-mg enoxacin dose was significantly decreased, by 73 and 49%, when Maalox TC was administered 0.5 and 2 h before enoxacin, respectively. Enoxacin bioavailability was not significantly altered when the antacid was given 8 h before or 2 h after enoxacin administration. Ranitidine, administered intravenously 2 h before enoxacin, also significantly decreased enoxacin bioavailability, by 40%. The correlation between the proximity of antacid administration and the magnitude of the decrease in enoxacin bioavailability supports complexation as the mechanism of the antacid-enoxacin interaction. However, reduction of enoxacin bioavailability by ranitidine suggests that elevated gastric pH may also play a role in the antacid-enoxacin drug-drug interaction.

Adolescent↗
PubMed1989

Lymphoplasmacytoid lymphoma elaborating lambda chain paraprotein with amyloid deposition in Sjögren's syndrome.

A woman presented with painful enlargement of her parotid and submandibular glands. She was shown to have the previously unreported combination of idiopathic thrombocytopenic purpura, Sjögren's syndrome, Hashimoto's disease, and myasthenia gravis. Parotid gland biopsy and bone marrow examination showed the presence of a rare lymphoplasmacytoid lymphoma. There was amyloid deposition in the parotid glands, gums and on muscle biopsy. Immunohistochemical staining of the parotid lymphoma and amyloid was monotypic for lambda light chains, and there was also a lambda chain paraprotein. It is felt that the lymphoplasmacytic lymphoma was responsible for the light chain amyloidosis.

Adult↗
PubMed1989

Relative safety of intravenous digital subtraction angiography over other methods of carotid angiography and impact on clinical management of cerebrovascular disease.

Data from a multicentre survey based on three London teaching hospitals on the relative safety and clinical utility of intravenous carotid digital subtraction angiography (DSA) over intra-arterial DSA and conventional carotid angiography are presented. The incidence of stroke during intra-arterial DSA was 0.7% (n = 538) and during conventional angiography was 0.8% (n = 780). The incidence of stroke during intravenous DSA was zero (n = 3710). When it constituted the initial investigation, intravenous DSA achieved a 93.8% replacement value over intra-arterial studies as a whole (n = 474) and 89% replacement value for patients having carotid endarterectomy (n = 99). It was also noted that the installation of DSA equipment at one unit coincided with a sixfold increase in the number of carotid angiographic examinations and an almost threefold increase in carotid endarterectomies.

Angiography, Digital Subtraction↗
PubMed1988

Age-dependent variation for inducibility of metallothionein genes in mouse liver by cadmium.

Cadmium is a toxic metal that induces the expression of metallothionein genes in many tissues and that binds avidly to metallothionein, a soluble transition metal binding protein. The present study examined the temporal pattern and magnitude of accumulation of metallothionein mRNA in liver of C57BL/6J mice of various ages treated with cadmium. In adult female mice, accumulation was dependent on the dosage level of cadmium and related to the concentration of this metal in liver. The accumulation of metallothionein mRNA in liver depended on age at exposure to cadmium. Intraperitoneal administration of 2 mg of cadmium per kg provoked small increases (two- to threefold) in levels of metallothionein mRNA in livers of 7- and 14-day-old mice. In contrast, cadmium treatment of 28- and 56-day-old mice resulted in 12- to 19-fold increases in levels of metallothionein mRNA in liver with maximum increases occurring 3 to 4 hr after treatment. Because similar patterns for the accumulation of cadmium of liver were found in 7-, 28-, and 56-day-old mice, observed age-dependent differences in induction of metallothionein mRNA in liver were probably not due to differences in the accumulation of cadmium in this organ. Taken together, these data suggest that tissue-specific factors controlling the expression of metallothionein genes may account for developmental variation in the inducibility of these genes by cadmium. Ontogenic variation in accumulation of metallothionein mRNA after cadmium treatment may be a factor in developmental variation in the acute lethality of cadmium in C57BL/6J mice.

Age Factors↗
PubMed1988

Distribution and retention of organic and inorganic mercury in methyl mercury-treated neonatal rats.

Seven-day-old Long Evans rats received one mumol of 203Hg-labeled methyl mercury/kg sc and whole body retention and tissue distribution of organic and inorganic mercury were examined for 32 days postdosing. Neonates cleared mercury slowly until 10 days postdosing when the clearance rate abruptly increased. During the interval when whole body clearance of mercury was extremely slow, methyl mercury was metabolized to inorganic mercury. Peak concentration of mercury in kidney occurred at 2 days postdosing. At 32 days postdosing, 8% of mercury in kidney was in an organic from. Liver mercury concentration peaked at 2 days postdosing and organic mercury accounted for 38% at 32 days postdosing. Brain concentrations of mercury peaked at 2 days postdosing. At 10 days postdosing, organic mercury accounted for 86% of the brain mercury burden, and, at 32 days postdosing, for 60%. The percentage of mercury body burden in pelt rose from 30 to 70% between 1 and 10 days postdosing. At 32 days postdosing pelt contained 85% of the body burden of mercury. At all time points, about 95% of mercury in pelt was in an organic form. Compartmental analysis of these data permitted development of a model to describe the distribution and excretion of organic and inorganic mercury in methyl mercury-treated neonatal rats.

Animals↗
PubMed1988

The effect of renal impairment and haemodialysis on single dose pharmacokinetics of oral enoxacin.

The effect of renal impairment on the single dose pharmacokinetics of oral enoxacin was studied in 28 volunteers with creatinine clearances ranging from less than 15 to 120 ml/min, including patients undergoing chronic haemodialysis. Following an overnight fast, 400 mg of enoxacin was administered orally to each subject. Blood and urine samples were collected at predetermined times for 48 and 72 h, respectively. Plasma and urine samples were assayed for enoxacin and for oxo metabolite concentrations by a specific high performance liquid chromatographic method. Area under the concentration-time curve from time 0 to infinity (AUC0-infinity) was increased in subjects with renal impairment. Plasma half-life (10.6-11.6 h) in volunteers with severe renal impairment was approximately double the 5.2 h half-life found in subjects with normal renal function, and this should result in steady-state enoxacin concentrations approximately double those measured in normal subjects given equivalent doses. Haemodialysis did not remove significant amounts of enoxacin. A significant correlation between creatinine clearance and enoxacin renal clearance was observed (r = 0.97).

Administration, Oral↗
PubMed1988

Hypertriglyceridaemia and diabetes mellitus: cause or effect?

Two patients with hypertriglyceridaemia which was diagnosed several years before the onset of diabetes are described. In the first case a 54-year-old man presented with hypertriglyceridaemia and normal glucose tolerance. After 4 years he developed severe hypertriglyceridaemia (22 mmol/l) which was first ascribed to poor compliance but soon afterwards diabetes was diagnosed and good blood glucose control minimized the hypertriglyceridaemia. The second patient, a female, aged 27 years, with the polycystic ovarian syndrome, presented with eruptive xanthoma after several years of mild hyperlipidaemia. There was severe hyperlipidaemia (triglyceride 140 mmol/l, cholesterol 42 mmol/l) which required urgent plasmapheresis. Diabetes was diagnosed and treated with insulin at this time but the patient was taking the oral contraceptive pill and also had a deficiency of apolipoprotein CII.

Adult↗
PubMed1988

Computerised axial tomography and magnetic resonance scanning in the Tolosa-Hunt syndrome.

A 50-year-old Asian male presented with a left sixth nerve palsy, left temporal pain, and rapidly deteriorating visual acuity in the left eye. A high resolution CT scan and magnetic resonance scan showed a left retro-orbital enhancing lesion extending from the lateral margin of the cavernous sinus on to the greater wing of the sphenoid and into the left orbit. Arteriography was normal. On high dose steroid therapy there was total resolution of the lesion. The value of imaging techniques in this condition is discussed.

Dexamethasone↗
PubMed1988

Assessment of cerebral haemodynamic reserve: correlation between PET parameters and CO2 reactivity measured by the intravenous 133 xenon injection technique.

Regional cerebral blood flow (CBF), oxygen utilisation, fractional oxygen extraction (OER) and cerebral blood volume (CBV) were measured by positron emission tomography (PET) in 21 patients with occlusive carotid artery disease. In the same patients, measurements of cerebral CO2 reactivity were performed using the intravenous xenon-133 technique. A significant correlation was found in symptomatic hemispheres between the CBF/CBV ratio and CO2 reactivity. Four patients had significant increases in OER and this was associated with a reduction in CBF/CBV ratio implying exhaustion of haemodynamic reserve. CO2 reactivity was reduced below 1.5% mm Hg in all four cases with raised OER but only in two cases with normal OER. In patients with CO2 reactivities above 1.5% mm Hg, OER was normal in all cases. It is concluded that measurements of CO2 reactivity provide a satisfactory method for assessing cerebral haemodynamic reserve.

Aged↗
PubMed1988

Irregularly shaped small shadows on chest radiographs, dust exposure, and lung function in coalworkers' pneumoconiosis.

The predominant shapes of small opacities on the chest radiographs of 895 British coalminers have been studied. The aims were to determine whether irregular (as distinct from rounded) small opacities can be identified reproducibly, whether their occurrence is related to dust exposure, and whether they are associated with excess prevalence of respiratory symptoms or impairments of lung function. Six of the doctors responsible for regular radiological surveys of all British coalminers each classified all 895 radiographs twice and independently, using the International Labour Organisation's 1980 classification system. The majority view was that 39 films showed predominantly irregular small opacities, 131 showed predominantly small rounded opacities, and 587 showed no small opacities. Readers' opinions varied about the presence and shapes of shadows on the other 138 films. In general, consistency between readers (and within readers on repeated viewings) was satisfactory. The occurrence and profusion of irregular shadows were related significantly both to the men's ages and additionally to their cumulative exposure to respirable coalmine dust as determined from 15 years' dust monitoring close to where the miners had worked. For any given level of exposure, the average level of profusion of the small irregular opacities was less than the corresponding profusion of small rounded opacities. The prevalence rates of chronic cough and phlegm, and of breathlessness, were higher in those with small irregular opacities than in those with no small opacities (category 0/0), but the differences were not statistically significant after adjustment for other factors including smoking habits. The presence of irregular (but not rounded) small shadows was associated with an impairment in respiratory function averaging about 190 ml deficits in both FEV1 and FVC. These deficits were not explicable in terms of the men's ages, body sizes, and smoking habits and they were in addition to the lung function losses attributable to the miners' dust exposure as such. It is concluded that the presence and profusion of small irregular opacities should be taken into consideration when assessing the severity of coalworkers' simple pneumoconiosis.

Age Factors↗
PubMed1988

Failure of the cold pressor test to predict hypertension in black physicians: the Meharry Cohort Study.

As part of a longitudinal study of precursors for hypertension and atherosclerosis in a cohort of 315 black physicians, the predictive values of cold pressor reactivity were assessed. At initial evaluation, cold pressor tests were performed on all members of the cohort. At the 23- to 30- year follow-up, the participants were again examined and tho cumulative incidence of hypertension was analyzed by the Kaplan-Meier curves in relationship to cold pressor reactivity. The relationship between follow-up hypertension status and baseline cold pressor reactivity was also examined in a logistic regression analysis in which other potential confounders were controlled.The cold pressor test had no value in predicting the occurrence of primary hypertension.

Black People↗