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Biomedical subjects

V Marks

Publications and source records attributed to V Marks.

At least 109 records · Page 6Linked to original sources
PubMed1988

Intestinal absorption of oxalate by xylitol-treated rats and mice.

The absorption of 14C-labelled oxalic acid was studied in Wistar rats, CD-1 mice and NMRI mice. Oxalic acid in solution was given to the animals by gavage either with water alone or with 0.625 g/kg b.w. of xylitol. Both xylitol-adapted animals and animals not previously exposed to xylitol were used. Adaptation to xylitol diets enhanced the absorption and urinary excretion of the label (oxalic acid) in both strains of mice but not in rats. Earlier studies have indicated a high incidence of bladder calculi in mice but not in rats fed high amounts of xylitol. The results of the present study offer one likely explanation for the increased formation of bladder calculi as a result of oversaturation of urine with oxalate.

Administration, Oral↗
PubMed1988

Caffeine clearance and biotransformation in patients with chronic liver disease.

1. The clearance and biotransformation of caffeine (1,3,7-trimethylxanthine) were investigated in eight healthy control subjects and 16 patients with cirrhosis, by measuring serial serum caffeine concentrations and recoveries of methylxanthine metabolites in urine for 48 h after a 400 mg oral caffeine load. 2. In the control group, the mean (+/- SD) serum caffeine clearance was 1.3 +/- 0.4 ml min-1 kg-1 and a mean of 56.4 +/- 16.5% of the administered caffeine was recovered from the urine over 48 h as methyluric acids and methylxanthines. The majority of the metabolites were excreted in the first 24 h period and only 2.0 +/- 1.4% of the administered caffeine was excreted unchanged. 3. Patients with compensated cirrhosis (n = 10) metabolized caffeine similarly to the control subjects. Thus the mean serum caffeine clearance was 1.4 +/- 1.2 ml min-1 kg-1 and a mean of 57.2 +/- 11.7% of the administered caffeine was recovered from the urine over 48 h. The majority of the metabolites were excreted in the first 24 h; the pattern of metabolic excretion was unaltered and only 2.2 +/- 0.9% of the administered caffeine was excreted unchanged. 4. In the patients with decompensated cirrhosis (n = 6), significant changes were observed in caffeine metabolism. The mean serum caffeine clearance (0.4 +/- 0.2 ml min-1 kg-1) was significantly impaired compared with controls (P less than 0.01) and a significant delay was observed in metabolite excretion in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Modifications of gastric inhibitory polypeptide (GIP) secretion in man by a high-fat diet.

1. Five healthy volunteers (usual fat intake 103 (SE 9) g/d and energy intake 9855 (SE 937) kJ/d were given on two separate occasions (a) 100 g oral glucose and (b) sufficient intravenous (IV) glucose to obtain similar arterialized plasma glucose levels to those after oral glucose. 2. Subjects increased their fat intake by 68 (SE 9.6)% for 28 d by supplementing their diet with 146 ml double cream/d (fat intake on high-fat diet (HFD) 170 (SE 8) g/d; energy intake 12347 (SE 770)). 3. The 100 g oral glucose load was repeated and IV glucose again given in quantities sufficient to obtain similar arterialized blood glucose levels. Immunoreactive plasma insulin, C-peptide and gastric inhibitory polypeptide (GIP) were measured. 4. Plasma GIP levels were higher following oral glucose after the HFD (area under plasma GIP curve 0-180 min 1660 (SE 592) v. 2642 (SE 750) ng/l.h for control and HFD respectively; P less than 0.05). Both insulin and C-peptide levels were significantly higher after oral than after IV glucose (P less than 0.01) but neither were affected by the HFD. Glucose levels were lower following the HFD after both oral and IV glucose (area under plasma glucose curve 0-180 min, following oral glucose 6.7 (SE 0.3) mmol/l.h for control and 4.2 (SE 0.6) mmol/l.h for HFD; P less than 0.01). 5. Glucose-stimulated GIP secretion was thus enhanced by the HFD. Insulin secretion in response to oral glucose was unchanged, in spite of an improvement in glucose tolerance. 6. The improvement in glucose tolerance post-HFD could possibly be due to a GIP-mediated inhibition of hepatic glycogenolysis, or a decreased rate of glucose uptake from the small intestine.

Adult↗
PubMed1988

The effect of dietary modification and hyperglycaemia on gastric emptying and gastric inhibitory polypeptide (GIP) secretion.

1. Five healthy volunteers whose usual fat and energy intakes were moderately high (fat intake 155 (SE 11) g/d; energy intake 13683 (SE 909) kJ/d) were given on two separate occasions (a) 96 g fat and (b) 96 g fat and intravenous (IV) glucose (250 g glucose/l; 100 ml followed by a 2 ml/min infusion for 180 min). 2. Subjects continued on a low-fat diet for 35 d (fat intake 25 (SE 4) g/d; energy intake 6976 (SE 539) kJ/d) and the tests repeated. 3. The gastric inhibitory polypeptide (GIP) response to oral fat was significantly attenuated by IV glucose whilst subjects were consuming their normal diets and the GIP response to fat alone was significantly diminished during the low-fat diet. Post-prandial plasma triglycerides, light scattering indices (LSI; an index of post-prandial chylomicronaemia) and paracetamol levels paralleled the integrated GIP responses on both normal and low-fat diets. 4. The study of oral fat with or without glucose was repeated on seven further volunteers consuming their usual diet, substituting 10 MBq 99Tcm-labelled tin colloid for the paracetamol to investigate the rate of gastric emptying by radionuclide imaging. 5. Plasma GIP, insulin, triglyceride and LSI levels were similar to those found in the first study. IV glucose almost doubled the gastric emptying time of the oral fat load (half emptying time (t1/2) 148 (SE 11) min after fat alone and 224 (SE 18) min after fat and IV glucose). Post-prandial plasma motilin levels were significantly depressed by IV glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

A direct assay for proinsulin in plasma and its applications in hypoglycaemia.

A direct radioimmunoassay in unextracted plasma is described. The assay has a sensitivity of 4 pmol/l (2 standard deviation from zero). The proinsulin antiserum was immuno-adsorbed against human C-peptide and insulin coupled to glass beads. Cross-reactivity of the antiserum was assessed and shown to be less than 0.01% with both peptides. In normal healthy fasting subjects the plasma proinsulin level was 6.7 +/- 1.7 pmol/l (n = 17) (mean +/- SD). Fasting proinsulin levels in non-insulin dependent diabetics were significantly elevated compared with non diabetics (14.2 +/- 2 pmol/l (n = 11) vs 6.7 +/- 1.7 (n = 17) P less than 0.005). The insulin/proinsulin ratio was 3.4:1 in the non-insulin dependent diabetic compared with 6:1 in non-diabetics. Samples from 21 insulinoma patients were assayed and mean fasting plasma proinsulin level was 255 pmol/l +/- 479 when the patients were hypoglycaemic. The range in pro-insulin levels was large (30-2300 pmol/l). Mean fasting proinsulin level in three hypoglycaemic subjects due to sulphonylurea overdose was 15.7 +/- 2.3 pmol/l. The molar ratio of proinsulin to insulin was 1:6 in healthy subjects, 1:1 in insulinoma patients and 10:1 in sulphonylurea induced hypoglycaemic patients.

C-Peptide↗
PubMed1988

Application of radioimmunoassay to monitor treatment of human cerebral gliomas with bleomycin entrapped within liposomes.

A radioimmunoassay was assessed for its suitability for monitoring the blood and urinary concentrations of bleomycin entrapped within large unilamellar liposomes in patients receiving therapeutic doses of the drug. Bleomycin entrapped within liposomes was administered by direct intracerebral injection to three patients with grade III to IV cerebral gliomas, twice weekly for up to six weeks. No clinically important toxic effects were observed which could have been attributed to these preparations, although all three patients showed progressive deterioration in their clinical condition. This type of treatment may be more beneficial to patients at an earlier stage of their disease.

Adolescent↗
PubMed1988

Ectopic release of GHRH and ACTH from an adenoid cystic carcinoma resulting in acromegaly and complicated by pituitary infarction.

A 23 year old man presented with a tumour mass in the lung. Subsequent investigation showed ectopic secretion of adrenocorticotrophic hormone (ACTH) and growth hormone releasing hormone (GHRH) from an adenoid cystic carcinoma. The patient progressed to show the clinical effects of long term exposure to high blood levels of both growth hormone and cortisol. The case was complicated by pituitary infarction. The very high blood levels of ACTH, growth hormone (GH) and GHRH proved resistant to treatment with the somatostatin analogue, SMS 201-995, and a possible side effect of the drug is reported. To our knowledge this is the first reported case of ectopic hormone secretion by an adenoid cystic carcinoma.

Acromegaly↗
PubMed1988

The order of islet microvascular cellular perfusion is B----A----D in the perfused rat pancreas.

In order to determine whether microvascular blood flow is important in the regulation of intra-islet cellular interactions, rat pancreata were isolated and perfused in vitro, both anterogradely or retrogradely, with and without anti-insulin or anti-somatostatin gamma-globulin. Expressed as percent change, anterograde infusion of insulin antibody increased efflux concentrations of glucagon (110 +/- 20%, P less than 0.0005) and somatostatin (2,112 +/- 73%, P less than 0.0005) above their respective control. Retrograde infusion of insulin antibody did not affect efflux concentrations of glucagon (P less than 0.50) or somatostatin (P less than 0.50). The anterograde infusion of anti-somatostatin antibody had no effect upon insulin (P less than 0.50) or glucagon (P less than 0.50) efflux concentrations, whereas retrograde anti-somatostatin antibody infusion produced immediate increases in efflux concentrations of both insulin (115 +/- 33%, P less than 0.0005) and glucagon (77 +/- 8%, P less than 0.0005). These results strongly suggest that (a) the vascular compartment is important in the regulation of intra-islet cellular interactions and further suggest that (b) the order of islet cellular perfusion and interaction is from the B cell core outward to the mantle, and (c) the mantle is further subordered with the majority of D cells downstream or distal to the majority of A cells. Thus, in the vascular compartment, B cells inhibit A-cell secretion and A cells stimulate D-cell secretion.

Animals↗
PubMed1988

The effect of storage temperature and physical state on the performance of antisera in radioimmunoassay after long-term storage.

The performance in radioimmunoassay of four antisera after storage at temperatures ranging from -40 degrees C to room temperature, in three physical states (frozen, liquid or freeze dried) was investigated over a 3-year period. No deterioration in antiserum performance in terms of precision and accuracy of quality control serum measurement or recovery of ligand was apparent under any of the storage conditions studied. Some lowering of titre became apparent in two of the antisera over the study period. Deterioration was most marked when antiserum was stored lyophilised at room temperature. Storage of antiserum frozen confers no advantage over storage at 4 degrees C provided precautions are taken to minimise bacterial contamination when storing antiserum in liquid form.

Humans↗
PubMed1988

Essential considerations in the provision of near-patient testing facilities.

(1) Near-patient testing (NPT) is both practicable and in some situations desirable. (2) Like all new technologies its apparent simplicity often belies its complexity and masks the need for attention to detail in order to achieve optimum effects and avoid disasters. (3) Though technically unskilled individuals are capable of using it, they must undergo training in the elements of safety, sample collection, quality control, quantitation and documentation before being authorized to provide analytical services for patients. (4) Health Authorities should be encouraged to adopt a policy of integration of NPT and clinical laboratory services in order to reduce unplanned use and abuse of NPT facilities which is not only wasteful and divisive, but also dangerous. This has recently been emphasized in the United Kingdom by the release of a Hazard Notice (HN (Hazard) (87) 13) by the Department of Health and Social Security. The experienced clinical biochemist will, by virtue of training and experience, usually be the most suitable person in a Health District to advise on many of the issues involved in NPT. It should therefore, be the responsibility of laboratory staff to work with management, clinical, and nursing staff to: choose appropriate sites for the various levels of service to be provided to meet a clinical need; select the equipment and reagents to be employed; provide training in the use of the apparatus, quality control and safety; authorize accredited users and oversee the quality assurance programme. (5) Laboratory staff will need to involve themselves closely in the financial implications of NPT both for the laboratory's benefit and that of clinical practice within the hospital and/or community as a whole.

Chemistry, Clinical↗
PubMed1988

Tumour formation and insulin secretion by clonal RINm5F cells following repeated subcutaneous transplantation in NEDH rats.

The effects of repeated s.c. transplantation of clonal insulin-secreting RINm5F cells in NEDH rats on tumour morphology, insulin-glucose homeostasis and the function of RINm5F cells re-established in culture were examined after maintenance in vivo for periods of up to 308 days. Transplantation of RINm5F cells for ten consecutive passages consistently produced a single encapsulated vascularized tumour associated with the development in recipient rats of hyperinsulinaemia, hypoglycaemia and eventual neuroglycopenic coma. At the tenth passage, tumour-bearing rats exhibited a markedly enhanced rate of insulin-stimulated glucose uptake by 19 days, with evidence of a large and variable insulin response to i.p. glucose. Survival was 22 +/- 2 days, and resected RINm5F cell tumours exhibited weak immunostaining for insulin in scattered cells, with strands of fibrous tissue separating clusters of tumour cells many of which had distinct polarity. There was no detectable immunostaining for glucagon, somatostatin or pancreatic polypeptide. The insulin content and insulin secretory output of RINm5F cells re-established in culture after 20, 146, 259 or 308 days propagation in vivo were generally enhanced compared with non-passaged RINm5F cells. The magnitude of the effect was not appreciably affected by the duration of maintenance in vivo, but it was critically dependent upon the subsequent period of culture in vitro. Thus, whereas 2-day cultured RINm5F cells from the eighth tumour passage exhibited a greater than 100-fold increment of insulin content and release, with enhanced secretory responsiveness to leucine, arginine, theophylline, K+ (25 mmol/l) or Ca2+ (7.6 mmol/l), RINm5F cells cultured for a further 19 days had almost completely lost the attributes resulting from 259 days of maintenance in vivo. The results indicate substantial enhancement of the functional capabilities of RINm5F cells in vivo, and suggest that the resulting tumours afford a novel model in NEDH rats of responsive trabecular-type insulinomas.

Adenoma, Islet Cell↗
PubMed1988

Hypophosphataemic osteomalacia and alcoholism: a possible link.

Sporadic adult-onset hypophosphataemic osteomalacia is rare and its pathogenesis is unknown. A renal tubular defect, acquired on a toxic basis, has been proposed as the mechanism. Recent evidence suggests that alcohol can cause renal tubular damage. The history and stigmata of alcohol abuse in the present case implicate alcohol as the most likely cause of this patient's hypophosphataemic osteomalacia.

Adult↗
PubMed1987

The effect of sodium aurothiomalate (myochrysin) on the distribution of calcium, magnesium, copper, zinc and iron in the rat.

Sodium aurothiomalate was given to male Wistar rats (initial body weights: 150 g) by subcutaneous (s.c.) injection at doses of up to 7.5 mg/kg (corresponding to 4.27 mg gold/kg), twice a week, for 4-5 weeks. The concentrations of Ca, Mg, Fe, Cu and Zn were measured in serum, urine, faeces and in the liver, kidney, spleen, heart, lung, testis, bone and muscle. Kidney cytosol was separated by gel chromatography and the fractions analysed for protein, copper, zinc, iron and gold concentrations. The concentration of copper was increased 5-fold in kidney while smaller increases of zinc in kidney, copper in muscle, iron in muscle and testis and calcium in spleen were found. There was a significant reduction in the concentration of copper in serum. Kidney cytosol from gold-treated but not from control animals contained a low molecular weight protein which was associated with copper, zinc and gold. The rats developed proteinuria and microscopic changes to renal tubular cell structure were also observed. It is suggested that the gold-induced accumulation of copper may follow from an increased rate of synthesis of metallothionein and could be responsible for the renal dysfunction which develops in a proportion of rheumatoid arthritis patients who are treated with gold.

Animals↗
PubMed1987

Immunocytochemical localisation of VP16-213 in normal and malignant tissues.

Immunocytochemistry has been used to visualise the distribution of the anti-cancer drug VP16-213 in tissues from normal and leukaemic mice, and in EMT6 mammary tumours. Uptake of the drug into EMT6 tumour tissue was poor compared to uptake into normal tissues (liver, kidney, heart, small intestine). Uptake of the drug into tissues from L1210 mice was greater than that into normal tissues. Immunocytochemistry promises to be a very useful additional technique for studying the distribution of drugs given singly or in combination, specific organ toxicities, and mechanisms of resistance.

Animals↗