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Biomedical subjects

V M Duncombe

Publications and source records attributed to V M Duncombe.

52 records · Page 3Linked to original sources

Studies on intestinal calcium absorption in patients with idiopathic hypercalciuria.

Using an in vitro method, the uptake of radio-labelled Ca2+ by jejunal biopsy specimens from control subjects, patients with idiopathic hypercalciuria and patients with renal stones without hypercalciuria, were compared. Radio-labelled Ca2+ uptake was investigated over the concentration range 0.1-5.0 mmol/l. For all subjects there was a linear relationship between Ca2+ uptake and medium concentration suggesting that Ca2+ uptake was a passive process. There was no significant difference in Ca2+ uptake between control subjects and patients with renal stones without hypercalciuria. Patients with idiopathic hypercalciuria, both absorptive and renal subtypes, showed increased Ca2+ uptake at all incubation medium concentrations. Assays of various biochemical parameters including alkaline phosphatase, Ca2+-activated ATPase, cyclic AMP and Ca2+-binding protein, in jejunal biopsy specimens showed no significant differences between control subjects and patients with idiopathic hypercalciuria. The results suggest that the intestinal abnormality in idiopathic hypercalciuria is due to enhanced permeability of the brush border membrane to Ca2+, possibly mediated by alterations in membrane lipids.

Calcitriol↗

A prospective study of persistent diarrhoea.

A prospective study was undertaken in 100 patients with diarrhoea to identify the causes and to better define the prevalence of the irritable bowel syndrome (IBS) and to determine if there was a diagnostic symptom complex evident in patients with IBS. A diagnosis of IBS was made in 28 patients and in this group the prevalence of lactase deficiency was found to be 40%. Pain in association with urgency was usual and urgency occurring in the absence of pain was more likely to be found in association with an organic colonic lesion. The two most important symptoms which distinguish IBS from other causes were blood in the motions and weight loss. Giardia lamblia were found in nine patients and 15 patients responded to an empirical course of either metronidazole or tinidazole, without a positive diagnosis of giardiasis being made. Fourteen patients had inflammatory bowel disease and a variety of drugs were responsible for diarrhoea in 10% of patients. Sigmoidoscopy and small bowel biopsy were the most valuable diagnostic investigations.

Adolescent↗

The effect of iron and protein deficiency on plasma levels and parasite uptake of [14C] fenbendazole in rats infected with Nippostrongylus brasiliensis.

The Nippostrongylus brasiliensis-rat model was used to determine whether iron and protein deficiency, which are commonly associated with parasitic infections, affected the pharmacokinetic behaviour of fenbendazole as measured by plasma concentrations and uptake by worms. Plasma 14C concentrations after [14C] fenbendazole administration were higher in iron and protein-deficient rats than in sufficient rats. However, the uptake of 14C by N. brasiliensis in iron and protein-deficient rats was significantly less than in worms from diet-sufficient rats. The reduced anthelmintic uptake by worms in protein and iron-deficient hosts may account, in part, for reduced anthelmintic efficacy under these circumstances. These findings are relevant to understanding variations in response to chemotherapy in populations of parasitised hosts containing malnourished individuals.

Animals↗

Delayed expulsion of the nematode Nippostrongylus brasiliensis from rats on a low protein diet: the role of a bone marrow derived component.

Rats on a low protein diet, containing 10% casein as the only source of protein, have an impaired capacity to expel primary infections with the nematode Nippostrongylus brasiliensis and remain susceptible to reinfection. In the present study, the transfer of syngeneic bone marrow cells to rats on a low protein diet reconstituted the expulsion mechanism allowing parasite rejection to occur at the same rate as rats on a sufficient diet. Serum transfer, on the other hand, did not significantly alter the rate of worm expulsion. These results demonstrate that a bone marrow derived component plays an important role in the impaired immunity of rats fed a low protein diet.

Animals↗

The effect of iron deficiency, protein deficiency and dexamethasone on infection, re-infection and treatment of Giardia muris in the mouse.

The association between nutrient deficiencies, steroid administration, anti-flagellate therapy and giardiasis was examined using the Giardia muris/mouse model. Administration of steroids to BALB/c mice resulted in persisting high levels of infection with G. muris, whereas untreated animals were able to eliminate this parasite. In addition, steroid treatment significantly reduced the efficacy of anti-flagellate therapy. Protein-deficient mice eliminated the parasite at the same rate as mice on an optimum diet and also developed strong acquired resistance to re-infection. A similar pattern was observed in iron-deficient mice, except that the number of parasites that became established during the first 2 weeks of infection was significantly reduced. Thus, there was no evidence of synergism between iron and protein deficiency and infection in this model.

Animals↗

The effect of iron and protein deficiency on the development of acquired resistance to reinfection with Nippostrongylus brasiliensis in rats.

Iron and protein deficiency delays the immunological rejection of Nippostrongylus brasiliensis from the small intestine of rats undergoing a primary infection with the parasite. In the present study, iron and protein deficiency significantly reduced acquired resistance to reinfection with N. brasiliensis. Repletion of deficient animals with iron and protein restored their capacity to mount an effective immune response to a secondary infection with the parasite. These results suggest that chemotherapy of helminthiasis should be integrated with nutritional supplementation.

Animals↗

Nippostrongylus brasiliensis infection in the rat: effect of iron and protein deficiency on the anthelmintic efficacy of mebendazole, pyrantel, piperazine, and levamisole.

The benzimidazole anthelmintics mebendazole and fenbendazole have been shown to be much less effective against Nippostrongylus brasiliensis infections in the rat on a combined iron and protein deficient diet. In the present experiments it was shown that the anthelmintic efficacy of mebendazole was significantly impaired in the rat on either an iron deficient or a protein deficient diet. Furthermore, iron and protein deficiency reduced the efficacy of the anthelmintics pyrantel and piperazine but not levamisole. The finding that nutritional deficiencies reduce anthelmintic efficacy may well be relevant to worm eradication programmes in iron deficient and protein calorie malnourished populations.

Anemia, Hypochromic↗

Histopathology in giardiasis: a correlation with diarrhoea.

There is controversy both in regard to the severity of small bowel mucosal damage attributable to giardiasis and to the causal relationship of these changes to the associated diarrhoea. In this series of 17 consecutive patients with giardiasis, small bowel histology and diarrhoea were independently assessed and compared. Disaccharidase assays were performed in 16 of these patients and a repeat biopsy obtained in seven cases. On histological examination the villous architecture varied from normal to sub-total villous atrophy. When these changes were compared with the severity of diarrhoea, a direct correlation was obtained, the more severe symptoms being associated with the more severe villous changes. Repeat biopsy after treatment demonstrated improvement in the histology which correlated with improvement in diarrhoea. Lactase activity was low in all patients with moderate or severe diarrhoea as well as in some patients with mild diarrhoea, two of whom had normal histology. This series demonstrates the occurrence of a spectrum of mucosal changes in giardiasis and supports the concept that these changes mediate the diarrhoea associated with this gut parasite.

Adolescent↗

Suppression of rejection of Nippostrongylus brasiliensis in iron and protein deficient rats: effect of syngeneic lymphocyte transfer.

Rejection of Nippostrongylus brasiliensis is impaired in iron and protein deficient rats and this suggests that iron and protein deficiency directly or indirectly suppresses the immune response. The site of the immunological defect in deficient rats was investigated using the technique of cellular transfer of resistance. The functional activity of immune mesenteric lymph node cells obtained from iron and protein deficient donors was not depressed as measured by their capacity to cause parasite rejection in nutritionally sufficient recipients. In contrast, immune lymph node cells obtained from either sufficient or deficient donors did not result in parasite rejection in iron and protein deficient recipients. These results indicate that there is no permanent defect of lymphocyte function in iron and protein deficient rats and suggest that either some other component of the rejection mechanism is defective, or that lymphocyte function is blocked in an iron and protein deficient environment.

Animals↗

Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics.

Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities.

Animals↗

Effect of iron and protein deficiency on the expulsion of Nippostrongylus brasiliensis from the small intestine of the rat.

The relationship between iron deficiency and protein deficiency and infestation of the rat with the nematode Nippostrongylus brasiliensis was investigated. There was a significant delay in the expulsion of N. brasiliensis from the small intestine of both iron deficient and protein deficient animals and those with a combined deficiency of iron and protein. Iron repletion returned the time of worm expulsion to normal and this would appear to be related to iron deficiency per se rather than to anaemia. Antibody initiated damage to worms was normal in the control animals and in animals with nutritional deficiencies. This suggests that the defect in worm expulsion occurs either in the cell-mediated immune system or in one of the other mediators of expulsion. Extrapolation to the human situation has important therapeutic implications in that iron and protein deficiency may play an important role in the perpetuation of helminth infestations. Thus, to be successful antihelminth therapy should be accompanied by iron and protein supplementation.

Ancylostomatoidea↗

Double-blind trial of cholestyramine in post-vagotomy diarrhoea.

The effect of cholestyramine in post-vagotomy diarrhoea has been assessed under double-blind conditions. Cholestyramine produced a significant improvement in frequency, urgency, and consistency of stool as well as episodic diarrhoea. Faecal bile acid excretion was significantly higher in the post-vagotomy group when compared with normal controls. These findings confirm the effectiveness of cholestyramine and support the concept of a bile acid mediated aetiology in post-vagotomy diarrhoea.

Bile Acids and Salts↗

The diagnosis and management of acute viral hepatitis.

While there is a declining incidence of many infectious diseases, viral hepatitis persists as a major problem. In fact, there would appear to be an increasing incidence of hepatitis B paralleling the rising problem of drug addiction. The discovery of Australia antigen, now called hepatitis B surface antigen (HBsAG), represented a major breakthrough in our understanding of viral hepatitis. More recently, serological tests have become available for hepatitis A virus (HAV) which will further facilitate our understanding of acute and chronic hepatitis.

Acute Disease↗

In-vitro calcium uptake by jejunal biopsy specimens from patients with idiopathic hypercalciuria.

In-vitro calcium influx was measured in jejunal biopsy specimens from 10 men with idiopathic hypercalciuria. Calcium uptake in these adults was a passive process which was not sensitive to inhibition by 2,4 dinitrophenol and sodium fluoride, and showed no evidence of carrier saturation. In 7 of 10 patients with idiopathic hypercalciuria calcium uptake was above the normal range, and the mean uptake for all patients was significantly higher than in 10 control subjects (p < 0.01). The kinetic features suggest that this increased influx was the result of increased brush border permeability to calcium ions.

Adult↗