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Biomedical subjects

J D Maxwell

Publications and source records attributed to J D Maxwell.

At least 109 records · Page 6Linked to original sources
PubMed1980

Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth.

In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol (ergocalciferol, 1000 IU/day) was administered to 59 women and placebo to 67 controls during the last trimester. The two groups had similar distributions of maternal age, height, parity, number of vegetarians, countries of origin, and sex and gestation of the infants. At entry to the trial maternal serum 25-hydroxy vitamin D (25-OHD) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians. Mothers in the treatment group gained weight faster in the last trimester than those in the control group, and at term they and their infants all had adequate plasma 25-OHD concentrations, Mothers and infants in the control group, however, had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase (bone isoenzyme) activity. Five of these infants developed symptomatic hypocalcaemia. Almost twice as many infants in the control group were small for gestational age (29% v 15%), but there were no significant differences between the two groups of infants in antropometric measurements. Infants in the control group, however, had larger fontanelles, suggesting impaired ossification of the skull. Because of the benefits to mothers and infants in the treatment group and the absence of side effects, vitamin D supplements should be given to all pregnant Asian women in the United Kingdom.

Alkaline Phosphatase↗
PubMed1979

Intestinal bacterial metabolism of protein and bile acids: role in pathogenesis of hepatic disease after jejuno-ileal bypass surgery.

Jejunal bacterial colonization and intestinal metabolism of bile acids and protein by bacteria have been investigated in 12 patients with abnormal liver histology following jeujno-ileal bypass surgery for obesity. Aerobic and/or anaerobic colonic flora was present in jejunal aspirates from 8 of 12 bypass patients, but in none of the controls. Intestinal protein metabolism and bile acid deconjugation (measured by urinary indican excretion and 14C-glycocholic acid breath test) was significantly enhanced in bypass patients. Intestinal bacterial overgrowth, with abnormal intestinal metabolism by bacteria of ingested nutrients and bile acids, could contribute to hepatic disease after bypass surgery via the production of endogenous hepatotoxins.

Adult↗
PubMed1979

Treatment of overt CNS leukemia.

At this time, methotrexate and CNS radiotherapy used together offer the best chance for prolonged remissions in children who develop overt CNS leukemia. Toxicity is a major problem. Unless a lower dose of radiation is used, the contribution of radiotherapy to neurotoxicity cannot be reduced. However, the toxicity of intrathecal methotrexate can be reduced by using Elliot's B as a diluent, combining methotrexate with hydrocortisone, and using a standard dose after the age of 3 years rather than a dose based on body surface area. Fortunately, the incidence of CNS leukemia has decreased over the years due to prophylactic CNS therapy. However, when a CNS relapse does occur, it carries a grave prognosis and is therefore still a significant problem necessitating continued research.

Adrenal Cortex Hormones↗
PubMed1978

Plasma vitamin D-binding globulin in vitamin D deficiency, pregnancy and chronic liver disease.

Plasma concentrations of vitamin D-binding globulin were measured by radial immunodiffusion in healthy subjects, pregnancy, and during oestrogen therapy. Subjects with disorders of vitamin D metabolism (dietary deficiency, malabsorption, anticonvulsant therapy, chronic liver disease) were also studied. Neither sex nor age influenced the plasma vitamin D-binding globulin concentration in healthy subjects, but there was a significant increase in concentration during pregnancy and oestrogen therapy. Elevated levels were found in vitamin D deficient elderly but not younger subjects, while levels in subjects with chronic liver disease were significantly reduced. Normal levels of vitamin D-binding globulin were present in hypervitaminosis D and no vitamin D-binding globulin was detected in human milk. No correlation was observed between plasma 25-hydroxycholecalciferol levels and plasma vitamin D-binding globulin concentrations.

Adult↗
PubMed1977

Hepatic structure and function after modified jejunoileal bypass surgery for obesity.

The most serious adverse effect of standard intestinal bypass for obesity is the high incidence of hepatic dysfunction and death from hepatic failure. We therefore examined the long-term effects of a modified form of jejunoileal bypass (in which a greater continuous length of ileum is retained), on liver function in 120 patients. Substantial weight loss (119-0+/-SD 23-3 kg to 82-3+/-18-8 kg) occurred during the first nine months after surgery, accompanied by a significant rise in serum concentrations of bilirubin, alanine transferase, and alkaline phosphatase, and a significant reduction in albumin concentrations. Biochemical changes were unrelated to weight loss or halothane anaesthesia. After weight stabilisation liver function reverted to normal, and four years after bypass sulphobromophthalein retention and hepatic histology did not differ from those in obese controls. There were two postoperative deaths. Three other patients died during the period of rapid weight loss with severe hepatic steatosis. While transient mild impairment of liver function is common after modified jejunoileal bypass, clinically significant hepatic dysfunction is a rare and unexplained early complication.

Adult↗
PubMed1977

Altered vitamin-D metabolism in pregnancy.

Low levels of plasma-25-hydroxy-vitamin-D (25-OHD) (less than 16 nmol/1) were found in 33% of a group of pregnant women studied in South London. Non-White women in the last 10 weeks of pregnancy had significantly reduced levels compared with non-pregnant controls (P less than 0.02). Plasma-25-OHD was unrelated to dietary vitamin-D intake, age, parity, social class, plasma-calcium, and plasma-albumin. Reduction of plasma-25-OHD could contribute to the fall in plasma-calcium during pregnancy, and may result from enhanced maternal metabolism or increased utilisation of vitamin D by the fetus.

Alkaline Phosphatase↗
PubMed1976

Effect of lead on hepatic delta-aminolaevulinic acid synthetase activity in the rat: a model for drug sensitivity in intermittent acute porphyria.

The hereditary hepatic porphyrias are disorders of porphyrin and haem synthesis characterized by a marked idiosyncrasy towards a variety of lipid soluble drugs. Most of these agents are inducers of the haemoprotein cytochrome P450, the terminal oxidase in drug metabolism. The primary genetic defect in intermittent acute porphyria is a partial deficiency of uroporphyrinogen I synthetase, which may result in a secondary derepression of delta-aminoaevulinic acid synthetase, the rate-limiting enzyme in the haem pathway. Analogous defects at more distant sites may explain the other hereditary hepatic porphyrias. As drug sensitivity may be related to the defect in haem synthesis, we investigated the effects of experimental partial blocks in haem synthesis produced by lead in rats. Drug effects on delta-aminolaevulinic acid synthetase, cytochrome P450, And drug metabolism were studied. Our findings indicate: a) While partial impairment of haem biosynthesis has only minor effects on delta-aminolaevulinic acid synthetase activity, it greatly enhances the sensitivity of delta-aminolaevulinic acid synthetase to induction by drugs and steroids, which when given alone, have little or no inducing effect on the enzyme. b) The experimental partial block in haem synthesis delays and impairs drug-mediated induction cytochrome P450 and drug metabolism in vitro. The findings may explain why a large number of structurally unrelated compounds with little effect on normal liver can precipitate "aucte porphyria".

5-Aminolevulinate Synthetase↗
PubMed1973

Use of computer-assisted model in diagnosis of drug hypersensitivity jaundice.

Of 374 patients with jaundice seen in the liver unit over a four-year period 21 were finally thought to be hypersensitive to one of seven different drugs. The clinical, laboratory, and histological features were often difficult to distinguish from those of viral hepatitis, tumour of the extrahepatic biliary tree, or primary biliary cirrhosis. A computer-assisted diagnostic model made use of minor differences, and made a correct diagnosis in all patients. Even when information about drug ingestion was left out it was still correct in 81% of patients. Sixty-four other patients gave a history of ingestion of potentially hepatotoxic drugs of whom 62 were correctly diagnosed by the computer. In the complete series of 374 patients only two were incorrectly computed to have drug jaundice when there was no history of drug ingestion.Two additional patients became jaundiced after exposure to drugs, but were found to have primary biliary cirrhosis.

Biliary Tract↗
PubMed1973

Use of sequential Bayesian model in diagnosis of jaundice by computer.

A sequential Bayesian model has been developed for a computer and used to diagnose jaundiced patients admitted to hospital. Up to 102 items of information from the history, physical examination, and special investigations available within 48 hours of admission were collected on 309 patients. The results from these patients were used to calculate the probabilities of 11 possible diseases in 65 new patients and also to place patients into groups for medical or surgical treatment.The overall accuracy of the model in diagnosing patients as having one of 11 diseases was 69%, and where the final probability reached > 0.96, it was 89%. The overall accuracy in making a medical or surgical decision was 89%, and where the final probability reached > 0.96 it was 94%.Improvement in accuracy should result as the number of cases seen with rare conditions increases, and probably a similar model could be developed and used to make most use of those indicants with the highest cost-effectiveness.

Acute Disease↗
PubMed1972

Folate deficiency after anticonvulsant drugs: an effect of hepatic enzyme induction?

Serum and red cell folate levels were reduced in 59% and 58% respectively of 75 children with epilepsy attending a residential school. The degree of folate deficiency was significantly related to increased hepatic microsomal enzyme activity, assessed from increased urinary excretion of D-glucaric acid and also correlated with the daily dose of anticonvulsant taken. Anticonvulsant drugs are known to have inducing properties, and since folate is required as a cofactor in drug hydroxylations it is suggested that folate depletion results from increased demand for the cofactor after induction of drug-metabolizing enzymes. As folate deficiency may ultimately limit drug metabolism this hypothesis would explain why blood phenytoin levels decrease and fit control may worsen after correction of folate deficiency in epileptic patients.

Adipates↗
PubMed1971

Altered calcium metabolism in epileptic children on anticonvulsants.

A survey of 105 epileptic children aged 10-16 years at a residential school who were taking anticonvulsant drugs showed reduced serum calcium levels in 30% and a raised serum alkaline phosphatase in 24%. Urinary D-glucaric acid excretion, a quantitative index of hepatic enzyme induction, was raised in 94% of the children, and statistical analysis showed a significant inverse correlation with the level of serum calcium. These findings give further support for the view that an important factor in the development of the hypocalcaemia and occasional clinical osteomalacia in epileptics on anticonvulsant drugs is an alteration of vitamin-D metabolism in the liver as a result of microsomal enzyme induction. As a consequence there is an increased requirement for vitamin D which may not be met by average intakes in Britain.

Adipates↗