The insulin response to intravenous fructose in maturity-onset diabetes mellitus and in normal subjects.

Insulin responses to intravenous fructose and glucose were measured in 15 patients with maturity-onset diabetes mellitus. In eight patients given fructose first the insulin responses to fructose and glucose were similar. In seven patients given glucose first the insulin response to subsequently infused fructose was significantly greater than to glucose. Multiple regression analysis showed that the ratio of the fructose to glucose insulin response, assessed by area under the insulin serum concentration-time curve (F/G ratio) in individual patients, correlated most closely with prefructose infusion plasma glucose. Similar analysis, applied to results in 27 normal subjects, showed that the most important determinant of the insulin response to fructose in this group also was the immediate prefructose infusion plasma glucose. Thus in diabetics, as in normal controls, the response of the beta cell to intravenous fructose appears to be sensitively set by the ambient plasma glucose concentration at the onset of fructose infusion.

Calcium antagonists and hormone release: effect of nifedipine on luteinizing hormone-releasing hormone and thyrotropin-releasing hormone-induced pituitary hormone release.

In vitro evidence suggests that calcium is involved in the release of anterior pituitary hormones. Therefore, we studied the effect of the slow calcium channel blocker or calcium antagonist nifedipine on the FSH and LH responses to LRH and the TSH and PRL responses to TRH in vivo. Nine normal male subjects were studied on two occasions, and nifedipine (20 mg, by mouth, or matching placebo) was administered in a randomized single blind manner. Blood pressure and heart rate were measured at 0 and 30 min. The patients then received TRH (200 micrograms) and LRH (100 micrograms) iv. Blood levels of FSH, LH, TSH, and PRL were measured by RIA at 0, 30, 50, 60, and 120 min. Nifedipine lowered diastolic blood pressure significantly (--12 +/- 8 mm Hg; P less than 0.005) and increased heart rate (+ 17 /*- 10 beats/min; P less than 0.005), but had no effect on either baseline hormone levels or the incremental response of any hormone to its secretagogue. In contrast to the results of previous studies with verapamil, nifedipine does not inhibit the release of pituitary hormones. More information is required on the precise intracellular actions of these drugs before they can be used to study the role of calcium in hormone release. Nifedipine, however, may be less likely to influence pituitary function than verapamil.

A possible relationship between high-extraction cereal and rickets and osteomalacia.

The evidence of the present study suggests a strong and possibly causal relationship between high-extraction cereal and rickets and osteomalacia. It seems likely that this occurs when vitamin-D status is border-line. The rachitogenic component of high-extraction cereal remains to be identified; dietary phytate now seems unlikely and phytate-derived polyphosphate esters or dietary phosphorus may be incriminated. The present study strongly indicates that Mellanby's original suggestion of an "anti-calcifying substance" in high-extraction cereal remains valid.

Elevation of serum gamma-glutamyl transpeptidase in end-stage chronic renal failure.

The serum gamma-glutamyl transpeptidase (GGT) was measured on 32 randomly selected patients about to commence or already on chronic haemodialysis. Raised values were found in 12 patients (37%). None of these patients had received drugs known to affect hepatic microsomes and all had normal liver function tests. The possible significance of this surprising finding is discussed.

Excessive beer consumption and beri-beri.

Alcohol-induced 'wet' or cardiac beri-beri is reported in two middle-aged males who consumed excessive amounts of beer. The high carbohydrate and satiety value of beer together with its low thiamine content places the alcoholic beer drinker at particular risk of thiamine deficiency.

The prevention of vitamin D deficiency in the elderly.

Vitamin D deficiency is common in the house-bound and institutionalised elderly population of Britain. A study of patients over 65 years discharged with a diagnosis of osteomalacia from Greater Glasgow Health Board hospitals between 1970 and 1981 inclusive showed a low incidence in the 65 to 74 years age group but a steeply rising incidence in older age groups. The majority (83%) of patients were female. The fortification of margarine, butter and milk with concentrations of vitamin D acceptable to the general population does not produce significant elevations in serum 25-hydroxyvitamin D (25-OHD) levels in vitamin D-deficient elderly patients. Low intensity background ultraviolet radiation (UVR) and intermittent high intensity UVR produce significant elevations in serum 25-OHD levels in elderly patients but both methods have disadvantages which limit their widespread use. Vitamin D supplements equivalent to 10 micrograms daily produce significant elevations in serum 25-OHD levels in vitamin D-deficient elderly patients. A vitamin D supplement policy for the housebound and institutionalised elderly population of Britain is required.

Do anticonvulsant drugs commonly induce osteomalacia?

Twenty adult epileptic out-patients who had received anticonvulsant therapy for a mean duration of 15 years were assessed for clinical, biochemical, radioisotopic and bone biopsy evidence of osteomalacia. Occasional biochemical abnormalities were demonstrated but no individual subject was found to have osteomalacia. There is increasing evidence to cast doubt on the existence of a strong relationship between anticonvulsant drugs and osteomalacia. This evidence is reviewed and it is concluded that in the presence of adequate sunlight exposure anticonvulsant therapy alone is most unlikely to lead to osteomalacia in adults.

Amylase thermolability in body fluids.

The thermolability of amylase was measured in saliva, pancreatic juice, urine, adult and neonatal sera. The mean percentage thermolability from these fluids was 100%, 99%, 87%, 44% and 23% respectively. In patients with acute pancreatitis and mumps the amylase was 84% and 83% thermolabile during the acute phase. On resolution of the pancreatitis this dropped towards normal. Patients with a pancreatic pseudocyst showed a high mean percentage thermolability (82%). These results could suggest that a component of amylase in human serum is not of pancreatic or salivary origin. In addition, this simple technique may be helpful in the diagnosis of pancreatic pseudocyst.

Cord gamma glutamyl transpeptidase activity and neonatal jaundice.

gamma Glutamyl transpeptidase (GGT) activity was measured in normal neonates and in maternal serum post partum. Levels were above the normal adult range (35I U/1) in all neonates and a significant correlation was bound between enzyme activity and bilirubin levels on day 7(P less than 0-005). The mean bilirubin level on days 4 and 7 was higher in babies with cord values less than 90 IU/1. In certain circumstances increased plasma GGT activity may serve as an index of enzyme induction. However, our results suggest that raised levels in the neonate may reflect hepatic microsomal damage with subsequent impairment of bilirubin conjugation. Further evaluative studies of cord GGT activity in neonates at risk, with a view to early prophylactic or therapeutic measures, are indicated.

The significance of the incidental finding of basal ganglia calcification on computed tomography.

Basal ganglia calcification was found as an incidental finding in 42 out of 7000 patients who underwent computed tomography. The calcification showed on plain skull radiography when the maximum density on computed tomography exceeded 100 Hounsfield units. The 26 patients with basal ganglia calcification detected on computed tomography who were available for follow-up, were investigated with matched controls. No clinical features of basal ganglia calcification were noted. Twenty-four patients had no significant metabolic abnormality and two patients had parathyroid disorder identified.

The role of cereals in the aetiology of nutritional rickets: the lesson of the Irish National Nutrition Survey 1943-8.

1. Review of the evidence of the Irish Nutrition Survey concerning a market rise in the incidence of rickets in Dublin in 1942 concludes that a rise in the extraction rate of the national flour from 70 to 100% was principally responsible. 2. This rise and subsequent decrease in incidence as the extraction rate of flour was reduced is not explained by changes in the proportion of children protected by vitamin D supplements or by small changes in dietary vitamin D intake. 3. The evidence suggests that nutritional rickets in man cannot be explained on the basis of deficient vitamin D intake alone, whether derived from diet or u.v. radiation.

Relationships between radiological and biochemical evidence of rickets in Asian schoolchildren.

One hundred Asian schoolchildren provided evidence of the relationships between radiological and biochemical evidence of rickets in a vitamin D-deficient population. In a retrospective study of the X-rays of 56 children the variables serum alkaline phosphatase, inorganic phosphorus and age provided a discriminant function which correctly classified 10 of 11 children with radiological evidence of rickets and 44 of 45 children with negative or marginally abnormal X-rays. When the discriminant function was applied to a prospective study of 44 children, three children with radiological evidence of rickets were correctly classified together with 38 of the remaining 41 children with negative or marginally abnormal X-rays. Serum alkaline phosphatase was the most important variable in the discriminant analysis, followed by serum inorganic phosphorus and age. Low levels of serum 25-hydroxy vitamin D (25-OHD) are of little value in predicting the severity of radiological evidence of rachitic bone disease in a vitamin D-deficient population.

Asian osteomalacia is determined by dietary factors when exposure to ultraviolet radiation is restricted: a risk factor model.

Twenty-seven previously osteomalacic and 77 normal Asian women participated in a seven-day survey of dietary intake and daylight outdoor exposure. Individual levels of daylight outdoor exposure discriminated poorly between normal and osteomalacic women. The presence of osteomalacia was strongly related to varying degrees of vegetarianism. Lactovegetarianism (no meat, fish or egg consumption) was associated with significantly greater osteomalacic risk than ovolactovegetarianism (no meat or fish consumption). Unlike Asian rickets, high-extraction wheat cereal as chapatti was not a significant risk factor for osteomalacia in Asian women and dietary fibre was a less important risk factor than absent dietary meat, fish or egg. When exposure to ultraviolet radiation is limited, Asian osteomalacia (and Asian rickets) are determined by dietary factors.

Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy.

An evaluation of the thiamine, riboflavin and pyridoxine (vitamin B1, B2 and B6) status of 60 patients with recurrent mouth ulcers was performed. Seventeen patients (28.2%) were found to be deficient in one or more of these vitamins. Replacement therapy of these vitamins was given to a study group of deficient patients and a non-deficient group for one month. At the end of therapy and after a follow-up period of 3 months, only those patients who had a B complex deficiency had a significant sustained clinical improvement in their mouth ulcers. Vitamin B1, B2 and B6 deficiencies should, therefore, be considered as another possible precipitating factor in recurrent aphthous ulceration.

Amylase thermolability as a screening test for pancreatic pseudocysts.

Amylase thermolability was determined by heating sera from control patients and patients with acute pancreatitis and pancreatic pseudocysts at 65 degrees C for 15 min. Normal serum amylase was 44 per cent thermolabile, but increased to 84 per cent thermolability during the hyperamylasaemia of acute pancreatitis, and returned to normal on resolution of the pancreatitis. In 9 patients with a pancreatic pseudocyst, although the total amylase level had almost returned to normal limits, 79 per cent of the amylase remained thermolabile. Amylase thermolability appears to be a simple screening test for pancreatic pseudocyst formation secondary to acute pancreatitis.

Biochemical response of late rickets and osteomalacia to a chupatty-free diet.

Eight Pakistani children with late rickets and two Pakistani women with osteomalacia were given a chupatty-free diet for seven weeks, substituting leavened bread of lower extraction. On this diet serum calcium levels rose to normal or near normal, levels of serum inorganic phosphorus rose slightly but significantly, and serum alkaline phosphatase levels showed a definite rise indicative of healing bone disease. It is concluded that the high phytate content of unleavened bread is the major cause of late rickets and osteomalacia in Pakistani and Indian communities in the United Kingdom. The simplest prophylactic measure seems to be the additional fortification with calcium carbonate of the high extraction flour used in preparing unleavened bread.

Rickets and osteomalacia in the Glasgow Pakistani community, 1961-71.

The prevalence of vitamin D deficiency was reassessed in April and May 1971, 10 years after the discovery of widespread late rickets and osteomalacia in the Glasgow Pakistani community. Evidence of vitamin D deficiency was found in 28 out of 115 adults and children examined (24%). Children at the age of puberty were most severely affected by rickets, whereas most infants and younger children in the survey were protected by vitamin D supplements. Mild biochemical osteomalacia was common in Pakistani women.A total of 21 Pakistani and Indian children with rickets were admitted to Glasgow hospitals during 1968-70. These comprised 10 children with infantile rickets and 11 with late rickets. Four of the latter group required osteotomy for severe rachitic deformity.Late rickets and osteomalacia in Pakistani and Indian immigrants are not primarily due to nutritional deficiency of vitamin D, though the high phytate content of their diet may be of aetiological importance. A combination of environmental, social, and endogenous factors, the relative importance of which is not at present clear, may also be involved. Advice on the prophylaxis of vitamin D deficiency should be given to all Pakistani and Indian communities in the United Kingdom.

Policy for prevention of Asian rickets in Britain: a preliminary assessment of the Glasgow rickets campaign.

Evidence of continuing hospital admissions of patients with Asian rickets and osteomalacia led to a further attempt to provide more effective preventive measures for the Glasgow Asian community. Dose-response studies showed that the equivalent of 10 microgram of vitamin D daily would provide effective prophylaxis, and a general practice survey showed that self-administered vitamin D supplements would reduce the prevalence and severity of Asian rickets. A multidisciplinary working group devised a preventive campaign based on the free issue of vitamin D supplements on demand to children who required them. Supported by a health education programme for community health personnel and the Asian community, the first 16 months of the campaign produced an eight-fold rise in the issue of supplements to older Asian children and a 33% increase in their issue to infants of all ethnic groups. Because more children are receiving vitamin D supplementation the campaign seems likely to reduce the prevalence of Asian rickets in Glasgow.