Search

The introduction of proton pump inhibitors (PPIs) in the late 1980s optimised the medical treatment of acid-related disorders. They are potent medications and have a good safety profile. However, long-term therapy with PPIs may carry undesired side effects, one of which is hypomagnesaemia. This entity is likely to be under-reported. We present a clinical case which illustrates this important clinical problem. We present the case of a 73-year-old woman who was admitted to the hospital with supraventricular tachycardia due to hypomagnesaemia while using lansoprazole, followed by the literature review on this subject. In our patient after the intravenous magnesium replenishment, her arrhythmia resolved. After stopping her PPI her serum magnesium remained within reference values without oral supplementation. We believe that more attention towards this underdiagnosed side effect is required. Serum magnesium concentration should be checked in patients on PPIs if they are unwell or present with arrythmia.

Background: Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFE C282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma is uncertain. We have carried out a cross-sectional study to determine the proportion of diagnosed hepatocellular carcinoma patients who are homozygous for the HFE C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia., Methods: Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for HFE C282Y mutations; the data produced were compared with the frequency of HFE mutations in a large sample of the local population. Data were also retrieved from the East Anglian Cancer Intelligence Unit to determine the annual incidence of hepatocellular carcinoma; and from appropriate life tables., Results: Eight out of 144 of the cases were homozygous for the HFE C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male HFE C282Y homozygotes were more likely to be diagnosed with hepatocellular carcinoma (odds ratio [OR] = 14, 95% confidence interval [CI] = 5-37). For this population, we estimate that the penetrance of the HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females., Conclusion: In this population, we found that only a very small proportion of homozygotes for the HFE C282Y mutation developed hepatocellular carcinoma. However, individuals with this genotype have a significantly increased risk of this rare disease relative to those who do not carry the mutations.

Most individuals diagnosed with hereditary hemochromatosis have mutations in both copies of the HFE gene, with such mutations being common in populations of north European origin. The number of individuals currently diagnosed and treated for hemochromatosis is small relative to the number carrying two HFE mutations. Studies searching for undiagnosed hemochromatosis cases among disease cohorts have generally failed to find the number of cases that would be expected if disease were the commonest outcome for individuals with two C282Y HFE mutations. Our aim was to test the hypothesis that individuals with two HFE mutations would be under-represented in an elderly population because many would have died from disease caused by hemochromatosis before they reached old age. This is a cross-sectional study of elderly patients referred for full blood counts at the Norfolk and Norwich University Hospital. We screened blood samples from 1,000 elderly men (aged 85 and over) and women (aged 89 and over) for the C282Y, H63D, and S65C mutations of the HFE gene. We also analyzed any recent laboratory data relevant to signs of hemochromatosis. None of the ten possible genotypes was significantly under- or over-represented compared to the expected frequency calculated from the Hardy-Weinberg equation. Four C282Y homozygotes were found. There were few significant differences in the laboratory findings between the genotypes. Our data suggest that most people with HFE mutations survive to old age and do not suffer from signs of iron overload and hemochromatosis.

Background: Most patients with haemochromatosis have mutations of the HFE gene. However, the risk to people with HFE mutations of developing disease manifestations of haemochromatosis is not known., Aims: To determine the risk of developing cirrhosis and liver cancer in individuals with HFE mutations in a population where few people were being treated for haemochromatosis., Methods: 215 archive biopsy specimens of liver cancer (n=34) and cirrhosis (n=190) were retrieved from histology archives. Blood samples from 1000 individuals from the normal population were also collected. DNA was extracted from the biopsy specimens and exons 2 and 4 of the HFE gene were amplified using polymerase chain reaction. The products were analysed for the C282Y (845A) and H63D (187G) mutations., Results: Three (8.8%) patients from the liver cancer group were homozygous for the C282Y mutation. Five (2.6%) patients from the cirrhosis group were homozygous for the C282Y mutation. One case fell in both the liver cancer and cirrhosis groups. C282Y homozygosity was thus significantly more frequent in both groups than in the normal population. These 215 cases are representative of a population of about 250 000 over 20 years. During this period we estimate that about 260 births or deaths of C282Y homozygous individuals occurred within this population., Conclusions: A diagnosis of liver cancer or cirrhosis is rare in the lifetime of individuals from this population who are homozygous for the C282Y mutation (2.5%; upper 95% confidence interval (CI) = 8%). Similarly liver disease is rare among C282Y/H63D compound heterozygotes (1%; upper 95% CI = 3.5%).

We have examined normal individuals and all the patients currently being treated for hemochromatosis at the Norfolk and Norwich hospital for mutations in the HLA-H gene. We found a gene frequency in 200 normal subjects for teh 845A (C282Y) allele of 0.085, corresponding to a carrier frequency of 17% which is among the highest reported anywhere in the world. The frequency for the less penetrant 187G (H63D) allele was 0.16 among 58 of the normal subjects, which corresponds to a carrier frequency of 32%. All 18 hemochromatosis patients were homozygous for the 845A allele which is not significantly different from other reports in our subset of 12 unrelated patients. These findings present a snapshot of a relatively stable population containing a predicted 3,500 individuals homozygous for the 845A allele but not diagnosed with hemochromatosis. This population will be an excellent model for studies on the penetrance of the 845A homozygous genotype and population screening.

We assessed consumption of fruit and vegetables amongst patients with ulcerative colitis, colorectal polyps or previous carcinoma. The dietary intakes for 119 patients attending a gastroenterology clinic for colonoscopy were assessed using a questionnaire. A single age- and sex-matched control subject was recruited for each patient. The patients consumed 12.8% less energy than the controls (P < 0.02) and 28.9% less fruit and vegetables (P < 0.0001). Patients with neoplastic disease consumed 21% less fruit and vegetables than the controls (n = 60; P < 0.01). This group of patients at increased risk of colorectal cancer selected diets containing significantly less fruit and vegetables than symptomless controls.

Abnormal intestinal crypt cell proliferation is considered to be an important early risk marker for colorectal cancer but measurement of the rate and spatial distribution of cell division by histochemical localization of DNA synthesis is labour-intensive and expensive. We developed and evaluated a simpler technique for measurement of these parameters using direct visual analysis of mitotic figures in microdissected crypts. The direct crypt analysis technique was applied to colorectal biopsies from patients with ulcerative colitis or no mucosal abnormality. A characteristic shift of cell division toward the intestinal lumen was detected in patients with ulcerative colitis. The direct method was validated using rats fed diets containing cellulose, or guar gum to stimulate mucosal cell proliferation. The crypt cell proliferation rate (CCPR) was measured by the metaphase-arrest technique and the results were compared with direct crypt analysis. There was a fivefold range of CCPR values at three sampling sites across the dietary groups. An excellent linear correlation between the results by the two techniques was obtained (r = 0.98; P < 0.001). In a second experiment the spatial distribution of dividing cells between five zones in colonic crypts, determined by the new method or by staining with BrdU, was compared. Good agreement was again achieved. Visual analysis of intact crypts is a valid technique for the measurement of crypt cell cytokinetics and it is particularly suited for use in a clinical environment.

Elemental diet is as effective in producing remission of Crohn's disease (CD) as is corticosteroid treatment, but most patients relapse soon after resumption of a normal diet. We have investigated the efficacies of dietary modification and oral corticosteroids in maintaining remission achieved with elemental diet. In a multicentre trial, 136 patients with active CD were started on elemental diet and other treatment was withdrawn. 43 (31%) declined to continue elemental diet for 14 days, but 78 (84%) of the remaining 93 achieved remission and were randomly assigned corticosteroids (38) or diet (40). Corticosteroid treatment started at 40 mg prednisolone daily, which was tapered and stopped after 12 weeks; that group received dietary advice on healthy eating. The diet group received "tapered" placebo and were instructed to introduce one new food daily, excluding any that precipitated symptoms. Assessment of progress for up to 2 years was made by physicians unaware of group assignment. Intention-to-treat analysis showed median lengths of remission of 3.8 (interquartile range 5.0) months in the corticosteroid group and 7.5 (15.3) months on diet, and relapse rates at 2 years, adjusted for withdrawals, of 79% and 62%, respectively (p = 0.048). Clinical improvement in the diet group was associated with significant changes in plasma albumin and alpha 1-antichymotrypsin concentrations and erythrocyte sedimentation rate. Food intolerances discovered were predominantly to cereals, dairy products, and yeast. Diet provides a further therapeutic strategy in active Crohn's disease.

Two patients with intestinal submucosal diaphragm disease associated with non-steroidal anti-inflammatory drugs are presented. The jejunum was affected in one, and in the other the ascending colon. Most previously reported cases have shown ileal disease and no case to date has shown involvement of the colon. The reasons for the localisation of these diaphragms remain unclear.

Genetic linkage studies were performed in 12 British families with von Hippel-Lindau disease (VHL) using RFLPs at three loci (DNF15S2, THRB, RAF1) on the short arm of chromosome 3. Linkage was detected between the VHL disease locus and RAF1 with a maximum lod score of 3.88 at a recombination fraction of 0.05 (confidence interval 0.003-0.18). Multipoint linkage analysis suggested that the most likely location for the VHL disease locus is telomeric to THRB. These results confirm earlier reports localizing the VHL gene to the short arm of chromosome 3, and provide no evidence for genetic heterogeneity.

An epidemiological survey of Crohn's disease in the city of Derby showed that the incidence of the condition increased from 0.7/10(5) per year between 1951 and 1955 to 6.67/10(5) per year between 1981 and 1985 but seemed to reach a plateau between 1976 and 1985. Large bowel Crohn's disease was more common in patients presenting aged 60-79 years than in those aged 20-39 years. The increase in incidence was not solely due to the detection of milder disease. There was no evidence that the Asian (Indian subcontinent) population of Derby was resistant to the development of Crohn's disease.

Previous studies in infants and in the elderly have shown that a low body weight is associated with a defect in thermoregulation and an increased risk of hypothermia. In the present study, thermoregulatory responses to a cooling stimulus were measured in 10 young and middle-aged patients who lost at least 10 per cent of their body weight during illness. Investigations were performed before and after restoration of body weight (mean weight gain 7.2 kg, SE 1.2 kg, p less than 0.001). The cooling stimulus was provided by a special suit perfused with water at 28 degrees C and then at 23 degrees C. Before weight gain, there was no increase in metabolic rate in response to cooling, despite a fall in core temperature. Following weight gain, the thermogenic response to cooling was restored towards normal. Peripheral vasoconstriction, the principal mechanism for heat conservation, was similar before and after weight gain. The thermogenic response to an infusion of adrenaline (25 ng/kg/min) was not abolished by weight loss, suggesting that the defect in cold-induced thermogenesis following weight loss is due to a change in central control mechanisms of thermoregulation, and not to tissue unresponsiveness. The phenomenon of abnormal thermoregulation following weight loss and the return to normal with subsequent weight gain may be clinically important, particularly in the elderly, since quite small falls in core temperature may impair both neuromuscular coordination and cerebral function.

A 30 year old man with von Hippel-Lindau syndrome presented with obstructive jaundice caused by a carcinoid tumour of the mid- and upper common bile duct. This association is probably causally related in view of the propensity for patients with von Hippel-Lindau syndrome to develop neuroendocrine tumours.

The effects of 48-h starvation on the physiological responses to a 30-min infusion of epinephrine at 25 ng.min-1.kg body wt-1 were studied in 11 normal-weight healthy young subjects. Starvation led to considerable alterations in basal metabolism including a significant (mean 3.6%) increase in resting metabolic rate. During the infusions, plasma epinephrine concentration rose less in the starved state (+1.47 nmol/l) than in the normally fed state (+1.73 nmol/l) (SE 0.06 nmol/l; P less than 0.05). The maximum increments (mean +/- SE) in heart rate induced by epinephrine were 11.9 +/- 1.3 beats/min in the normally fed state and 20.1 +/- 2.0 beats/min in the starved state (P less than 0.001); the corresponding mean increments in blood glycerol concentration were 0.07 and 0.14 mmol/l (SE 0.01 mmol/l; P less than 0.01). The increase in the metabolic rate above base line during the final 10 min of the epinephrine infusion was 0.58 +/- 0.18 kJ/min in the normally fed state and 0.78 +/- 0.14 kJ/min in the starved state (P less than 0.01). The chronotropic, lipolytic, and thermogenic effects of infused epinephrine were therefore enhanced by prior starvation, despite the lower plasma epinephrine levels.

1. On two separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline [0.27 nmol (50 ng) min-1 kg-1] or saline (154 mmol/l NaCl), plus ascorbic acid (5.68 mmol/l), over 30 min. 2. On each occasion, the subjects were exposed to distal body subatmospheric pressure (DBSP), 0 to 50 mmHg (0 to 6.65 kPa) in 10 mmHg (1.33 kPa) steps, before infusion, during the final 15 min of the infusion, and at 15 min and 30 min after the cessation of the infusion. 3. Venous adrenaline concentrations of 2.85 +/- 0.22 nmol/l were achieved during the adrenaline infusion, compared with 0.49 +/- 0.07 nmol/l during the saline infusion (P less than 0.001). At 15 min and at 30 min after cessation of the adrenaline infusion, venous adrenaline concentrations had fallen to levels similar to those achieved after the cessation of the saline infusion. 4. Heart rate rose significantly from 58 +/- 4 beats/min to 67 +/- 4 beats/min during the adrenaline infusion (P less than 0.05), but there was no further significant change in response to 50 mmHg (6.65 kPa) DBSP. At 30 min after the cessation of the adrenaline infusion, heart rate rose from 60 +/- 4 beats/min to 78 +/- 7 beats/min in response to 50 mmHg DBSP. This increase was significantly greater than that observed before the adrenaline infusion [58 +/- 4 beats/min to 69 +/- 7 beats/min during 50 mmHg (6.65 kPa) DBSP; P less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)

The nutritional status in 17 patients with unresectable carcinoma of the oesophagus or cardia was assessed before and one month after endoscopic intubation by measurement of body weight, triceps skinfold thickness, midarm circumference and serum albumin concentration. There was a significant increase in dietary energy intake and weight loss was arrested in 10 patients. A weight gain of 3 kg or more was recorded in six cases of which two put on 8.4 and 9.4 kg respectively with concommitant increases in midarm circumference. It is concluded that endoscopic intubation of carcinoma of the oesophagus or cardia commonly benefits nutritional status by relieving dysphagia.

In order to investigate the effects of anaesthetic induction with a single bolus dose of etomidate on the endocrine response to a standard surgical stress, five patients were randomly allocated to receive etomidate and five to receive thiopentone as an induction agent prior to elective inguinal hernia repair. The group receiving etomidate showed a significant suppression in the circulating level of cortisol at 90 and 120 min post-induction (P less than 0.001) and an elevation in their plasma adrenocorticotrophic hormone at 240 and 360 min post-induction (P less than 0.001). The effect of a bolus dose of etomidate upon circulating cortisol levels was transient and no cardiovascular instability was noted during the study. The etomidate group also showed suppression of their circulating testosterone levels at 90 min post-induction (P less than 0.001), suggesting that etomidate inhibits steroidogenesis at a site other than 11 beta-hydroxylase.

Three patients admitted to the intensive care unit after multiple injury were observed to suffer episodes of adrenocortical insufficiency suggested by clinical manifestations and confirmed by appropriately low cortisol concentrations. This prompted a prospective study of pituitary-adrenocortical function in six multiply injured patients, three of whom showed evidence of adrenocortical suppression. The only factor common to the six patients with abnormally low adrenocortical function was an association between periods of adrenocortical suppression and intravenous infusion of etomidate; when the drug was stopped adrenocortical function was restored, and renewed administration of the drug caused further inhibition. Etomidate infusions lasting only six hours were found to cause low, flat responses to short tetracosactrin tests and grossly raised plasma concentrations of adrenocorticotrophic hormone, suggesting direct suppression of the adrenal cortex. Median plasma cortisol concentrations measured at 0900 were significantly lower and median plasma concentrations of adrenocorticotrophic hormone measured at 0900 were significantly higher in the three patients studied prospectively who were receiving etomidate infusions compared with the three patients who did not receive etomidate (p = 0.05).

Two cases of type III glycogen storage disease are reported in adults; the occurrence of cirrhosis in one case illustrates the potential development of chronic liver disease in this condition. The other was the oldest patient with this condition found in a review of published reports. Electron microscopy of peripheral blood leucocytes to demonstrate excess glycogen was found to be a quick and useful aid to diagnosis. Histology of these adult cases showed a distribution of hepatocyte vacuolation which has not been previously recorded.

Ten healthy male subjects ingested ethanol (BP; 0.5 g/kg body weight) after an overnight fast, on two separate occasions, at environmental temperatures of either 21 degrees C or 30 degrees C. The mean maximal fall in deep body temperature was not significantly different on the two occasions, being 0.18 degrees C and 0.17 degrees C respectively. Metabolic rates throughout the experiments at the two temperatures were not significantly different. The vasodilatation of the hand and forearm vascular beds after ethanol ingestion was markedly reduced at the lower environmental temperature. In three subjects who ingested a higher dose of ethanol (BP; 1.0 g/kg body weight) after an overnight fast, at an environmental temperature of 21 degrees C, the mean maximum fall in core temperature was 0.15 degrees C, which was not significantly different from the change seen after consumption of the lower dose of ethanol. It is likely that the failure of ethanol ingestion to provoke hypothermia at the lower environmental temperature was due to the attenuated vasodilatation observed under these conditions.

Finger tremor was measured in six normal subjects during intravenous infusions of adrenaline (10 ngkg-1min-1 and 50 ngkg-1min-1) resulting in venous plasma adrenaline concentrations within the physiological range (0.77 +/- 0.08 and 2.28 +/- 0.18 nmoll-1). Tremor amplitude significantly increased after 15 and 25 minutes infusion at the higher dose of adrenaline. The lower dose of adrenaline increased tremor in three of the six subjects.

The nature and time-course of acute piroxicam-induced gastric mucosal injury was determined in ten healthy volunteers treated with 10 mg piroxicam twice daily by mouth for 21 days. Mucosal injury was measured endoscopically by visual analogue scales and by the method of Lanza, and luminal blood loss by haemoglobin measurements in gastric washings, 10 h after the first drug dose and then after 5, 10 and 21 days. Acute mucosal injury, consisting mainly of haemorrhagic lesions in the gastric body, developed to a maximum extent within 10 h of the first dose of piroxicam, and did not increase thereafter. By contrast intraluminal bleeding increased little for 10 days and then rose significantly at 21 days, when plasma piroxicam levels reached values likely to affect platelet function. We conclude that gastric mucosal injury and bleeding may be dissociated and may constitute different targets for prophylaxis. Gastric mucosal injury is probably exerted topically as it is maximal at low plasma drug concentrations, whereas bleeding may arise because of interference with platelet-dependent mechanisms.

Over the last 4 yr 302 Celestin dilatations have been performed in 100 patients with benign esophageal strictures. Patients presenting with tighter strictures have a significantly increased need for subsequent dilatation (p less than 0.001). The technique described permits rapid turnover of patients in the endoscopy suite and may be used in even the most elderly patients.

Over an 11-year period 132 patients with achalasia underwent a total of 253 pneumatic bag dilatations of the cardia as the initial treatment. Adequate symptomatic relief was obtained in the majority, but 16 needed cardiomyotomy after pneumatic dilatation had failed to give lasting symptomatic relief. Older patients, aged 60 years or more, showed longer-lasting improvement with pneumatic dilatation than did younger ones and only 1 patient over 50 required cardiomyotomy. Benefit from pneumatic dilatation showed a closer relationship to age than to oesophageal diameter. Of 50 patients followed for more than 5 years, 48% required no further treatment, 40% needed at least one further dilatation to achieve symptomatic relief and 12% came to cardiomyotomy. This study suggests that pneumatic dilatation is safe, effective and particularly useful in the management of the elderly achalasic patient.

Emepronium bromide, a drug used to control urinary frequency, has been reported as causing oesophageal ulceration but not stricture formation. This paper presents 3 cases in which the use of emepronium bromide preceded development of an oesophageal stricture and suggests that the drug played a causative role.

A computerised on-line method of recording oxygen consumption and carbon dioxide excretion from an 'open-circuit' system has been developed and validated. This system enables rapid collection and expression of the data in numerical form.

To assess the value of pneumatic dilatation of the cardia, 63 patients with achalasia have undergone a total of 107 Rider-Moeller dilatations over the last six years. There was a marked improvement in swallowing immediately after dilatation in all but two patients, there were no deaths attributable to the procedure and serious complications were rare (1.6% of patients). The first 50 cases have been followed from nine to 73 months after their initial dilatation (mean follow-up 29.7 months). Twenty nine patients (58%) have not required a further dilatation, 19 patients (38%) required between one and three further dilatations and two patients (4%) required four more dilatations. Continuing need for further dilatation was significantly greater in those patients aged under 45 years than in those aged 45 or more at the time of their initial dilatation (p less than 0.001). Cardiomyotomy was necessary in five patients (10%), because of poor response to pneumatic dilatation; all five cases were under 45 years old at their initial dilatation. Pneumatic dilatation is a safe and effective treatment for achalasia, particularly in the older patient, and in our opinion should be the initial treatment for all patients with achalasia, reserving surgical cardiomyotomy for those who do not respond to several dilatations.

The effect of insulin-induced hypoglycaemia on gastro-jejunal motility was studied in five, healthy, male subjects using tethered, pressure sensitive, radiotelemetry capsules. Thirty minutes after the intravenous injection of soluble insulin (0.15 unit/kg body weight), a significant reduction in blood glucose concentration (control: 5.26 +/- 0.19 SEM mmol/l; insulin: 1.48 +/- 0.44 mmol/l; P less than 0.001) was associated with a rise in heart rate (mean peak rise 29 +/- 8 beats/min, P less than 0.05), systolic arterial blood pressure (mean peak rise 28 +/- 4 mmHg, P less than 0.01) and plasma pancreatic polypeptide concentration (control: 20 +/- 7 pmol/l; insulin: 287 +/- 66 pmol/l; P less than 0.01). These events coincided with a short period of jejunal motor activity, which was not associated with gastric motor activity nor with raised plasma motilin concentrations. During the control study, there were no changes in blood glucose concentration, heart rate, arterial blood pressure or plasma pancreatic polypeptide concentrations, and there was no jejunal motor activity. The interval between successive gastric migrating motor complexes (MMC) was not significantly different in the insulin and control studies (control: median interval 110 min, range 108-148 min; insulin: median interval 124 min, range 115-125 min), suggesting that the fasting gastrojejunal MMC and jejunal motor activity arose independently. Insulin-induced hypoglycaemia is accompanied by jejunal motor activity, which may underlie the abdominal symptoms associated with hypoglycaemia.

This study was performed to determine whether the administration of intravenous fluids, isosmolar with plasma, activated the sympathetic nervous system, thereby causing changes in cardiovascular variables. On four separate occasions, six young, healthy men were studied for 30 min before and, for 40 min after a 60 min period of either (a) intravenous infusion of 500 ml of 5% dextrose, (b) intravenous infusion of 500 ml of a mixture of 10% Intralipid and saline (154 mmol NaCl 1(-1)), (c) intravenous infusion of 500 ml of saline (154 mmol NaCl 1(-1)) or (d) no intravenous infusion. Venous plasma noradrenaline and adrenaline concentrations did not change significantly during any of these interventions. The venous plasma insulin level rose during infusion of 5% dextrose (p<0.001). The respiratory exchange ratio rose during the dextrose infusion and fell during the infusion of the Intralipid and saline mixture (p<0.01). Hand and calf blood flows and vascular resistances were not significantly affected by any procedure. Similar, small, changes in heart rate, arterial blood pressure, metabolic rate, core temperature and mean skin temperature were observed during the four protocols. The provision of small amounts of metabolic substrate, as either glucose or fat, led to rapid changes in fuel utilisation. However, under the conditions of the present experiments, there was no evidence of activation of the sympathetic nervous system.

On three separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline, 50 ng min-1 kg-1 (high A), adrenaline, 10 ng min-1 kg-1 (low A) or sodium chloride solution (saline: 154 mmol of NaCl/l) plus ascorbic acid, 1 mg/ml (control), over 30 min. Venous adrenaline concentrations of 2.19 +/- 0.15 nmol/l, 0.73 +/- 0.08 nmol/l and 0.15 +/- 0.03 nmol/l were achieved during the high A, low A and control infusions respectively. Heart rate rose significantly by 19 +/- 3 beats/min (high A) and by 6 +/- 1 beats/min (low A). Heart rate remained significantly elevated 30 min after cessation of the high A infusion, despite venous plasma adrenaline concentration having fallen to control levels. The diastolic blood pressure fell during the high A and low A infusions, but the systolic blood pressure rose only during the high A infusion. Vasodilatation occurred in the calf vascular bed during both high A and low A infusions. The changes in hand blood flow and hand vascular resistance were not statistically significant, although there was a tendency to vasoconstriction during the infusion of adrenaline. Metabolic rate rose significantly by 23.5 +/- 1.8% (high A) and by 11.8 +/- 1.6% (low A). Metabolic rate remained elevated between 15 and 30 min after termination of the high A infusion. There was an initial transient increase in respiratory exchange ratio (RER) during the adrenaline infusions. During the later stages of the adrenaline infusions and after their cessation, RER fell, probably reflecting increased fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

An epidemiological survey in the City of Derby from 1976 to 1985 indicated that there was no significant difference in the incidence of Crohn's disease in West Indians (4.5-5.6/10(5)/yr) and the caucasian population (7.0/10(5)/yr). These results indicate that West Indians are not genetically protected against the development of Crohn's disease.

Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution.

With use of a liquid-conditioned coverall, the thermoregulatory responses to a lowering of environmental temperature from 35 degrees C to 23 degrees C were assessed in eight normally nourished and six undernourished elderly female patients, during their convalescence after surgical repair of a fracture of the femoral neck. There was no difference in the peripheral vasoconstriction of the two groups in response to a cold environment. On lowering the environmental temperature, the increase in metabolic rate was significantly impaired in the undernourished group compared with the normally nourished group (P less than 0.05). There was a small decrease in core temperature in the undernourished group (median change -0.1 degree C) during the period of exposure to the lowest environmental temperature (23 degrees C). This was significantly different from the lack of change (median change 0 degrees C) in core temperature observed in the normally nourished group (P less than 0.05). This defect of thermogenesis may underlie the propensity of undernourished elderly patients to suffer hypothermia and fracture of the femoral neck in the winter months.

1. The cardiovascular and metabolic responses to low doses of isoprenaline (15 and 5 ng min-1 kg-1 body weight infused over 30 min) were determined in six healthy males. The study was performed to investigate whether there were sustained effects after the termination of the isoprenaline infusion, as has been observed previously after the infusion of adrenaline. 2. The isoprenaline infusions produced dose-dependent increases in heart rate, systolic blood pressure and metabolic rate, but similar increases in calf blood flow and decreases in diastolic blood pressure for the two infusion rates. Finger tremor was increased in amplitude by the 15 ng min-1 kg-1 infusion only. The changes in each of these physiological variables largely resolved within a few minutes of discontinuing the isoprenaline infusions. 3. There were no changes in arterialized venous plasma adrenaline or noradrenaline levels during the isoprenaline infusions. Mean peak plasma isoprenaline levels were 0.16 +/- 0.02 nmol/l during the 5 ng min-1 kg-1 infusion and 0.71 +/- 0.05 nmol/l during the 15 ng min-1 kg-1 infusion. 4. Plasma insulin levels increased with isoprenaline but blood glucose concentrations were unchanged, consistent with a direct effect of isoprenaline on beta 2-adrenoceptors mediating insulin release from pancreatic beta-cells. Blood glycerol concentration also increased with isoprenaline but blood lactate concentration was unaltered. 5. The present study demonstrates pronounced cardiovascular and metabolic effects of low dose isoprenaline infusions. Differences in the rate of resolution of the changes induced by isoprenaline and by adrenaline seen in previous studies may result from a significant difference in their metabolism.

The [14C]-triolein absorption test has been assessed using a preprepared fat meal in a procedure that can be completed within a working day on an inpatient or outpatient basis. An initial study showed complete discrimination between 30 control subjects and 13 patients with raised faecal fat excretion. A prospective evaluation in 57 patients under investigation for gastrointestinal disease showed a sensitivity of 85% and specificity of 93% (100% if two obese subjects are excluded). The test discriminates satisfactorily between patients with and without fat malabsorption and makes the measurement of faecal fat unnecessary in most circumstances.

Two patients with primary haemochromatosis are reported in whom hepatocellular carcinoma supervened despite removal of excess iron after venesection therapy. These are the first patients described in whom hepatocellular carcinoma has complicated primary haemochromatosis in the absence of concomitant cirrhosis.

During the period 1972-85, 3712 splenectomies were performed in the Trent region giving a mean splenectomy rate of 5.8 per 100,000 population per year. Of these, 37.4% were incidental to other surgical operations and 23.4% were as a result of trauma. During this period there was a marked reduction in the splenectomy rate in children aged under 10 years for trauma and for haematological diseases. No such reduction was observed in older patients for these indications. Splenectomy for lymphoma fell progressively after 1977.

As is well recognized, activities of creatine kinase (CK, EC 2.7.3.2) and lactate dehydrogenase (EC 1.1.1.27) in plasma may be substantially increased in hypothyroidism. We emphasize here that an increase and decrease in CK-MB isoenzyme, characteristic of acute myocardial infarction, can occur in hypothermic myxedema coma without myocardial infarction.