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Biomedical subjects

W D Neithercut

Publications and source records attributed to W D Neithercut.

At least 37 records · Page 2Linked to original sources
PubMed1992

Helicobacter pylori-related hypergastrinaemia is not due to elevated antral surface pH. Studies with antral alkalinisation.

It has been postulated that Helicobacter pylori-related hypergastrinaemia is due to bacterial ammonia raising antral surface pH and thus preventing acid inhibition of gastrin release. If true, the infection should not alter gastrin release at neutral intragastric pH. To test this, we have studied basal and meal-stimulated gastrin at uncontrolled pH and at pH greater than 6 in duodenal ulcer patients before and after eradication of H. pylori. The median integrated gastrin response to the meal alone was 2525 ng/l.min (range, 550-8725) before and 725 ng/l.min (range, 250-2925) after eradication of H. pylori (p less than 0.01). The corresponding values when intragastric pH was maintained above 6 were 3700 ng/l.min (range, 1900-14,100) and 1400 ng/l.min (range, 400-3400) (p less than 0.01). The median reduction in gastrin after eradication of H. pylori was thus similar when the meal was taken at uncontrolled pH (61%; range, 0-97%) and at pH greater than 6 (69%; range, 36-89%). Likewise, 5 h of gastric alkalinisation did not cause the basal gastrin values when H. pylori was eradicated to increase to those observed when H. pylori was present. These findings indicate that the hypergastrinaemia is not due to elevated antral surface pH.

Adult↗
PubMed1991

Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations.

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.

Adult↗
PubMed1991

Is Helicobacter pylori associated hypergastrinaemia due to the bacterium's urease activity or the antral gastritis?

Eradication of Helicobacter pylori is associated with a fall in serum gastrin but the way in which the infection raises the serum gastrin concentration is not clear. It may be related to the ammonia produced by the bacterium's urease stimulating gastrin release by the antral G cells. Alternatively, the antral gastritis induced by the infection may modify the regulation of gastrin release. We have examined serum gastrin in 10 patients before and 24 hours after starting triple anti-H pylori treatment consisting of tripotassium dicitrato bismuthate 120 mg four times daily, metronidazole 400 mg three times daily, and amoxycillin 500 mg three times daily. The urease activity, assessed by the 20 minute value of the 14C-urea breath test, fell from a median of 176 (range 116-504) kg% dose/mmol CO2 x 100 pretreatment to 5 (2-15) at 24 hours (p less than 0.005). The median antral gastritis score was 6 (4-6) pretreatment and fell to 3 (2-5) at 24 hours (p less than 0.02), and this was due to resolution of the polymorphonuclear component. Despite this complete suppression of bacterial urease activity and partial resolution of antral gastritis the median basal gastrin concentration remained unchanged, being 57 ng/l (45-77) pretreatment and 59 ng/l (45-80) at 24 hours and the median integrated gastrin response to a standardised meal was also unaltered, being 4265 ng/l/min (range 1975-8350) and 4272 ng/l/min (range 2075-6495) respectively. These findings do not support a causal association between H pylori urease activity and hypergastrinaemia and show rapid improvement of antral gastritis after starting anti-H pylori treatment.

Adult↗
PubMed1991

Effect of inhibition of Helicobacter pylori urease activity by acetohydroxamic acid on serum gastrin in duodenal ulcer subjects.

The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection.

Adult↗
PubMed1991

Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.

Adolescent↗
PubMed1991

Harnessing of urease activity of Helicobacter pylori to induce self-destruction of the bacterium.

Eradication of Helicobacter pylori with currently available antibacterial agents is unsatisfactory due to the risk of side-effects and the emergence of resistance. The organism rapidly dies in vitro in the presence of urea at pH 6. When incubated in citrate buffer (pH 6) plus urea (10 mM) the five minute survival was 26% compared with 96% without urea and the survival progressively decreased with increasing urea concentrations, being only 9% in 50 mM urea. The bactericidal effect depended on pH as the organism survived in citrate buffer (pH 7) plus urea (50 mM). The death of the organism at pH 6 in the presence of urea was prevented by the addition of the competitive urease inhibitor hydroxyurea. These findings indicate that destruction of the organism is mediated by its exceptionally high urease activity. Harnessing this enzyme to induce self-destruction could provide a new approach to eradicating this common infection.

Buffers↗
PubMed1991

Suicidal destruction of Helicobacter pylori: metabolic consequence of intracellular accumulation of ammonia.

The role of pH, citrate buffer, and urea were investigated in the suicidal destruction of Helicobacter pylori, with particular reference to the organism's urea and ammonia metabolism. The median five minute survival of H pylori in the presence of 50 mmol/l urea in 0.2 M citrate buffer at pH 6.0 was only 14%, compared with 53% in the same solution at pH 7.0. The median amount of ammonium released into the incubating solution over five minutes was lower at pH 6.0 (9 mumol) than at pH 7.0 (18 mumol) despite similar uptake of urea. The median five minute survival of H pylori in 0.2 M citrate buffer, pH 6.0, decreased from 89% to 14% when the urea concentration was increased from 1 mmol/l to 50 mmol/l. Likewise, the recovery in the incubating solution of ammonia resulting from the hydrolysis of urea fell from 27% to 3% when the initial urea concentration was increased from 1 mmol/l to 50 mmol/l. Survival of H pylori in the presence of 30 mmol/l urea at pH 6.0 was compared in 0.2 M citrate, acetate, and phosphate buffers. The median five minute survival was less in the citrate buffer, at 29%, than in either the acetate buffer 80% or the phosphate buffer 100%. The percentage recovery of ammonia was similar in the three buffers. These findings indicate that the suicidal destruction of the bacterium may be explained by intracellular accumulation of ammonia due to production in excess of the rate of excretion.

Ammonia↗
PubMed1991

Medical training in clinical biochemistry (chemical pathology) in Scotland 1985-1989.

A questionnaire was sent to 35 doctors who were believed to have trained in clinical biochemistry in Scotland between 1 January 1985 and 31 December 1989. Thirty replies were received from 23 individuals who were still employed in the specialty (including seven consultants and nine senior registrars) and from seven individuals who had left. Twenty considered that training within the laboratories in which they were employed had not been satisfactory. The main emphasis of training was directed towards reporting duties, clinical liaison, research, teaching and outpatient clinics. Little training was provided for the development of analytical experience, personnel selection and laboratory management. Those surveyed identified poor training in laboratory management as the main aspect of training which required improvement.

Adult↗
PubMed1990

Persistent nephrogenic diabetes insipidus, tubular proteinuria, aminoaciduria, and parathyroid hormone resistance following longterm lithium administration.

We report a patient who developed persistent nephrogenic diabetes insipidus associated with renal tubular acidosis, renal resistance to parathyroid hormone, aminoaciduria and proximal tubule pattern proteinuria in the presence of a reduced glomerular filtration rate (19-24 ml/min). A review of the previous reports of persistent nephrogenic diabetes insipidus revealed that in all patients the glomerular filtration rate had been less than 60 ml/min at presentation. Chronic renal failure may therefore predispose to the development of persistent nephrogenic diabetes insipidus in patients receiving lithium.

Acidosis, Renal Tubular↗
PubMed1990

Delayed diagnosis of Addison's disease.

Addison's disease may be difficult to diagnose because of the non-specificity of the most frequently occurring symptoms. Hyponatraemia, hyperkalaemia, and uraemia are commonly detected in sera from patients with Addison's disease. We report two patients in whom the diagnosis was delayed, despite typical biochemical abnormalities in their sera during initial presentation. A computer search of 4 weeks of biochemical data (9862 requests for electrolytes) indicated that these typical biochemical abnormalities occurred commonly in other patients, increasing the difficulty of the clinical biochemist in detecting Addison's disease. Awareness of this problem, in combination with adequate clinical information, should enable the clinical biochemist to assist in the earlier diagnosis of Addison's disease.

Addison Disease↗
PubMed1989

Effect of calcium, magnesium and sodium ions on in vitro nucleation of human gall bladder bile.

The effect of increasing the calcium, magnesium and sodium concentration in gall bladder bile samples from 21 patients with gall stones and nine controls on the in vitro rate of formation of cholesterol microcrystals and numbers of cholesterol microcrystals formed was examined. Addition of these cations to raise the mean maximum concentration of calcium ions to 19.8 mmol/l, of magnesium ions to 20 mmol/l and sodium ions to 998 mmol/l did not trigger nucleation in control bile samples or samples from patients with gall stones. Increasing the mean concentration of calcium ions to 8.6 mmol/l and of sodium to 320 mmol/l increased the numbers of cholesterol monohydrate crystals/0.1 mm3 counted by light polarisation phase contrast microscopy at the time of nucleation in samples from patients with gall stones from a median of 2 (range 1-10) in control portions to 18 (range 2-128) for calcium ions and 10 (range 2-141) for sodium ions (p less than 0.001). Calcium and magnesium ions were more effective than sodium ions, and calcium ions could increase crystal numbers at concentrations found in samples from patients with gall stones, median 4.6 mmol/l (range 2.7-16.9 mmol/l). The concentrations of calcium and magnesium present in bile may therefore influence the rate of development of gall stones.

Bile↗
PubMed1989

On-call service: the role of chemical pathologists.

The workload of the chemical pathology advisory on-call service was investigated. Over three years 317 calls were recorded, giving a mean of nine calls a month. Seasonal variation in the number of calls was observed, with an increase in calls during December, January, and February. Requests for the arrangement of analysis accounted for 231 calls, while there were 98 requests for advice. Authorization of a request for analysis was the outcome of 156 calls. Advice with respect to investigation, treatment, or interpretation of results was offered during 173 calls. The acute medical and surgical wards, the accident and emergency department, renal unit and intensive care unit accounted for 198 of the calls. The two analyses most frequently requested, through the advisory on-call service, were serum digoxin and blood ethanol, with 51 and 33 requests, respectively. The "acute" wards and accident and emergency department had the greatest request rate, accounting for 35 of the requests for digoxin and 26 of the requests for blood ethanol. The acute care areas were responsible for the major part of the workload, and a clinical requirement for the services of chemical pathologists out of hours, was observed.

Blood Chemical Analysis↗
PubMed1989

Drug therapy in patients with diabetes mellitus: an audit.

The drug therapy prescribed for 412 diabetic patients attending an outpatient clinic over a 12 week period was recorded to try and identify potential therapeutic problems. Over 90% of the patients were prescribed at least one drug (including insulin) with oral hypoglycaemic agents prescribed for 86% of non-insulin requiring diabetics. 19% of patients were prescribed more than three drugs and few patients took drug combinations. Of patients prescribed either glibenclamide or chlorpropamide, 63% were aged 65 yr or older. Despite their potential adverse clinical and biochemical effects, diuretics and beta-blockers were commonly prescribed, especially in hypertension. The prescribing of "newer" anti-hypertensive drugs, combination products in patients taking a multiple drug regimen, and the potential dangers of sulphonylureas in the elderly are three areas where alteration of prescribing habits may be of value.

Adrenergic beta-Antagonists↗
PubMed1988

Glycemic control and raised serum alanine aminotransferase activity in treated diabetes mellitus.

The prevalence of raised serum liver-associated enzyme activity in stabilised, treated diabetic outpatients without concurrent hepatobiliary disease was investigated using a retrospective computer search of biochemical data. The frequency of raised alanine aminotransferase, aspartate aminotransferase, or gamma glutamyl transferase activity found among diabetic, general medical and respiratory outpatients was compared with that found in apparently healthy controls. It was established that a raised activity of any of the three enzymes occurred with a similar frequency in each outpatient group. However, only with alanine aminotransferase did the frequency of elevation (7.1%) in the patients with previously diagnosed hepatobiliary disease exceed that of healthy controls. A raised alanine aminotransferase activity in diabetic outpatients was associated with good glycemic control (hemoglobin A1 less than 8%, p less than 0.02) and treatment with oral hypoglycaemic agents (p less than 0.001).

Alanine Transaminase↗
PubMed1988

Nosocomial dysnatremia.

Patients who exhibited both hyponatremia and hypernatremia during a single admission were identified by a review of their biochemistry data. The mortality of patients who developed either hypernatremia or hyponatremia, followed by the opposite abnormality within less than or equal to 10 days, was 42%. This was greater than the 8.2% mortality for an age-, sex-, and admission-matched normonatremic control group (P less than 0.01, chi 2). Eight of the 10 patients who died had had a change in the sodium concentration in serum greater than 20 mmol/L. The interval (days) between the maximum and minimum sodium concentrations in the survivors and those who died was not statistically different. We found no specific clinical features that could be used to predict the development of this biochemical abnormality.

Adult↗
PubMed1987

Nutritional survey of patients in a general surgical ward: is there an effective predictor of malnutrition?

A survey of patients in a general surgical ward was undertaken to establish biochemical and anthropometric standards which could be used to detect malnourished patients in hospital. Results of biochemical and anthropometric tests of nutritional status were compared with assessment by a clinician and the quick nutritional index of Seltzer. Triceps skinfold thickness and serum albumin concentrations indicated that 29% and 35% of patients, respectively, were undernourished compared with 16% by clinical assessment and 17% by the quick nutritional index. Significant correlations (p less than 0.001) between serum albumin and transferrin concentrations and arm muscle area were found for men but not for women. Poor nutritional specificity and sensitivity of some anthropometric and biochemical tests may account for the difference in the level of undernutrition found by these tests and clinical assessment. This shows the importance of the choice of test in influencing the level of undernutrition detected.

Adolescent↗