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Biomedical subjects

J G Ratcliffe

Publications and source records attributed to J G Ratcliffe.

At least 55 records · Page 3Linked to original sources

Multiple hormone secretion by a human pancreatic glucagonoma in culture.

A patient presenting clinically with the glucagonoma syndrome had high plasma glucagon levels (1920 ng/l) and at laparotomy, a pancreatic islet cell tumour was removed. The tumour was dispersed and placed in culture where it remained viable for 63 days. The tumour cells secreted immunoreactive (IR) glucagon at levels up to 2400 ng/l as detected by a C-terminal glucagon specific antibody and 85 400 ngequiv./l as measured by an N-terminal glucagon specific antibody. The difference between these two levels was attributed to the presence of different molecular forms of glucagon measured with the N-terminal specific antibody. IR insulin (up to 302 mU/l) and IR somatostatin (up to 2500 ng/l) were also detected. There was no direct or inverse correlation between different hormone levels. Small but significant levels of N-terminal and C-terminal vasoactive intestinal peptide (VIP) were detected in some cultures but there was no evidence of gastrin or ACTH. Glucagon and somatostatin secretion persisted for the duration of the culture (63 days) but insulin concentrations declined. Incubation of cultures with somatostatin (1 ng/ml) caused a 75% decrease in glucagon levels, while insulin (1000 mU/l) produced a 70% inhibition of somatostatin.

Adenoma, Islet Cell↗

Leucocyte esterase-nitrite screening method for pyuria and bacteriuria.

The value of the one minute leucocyte esterase-nitrite chemical strips as a screening procedure for detecting appreciable levels of pyuria and bacteriuria was assessed by comparison with microscopy and culture results. The likelihood that a negative leucocyte esterase result indicated less than 10 white cells/cu mm by microscopy (the negative predictive value), was 90.1% and that a negative nitrite result indicated less than 10(5) organisms/ml was 91.3%. There were many false positive results with both tests, however, and the overall predictive value of a positive leucocyte esterase or nitrite test, or both, was low. The leucocyte esterase-nitrite strip was neither sufficiently sensitive nor specific enough to be used as a cost effective method for screening urines in the laboratory.

Bacteriuria↗

Gastrin and gastric secretion in patients with recurrent peptic ulceration--unexpected correlations.

The role of gastrin in the pathogenesis of recurrent peptic ulceration is not established although it is known that plasma gastrin levels are frequently elevated after vagotomy. This study aims to determine whether there is a relationship between gastrin and gastric secretion in patients with and without recurrent ulceration after surgery for duodenal ulceration (DU). The basal acid output (BAO) in 23 and the peak acid output to pentagastrin (PAOPg) in 10 patients with symptomatic recurrent ulcers after DU surgery were determined along with the BAO and PAOPg in 10 control patients who were asymptomatic following DU surgery. The fasting plasma gastrin was determined in all patients and correlated with the acid output. An inverse correlation was demonstrated between the BAO and plasma gastrin in the asymptomatic patients (p less than 0.05) and the patients with proven recurrent ulcers (p less than 0.01) and there was a direct correlation between the PAOPg and plasma gastrin in the recurrent ulcer group (p less than 0.05) which was not observed in the control group. It is suggested that in a subgroup of recurrent ulcer patients 'G cell hyperfunction' may occur and this may have a role in the aetiology of this condition.

Adolescent↗

Differences between peptic ulcer and control patients on the basis of the response to secretin.

The secretin injection test is considered a useful adjunct to the diagnosis of gastrinoma, although it may lack specificity. This study determined whether the release of gastrin in response to secretin was different in duodenal ulcer and control patients. Tests were performed on 10 duodenal ulcer patients, 10 normal control subjects, 20 patients asymptomatic after ulcer surgery, of whom 13 had a vagotomy and drainage, 4 a highly selective vagotomy and 3 a vagotomy and antrectomy. The secretin test was also performed in 49 patients with endoscopically proven recurrent ulcers. The surgery performed in this latter had consisted of a vagotomy and drainage in 36, a highly selective vagotomy in 7 and a vagotomy and antrectomy in 6 patients. The basal plasma gastrin level was similar in normal controls, duodenal ulcer patients and patients with vagotomy and antrectomy, both with and without recurrent ulcers. The level was elevated in all the other groups of patients with vagotomy both with and without recurrent ulcer. The plasma gastrin did not change significantly after secretin injection in the normal control or asymptomatic ulcer surgery patients, but rose in the duodenal ulcer patients and all the groups of patients with recurrent ulcer. Most of these increases were validated statistically as were the differences in response between the ulcer and control patients. These results indicate that there are differences in the plasma gastrin response to intravenous secretin between active duodenal ulcer and control patients. This findings may aid our understanding of the pathophysiology of peptic ulcer disease and explains the lack of specificity of the secretin test.

Adolescent↗

Changes in erythrocyte transketolase activity and the thiamine pyrophosphate effect during storage of blood.

Whole blood and washed erythrocytes from nutritionally normal and abnormal elderly patients were stored at room temperature, 4 degrees C and -20 degrees C for up to 14 days. In both groups, and under all storage conditions, the erythrocyte transketolase (ETK) activity and the thiamine pyrophosphate (TPP) effect decreased with time of storage. The ETK activity for specimens stored at -20 degrees C decreased significantly by day 14 (P less than 0.05). The TPP effect in specimens stored at -20 degrees C decreased significantly in the nutritionally abnormal group at 4 days (P less than 0.05) and in the nutritionally normal group by day 14 (P less than 0.05). These significant changes in ETK activity and TPP effect with storage can lead to misleading interpretation of thiamine nutritional status.

Aged↗

Measurement of low concentrations of bovine thyrotrophin by iodide uptake and organification in porcine thyrocytes.

Thyrocytes isolated from porcine thyroids by mechanical and enzymatic dispersion and cultured in Eagle's minimal essential medium, supplemented with 5% (v/v) fetal calf serum, glutamine and cortisol, formed a continuous monolayer within 48 h. This monolayer was without cytochemical peroxidase and diaphorase (NADPH reoxidation) activity. In the presence of bovine thyrotrophin (bTSH; 50 mu./l) the cells developed a follicular-like architecture which was maximal at 4 days before reverting back to a uniform monolayer at 6 days. There were no detectable changes in the total DNA content over this period. The follicular structures had marked diaphorase and peroxidase activity, the latter being apically distributed. Concomitant with follicle formation bTSH induced uptake and organification of iodide presented to the cells during the last 6 h of culture. The extent of this process depended on the dose of bTSH and the duration of stimulation. The most sensitive effects for both iodide uptake and organification occurred with 1 mu. bTSH/l and were maximal with 100 mu./l. Uptake and organification were increased 20 +/- 8-fold and 9.6 +/- 2-fold (n = 10) respectively over the control with 100 mu./l and the doses of bTSH at which a half maximal response was seen (ED50) were 15 +/- 2 and 7 +/- 1 (S.D) mu./l (n = 10) respectively. On changing the culture medium to a serum-free system using HB101 culture medium the stimulation time for the most sensitive bTSH effect was reduced to 2.5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pre-operative carcino-embryonic antigen and survival in patients with colorectal cancer.

The relationship between pre-operative levels of carcino-embryonic antigen (CEA), resectability of the primary tumour, the extent of tumour spread and subsequent survival was studied in 333 patients with colorectal cancer. Twenty-five per cent of patients undergoing 'curative' resection had elevated CEA levels compared with fifty-six per cent of patients receiving palliative treatment. Twenty-five per cent of patients with Dukes B or C tumours had elevated pre-operative CEA levels compared with seventy per cent of patients with stage D disease. In patients undergoing 'curative' resection there was no correlation between pre-operative CEA levels and subsequent survival. In patients undergoing palliative resection, elevated pre-operative CEA levels were associated with poor survival. Although pre-operative levels of CEA reflect the extent of the underlying disease process, estimations of pre-operative CEA levels are of limited value in predicting patients with a poor prognosis following curative resection for colorectal carcinoma.

Carcinoembryonic Antigen↗

Paracetamol metabolites in the neonate following maternal overdose.

A case of paracetamol overdose in a 36 week pregnant woman is described. The baby was delivered by Caesarian section 6 h after the overdose. The mother but not the baby was treated with N-acetylcysteine and neither suffered liver damage. The plasma paracetamol half-life was prolonged to 10 h in the neonate compared to 2.5 h in the mother and was unaffected by a two volume exchange transfusion. The pattern of urinary metabolites in the neonate was similar to that observed in the mother, but there was a marked delay in the time taken to reach peak plasma concentrations of metabolites. This is consistent with a very slow biotransformation of the drug and may explain the relative resistance of very young children to the hepatotoxicity of paracetamol. There was no evidence of limited or decreasing capacity in sulphate conjugation nor was sulphation the major metabolic pathway. In retrospect both the obstetrical intervention and the exchange transfusion were unnecessary.

Acetaminophen↗

The effects of prolonged bromocriptine administration on PRL secretion GH and glycaemic control in stable insulin-dependent diabetes mellitus.

Plasma glucose, PRL and GH concentrations were measured at hourly intervals over a 24-h period before and after oral bromocriptine administration in a dosage of 7.5 mg/day for 6 weeks in nine stable insulin-dependent diabetic men. The pattern of PRL secretion was noted to be normal in stable diabetes (with a mean concentration of 205 mu/l +/- 23 SEM) and was effectively suppressed by bromocriptine (to a mean concentration of 51 mu/l +/- 2 SEM). This suppression of PRL secretion caused no major alteration in glycaemic control, mean plasma glucose for the group was 10.6 mmol/l +/- 3.4 SD before and 9.6 mmol/l +/- 3.1 SD after bromocriptine administration. Bromocriptine produced no change in plasma glucose or GH profiles. It is concluded that PRL secretion is not a major influence on carbohydrate metabolism in stable diabetics.

Adult↗

The prevalence of gastrinomas in recurrent peptic ulceration.

The prevalence of gastrinomas and the Zollinger-Ellison syndrome is unknown. In order to examine a high risk group of patients, basal and secretin-provoked plasma gastrin levels were determined in 50 consecutive patients, predominantly from the west of Scotland. All had endoscopically proven recurrent peptic ulceration following duodenal ulcer surgery. This resulted in three cases strongly suspected of having a gastrinoma. Further investigations including exploratory laparotomy were unable to demonstrate a gastrinoma in two, but the evidence suggested an occult tumour in one. In this remaining unoperated patient, the serum gastrin returned to normal. The reference range for both basal and secretin stimulated gastrin response and percentage change has been determined in normal control subjects (n = 10) and in primary ulcer patients (n = 20). It is concluded that in this study, gastrinomas had a less than 2 per cent prevalence in patients presenting with recurrent peptic ulceration. As the diagnosis of a gastrinoma changes the surgical approach, conducting screening tests still seems warranted.

Adolescent↗

Second laparotomy following 'curative' resection for colorectal cancer.

Second laparotomy was undertaken in 63 patients with suspected local recurrence following 'curative' resection for colorectal cancer. Nine patients proved to have benign disease and 4 a new cancer. Local tumour recurrence was confirmed in 50 patients. Of these, 19 underwent further resection of the tumour, 19 had palliative colostomy or bypass, and laparotomy only was performed in 12. Five of 15 patients undergoing secondary 'curative' resection survived 1 year and 3 survived 18 months. In contrast only 6 of the remaining 35 patients survived 1 year and none survived 18 months. Second laparotomy may be of benefit in a small number of patients with local recurrence following apparently curative resection for colorectal cancer.

Colonic Neoplasms↗

Immunoassay of blood spot TSH; development of a rapid two-site immunoradiometric assay and comparison with radioimmunoassay as a screening method for neonatal hypothyroidism.

The development of a two-site immunoradiometric assay (IRMA) for thyrotropin (TSH) eluted from dried blood filter paper discs is described and compared with a conventional TSH radioimmunoassay (RIA) as a screening procedure for neonatal hypothyroidism. The iodinated antibody for the IRMA is prepared by a reproducible four step procedure. Specific antibody is selected from whole TSH antiserum with TSH covalently linked to microparticulate cellulose, iodinated as the solid phase antigen-antibody complex, and eluted by repeated changes in pH from 3 to 10. The pooled eluted material is finally purified by Sepharose 6-B gel chromatography to recover labelled monomeric anti-TSH IgG. Solid phase antibody for the IRMA is prepared by covalently linking a partially purified IgG fraction of TSH antiserum to carbonyldiimidazole-activated microparticulate cellulose. Typically yields of 2-3 mg protein per 100 mg cellulose (2-3%, w/w) are obtained. The two-site IRMA involves a primary incubation of excess labelled TSH antibody and the blood disc for 16-18 h at pH 8 and a secondary 3 h incubation under agitation, with solid phase TSH antibody. Bound and free fractions are separated by a semi-automated washing procedure. Compared with the conventional RIA, the two-site IRMA is quicker (results available within 24 h compared to 3 days for RIA), more precise at clinically important TSH levels (25-30 mU TSH/l), and more sensitive (detection limit less than w mU/l compared to 6 mU/l for RIA). The two-site IRMA is technically simpler than RIA and has proved rugged in routine practice. TSH levels in filter paper blood spots prepared from whole blood with levels of standard TSH (MRC 68/38) within the range 6 to 200 mU/l, correlated well in both assays (r = 0.969). Recoveries of 98% and 104% were demonstrated for the two-site IRMA and RIA, respectively. It is concluded that the two-site TSH IRMA has advantages over conventional RIA in speed, sensitivity, precision and ruggedness and can be recommended as an efficient screening procedure for neonatal hypothyroidism.

Autoanalysis↗

Cryosurgery or microsurgery in the management of acromegaly.

Fifty-six patients with growth hormone-secreting pituitary adenomas, 28 treated by cryoablation and 28 by microsurgery, have been followed up from three to eight years. Mean serum growth hormone concentrations were less than 10 mU/L in 19 patients (68%) after microsurgery as compared with seven (25%) after cryosurgery. Hypopituitarism and operative complications were more frequent after cryosurgery. Transsphenoidal microsurgery was particularly successful in reducing growth hormone secretion without impairing normal pituitary function, when the patient had not been previously treated by another method.

Acromegaly↗

Ectopic hormones.

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APUD Cells↗