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Biomedical subjects

J N Primrose

Publications and source records attributed to J N Primrose.

At least 55 records · Page 3Linked to original sources
PubMed1993

Peri-operative modulation of cellular immunity in patients with colorectal cancer.

The peri-operative cellular immune response is depressed in patients with gastrointestinal cancer, a factor which may facilitate malignant dissemination. We have investigated the effects of peri-operative rIL-2 and a combination of rIL-2 and interferon-alpha (IFN-alpha) on both peripheral blood lymphocyte function and number in patients undergoing surgical resection for colorectal cancer. Fifty-two patients were randomly allocated to either control, rIL-2 or rIL-2 with IFN-alpha treatment arms. In vitro studies were performed pre-operatively and on post-operative days 1, 4, 7 and 10. Natural killer (NK) and lymphokine-activated killer (LAK) cell function were profoundly depressed in control patients (P < 0.001; P < 0.01), an effect abrogated in both treatment groups; indeed NK function was augmented in the rIL-2 and IFN-alpha group on the first post-operative day in association with an increase in the percentage of cells expressing CD16 and CD56 (P < 0.01). Flow cytometric analysis of lymphocyte subsets in the control group was unremarkable, except for an early post-operative fall in numbers of lymphocytes. Treatment with either rIL-2 or rIL-2 and IFN-alpha produced an initial profound reduction in T lymphocyte numbers, followed by a 'rebound' lymphocytosis of activated CD3+ T cells, as demonstrated by a significant increase in co-expression of CD25, CD38 and CD45RO. No significant differences were observed between either of the treatment groups. Adjuvant immunotherapy affects peri-operative anti-tumour immune responses, and this may influence long term outcome in patients undergoing surgery for gastrointestinal cancer.

Colorectal Neoplasms↗
PubMed1993

The effect of intravenous ranitidine on the intragastric pH of preterm infants receiving dexamethasone.

Gastric perforation is a catastrophic, albeit uncommon, side effect of steroid treatment for premature infants with bronchopulmonary dysplasia (BPD). A reduction of intragastric acidity may protect against peptic ulceration. The effect of different doses of ranitidine, given as intravenous infusions, on intragastric acidity in premature neonates was therefore examined. Ten consecutive, enterally starved, infants receiving dexamethasone (0.6 mg/kg) for BPD were enrolled. Intragastric pH was continuously monitored on the day before steroid treatment and on the four following days, initially without H2 blockade and then using a continuous intravenous infusion of ranitidine at 0.031, 0.0625, and 0.125 mg/kg/hour. An infusion of 0.0625 mg/kg/hour of ranitidine was sufficient to increase and maintain gastric pH above 4; the authors therefore use this infusion during dexamethasone administration as possible prevention of gastric perforation.

Bronchopulmonary Dysplasia↗
PubMed1993

Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer.

The systemic IgG response to Helicobacter pylori was examined in 70 patients with gastric cancer. H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA), and serological recognition of H pylori antigens was characterised by western blotting. A percentage of 78.5 were seropositive by ELISA. Two of five patients under age 50 were seronegative. Positivity was unrelated to age, sex, tumour type, or site. Ninety one per cent of ELISA positive cancer patients recognised the H pylori cytotoxin associated 120 kilodalton (kD) protein, significantly more than a control group of 47 ELISA positive patients with non-ulcer dyspepsia (72%). Four of 15 ELISA negative cancer patients also showed recognition of this protein in western blots. Mucosal IgA responses to H pylori were examined by immunoblotting supernatants of in vitro cultured resected antral mucosa in an overlapping group of 19 gastric cancer patients. Eighteen had a positive response, including 10 of 11 negative for H pylori by biopsy urease testing. The systemic and local immunoblotting results show that the high seroprevalence of H pylori antibodies detected by ELISA is nevertheless an underestimate of past infection. Dyspepsia screening policies based solely on H pylori ELISA would miss some young patients with gastric cancer. Further study of the relation of the H pylori cytotoxin to gastric precancerous lesions is warranted.

Adenocarcinoma↗
PubMed1993

Somatostatin binding in human gastrointestinal tissues: effect of cations and somatostatin analogues.

This study characterises the somatostatin binding site in human gastrointestinal cancer and mucosa in terms of cationic specificity and relative affinity for three somatostatin analogues. Competitive displacement assays were performed on plasma membranes from human gastric and colonic tissues using radiolabelled somatostatin-14 as ligand. Comparison was made with the somatostatin binding site in rat cerebral cortex. In gastrointestinal tissue, magnesium decreased and sodium increased specific binding. By contrast, in rat cerebral cortex, the converse cationic effect was seen. These changes resulted from alterations in receptor density, with no change in receptor affinity. Displacement studies were then performed with somatostatin-14 and somatostatin analogues RC-160, somatuline, and octreotide. RC-160 and somatuline displaced radiolabel from binding sites in gastric and colonic cancer and mucosa with 10-fold lower affinity than the native peptide. Octreotide did not displace radioligand in gastric or colonic cancer at any concentration tested. By contrast, in rat cortex, although all three analogues displaced with a lower affinity than the native peptide, there was no difference between analogues. These data suggest a distinct somatostatin receptor subtype in gastrointestinal tissues.

Adenocarcinoma↗
PubMed1993

Immunocytochemical localisation of parietal cells and G cells in the developing human stomach.

Previous studies on the distribution of parietal cells and G cells in normal adult stomachs have shown that in about 20% of specimens parietal cells extended to the pylorus. This study aimed to examine the distribution of parietal cells and G cells in the body and antrum of the developing human stomach in relation to anatomical landmarks, using histological and immunocytochemical methods. In all 15 fetal stomachs examined, parietal cells extended to the pylorus and expressed intrinsic factor and hydrogen-potassium-ATPase activity from week 13 of gestation. By contrast, in only one of the five infant stomachs did parietal cells extend to the pylorus: this is identical to the distribution in the adult. G cells developed in the antrum from 18 weeks' gestation and their distribution did not differ between the fetal and infant stomachs. These findings indicate that parietal cells disappear from the antrum of the stomach in the third trimester of pregnancy, but this process fails to occur in approximately 20% of the population.

Adult↗
PubMed1992

Perioperative immunotherapy with recombinant interleukin 2 in patients undergoing surgery for colorectal cancer.

Major surgery impairs the cellular immune response. We have therefore studied the immunological effects of low-dose recombinant interleukin 2 given to patients undergoing surgery for colorectal cancer to determine whether this agent has potential in perioperative adjuvant immunotherapy. Patients were randomly allocated to control (n = 13) or treatment groups (n = 12). Immunological studies of both lymphocyte function and subset number were performed preoperatively and on Days 1, 4, 7, and 10. Treatment with recombinant interleukin 2 prevented the postoperative fall in both natural killer and lymphokine-activated killer cell cytotoxicity, clearly demonstrated in the control group. The treatment group also showed in vivo T-cell activation with an initial lymphopenia followed by a rebound lymphocytosis and upregulation of the subset markers CD25 (interleukin 2 receptor) and CD45RO (T-memory cells). These combined effects may have important consequences in controlling metastatic dissemination of tumor during the vulnerable perioperative period.

Aged↗
PubMed1992

Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity.

The aim of this study was to determine the effects of the surgical treatment of morbid obesity on some aspects of haemostatic and fibrinolytic function. Measurement of haemostatic and fibrinolytic factors was performed before and again 6 and 12 months after operation in 19 patients suffering from morbid obesity. Surgical treatment resulted in a mean decrease in body weight of 50 kg at 6 months and 64 kg at 12 months. Weight loss was accompanied at 12 months by significant reductions in median (interquartile range) concentrations of serum cholesterol from 5.3 (4.5-6.2) mmol/l to 3.6 (2.9-4.6) mmol/l; factor VII from 113 (92-145)% of normal to 99 (85-107)%; of fibrinogen from 3.5 (3-9.3) g/l to 2.8 (2.4-3.8) g/l; and of plasminogen activator inhibitor-1 (PAI-1) activity from 21 (11-30) IU/ml to 6.3 (5-10) IU/ml. The decrease in PAI-1 activity probably accounted for a significant reduction in euglobulin clot lysis time. Tissue plasminogen activator activity was undetectable in most patients pre-operatively but increased slightly after 1 year to 110 (100-204) mIU/ml. There were no significant changes in plasma levels of KCCT, factor VIII, von Willebrand factor antigen, alpha-2-antiplasmin, antithrombin III, protein C antigen, beta thromboglobulin, platelet factor 4, fibrinopeptide A or platelet count. These findings provide support for the hypothesis that the surgical treatment of morbid obesity may have a long-term beneficial effect on mortality from cardiovascular and thromboembolic disease.

Adult↗
PubMed1992

Somatostatin binding in normal and malignant human gastrointestinal mucosa.

Somatostatin is a regulatory peptide implicated in the control of cellular proliferation in epithelial tissues and this regulation may occur directly via membrane bound receptor activation. The aim of this study was to investigate somatostatin binding in human gastrointestinal cancer and normal mucosa. Plasma membranes were prepared from specimens of tumour and normal mucosa from 51 patients undergoing surgical resection for malignancy (28 gastric, 23 colorectal). Using a competitive displacement assay, specific 125I-tyrosine-11-somatostatin-14 binding to plasma membranes was assessed and and characterised in terms of receptor affinity (Kd) and maximum binding capacity (Bmax) as determined by Scatchard analysis. Specific low affinity (Kd = 166 nM), high capacity (Bmax = 1.2 pmol mg-1 protein) somatostatin binding was demonstrated in 22 of the gastric cancers and 17 of the colorectal cancers (Kd = 140 nM, Bmax = 1.8 pmol mg-1 protein). Similar affinity and binding capacity was demonstrable in normal mucosal samples. High affinity receptors for somatostatin were expressed by one gastric carcinoma (Kd = 0.9 nM; Bmax = 0.23 pmol mg-1 protein). Thus, low affinity, high capacity binding is a common feature of gastrointestinal tumours and normal mucosa, and high affinity receptors may occasionally be demonstrated. The functional significance of these low affinity binding sites requires elucidation to determine whether long-acting somatostatin analogues may have therapeutic benefit in gastrointestinal malignancy.

Aged↗
PubMed1992

Night-time or morning dosing with H2-receptor antagonists: studies on acid inhibition in normal subjects.

H2-receptor antagonists are conventionally given at night. However, it remains unproven whether this regimen affords superior acid inhibition or healing rates for patients with duodenal ulcers compared to morning dosing. We have therefore examined the acid inhibitory effect of 300 mg ranitidine at night compared to 300 mg ranitidine in the morning in 8 normal male subjects. Intragastric acidity was measured by the radiotelemetry method and acid inhibition calculated from the percentage decrease in the area under the curve for hydrogen ion activity against time. Night-time ranitidine resulted in a significantly better (P less than 0.02) decrease of intragastric acidity than the same dose given in the morning (66.8 (61.8-77.6)% vs. 34 (15.5-49.1)%). This difference was found to be due to the fact that morning ranitidine inhibited gastric acid secretion when the intragastric acidity was already buffered by food. These data support the superiority of nocturnal dosing with H2-antagonists.

Adult↗
PubMed1991

Autologous transfusion: an alternative to transfusion with banked blood during surgery for cancer.

Autologous blood transfusion in surgery for cancer has been avoided because of the metastatic potential of reinfused malignant cells. This study determined whether viable tumour cells remain in the red cell concentrate after separation and whether blood transfusion filters remove these tumour cells before reinfusion. Units of banked blood were inoculated with tumour cell lines: breast cancer SKBr3; colon cancer COLO 320; lymphoma Daudi; erythroleukaemia K562. After processing with the Cell Saver, aliquots of the red cell concentrate and waste saline wash were examined for tumour cells and cultured. Tumour cells from all four cell lines were identified in the red cell concentrate but not in the waste saline wash. All the cell lines except Daudi grew from the red cell concentrate. Experiments on two of the cell lines (SKBr3 and COLO 320) were performed in which the red cell concentrate was either unfiltered (control) or filtered with SQ40S blood transfusion filter or RC100 leucocyte depletion filter. Both cell lines were present in the control samples and after filtration with SQ40S filters, and cells from these samples grew normally in culture. No tumour cells were evident after filtration with the RC100 filters and no growth of either cell line was found after 1 week in culture. The Cell Saver in combination with RC100 filters may be suitable for use during the surgical treatment of malignant disease.

Blood↗
PubMed1991

Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis.

N-nitroso compounds (NOC) are strongly implicated in the causation of cancer of the stomach and it has been suggested that ascorbic acid might reduce the risk of gastric cancer by preventing their formation within gastric juice. However, until recently there have been no measurements of gastric juice ascorbic acid concentrations. We have measured both gastric juice ascorbic and total vitamin C (ascorbic acid and dehydroascorbic acid). Our findings suggest that ascorbic acid is secreted into the gastric lumen so that gastric juice concentrations are often greater than those in plasma. Gastric pathology affects this secretion, leading to values in gastric juice that are lower than plasma levels. Stimulation of gastric secretion does not raise vitamin C concentrations in individuals whose values are initially low. The role of ascorbic acid in preventing formation of NOC and protecting against gastric cancer is discussed in the light of these findings.

Ascorbic Acid↗
PubMed1990

Is antral gastrin important in the resistance of duodenal ulcers to H2 receptor antagonists or in recurrent ulceration after highly selective vagotomy?

Basal serum gastrin, integrated gastrin response to a meal, and integrated gastrin response to insulin induced hypoglycaemia were measured in 60 patients with duodenal ulcer before and after elective highly selective vagotomy to determine whether antral gastrin has a role in resistance to H2 receptor antagonist treatment which the patients had received before surgery or in the development of recurrent ulceration after vagotomy. The basal gastrin, integrated gastrin response to a meal, and the integrated gastrin response to insulin were similar in patients whose ulcers healed after H2 receptor agonist treatment or were refractory to at least three months of this treatment. The same parameters measured before or after highly selective vagotomy were similar in patients who eventually developed recurrent ulceration compared with those who did not. As expected the basal and meal stimulated (but not insulin stimulated) serum gastrin values increased after highly selective vagotomy. Ulcer patients with particularly high gastrin values (whether basal or stimulated) were not more resistant to H2 receptor antagonist treatment or prone to develop ulcer recurrence after highly selective vagotomy. This study suggests that antral gastrin is not important in 'resistance' of duodenal ulceration either to H2 receptor antagonist treatment or to highly selective vagotomy.

Adolescent↗
PubMed1990

Octreotide in the treatment of the dumping syndrome.

The effects of octreotide were investigated in 10 patients with dumping syndrome consequent on gastric surgery. A subcutaneous injection of 50 or 100 micrograms octreotide had a significant beneficial effect on certain objective measurements of dumping: packed cell volume, pulse, and blood pressure in patients with early dumping and blood glucose in those with late dumping. Symptoms were also remarkably reduced, as judged subjectively. Long-term self-administered octreotide, initially 50 micrograms b.i.d. and rising to 100 micrograms t.i.d. as necessary, in 5 patients caused improvement in symptoms in 2. In summary, octreotide has an objective effect on dumping and clinical studies suggest a role for octreotide in patients with severe symptoms.

Adult↗
PubMed1990

The effects of 15 days of dosing with placebo, sufotidine 600 mg nocte or sufotidine 600 mg twice daily upon 24-hour intragastric acidity and 24-hour plasma gastrin.

The acid inhibitory effect of sufotidine, a potent, long-lasting, competitive H2-receptor antagonist, was studied in 12 healthy males in a double-blind, randomized, three-way cross-over study of the effect of placebo, sufotidine 600 mg nocte and sufotidine 600 mg b.d. given over 15 days. On day 1 and 15 of dosing with each regimen, each subject's 24-h ambulatory intragastric acidity was measured by radiotelemetry and 24-h plasma gastrin profiles were derived from hourly venous blood samples. Acid suppression was calculated as the decrease in the area under the curve of hydrogen ion activity vs time from that observed on placebo, and 24-h plasma gastrin calculated as the area under the curve of plasma gastrin concentration vs time. Twenty-four hour intragastric acidity during the fifteenth day of dosing with sufotidine 600 mg nocte and sufotidine 600 mg b.d. did not differ significantly, but on the first and fifteenth day of dosing nocturnal acidity was decreased to a greater extent by sufotidine 600 mg nocte than sufotidine 600 mg b.d. (P less than 0.005). After 15 days, the acid suppression afforded by sufotidine 600 mg b.d. was significantly attenuated (P less than 0.0005); this was associated with a rise in 24-h plasma gastrin (P less than 0.001). Thus, tolerance to the acid inhibitory effect of H2-receptor antagonists exists and is of rapid onset. We suggest that tolerance is mediated by the temporally associated rise in 24-h plasma gastrin, but we cannot exclude the possibility that other mechanisms, such as up-regulation of H2-receptors, also play a part.

Adult↗
PubMed1990

Aortocaval fistulas and the use of transvenous balloon tamponade.

Six cases of acute aortocaval fistula are reported, which illustrate the difficulties of diagnosis and management in a rare life-threatening condition. Five cases arose from spontaneous rupture of aortic aneurysms and one from trauma. In four cases the diagnosis was made before surgery. Useful diagnostic features included inappropriate jugular venous distension in five patients, lower abdominal and trunk cyanosis in three patients and a palpable thrill in three patients. Preoperative diagnosis permitted attempts to control venous haemorrhage in three cases, one by balloons through the aortic sac and two by transvenous positioning of balloon catheters in the vena cava before aortic opening. The use of transvenous balloon catheters was found to be helpful in reducing haemorrhage. Four patients left hospital alive. Preoperative recognition of the signs of an acute aortocaval rupture and preliminary balloon tamponade appear to be valuable in the management of acute aortocaval fistulas.

Aged↗
PubMed1989

Somatostatin analogue SMS 201-995 (octreotide) as a possible solution to the dumping syndrome after gastrectomy or vagotomy.

The dumping syndrome, which may follow partial gastrectomy or truncal vagotomy and drainage, may be refractory to treatment. The aim of this study was to determine the effect of the somatostatin analogue, SMS 201-995 (octreotide), on dumping provoked by hypertonic glucose. Ten patients with symptoms and signs of dumping were studied. After a dumping provocation test with placebo, all patients developed severe symptoms: seven patients had early dumping, two had both early and late dumping and one had late dumping alone. With either 50 or 100 micrograms SMS 201-995, the symptoms of early dumping were much reduced in all patients, and those of late dumping were completely abolished. The packed cell volume, pulse and systolic blood pressure changes of early dumping were significantly reduced by SMS 201-995 and the fall in blood glucose in patients with late dumping was abolished. SMS 201-995 may be a useful treatment for early and late dumping.

Adult↗
PubMed1989

The value of postoperative chest radiology after major abdominal surgery.

A prospective study was carried out in which a chest radiograph was performed routinely on the third postoperative day on 35 consecutive patients who had elective abdominal surgery. The aim was to determine whether clinical symptoms and signs could be correlated with the radiographic appearances and whether the routine use of such an X ray could detect serious chest pathology before clinical signs developed. Thirteen patients (37%) had radiological evidence of complications and all had symptoms and (or) signs which suggested postoperative chest pathology. The 22 patients (63%) who had no radiological abnormality, could be subdivided clinically into those who were normal (29%) and those who had symptoms and (or) signs (34%). There was no significant difference between the groups in terms of previous surgery, sex, smoking, nature of surgical incision, age or duration of anaesthesia. There was a poor correlation between the diagnosis of the chest abnormality detected clinically and the diagnosis suggested by the radiographs. These findings suggest that a routine postoperative chest X ray is unnecessary in the absence of clinically detectable chest pathology.

Abdomen↗