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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 883 records · Page 49Linked to original sources
PubMed1983

Vasoactive intestinal polypeptide in the normal and unstable bladder.

The possible involvement in idiopathic detrusor instability of a newly discovered type of autonomic nerve containing vasoactive intestinal polypeptide (VIP) has been studied. Immunocytochemistry and radioimmunoassay, using specific antibodies against VIP, were carried out on 20 biopsy specimens from the bladders of patients with detrusor instability and 20 specimens from control patients. The concentration of VIP in the unstable bladders was found to be markedly reduced from 36.52 +/- 4.8 pmol/g (mean +/- SEM) to 7.62 +/- 1.84 pmol/g (P less than 0.01). The number of VIP immunoreactive nerves was greatly decreased in all of the layers but particularly in the muscle layer of the unstable bladder in comparison with the controls. These findings may provide important information about the mechanism of this disorder.

Adult↗
PubMed1983

Prostatic cancer: treatment with long-acting LHRH analogue.

Fifteen patients with advanced carcinoma of the prostate were treated with a luteinising hormone releasing hormone agonist ICI 118 630. Three of 5 patients who had failed conventional hormone therapy have had a marked alleviation of bone pain, though no objective evidence of disease regression. Nine of 10 patients previously untreated have shown objective evidence of disease response. This drug appears to have advantages over conventional hormone therapy.

Aged↗
PubMed1983

The effects of naloxone on circulating metabolites, glycoregulatory hormones and gut peptides during pelvic surgery.

The role of endogenous opioid peptides in mediating the endocrine and metabolic response to pelvic surgery was investigated. Fourteen patients were studied; seven were infused with the specific opioid antagonist, naloxone, at a rate of 20 micrograms kg-1 (body weight) hr-1, while the remainder acted as a control group. Naloxone exacerbated the glycaemic response to surgery but had no statistically significant effect on changes in the glycoregulatory hormones, pancreatic glucagon, insulin, cortisol and growth hormone. However, there was a wide individual variation in the glucagon response to naloxone with marked stimulation in some patients. Naloxone infusion increased plasma pancreatic polypeptide secretion during the 1st hour of surgery and reversed the decline in plasma motilin concentrations, but had no effect on circulating somatostatin, vasoactive intestinal polypeptide, gastrin, enteroglucagon and neurotensin values. We conclude that endogenous opioid peptides have only a limited role in modulating the endocrine and metabolic response to surgery.

Blood Glucose↗
PubMed1983

Topical capsaicin pretreatment inhibits axon reflex vasodilatation caused by somatostatin and vasoactive intestinal polypeptide in human skin.

1 Wheal and flare reactions are described following intradermal injections of somatostatin, vasoactive intestinal polypeptide, substance P and histamine in normal human forearm skin. Bombesin failed to produce a significant wheal and flare.2 Pretreatment of skin with capsaicin in all cases dramatically inhibited the flare but not the wheal. This result is in accord with the hypothesis that capsaicin blocks the effector side of the axon reflex, perhaps by depleting nerve terminals of vasodilatory peptide(s).

Administration, Topical↗
PubMed1983

Neurotensin and antinatriuresis in the conscious rabbit.

The mechanism of alteration in renal sodium excretion in response to dietary changes is complex and poorly understood. A gut 'sensor' might exist which regulates the renal response and this may involve one or more of the now ubiquitous gastrointestinal peptides. Several of these gut peptides, including neurotensin, have been found within the kidney. Plasma levels of neurotensin, which is both a circulating hormone and putative neurotransmitter, rise promptly on feeding. When infused into the conscious rabbit, neurotensin produces a dose-related fall in renal sodium excretion.

Animals↗
PubMed1983

Metabolic and endocrine consequences of depriving preterm infants of enteral nutrition.

Plasma enteroglucagon, pancreatic polypeptide, gastrin, motilin, neurotensin, gastric inhibitory polypeptide, secretin, vasoactive intestinal peptide and blood glucose, alanine, ketone bodies, lactate and pyruvate were measured on the sixth postnatal day in (a) a group of 10 preterm infants who on account of hyaline membrane disease had not received enteral feeding since birth and (b) before and at 55, 90, and 120 minutes after feeding in a group of healthy preterm infants fed three-hourly on human milk. Gut hormones were also measured in umbilical venous cord blood. The infants receiving regular boluses of milk from birth demonstrated postnatal surges in preprandial concentrations of gut hormones together with cyclical hormonal responses to feeding. None of these changes were seen in infants receiving intravenous fluids. The latter infants also had lower concentrations of blood alanine, glycerol and hydroxybutyrate and lacked the phasic changes in intermediary metabolites seen in the infants receiving enteral boluses of milk. Thus deprivation of enteral feeding results in a profound alteration of the metabolic and endocrine milieu which may have important effect on the process of adaptation to postnatal life.

Hormones↗
PubMed1983

Growth hormone response to feeding in term and preterm neonates.

Plasma growth hormone concentrations were measured in 248 healthy term and preterm infants. At birth growth hormone concentrations in cord blood from both term and preterm babies were approximately 100-fold higher than those in blood drawn from healthy adults. By the sixth postnatal day basal pre-feed levels had fallen in term neonates by 65% and a marked postprandial rise was apparent; preterm infants did not show this initial fall in preprandial hormone levels nor was any response to feeding seen. However a fall in preprandial concentrations accompanied by the development of postprandial surges in growth hormone occurred during the next 2 weeks so that by 24 days the postprandial rise was similar to that of term neonates on the sixth day. We conclude that although the initial postnatal changes in plasma growth hormone concentrations are different in preterm and term infants, feeding is a major stimulus to growth hormone secretion in both groups of neonates. Further work is needed to define the precise role of this hormone in neonatal metabolic adaptation.

Growth Hormone↗
PubMed1983

Colonic motor and vascular responses to pelvic nerve stimulation and their relation to local peptide release in the cat.

1. The effects of stimulation of the pelvic nerves in atropinized cats at continuous, low frequencies from 1 to 16 Hz (continuous stimulation) were compared with those of stimulation at higher frequencies (10-160 Hz) delivered in 1 s bursts at 10 s intervals (stimulation in bursts), the latter simulating a commonly observed discharge pattern in vivo. Both types of stimulation evoked a transient vasodilatation. Stimulation in bursts at 20 and 40 Hz evoked more pronounced vasodilatations than continuous stimulation delivering exactly the same number of impulses over the whole period of excitation. 2. Stimulation of the pelvic nerves in bursts failed to elicit an effective contraction of the colon at any frequency tested, whereas continuous stimulation invariably evoked a contraction. 3. There was a clear-cut increase in the output of vasoactive intestinal polypeptide during both continuous and intermittent stimulation of the pelvic nerves. Stimulation in bursts caused a small but significant increase in the output of somatostatin but there was no change in the output of substance P in response to either type of pelvic nerve stimulation. 4. The colonic muscular contraction in response to continuous stimulation of the pelvic nerves was not affected by somatostatin when infused intra-arterially at the large dose of 1.0 microgram/min. 5. It is concluded that the colonic responses of atropinized cats to pelvic nerve stimulation can be substantially altered merely by changing the pattern of stimulation. Thus, whereas continuous stimulation produces both muscular contraction and vasodilatation, stimulation in bursts favours vasodilatation but is ineffective in eliciting colonic contraction.

Animals↗
PubMed1983

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species.

Animals↗
PubMed1983

Endocrine responses to exogenous bombesin and gastrin releasing peptide in conscious calves.

The effects of I.V. infusions of synthetic amphibian bombesin and porcine gastrin releasing peptide (GRP), at a dose of 5 pmol/kg. min for 30 min, have been investigated in conscious calves 3-6 weeks after birth. The protocols produced a closely similar rise in the bombesin-like immuno-reactivity of the arterial plasma of 208 +/- 14 pmol/l (bombesin) and 210 +/- 32 pmol/l (GRP) which fell exponentially with a half-life of about 3 min when the infusions were terminated. Neither peptide produced a discernible change in mean heart rate or aortic blood pressure, or in the mean arterial plasma concentrations of enteroglucagon, gastric inhibitory peptide (GIP), gastrin or cholecystokinin (CCK). GRP, but not bombesin, produced a small but significant rise in the mean plasma somatostatin concentration. Both peptides produced a significant rise in mean plasma pancreatic glucagon and pancreatic polypeptide concentration and proved to be exceptionally potent insulinotropic agents. These responses were associated with a rise in plasma glucose concentration which could not be attributed to a direct action of GRP on the liver. The distribution of bombesin-like immunoreactivity in the gastrointestinal tract was consistent with the findings of other workers who have concluded that it is restricted to nerve terminals. However, our other findings show that GRP is capable of acting as a true hormone.

Animals↗
PubMed1983

Neural vasodilator control in the rectum of the cat and its possible mediation by vasoactive intestinal polypeptide.

Vascular and motor responses in the rectum to pelvic nerve stimulation are described in the anaesthetized cat and compared with corresponding effects observed in the colon. The responses comprise a cholinergic and a non-cholinergic component, and an attempt has been made to elucidate the latter. Pelvic nerve stimulation evoked a pronounced and well maintained vasodilator response in the rectum whereas that in the colon was transient. Maximal vasodilatation occurred at much lower stimulus frequencies in the rectum (2-4 Hz) than it did in the colon (8-16 Hz) and maximal blood flow under these conditions was also greater in the rectum (greater than 200 ml 100 g-1 min-1) than the colon (less than 150 ml 100 g-1 min-1). Muscarinic blockade further curtailed the colonic vasodilator response to pelvic nerve stimulation, whereas the rectal dilatation was only slightly reduced in the presence of atropine. Pelvic nerve stimulation caused a substantial release of vasoactive intestinal polypeptide (VIP) from the rectum, which was related both in magnitude and duration to the vasodilatation. Intra-arterial infusions of VIP, which reproduced this rise in rectal venous VIP concentration, caused a rectal vasodilator response which closely resembled that during pelvic nerve stimulation after cholinergic blockade. The rectal vasculature was estimated to be 50-100 times more sensitive to VIP than the colonic vasculature. VIP therefore seems to be the most likely putative neurotransmitter responsible for non-cholinergic rectal vasodilatation. Stimulation of the pelvic nerves also caused rapid contractile motor responses before, and more gradual motor responses after, muscarinic blockade in both the colon and rectum, in the latter preceded by a non-cholinergic relaxation. These patterns of motor activity largely confirm previous results. Infusions of substance P effectively mimicked the non-cholinergic contractile motor responses but failed to demonstrate significant release of this peptide during pelvic nerve stimulation in the present experiments. However, substance P is rapidly inactivated and might possibly be involved in these responses. Stimulation of the pelvic nerves in bursts at high frequencies (up to 80 Hz), simulating a discharge pattern observed electrophysiologically in vivo, was effective in eliciting all the above responses, with the exception of the colonic contraction.

Animals↗
PubMed1983

Peptide immunoreactive nerves and cells of the guinea pig gall bladder and biliary pathways.

Using the methods of immunocytochemistry and radioimmunoassay, five peptides (vasoactive intestinal polypeptide (VIP), substance P, somatostatin, met-enkephalin, and bombesin) have been found in the gall bladder and the biliary tracts of guinea pig and each of them possesses a characteristic distribution pattern. Networks of nerves containing each peptide were found in the smooth muscle, around blood vessels and, occasionally, in the lamina propria. The distribution of the peptide immunoreactive nerves in the gall bladder and biliary tract is similar to those found in the gut. Vasoactive intestinal polypeptide (11 +/- 1.5 pmol/g in the sphincters, mean +/- SEM) and substance P (21.5 +/- 1.8 pmol/g in the common bile duct) were found to be the most abundant peptides and a few VIP and substance P immunoreactive neurones were localised in the ganglionated plexus. Bombesin immunoreactive nerves were mainly seen in the sphincter of Oddi, where the mean concentration of extractable bombesin was 14.6 +/- 2 pmol/g. Somatostatin immunoreactive mucosal endocrine cells were identified in the epithelium of the common bile duct and the sphincter. The extractable somatostatin in these regions were 76 +/- 19 pmol/g and 162 +/- 30 pmol/g respectively.

Animals↗
PubMed1983

Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine.

Using sensitive and specific radioimmunoassays, concentrations of hormonal peptides have been measured in small biopsies taken from the human stomach, duodenum, and proximal jejunum. Comparison is made of these hormone concentrations and the number of respective endocrine cells present determined by quantitative immunocytochemistry. Immunoreactive somatostatin, VIP, motilin, and gastrin were detected in all regions examined, whereas secretin and GIP were undetectable in antral extracts. Enteroglucagon-like immunoreactivity was present only at and beyond the ligament of Treitz, although a few enteroglucagon-producing cells were shown by immunocytochemistry in the duodenum. The variation of hormone concentration was found to be small in these biopsies of normal tissue within each region of the gut examined, indicating that representative hormone concentrations may be reliably obtained from small biopsy tissues. An attempt has been made to establish reference values for gut hormone concentrations in such biopsies; this may allow future study of any changes in concentration that may occur in pathological conditions.

Adult↗
PubMed1983

Autoantibodies to gut hormone secreting cells as markers of peptide deficiency.

Autoantibodies reacting with endocrine cells in the gastrointestinal mucosa were found by indirect immunofluorescence in 22 out of 268 sera (8.2%) obtained from patients with coeliac disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, and from subjects without bowel disease. A double immunofluorescence technique showed that the autoantibodies reacted with cells secreting gastric inhibitory polypeptide (glucose dependent insulinotropic polypeptide, GIP), secretin, somatostatin or enteroglucagon. Most sera contained antibodies against more than one cell type. Neither the presence of a particular antibody nor the pattern of antibody combinations appeared to be specific for any diagnostic category. The mean plasma GIP concentrations, however, both fasting and two hours after a test meal, were significantly lower in subjects with GIP cell autoantibodies. Thus gut hormone cell autoantibodies may be markers of impaired hormone secretion.

Adolescent↗
PubMed1983

Two patients with pancreatic apudomas secreting neurotensin and VIP.

Two patients have been studied with a two and a half and nine year history of metastatic pancreatic apudoma. In both patients the main feature was chronic watery diarrhoea with remissions after partial tumour resection and streptozotocin therapy. Plasma levels of circulating VIP and neurotensin were persistently raised in both patients. Chromatographic analysis of the plasma showed that a significant proportion of the raised immunoreactivity of both peptides eluted in an identical position to pure VIP and neurotensin. The extremely high concentrations of neurotensin did not appear to result in any feature which would allow distinction from the classical VIPoma syndrome.

Adult↗
PubMed1983

Gut hormones in acute diarrhoea.

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

Acute Disease↗
PubMed1983

Neurotensin-secreting carcinoma of the bronchus.

Neurotensin, a neuroendocrine peptide present in gut and brain has previously been found in pancreatic tumours secreting several other peptides. We report here the first case of a patient with a neurotensin-secreting adenocarcinoma of the bronchus.

Adenocarcinoma↗