Biomedical subjects
A M Blackburn
Publications and source records attributed to A M Blackburn.
Assessment and screening of older people.
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Intravenous infusion of frusemide as treatment for ascites in malignant disease.
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Effect of prednisolone on hormone profiles during primary endocrine treatment of advanced breast cancer.
Various plasma hormones were measured in 13 pre- and 20 post-menopausal women with advanced breast cancer before and for 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice a day, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day. These patients were taken from a larger clinical trial which demonstrated a higher response to primary endocrine therapy when prednisolone was added. Levels of dehydropiandrosterone sulfate were depressed in patients receiving prednisolone, confirming adrenal suppression. Estradiol levels were reduced in all patients, while luteinizing hormone and follicular stimulating hormone increased after ovarian irradiation, but all three hormones fell during tamoxifen administration; no further changes were caused by the addition of prednisolone. Prolactin and thyroxine remained constant throughout the study. There were no differences between responders and nonresponders in hormone profiles or in changes in the profiles after treatment.
Plasma neurotensin release and gastric emptying in the dumping syndrome.
Seventy-three patients were studied after ingesting a liquid glucose meal, tagged with 113Indium. Nineteen of these patients were awaiting surgery for their duodenal ulcer, while 54 were studied postoperatively, 25 of whom experienced troublesome postprandial (dumping) symptoms in their daily lives. The radioactive marker emptied significantly faster in the symptomatic patients than in the symptomfree, pre and post-operative groups (initial emptying rate 3.45 +/- 0.23, compared with 1.16 +/- 0.19 and 1.27 +/- 0.15% fall in counts/min respectively; p less than 0.01). Initial (20 min) rises in the plasma concentrations of neurotensin-like immunoreactivity measured during the test correlated significantly with the rate of gastric emptying in all patients, being greatest in patients with dumping symptoms. Physiological concentrations of neurotensin have been shown to delay gastric emptying. The excessive rise in plasma neurotensin-like immunoreactivity in patients with dumping symptoms, presumably occurring as a result of the rapid passage of nutrients to the neurotensin-rich ileum, may possibly have a compensatory role in slowing further emptying from the stomach.
Gut hormone profile and gastric emptying in the dumping syndrome. A hypothesis concerning the pathogenesis.
Insulin, enteroglucagon, neurotensin, gastric inhibitory polypeptide (GIP), and motilin have been measured in plasma during an oral glucose test in 76 patients before or after different upper gastrointestinal operations for peptic ulceration. The patients were divided into three clinical groups in accordance with their spontaneous symptoms of dumping after ordinary meals: 26 postoperative patients into a dumping group, 30 postoperative patients into a non-dumping group, and 20 preoperative patients into a reference group. The fasting values of the five hormones were similar in the operated and non-operated groups. Insulin, enteroglucagon, neurotensin, and GIP rose significantly in all patients. The increment of insulin, enteroglucagon, and neurotensin was greater in the postoperative patients with dumping symptoms than in the postoperative and preoperative patients without dumping symptoms. All the patients had a small decrement of motilin. The resulting hypothesis is that an impaired neural control of the gastric emptying is the essential aetiological factor in the dumping syndrome. The excessively rapid delivery of the meal into the jejunum is the abnormal stimulus to the exaggerated hormone release. The response of the small intestine with regard to the hormone release is considered proportionate to the given stimulus. The abrupt fall in circulating blood volume is suggested to play a role in producing the polymorphic symptoms. Neurotensin and GIP cannot be excluded from being the factors arresting the rapid gastric emptying in patients whose neural control has been impaired after gastric surgery.
Effect of pectin on gastric emptying and gut hormone release in the dumping syndrome.
The effect of pectin on gastric emptying, gut hormone release, and symptoms was studied in four patients with dumping syndrome and in two healthy volunteers after ingestion of a hypertonic glucose meal with and without addition of pectin. The initial fraction emptied from the stomach was reduced in the patients, whose symptoms of dumping were abolished or alleviated by pectin. This change of the emptying seems to be caused by a prolonged stomach transit, probably due to the viscous nature of the pectin meal. Pectin had no effect on the gastric emptying of the volunteers. The motor activity of the stomach was not altered by pectin in either the patients or volunteers. In the patients insulin, enteroglucagon, neurotensin, and gastric inhibitory polypeptide rose to higher levels after the glucose meal than after the glucose-pectin meal. The individual differences in the hormone release were considered secondary to the altered gastric emptying produced by pectin.
Gastric emptying after peptic ulcer surgery. Some pathophysiological mechanisms of the dumping syndrome.
In 76 patients before or after different operations for peptic ulceration, the gastric emptying and changes in plasma volume and blood glucose were studied after ingestion of a radionuclide-labelled hypertonic glucose meal. The patients were divided into three clinical categories in accordance with their spontaneous symptoms of dumping after ordinary meals: (a) 26 postoperative patients formed a dumping group, (b) 30 postoperative patients formed a non-dumping group, and (c) 20 preoperative patients formed a control group. A precipitous early phase of gastric emptying was the only specific finding in patients with spontaneous symptoms of dumping. This early fraction of precipitous emptying was not present preoperatively or in patients without symptoms. It is concluded that the excessively rapid delivery of the hypertonic solution into the upper intestine is the primary stimulus leading to the changes in plasma volume and blood glucose observed in the dumping syndrome. The response of the jejunum with regard to the blood glucose and haematocrit rises is considered proportionate to the given stimulus.
Effect of neurotensin on pancreatic function in man.
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Humoral aspects of dumping syndrome.
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Plasma neurotensin in term and preterm neonates.
The new ileal peptide neurotensin has not been studied hitherto in the human neonate. Plasma concentrations of neurotensin were measured by radioimmunoassay in 276 healthy term or preterm infants either at birth or pre- or post-prandially during the neonatal period. In addition, a group of 10 6-day-old preterm infants were studied who had never been enterally fed on account of hyaline membrane disease. Plasma neurotensin values were obtained also in 12 healthy fasting adults. Term infants had higher plasma neurotensin concentration than preterm infants at birth. Both groups showed a significant postnatal surge in basal (pre-prandial) neurotensin concentrations exceeding adult values, but no postnatal neurotensin elevation was found in the unfed group. In preterm infants, who were studied further into the neonatal period than term infants, there was a progressive increase in the rise of neurotensin following a milk feed, with a massive neurotensin response by 24 days of age. In 6-day-old term infants, the neurotensin response to bottle feeding was significantly greater than to breast feeding. These findings add further weight to the concept that neurotensin may be of physiological importance as a gut hormone. The high neurotensin levels and large feed responses seen in neonates may indicate a unique role for neurotensin in early life.
Pancreatic endocrine responses to exogenous neurotensin in the conscious calf.
1. Responses to neurotensin have been investigated in conscious calves 2-5 weeks after birth given continuous I.V. infusions of the peptide for 15 min (5 pmol. kg-1 . min-1). 2. In control calves the concentration of the peptide in the arterial plasma had risen by 160 +/- 10 pmol/l at the end of the infusion,. after which it fell exponentially (t1/2: 1.4 min). 3. This dose of neurotensin produced no significant change in mean heart rate, aortic blood pressure, plasma gastrin or glucose concentration. 4. It was found that neurotensin could produce a pronounced rise in the concentration of both insulin and pancreatic polypeptide (PP) in the arterial plasma, together with a much smaller rise in pancreatic glucagon concentration. 5. Each of these three pancreatic endocrine responses was found to be glucose-sensitive within the range ca. 5.0-9.0 mmol/l. Hyperglycaemia potentiated insulin release and inhibited release of PP and glucagon. 6. The results are discussed in relation to the findings of other workers in other species.
Pancreatic endocrine responses to physiological changes in plasma neurotensin concentration in the calf.
1. Plasma neurotensin concentration was found to increase by between 3 and 18 pmol/l 20 min after feeding in conscious 2-6 week old calves. 2. Synthetic bovine neurotensin was infused I.V. at a dose which reproduced the rise in the plasma concentration (1 pmol. kg-1 min-1), in calves of the same age, which were also receiving a continuous I.V. infusion of glucose (0.03 mmol. kg-1. min-1) to mimic alimentary hyperglycaemia. Under these conditions neurotensin caused a significant rise in the mean concentration of both insulin and pancreatic polypeptide (PP), but not that of glucagon, in the arterial plasma. 3. The rise of plasma insulin concentration, but not that of PP, in response to the same dose of neurotensin was strongly potentiated during infusions of exogenous amino acids. There was also a significant rise in plasma glucagon concentration in response to neurotensin in the calves given amino acids. 4. It is concluded that neurotensin is a physiological incretin in the calf.
Pancreatic tumours produce neurotensin.
Tumour tissue may secrete substances which are not normally secreted by the original tissue. We have found that 6 out of 21 pancreatic tumours producing vasoactive intestinal peptide also produce neurotensin-like peptides. These are sometimes secreted and very high plasma levels of neurotensin-like immunoreactivity may be found in the circulation.
The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.
The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.
Breast vs bottle: endocrine responses are different with formula feeding.
Differences in pancreatic and gut-hormone release between breast-fed and bottle-fed infants have not been documented although these hormones may play a key role in postnatal adaptation. In a study of 77 six-day-old healthy term infants, bottle-fed neonates ('Cow and Gate Premium') had significant changes in plasma-concentrations of insulin, motilin, enteroglucagon, neurotensin, and pancreatic polypeptide after feeding, whereas in breast-fed infants these changes were reduced or absent. Basal levels of gastric inhibitory polypeptide, motilin, neurotensin, and vasoactive intestinal peptide were also higher in the bottle-fed infants than in those who were breast-fed. These findings may partly explain differences in the deposition of subcutaneous fat and in stool frequency between breast-fed and bottle-fed neonates.
Effect of neurotensin on gastric function in man.
Neurotensin is a peptide recently discovered in the human ileum and it is released into plasma after ingestion of food. Neurotensin was infused intravenously into 12 healthy volunteers at a mean dose of 2.4 pmol/kg/min, the mean rise in plasma levels being 89 +/- 8 pmol/l. An inhibition of both gastric acid and pepsin output, and also a delay in gastric emptying of oral glucose, were observed. Neurotensin may therefore have a physiological role in modulating gastric function in man.