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Biomedical subjects

I M Modlin

Publications and source records attributed to I M Modlin.

At least 271 records · Page 15Linked to original sources

Radioimmunoassay measurement of substance P release following a meat meal.

We report the development of a sensitive and specific radioimmunoassay for substance P based on a new extraction technique for this peptide. In this technique, substance P-like immunoreactivity (SPLI) was extracted from midly acidified plasma successively with 0.05M ammonium sulfate and ethanol; recovery was almost quantitative (89.5 +/- 3.2%) and was independent of concentration. Basal substance P levels averaged 22 +/- 3 pg/ml in 33 dogs. Following initiation of a high-protein meal, mean SPLI levels in three dogs (in a total of 12 experiments) increased significantly from 26 +/- 3 to a peak of 37 +/- 4 pg/ml at 15 minutes, after which they slowly returned to the initial levels.

Animals↗

Carcinoid syndrome.

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Antineoplastic Agents↗

Failure of bombesin to alter anterior pituitary hormone secretion in man.

Because of the stimulating effects of bombesin on growth hormone and prolactin secretion in the rat, we have studied the effects of bombesin infusions on anterior pituitary hormone secretion in man. Biological activity of the infused bombesin was confirmed by observing a brisk increase in serum gastrin concentrations and in gastric acid secretion during the lowest dose of bombesin infused. We could demonstrate no effect of bombesin in doses fro 200-600 pmol.kg-1.h-1 on growth hormone, prolactin, thyrotrophin, luteinizing hormone and follicle stimulating hormone.

Bombesin↗

Multiple endocrine neoplasia: Part II. Sipple's syndrome.

Multiple endocrine neoplasia (MEN) type II is a genetically inherited disorder characterized by a combination of medullary carcinoma of the thyroid, phaeochromocytomas and, more rarely, hyperparathyroidism. A subgroup of patients who do not have the same genetic inheritance pattern have in addition a Marfanoid habitus and multiple mucosal neuromas. The phaeochromocytomas cause paroxysmal hypertensive crises due to catecholamine surges, and are diagnosed most easily by elevated levels of urinary vanillylmandelic acid. Medullary carcinoma presents as a thyroid nodule and is often associated with flushing or diarrhoea. Measurement of plasma thyrocalcitonin levels permits diagnosis and detection of affected members of the family. It is unusual for hyperparathyroidism to be asymptomatic or to require treatment. Bilateral adrenalectomy should always be performed since both adrenals are involved, even if an overt tumour is only apparent in one. Total thyroidectomy for medullary carcinoma is indicated once the phaeochromocytomas have been removed. Affected families should be regularly screened to detect overt cases.

Adrenal Gland Neoplasms↗

Multiple endocrine neoplasia: Part I. Wermer's syndrome.

Multiple endocrine neoplasia (MEN) type I is a genetically inherited disorder which predominantly involves the parathyroid and pituitary glands and pancreatic islets. Symptoms relevant to each endocrine gland may be present individually or in combination, since the tumours or hyperplasia can occur either synchronously or alone. Measurement of plasma hormone levels, endocrine function tests and radiological examination are necessary to make the diagnosis. Resection of the affected glands or treatment with specific pharmacotherapy is required for control of the disease. Long-term follow-up examination is vital to detect the appearance of lesions in other endocrine glands or the development of metastases. Screening of relatives and genetic counselling are important in the management of affected families.

Diagnosis, Differential↗

Evidence that the cholinergic enteropancreatic reflex may be independent of cholecystokinin release.

Studies were performed in four dogs with chronic gastric and pancreatic fistulas following intraduodenal perfusion with 10 mmole hr-1 of sodium oleate for 30 minutes. Radioimmunoassay (RIA) of plasma CCK LI was undertaken by an RIA method using labeled, desulfated CCK 8 I125 and an antiserum raised to CCK 8. The detection limit for the assay was 0.25 to 0.5 fmole and the lowest detectable plasma level was 5 to 10 fmoles ml-1. Since there was equal cross-reactivity to gastrin, a gastrin-specific assay also was employed to evaluate any changes in gastrin levels. After oleate infusion the plasma CCK increment above basal was 50 +/- 11 fmoles ml-1, with return to basal levels after 60 minutes. Administration of atropine significantly (P less than 0.01) inhibited the release of CCK in the first 20 minutes. Thereafter CCK release was not reduced. Plasma gastrin values did not change before and after oleate perfusion. Pancreatic protein output increased from 72 +/- 12 to 420 +/- 55 mg/10 min-1 after oleate administration. However, after atropinization the rise in pancreatic protein output was significantly lower (152 +/- 36 mg/10 min-1) (P less than 0.01). We have shown that, using our RIA method, there is a measurable rise in plasma CCK LI after intraduodenal oleate. After atropinization the CCK response was decreased significantly during the first 30 minutes, but was virtually unchanged during the second 30 minutes, when the fall in pancreatic protein output was most marked. We conclude that the cholinergic mechanism which plays a role in the endogenous stimulation of pancreatic protein secretion by intraduodenal oleate cannot be explained simply be decreased CCK release. This mechanism may be hormonal, distinct from secretin, or neural possibly, via activation of an enteropancreatic reflex.

Animals↗

Effect of motilin on the rate of gastric emptying and gut hormone release during breakfast.

The effect of an infusion of natural motilin on the rate of gastric emptying of a standard breakfast was studied in 5 subjects using Caesium 129-tagged resin particles. Emptying rates were measured on 4 separate days. On 2 days, the subjects receive only saline (controls), while on the other 2 days a motilin infusion of 0.34 pmol/kg/min for 60 min, followed by 0.68 pmol/kg/min for 60 min, was given. All infusions were blind and given in random order. At the end of the low-dose motilin infusion 31 +/- 4% of the meal had emptied, compared with 17 +/- 2% with saline infusion (P less than 0.01). A similar effect was also seen with the high-dose infusion. Plasma motilin concentrations rose from a basal of 68 +/- 13 pmol/liter to 126 +/- 10 pmol/liter during low-dose motilin infusion and to 170 +/- 11 pmol/liter during the high dose. No significant change in basal or postprandial levels of glucose, gastrin, pancreatic glucagon, pancreatic polypeptide, gastric inhibitory peptide, enteroglucagon, or vasoactive intestinal peptide was noted, but postprandial insulin release was greater during motilin infusion.

Adult↗

Endocrine tumors of the pancreas.

The identification and description of a widely dispersed group of cells of common origin and biochemical characteristics, APUD cells, has allowed a better understanding and classification of endocrine tumors of the pancreas. Similarly, it has enabled the relationships between the endocrine tumors of the multiple endocrine neoplasia type I syndrome and the endocrine tumors of the pancreas to be better appreciated. This has facilitated both diagnosis and management of these conditions. The pluripotentiality of the cells of the APUD system combined with the certain existence of many unidentified peptides suggests the likelihood of other undescribed pancreatic endocrine tumors. Many of these are probably part of the heterogenous group of neoplasms currently designated as carcinoids, since their secretory products and exact cell types are not known. The recognition of the physiologic characteristics and cells of origin of these peptides, amines or other bioactive agents will allow delineation of the symptom complex and the identification of further functional tumors of the pancreas. The development of plasma radioimmunoassays for the various hormones and the appreciation of the specific clinical syndromes related to each tumor have enabled earlier diagnosis. The understanding of the hormonal physiopathologic functions has led to the evolution of specific therapeutic maneuvers. Provocative tests have allowed increased precision of the differential diagnosis, while selective arteriography and pancreatic venous sampling have greatly enhanced the accuracy of topical localization. The role of operation in tumor removal is still prominent, but malignant and recurrent tumors may now also be controlled with specific pharmacotherapy or appropriate endocrine cytotoxic agents. The use of peptides with antagonistic actions or the administration of specific antibodies to the active tumor products are areas of therapy that require further exploration.

Adult↗

Diagnosis and management of obscure gastrointestinal bleeding.

Twelve consecutive patients presenting with unexplained recurrent gastrointestinal bleeding were investigated by selective visceral angiography. A cause for the bleeding was shown in all 12 cases, and in eight the lesion responsible was diagnosed radiologically as an area of angiodysplasia. Abnormal areas were pinpointed by fluoroscopy and examination of the resected bowel with a dissecting microscope after injecting the vessels with barium. Histologically these areas had various microvascular abnormalities. Angiodysplasia is a useful descriptive radiological term, but does not seem to represent a single pathological entity.

Adult↗

VIPomas and the watery diarrhoea syndrome.

Vaso-active intestinal polypeptide (VIP) is a recently discovered polypeptide widely distributed throughout the gastro-intestinal tract and nervous system. Elevated plasma VIP levels are found in gut and neural endocrine tumours producing the watery diarrhoea syndrome. Fifty per cent of these tumours are intrinsically malignant and the mortality rate may be as high as 30% even from the bening growths owing to the serious metabolic sequelae of the syndrome. The plasma VIP level is not elevated in any other non-tumourous diarrhoeal condition. The biological action of VIP closely resembles the clinical features of the Verner-Morrison syndrome and experimental evidence strongly suggests that VIP is the causal agent. The measurement of plasma VIP is of exceptional diagnostic value, since detection of elevated levels enables early removal of the tumour and may be life-saving.

Adrenal Gland Neoplasms↗

Plasma vasoactive intestinal polypeptide (VIP) levels and intestinal ischaemia.

Vasoactive intestinal polypeptide (VIP) is released into the portal circulation in large quantities by ischaemic bowel. In view of its known high concentration in the gut and potent vasoactive properties it may well be implicated in the pathogenesis of the serious haemodynamic changes produced by gut ischaemia.

Animals↗