Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 91 records · Page 5Linked to original sources

PubMed1986

Effects of intraluminal perfusion with serotonin on jejunal motility.

Five dogs with chronic doubly cannulated proximal jejunal Thiry-Vella loops were studied to evaluate the role of luminal and circulating serotonin on intestinal intraluminal pressure quantitated using computer-assisted planimetry. Luminal perfusion with serotonin (50 micrograms/min) for 60 min resulted in a significant increase in luminal pressure. Upon cessation of infusion, intraluminal pressures rapidly returned to basal. While 4% lidocaine had no effect on basal intraluminal pressure, the drug almost abolished the pressure response to luminal serotonin. In contrast, atropine lowered mean baseline intraluminal pressures and also markedly inhibited the response to subsequent perfusion with serotonin. These data suggest that the motility response to intraluminal serotonin is neurally mediated. Intravenous serotonin infusion (3.3 micrograms/kg/min), which raised circulating levels of the amine to those noted after a standard meal, increased intraluminal pressures to a maximum similar to those noted after luminal perfusion; after cessation of infusion, pressures rapidly returned to basal. These observations support a physiologic role for serotonin in the modulation of intestinal motility.

Animals↗

PubMed1986

Effect of luminally administered serotonin and substance P on jejunal handling of water and electrolytes.

This study was initiated to evaluate the effect of luminally administered serotonin (5-hydroxytryptamine) and substance P on jejunal handling of water and electrolytes. Five dogs with chronic cannulated jejunal Thiry-Vella loops were studied. The isolated jejunal segments were perfused at 2 ml/min for 2 hours with an isosmotic, isothermic perfusate containing labeled polyethylene glycol for recovery calculation. Fluxes of water and sodium, chloride, and potassium were calculated during 30 minute baseline, 60 minute study, and 30 minute recovery periods. Substance P was administered intraluminally at 25 pg/ml, whereas serotonin was perfused at 600 ng/ml. Neither hormone was absorbed into the portal circulation. Intraluminal serotonin converted absorption to secretion of water from 43 +/- 23 to -105 +/- 25 microliters/min, sodium from 7.3 +/- 3.1 to -15.7 +/- 4.1 microEq/min, chloride from 4.4 +/- 3.4 to -16.4 +/- 3 microEq/min, and potassium from 0.16 +/- 0.20 to -0.86 +/- 0.17 microEq/min. Secretion ceased on cessation of serotonin perfusion. Substance P perfusion induced secretion of chloride (3.6 +/- 1.9 to -9.2 +/- 2.9 microEq/min) but only significantly decreased absorption of water (73 +/- 13 to 13 +/- 21 microliters/min) and sodium (8.1 +/- 1.9 to 0.2 +/- 3.1 microEq/min); in contrast, there was no significant change in jejunal handling of potassium.

Animals↗

PubMed1986

Verapamil reversal of serotonin-induced jejunal secretion of water and electrolytes in awake dogs.

Intestinal handling of water and electrolytes was monitored in 5 conscious dogs with chronic 25-cm Thiry-Vella loops of proximal jejunum using a neutral isosmotic perfusate containing [14C]polyethylene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na+, and Cl-, and there was minimal nonsignificant secretion of K+. Intravenous serotonin infusion (30 micrograms/kg X min) increased circulating hormone levels to 937 +/- 131 ng/ml and induced significant secretion of water (-150 +/- 52 microliter/min), Na+ (-22.8 +/- 8.4 microEq/min), Cl- (-23.5 +/- 6.0 microEq/min), and K+ (-1.79 +/- 0.34 microEq/min). Simultaneous infusion of verapamil, a calcium channel blocker, at 8.3 micrograms/kg X min, reversed the intestinal secretion to absorption of all these parameters (144 +/- 32 microliter/min, 15.1 +/- 5.1 microEq/min, 10.3 +/- 3.0 microEq/min, and 0.12 +/- 0.23 microEq/min, respectively). This was accompanied by a significant improvement in the clinical appearance of the animals, decreased visible agitation, and cessation of defecation. Cessation of verapamil infusion (leaving the serotonin infusion unopposed) resulted in prompt return to the secretory state. Serum electrolytes did not change significantly, with the exception of potassium, which fell from 5.1 +/- 0.2 to 4.1 +/- 0.1 mg/dl. In control experiments (no serotonin), verapamil had an insignificant stimulatory effect on the absorption of water, Na+, and Cl- whereas the effect on K+ was significant (-0.2 +/- 0.2 to +0.4 +/- 0.1 microEq/min; p less than 0.05). These data support the role of calcium in modulating the effects of serotonin, and they suggest a new promising technology for the management of serotonin-induced intestinal secretion such as that seen in the carcinoid syndrome.

Animals↗

PubMed1986

Intraluminal release of serotonin during the interdigestive migrating complex in the canine small intestine.

Intraluminal release of serotonin (5-HT) was evaluated in relation to the interdigestive migrating complex (IMC) in the canine small intestine. Thirty-Vella loops (TVL) were constructed in the proximal jejunum of eight dogs. After recovery, the loops were continuously perfused with normal saline at 37 degrees C and changes in intraluminal pressure recorded. For each 10-min period, a motility index (MI) was calculated using computer-assisted planimetry and expressed in mm2/10 min. Serotonin contents in the effluent perfusates were measured by radioimmunoassay. A characteristic phasic motor activity was recognized in the TVL with periods of rest or minimal activity (MI = 406 +/- 45 mm2/10 min, Phase I) alternating with periods of vigorous activity (MI = 2082 +/- 134 mm2/10 min, Phases II and III). Serotonin was constantly found in the effluent perfusates in relatively high concentrations, but 5-HT levels did not vary significantly with intestinal activity; levels averaged 120 +/- 19 ng/ml during Phase I and 110 +/- 13 ng/ml during phases II and III. We conclude that intraluminal 5-HT plays no major role in the physiologic local regulation of the canine IMC in the small intestine.

Animals↗

PubMed1986

The effects of thyroid hormones on the formation of stress ulcers in the rat.

The Low T3 Sick Syndrome is a syndrome of low triiodothyronine (T3), low to normal thyroxine (T4), and a nonelevated thyrotropin despite the low T3 levels. This syndrome is frequently encountered in critically ill patients. These same patients are also at higher risk to develop acute stress ulcerations. The objective of this study was to access the effects of low circulating thyroid hormone levels on the development of stress ulcers in the rat. Rats having had previous surgical thyroidectomies were subjected to individual restraint stress; these animals had a significantly increased incidence of stress ulcers when compared to euthyroid stressed controls (1.6 +/- 0.4 ulcers vs 0.5 +/- 0.2 ulcers per animal, P less than 0.05). Surgically thyroidectomized (hypothyroid) animals who were given T3 replacement and then stressed, had ulcer rates similar to normal stressed controls (0.5 +/- 0.2 ulcers per animal). We conclude that low circulating thyroid hormones have an ulcerogenic effect, and that replacement of T3 in rats with surgical hypothyroidism reverses this effect.

Animals↗

PubMed1986

Regional and selective changes in blood flow of the feline small intestine induced by endoluminal serotonin.

A physiological role for endoluminal serotonin (5-HT) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of 5-HT. The upper jejunal segment was initially perfused with saline, followed by 5-HT in saline, and finally perfused with saline alone. The lower jejunal segment served as a control with constant perfusion with saline. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with 5-HT caused a selective muscular hyperaemia of the experimental gut segment, which was normalised upon subsequent saline perfusion. The blood flow to the saline perfused control segment was unchanged. This was also the case for control tissues; that is, adjacent small intestinal regions and kidneys. The 5-HT-induced muscular hyperaemia was confined to the experimental gut segment and seems to be mediated by a local cholinergic neural mechanism, activated from the mucosa, since the hyperaemic response was prevented by muscarinic blockade or local anaesthesia applied to the luminal surface of the experimental segment. The vascular response does not seem to involve 5-HT2 receptors, since selective blockade of such receptors did not prevent 5-HT-induced hyperaemia.

Animals↗

PubMed1986

Studies on the mucosal hyperaemia of the feline small intestine observed at endoluminal perfusion with substance P.

Substance P-like immunoreactivity (SPLI) was found in the luminal contents of the feline small intestine. A physiological role for endoluminal substance P (SP) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of SP. A jejunal segment was initially perfused with saline, followed by SP in saline, and finally perfused with saline alone. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with SP caused a selective mucosal/submucosal hyperaemia of the experimental jejunum, which was normalized upon subsequent saline perfusion. Since neither acute vagotomy, local neural blockade (TTX, lidocaine), adrenergic blockade (phenoxybenzamine, propranolol), cholinergic blockade (hexamethonium, atropine), histamine - nor prostaglandin blockade - could antagonize the hyperaemic effects of luminally administered SP, it is suggested that this effect is directly paracrine in nature. Substance P may be released from SP nerves on physiological stimulation, that is, augmented vagal tone by a meal, and act at the effector cell, that is, vascular smooth muscle.

Adrenergic alpha-Antagonists↗

PubMed1986

Substance P-induced intestinal secretion of water and electrolytes.

This study was initiated to determine if raised (carcinoid) plasma concentrations of substance P induced jejunal secretion of water and electrolytes. Five dogs had isolated and cannulated 25 cm jejunal segments perfused at 2 ml/min with a neutral, isotonic perfusate. Saline, 1.0 ml, was infused intravenously during basal and recovery periods, while substance P was administered intravenously at 75 ng/kg/min (55 pmol/kg/min) during the four 15 minute experimental periods. Infusion increased plasma SP concentrations from basal (5.8 +/- 1.3 pg/ml) to a mean plateau level of 121.2 +/- 25.2 pg/ml (mean +/- SEM). During SP infusion, intestinal secretion of water, Na+, and Cl- were documented (H2O basal +102 +/- 60 to SP -275 +/- 60; microliter/min; Na+ basal +19.8 +/- 7.2 to SP -23.2 +/- 7.5 microEq/min; Cl- basal 21.7 +/- 7.5 to SP -16.5 +/- 5.6 microEq/min). Under basal conditions, there was minimal secretion of potassium (-0.264 +/- 0.282 microEq/min); during SP infusion, K+ flux was altered to significant secretion (-1.784 +/- 0.271 microEq/min). Serum concentrations of Na and Cl were unchanged during SP infusion, but serum potassium concentrations fell from 4.64 +/- 0.12 to 3.85 +/- 0.40 mEq/l. The data demonstrate that substance P at levels noted in the carcinoid syndrome induces significant jejunal secretion of water and electrolytes in the dog.

Animals↗

PubMed1986

Comparative effects of ketanserin, atropine and methysergide on the gastrointestinal effects of hyperserotoninemia in the awake dog.

Intestinal handling of water and electrolytes and motility were monitored in conscious dogs with chronic 25-cm Thiry-Vella loops of proximal jejunum. Absorption/secretion was quantitated using a neutral isosmotic perfusate containing [14C]polyethylene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na+ and Cl-, while there was no net action on K+. Intravenous serotonin infusion (30 micrograms/kg/min) increased circulating levels of serotonin to a mean of 1556 +/- 191 ng/ml within 15 min of the commencement of the infusion. The infusion induced a significant secretion of water (mean -73 +/- 7 microliters/min) and electrolytes (sodium -10.4 +/- 0.7 muEq/min; potassium -0.8 +/- 0.05 muEq/min; chloride -12.4 +/- 1.0 muEq/min) in the dogs and all showed signs of hyperserotoninemia (salivation, loose bowel movements, tachypnea). After administration of ketanserin (33 micrograms/kg/min), a significant reduction in secretion was demonstrated (water +20.8 +/- 16.1 microliters/min; sodium 7.2 +/- 3.0 muEq/min; potassium -0.02 +/- 0.1 muEq/min; and chloride -1.9 +/- 2.8 muEq/min) as well as reduced motor activity. A similar antisecretory effect was demonstrated with atropine infusion (20 micrograms/kg/min), although this drug had a far more significant effect on the gastrointestinal motility recorded in the loop. Infusion of methysergide (33 micrograms/kg/min) did not significantly affect secretion (water -111.4 +/- 59.0 microliter/min; sodium -17.4 +/- 9 muEq/min; potassium -0.9 +/- 0.4 muEq/min; chloride -20.3 +/- 7.0 muEq/min). These results suggest possible actions which may make ketanserin useful in the treatment of symptoms of the carcinoid syndrome.

Animals↗

PubMed1985

The influence of cholinergic and adrenergic blockade on the portal release of substance P in the cat.

The effect of efferent electrical stimulation of the divided thoracic vagus nerves on the release of substance P-like immunoreactivity (SPLI) into the portal vein was studied in anesthetized cats. Under basal conditions portal SPLI levels were fairly constant. During the first 5 min of vagal stimulation there was a significant increase of the portal plasma levels of SPLI. Since we have demonstrated that infracardiac vagal stimulation causes only minor changes in small intestinal bloodflow, a true vagal neurogenic release of SPLI seems likely. We have shown that SPLI is exclusively localized within feline gut neurons (not the enterochromaffin (EC) cells). Thus, SPLI released into the portal circulation probably represents overflow of transmitter into the circulation. Neither blockade of cholino- or adrenoceptors nor ganglionic blockade influenced the enhanced release of SPLI induced by vagal stimulation, suggesting activation of SP neurons via nonclassical receptors.

Animals↗

PubMed1985

Verapamil inhibition of lymphocyte proliferation and function in vitro.

Calcium is a divalent cation which acts both as a cofactor for critical protein function and as a "second signal" to trigger cytosol events after membrane depolarization. The presence of calcium is critical to T-lymphocyte function. Verapamil is a calcium channel blocker at the membrane level and may affect cytosol calcium-calmodulin as well. Verapamil effect was measured on two assays of lymphocyte proliferation (concanavalin A and phytohemagglutinin lectin and alloantigen stimulated) and on cell-mediated cytotoxicity. Verapamil inhibited proliferation at 10(-5) M doses and abrogated it at 10(-4) M. Verapamil interferes with critical calcium-mediated events in T lymphocyte proliferation and function. T-lymphocyte calcium channel blockade may be an effective immunosuppressive strategy.

Animals↗

PubMed1985

Secretory effects of intravenous serotonin on the proximal jejunum of the awake dog.

The intestinal secretory effects of hyperserotoninemia were studied in conscious dogs with cannulated, exteriorized chronic proximal jejunal segments. A basal absorptive state for water and electrolytes was significantly changed to a secretory state for water, sodium ion, chloride ion, and potassium ion when serotonin was infused intravenously at 30 micrograms/kg per minute. This effect disappeared with the cessation of the infusion. During infusion, whole blood serotonin concentrations were similar to those in patients with the carcinoid syndrome. Diarrhea developed in all animals studied during infusion, and significant hypokalemia also occurred. These results support a primary role for serotonin in the pathogenesis of diarrhea associated with the carcinoid syndrome.

Animals↗

PubMed1985

Prolonged enteral nutrition in malnourished patients with nonelemental feeding. Reappraisal of surgical technique, safety, and costs.

In a 2 year period, 60 consecutive feeding enterostomies were placed in malnourished patients. The major complication rate was 1.6 percent. Total complications were 8 percent. Thirty day mortality was 13 percent. Nearly all patients were given isosmotic nonelemental diets. The incidence of diarrhea was 2 percent with this regimen. Four of five patients given elemental diets had diarrhea. Serum albumin levels increased significantly from a preoperative mean of 2.75 to 3.03 g/dl. Best overall results were achieved in patients undergoing upper gastrointestinal surgery or pancreatobilary procedures for nonmalignant lesions. More than $60,000 was saved in 2 years by substituting isosmotic formulas for elemental ones. It appears that many patients are given elemental formulas who do not actually require them. Since isosmotic solutions will not infuse through needle catheters, we advocate placing 12 F. catheters and have documented the safety of this change. By using these larger catheters, the surgeon will not lose the option of using isosmotic preparations. We have shown these preparations to be nutritionally effective with a marked lessening of diarrhea and a cost approximately a sixth of that of elemental products.

Aged↗

PubMed1985

Effect of exogenous somatostatin infusion on gastrointestinal blood flow and hormones in the conscious dog.

The purpose of this study was to investigate the effects of intravenous somatostatin infusion on gastrointestinal blood flow and hormone release in conscious dogs. Gastric, duodenal, jejunal, and pancreatic blood flows, quantitated using radioactive microspheres, were significantly decreased during somatostatin infusion (200 and 500 ng/kg min), resulting in an overall 30% reduction in summed portal blood flow. Fasting blood levels of glucose fell an average of 10 mg/dl. Immunoreactive insulin, gastrin, glucagon, and pancreatic polypeptide were all profoundly suppressed by somatostatin infusion. Our studies provide one possible explanation for somatostatin's apparent effectiveness in the control of upper gastrointestinal hemorrhage.

Animals↗

PubMed1985

The pentagastrin test in the diagnosis of the carcinoid syndrome.

Serotonin (5-HT) and substance P (SP) were assayed in peripheral blood in patients with known midgut carcinoids and hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal response was evaluated by two provocation tests, pentagastrin (PG) injection or calcium infusion. Pentagastrin caused flushing and gastrointestinal symptoms and elevated levels of circulating 5-HT, but not of SP. Pretreatment with a 5-HT2 receptor blocking agent (ketanserin) alleviated gastrointestinal symptoms but had no influence on either 5-HT release or PG-induced flushing. Calcium infusion induced carcinoid symptoms in only two of six patients, which were associated with elevated 5-HT levels (whereas elevated SP levels were seen in only one patient). We conclude that 5-HT is important for the development of gastrointestinal symptoms but not of flushing. Ketanserin may alleviate gastrointestinal symptoms but does not influence PG-induced release of 5-HT. Substance P and 5-HT do not seem to share a common release mechanism. It appears that PG testing is superior to calcium infusion as a provocative test in patients with the carcinoid syndrome.

Carcinoid Tumor↗

PubMed1985

The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine.

Endoluminal release of serotonin (5-HT), substance P (SP), and motilin was quantitated after thoracic vagal nerve stimulation in the cat. In duodenum and jejunum, simultaneous release of these compounds was observed. In contrast, vagal stimulation did not augment the rate of luminal secretion of either 5-HT or SP in the distal ileum. Immunohistochemical studies demonstrated 5-HT in both enterochromaffin (EC) cells and nerves throughout the small bowel. However, we were unable to visualize any SP-containing EC cells in the cat, which suggests that the source of luminal SP in this species must be intramural nerves.

Animals↗

PubMed1985

Verapamil inhibition of the intestinal effects of substance P.

The undecapeptide substance P (SP) is contained in enterochromaffin cells and circulates in high concentrations in patients with carcinoid syndrome. We have previously reported that elevated SP levels, simulating those reported in patients with carcinoid syndrome, induce profound changes in intestinal water and electrolyte secretion, motility, and blood flow in a canine model. The purpose of this study was to attempt to block the effects of circulating carcinoid levels of SP on intestinal secretion and motility with the calcium channel blocker verapamil. In five dogs a chronic proximal jejunal Thiry-Vella loop was constructed, and after a 2-week recovery the loops were perfused with an isotonic test solution containing 14C-polyethylene glycol as a volume marker. Motor activity was measured by changes in intraluminal pressure and a motility index was calculated with computer-assisted planimetry and expressed as square millimeters per 5 minutes. After a 30-minute baseline period, SP was infused at 50 ng/kg/min for 90 minutes. SP circulating levels rose from a baseline of 6.2 +/- 1.3 pg/ml to a peak of 93.3 +/- 3.1 pg/ml during this infusion. Thirty minutes after the start of this SP infusion, a simultaneous infusion of verapamil (5.0 micrograms/kg/min) was begun at a separate site. During SP infusion there was a significant secretory response of water (-48 +/- 12 microliters/min), Na+ (-7.7 +/- 2.5 microEq/min), Cl- (-8.8 +/- 2.7 microEq/min) and K+ (-0.57 +/- 0.14 microEq/min), and hypermotility (motility index: 1479 +/- 138 mm2/5 min). When verapamil was added a reversal of secretion to net absorption was observed (water: + 116.9 +/- 15.6 microliter/min; Na+: + 13.8 +/- 2.1 microEq/min; Cl-: + 5.5 +/- 2 microEq/min; K+: + 0.38 +/- 0.9 microEq/min) (p less than 0.05). In addition, there was a reduction in motility (motility index: 853 +/- 92 mm2/5 min; p less than 0.05). These results confirm that SP has profound effects on both intestinal motility and secretion and that calcium channel blockade reduces these effects significantly.

Animals↗

PubMed1985

The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin.

The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid-gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease.

Aged↗