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Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 55 records · Page 3Linked to original sources

Goiters and airway problems.

Even though thyroid enlargement occurs commonly, the incidence of goiter has decreased in the United States due to the routine use of iodized salt. We continue to see a large number of patients with neglected goiters that cause airway compression. The progressive nature of this disease occasionally results in severe tracheal compression and acute airway distress. We treated 120 patients with airway compression secondary to goiters during a 7-year period. Thirty patients presented initially with acute airway distress requiring either intubation or semiemergent surgery. The decision to operate was based primarily on clinical evaluation and airway films. Ninety patients had substernal goiters. Only one patient required sternal splitting. If one lobe was enlarged causing tracheal deviation, lobectomy was performed; if both lobes were enlarged, subtotal thyroidectomy was performed. Two patients required tracheostomy. There were no operative deaths, and morbidity was limited to minor wound problems. It is important to consider early surgical decompression whenever tracheal compression is caused by goiters, especially if the patients are symptomatic or there is mediastinal extension.

Adult↗

The effect of small intestinal transplantation on intraluminal levels of serotonin and substance P.

This study was performed to examine the effect of transplantation, and thus extrinsic denervation, of the small intestine on intraluminal release of serotonin and substance P. Heterotopic 40-cm-long proximal (jejunal) small intestinal isografts were performed in six 200- to 250-g adult male Lewis rats under general anesthesia. Bowel ends were exteriorized as ostomies. Six Lewis rats with neurovascularly intact 40-cm proximal small bowel Thiry-Vella loops exteriorized as ostomies served as the control animals. On the seventh postoperative day, the intestinal loops were perfused at 0.5 ml/min for three 10-min periods with normal saline followed by an equilibrium period and then for three 10-min periods with 20% dextrose. Perfusates were collected for each period and levels of serotonin and substance P were determined by radioimmunoassay. Intraluminal serotonin levels rose from 29 +/- 9 ng/ml during saline perfusion to 115 +/- 28 ng/ml during intestinal perfusion with 20% dextrose in the innervated loops and from 21 +/- 7 ng/ml to 94 +/- 26 ng/ml in the transplanted loops. While there was a statistically significant increase in mean intraluminal serotonin levels following perfusion with 20% dextrose in both the control and transplant groups, there was no difference in the intraluminal serotonin response between controls and transplant recipients. In contrast, 20% dextrose had no effect on luminal release of substance P in either group. These results indicate that extrinsic denervation of the small intestine has no effect on the intraluminal serotonin response to stimulation and suggest that serotonin and substance P are not released into the intestinal lumen by the same regulatory mechanisms.

Animals↗

Acute hypocalcemic effect of ethanol in dogs.

Ethanol has been shown to reduce serum calcium in multiple animal studies. However, in human studies done using lower doses of alcohol, only inconclusive results have been obtained. This study was undertaken to evaluate the effects of varying doses of oral ethanol on total serum calcium. Fifteen adult mongrel dogs (17-25 kg) were divided into three groups which differed in the dosage of ethanol given. Group I animals received 0.5 g/kg of ethanol; Group II, 1.0 g/kg ethanol; and Group III, 2.0 g/kg of ethanol. Venous blood was sampled for estimation of concentrations of total serum calcium and ethanol. In the animals in Group I, serum calcium levels were unchanged by the ethanol. In both Groups II and III, significant reductions in serum calcium were demonstrated, which occurred within 5 min of intoxication. The mean decrease in serum calcium in Group III animals was significantly greater than that in either Group I and II. We conclude that the rapid hypocalcemic effect requires a threshold amount of ethanol before it becomes chemically evident. This critical value in dogs approximated 1 g/kg which results in a mean peak serum alcohol concentration of 117 +/- 6 mg/dl.

Alcoholic Intoxication↗

Contraction of canine stomach and small bowel by intravenous administration of serotonin. A physiologic response?

Serotonin is found in large quantities in the gastrointestinal tract, where it can increase gastrointestinal motility. Whether this response represents a physiologic event has not previously been shown. In our investigation eight conscious dogs were fitted with strain gauges to monitor motility responses to serotonin. When infused intravenously, serotonin significantly increased the contraction rate and force of canine stomach, small bowel, and isolated Thirty-Vella loops. Whole blood serotonin levels monitored by radioimmunoassay showed no significant increase in levels during these infusions. Serotonin may have a physiologic function in the mediation of gastrointestinal motility.

Animals↗

Paraesophageal hernia.

We have reviewed our experience with eight patients with paraesophageal hernias surgically repaired at this institution during an 18-month period. Three of these patients required emergent operation, and although the morbidity was higher in this group than in those undergoing elective surgery, no mortalities occurred in either group. The potential for the development of life threatening complications warrants immediate surgery on patients who are diagnosed to have paraesophageal hernias, even if asymptomatic. We recommend a transabdominal approach for the performance of a crural repair and an antireflux procedure.

Aged↗

Immunocytochemical localization of estrogen and progesterone receptors in human thyroid.

The presence of steroid hormone receptors has previously been suggested in thyroid tissue by biochemical means. Our studies were designed to confirm these results and to localize the specific receptor-containing cell type using a novel immunocytochemical method. Monoclonal antibodies specific to estrogen receptors (ER) and progesterone receptors (PgR) were used to localize these steroid hormone receptors in the human thyroid gland. Frozen tissue sections from surgical specimens excised from 22 patients of both sexes with benign thyroid disease were studied. The sections were incubated with rat antiestrophilin and antiprogesterone receptor antibodies and were then exposed to rabbit anti-rat IgG and to rat peroxidase-antiperoxidase complex. The reaction product was visualized with diaminobenzidine tetrahydrochloride and hydrogen peroxide. Four specimens were positive for both ER and PgR, 16 were ER-positive and PgR-negative, and two were negative for both ER and PgR. Positive reactivity was limited to the follicular lining cell nuclei and varied from focal to diffuse. The immunohistochemical findings confirmed the presence of ER and PgR in the thyroid tissue and demonstrated for the first time that these receptors are present only in the nuclei of the lining cells of the thyroid follicle. The role of steroid hormone receptors in the thyroid in health and disease remains to be explained.

Antibodies, Monoclonal↗

The role of serotonin in the canine secretory response to cholera toxin in vivo.

This study was initiated to evaluate the role of serotonin in cholera toxin-induced jejunal secretion of water and electrolytes. Chronic Thiry-Vella loops, constructed in six dogs, were perfused with an isosmotic neutral perfusate containing [14C]polyethylene glycol as the recovery marker. Fluxes of water, sodium, chloride and potassium were calculated and immunoreactive serotonin levels were measured in blood and effluent perfusates. Intraluminal application of 20 micrograms of cholera toxin induced secretion; fluxes of water (basal, 32.3 +/- 11.1; 6 hr, -541 +/- 35 microliter/min), sodium (basal, 9.0 +/- 2.8; 6 hr, -78.3 +/- 5.6 microEq/min), chloride (basal, 3.8 +/- 1.5; 6 hr, -65.7 +/- 4.0 muEq/min) and potassium (basal, 0.10 +/- 0.08; 6 hr, -2.80 +/- 0.18 muEq/min) were all significantly different from basal. Serum electrolytes remained normal, except that potassium fell from 4.9 +/- 0.5 to 3.9 +/- 0.2 mEq/l. Although circulating serotonin levels did not change from base line (180.9 +/- 29.3 ng/ml), effluent concentrations increased significantly from 68.2 +/- 4.6 to 81.1 +/- 5.0 ng/ml (at 3 hr) and jejunal outputs increased from 136.6 +/- 10.2 to 205.1 +/- 10.1 ng/min (at 6 hr). In a separate set of experiments, verapamil was infused i.v. (12.5 micrograms/kg/min) during the 4th hr in four dogs exposed to cholera toxin. The lower dose of toxin (5 micrograms) induced secretion which was unaffected by the calcium channel blocker. In another series of studies, ketanserin (a 5-HT2 receptor blocker) was infused i.v. at 33 micrograms/kg/min during the 4th hr in four additional dogs exposed to the lower dose of cholera toxin. This potent serotonin antagonist failed to inhibit cholera toxin-induced jejunal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of female sex hormones and pregnancy on gallbladder prostaglandin synthesis.

To investigate whether female sex hormones and pregnancy induce increased gallbladder synthesis of prostaglandin I2 (PGI2) and prostaglandin E (PGE), we used an in vitro incubation chamber to quantitate the effects of progesterone, estrogen, pregnancy, and pregnancy plus a 2%-cholesterol diet on mucosal and serosal PGI2 and PGE production by the rabbit gallbladder. Neither the female sex hormones nor pregnancy alone caused a significant increase in PGI2 or PGE synthesis. The gallbladders of cholesterol-fed, pregnant rabbits demonstrated significant increases only in serosal synthesis of PGI2. This increased production was equivalent to that noted for gallbladders from nonpregnant rabbits fed a high-cholesterol diet. There were no increases in mucosal synthesis of PGE or of PGI2. Thus, neither elevated levels of progesterone or estrogen nor pregnancy is directly responsible for the increased PGI2 activity in the female gallbladder; conversely, this effect seems to be mediated by the increased biliary concentrations of cholesterol.

Animals↗

Antiviral activity of a synthetic analog of prostaglandin A in mice infected with influenza A virus.

We have previously shown that prostaglandins of the A series potently inhibit virus replication in several virus-host systems in vitro. In the present report we have studied the effect of a long-acting synthetic analog of PGA, 16,16-dimethyl-PGA2(Di-M-PGA2), on virus infection in vivo, using as a model Balb/c mice infected with influenza A (PR8) virus. Depending upon the dose of viral inoculum, PR8 virus caused the death of 50 to 100% of the animals in a period of 8-20 days. Di-M-PGA2-treatment significantly increased mouse survival by an average of 40%, independently of the dose of inoculum and the age of the animals. The fact that Di-M-PGA2-treatment decreased virus titers in the lungs and did not alter the host immune response, suggested that PGA's therapeutic action was due to suppression of virus replication. Finally, two anti-inflammatory compounds, which inhibit prostaglandin synthesis, aspirin and indomethacin, were shown not to significantly alter mouse survival in this system.

Animals↗

Effects of intravenous calcium on release of serotonin into jejunal lumen and portal circulation.

The effect of intravenous calcium bolus (180 mg in 10 ml normal saline over 25-30 sec) on the release of serotonin into the jejunal lumen and the portal and peripheral venous circulation was studied. Proximal jejunal 25-cm cannulated Thiry-Vella loops were perfused with a neutral physiological buffer in an isoperistaltic direction at 2 ml/min. One minute after the calcium bolus, serum calcium levels increased from 8.7 +/- 0.3 to 14.2 +/- 0.8 mg/dl. Jejunal luminal concentrations of 5HT increased from 135 +/- 21 to 208 +/- 44 ng/ml at the same time; luminal levels peaked at 236 +/- 27 ng/ml at 7 min and slowly returned to baseline. In contrast, portal and systemic venous concentrations did not change after intravenous calcium bolus. The data support the contention that there are independent mechanisms for the release of serotonin into the bowel lumen and the blood stream.

Animals↗

Prostaglandins and surgical diseases: Part II.

Prostaglandins are important in the allograft response. Allograft antigenic stimulation causes release of prostaglandins both in vivo and in vitro. Macrophages and monocytes are the cells that produce the prostaglandins from arachidonic acid via the cyclooxygenase pathway. Prostaglandins exert immunosuppressive effects at several steps on both afferent and efferent phases in the cell-mediated immune system: reduction of Ia expression in antigen-presenting cells, inhibition of IL-1 and IL-2 production, and activation of suppressor cells. The immunosuppressive effects of blood transfusions and essential fatty acids appear to be mediated by PGE.

Animals↗

Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms.

The mechanisms controlling vagally induced release of serotonin-like immunoreactivity (5-HTLI) into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI into the portal vein. The vagally induced release of 5-HTLI into portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by previous removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animals it was shown that vagally induced release of 5-HTLI into portal circulation was mediated by adrenoceptor mechanisms, while endoluminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be quantitatively small in comparison with the release into portal circulation.

Animals↗

Segmental intestinal transplantation in rats with resected entire small bowel, ileocecal valve, and cecum.

Segmental intestinal transplantation was studied in a rat model of severe short gut syndrome across major histoincompatibility barriers. Lewis (RT1l) recipient rats whose entire small bowel (approximately 80 cm), ileocecal valve, and cecum were resected and who had no transplant, uniformly died of malabsorption on Day 9.8 +/- 0.4 (n = 11). Without cyclosporine, allograft recipients (n = 2), died of rejection on Days 8 and 10. Recipient animals with 20-cm jejunum and 40-cm jejunal transplants from Buffalo (RT1b) rats and treated daily with cyclosporine (5 mg/kg/day) intramuscularly (Days 0-28) and vitamin B12 (every other week) enjoyed significantly prolonged survival to Day 58.2 +/- 13.7, P less than 0.003, n = 10, and Day 129.1 +/- 7.4, P less than 0.001, n = 10, respectively. While 7 of 10 rats in the 20-cm jejunal transplant group died of malabsorption between Days 14 and 58, none of 10 animals in the 40-cm jejunal transplant group died of this complication. Four of 10 rats in the 40-cm jejunal transplant group thrived at 150 days after the operation, at which time they were sacrificed. Morphologically, the grafts demonstrated hypertrophic changes. The data from this study suggest that intestinal allografts have pronounced intestinal adaptative characteristics. Using segmental jejunal grafts, intestinal transplantation is an effective surgical modality for the short gut syndrome in the rat.

Animals↗

Regulatory mechanisms in the luminal and portal release of vasoactive intestinal polypeptide during vagal nerve stimulation in the cat.

The effect of vagal stimulation in chloralose-anesthetized cats on release of vasoactive intestinal polypeptide into the jejunal lumen and portal venous blood was tested simultaneously, and the effect of atropine and hexamethonium was investigated to elucidate the regulatory mechanisms involved in the release. Vagal stimulation caused a significant increase in vasoactive intestinal polypeptide concentrations in the luminal perfusates. A significant concomitant increase was seen in portal plasma. Gel filtration chromatography of luminal and portal samples demonstrated that the vasoactive intestinal polypeptide coeluted with synthetic porcine vasoactive intestinal polypeptide. Vasoactive intestinal polypeptide infusion at 80 and 160 pmol/kg.min produced portal plasma levels of at least 3000 pM but did not increase vasoactive intestinal polypeptide concentrations in the luminal perfusates. Thus, luminal vasoactive intestinal polypeptide originates from gastrointestinal tissue rather than by transduction from the circulation. Vagally induced release of vasoactive intestinal polypeptide into the lumen and portal plasma was not abolished by atropine but was totally suppressed by hexamethonium. The regulatory mechanisms controlling the parallel release of vasoactive intestinal polypeptide into both the jejunal lumen and portal circulation are identical and involve a non-muscarinic process which is under cholinoceptive, nicotinic control.

Animals↗

Is parotid lymphadenopathy a new disease or part of AIDS?

This report describes a series of 15 patients who presented with masses in the tail of the parotid gland which proved at biopsy to be benign hyperplastic lymphadenopathy similar to lymphoepithelial hyperplasia. There were 11 male and 4 female patients. All had a history of intravenous drug use. Ten patients complained of pain. Six patients had smaller masses on the contralateral side of the gland, whereas seven patients had minor axillary adenopathy. Needle aspiration was performed in 12 patients; although not conclusively diagnostic, it ruled out primary salivary tumors. Thick purulent material was aspirated in five patients. All 15 patients underwent parotid exploration. It was apparent after raising the flap that the disease was related to intraparotid and periparotid lymph nodes. Lymphadenopathy in the jugular region, which was not appreciated preoperatively, was also noted in all patients. Each patient underwent exposure of the main trunk of the facial nerve and limited superficial parotidectomy. The postoperative course in each patient was uneventful and no patient had a facial nerve deficit. Cerebral toxoplasmosis developed in one patient who died 3 months after surgery; AIDS developed in one other patient. Human immunodeficiency virus (HIV) titers were not performed routinely because none of the patients came for regular follow-up. None of these patients demonstrated lymphoma at the time of this procedure. Parotid lymphadenopathy, which occurs primarily in intravenous drug users, appears to be an early manifestation of pre-AIDS or AIDS-related complex. If patients have no other sizable lymphadenopathy for biopsy, we advocate exploration of the parotid region and excision of periparotid and intraparotid lymph nodes.

Acquired Immunodeficiency Syndrome↗