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Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 73 records · Page 4Linked to original sources

Prosthetic reconstruction of the trachea.

Tracheal reconstruction has been a difficult and challenging problem over the years, mainly because of graft infection and extrusion. A small segment of the trachea can be resected and primary anastomosis can be performed easily with satisfactory results. The problem is always complex when a substantial portion of the trachea must be resected. A variety of prosthetic materials have been used, both in experimental animals and human subjects, with limited short-term success. This study describes an experiment using polytetrafluoroethylene (PTFE) grafts in dogs. PTFE patch and interposition grafts were used for tracheal reconstruction with very satisfactory results. Inflammatory reaction near the grafts and nonincorporation of long graft segments continue to be problems, but despite this, prosthetic reconstruction of the trachea using PTFE provided very satisfactory results in our experimental study.

Animals↗

Exposure of the internal carotid artery near the skull base: the posterolateral anatomic approach.

Internal carotid injuries in zone III near the base of the skull are technically the most challenging of the carotid injuries. Diagnostic angiography is important to evaluate the exact site and extent of injury and the presence or absence of prograde flow in the injured segment. Vascular repair in this area is highly dependent on the adequacy of surgical exposure. Previous approaches have emphasized displacement of the mandible either by subluxation or mandibulotomy. Problems related to mandibulotomy, such as intraoral contamination, infection, and nonunion, are potential complications of this approach to the high carotid artery. In addition, it does not give adequate exposure of the internal carotid artery at the critical area, near the base of the skull. Experience gained from the extended radical neck dissection exposing the internal carotid artery up to the skull base has demonstrated that a posterolateral anatomic approach can provide superior exposure of the high carotid artery with lower morbidity and shortened operative time. This surgical approach involves cutting the sternomastoid muscle close to the mastoid and dissecting all the tissues away from the surface of the mastoid. Dividing the posterior belly of the digastric and styloid group of muscles assists in exposure of the internal carotid artery. Rarely, dissection of the facial nerve and removal of the tail of parotid add additional access to this area. This article describes the stepwise anatomic approach to the internal carotid artery near the base of the skull.

Adult↗

Changes in extravascular lung water and fatty acids in a hyperdynamic canine model of sepsis.

Several mediators, including fatty acids, have been postulated to induce the increase in permeability of the pulmonary endothelium and subsequent accumulation of extravascular lung water (EVLW) which are generally considered to be among the first events in the development of adult respiratory distress syndrome. In a canine model of hyperdynamic sepsis (hemodynamically similar to human sepsis) changes in EVLW and in concentrations of different fatty acids in the aortic and pulmonary arterial blood were measured. Two days after induction of sepsis, EVLW increased from 6.6 +/- 0.6 to 9.2 +/- 1.0 ml/kg, and the pulmonary arterial concentration of oleic acid increased from 52 +/- 4 to 73 +/- 5 mg/dl. Three days after induction of sepsis, EVLW increased further to 14.4 +/- 3.8 ml/kg and the mean concentration of oleic acid increased to 74 +/- 7 mg/dl. Twenty-four hours later, both EVLW and the mean pulmonary arterial concentration of oleic acid were not different from basal. We postulate that oleic acid, a known inducer of experimental ARDS, is one of the mediators of endothelial damage of the lung during sepsis.

Animals↗

Meal-stimulated release of methionine-enkephalin into the canine jejunal lumen.

Application of enkephalins to the luminal surface of the bowel augments intestinal absorption. However, to date, endogenous enkephalins have not been demonstrated within intestinal luminal fluid. To determine whether enkephalins are present in the intestinal lumen, five adult dogs had 25-cm chronic jejunal Thiry-Vella loops constructed. Dogs were studied in the awake, fasted state. Jejunal loops were perfused with isoosmotic, neutral Krebs buffer containing protease inhibitors. After basal sampling, the dogs received a high fat meat meal. Collections were made during the meal and for 60 min postprandially. Luminal met-enkephalin levels were determined by radioimmunoassay and confirmed by HPLC. HPLC separation of luminal samples demonstrated two immunoreactive peaks which co-eluted with pure met-enkephalin and met-enkephalin-sulfoxide. Basal met-enkephalin outputs averaged 52 +/- 13 ng/min. The meal significantly increased mean luminal met-enkephalin output to 137 +/- 71 ng/min. During the initial 20-min postprandial period, output remained elevated (180 +/- 73 ng/min), after which it returned to basal levels. We conclude that met-enkephalin is present in the jejunal lumen, and that luminal release of this opioid is augmented by a meal.

Animals↗

Release of vasoactive intestinal peptide during hyperdynamic sepsis in dogs.

Vasoactive intestinal peptide (VIP) is a potent vasodilator that has been reported to be a mediator of the hemodynamic changes in endotoxin-induced hypodynamic septic shock. We investigated the release of VIP in a hyperdynamic model of sepsis in awake, conscious dogs similar to that of sepsis in human beings. Sepsis was induced by intraperitoneal implantation of a fibrin clot containing live Escherichia coli (0.9 +/- 0.2 X 10(9) organisms per kilogram of body weight). All dogs developed hyperdynamic sepsis with increased cardiac output and decreased systemic vascular resistance. During the first 24 hours of sepsis, VIP was released without a concomitant decrease in blood pressure, suggesting that during septic shock it was released by a direct mechanism rather than as a result of hypotension. During peak VIP release (2 to 4 hours after induction of sepsis) no decreases in systemic vascular resistance or mean arterial pressure were observed. This suggests that mediators other than VIP may be responsible for the vasodilation observed during sepsis. The precise role of VIP during sepsis is therefore yet to be clarified.

Animals↗

Complications of thyroid surgery performed by residents.

The purpose of this report is to study the incidence of complications in thyroid surgery performed by the residents in a surgical training program. This is a report of complications in 200 consecutive thyroidectomies performed by residents with attending surgeons' assistance. There were 128 female and 72 male patients, ranging in age from 16 to 89 years. Ten patients had undergone previous thyroid surgery. There were 40 total thyroidectomies, 38 subtotal thyroidectomies, and 122 lobectomies with isthmusectomy. Preoperative and postoperative evaluation of the vocal cords was a standard routine. Identification of the recurrent laryngeal nerve was routine except in patients with large goiters, who underwent intracapsular subtotal thyroidectomy. An attempt was made to identify and preserve all four parathyroid glands. Even in lobectomy procedures, the ipsilateral parathyroids were identified and preserved. Parathyroid autotransplantation into the sternomastoid muscle was performed in thirteen instances, whenever any of the parathyroids was devascularized. Complications included superior laryngeal nerve palsy (one case) and temporary recurrent laryngeal nerve palsy (one case). There was only one patient in whom temporary hypoparathyroidism developed. In three patients hematomas developed in the recovery room and reexploration was required. Two diabetic patients had wound infections develop that required drainage. Seromas and minor wound collections were noted in 6% of the patients. The incidence of major postoperative complications of thyroidectomy is low, even when residents are the primary surgeons. Thyroidectomy appears to be a safe operation in the hands of residents with close supervision and assistance by the attending surgeons.

Adolescent↗

The effects of cyclosporine on varying segments of small-bowel grafts in the rat.

The relationship between the cyclosporine A (CSA) dose and rejection of varying lengths of small-bowel grafts was studied in a rat heterotopic microsurgical small-bowel transplantation model involving a haploidentical strain combination. When Lewis X Brown Norway F1 hybrid (LBN) small-bowel grafts were transplanted into Lewis (LEW) rats without CSA, all grafts in the proximal 10 cm, the proximal 40 cm, and the entire (approximately 80 cm) small bowel were rejected on days (mean +/- SEM) 6.6 +/- 0.2 (n = 11), 7.0 +/- 0.4 (n = 6), and 7.8 +/- 0.7 (n = 6), respectively. A 10-day course (days 0-9) of CSA 2 mg/kg significantly (p less than 0.05) prolonged the survival of the proximal 10 cm, the proximal 40 cm, and the entire small bowel allografts to days 18.8 +/- 1.7 (n = 5), 16.5 +2- 1.3 (n = 6), and 13.5 +/- 1.0 (n = 4), respectively. Similarly, the CSA 5 mg/kg regimen significantly (p less than 0.05) delayed the rejection of the 10 cm, the 40 cm, and the 80 cm small-bowel grafts to days 50.2 +/- 7.2 (n = 6), 47.7 +/- 2.6 (n = 3), and 40.3 +/- 5.8 (n = 3), respectively. However, 6 of 12 rats treated with CSA 5 mg/kg died of pneumonia, and these animals were all in groups with the 40 cm and 80 cm grafts. When these animals were included in calculations of rejection-free survival, the averages for the 40 and 80 cm groups treated with CSA 5 mg/kg were 34.2 +/- 6.4 and 28.7 +/- 6.1 days, respectively. CSA suppressed rejection of small-bowel allografts in a dose-related fashion. More important, significantly (p less than 0.05) lower doses of CSA were necessary for rats that received shorter intestinal grafts. In fact, the relationship between rejection and CSA dose in the 10 cm grafts was characterized by the formula: day of rejection = 9.3 [CSA dose]1.03. We conclude that the ideal small intestinal graft should be the smallest possible segment that maintains adequate nutrition and CSA doses should be matched for segment lengths.

Animals↗

The prostaglandin response to cholesterol feeding by the rabbit gallbladder in vitro.

Eleven rabbits (five female, six male) were fed a high (2%) cholesterol diet for 2 weeks. Twelve control rabbits (six female, six male) were fed standard rabbit chow. As expected, the cholesterol feeding raised serum and bile cholesterol concentrations and increased the lithogenic indexes. The gallbladders were harvested, and the mucosa and serosa were separately exposed to arachidonic acid in an in vitro incubation chamber at 37 degrees C. Cholesterol feeding stimulated the rates of synthesis of PGI2, but this effect was limited to the serosa (and not the mucosa) of gallbladders from female (but not male) animals. In contrast, cholesterol did not induce any changes in PGE biosynthesis.

Animals↗

Progesterone receptors in the human heart and great vessels.

Progesterone receptors (PgR) were identified in 31 of 50 specimens of human (men and women) thoracic ascending aorta, internal carotid, coronary artery, and left atrial appendage. This was accomplished with a peroxidase-antiperoxidase immunocytochemical assay employing a highly specific monoclonal antibody to primate PgR. In the aorta, specific staining was seen in the nuclei of smooth muscle cells and endothelium of intima, media, and adventitia. In the myocardium, staining was localized to the nuclei of the myocardial fibers. In internal carotid and coronary arteries, PgR was localized to endothelial nuclei of intima, and in vascular channels within the atherosclerotic plaques. PgR was also visible in the smooth muscle cell nuclei of uninvolved media and intima and at the plaque periphery. In contrast, receptor was not identified in vessels of the human uterus, breast, prostate, kidney, or gastrointestinal tract. These findings suggest that the heart and great vessels are target organs for steroid hormones.

Adult↗

Regulatory mechanisms in endoluminal release of serotonin and substance P from feline jejunum.

The mechanisms controlling vagally induced 5-HT and SP release into the jejunal lumen were studied in the cat. In control animals, electrical vagal nerve stimulation doubled the rate of endoluminal secretion of 5-HT and SP. Propranolol pretreatment did not alter luminal secretion of these hormones. Atropine suppressed motor function and induced dose-related inhibition of vagal release of endoluminal 5-HT, but not of SP; the response to hexamethonium pretreatment was similar to that of atropine. In contrast, superior cervical ganglionectomy did not alter stimulated endoluminal 5-HT release but it completely abolished release into the portal vein. The portal 5-HT release was not affected by ganglionic blockade. The data suggest that vagally mediated 5-HT release into the lumen and the portal circulation are mediated by different neural mechanisms, the former cholinergic, the latter presumably adrenergic; and release of feline 5-HT and SP are independent, suggesting two intestinal sources, the EC cell for 5-HT and peptidergic neurons for SP.

Animals↗

Intraluminal release of serotonin, substance P, and gastrin in the canine small intestine.

Several gastrointestinal hormones have been found in the intestinal lumen, but as yet their physiologic role is not yet clear. We have previously shown in anesthesized animals that electrical vagal stimulation provokes simultaneous intraluminal release of serotonin (5-HT) and substance P (SP). The aim of this study was to investigate if a physiologic stimulus, a meal, releases 5-HT, SP, and gastrin (G) into the canine jejunum. In 10 dogs, chronic jejunal Thiry-Vella loops were perfused with saline (37 degrees C) before and after: a test meal; atropine, 0.2 mg/kg intravenously before the meal; atropine alone at the same dose; propanolol, 0.5 mg/kg intravenously before the meal; and propanolol alone at the same dose. Effluent perfusates and peripheral blood samples were assayed by radioimmunoassay for concentrations of 5-HT, SP, and G. Large amounts of all three humoral agents were found intraluminally during the interdigestive period. The meal resulted in increased circulating levels of 5-HT, SP, and G, while intraluminal concentrations of 5-HT and SP but not G increased following the meal. Both atropine and propanolol pretreatment significantly reduced this response, while alone, these drugs did not affect basal values. We postulate that 5-HT and SP released into the intestinal lumen in response to a meal act as local neurocrine/paracrine modulators. Their release mechanisms appear to be under both cholinergic and adrenergic control.

Animals↗

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

The mechanisms controlling vagally induced serotonin-like immunoreactivity (5-HTLI) release 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 to the portal vein. The vagally induced release of 5-HTLI to the portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by prior 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 animal it was shown that vagally induced release of 5-HTLI to the portal circulation was mediated by adrenoceptor mechanisms, while the luminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be qualitatively small in comparison with the release into the portal circulation.

Animals↗

In vivo potentiation of cyclosporine immunosuppression by calcium antagonists.

We have shown that the addition of verapamil, a calcium channel blocking agent, or trifluoperazine, a phenothiazine, to a regiment using the immunosuppressive agent Cs significantly enhances heterotopic cardiac allograft survival in an ACI to Lewis transplant model. This work verifies previous in vitro work from our laboratory and offers a potential therapeutic strategy to decrease the dose of Cs needed for effective immunosuppression while perhaps lessening its dose-related side effects.

Animals↗

The effects of size and site of origin of intestinal grafts on small-bowel transplantation in the rat.

This study was initiated to evaluate the effects of varying the length and site of origin of small-intestine transplants on rejection and on graft-versus-host disease (GVHD). Eighty rats had heterotopic transplants performed with systemic venous drainage of the grafts. The host native bowel was left in situ and no immunosuppressive agents were used. Twenty male Lewis inbred (LEW) rats who received isogenic grafts survived without any evidence of rejection or GVHD. When intestine from Lewis X Brown Norway hybrid rats (LBN) was transplanted into LEW rats, rejection occurred between day 6 and 9 and the time of onset of rejection was not influenced either by the length of transplanted bowel (10 to 80 cm, n = 6 each) or by whether the graft was from the jejunum or the ileum. However, rates of survival for 100 days from rejection were significantly better if 10 cm (100%) or 20 cm (84%) was transplanted than if the grafts were 40 cm or more in length (56%). The LBN recipients of LEW allografts developed GVHD on days 7 through 9, and this response was similarly unrelated to the length or segment of bowel transplanted. However, host survival was quite dependent on graft segment length and site of origin. All animals who received 20 cm or less of proximal bowel survived (with GVHD but no evidence of rejection). While 50% of the animals that received proximal intestinal grafts 40 cm in length survived GVHD, none who received identical-sized grafts from the distal ileum survived (all were dead by day 20). Our data document that the results of small-intestine transplantation is dependent on the length and site of origin of the grafts.

Animals↗

Acute airway distress due to thyroid pathology.

Patients with multinodular goiter or related thyroid disorders rarely have acute airway distress due to tracheal deviation or compression. However, our institution cares for a large number of patients with untreated multinodular goiters, and in the progression of this disorder, tracheal deviation and airway problems are relatively common. During the past 4 years, we have cared for 24 patients who were admitted with acute, life-threatening airway distress that required emergency intervention. Nine patients had emergency intubation, the remaining 15 had stridor on admission and underwent emergency operations. The series consists of 19 females and five males whose ages ranged from 37 to 89 years. Only four patients had malignant thyroid lesions (two papillary-follicular, two anaplastic), and two of these had multiple pulmonary metastases. Fifteen of the patients with multinodular goiters had a mediastinal extension that led to marked tracheal deviation. Three patients had recurrent multinodular goiters decades after previous surgery. Twenty-one patients underwent surgery at our institution, and all did well. Only one patient required sternotomy for thyroidectomy. Two patients required tracheostomy procedures, one because of tracheomalacia and the other because of poor pulmonary reserve. Interestingly, two patients had acute symptoms when in their third trimester of pregnancy. We have routinely used the laryngoscope (fiberoptic rigid or flexible) for preoperative and postoperative evaluation of the vocal cords and for determination of the condition of the larynx. On the basis of our experience with acute airway distress, we strongly advocate elective surgery for patients with multinodular goiter at the first sign of tracheal compression, especially if they have mediastinal extension.

Acute Disease↗