The purpose of this study was to compare the 5-hydroxytryptamine (5-HT) receptor subtypes involved in secretion of water and electrolytes (sodium, potassium, and chloride) induced by luminally administered serotonin in rat jejunum and ileum in vivo. Ketanserin partially inhibited and ICS 205-930 totally inhibited serotonin-evoked secretion. Ketanserin induced mild basal secretion while ICS 205-930 alone reduced basal absorption. There were no differences in the effects of ketanserin or ICS 205-930 on serotonin-induced secretion by rat jejunum versus ileum. Neither N -acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide nor methysergide altered the secretary effect of serotonin in rat ileum. The substituted henzamides, cisapride, and BRL 24924, and the 5-HT4 agonist, 5-methoxytryptamine, induced water and electrolyte secretion. While BRL 24924 did not alter the subsequent serotonin-induced secretory fluxes, cisapride slightly inhibited the induced secretion. These results suggest that (1) in both segments of the intestine, 5-HT2, 5-HT3, and/or 5-HT4 receptor subtypes are involved in the regulation of intestinal transport of water and electrolytes under basal conditions; (2) serotonin-induced water and electrolyte secretion is mediated by pathways involving 5-HT2, 5-HT3, and 5-HT4 receptor subtypes in both rat jejunum and ileum; (3) 5-HT1 receptors do not seem to be involved in the mediation of intestinal water and electrolyte transport; (4) these effects are similar to those described for systemically administered 5-HT.

Thyroid diseases and surgery for thyroid neoplasms are both very common. Several complications of thyroidectomy are well known. Some of these are quite disturbing, such as recurrent laryngeal nerve injury and permanent hypoparathyroidism. However, postoperative hematoma often in the recovery room may be fatal. Close observation and early intervention are of utmost necessity in the post-thyroidectomy period. In a series of 600 thyroidectomies performed over a period of 11 years, eight patients developed postoperative hematoma. Seven of them underwent re-exploration, while one patient was treated conservatively. Two patients had second re-exploration for hematoma reaccumulation. All patients recovered very well after re-exploration except one elderly patient who required ventilatory support due to poor pulmonary reserve; after a week of ventilatory support and a tracheostomy, she too recovered well. One patient had the hematoma re-explored as late as 24 hours after the operation, while the remainder were re-explored within 4-6 hours after the initial procedure. Because of the extent of edema of the larynx and pharyngeal wall, it is very important that a senior, experienced person perform intubation in these patients. It is also very important to recognize that when the patients lie down flat, they may develop acute airway distress; hence, one must be prepared to intubate them emergently. We recommend close recovery room observation after thyroidectomy and early exploration and evacuation of hematoma in all patients who develop postoperative hematoma. A conservative approach may be considered in selected patients with minimal hematoma and no progression. However, it generally takes a long time for the hematoma to resorb. A better understanding of the complications of thyroidectomy will minimize morbidity and make thyroidectomy a safer procedure and a surgical triumph.

1. The possible involvement of eicosanoids, cyclic adenosine monophosphate (c-AMP), and inositol 1,4,5-trisphosphate (IP3) in serotonin-(5-hydroxytryptamine-) induced secretion in rat ileum in vivo was studied. 2. Serotonin caused a significant increase in mean Ip3 levels. Indomethacin reduced serotonin-induced secretion of water by 28%. Thus, Ip3 and eicosanoids appear to be intracellular mediators of serotonin-induced secretion in rat ileum. 3. Serotonin, BRL 24924, and cisapride all inhibited theophylline-induced increases in c-AMP concentrations in rat ileal segments. Neither BRL 24924 nor cisapride caused any change in Ip3 levels. 4. These data suggest that a 5-HT2 receptor dependent on Ip3 and eicosanoids is involved in mediating in serotonin-induced secretion in rat small intestine.

A new model of ex vivo vascularly perfused, isolated rat ileum was developed and evaluated. Segments of distal ileum (approximately 5 cm) from male Wistar rats were isolated on their vascular pedicles. Perfusion through an aortic cannula with oxygenated (95% O2, 5% CO2) Krebs solution containing 5% bovine albumin, 5.6 mM glucose, and 25 mM mannitol at 37°C was initiated immediately after interruption of blood flow. The bowel preparations, including the abdominal aorta, were then transferred to a perfusion chamber. Perfusion pressure was maintained by gravity at 40 mm Hg. Flow was measured with an electromagnetic flow probe. The portal vein, together with the lymphatics, drained freely into collection tubes. The bowel lumen was perfused at 0.85 ml/min with isotonic modified Krebs solution containing [14C]polyethylene glycol, and the luminal perfusion pressure was monitored. Luminal effluents were collected through a large-bore outlet tubing. As determined by histology, O2 consumption, vascular reactivity, and mucosal permeability, the preparations were viable for at least 60 min of perfusion. With this model, a vasoconstrictor effect of the α2-adrenoceptor agonist clonidine was documented for the first time in isolated rat bowel.

This study was performed to determine the extent to which intestinal transplants undergo functional and morphologic compensation. Animals were studied after 25 days to document how rapidly the changes occurred and after 150 days to establish whether the effects were maintained long term. Lewis isografts and Lewis Brown Norway F1 allograft recipient rats had comparable degrees of morphologic (increased bowel diameter, crypt depth, and villus height) and functional (absorption of 3H-glucose, 14C-maltose, and cyclosporine) compensation. These changes were already present by day 25 and persisted until at least day 150. The results were independent of the loss of extrinsic innervation or the intramuscular administration of cyclosporine (5 mg/kg/day). These observations support the usefulness of segmental intestinal transplantation in the treatment of surgically induced short bowel syndrome.

Despite the widespread availability of firearms, stab wounds to the abdomen, back, and flank continue to account for a significant number of injuries. The proper sequencing of diagnostic modalities in this patient group is constantly undergoing change. We report our experience with these injuries and present a new algorithm for the use of currently available diagnostic procedures. In 1987, 162 patients were seen, 103 with anterior abdominal wounds and 59 with back and flank wounds. Patients with shock, peritonitis, and evisceration were resuscitated and explored. The remainder of the cohort underwent tap and lavage, and patients with a negative study were observed. Patients with back and flank wounds underwent contrast enhanced computerized tomographic enemas (CECTE). Seventeen patients underwent immediate exploration and 108 of the 162 patients were spared exploration. Fifty-four patients were explored with six negative laparotomies. Of the 126 taps and lavages, the false positive rate was zero, and only one patient had a false negative study. Of the 47 CECTE studies, only three were interpreted as an indication for angiography which proved negative, and all patients were safely observed. The overall mortality was 4.3%, including three patients without vital signs on admission and four who expired intraoperatively due to irreversible shock. We concluded that this algorithm can be safely applied to patients with these injuries with a high degree of specificity and sensitivity.

Injection of the structurally related peptides, endothelin-1 and vasoactive intestinal contractor (VIC), into a branch of the superior mesenteric artery in anesthetized cats caused dose-dependent reductions in blood flow in the portal vein and inferior mesenteric artery. The maximum effect occurred after 1 minute and was more prolonged in the portal vein. The effects of the two peptides were not significantly different. The colonic output of vasoactive intestinal polypeptide (VIP) into portal venous blood was decreased significantly by endothelin-1 and VIC, returning to baseline more rapidly than blood flow. When norepinephrine was injected to produce comparable reductions in blood flow, the output of VIP into portal venous blood was not altered significantly. These results suggest that inhibition of output of the vasodilator VIP contributes to the vasoconstrictor effects of endothelin-1 and VIC in the feline colonic vascular bed.

The effects of ethanol on simultaneous jejunal handling of calcium and glucose were studied in long-term canine jejunal Thirty-Vella loops. The loops were perfused intraluminally in a random sequence with physiologic buffer, buffer containing 3.5% ethanol, and buffer containing 7% ethanol. The addition of 3.5% or 7% ethanol to the buffer reduced the net absorption of glucose by 13% and 26%, respectively. The addition of 7% but not 3.5% ethanol significantly increased the net secretion of calcium (168% of basal). In contrast, luminal perfusion with ethanol did not significantly alter intestinal handling of water, sodium, or potassium. Serum calcium and glucose levels were similarly unaffected by the ethanol perfusion. Mean serum ethanol levels were all less than 10 mg/dl. We conclude that intraluminal ethanol has a significant effect on the jejunal handling of glucose and calcium, and this effect is not dependent on systemic intoxication.

The aim of this study was to determine whether short-segment jejunal allografts maintained the viability and nutritional status of outbred recipient pigs treated with low-dose cyclosporine. The animals were subjected to total small bowel resection (from the ligament of Treitz to the ileocecal valve, approximately 15 m). Short-gut control animals (n = 8) who had no transplant died of malabsorption on day 62.5 +/- 4.1 (mean +/- SEM). Without cyclosporine immunosuppression, recipients (n = 5) of 3 m to 4 m jejunal allografts died of rejection on day 8.8 +/- 0.7. However enterectomized pigs (n = 11) who had segmental jejunal allograft transplants and were treated with cyclosporine (10 mg/kg/day) demonstrated significantly prolonged survival (to day 80.9 +/- 22.3; p less than 0.05). By 180 days after transplant, surviving animals increased their weight by almost 40%. In conclusion short-segment jejunal allografts significantly improved the mortality and morbidity rates from surgically created short bowel syndrome in pigs.

Prognostic factors in well-differentiated thyroid cancer are age of the patient and grade, size, distant metastasis, and extracapsular spread of the disease. However, the surgeon is often not sure about the pathologic diagnosis of thyroid nodules. The accuracy of preoperative studies, such as ultrasonography and thyroid scanning, is limited. The most cost-effective test is fine-needle aspiration, the accuracy of which exceeds 80% in most series. However, a large group of nodules exist for which aspiration cytologic studies are considered to be either suspicious or indeterminate. The decision about the extent of thyroidectomy may be difficult in these patients. Intraoperative frozen section may help the surgeon to distinguish benign from malignant lesions, but as in fine-needle aspiration, the major problem is the distinction between follicular adenoma and follicular carcinoma. The frozen section diagnosis of follicular adenoma was changed to follicular carcinoma in one third of the cases (13 of 38 cases). The decision about the extent of thyroidectomy in patients with follicular adenomas was based on other prognostic factors, such as age and sex of the patient and the size of the nodule. The accuracy of frozen section diagnosis was 95%. Our experience suggests that decisions regarding the extent of thyroidectomy can best be made by preoperative fine-needle aspiration with confirmation by frozen section diagnosis in equivocal cases.

The purpose of this study was to assess the accuracy of frozen sections performed during thyroid surgery and to define any pitfalls they may have. The material includes a series of 190 frozen section examinations of thyroid pathology. The overall accuracy of frozen section in this series was 95%. There were no false positives in our series and false negatives related to only follicular adenomas. In two patients, the report was deferred for permanent slide examination. Nine patients had lesions reported as malignant; however, the distinct cell type was not designated on frozen section. Eight specimens initially reported to have follicular adenoma on frozen section turned out to have angioinvasion or capsular invasion indicative of follicular carcinoma. Minor discrepancies between frozen and permanent sections in the types of benign disease were noted occasionally, but were not clinically significant. There was a discrepancy in the diagnosis of Hashimoto's thyroiditis on three occasions. The major discrepancy in patients with malignant pathology was related to the cell type. The diagnosis of anaplastic thyroid cancer, though suspected, was deferred for permanent sections in all cases. The diagnosis of medullary cancer of thyroid was difficult to make on frozen section. The major problem with frozen section was the diagnosis of follicular adenoma versus carcinoma. The benign diagnosis was changed in eight instances (out of 24 frozen sections) from follicular ademona to follicular carcinoma. Because of this experience, we do not provide the frozen section diagnosis to the patient and we wait until the final diagnosis is available.

The effect of the vasoactive intestinal polypeptide (VIP) antagonist [N-Ac-Tyr1,D-Phe2]-GRF-(1-29)-NH2 on pelvic nerve-induced colonic vasodilation and VIP release was investigated in chloralose-anesthetized cats. VIP antagonist (10 and 50 nmol/kg in saline) or saline alone was injected into a branch of the superior mesenteric artery immediately before bilateral pelvic nerve stimulation. The increase in conductance in the inferior mesenteric artery during pelvic nerve stimulation was reduced in an apparently dose-dependent fashion by the VIP antagonist (by 35 +/- 10 and 42 +/- 9%, respectively) compared with the pelvic nerve-induced increase in conductance after injection of saline alone. Injection of the VIP antagonist (50 nmol/kg) did not alter conductance in the absence of pelvic nerve stimulation. VIP was released into portal venous blood during pelvic nerve stimulation in the presence of the antagonist (from 103 +/- 29 to 165 +/- 45 pmol/l). This was not significantly different from release in the presence of saline. The effect of the VIP antagonist (10 nmol.kg-1.min-1) on inferior mesenteric arterial vasodilation induced by exogenous VIP was also quantitated. The increase in conductance after VIP injection (0.2 nmol/kg) was significantly reduced when accompanied by simultaneous infusion of the VIP antagonist (by 54 +/- 6%) compared with the increase in conductance during simultaneous infusion of saline. We conclude that [N-Ac-Tyr1,D-Phe2]-GRF-(1-29)-NH2 is an inhibitor of pelvic nerve-induced vasodilation in the feline colon and does not act by modulating VIP release.(ABSTRACT TRUNCATED AT 250 WORDS)

Denervation of the gut, resulting in altered bowel function, has been viewed as an impediment to the clinical success of small intestinal transplantation. This study examined the effect of complete extrinsic denervation of the jejunum and ileum on tissue levels of VIP, SP, and 5-HT in a rat model of small intestinal transplantation. Orthotopic total small bowel isograft transplants were performed in 18 Lewis inbred rats. Sham operations consisted of occluding the superior mesenteric artery of 18 Lewis rats for 10 minutes to provide comparable degrees of ischemia. Six rats from each group were sacrificed 1, 2, and 4 weeks following transplantation or sham operation. The jejunum and ileum were removed and extracted in acid for measurement of VIP, SP, and 5-HT by radioimmunoassay. There were no statistically significant differences in the jejunal or ileal content of VIP or 5-HT or the jejunal content of SP between the transplant and sham groups. An initial decrease in ileal SP content at 1 week following transplantation was no longer evident by the fourth week. We conclude that the extrinsic denervation of small intestinal transplantation has minimal effects on the intestinal content of VIP, SP, and 5-HT and should not significantly affect physiologic function controlled by these gastrointestinal hormones.

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.

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.

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.

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.

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.

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.