The oxytocin secretory response to dopamine receptor agonists in male and female monkeys.
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Animals↗
Biomedical subjects
J L Cameron
Publications and source records attributed to J L Cameron.
Internal pancreatic fistula.
Internal pancreatic fistulae are well-recognized complications of inflammatory pancreatic disease. From 1963 to 1990, 50 patients with either pancreatic ascites (34), pancreatic ascites and pleural effusion (7), or pancreatic pleural effusion (9) were treated. Initial therapy was conservative, consisting of gastrointestinal rest, serosal apposition with paracentesis or thoracentesis, with or without the administration of anti-secretagogues. This therapy was successful in 21 of 42 patients, but 5 deaths occurred. Operative therapy was performed in 24 patients. There was one surgical failure and two deaths early in the experience. Ten of our final 16 patients underwent liver biopsy, and all 10 were found to have cirrhosis. All patients, even those with documented cirrhosis, should have routine amylase and albumin determinations on ascitic or pleural fluid. Internal pancreatic fistulae should be treated initially nonoperatively; if this is ineffective, operative therapy has an acceptably low morbidity and mortality.
Adolescent↗
Spectrum of cystic tumors of the pancreas.
The pathologic and clinical classification, as well as the behavior, of cystic tumors of the pancreas has been the subject of controversy. We retrospectively reviewed 50 patients with a diagnosis of cystic tumor of the pancreas observed at The Johns Hopkins Hospital from 1984 to 1991. These tumors were classified into three broad groups: I, cystadenoma; II, cystadenocarcinoma; and III, adenocarcinoma with mucin production or an associated cyst. The three groups did not differ with respect to age or sex. The most common clinical presentation was abdominal pain. Symptoms and signs among the three groups were similar except that patients with cystadenomas were less likely (p less than 0.05) to be jaundiced and more likely (p less than 0.05) to be asymptomatic. Radiologic findings on computerized tomography, cholangiography, and arteriography also overlapped, making precise preoperative determination of tumor type difficult. Operative classification was also often not possible. The resectability rate (Group I, 91%; Group II, 67%; Group III, 53%) and 5-year survival rate (Group I, 90%; Group II, 72%; Group III, 14%) correlated with careful pathologic determination. Cystic tumors of the pancreas represent a spectrum of disease ranging from benign cystadenoma to adenocarcinoma masquerading as cystadenocarcinoma. We recommend resection whenever possible, even when preoperative evaluation suggests benign disease.
Actuarial Analysis↗
Acute effects of a nucleoside analog dideoxyinosine (DDI) on the pancreas.
Dideoxyinosine (DDI, Videx) is a recently developed nucleoside analog with activity against the human immunodeficiency virus. A significant number of patients with AIDS or AIDS-related complex treated with DDI have developed acute pancreatitis. This study was performed to investigate the acute effects of DDI on the pancreas utilizing an isolated ex vivo perfused canine pancreas preparation. Control preparations remained normal throughout a 4-hr perfusion period. The addition of 12.5 mg of DDI to the perfusate (ca. 100 mumol/liter) did not induce any changes in the preparation. The addition of 62.5 mg of DDI to the perfusate (ca. 500 mumol/liter) did not induce changes in the gross appearance, weight gain, or amylase activity. However, the arterial pressure and the oxygen consumption of the preparation decreased significantly after the administration of DDI. The amount of zymogen in the acinar cells also decreased, as evaluated by electron microscopy. Protein secretion increased temporarily, probably as a result of acinar cell emptying (increased secretion without new synthesis). Water and bicarbonate secretion were also increased during the fourth perfusion hour.
Animals↗
Carcinoma of the body and tail of the pancreas.
Recently, several institutions have reported improved results in the treatment of patients with carcinoma of the head of the pancreas. In an attempt to determine whether similar trends could be demonstrated for patients with carcinoma of the body and tail of the pancreas, the records of all 113 patients with an adenocarcinoma of the body or tail of the pancreas treated at The Johns Hopkins Hospital between 1972 and 1989 were reviewed. The patients were divided into two groups: those diagnosed between 1972 and 1982 (41 patients) and those between 1983 and 1989 (72 patients). No significant differences in tumor stage were observed between the two groups. The proportion of patients who underwent surgery decreased from 68% to 47% (p = 0.02). The number of patients who had bypass operations (15% versus 17%) or pancreatic resection (5% versus 10%) was similar in the two groups, but the proportion of patients who underwent exploratory laparotomy with biopsy only decreased from 49% to 21% (p = 0.002). The postoperative 30-day mortality (7% versus 3%), postoperative morbidity (18% versus 21%), median survival (4 months versus 3 months), and the 1-year survival (8% versus 9%) did not differ significantly between the two groups. One patient survived for 6 years after resection, and another patient is still alive 3 years after resection. Thus, unlike adenocarcinoma of the head of the pancreas, it appears that treatment results for patients with adenocarcinoma of the body or tail of the pancreas have not improved in recent years, the only change being a decreased need for exploratory laparotomy with biopsy only.
Actuarial Analysis↗
Patterns of ileal recurrence in Crohn's disease. A prospective randomized study.
To gain information on the pathogenesis of ileal recurrence, 86 patients with Crohn's disease undergoing their first ileocolic resection were randomized to receive either an end-to-end (n = 47) or side-to-end (n = 39) anastomosis. The demographic and clinical characteristics of both groups were similar. There were no statistically significant differences between the two groups in postoperative complications or in the subsequent development of symptomatic or documented recurrences. Among the 43 patients with follow-up in the end-to-end anastomosis group, there were 10 documented ileal recurrences (23%), and all involved distal ileum in the characteristic preanastomotic location. Among the 35 patients with follow-up in the side-to-end anastomosis group, there were 11 documented recurrences (31%, not significant). The ileal recurrence pattern could be determined accurately in five of these 11 patients and involved the ileum adjacent to the colon, but spared the distal ileum in the blind pouch. This study suggests that the fecal stream and reflux of colonic contents are important factors in determining the pattern of ileal recurrence after ileocolectomy for Crohn's disease.
Adult↗
Biliary tract complications following laparoscopic cholecystectomy: imaging and intervention.
Radiologic studies and interventional procedures were performed in a series of 13 patients with biliary complications following laparoscopic cholecystectomy, and the results were evaluated. Two categories of ductal complication--minor and major--were found. Minor complications (n = 6) included bile leaks and bilomas; these were managed with percutaneous techniques or simple surgical repair. Major complications (n = 8), consisting primarily of common hepatic duct injuries or strictures, were markedly resistant to percutaneous therapy, requiring major surgical repair (hepaticojejunostomy). Percutaneous treatment of recurrent strictures after primary repair was undertaken in three patients. Diagnostically, radionuclide imaging appeared most helpful in screening for biliary complications of laparoscopic cholecystectomy, supplemented by endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic cholangiography for definitive diagnosis.
Adult↗
Primary sclerosing cholangitis: palliative surgery or transplantation?
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Adolescent↗
Suppression of luteinizing hormone secretion during food restriction in male rhesus monkeys (Macaca mulatta): failure of naloxone to restore normal pulsatility.
Short periods of fasting have been shown to cause a significant slowing of pulsatile LH secretion in men and male rhesus monkeys, which appears to result from a slowing of GnRH drive to the reproductive axis. To determine whether an increased activity of endogenous opioid peptides causes this slowing of pulsatile LH secretion, the ability of naloxone administration to reverse the fasting-induced suppression of LH secretion was tested. For this study, 6 adult male rhesus monkeys, with indwelling femoral and jugular venous catheters, were maintained on tether/swivel systems. Naloxone was administered to monkeys as a continuous infusion (0.25 mg/kg/h, with an initial loading dose of approximately 1.0 mg) for 8 h (16.00 to 24.00 h) on a day of normal feeding and again on a day of fasting. The LH response to naloxone was determined by collecting blood samples every 15 min from 12.00 to 24.00 h. LH pulse frequency on a day of normal feeding was 4.0 +/- 0.52 pulses/8 h, and naloxone administration on a day of feeding increased LH pulse frequency to 6.8 +/- 0.86 pulses/8 h. On a day of fasting, LH pulse frequency was 1.67 +/- 0.67 pulses/8 h, and naloxone administration on a day of fasting slightly, but not significantly, increased LH pulse frequency to 2.5 +/- 0.51 pulses/8 h. Similar studies were performed with a higher dose of naloxone (0.625 mg/kg/h, with an initial loading dose of approximately 2.0 mg) and again naloxone administration did not reverse the effects of fasting on pulsatile LH secretion. These results suggest that the slowing of pulsatile LH release that occurs with short periods of food restriction does not result from increased secretion of endogenous opioid peptides.
Animals↗
Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys.
Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.
Animals↗
Effect of naloxone administration upon the diurnal concentrations of oxytocin in the cerebrospinal fluid of rhesus and cynomolgus monkeys.
A diurnal pattern in oxytocin concentrations is present in cerebrospinal fluid (CSF) removed from the spinal subarachnoid space of monkeys, with elevated levels occurring in the early light hours. In order to investigate the possible role of endogenous opioid peptides in the generation of this oxytocin rhythm, we administered naloxone (0.4 mg/kg/h x 48 h) to rhesus and cynomolgus monkeys and examined the effects on the diurnal pattern of oxytocin in CSF collected from the lumbar subarachnoid spinal space. Monkeys maintained on jacket/tether/swivel systems and in a 12 h light: 12 h dark cycle (lights on 07.00-19.00 h) were implanted with temporary spinal subarachnoid catheters. CSF was continuously collected from the lumbar subarachnoid space and assayed for oxytocin. Oxytocin concentrations in CSF showed a diurnal variation with peak and nadir concentrations during light and dark hours, respectively. The lumbar CSF concentrations of oxytocin were not significantly different during naloxone vs. saline infusion. Plasma oxytocin concentrations, measured in the same animals, displayed no diurnal variation and were not significantly different during naloxone vs. saline infusion. We conclude that naloxone administration for 48 h does not perturb the diurnal variation in oxytocin concentrations in the CSF of monkeys. Mu opioid receptors are unlikely to be involved in modulating the diurnal rhythm of oxytocin in the CSF of monkeys.
Animals↗
Effects of cysteamine administration on somatostatin biosynthesis and levels in rat hypothalamus.
A single injection of cysteamine (CSH; 2-aminoethanethiol; 300 mg/kg, sc) into male rats produced a rapid decline in immunoreactive somatostatin (IR-SRIF) levels in the hypothalamus (to 20% of preinjection values within 12 h) which persisted for several days. The levels of both somatostatin-14 (SRIF-14) and somatostatin-28 (SRIF-28) were reduced. In contrast, the levels of somatostatin-28(1-12) were unaffected. Most (80-90%) of the lost SRIF molecules (both SRIF-14 and SRIF-28) could be recovered from CSH-injected rats by subjecting hypothalamic samples to denaturing, reducing, and reoxidizing conditions. These results suggest that CSH does not deplete the hypothalamus of SRIF molecules, but, instead, alters their chemical structures, rendering them undetectable using a SRIF-14-directed RIA. CSH injection also caused a rapid and complete suppression (within 1 h) of [35S]cysteine incorporation into SRIF-14 and SRIF-28. This reduction, however, was short-lived; normal incorporation rates returned within 10 h of drug administration. CSH did not influence [35S] cysteine incorporation into acid-precipitable protein or [35S]cysteine specific activity in the hypothalamus. In addition, [35S]SRIF molecules were not recovered from hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing, and then reoxidizing conditions. These findings indicate that CSH injection causes a true, but short-lived (1- to 10-h), suppression of hypothalamic SRIF-14 and SRIF-28 formation. Finally, biosynthesis studies of longer duration revealed no prolonged effects of CSH. The drug produced no changes 4, 24, or 72 h postinjection in hypothalamic levels of the prepro-SRIF mRNA. Moreover, two injections of CSH, separated by 3 days, which continuously suppressed IR-SRIF levels for almost 1 week, caused only a transient suppression of [35S]SRIF-14 and [35S]SRIF-28 synthesis after each injection. These results indicate that the SRIF biosynthetic pathway is not activated by the prolonged CSH-induced depletion of IR-SRIF stores.
Animals↗
Dopaminergic stimulation of oxytocin concentrations in the plasma of male and female monkeys by apomorphine and a D2 receptor agonist.
Administration of the dopamine receptor agonist apomorphine causes a dose-dependent increase in plasma oxytocin concentrations and dose-specific behavioral changes in rodents. To investigate whether dopamine receptor agonists will elicit similar neuroendocrine and behavioral effects in primates, we administered graded doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY 208-243 and LY 163502, to monkeys and monitored plasma concentrations of oxytocin and behavior. Five female rhesus, two male rhesus, and two male cynomolgus monkeys had chronic indwelling venous catheters implanted and were maintained on standard jacket/tether/swivel systems to allow remote blood sample collection. During experiments, blood samples were collected 10 and 5 min before drug injection and at 2- to 120-min intervals after each injection. Apomorphine (50-400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent stimulations of oxytocin secretion. CY 208-243 (100-400 micrograms/kg) did not significantly affect oxytocin secretion. Low doses of apomorphine (50-100 micrograms/kg) and LY 163502 (10-25 micrograms/kg) elicited yawning, and high doses of apomorphine (200-400 micrograms/kg) and LY 163502 (50-100 micrograms/kg) elicited stereotypic behaviors. No behavioral effects of CY 208-243 (100-400 micrograms/kg) were observed. The magnitude of the oxytocin secretory responses varied among animals, but was similar in male and female monkeys. In summary, apomorphine and LY 163502 both elicited dose-related stimulation of oxytocin secretion coupled with dose-specific behavioral changes in male and female monkeys, while no effects of CY 208-243 on these parameters were observed. We conclude that dopamine receptor agonists, and in particular D2 agonists, may be useful tools for studies exploring the physiological and behavioral actions of oxytocin in primates.
Animals↗
Gastric and duodenal obstruction in patients with cholangiocarcinoma in the porta hepatis: increased prevalence after radiation therapy.
OBJECTIVE: Our objective was to study the imaging findings in patients who had gastric and duodenal obstruction as a long-term complication of cholangiocarcinoma and to determine if the obstruction was associated with radiation therapy. MATERIALS AND METHODS: Between 1973 and 1989, 96 patients had either curative resection or palliative stenting for cholangiocarcinoma involving the hepatic duct bifurcation. Sixty-three (66%) also received adjuvant radiation therapy ranging from 4960 to 7220 rad (cGy). Gastric outlet or duodenal obstruction or both developed subsequently in seven of the 63 patients treated with radiation therapy. Radiographic studies, including upper gastrointestinal series and CT, and medical and surgical records for these seven patients were retrospectively reviewed. RESULTS: Upper gastrointestinal series in the seven patients with obstruction showed narrowing of the lumen, deformity and enlargement of gastric and duodenal mucosal folds, and delayed gastric emptying. CT performed in five of the seven patients showed thickening of the wall of the gastric antrum and small bowel and retained food and fluid within the stomach. All seven patients required gastrojejunostomy; at surgery, dense adhesions and fibrosis were found, and it was not evident whether the obstruction was due to the tumor or to radiation fibrosis. However, because this complication was seen only after radiotherapy, it was presumed to be radiation fibrosis. CONCLUSION: Our experience suggests that radiation therapy increases the risk of postoperative gastric and duodenal obstruction in patients undergoing surgery for cholangiocarcinoma.
Adenoma, Bile Duct↗
The current status of the Whipple operation for periampullary carcinoma.
In an address delivered before the Boston Surgical Society in 1942, Whipple made the following statement: The radical operation for these tumors of the ampullary region and pancreas, based on the principle of wide, en bloc removal of the tumors, as required in modern cancer surgery, is evidently in an evolutionary stage. Many more cases, with five-year survivals, will be required before valid claims can be made for the operations as done at present. In the nearly 50 years since this address, the Whipple operation has undergone numerous modifications and technical refinements. A number of recent clinical studies clearly demonstrate that this procedure now can be performed with acceptable morbidity and mortality, and that long-term survival is possible even for patients with adenocarcinoma of the head of the pancreas. The decline in operative morbidity and mortality has been achieved largely through advances in surgical technique. Further improvements in survival for patients with periampullary tumors are likely to occur through the development of more effective adjuvant therapy and improved understanding of the biologic behavior of these tumors.
Algorithms↗
Second primary lesions in the biliary tree after successful resection of ampullary carcinoma.
Two patients are described who had an adenocarcinoma at the site of the hepaticojejunostomy 5 and 15 years after pancreaticoduodenectomy for an ampullary adenocarcinoma. Both patients had symptoms and signs of biliary obstruction. Both tumors were identified by upper endoscopy and resected at laparotomy. In both patients the tumor was considered a new primary carcinoma rather than a recurrent or metastatic carcinoma. Evidence to support this was the finding of an intraepithelial component of the tumor in the resection specimens of both patients, the fact that the tumors were on the luminal side of the distal bile duct in both cases, lack of other evidence of recurrent or metastatic tumor, and the time interval between the pancreaticoduodenectomy and the development of the new tumor.
Adenocarcinoma↗
Current management of benign bile duct strictures.
Benign bile duct strictures remain one of the most difficult problems encountered by the hepatobiliary surgeon. The vast majority of bile duct strictures occur as a complication of cholecystectomy. The patients may present early in the postoperative period with evidence of a biliary leak or months to years later with the development of jaundice or cholangitis. The essential first step of management consists of delineation of the proximal biliary anatomy. Current management techniques include either operative biliary reconstruction or nonoperative balloon dilatation by either the percutaneous transhepatic or endoscopic routes. The best form of surgical reconstruction of the biliary tree is a biliary-enteric anastomosis from the proximal bile duct to a Roux-en-Y limb of jejunum. In these cases, we favor the use of long-term postoperative biliary stenting using Silastic stents. Recent retrospective, nonrandomized results from our institution favor this surgical technique over nonoperative dilatation. Primary sclerosing cholangitis is a rare cause of biliary strictures. The etiology of sclerosing is unknown, but its association with ulcerative colitis and other diseases suggest an autoimmune condition. The diagnosis is confirmed by typical cholangiographic findings of multiple areas of stricture and dilatation. No medical management has proven to be successful. Surgical management for symptomatic patients includes resection of the hepatic bifurcation with long-term transhepatic stenting of the biliary tree for patients with primarily extrahepatic and/or hilar disease and with no evidence of cirrhosis. In patients with primarily intrahepatic strictures or advanced cirrhosis, liver transplantation is the treatment of choice. Benign strictures due to other causes, such as chronic pancreatitis, calculous biliary disease, sphincter of Oddi stenosis, duodenal Crohn's disease, peptic ulcer, or perivaterian duodenal diverticula usually can be managed by choledochoduodenostomy or choledochojejunostomy without long-term stenting. The management of other rare benign biliary strictures is dependent upon their extent and underlying etiology.
Catheterization↗
Lung injury produced by pancreatic proteases in dogs.
With an isolated, blood-perfused canine lung-lobe preparation, the potential role of reactive oxygen metabolites and neutrophils in pancreatic protease (alpha-chymotrypsin)-induced acute lung injury was studied. Administration of alpha-chymotrypsin caused a low-pressure pulmonary edema (mean lung lobe weight increased from 71 to 197 gm). Pretreatment with superoxide dismutase alone did not attenuate the injury (58 to 166 gm), but when combined with catalase, the injury was significantly ameliorated (64 to 107 gm). However, depletion of circulating leukocytes did not attenuate the injury (69 to 200 gm). These findings suggest that circulatory proteases can cause lung injury by a mechanism that is mediated, at least in part, by toxic oxygen metabolites that are not of neutrophil origin.
Animals↗