Search PubMed⌕ Search

Biomedical subjects

J L Cameron

Publications and source records attributed to J L Cameron.

At least 163 records · Page 9Linked to original sources

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↗

A comparative analysis of the distribution of prosomatostatin-derived peptides in human and monkey neocortex.

Comparative analyses were made of the immunohistochemical and biochemical distributions of three prosomatostatin-derived peptides (PSDP) in human, perfused monkey, and unperfused monkey neocortex. The PSDP we examined were the tetradecapeptide somatostatin 14 (SS14); the N-terminal extension of this peptide, somatostatin 28 (SS28); and somatostatin 28(1-12) (SS28(1-12)). In immunohistochemical experiments, numerous SS28-immunoreactive perikarya were located in both superficial and deep layers of perfused monkey cortex, but none were present in the cerebral cortex from unperfused monkey or autopsied human brains. In contrast, the number of SS28(1-12)-immunoreactive neurons was five times greater in the superficial cortical layers of unperfused monkey than of perfused monkey brain. Moreover, unperfused monkey and human cortex contained notably more SS14-immunoreactive processes than perfused monkey cortex. These data suggested that SS28 may have been converted into SS14 and SS28(1-12) in unperfused tissue during the post-mortem interval. This hypothesis was examined biochemically by measuring the levels of immunoreactivity of SS14, SS28, and SS28(1-12) in samples of unperfused monkey cortex frozen at different time intervals after removal from the brain. Samples frozen 10 minutes or longer after removal contained only 10-20% the level of SS28 immunoreactivity measured in samples frozen immediately or 1 minute after removal. The levels of SS14 and SS28(1-12) immunoreactivity did not demonstrate such reductions, and may instead have increased at early time points. To further characterize post-mortem effects on PSDP and to explore for species differences, we performed a detailed comparison of the regional, laminar, and cellular distribution of SS28(1-12) immunoreactivity under the three conditions. A progressive loss of immunoreactivity, particularly in radial fibers, was found at increasing post-mortem intervals in unperfused monkey neocortex, indicating that differences in density and distribution of immunoreactive fibers between human and perfused monkey may result from post-mortem peptide degradation in unperfused tissue. In contrast, the larger size of SS28(1-12)-immunoreactive white matter neurons in humans as compared to monkeys appeared partially due to a post-mortem effect but also reflected a species difference. In addition, the density of white matter neurons was found to be significantly greater in human than in perfused or unperfused monkey. These data indicate that any study of human autopsy material must be assessed in light of possible post-mortem effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reoperative surgery for periampullary adenocarcinoma.

In recent years, the morbidity, mortality, and long-term survival of patients undergoing surgery for periampullary adenocarcinoma have improved. These changes have prompted us to reoperate on patients who have previously undergone pancreatobiliary surgery, many of whom were initially considered to have unresectable lesions. From 1979 to 1990, 38 patients with pancreatic and 17 patients with nonpancreatic periampullary adenocarcinoma underwent reexploratory surgery at The Johns Hopkins Hospital, Baltimore, Md. Thirty-three (60%) of these 55 patients had resection at the time of second laparotomy. Of the 46 patients undergoing reexploratory surgery with an intent to resect, the overall resection rate was 72% (33), 64% (16/25) for pancreatic and 100% for nonpancreatic periampullary adenocarcinoma. Postoperative complications occurred in 21 patients (38%), but only one patient (2%) died following surgery. Mean survivals from reexploratory surgery were 6.9 months for the 22 patients with pancreatic cancer undergoing palliative surgery, 20.5 months for the 16 patients with resectable pancreatic cancer, and 33.0 months for the 17 patients with nonpancreatic periampullary adenocarcinoma undergoing resection. We conclude that in carefully selected patients, reoperative surgery for periampullary cancer (1) provides a significant resection rate, (2) can be performed safely, and (3) offers a chance for long-term survival.

Adenocarcinoma↗

Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer.

Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.

Adult↗

Choledochal cysts: role of noninvasive imaging, percutaneous transhepatic cholangiography, and percutaneous biliary drainage in diagnosis and treatment.

Choledochal cysts are an uncommon anomaly of the biliary system; findings include cystic dilatation of the extrahepatic biliary tree, intrahepatic biliary tree, or both. In the past 7 years, 13 patients with choledochal cysts have been seen at the authors' institution for evaluation and presurgical intervention. Percutaneous transhepatic cholangiography (PTC) was performed in 13 patients. Sixteen percutaneous biliary drainage (PBD) procedures were performed in 11 patients, computed tomography was performed in six patients, and ultrasound was performed in two. PTC proved to be an important imaging modality because of its superior ability to define the cyst anatomy, site of biliary origin of the cyst, and extent and detail of both extrahepatic and intrahepatic disease, that is, intraductal strictures and calculi. PBD proved valuable in preoperative intervention, as an aid in surgical reconstruction, and in postoperative care. The role of these two modalities in the diagnosis and treatment of patients with choledochal cysts, in addition to clinical aspects of the disease, is discussed.

Adult↗

Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis.

Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.

Acute Disease↗

Prevalence of infection with human immunodeficiency virus in elective surgery patients.

An anonymous survey of elective surgery patients was performed to assess prevalence of antibody to human immunodeficiency virus (HIV) in a large urban hospital. Of 4087 patients evaluated, 18 (0.4%) were found to be infected with HIV as confirmed by a positive Western blot antibody test. Assessment of risk factors demonstrated that patients with a history of a blood transfusion did not differ in demographics or rate of infection from the population as a whole. Of the 18 HIV infected patients, 13 gave an admission history of one or more risk factors, including 10 with a history of a prior positive test. Only five, or 0.12% of the patients, provided no history of a risk factor or a history of transfusion only. The authors conclude that the prevalence of HIV infection among elective surgery patients is low, and that there would not be any substantial benefit from screening such patients for antibody against HIV.

AIDS Serodiagnosis↗

Pancreatic cancer cell DNA content correlates with long-term survival after pancreatoduodenectomy.

The DNA content of 47 adenocarcinomas arising in the head of the pancreas from patients who had undergone successful pancreatoduodenectomy was measured. The DNA measurements of each tumor were made without knowledge of the clinical course by absorption cytometry performed on Feulgen-stained nuclei that had been disaggregated from pancreatic cancer tissue blocks. Forty-seven evaluable DNA distributions were obtained from specimens taken between 1975 and 1988. Of the 47 tumors, 19 (40%) were diploid and 28 (60%) were aneuploid cancers. The 19 patients with diploid cancers had a median survival time of 25 months. Median survival of the 28 patients with aneuploid cancers was 10.5 months. This difference was statistically significant (p = 0.003). A multivariate life table regression analysis demonstrated that the ploidy and proliferative index as determined by absorption cytometry were independent prognostic factors, as strong as or stronger than the number of positive nodes and tumor size. Thus cellular DNA content appears to be one of the most important predictors of survival in patients with adenocarcinoma of the head of the pancreas who have successfully undergone a pancreaticoduodenectomy.

Adenocarcinoma↗

The role of acetaldehyde in the pathogenesis of acute alcoholic pancreatitis.

Acetaldehyde (AA), the first product of ethanol metabolism, has been suggested as an important mediator in alcoholic pancreatitis, but experimental evidence has not been convincing. Prior work using the isolated perfused canine pancreas preparation has suggested that toxic oxygen metabolites generated by xanthine oxidase (XO) may mediate the early injury in pancreatitis. Xanthine oxidase is capable of oxidizing AA, and during this oxidation free radicals are released. The hypothesis that acute alcoholic pancreatitis may be initiated by AA in the presence of active XO (converted from xanthine dehydrogenase [XD]) was tested in the authors' experimental preparation by converting XD to XO by a period of ischemia, and infusing AA. Control preparations remained normal throughout the 4-hour perfusion (weight gain, 7 +/- 4 g; amylase activity, 1162 +/- 202 U/dL). One hour of ischemia or infusion of AA at 25 mg/hr or at 50 mg/hr without ischemia did not induce changes in the preparation. Acetaldehyde at 250 mg/hr induced minimal edema and weight gain (16 +/- 4 g; p less than 0.05), but not significant hyperamylasemia. Changes also were not observed when 1-hour ischemia was followed by a bolus of ethanol (1.5 g) or sodium acetate (3.0 g), or by infusion of 25 mg/hr of AA. One hour of ischemia followed by infusion of AA at 50 mg/hr or at 250 mg/hr induced edema, hemorrhage, weight gain (22 +/- 7 g [p less than 0.05] and 26 +/- 17 g [p less than 0.05]) and hyperamylasemia (2249 +/- 1034 U/dL [p less than 0.05] and 2602 +/- 1412 U/dL [p less than 0.05]). Moreover infusion of AA at 250 mg/hr after 2 hours of ischemia potentiated the weight gain (62 +/- 20 g versus 30 +/- 14 g [p less than 0.05]), but not the hyperamylasemia (3404 +/- 589 U/dL versus 2862 +/- 1525 U/dL) as compared with 2 hours of ischemia alone. Pancreatitis induced by 1 hour of ischemia followed by AA at 50 mg/hr could be inhibited by pretreatment with the free radical scavengers superoxide dismutase and catalase and ameliorated with the XO inhibitor allopurinol. The authors conclude that AA, in the presence of active XO, can initiate acute pancreatitis in the isolated canine pancreas preparation and may be important in the initiation of acute alcoholic pancreatitis in man. Toxic oxygen metabolites appear to play an important intermediary role.

Acetaldehyde↗

Metabolic cues for the onset of puberty.

The hypothesis that the timing of puberty is at least in part stimulated by some 'metabolic signal' that tells the central control system of the reproductive axis that the body is becoming large enough, and that there are enough metabolic fuel stores, to support reproductive function has received considerable attention over the past several decades. However, direct experimental support for the hypothesis that mild metabolic changes, such as those that occur slowly during development, are actually capable of modulating reproductive function has been lacking. Our recent studies have shown that very brief periods of fasting in both male rhesus monkeys and men can modify the pulsatile release of LH and testosterone. In monkeys, missing a single meal is associated with a suppression of mean plasma LH, FSH and testosterone concentrations, and with a slowing of the frequency of pulsatile LH secretion. Current studies are aimed at identifying the specific metabolic signals which cause these changes. It is hoped that the results of these studies will eventually help to answer the question of whether normal metabolic changes occurring during development play a role in timing puberty onset.

Animals↗

Suppression of pulsatile luteinizing hormone and testosterone secretion during short term food restriction in the adult male rhesus monkey (Macaca mulatta).

To determine whether signals occurring during the early stages of undernutrition can have a suppressive effect on the central drive to the reproductive axis, the effects of 1 day of fasting on pulsatile LH and testosterone secretion were examined in adult male rhesus monkeys. Monkeys were maintained with chronic indwelling venous catheters on tether/swivel systems. One day of fasting caused a small weight loss of 0.1-0.2 kg, which represented a loss of 1-3% of the initial body weight. On a day of normal feeding monkeys showed a mean of 4.57 +/- 0.53 LH pulses/12 h (measured from 1900-0700 h). On a subsequent day of fasting LH pulse frequency was significantly reduced to 1.86 +/- 0.46 pulses/12 h (P less than or equal to 0.05). Likewise, there was a similar decrease in testosterone pulse frequency on a day of fasting. The substantial decrease in LH/testosterone pulse frequency was not caused by the intensive blood-sampling regimen, in that collection of blood samples for 12 h on 2 consecutive days of normal feeding did not result in a decrease in either LH or testosterone pulse frequency. Administration of exogenous GnRH in doses of 0.05-0.3 microgram/kg caused LH pulses of similar magnitudes on a day of normal feeding and a day of fasting, suggesting that the decrease in LH pulse frequency during the day of fasting reflects a decrease in GnRH stimulation of the pituitary rather than a loss of pituitary sensitivity to GnRH. Measurement of pulsatile LH across 3 consecutive days (e.g. a day of normal feeding, a day of fasting, and a day of refeeding) indicated that LH pulse frequency is slow before the time that the meal is missed on the second day and remains low throughout the day of fasting (normal feeding, 7 +/- 1.16 pulses/24 h; fasting, 3.33 +/- 0.33 pulses/24 h). Refeeding a normal meal at 1100 h on the third day resulted in an immediate and sustained increase in pulsatile LH secretion above normal frequency (11.07 +/- 0.33 pulses/24 h). These results indicate that very brief periods of undernutrition can significantly suppress the central drive to the reproductive axis in male rhesus monkeys, and this suppression can be rapidly reversed by refeeding. These findings argue against the hypothesis that undernutrition only suppresses central drive to the reproductive axis once a substantial amount of body weight has been lost.

Animals↗

Restoration of pulsatile luteinizing hormone secretion after fasting in rhesus monkeys (Macaca mulatta): dependence on size of the refeed meal.

In men and adult male rhesus monkeys brief periods of fasting (i.e. 1-2 days) can often lead to a suppression of hypothalamic-pituitary-testicular axis activity, marked by decreased circulating concentrations of LH, FSH, and testosterone. Refeeding a normal meal can rapidly restore normal secretory patterns of LH and testosterone. To learn more about the nature of the signal that links reproductive hormone secretion to nutrient intake, we examined whether the degree of restoration of pulsatile LH and testosterone secretion after a brief period of fasting is influenced by the size of the refeed meal. Adult male rhesus monkeys had indwelling venous catheters surgically implanted and were maintained on swivel/tether systems for remote collection of blood samples. Monkeys were fasted for 1 day and then on the following day they were refed one of five meals which varied in size and calorie content (i.e. 0 Cal/0 pellets Purina monkey chow; 100 Cal/5 pellets; 200 Cal/10 pellets; 300 Cal/15 pellets; or 600 Cal/30 pellets). Blood samples were collected from 0800-2400 h at 20-min intervals on the days of refeeding and assayed for LH and testosterone content. After a day of fasting, the frequency of pulsatile LH secretion the following morning was very low (0.56 +/- 0.1 pulses/3 h, measured from 0800-1100 h). When monkeys were not refed (i.e. were subjected to a second day of fasting; 0 pellet group) LH pulse frequency remained low [2.88 +/- 0.72 pulses/13 h, measured from 1100-2400 h (equivalent to 0.66 pulses/3 h)] throughout the day and evening hours. Refeeding monkeys 5, 10, 15, and 30 pellets caused a progressive stimulation of pulsatile LH secretion (3.17 +/- 0.54, 3.67 +/- 0.56, 5.5 +/- 0.67, and 6.38 +/- 0.53 pulses/13 h, respectively). Like LH pulse frequency, mean circulating LH and testosterone concentrations progressively increased as the size of the refeed meal was increased. For all three parameters (i.e. LH pulse frequency, mean LH concentration, and mean testosterone concentration) there was a significant, P less than or equal to 0.001, linear trend with increasing meal size. These findings indicate a very strong relation between the level of nutritional intake and the level of central drive to the reproductive axis during nutritional recovery from fasting, and suggest a physiological parameter that responds in a progressive fashion to increasing food intake serves as the signal to link central drive to the reproductive axis to changes in nutrient intake.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗