Search PubMed⌕ Search

Biomedical subjects

H A Pitt

Publications and source records attributed to H A Pitt.

At least 145 records · Page 8Linked to original sources
PubMed1989

Caffeine prevents cholesterol gallstone formation.

Methylxanthines are known to inhibit in vitro gallbladder absorption. Increased gallbladder absorption has been observed during formation of cholesterol gallstones. Therefore we tested the hypothesis that caffeine would inhibit in vivo gallbladder absorption and thus prevent formation of cholesterol gallstones. Sixteen adult male prairie dogs received a control nonlithogenic diet, and 16 were fed a diet containing 1.2% cholesterol. Half of the animals in each group received caffeine in their drinking water. Gallbladder and hepatic bile were examined microscopically and analyzed for biliary lipids and electrolytes. The gallbladder/hepatic bile ratios of bile acids and sodium were calculated as indices of gallbladder absorption. All eight animals receiving the 1.2% cholesterol diet formed cholesterol gallstones, whereas none of the eight animals fed the cholesterol diet plus caffeine formed gallstones. The cholesterol saturation index was similar, however, in both groups. In animals fed a control diet, the administration of caffeine significantly increased hepatic bile flow and decreased the gallbladder/hepatic bile ratio for both bile acids (5.4 +/- 0.9 vs 3.6 +/- 0.3; p less than 0.05) and sodium (1.26 +/- 0.03 vs 1.12 +/- 0.03; p less than 0.01). In animals fed the high-cholesterol diet, caffeine significantly decreased the ratios for both bile acids (9.0 +/- 1.6 vs 5.3 +/- 0.6; p less than 0.05) and sodium (1.37 +/- 0.06 vs 1.21 +/- 0.01; p less than 0.05), lowered gallbladder bile protein levels, normalized gallbladder stasis, and lowered serum cholesterol levels. In summary, caffeine prevented formation of cholesterol gallstones in this experimental model. The effect of caffeine may be the result of alterations in multiple biliary parameters including the inhibition of gallbladder absorption.

Absorption↗
PubMed1989

Acute cholecystitis occurring as a complication of percutaneous transhepatic drainage.

Sepsis is a common occurrence during long term transhepatic biliary drainage. Most of these episodes are attributed to cholangitis, are relatively minor and can be managed nonoperatively. During a 42 month period, nine patients who had sepsis develop after biliary drainage were found to have acute cholecystitis, a complication not previously noted after this procedure. Seven of the nine patients had an underlying malignant lesion, and three of these patients had undergone percutaneous biliary drainage for palliation of unresectable or metastatic tumor. Eight of the nine patients underwent cholecystectomy whereas percutaneous cholecystostomy was used in one patient with an unresectable cholangiocarcinoma. Operative and pathologic evidence of acute cholecystitis was present in all, but only two patients had gallstones. Seven patients survived the surgical procedure and were discharged at an average of 11.7 days postoperatively. Based on this series, we propose that acute cholecystitis should be considered as a source of sepsis in patients undergoing biliary drainage who do not respond to antibiotics and catheter manipulations. Moreover, cholecystectomy should be performed at the time of laparotomy, if prolonged transhepatic drainage is planned for unresectable malignant conditions.

Acute Disease↗
PubMed1988

Indolent presentation of pancreatic abscess. Experience with 100 cases.

One hundred cases of pancreatic abscess were identified at five hospitals affiliated with UCLA between 1973 and 1985. Patients were included if a pancreatic mass or phlegmon followed an episode of pancreatitis, if the clinical impression was pancreatic abscess, and if drainage cultures were positive. Less than three Ranson's signs were present on admission in 72% of patients. The admission temperature was less than 38.3 degrees C in 71% of patients, and 27% of patients never had a fever. Abdominal tenderness was absent in 40% of patients. The admission amylase concentrations and white blood cell counts were normal in 36% and 23% of patients, respectively. Extensive débridement, external drainage, and a low threshold for reoperation were the mainstays of surgical therapy. Twenty patients (20%) died, but Ranson's signs did not predict outcome. pancreatic abscess may have an insidious presentation. A high index of suspicion, early computed tomographic scanning, and diagnostic needle aspiration may be necessary to establish this diagnosis.

Abscess↗
PubMed1988

Neuropeptide Y: a candidate neurotransmitter for biliary motility.

Neuropeptide Y (NPY) is a recently discovered polypeptide found in neurons throughout the gastrointestinal tract and in especially high concentrations in the biliary tree. This study was designed to test the functional significance of these high concentrations in the biliary tree by determining the effect of intravenous NPY on sphincter of Oddi and gallbladder motility. In adult male prairie dogs a side-hole, pressure-monitored perfusion catheter was placed through a choledochotomy into the duodenum and positioned in the sphincter of Oddi. A perfusion catheter was also placed in the gallbladder fundus. Sphincter of Oddi and gallbladder pressures were recorded before and during intravenous infusions of NPY at doses of 10, 100, and 500 ng/kg/min. Each dose was administered to seven separate animals. No effects were seen at the 10 or 100 ng/kg/min doses. NPY at the 500 ng/kg/min dose significantly increased sphincter of Oddi phasic wave frequency, amplitude, and motility index (MI = F X A). In addition, gallbladder pressure was significantly increased after 20 min of intravenous infusion of NPY at the 500 ng/kg/min dose. No significant changes in blood pressure were noted. These data suggest that in the prairie dog, systemic intravenous infusion of NPY significantly increases sphincter of Oddi phasic wave activity and gallbladder pressure. These findings are similar to those observed with intravenous cholecystokinin but opposite of those seen with peptide YY in this species. We hypothesize that neuropeptide Y may be an important neurotransmitter or neuromodulator regulating bile flow.

Animals↗
PubMed1988

Gastrosphincter of Oddi reflex.

Gastric distention is known to stimulate gallbladder contraction as well as gastric acid and pancreatic exocrine secretion by way of neural reflexes. Gallbladder distention, in turn, has been shown to affect sphincter of Oddi motility. Since gastric distention may accompany endoscopic or operative biliary manometry, we tested the hypothesis that gastric distention alters sphincter of Oddi motility. In the prairie dog model, gastric distention with acid (0.1 M hydrochloric acid, pH 1.3) and alkaline (10(-5) sodium hydroxide, pH 8.8) isotonic saline solutions both resulted in significant increases in sphincter of Oddi phasic wave frequency, amplitude, and motility index. Similarly, gallbladder pressure increased during both distention periods, thus confirming the previously described pylorocholecystic reflex. These responses were abolished by systemic pretreatment with atropine, suggesting that this reflex is cholinergically mediated. These data suggest the presence of a gastrosphincter of Oddi reflex whereby gastric distention stimulates sphincter of Oddi motility in the prairie dog. We conclude that gastric distention is an important variable to be controlled when performing endoscopic or operative sphincter of Oddi manometry.

Ampulla of Vater↗
PubMed1988

Resection of hepatic duct bifurcation and transhepatic stenting for sclerosing cholangitis.

Thirty-one patients with sclerosing cholangitis underwent reconstruction of their hepatic duct bifurcation and long-term stenting between 1980 and 1987. Indications for surgery were persistent jaundice in 29 and recurrent cholangitis in two. The mean serum bilirubin level before surgery was 10.4 mg/dl. Liver biopsy revealed that 26 patients had varying degrees of hepatic fibrosis, and five patients had progressed to secondary biliary cirrhosis. In 29 patients the major obstructive duct disease was at or near the hepatic duct bifurcation, and in two patients it was in the distal common duct. The operative procedure consisted of: (1) excision of the hepatic duct bifurcation and extrahepatic biliary tree, (2) dilatation of the intrahepatic ducts, (3) insertion of Silastic transhepatic biliary stents, and (4) bilateral hepaticojejunostomies. Two of the five patients (40%) with cirrhosis died after surgery. In contrast, only one of 26 patients (3.9%) with hepatic fibrosis died after operation. The 1-, 3-, and 5-year actuarial survival rates for patients with cirrhosis were 20%, 20%, and 20%, respectively. The only long-term survivor underwent a liver transplant. The 1-, 3-, and 5-year actuarial survival rates for patients with hepatic fibrosis were 92%, 87%, and 71%, respectively. In addition, the mean serum bilirubin levels of patients with hepatic fibrosis at 1, 2, 3, 4, and 5 years were 3.4 mg/dl, 2.9 mg/dl, 4.0 mg/dl, 5.4 mg/dl, and 4.3 mg/dl, respectively. Two of the long-term survivors subsequently underwent a liver transplant. Patients with sclerosing cholangitis, persistent jaundice, and biliary cirrhosis should be referred for consideration of liver transplantation. However, in the absence of biliary cirrhosis, if the major obstructive disease is at the hepatic duct bifurcation, primary biliary reconstruction and long-term stenting should be considered.

Adult↗
PubMed1988

Gross anatomy of the liver, biliary tree, and pancreas in the black-tailed prairie dog (Cynomys ludovicianus).

The gross anatomy of the liver, extrapetatic biliary tree, sphincter of Oddi, and pancreas in the black-tailed prairie dog (Cynomys ludovicianus), a widely used animal model for investigations into biliary physiology, pathophysiology, and pathology, was studied in 10 animals. The liver consists of 4 lobes, the left lateral, median, right lateral, and caudate. The gallbladder lies on the ventral surface of the right lobule of the median lobe. The cystic and hepatic ducts unite to form the common bile duct which enters the duodenum approximately 5 mm distal to the pylorus. The lower end of the common duct dilates forming an ampulla which is surrounded proximally by a band of circular muscle fibres which constitute the choledochal sphincter. The pancreatic duct opens separately into the duodenum approximately 80 mm from the pylorus. Earlier physiologic studies have demonstrated that the choledochal sphincter has intrinsic motility distinct from the duodenum.

Animals↗
PubMed1988

Sclerosing cholangitis.

PSC is an unusual disease of unknown etiology. In fact, sclerosis of the bile ducts may be the result of multiple factors, including autoimmune, bacterial, congenital, drug, or viral agents. The most commonly associated diseases are ulcerative colitis and chronic pancreatitis. Except for the earliest stages of the disease, liver histology is not specific. Most patients present with jaundice, pain, and pruritus, although an increasing number of asymptomatic patients with inflammatory bowel disease and abnormal liver function are being diagnosed. Cholangiography is the key to the diagnosis and is usually pathognomonic except in the unusual case where PSC is confused with cholangiocarcinoma. Multiple forms of medical therapy have been tried, including steroids, azothiaprine, D-penicillamine, colchicine, cholestyramine, and antibiotics. To date, however, none of these medications has altered the course of this disease. In recent years, balloon dilation of biliary strictures has been accomplished via endoscopic and percutaneous transhepatic approaches. However, in patients with PSC these nonoperative manipulations must be done repeatedly, may require multiple general anesthetics, and are difficult to perform. A direct surgical approach to the biliary tree with prolonged transhepatic stenting is indicated in patients with severe hilar or extrahepatic stricturing, persistent jaundice and/or recurrent cholangitis, and no evidence of cirrhosis. Hepatic transplantation should be reserved for patients with PSC who have well-established cirrhosis and in whom other therapeutic options have failed.

Bile Ducts↗
PubMed1988

Peptide YY inhibits cholecystokinin-stimulated sphincter of Oddi activity in the prairie dog.

Peptide YY (PYY), a recently discovered gut peptide, has been shown to have a number of actions that are antagonistic to the effects of cholecystokinin. This study was designed to determine whether PYY would inhibit cholecystokinin-stimulated sphincter of Oddi activity in the prairie dog. In 12 prairie dogs PYY was infused intravenously at 1, 10, and 100 ng/kg/min, and arterial blood samples were obtained. A dose-response curve was obtained, with the 10 ng/kg/min dose producing serum levels of 725 pg/ml. In seven additional prairie dogs a side-hole, pressure-monitored perfusion catheter was passed into the duodenum through a choledochotomy and positioned in the sphincter of Oddi. A perfusion catheter was also placed in the gallbladder fundus. Sphincter of Oddi and gallbladder pressures were recorded before and during 20-minute infusions of cholecystokinin and then cholecystokinin plus PYY at 10 ng/kg/min. PYY significantly inhibited cholecystokinin-stimulated sphincter of Oddi phasic wave frequency (3.8 +/- 0.2 vs 3.3 +/- 0.4; p less than 0.05) and sphincter of Oddi motility index (26.2 +/- 4.3 vs 18.7 +/- 4.8; p less than 0.025) but did not affect the increase in gallbladder pressure induced by cholecystokinin. These findings are consistent with other known anticholecystokinin effects of PYY. We conclude that PYY may also inhibit sphincter of Oddi activity in the prairie dog by an anticholecystokinin effect, thus reducing flow through the sphincter.

Ampulla of Vater↗
PubMed1987

Agents for gallstone dissolution.

Numerous methods are presently available for gallstone dissolution, including oral bile salts; cholesterol solvents such as mono-octanoin and methyl tert-butyl ether; calcium or pigment solvents such as EDTA and polysorbate; mechanical extraction techniques through a T-tube tract or after endoscopic sphincterotomy; or fragmentation methods such as ultrasonography or electrohydraulic lithotripsy, lasers, and extracorporeal shock waves. Which, if any, of these methods will be appropriate for an individual patient depends on the type of stones, whether they are in the gallbladder or bile ducts, whether access to the biliary tree is available, the patient's age and general medical condition, and the availability of expert radiologists, endoscopists, and newer equipment. In the United States, the only available oral bile salt for cholesterol gallstone dissolution is chenodeoxycholate. Ursodeoxycholate, which is more rapid and less toxic, has not been approved by the Federal Drug Administration. These agents are most effective in thin women with small, floating, radiolucent cholesterol gallstones in a functioning gallbladder. Only about half of this small subset of patients, however, will experience partial or complete dissolution of stones in 6 to 12 months. Moreover, recurrence is very likely, and the potential toxicity of long-term therapy is unknown. Thus, for most patients, cholecystectomy remains the most cost-effective and, perhaps, safest option. Intragallbladder instillation of methyl tert-butyl ether and extracorporeal shock wave therapy are also likely to be applicable to only small subsets of patients and to be associated with high recurrence rates. In patients with retained ductal cholesterol stones and access to the biliary tree, mono-octanoin therapy is advantageous in that it can be begun as soon as cholangiography demonstrates no extravasation. In properly selected patients, a 90 percent success rate with mono-octanoin infusion can be expected within a week. Radiologic or endoscopic extraction techniques require maturation of a relatively straight T-tube tract but are not dependent on the type of stone. In the hands of experts, these techniques are highly successful. In postcholecystectomy patients without access to the biliary tree, endoscopic sphincterotomy has become the preferred method of management and can be expected to succeed in more than 90 percent of patients. At this point, the exact role for ultrasonic or electrohydraulic lithotripsy and lasers is unknown. However, these techniques may be applicable in the future in patients with retained bile duct stones in whom extraction and infusion techniques have failed.

Administration, Topical↗
PubMed1987

Duodenal acidification inhibits sphincter of Oddi motility in the prairie dog.

Recent studies have explored the influence of various hormones, peptides, and neural innervation on the sphincter of Oddi (SO). However, only older and conflicting data are available on the effect of intraduodenal (ID) perfusion of acid on SO activity. Therefore, we tested the hypothesis that acidification of the proximal small bowel would alter SO motility. In acute terminal experiments, 19 adult male prairie dogs underwent cannulation of the gallbladder (GB) with a pressure-monitored perfusion catheter. The common bile duct was cannulated proximally with a drainage catheter and distally with a triple-lumen, side-hole, closed-tip catheter with one port positioned in the SO. The duodenum was cannulated distal to the SO to allow perfusion of the proximal 30 cm of intestine with saline. SO phasic wave frequency (F), amplitude (A), and baseline pressure as well as GB pressure were measured for 40 min prior to and during ID perfusion of saline at pH 8.8, pH 6.0, or pH 2.0. A SO motility index (MI = F X A) was calculated for each 10-min period of the experiment. Infusion of saline at pH 8.8 had no effect on SO function. ID perfusion of saline at pH 6.0 reduced SO MI to 39% (P less than 0.05) and 34% (P less than 0.05) of control values at 20-30 and 30-40 min, respectively. ID saline at pH 2.0 reduced the SO MI to 51% (P less than 0.01) and 53% of control values during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampulla of Vater↗
PubMed1987

Prairie dog model for antimicrobial agent-induced Clostridium difficile diarrhea.

We have noted that prairie dogs given cefoxitin develop diarrhea and lose weight yet survive for periods of up to 4 weeks. Therefore, we tested the hypothesis that cefoxitin causes Clostridium difficile cecitis in prairie dogs. Six prairie dogs were given a single intramuscular dose of 100 mg of cefoxitin per kg of body weight, and six control animals received saline; both groups were sacrificed 1 week later. Controls had no diarrhea and lost 2% of their body weight, whereas cefoxitin-treated animals had diarrhea (P less than 0.001) and lost 16% of their body weight (P less than 0.001); one animals died 6 days after cefoxitin challenge. None of the controls yielded C. difficile or had cecal cytotoxin or pseudomembranes detected. Cecal contents from all cefoxitin-treated animals, however, yielded C. difficile (P less than 0.01) and had cecal cytotoxin present (P less than 0.01). Four of five surviving animals also had cecal pseudomembranes present (P less than 0.01). These results demonstrate that in prairie dogs cefoxitin induces C. difficile cecitis. We conclude that the prairie dog is another model for the study of antibiotic-induced diarrhea. The disease in prairie dogs may have a more chronic course than in other animal models of C. difficile-induced diarrhea and may be useful as a model for studying certain aspects of C. difficile-induced diarrhea.

Animals↗
PubMed1987

Influence of motilin and cholecystokinin on sphincter of Oddi and duodenal mobility.

The sphincter of Oddi and the duodenum exhibit cyclical activity in phase with the migrating myoelectric complex. Both motilin and cholecystokinin have been shown to modulate gastrointestinal and sphincter of Oddi motility. However, previous studies have not monitored the effects of these hormones on simultaneously recorded sphincter of Oddi and duodenum pressures. The present investigation was undertaken, therefore, to determine the influence of both motilin and cholecystokinin on simultaneously recorded sphincter of Oddi and duodenal motility. In seven anesthetized prairie dogs, a triple-lumen, side-hole, pressure-monitored perfusion catheter was positioned with the proximal port in the sphincter of Oddi and the distal port in the duodenal lumen. Sphincter of Oddi and duodenal motility was recorded before and during 20-min infusions of motilin and cholecystokinin octapeptide (CCK-8) at 1, 10, and 100 ng.kg-1.min-1. Both hormones produced dose-related increases in sphincter of Oddi and duodenal motility. No response was observed with either hormone at 1 ng.kg-1.min-1. At 10 ng.kg-1.min-1, the duodenum was slightly more sensitive to motilin than to CCK-8, while the sphincter of Oddi was equally affected by both hormones. At 100 ng.kg-1.min-1, both hormones stimulated the sphincter of Oddi and the duodenum equally. These data indicate that in the prairie dog, both motilin and cholecystokinin stimulate sphincter of Oddi and duodenal motility.

Ampulla of Vater↗
PubMed1987

Risks of percutaneous transhepatic drainage in patients with cholangitis.

Percutaneous transhepatic biliary drainage (PTD) has been advocated as a method of achieving biliary decompression in patients with cholangitis. However, the risk of PTD in these patients has not been determined. Therefore, we reviewed the records of 95 consecutive PTD patients, 30 (32%) of whom had cholangitis. Forty-four (46%) of the 95 patients underwent PTD as a preoperative measure; the remaining 51 (54%) had PTD for palliation of end-stage malignancies. Thirty-day mortality and overall morbidity were 17% and 30%, respectively, in the patients with cholangitis and 15% and 28% in the patients without cholangitis. These differences were not statistically significant. However, patients with cholangitis had a significantly higher (p less than .05) incidence of post-PTD bacteremia. In patients undergoing PTD for palliation, both mortality (25%, p less than .01) and morbidity (35%) were higher than in those being drained preoperatively. This analysis suggests that PTD can be performed safely in patients with cholangitis and that the patient's underlying disease process is more important than the presence of cholangitis in determining the outcome.

Adolescent↗
PubMed1987

Antibiotics in infections of the biliary tract.

The combination of a penicillin and an aminoglycoside has been recommended as the initial treatment of choice for patients with infections of the biliary tract. However, elderly, septic, patients with jaundice have a high incidence of renal problems. For this reason, amingolycoside treatment of these patients must be reevaluated as newer less nephrotoxic agents become available. We, therefore, performed a prospective, randomized trial of ampicillin plus tobramycin, cefoperazone and piperacillin in patients with biliary tract infections. During a 20 month period, 106 patients with acute cholecystitis (53) or cholangitis (53), or both, received one of these antibiotic regimens for a minimum of five days. In patients with acute cholecystitis, ampicillin plus tobramycin, cefoperazone and piperacillin had clinical cure rates of 85, 95 and 95 per cent, respectively. In patients with cholangitis, however, cure rates for the three regimens were 85, 56 (p less than 0.05 versus ampicillin plus tobramycin) and 60 per cent (not significant versus ampicillin plus tobramycin), respectively. Moreover, 13 per cent of the patients receiving cefoperazone had an increased prothrombin time and three of 39 patients receiving this antibiotic had clinical problems with bleeding. Nephrotoxicity was greatest in patients with cholangitis receiving ampicillin plus tobramycin, 10 per cent, as compared with 3 per cent in those who did not receive an aminoglycoside. This difference, however, was not statistically significant. It was concluded that piperacillin should be considered for antibiotic management of patients with acute cholecystitis and that further studies are necessary in patients with cholangitis to determine whether or not newer agents should replace penicillin and aminoglycoside combinations.

Ampicillin↗
PubMed1987

Percutaneous aspiration of peripancreatic fluid collections: a safe method to detect infection.

During the past 5 years, we have used percutaneous aspiration of peripancreatic fluid collections guided by computed tomography (CT) or ultrasonography (US) to facilitate diagnosis of infection in selected cases. Fifteen of 18 patients undergoing guided needle aspiration had persistent fevers (greater than 38.3 degrees C). The three afebrile patients all had abdominal pain and leukocytosis, and two of the three also had elevated serum amylase levels. Percutaneous aspiration was guided by CT in 14 patients and by US in four. On the basis of aspirate Gram stains and cultures, as well as surgical (15) and percutaneous drainage (1) findings, the final diagnosis was pancreatic abscess in nine patients, infected pseudocyst in four, uninfected pseudocyst in four, and cystadenoma in one. Diagnosis based on percutaneous aspiration was correct in 17 of 18 patients (94%), and no complications could be directly attributed to the procedure. We conclude that CT- or US-guided percutaneous aspiration is a safe and accurate diagnostic procedure for patients with peripancreatic fluid collections in whom secondary infection is suspected.

Abscess↗
PubMed1987

Cholecystectomy alters the hormonal response of the sphincter of Oddi.

We have previously described a cholecysto-sphincter of Oddi reflex whereby sphincter of Oddi (SO) motility is mediated in part by the degree of gallbladder distension. Therefore, we tested the hypothesis that cholecystectomy alters the response of the SO to endogenous and exogenous hormonal stimulation. Eight months after sham laparotomy (n = 8) or cholecystectomy (n = 10), prairie dogs were anesthetized with alpha-chloralose. The common bile duct was cannulated distally with a side-hole, pressure-monitored catheter perfused with degassed water at 0.15 ml/min. The duodenum was cannulated distal to the SO to allow perfusion of the proximal 30 cm of intestine with 20 mmol/L sodium oleate at 0.4 ml/min. In animals undergoing sham laparotomy the gallbladder was cannulated, aspirated, and kept empty throughout the experiment. SO phasic wave frequency (F), amplitude (A), and baseline pressure were measured for 60 minutes before and during intraduodenal (ID) perfusion of sodium oleate and then for 60 minutes before and 30 minutes during intravenous (IV) infusion of cholecystokinin-octapeptide (CCK-OP) at 10 ng/kg/min. A SO motility index (MI) (MI = F X A) was calculated for each 10-minute period. Common duct diameter and resting SO motility were unaltered 8 months after cholecystectomy. In animals that had sham laparotomy ID infusion of sodium oleate reduced SO MI by 46% (p = 0.06) and 75% (p less than 0.05) at 30 and 60 minutes, respectively, whereas in animals that had cholecystectomy the reduction in SO MI was only 6% and 25% (p less than 0.05) during the same periods. In animals that had sham laparotomy IV CCK-OP increased the SO MI by 175% (p less than 0.05), but in the animals that had cholecystectomy IV CCK-OP increased SO MI by only 60% (no significance). These findings indicate that after cholecystectomy resting SO motility is unaltered, but the response to ID sodium oleate and to IV cholecystokinin is blunted. We suggest that cholecystectomy alters neural pathways that mediate the normal response of the SO to endogenous and exogenous hormonal stimulation.

Ampulla of Vater↗