Biomedical subjects

H A Pitt

Publications and source records attributed to H A Pitt.

At least 19 recordsLinked to original sources

PubMed1992

Patients with uncomplicated cholelithiasis acidify bile normally.

Reports have suggested that patients with gallstones have gallbladder bile that is less acidic and more saturated with calcium carbonate than patients without gallstones. This failure to acidify bile may play a role in the formation of gallstones. We, therefore, compared gallbladder bile pH, ionized calcium, and calcium carbonate saturation index from patients undergoing either incidental gallbladder removal (controls, n = 23) or elective cholecystectomy for gallstones (n = 55). Gallstones were classified as either cholesterol (n = 39) or black pigment (n = 16) stones. No difference in gallbladder bile pH was noted among the controls, cholesterol stone, and pigment stone patients. In addition, no difference in ionized calcium concentration or CCSI was noted among the three groups. The pH in additional patients (n = 49) with acute cholecystitis, common bile duct obstruction, biliary tract infection, and cystic duct obstruction was significantly more acidic. We conclude that neither a defect in bile acidification nor increased saturation of calcium carbonate explains why human cholesterol or pigment gallstones form.

Adult↗

PubMed1992

Effect of cholecystectomy on gallbladder bile composition.

Human bile samples are commonly used in biliary research; however, the optimal sampling technique is not known. The current study examines whether bile obtained prior to operative manipulation of the gallbladder differs in composition from samples obtained after cholecystectomy. Gallbladder bile samples were obtained from 26 patients undergoing cholecystectomy. An initial sample was obtained prior to manipulation or devascularization of the gallbladder, and a second sample was obtained after the removal of the gallbladder from the operative field. Gallbladder bile pH and total protein were significantly increased in the postcholecystectomy samples. Bile obtained after cholecystectomy also contained significantly less phospholipid. Gallbladder bile cholesterol, total bile acids, bilirubin, ionized and total calcium, cholesterol saturation index, and total lipids were similar between techniques. These results indicate that manipulation of the gallbladder during cholecystectomy produces alterations in gallbladder bile composition. These results also emphasize the need for consistent sampling technique when obtaining samples for biliary research.

Bile↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

Selective cholangiography. Current role in laparoscopic cholecystectomy.

The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employing an algorithm of selective cholangiographic evaluation is reported. Preoperative or postoperative endoscopic retrograde cholangiography was performed whenever stones were suspected clinically. Preoperative endoscopic retrograde cholangiography was performed in 44 patients (11%), in whom 14 (3.5%) had an endoscopic sphincterotomy with extraction of common bile duct stones. Intraoperative cholangiography was performed in only eight patients (2%) almost exclusively to acquire experience with the technique, and all cholangiograms were normal. Laparoscopic cholecystectomy was successfully completed in 96% of the patients. There were no deaths in this series, and major complications occurred in only 5% of patients. Two patients (0.5%) had a significant common bile duct injury that was recognized and successfully repaired at the initial operation. No late common bile duct strictures have been recognized. Six patients (1.5%) underwent postoperative endoscopic retrograde cholangiography for suspected common bile duct stones, with three patients requiring endoscopic sphincterotomy and stone extraction. This experience suggests that the use of preoperative and postoperative endoscopic retrograde cholangiography can be based on clinical presentation and laboratory evaluation and does not need to be performed routinely. Routine intraoperative cholangiography is not necessary in most patients undergoing laparoscopic cholecystectomy. The authors conclude that laparoscopic cholecystectomy can be performed safely with the selective use of cholangiography.

Adolescent↗

PubMed1992

Long-term intraperitoneal insulin delivery.

Over the past 5 years, 21 patients with insulin-dependent diabetes mellitus have been managed at the Johns Hopkins Medical Institutions with variable rate, remotely controlled implanted insulin pumps. To date, nearly 70 patient-years of experience has been gained with intraperitoneal delivery of a new U-400 insulin with a surfactant. All 21 patients are alive after a mean of 39.3 months (range, 10 to 65 months) after insulin pump implantation. Nineteen of the 21 patients remain on intraperitoneal insulin, for a 5-year actuarial system survival of 90%. Glucose control was improved, especially during the first 16 months after pump implantation, without an increased incidence of severe hypoglycemia. Catheter blockage has been a significant problem, occurring in nine of the 21 patients (43%). Catheter occlusion has been successfully managed, however, with laparoscopic repair in seven of 10 attempts or with catheter change in four of five patients. Nevertheless, quality of life and patient acceptance remain excellent. Moreover, pre-existing nephropathy, neuropathy, and retinopathy have been surprisingly stable. With an aggressive policy of catheter change or laparoscopic clearance of catheter blockage, long-term intraperitoneal insulin delivery is now a safe and effective treatment for type I diabetics.

Adult↗

PubMed1992

Effect of octreotide on sphincter of Oddi and gallbladder motility in prairie dogs.

Somatostatin and its synthetic analogue, octreotide, inhibit gallbladder emptying and cause gallstones. Whether octreotide-induced alterations in sphincter of Oddi motility contribute to this process is unknown. We, therefore, examined the effect of octreotide on fasting and protein-stimulated sphincter of Oddi motility. In 25 anesthetized prairie dogs, sphincter of Oddi motility and gallbladder pressure were monitored during the intravenous administration of octreotide, cholecystokinin (CCK) octapeptide, atropine, the intraduodenal administration of casein, and combinations of these agents. Intravenous octreotide decreased fasting sphincter of Oddi motility index both with (59 +/- 19 vs. 84 +/- 28, P less than 0.05) and without (137 +/- 31 vs. 227 +/- 42, P less than 0.05) prior cholinergic blockade with atropine. Octreotide also prevented the increases in sphincter of Oddi motility and gallbladder pressure seen with intraduodenal casein. Exogenous CCK increased sphincter of Oddi motility index and gallbladder pressure despite the simultaneous administration of octreotide alone (357 +/- 109 vs. 137 +/- 31, P less than 0.07, and 11.2 +/- 1.0 mmHg vs. 9.6 +/- 0.6 mmHg, P less than 0.05) or the combination of octreotide and atropine (317 +/- 69 vs. 59 +/- 19, P less than 0.05, and 10.1 +/- 1.6 mmHg vs. 8.5 +/- 1.4 mmHg, P less than 0.05). We conclude that both a cholinergic and an octreotide-sensitive noncholinergic pathway stimulate fasting sphincter of Oddi motility in the prairie dog.

Animals↗

PubMed1992

Distribution of phosphatidylcholine molecular species between mixed micelles and phospholipid-cholesterol vesicles in human gallbladder bile: dependence on acyl chain length and unsaturation.

The partitioning of phosphatidylcholine (PC) molecular species between mixed micelles and vesicles was studied in each of seven human gallbladder biles. Biles were fractionated by Sephacryl S-300 SF gel filtration chromatography, and PC species in the micellar and vesicular fractions were quantitated by high performance liquid chromatography. Micelles were enriched in species containing unsaturated acyl groups (e.g., 16:1-18:2, 18:1-18:2, and 18:1-18:3); vesicles were enriched in more highly saturated species (e.g., 16:0-16:1, 16:0-18:1, and 18:0-18:1). Separate multivariate analyses for each bile demonstrated that the distribution of PC species between vesicles and micelles was related to the degree of sn-1 and sn-2 unsaturation, and sn-1, but not sn-2, chain length. In addition, the tendency to partition into the micellar phase was particularly marked when unsaturation was present at both the sn-1 and sn-2 positions. When this interaction was included in the multivariate analyses, the regression models accounted for virtually all of the variation in PC partitioning (for each of the seven patients r2 = 0.92-0.98, P less than 0.03). These results suggest that the partitioning of PC species between micelles and vesicles is strictly determined by sn-1 chain length and the degree of unsaturation at both the sn-1 and sn-2 positions. In light of recent reports that fatty acyl composition influences the cholesterol content of vesicles and micelles in model biles, these results raise the possibility that diet-induced alterations in the phospholipid species and the relative proportions of biliary lipid particles may influence the cholesterol-carrying capacity of bile.

Bile↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

Why does somatostatin cause gallstones?

Long-term administration of the somatostatin analogue, octreotide, is complicated by gallstone formation. Somatostatin is known to inhibit hepatic bile secretion and gallbladder emptying. However, the effect of octreotide on gallbladder bile composition remains unknown. Therefore, we tested the hypothesis that octretide would alter hepatic bile composition and cause gallbladder stasis, thereby increasing gallbladder bile solute concentrations. Fourteen control prairie dogs received daily saline injections, whereas 10 animals received 1 micrograms of octreotide subcutaneously three times per day for 5 days. Cholecystectomy and common bile duct cannulation were then performed. Octreotide increased hepatic bile concentrations of bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.05), and total protein (p less than 0.01). Rsa, an index of gallbladder stasis, was decreased (p less than 0.01) in the octreotide group. Gallbladder bile total calcium (p less than 0.05), bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.01), total protein (p less than 0.05), and total lipids (p less than 0.05) were increased in the octreotide group. Animals receiving octreotide also had decreased hepatic (p less than 0.05) and gallbladder (p less than 0.001) bile pH. No differences in cholesterol saturation index were observed. These data suggest that in the prairie dog, octreotide (1) alters hepatic bile composition, (2) causes gallbladder stasis, and (3) increases gallbladder bile calcium, bilirubin, protein, lipid, and hydrogen ion concentrations. We conclude that octreotide causes alterations in gallbladder bile composition that increase the likelihood of cholesterol and calcium bilirubinate precipitation.

Animals↗

PubMed1991

Cost-effectiveness of extracorporeal shock-wave lithotripsy versus cholecystectomy for symptomatic gallstones.

To evaluate the cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy for symptomatic gallstones, a model was constructed that projects charges and survival for both treatments. For a 45-year-old woman with one small stone, treatment with extracorporeal shock-wave lithotripsy rather than cholecystectomy is projected to result in an average gain of only 3 days of life and an average increase in direct medical charges of $1729 over 5 years of follow-up. The resulting marginal cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy is $216,000 of extra charges per year of life gained with extracorporeal shock-wave lithotripsy. Extracorporeal shock-wave lithotripsy is projected to be much more cost-effective for elderly than for young patients (10-20-fold difference), but considerably less cost-effective for multiple stones than a single stone (2-4-fold difference), and less cost-effective for women than men (twofold difference). Adjusting for effects of morbidity on quality of life, extracorporeal shock-wave lithotripsy is projected to have slightly better quality-adjusted survival than cholecystectomy for the small subset of patients with one stone (by 8 to 43 days at 5 years) but not for young patients with multiple stones. It is concluded that decisions about appropriate use of extracorporeal shock-wave lithotripsy should consider the effects of patient characteristics on clinical and economic outcomes.

Aged↗

PubMed1991

Bilirubin monoglucuronide promotes cholesterol gallstone formation.

Recent evidence suggests that cholesterol (Ch) solubility in bile is determined by a complex interaction of mixed micelles and lecithin-cholesterol vesicles. Bilirubin monoglucuronide (BMG), which binds to bile salts and incorporates into mixed micelles, may displace cholesterol from micelles into vesicles, thus favoring cholesterol monohydrate crystal precipitation. Therefore, we designed an experiment to test the hypothesis that BMG may enhance cholesterol gallstone formation without inducing cholesterol supersaturation. For 8 weeks, 28 adult male prairie dogs were fed either a control, nonlithogenic diet (0.03% Ch), a high carbohydrate diet (CHO) which has no cholesterol but increases hepatic bilirubin secretion, or the same CHO diet plus 0.03% Ch. Cholecystectomy was then performed, and bile was examined microscopically for stones or crystals and analyzed for BMG and biliary lipids. Cholesterol saturation index was calculated. Cholesterol gallstones were found in none of the control animals and in 13% of the CHO-fed animals. However, the addition of trace cholesterol to the CHO diet resulted in an 88% incidence of cholesterol gallstones (P less than 0.001 vs control, P less than 0.01 vs CHO, respectively). Gallbladder bile was unsaturated with cholesterol in all groups. (control = 0.65 +/- 0.05, CHO = 0.46 +/- 0.05, CHO + 0.03% Ch = 0.70 +/- 0.03). CHO feeding alone or with trace cholesterol significantly elevated gallbladder bilirubin monoglucuronide, phospholipid, and cholesterol concentrations when compared to controls. These data suggest that in the prairie dog a high carbohydrate diet with only trace amounts of cholesterol increases bilirubin monoglucuronide in gallbladder bile and causes cholesterol gallstone formation without inducing cholesterol supersaturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Short-term fasting increases biliary calcium and bilirubin.

Fasting has been associated clinically with the development of gallbladder sludge and pigment gallstones, both of which are composed primarily of calcium bilirubinate. Although fasting has been demonstrated to increase the cholesterol saturation of bile, its effect on biliary calcium and bilirubin has not been investigated. We, therefore, tested the hypothesis that short-term fasting would increase gallbladder bile calcium and bilirubin levels. Fifteen prairie dogs were studied. Seven animals were not fasted, whereas eight were fasted for 16 hr prior to acute experiments. Gallbladder and hepatic bile samples were obtained and analyzed for calcium, bilirubin, pH, and biliary lipids. Gallbladder bile ionized calcium levels were significantly increased in fasted animals (1.7 +/- 0.2 mM) compared to those in nonfasted animals (1.1 +/- 0.1 mM). Similarly, total calcium (4.3 +/- 0.5 mM vs 2.3 +/- 0.3 mM), total bilirubin (63 +/- 12 microM vs 29 +/- 8 microM), and bilirubin monoglucuronide (58 +/- 10 microM vs 22 +/- 8 microM) were significantly increased in the fasted group. Fasted animals were also noted to have an increased biliary cholesterol saturation index (0.57 +/- 0.04 vs 0.36 +/- 0.03) and decreased biliary pH (6.9 +/- 0.1 vs 7.6 +/- 0.1). These data indicate that in the prairie dog short-term fasting results in significant alterations in gallbladder bile composition. The increased concentrations of gallbladder calcium and bilirubin observed in these experiments may account, in part, for the formation of pigment gallstones and gallbladder sludge seen clinically with prolonged fasting.

Animals↗

PubMed1990

Predictive factors for bactibilia in acute cholecystitis.

Acute cholecystitis is well established as one of the high-risk factors bactibilla and wound infection. However, many patients with acute cholecystitis do not have bactibillia. Therefore, we analyzed 20 clinical and laboratory parameters in 49 patients with acute cholecystitis to determine which factor(s) predicted bactibilla. Twenty-one (42.9%) of 49 patients with pathologically proved acute cholecystitis had positive bile and/or gallbladder wall cultures. Univariate analysis suggested that a preoperative temperature greater than 37.3 degrees C, a total serum bilirubin level greater than 8.6 mumol/L, and a white blood cell count greater than 14.1 x 10(9)/L were the best predictors of bactibilia. Multifactorial analysis demonstrated that the 17 patients with zero or one predictive factor had a significantly lower chance of having bactibilia than the 32 patients with two or three predictive factors (6% vs 63%). We concluded that the culture status of patients with acute cholecystitis can be predicted preoperatively. We propose that patients with acute cholecystitis and zero or one of the predictive factors receive a single preoperative antibiotic dose. In patients with two or three predictive factors, antibiotics should be continued until culture data are available.

Acute Disease↗

PubMed1990

A history of the bilioenteric anastomosis.

The bilioenteric anastomosis has played an integral role in the surgical management of biliary tract disease during the past century. A wide variety of techniques for suturing a portion of the biliary tract to the digestive tract have been described since von Winiwarter's first cholecystoenterostomy. Many types of biliary stents have also been developed, although their exact role remains controversial. Many advances in preoperative and postoperative care have contributed to the low morbidity and mortality of current reconstructive biliary tract surgery.

Anastomosis, Surgical↗

PubMed1990

Pylorus preserving pancreatoduodenectomy: an overview.

Pylorus preserving pancreatoduodenectomy (PPPD) was reintroduced 12 years ago. Since that time, over 400 patients have undergone PPPD with approximately 41 per cent having chronic pancreatitis and 54 per cent having pancreatic and other periampullary malignancies. Reported 5-year survivals in this latter group have been comparable to those achieved by the classic Whipple procedure. The postoperative mortality rate in 339 reported patients has been 3.8 per cent. Postoperative morbidity, including delayed gastric emptying, has been similar to that of the classic Whipple operation. However, PPPD has been associated with fewer late problems with dumping, diarrhoea, delayed gastric emptying (8.6 per cent), and marginal ulceration (3.6 per cent). Moreover, most patients undergoing PPPD have been able to return to their preoperative and preillness weight. The additional advantage of decreased operative time makes PPPD an attractive alternative to the classic pancreatoduodenectomy.

Duodenum↗

PubMed1990

The effect of calcium on gallbladder absorption.

The absorption of water and electrolytes is an important physiologic function of the gallbladder which is altered during gallstone formation. Extracellular calcium and calcium channel antagonists are known to affect intestinal absorption, yet their effect on gallbladder absorption is less well defined. We, therefore, tested the hypothesis that changes in extracellular calcium or in calcium channels would alter gallbladder absorption. New Zealand white rabbit gallbladders were removed, filled with a modified Krebs buffer (Ca2+ = 0.7 mM), and suspended in an oxygenated bath of the same buffer. Water absorption was determined gravimetrically by obtaining serial gallbladder weights at 10-min intervals. After a 40-min control period, the serosal bathing solution was changed to one of four experimental solutions (n = 6 for each group): Ca2+ = 0.25, 0.7, or 1.2 mM or Ca2+ = 0.7 mM plus 0.1 mM verapamil. Absorption was determined during an 80-min experimental period with results expressed as the percentage change in gallbladder absorption compared to that of the control period. The 0.25, 0.7, and 1.2 mM Ca2+ groups did not show a significant change in absorption rate from their respective control rates. However, the verapamil group did demonstrate a significant (P less than 0.05) decrease in absorption rate of -69 +/- 8% by the end of the experimental period. These data demonstrate that verapamil inhibits gallbladder absorption while changes in serosal calcium concentration have no effect. We conclude that calcium channels and intracellular calcium may play an important role in modulating gallbladder absorption.

Absorption↗