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Biomedical subjects

H A Pitt

Publications and source records attributed to H A Pitt.

At least 73 records · Page 4Linked to original sources
PubMed1995

Potentially resectable pancreatic adenocarcinoma: spiral CT assessment with surgical and pathologic correlation.

PURPOSE: To evaluate the accuracy of spiral computed tomography (CT) in assessing the resectability of small pancreatic ductal adenocarcinoma and to correlate the CT findings with histopathologic and surgical findings. MATERIALS AND METHODS: Spiral CT scans obtained in 64 patients who underwent surgery for potentially resectable pancreatic adenocarcinoma were prospectively assessed for tumor resectability. CT findings were correlated with surgically assessed extent of tumor and pathologic findings. RESULTS: Fifty-seven (89%) of 64 carcinomas were detected with spiral CT. Twenty-four carcinomas were resectable at surgery and 40 were not. The average size of resectable tumors was 3.1 cm (range, 1.0-7.5 cm). The overall accuracy of spiral CT for assessing resectability was 70%. Of resected tumors, 14 were hypoattenuating compared with the remaining pancreas and 10 were isoattenuating. Eleven tumors showed neointimal proliferation in arterioles at histologic examination. CONCLUSION: Further progress in preoperative staging of pancreatic ductal adenocarcinoma with spiral CT should be directed toward improving detection of small pancreatic tumors and assessment of early metastatic disease.

Adenocarcinoma↗
PubMed1995

Gender influences sphincter of Oddi response to cholecystokinin in the prairie dog.

Although gallstones and disorders of biliary tract motility are both more common in women than men, sphincter of Oddi motility has not previously been compared between the sexes. In this study, cholescintigraphy (under ketamine and diazepam anesthesia) was used to determine gallbladder emptying rate and ejection fraction in response to cholecystokinin (CCK) in eight male and six female prairie dogs fed a nonlithogenic diet. Ten days later, under alpha-chloralose anesthesia, sphincter of Oddi phasic wave activity was monitored for 10-min intervals before (control), during 20 min of CCK infusion, and for 20 min after infusion. Gallbladder emptying rate and ejection fraction and baseline sphincter of Oddi frequency, amplitude, and motility index (= frequency x amplitude) did not differ significantly between the sexes. Sphincter of Oddi phasic wave frequency was increased during CCK infusion in both males and females, but the change in amplitude was significantly greater in females, than males. We conclude that the increased incidence of biliary tract disease in women may be due to altered sphincter of Oddi hormonal response.

Animals↗
PubMed1994

Cholesterol nucleates rapidly from mixed micelles in the prairie dog.

Current theory suggests that the nucleation of cholesterol in human bile requires the aggregation and fusion of cholesterol-enriched phospholipid vesicles. This theory is based on observations which do not exclude the precipitation of cholesterol from mixed micelles. The present study examines the role of mixed micelles and vesicles in the formation of cholesterol monohydrate crystals in the prairie dog. The intermicellar bile salt concentration of prairie dog gallbladder bile was determined using equilibrium dialysis. Model bile equivalent to gallbladder bile from cholesterol-fed prairie dogs was used as dialysant yielding the intermicellar (dialysate) concentration of 9 mM. Cholesterol carriers in gallbladder bile from 11 cholesterol-fed animals were then separated by Sephacryl S200 gel filtration chromatography using eluant buffer containing the intermicellar bile salt concentration. Gel filtration chromatography of fresh bile demonstrated that 100% of cholesterol was carried in the mixed micellar fraction with no vesicles observed in any of the 11 animals. The gallbladder bile nucleation time was 2.0 +/- 0.3 days for the cholesterol-fed animals. Gel filtration chromatography immediately after nucleation again revealed a single mixed micellar peak. These data indicate that cholesterol is carried exclusively in and nucleates rapidly from mixed micelles in the cholesterol-fed prairie dog and that cholesterol-phospholipid vesicles are not required in this process.

Animals↗
PubMed1994

Surgical rates and operative mortality for open and laparoscopic cholecystectomy in Maryland.

BACKGROUND: Since 1989, laparoscopic cholecystectomy has been widely adopted as a treatment for gallstone disease. We analyzed the association between the introduction of this procedure and three variables: the rate at which cholecystectomy was performed in Maryland, the characteristics of patients undergoing cholecystectomy in routine clinical practice, and operative mortality. METHODS AND RESULTS: We used 1985-1992 hospital-discharge data from all 54 acute care hospitals in Maryland, to identify open and laparoscopic cholecystectomies, characteristics of patients undergoing these procedures, and deaths occurring during hospitalizations in which these procedures were performed. The annual rate of cholecystectomy, adjusted for age, rose from 1.69 per 1000 state residents in 1987-1989 to 2.17 per 1000 residents in 1992, an increase of 28 percent (P < 0.001). As compared with patients undergoing open cholecystectomy, patients undergoing laparoscopic cholecystectomy tended to be younger, less likely to have acute cholecystitis or a common-duct stone, and more likely to be white and have private health insurance or belong to a health maintenance organization (P < 0.001). Although the operative mortality associated with laparoscopic cholecystectomy was less than that with open cholecystectomy (adjusted odds ratio, 0.22; 95 percent confidence interval, 0.13 to 0.37) and the overall mortality rate for all cholecystectomies declined from 0.84 percent in 1989 to 0.56 percent in 1992, there was no significant change in the total number of cholecystectomy-related operative deaths because of the increase in the cholecystectomy rate. CONCLUSIONS: In Maryland, although the adoption of laparoscopic cholecystectomy has been accompanied by a 33 percent decrease in overall operative mortality per procedure, the total number of cholecystectomy-related deaths has not fallen because of a 28 percent increase in the total rate of cholecystectomy.

Algorithms↗
PubMed1994

Estrogen inhibits sphincter of Oddi motility.

Gallstones and sphincter of Oddi dysfunction are both more common in women than men, suggesting that endogenous hormones may play an important role in these conditions. Female sex hormones are known to affect cholesterol metabolism and gallbladder motility. However, the effect of these hormones on the sphincter of Oddi has not previously been studied. We therefore tested the hypothesis that exogenous estrogen administration would inhibit sphincter of Oddi motility. Twenty-three male prairie dogs fed a nonlithogenic diet were studied. Under alpha-chloralose anesthesia, a side hole pressure-monitored perfusion catheter was positioned in the sphincter of Oddi and perfused with degassed water at 0.15 ml/min. Femoral arterial and venous catheters were placed. Sphincter of Oddi phasic wave frequency (F), amplitude (A), and motility index (MI = F x A), as well as arterial blood pressure (BP), were monitored for 10-min intervals before (control), during 20-min intravenous infusions of 0.1, 1, or 10 micrograms/kg beta-estradiol, and for 20 min after estradiol infusion. No response was observed at the 0.1- or 1-micrograms doses. Sphincter of Oddi motility was significantly (P < 0.05) reduced during estrogen infusion at the higher dose of 10 micrograms, primarily due to decreased phasic wave frequency. Sphincter motility remained depressed for at least 20 min following estrogen infusion. We conclude that estrogen effects on the sphincter of Oddi may contribute to the higher incidence of gallstones and sphincter dysfunction seen in premenopausal women.

Animals↗
PubMed1994

Human gallstones contain pronucleating nonmucin glycoproteins that are immunoglobulins.

OBJECTIVE: Pronucleating nonmucin glycoproteins in human cholesterol and black gallstones were isolated and identified. SUMMARY BACKGROUND DATA: Gallbladder bile contains nonmucin glycoproteins that are pronucleating of cholesterol monohydrate crystals. Little is known about the presence or activity of these proteins within gallstones. METHODS: Nonmucin glycoproteins were isolated from single cholesterol (n = 8), multiple cholesterol (n = 8), and black pigment (n = 8) gallstones by concanavalin A lectin-affinity chromatography. The proteins were separated by sodium dodecyl sulfate gradient electrophoresis. Western blot analysis was performed for Fab immunoglobulin fragments, and heavy chains from the immunoglobulin G, A, E, and M subclasses. A crystal observation time assay was performed on the combination of isolated nonmucin glycoproteins from gallstones and isolated Fab fragments. RESULTS: Nonmucin glycoproteins of molecular weights 10, 15, 17, 22, 28, and 208 kD were identified in gallstones. These six nonmucin glycoproteins shortened the crystal observation time by more than 50% (p < 0.01) compared with model bile. Western blot analysis confirmed the identity of the 22- and 28-kD proteins as immunoglobulin Fab fragments. These were seen in all gallstones, irrespective of the gallstone type. The isolated Fab 28-kD fragment from the gallstones of 23 patients shortened the extrapolated crystal observation time by 78% (p < 0.01). However, commercially available Fab fragments had no effect on either cholesterol crystal appearance or growth. CONCLUSIONS: Nonmucin glycoproteins that are pronucleating for cholesterol monohydrate crystals are also found in human cholesterol and black pigment gallstones. Fab immunoglobulin fragments were found in all gallstones irrespective of the gallstone type. Fab immunoglobulin fragments from gallstones shortened the crystal observation time but not crystal growth or total crystal content compared with model bile or commercially available Fab fragments. These data suggest that an antigen-immune (Fab) complex may contribute to cholesterol crystal function.

Bile Pigments↗
PubMed1994

Intrahepatic stones. The transhepatic team approach.

OBJECTIVE: The authors reviewed the combined interventional radiologic and surgical management of 54 patients with intrahepatic stones at the Johns Hopkins Hospital. The team approach used large-bore transhepatic stents to access the intrahepatic ducts until they were stone free. SUMMARY BACKGROUND DATA: Intrahepatic stones are uncommon in western countries. As a result, few American institutions have had much experience, and multiple management algorithms have been suggested. Nonoperative, operative, and combination surgical and nonoperative approaches have been advocated. At Johns Hopkins, combined surgical and percutaneous management has been used for 18 years. METHODS: This team approach includes (1) percutaneous placement of transhepatic access catheters, (2) surgery for underlying biliary disease and stone removal, and, when necessary (3) postoperative percutaneous choledochoscopy and stone removal through the transhepatic stents. RESULTS: The median age of the 54 patients was 50 years, and 32 were men. Biliary disease included 27 benign strictures, 7 sclerosing cholangitis, 5 choledochal cysts, 5 parasitic infections, 5 choledocholithiasis, and 5 biliary tumors. Fourteen patients (26%) were treated exclusively with percutaneous techniques. Forty patients (74%) had surgery, including 36 Roux-en-Y hepatico- or choledochojejunostomies with large-bore transhepatic stents. Eighteen of these 40 patients (45%) with multiple intrahepatic stones, strictures, or both required additional procedures after operation. No hospital deaths occurred after any of the percutaneous or surgical procedures. With a mean follow-up of 60 months, 94% of patients were stone free, 87% of patients were symptom free, and 73% have had their transhepatic stents removed. CONCLUSIONS: A combined radiologic and surgical approach with transhepatic stents is a safe and effective method for managing intrahepatic stones.

Adult↗
PubMed1994

Characterization of a small vesicular cholesterol carrier in human gallbladder bile.

OBJECTIVE: Cholesterol phospholipid vesicles play an important role in the nucleation of cholesterol in bile. Recent studies have identified an additional vesicle population in human bile. In this study, the role of these small vesicles as cholesterol carriers was examined. METHODS: Gallbladder bile was obtained from 60 patients at cholecystectomy. Large vesicles, small vesicles, lamellae, and mixed micelles were separated using gel filtration chromatography. RESULTS: Small vesicles were present in bile from the majority of patients both with and without cholesterol gallstones, whereas the void volume vesicle fraction was found almost exclusively in bile from patients with cholesterol gallstones. Both large vesicular and small vesicular cholesterol increased as total bile cholesterol concentration increased; however, the cholesterol-phospholipid ratio in the large vesicle fraction from patients with cholesterol stones was significantly greater than the ratio in small vesicles (1.6 +/- 0.3 vs. 1.0 < or = 0.1, p < 0.05). Whole bile cholesterol crystal appearance time was correlated significantly with the percentage of cholesterol transported by large vesicles (r = 0.63, p < 0.001) but not with the percentage of cholesterol present in small vesicles. Finally, large vesicles isolated by gel filtration chromatography formed cholesterol crystals faster than small vesicles (5.3 +/- 2 vs. 17.4 +/- 4 days, p < 0.01). CONCLUSIONS: These data suggest that a heterogenous population of vesicles is present in human gallbladder bile. As bile becomes saturated with cholesterol, it increasingly is solubilized by both small and large vesicles. The small vesicles have relatively less cholesterol and are more stable than the larger variety, from which cholesterol is most likely to precipitate.

Bile↗
PubMed1994

Choledochal cyst disease. A changing pattern of presentation.

OBJECTIVE: The authors compared the presentation, treatment, and long-term outcome of children and adults with choledochal cysts. SUMMARY BACKGROUND DATA: The typical patient with choledochal cyst disease has been the female infant with the triad of jaundice, an abdominal mass, and pain. However, the recent experience of the authors suggested that the disease currently is recognized more commonly in adults. METHODS: Forty-two patients (11 children, 32 adults) with choledochal cyst disease were treated primarily at this institution between 1976 and 1993. Patients presentation, clinical evaluation, and operative treatment were obtained from existing records. Long-term follow-up was obtained by records, physician, or direct patient contact. RESULTS: One child--but no adults--had the classic triad of jaundice, abdominal mass, and pain. Children were more likely to have two of the three signs or symptoms (82% vs. 25%; p = < 0.05). Adult patients most commonly had abdominal pain and were thought to have pancreatitis (23%) or acute biliary tract symptoms, prompting cholecystectomy (50%). The type of choledochal cyst seen in children and adults was similar; the fusiform extrahepatic (Type I) was most common (50%), and the combined intrahepatic and extrahepatic (Type IVA) was the next most prominent (33%). For both children and adults, treatment consisted of excision of the cyst and biliary reconstruction with a hepaticojejunostomy. There was no surgical mortality. Gallbladder or cholangiocarcinoma was identified in three adults (9.7%), two of which were manifest on presentation. Long-term follow-up revealed one patient with a biliary stricture and three patients with Type IVA cysts who had intrahepatic stones. CONCLUSIONS: Children and adults differ in presentation of choledochal cysts, with adults commonly having acute biliary tract or pancreatic symptoms. Surgical treatment with cysts excision and biliary bypass is safe and effective in children and adults with excellent long-term results that minimize the development of malignancy.

Adolescent↗
PubMed1994

An analysis of infectious failures in acute cholangitis.

To determine the factors responsible for therapeutic failures in acute cholangitis, a series of 127 patients was analyzed. There were 64 females and 63 males whose mean age was 57.2 years. Ninety-four (74.0%) of these patients were clinically cured with initial measures, whereas 33 patients (26%) failed initial therapy for an infectious reason. No differences were observed between the two groups in regard to age and gender. However, more patients in the group that failed had a malignant cause for their bile duct obstruction (72.7% vs. 42.6%, p < 0.01) and had a pretreatment positive blood culture (45.5% vs. 13.8%, p < 0.01). Patients who failed had a higher mean total bilirubin level (9.7 mg/dl vs. 5.5 mg/dl, p < 0.005) and more of them had a level greater than 2.2 mg/dl (97% vs. 69.9%, p < 0.001). Also, more bile cultures were initially positive (93.9% vs. 76.6%, p < 0.05) and more organisms were isolated per culture (3.88 vs. 2.86, p < 0.03) in the patients who failed. In addition, more patients failed who had two or more organisms in the bile (33% vs. 8.3%, p < 0.02). Patients in whom Candida, or any panresistant organism was isolated also tended to fail. Multivariant analysis showed that malignancy, bacteremia, bilirubin > or = 2.2 mg/dl, > or = 2 organisms in the bile and a panresistant organism were the best predictors of treatment failure with a serum bilirubin level > or = 2.2 mg/dl being the variable that increases a patient's log-odds ratio of failure the greatest.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation.

BACKGROUND: Several nonoperative and operative options are available for palliation of patients with unresectable hilar cholangiocarcinoma. This retrospective analysis compares the results of nonoperative percutaneous stenting and operative palliation in 65 patients. METHODS: Twenty-one patients were managed with percutaneous biliary stents (group A), and 44 patients underwent laparotomy (group B) with placement of large-bore silicone rubber transhepatic stents in 33. The two groups were similar with respect to age, gender, mean laboratory data, and cholangiographic extent of tumor. RESULTS: Group A and group B patients were comparable in hospital morbidity (67% vs 61%), hospital mortality (14% vs 7%), and mean initial hospital stay (27 vs 31 days). Survival was greater in group B laparotomy patients at 1, 3, and 6 months (p < 0.01), and median survival was 5 months for group A compared with 8 months for group B patients (p = 0.06). Group A patients who were managed with percutaneous stents required more stent changes per month of survival (0.5 vs 0.3, p = 0.06). However, group B patients who underwent operative palliation were more likely to undergo a second operation (0% vs 21%, p = 0.05), most often for duodenal or small-bowel obstruction. CONCLUSIONS: Operative placement of large-bore transhepatic stents may reduce cholangitis, delay hepatic failure, and prolong survival. We conclude that patients with unresectable hilar cholangiocarcinoma who are fit for surgery may benefit from operative palliation.

Adult↗
PubMed1994

Primitive neuroectodermal tumor arising in the pancreas.

Peripheral primitive neuroectodermal tumors (PNETs) are extra cranial primitive small round blue cell tumors showing histologic, immunohistochemical or electron microscopic evidence of neuroectodermal differentiation. They are most commonly encountered in the soft tissue or bone in children and young adults. We report an unusual case of a PNET arising in the pancreas. A 17-yr-old male presented with a pancreatic mass and underwent a pancreatoduodenectomy. Histologically, the neoplasm was composed of sheets of small round cells that stained for cytokeratin, neuron specific enolase, and 12E7 but not muscle specific action, desmin, common leukocyte antigen, chromogranin, synaptophysin, or other islet cell markers. The diagnosis of PNET in this unusual location was confirmed by cytogenetic analysis which showed the chromosomal translocation characteristics of PNETs, t(11;12)(q24;q12). This case highlights the difficulty in the diagnosis of PNET when it is present in visceral organs where other neuroendocrine neoplasms and adenocarcinomas are more common.

Adolescent↗
PubMed1994

The distribution of calcium salt precipitates in the core, periphery and shell of cholesterol, black pigment and brown pigment gallstones.

Calcium bilirubinate, palmitate, carbonate and phosphate have been identified in the cores of cholesterol and pigment gallstones, suggesting a role for precipitated calcium salts in the early events of gallstone formation. Previous studies that compared the calcium salt contents of cholesterol and pigment stones required destruction of gallstone structure. We have used scanning electron microscopy with windowless energy-dispersive x-ray microanalysis to determine the prevalence of calcium salts in a series of cholesterol (n = 105), black pigment (n = 35) and brown pigment (n = 6) gallstones obtained from 146 consecutive patients undergoing cholecystectomy. These techniques provide specific identification of cholesterol and individual calcium salts as they occur within the core, periphery and shell of gallstones without destroying stone structure. Calcium precipitates more than 0.5 micron in diameter can be detected in a cholesterol background at a detection limit of 0.01% by weight. Calcium salts were detected in the centers of 88% of cholesterol and 100% of black (p < 0.05 vs. cholesterol) and brown pigment stones. Calcium bilirubinate was identified in the cores of 54% of cholesterol and in all pigment stones (p < 0.001 black pigment vs. cholesterol). Calcium palmitate was detected in all brown pigment stones, in 39% of cholesterol stones (p < 0.001 vs. brown pigment) and in 31% of black stones (p < 0.01 vs. brown pigment). Peripheral calcium salts were detected less in cholesterol (19%) than in black or brown stones (100%, p < 0.05). Fourteen percent of cholesterol and black pigment stones were surrounded by shells containing mostly calcium carbonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Nitric oxide inhibits resting sphincter of Oddi activity.

The sphincter of Oddi has basal myogenic phasic activity that is modulated by neural and hormonal pathways. Stimulatory innervation to this organ is cholinergic, whereas the inhibitory pathways are unknown. Nitric oxide (NO), generated from L-arginine, relaxes gastrointestinal smooth muscle in vitro. We, therefore, hypothesized that resting sphincter of Oddi and duodenal motilities are regulated by a NO-mediated inhibitory pathway. In 23 anesthetized prairie dogs, systemic blood pressure and sphincter of Oddi and duodenal motilities were monitored during systemic infusion of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. L-NAME was infused alone and simultaneously with excess D- and L-arginine. L-NAME alone and L-NAME with D-arginine produced hypertension and increased sphincter of Oddi and duodenal motilities. L-arginine blocked these increases, suggesting that baseline sphincter of Oddi and duodenal motility regulation involves the generation of NO from L-arginine. We conclude that baseline sphincter of Oddi phasic activity is regulated by cholinergic stimulatory and NO-mediated inhibitory neural pathways.

Amino Acid Oxidoreductases↗
PubMed1993

Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy.

To assess the cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy from the payer's perspective, we estimated the probabilities of potential outcomes of each procedure, associated quality-of-life effects, and related direct medical charges and incorporated these estimates into a computerized simulation model. The model projects that laparoscopic cholecystectomy will be more effective than open surgery in terms of total mortality and quality-adjusted survival, for both sexes and all ages. Projected 5-year cumulative charges are lower for laparoscopic cholecystectomy than for open cholecystectomy ($5,354 versus $5,525 for 45-year-old women; $6,036 versus $6,830 for 45-year-old men), and the differences increase substantially with increasing age. We concluded that laparoscopic cholecystectomy is likely to be less costly and more effective than open cholecystectomy for most patients, as long as it does not routinely require preoperative cholangiography and is not associated with increased professional fees or increased risks of retained stones or bile duct injury.

Adult↗