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Biomedical subjects

T H Magnuson

Publications and source records attributed to T H Magnuson.

At least 19 recordsLinked to original sources

Utility of magnetic resonance cholangiography in the evaluation of biliary obstruction.

BACKGROUND: Evaluation of suspected biliary obstruction has traditionally involved a variety of imaging modalities including ultrasound, CT, and invasive cholangiography. These techniques have limitations because of poor visualization of intraductal stones (ultrasound and CT) and the need for an invasive procedure (ERCP and percutaneous transhepatic cholangiography). Magnetic resonance cholangiography (MRC) is a noninvasive imaging modality that provides good visualization of the hepatobiliary system. The aim of the present study was to determine the utility of MRC in evaluating patients with suspected biliary obstruction. STUDY DESIGN: One hundred forty-three patients were identified with suspected acute biliary obstruction and underwent MRC. Patient selection was based on clinical criteria including an elevation in serum liver chemistries or evidence of biliary ductal dilatation on conventional imaging. MRC was performed using a half-Fourier acquisition single-shot turbo spin-echo sequence involving single breath-hold rapid image acquisition. A final diagnosis was determined in each patient based on invasive cholangiography, findings at surgery, and clinical course. RESULTS: Of the 143 patients, 73 had an obstructing biliary lesion. A malignant process was identified in 25 patients with final diagnoses of pancreatic cancer (n = 15), ampullary cancer (n = 4), cholangiocarcinoma (n = 3), and hepatic or nodal metastases (n = 3). MRC correctly identified biliary obstruction in all these patients and accurately identified the level of biliary obstruction in 24 of 25 patients. Based on the MRC images alone, a malignant process was suspected in 21 of the 25 patients. Forty patients were found to have common bile duct stones and eight patients had a benign distal bile duct stricture. MRC correctly identified common bile duct stones in 37 patients with one false-positive exam (sensitivity = 92%; specificity = 99%). MRC also correctly identified distal biliary strictures in eight patients. In the remaining 70 patients, no definite biliary obstruction was identified by MRC, and in all patients the absence of mechanical obstruction was confirmed by invasive cholangiography or overall clinical course. CONCLUSIONS: This study demonstrates that MRC is able to accurately identify the level and cause of biliary obstruction in both malignant and benign disease. MRC may prove to be an important noninvasive tool in preoperative evaluation of patients with suspected biliary obstruction and identification of patients most likely to benefit from an invasive radiologic or surgical procedure.

Adolescent↗

Hospital volume can serve as a surrogate for surgeon volume for achieving excellent outcomes in colorectal resection.

OBJECTIVE: To examine the association of surgeon and hospital case volumes with the short-term outcomes of in-hospital death, total hospital charges, and length of stay for resection of colorectal carcinoma. METHODS: The study design was a cross-sectional analysis of all adult patients who underwent resection for colorectal cancer using Maryland state discharge data from 1992 to 1996. Cases were divided into three groups based on annual surgeon case volume--low (< or =5), medium (5 to 10), and high (>10)--and hospital volume--low (<40), medium (40 to 70), and high (> or =70). Poisson and multiple linear regression analyses were used to identify differences in outcomes among volume groups while adjusting for variations in type of resections performed, cancer stage, patient comorbidities, urgency of admission, and patient demographic variables. RESULTS: During the 5-year period, 9739 resections were performed by 812 surgeons at 50 hospitals. The majority of surgeons (81%) and hospitals (58%) were in the low-volume group. The low-volume surgeons operated on 3461 of the 9739 total patients (36%) at an average rate of 1.8 cases per year. Higher surgeon volume was associated with significant improvement in all three outcomes (in-hospital death, length of stay, and cost). Medium-volume surgeons achieved results equivalent to high-volume surgeons when they operated in high- or medium-volume hospitals. CONCLUSIONS: A skewed distribution of case volumes by surgeon was found in this study of patients who underwent resection for large bowel cancer in Maryland. The majority of these surgeons performed very few operations for colorectal cancer per year, whereas a minority performed >10 cases per year. Medium-volume surgeons achieved excellent outcomes similar to high-volume surgeons when operating in medium-volume or high-volume hospitals, but not in low-volume hospitals. The results of low-volume surgeons improved with increasing hospital volume but never equaled those of the high-volume surgeons.

Aged↗

Effect of reg protein on rat pancreatic ductal cells.

The pancreatic regenerating gene (reg I) is expressed in the exocrine pancreas and is involved in islet regeneration. Reg I protein has been shown to be mitogenic to beta- and ductal cell lines, but not mature islets. In this study, we tested the effect of two isolates of reg I on primary cultures of ductal cells. Rat pancreatic ductal cells were isolated by collagenase digestion and isolated colonies were maintained in culture. The cells were proven to be ductal in origin by their morphology and by immunofluorescent staining with epithelial markers. Reg I was isolated from human pancreatic extracts or from the rat acinar cell line AR42J by sequential ammonium sulfate precipitation and acid precipitation. Cells were cultured with doses of reg I for 72 h, pulsed with 10 microM bromodeoxyuridine (BrdU) for 2 h. After fixation, nuclei were double-stained with propidium iodide and BrdU monoclonal antibody. The percentages of nuclei positive for BrdU were calculated from at least five colonies per group. A 10-nM concentration of human reg I increased BrdU incorporation by 2.3-fold over controls, rat reg I increased it by 1.4-fold (p < 0.05). When compared to their effects on the ductal cell line ARIP, both human and rat reg I were 100 times more potent on the primary cultures of ductal cells. We conclude that human and rat reg I proteins are mitogenic to primary cultures of ductal cells. Although principally a product of the acinar cell, reg I appears to be a stimulus of ductal cell growth and, in this fashion, may modulate the expansion of the pancreatic ductal population during islet regeneration.

Animals↗

The changing face of mesenteric infarction.

Intestinal infarction remains a devastating event despite improvements in clinical recognition as well as diagnostic and therapeutic modalities. Recent changes in the etiology of this disease have not been examined. A retrospective review of 121 consecutive patients over a 6-year period was undertaken. Twenty-three patients died without operation, and mortality in the remaining 98 patients was 50 per cent. The only significant predictor of mortality was an elevated serum lactate at the time of diagnosis. Thirty-one patients (26%) developed infarction while hospitalized for another disease process; excluding patients with obstruction as the etiology of infarction caused this number to rise to 39 per cent. Nonocclusive mesenteric infarction was the most common disease process. The increased incidence of nonocclusive mesenteric infarction is likely due to the development of intestinal ischemia in already systemically ill patients. Nearly half of all cases of intestinal infarction due to nonobstructive causes develop in already hospitalized patients. The development of unexplained acidosis in a postoperative or critically ill patient should prompt a search for a reversible cause of mesenteric ischemia. Intestinal infarction may represent another example of the multisystem organ failure syndrome.

Case-Control Studies↗

Pancreatic reg gene expression is inhibited during cellular differentiation.

BACKGROUND AND OBJECTIVE: Factors that control pancreatic regenerating (reg I) gene expression are unknown, but it is believed that its expression may correspond with cellular differentiation. The authors recently demonstrated that reg I is expressed in AR42J, a rat acinar cell line whose state of differentiation can be modulated by dexamethasone. They used this line to study reg I expression during cellular proliferation and differentiation. METHODS: After treatment of cells with 10 nmol/L dexamethasone, proliferation was assayed by thymidine incorporation; differentiation by expression of elastase I mRNA. Reg I mRNA levels were measured using a rat reg I cDNA probe, and reg I protein levels assayed by enzyme-linked immunosorbent assay of cellular lysates with a polyclonal antibody. The effect of gastrin, cholecystokinin and glucagon on reg I expression was also studied. RESULTS: When compared with controls, treatment with dexamethasone caused thymidine incorporation to decrease and elastase mRNA levels to increase. Reg I mRNA decreased from controls of 100 +/- 16% to 40 +/- 18% (p < 0.05), and reg I protein levels decreased as well. Gastrointestinal hormones had no significant effect on either elastase or reg I gene expression. CONCLUSIONS: Expression of reg I inversely correlates with the level of cellular differentiation, can be modulated via the glucocorticoid receptor, and is a potential marker of gastrointestinal epithelial differentiation. Despite its presence within a pancreatic acinar cell line, reg I gene expression is not modulated by gastrointestinal hormones.

Animals↗

Laparoscopic cholecystectomy: applicability in the geriatric population.

Elderly patients with cholelithiasis are more likely than nonelderly patients to present with an acute complication of gallstone disease such as acute cholecystitis (AC), gallstone pancreatitis (GSP), or common bile duct stones (CBDS). These acute complications may make laparoscopic cholecystectomy (LC) more hazardous, with a potential increase in perioperative morbidity or need for open conversion. The applicability of LC in the geriatric population is, therefore, unclear. We reviewed 283 consecutive patients undergoing attempted LC. Patients were classified as presenting with complicated (AC, GSP, or CBDS) or uncomplicated gallstone disease. Elderly patients were significantly more likely than younger patients to present with AC (40% versus 18%), GSP (19% versus 6%), and CBDS (21% versus 5%) (all P < 0.05). Elderly patients with chronic, uncomplicated gallstone disease (n = 20) and nonelderly patients with uncomplicated disease (n = 159) had similar open conversion rates (5% and 7%, respectively). In contrast, the open conversion rate in elderly patients with complicated gallstone disease (n = 42) was significantly higher (50%) compared to nonelderly patients with complicated disease (n = 62; rate, 16%; P < 0.05). Perioperative morbidity and length of stay were also significantly increased in the elderly group, primarily due to the high percentage of elderly patients with complicated disease. These results suggest that elderly patients with uncomplicated gallstone disease appear to be excellent candidates for LC, and this should be considered before complicated disease develops. Conversely, early conversion or planned open cholecystectomy may be warranted in the elderly presenting with acute complications of cholelithiasis.

Aged↗

Pancreatic thread protein is mitogenic to pancreatic-derived cells in culture.

BACKGROUND & AIMS: Pancreatic thread proteins (PTPs) are acinar cell products and members of the regenerating gene (reg) family. reg expression increases during islet regeneration, is depressed during aging-related islet dysfunction, and may be important in beta-cell growth and maintenance. The aim of this study was to examine the genetic expression of reg in pancreatic-derived cells in vitro and the mitogenic effect of PTP/reg protein on these cells. METHODS: reg gene expression was measured by Northern analysis in three rat pancreatic cell lines: ARIP (ductal), AR42J (acinar), and RIN (beta-cell). PTP/reg protein was isolated from bovine and human pancreas. Cells were cultured with PTP/reg for 72 hours, and thymidine incorporation was measured. RESULTS: reg messenger RNA was detected in AR42J but not in ARIP or RIN. PTP/reg protein was mitogenic to RIN and ARIP in a dose-related fashion but not to AR42J. It was not mitogenic to cultured mature rat islets. CONCLUSIONS: reg messenger RNA is expressed in acinar but not in beta-cell or ductal pancreatic cell lines. PTP/reg protein was mitogenic to both beta-cell and ductal cell lines but not to mature, nondividing islets. This supports the hypothesis that PTP/reg protein is an acinar cell-derived mediator of beta-cell growth and may be involved in modulating the duct-to-islet axis.

Animals↗

Outcome following colon surgery in the octagenarian.

The results of colon surgery in all individuals aged 80 years or greater at one teaching institution during the 1987-1993 time period were reviewed. Sixty patients, ranging in age from 80 to 92 years, underwent 41 elective operations and 21 emergency procedures. Emergency procedures resulted in death or a major complication in over one-half of patients, and only six were ultimately able to return home. Conversely, elective procedures were relatively well tolerated, and 31 of 37 survivors returned immediately to independent living (P = 0.006). Mortality was 33.3 per cent in emergency cases versus 9.8 per cent in elective operations (P < 0.03). The occurrence of a postoperative complication increased the length of stay by an average of 12 days. These data suggest that elective colon surgery in the elderly produces results little different from the population at large. Conversely, emergency operations are associated with a high morbidity and mortality rate. Age alone should not be a determining factor in who undergoes an elective colon operation. Greater efforts should be made to screen elderly individuals to limit emergency surgery.

Age Factors↗

Minimally invasive management of acute superior mesenteric artery occlusion: combined urokinase and laparoscopic therapy.

Acute superior mesenteric arterial occlusion is a medical emergency mandating prompt diagnosis and therapy. Traditional management includes exploratory laparotomy with possible embolectomy or bowel resection. Unfortunately, these patients are often frail and elderly and tolerate open laparotomy poorly. In this report, we describe a patient with acute superior mesenteric artery occlusion successfully managed with a minimally invasive approach. The acute arterial occlusion was managed with intra-arterial fibrinolytic therapy, and bowel viability was assessed with diagnostic laparoscopy. This combined approach of arteriographic and laparoscopic therapy avoided exploratory laparotomy, and we believe that it is an important therapeutic option in select patients with acute mesenteric ischemia.

Acute Disease↗

Will stereotactic breast biopsy achieve results as good as current techniques?

Stereotactic procedures recently have been advocated to replace most needle localization and open biopsy procedures. In order to provide a baseline for comparison at our institution, a retrospective review of our results over the last 3 years was performed. During this time period, 496 biopsies were performed in 480 patients. Needle localization was done in 311 cases, whereas the remaining 185 biopsies were done for palpable masses. There were no significant differences in either the positive rate (19.0% vs 13.5%) or the infection rate (2.6% vs 1.6%) in the two groups. Follow-up of all patients has revealed no missed carcinomas and no referrals to a plastic surgeon for a poor cosmetic result. Current breast biopsy techniques yield good results, with acceptably low morbidity rates. Given that approximately one in five needle localization biopsies detects a malignancy, a negative result following a stereotactic biopsy may not preclude a needle localization procedure. It is therefore unlikely that stereotactic procedures will lead to an overall decrease in health care costs. Surgeon involvement will be crucial to assure best and most cost-effective results.

Adolescent↗

General surgical care in the nursing home patient: results of a dedicated geriatric surgery consult service.

BACKGROUND: Although recent interest has centered on diseases that require operation in the elderly, few data are available about the effects of surgical intervention on the frail nursing home patient. STUDY DESIGN: A longitudinal study was conducted of the nature of illness requiring operation and intervention in residents of a geriatric center associated with a tertiary care medical center. A unique consult service for the patients was established and all referrals were prospectively followed up. RESULTS: The actuarial 18-month survival of patients referred was 35 percent. Although maintenance care (e.g., decubitus ulcer, stoma, and enteral tube care) made up a substantial number of referrals (32.5 percent), common surgical diseases of the abdomen, breast, and vascular system were routinely encountered (55 percent). In patients undergoing surgery, the 30-day mortality rate was 8.5 percent, and the complication rate 9.4 percent. Although patients undergoing major abdominal and vascular procedures had a higher complication rate (17.6) percent than those undergoing lesser procedures (6.3 percent, p = 0.05), there was no difference in the 30-day mortality (9.8 compared with 6.3 percent, respectively) or 18-month actuarial survival (33 compared with 32 percent, respectively) rates. The overall actuarial survival was adversely affected by the presence of coronary artery disease (relative risk [RR], 3.27) and dementia (Mini-Mental State Examination score less than 24; RR, 2.39) and age older than 70 years (RR, 2.03). The overall survival was unaffected by the actual need for operation, the magnitude of the procedure performed, gender, the number of comorbid conditions, and the preoperative code (resuscitative) status. CONCLUSIONS: Although nursing home patients referred for surgical intervention have poor survival rates, the use of surgical procedures does not adversely affect overall survival. This supports the idea that care for this patient population is not futile, and quality of life, patient dignity, and relief of suffering can provide a alternative to curative therapy.

Actuarial Analysis↗

Cholecystectomy in the peritoneal dialysis patient. Unique advantages to the laparoscopic approach.

Laparoscopic cholecystectomy has proven to be a safe and effective treatment for symptomatic gallstone disease. Several subsets of patients, however, may not be candidates for the laparoscopic approach, including patients with morbid obesity, acute cholecystitis, and previous abdominal surgery. Because of peritoneal thickening and abdominal adhesions secondary to peritoneal dialysis, the applicability of laparoscopic cholecystectomy in patients maintained on chronic peritoneal dialysis is also unclear. We performed laparoscopic cholecystectomy on three peritoneal dialysis patients without intraoperative complications. We have noted several unique advantages to laparoscopic surgery in this patient population and advocate this approach in peritoneal dialysis patients requiring cholecystectomy.

Adult↗

Acute abdomen in the hemodialysis patient population.

BACKGROUND: The cause and frequency of the acute abdomen in patients undergoing hemodialysis are not well reported. Previous studies associate bowel infarction with hemodialysis, but dialysis generally is not implicated as a risk factor for mesenteric ischemia. METHODS: The records of 567 patients undergoing long-term hemodialysis during the period from July 1988 to June 1993 were retrospectively reviewed. RESULTS: Twelve patients (2.1% of the hemodialysis population) were admitted with acute abdominal pain or sepsis. They were demographically no different than their counterparts who did not have an acute abdomen. The final diagnoses were bowel infarction in 11 patients and acute pancreatitis in one. Principal areas of involvement were equally divided between large and small intestine and were due to nonocclusive mesenteric ischemia in all cases. Six patients had an occluded hemodialysis fistula on admission, suggesting hypotension and/or hypovolemia as a possible etiologic factor. Overall, mortality and major morbidity rates were 50% and 25%, respectively. CONCLUSIONS: An acute abdomen is a relatively uncommon problem in the hemodialysis population but is associated with a high mortality. Mesenteric infarction is the most common cause and should be the presumptive diagnosis until proven otherwise.

Abdomen, Acute↗

Dietary fish oil inhibits cholesterol monohydrate crystal nucleation and gallstone formation in the prairie dog.

BACKGROUND: Epidemiologic studies suggest that populations consuming a diet rich in fish oil have lower rates of both atherosclerotic heart disease and gallstones. The mechanisms underlying this inhibitory effect on cholesterol gallstone formation remain unclear. We therefore studied the effect of dietary fish oil on bile composition and cholesterol precipitation in an animal model of gallstone disease. METHODS: Adult male prairie dogs were fed a standard control diet (n = 12) or a lithogenic 1.2% cholesterol diet (n = 16). One half of the animals in each group had their diet supplemented with concentrated fish oil. RESULTS: After 14 days animals receiving the cholesterol diet all developed biliary cholesterol monohydrate crystals and gallstones. When fish oil was added to this high cholesterol diet, solid cholesterol crystal precipitation and gallstone formation were completely inhibited. This inhibition of gallstone formation was accompanied by a significant decrease in biliary calcium and total protein concentration. Microscopic cholesterol liquid crystals were evident in the bile of all of the animals fed the cholesterol plus fish oil diet. Dietary fish oil also significantly prolonged cholesterol monohydrate crystal observation time in animals receiving the lithogenic diet. CONCLUSIONS: These data suggest that dietary fish oil exerts a potent antilithogenic effect on cholesterol gallstone disease and may induce a stable liquid crystalline phase retarding nucleation.

Animals↗

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↗

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↗

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↗

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↗