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Biomedical subjects

K V Kowdley

Publications and source records attributed to K V Kowdley.

12 recordsLinked to original sources

Microsatellite instability and K-ras mutations associated with pancreatic adenocarcinoma and pancreatitis.

ras oncogene mutations and microsatellite instability (MIN) have been described in pancreatic cancer studies from paraffin blocks and fresh frozen tissue. We sought to determine whether they could be detected in endoscopic retrograde cholangiopancreatography-derived pancreatic juice. ras mutations were detected in the pancreatic juice of 40% (2 of 5) of patients with pancreatic cancer and 2 of 5 patients with pancreatitis. MIN was detected at a single locus in the pancreatic juice of 40% of pancreatic cancer patients and at > or = 2 loci of 100% of pancreatitis patients. The finding of MIN in pancreatitis specimens was verified in studies performed on paraffin blocks. MIN was not detected in normal pancreas controls. All of the cancer patients who had ras mutations in their pancreatic juice also had evidence of MIN at one or more loci (P < or = 0.05), suggesting that MIN is associated with the development of a ras mutation. More importantly, the finding of MIN in pancreatitis specimens suggests that MIN can occur in nonneoplastic conditions of the pancreas and may represent the saturation of an intact mismatch repair system.

Adenocarcinoma

Prophylactic colectomy or surveillance for chronic ulcerative colitis? A decision analysis.

BACKGROUND & AIMS: The treatment of patients with long-standing ulcerative colitis involving the entire colon is controversial. The aim of this study was to examine the effectiveness of surveillance colonoscopy or prophylactic colectomy on colon cancer mortality in patients with chronic ulcerative colitis. METHODS: Using decision analysis, computer cohort simulation of patients with ulcerative colitis was performed to evaluate 17 strategies including no colonoscopic surveillance, surveillance at varying intervals, and prophylactic proctocolectomy with ileal pouch-anal anastomosis. The model examined which biopsy results (low-grade dysplasia, high-grade dysplasia, or cancer) should lead to proctocolectomy and ileal pouch-anal anastomosis. Published data on the incidence of cancer with ulcerative colitis, the sensitivity and specificity of colonoscopy with biopsy, the risks of colonoscopy and surgery, and the prognosis with colon cancer were used. RESULTS: For a 30-year-old patient with pancolitis for 10 years, the model suggests that prophylactic colectomy would increase life expectancy by 2-10 months compared with surveillance and by 1.1-1.4 years compared with no surveillance. Surveillance would improve life expectancy by 7 months to 1.2 years compared with no surveillance. In sensitivity analysis, results were most affected by the cumulative incidence of cancer in patients with chronic ulcerative colitis. CONCLUSIONS: Either surveillance or prophylactic colectomy should increase life expectancy in patients with ulcerative colitis.

Adult

Future developments in endoscopic imaging.

Endoscopic imaging capabilities have significantly improved over the past 10 years. Improvements in fibreoptic technology have made possible the development of very thin endoscopes that can directly visualize the biliary and pancreatic ducts. The application of the CCD to endoscopy has made electronic endoscopy possible, and holds promise for stereoendoscopy. The ability to digitize endoscopic images can be developed to store, transmit, magnify, enhance and otherwise manipulate data obtained during endoscopy, and will probably be utilized routinely in the future. Laser and ultrasound technology are likely to enhance significantly our ability to examine ultrastructural aspects of gastrointestinal organs and surrounding tissues, and may play an important role in cancer surveillance programs. Vital staining techniques are likely to find widespread use in early cancer detection programmes, and may be useful to follow prospectively lesions observed or treated during endoscopy. Finally, the new developments in 'virtual imaging' may find applications in the field of gastrointestinal endoscopy and other 'minimally invasive' surgical procedures.

Diagnostic Imaging

Changes in small-intestine permeability with aging.

OBJECTIVE: To evaluate small-intestine mucosal integrity and permeability with advancing age as measured by the lactulose/mannitol absorption test in healthy subjects. DESIGN: Prospective cohort study. SETTING: Clinical research unit of the USDA Human Nutrition Research Center on Aging. STUDY PARTICIPANTS: Fifty-six subjects were recruited in three age groups: 20 to 39 years (n = 20), 40 to 59 years (n = 19), and > or = 60 years (n = 17). Subjects were healthy, community-dwelling volunteers. INTERVENTION: After an 8-hour fast, all subjects ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 6 hours and analyzed for lactulose and mannitol by high performance liquid chromatography. Twenty-four-hour urinary creatinine clearances were determined. MAIN OUTCOME MEASURES: Percentages of lactulose and mannitol excreted, the lactulose/mannitol ratio (x100), and the 24-hour creatinine clearance. RESULTS: With increasing age, both the percentage of lactulose excreted (P = 0.09) and the percentage of mannitol excreted (P = 0.05) tended to decrease progressively. The lactulose/mannitol ratio (x100) did not change with increasing age (P = 0.65) because both the percentages of lactulose and mannitol excreted declined. The creatinine clearance decreased markedly with advancing age (P < .001) and accounted for the decline in percentages of lactulose and mannitol excreted (P < .02). CONCLUSIONS: There is a progressive decline in the ability to excrete lactulose and mannitol with increasing age. This is probably attributable to a decline in renal function with advancing age. However, because of parallel decreases in lactulose and mannitol excretion, the lactulose/mannitol ratio does not change. Thus small-intestine "leakiness" does not increase with aging as measured by the lactulose/mannitol absorption test.

Adult

Hepatic copper content is normal in early primary biliary cirrhosis and primary sclerosing cholangitis.

In previous studies, the majority of patients with the cholestatic liver diseases, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), had increased hepatic copper (Cu) levels even in early stages of disease. We prospectively measured hepatic copper content by atomic absorption spectrophotometry in 55 patients with PBC, 6 patients with PSC, and 29 patients with other chronic noncholestatic liver diseases. Hepatic Cu content was normal in 22/61 (36%) of patients with PBC or PSC; 18 of the 22 did not have cirrhosis (82%). Hepatic Cu content increased with increasing stage of disease (r = 0.61, P < 0.001) and was positively correlated with serum total bilirubin (r = 0.6, P < 0.0001) and alkaline phosphatase (r = 0.5, P < 0.001). All patients with stage I and II disease had hepatic Cu < 150 micrograms/g dry weight, and all patients with hepatic Cu > 150 micrograms/g dry weight had stage III and IV disease. Hepatic Cu content is normal in early PBC and PSC. Copper accumulation in the liver in these cholestatic liver diseases is secondary to cholestasis rather than a primary phenomenon.

Alkaline Phosphatase

Delayed hemorrhage after percutaneous liver biopsy. Role of therapeutic angiography.

We report a patient on warfarin prophylaxis who had major intraperitoneal hemorrhage 17 days following percutaneous liver biopsy (PLBx). Selective hepatic angiography revealed a pseudoaneurysm of a branch of the right hepatic artery, associated with an arterio-portal venous fistula. Ultrasound with Doppler studies showed flow through the pseudoaneurysm. Embolization with platinum micro-coils resulted in cessation of flow through the pseudoaneurysm, and closure of the arterio-portal venous fistula. Anticoagulation was then resumed without recurrent bleeding. Pseudoaneurysms and arteriovenous fistulas may be mechanisms by which delayed bleeding occurs after PLBx. Doppler ultrasonography and hepatic angiography are useful in the evaluation and management of this event.

Aged

Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption.

This report describes a patient in whom a severe vitamin E deficiency developed secondary to an intestinal malabsorptive disorder. In vivo and in vitro impairment of T-cell function, as well as a polyneuropathy, were observed in conjunction with this vitamin deficiency. Repletion of the vitamin deficiency was associated with marked improvement in the T-cell functions and modest improvement in the neuropathy. Observations in this patient suggest that severe vitamin E deficiency in humans may impair T-cell activity and that correction of the deficient state may reverse these T-cell abnormalities. Further studies will need to be performed to confirm these findings.

Fats

Prolonged cholestasis due to trimethoprim sulfamethoxazole.

Drug-induced liver injury due to trimethoprim sulfamethoxazole is rare and classified as an unpredictable or idiosyncratic type of hepatotoxic reaction. Early reports suggested that the pattern of liver injury in the majority of cases is mixed hepatocellular-cholestatic. The current report describes two cases of severe, prolonged cholestasis after treatment with trimethoprim sulfamethoxazole; intractable pruritus and abnormal liver test results lasted for 1-2 years after discontinuation of the drug. Liver biopsy specimens showed a cholestatic pattern of liver injury and only minimal hepatocellular necrosis or inflammation. Recent case reports suggest that cholestasis alone may occur after the use of trimethoprim sulfamethoxazole; these two additional cases show that cholestasis may be quite prolonged.

Adult

Urokinase in gastrointestinal tract bleeding.

Selective urokinase infusion into the superior mesenteric artery allowed the accurate determination of the site of small bowel bleeding in a patient with recurrent lower gastrointestinal bleeding who bled despite resective surgery and who had negative findings on four angiograms. Fibrinolytic agents are useful in rare cases in which the need for successful and accurate diagnosis outweighs the risks of reactivating the bleeding.

Angiography