Changes in High‐energy Phosphate Metabolism and Cell Morphology in Four Models of Acute Experimental PancreatitisNORDBACK, ISTO H.; CLEMENS, JEFFREY A.; CHACKO, VADDAPPURAM P.; OLSON, JEAN L.; CAMERON, JOHN L.
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Previous studies using the isolated ex vivoperfused canine pancreas preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p < 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.
Aortic Dissection with the Entrance Tear in the Descending Thoracic Aorta Analysis of 40 Necropsy PatientsROBERTS, CHARLES S.; ROBERTS, WILLIAM C.
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Clinical and necropsy findings are described in 40 patients who had aortic dissection with the entrance tear in the descending thoracic aorta. Their ages at death ranged from 39 to 91 years (mean, 66 years); 24 (60%) were men and 16 (40%) were women. Systemic hypertension was present by history in 33 patients (83%) and the hearts were of increased weight in 78%. Of the 40 patients, 31 (78%) had no operative intervention, while 9 (22%) underwent operation for aortic dissection. Of the 31 patients without operative therapy, the diagnosis of aortic dissection was established in life in 9 patients (29%) and at necropsy in 22 (71%). The interval from aortic dissection to death was 30 days or less in 13 patients (42%); rupture of the false channel was the cause of death in 9 patients (69%), renal failure in 2 (15%), and the cause was unclear in 2 (15%). The interval from aortic dissection to death was more than 30 days in 18 (58%) of the 31 patients without operative therapy. The cause of death in these 18 patients was related to the dissection in 11 (61%) (rupture of the false channel in 5; renal failure from dissection in 3, and rupture of the false channel of a second acute dissection in 3), but in the other 7 patients (39%) death was unrelated to the dissection but a nonfatal complication, specifically stenosis of the true channel from compression by a thrombus-filled false channel, occurred in 4 of these 7 patients. Thus only 3 (10%) of the 31 patients without operative therapy had no complications of aortic dissection. All nine patients who underwent operation had had an aortic dissection within 30 days, and the operation was performed because of a major complication of the dissection. Four patients survived 8 to 84 months after the operation. Thus early operative intervention (before the appearance of complications) appears justified in patients with aortic dissection with the entrance tear in the descending thoracic aorta to prevent rupture of the false channel acutely or after initial healing; to prevent renal failure from compression of renal arteries by an aneurysmal false channel; to prevent true channel stenosis from compression by a thrombus-filled false channel; and possibly to prevent the recurrence of acute dissection.
Have Changing Treatment Patterns Affected Outcome for Operable Breast Cancer? Ten‐year Follow‐up in 1288 Patients, 1965 to 1978CODY, HIRAM S.; LAUGHLIN, EDWARD H.; TRILLO, CARLOS ; URBAN, JEROME A.
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From 1965 to 1978, 1288 patients with primary operable breast cancer were treated by the senior author, using extended radical (ERM), radical (RM), and modified radical (MRM) mastectomy operations exclusively. Results were analyzed for trends in overall and disease-free survival, and patterns of local and distant relapse, the years 1965 to 1970 versus1971 to 1974 versus1975 to 1978. Significant changes (p < 0.00001) from 1965 to 1978 included progressively earlier stage of disease, less frequent use of RM and ERM, a decline in the use of postoperative radiotherapy, and the introduction in 1975 of multidrug adjuvant chemotherapy. Ten-year disease-free survival rates improved significantly for all patients (by 11%, p = 0.00004) and for node-negative (by 12%, p = 0.0024), node-positive (by 8%, p = 0.012), clinical stage II (by 15%, p = 0.0022), and pathologic stage II (by 12%, p = 0.016) disease. Ten-year local recurrence for all patients was 3% (local only) and 2% (local with distant metastasis), and survival from date of recurrence for all patients failing treatment increased two times (p < 0.0001) for patients treated most recently. As the primary surgical treatment of breast cancer continues to become more moderate, the promise of systemic adjuvant therapies can be realized only with continued emphasis on earlier diagnosis and maximal local control of disease.
The Fetus as a Patient Surgical ConsiderationsHARRISON, MICHAEL R.; ADZICK, N. SCOTT
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The diagnosis and treatment of human fetal defects has evolved rapidly over the past decade due to improved fetal imaging techniques and better understanding of fetal pathophysiology derived from animal models. The detection of a fetal anomaly may now lead to a change in the timing of delivery, a change in the mode of delivery, or prenatal treatment. Because most therapeutic maneuvers involve some risk to the fetus and mother, there must be a reasonable expectation that the procedure is feasible, safe, and effective before it can be attempted in humans. This requires reliable information about the pathophysiology and natural history of the disease process, the efficacy of fetal surgical intervention in ameliorating the disease, and the feasibility and safety of the proposed intervention. This paper focuses on the rationale and initial clinical experience with fetal surgery for a variety of life-threatening fetal anatomic defects.
Experimental Obliterative Gholangitis A Model for the Study of Biliary AtresiaSCHMELING, DAVID J.; OLDHAM, KEITH T.; GUICE, KAREN S.; KUNKEL, ROBIN G.; JOHNSON, KENT J.
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Noninfectious obliterative cholangitis results from biliary tract inflammation in clinical conditions such as biliary atresia and sclerosing cholangitis. The purpose of this study was to develop an animal model of noninfectious biliary tract inflammation and fibrosis. An implantable osmotic pump was connected to a catheter placed into the gallbladder of hamsters. Phorbol myristate acetate (PMA) was infused into the biliary tract for periods of 6 hours to 28 days. After 7 days the animals developed neutrophil infiltration, cellular necrosis, and edema of the biliary ducts. After 14 days, the animals demonstrated intrahepatic cholestasis with bile duct fibrosis and acute and chronic inflammatory cell infiltration. By 28 days pronounced portal fibrosis was present, some of which created an early bridging cirrhosis pattern. In addition there was evidence of neocholangipgenesis. We conclude that long-term PMA infusion into the biliary tract generates an inflammatory response characterized by obliterative cholangitis and fibrosis, sharing many of the histologie features of human biliary atresia. This model may provide a relatively simple technique for investigating the process of nqnpyogehic biliary tract inflammation.
Biliary Response to Glucagon in HumansBRANUM, GENE D.; BOWERS, BERT A.; WATTERS, CHRISTOPHER R.; HAEBIG, JON ; CUCCHIARO, GIOVANNI ; FAROUK, MARWAN ; MEYERS, WILLIAM C.
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Glucagon has been demonstrated to have profound effect on biliary secretion in several species. Glucagon's biliary effects were studied in humans following biliary tract surgery. Nine patients underwent common bile duct exploration and insertion of a balloon-occludable t tube. An aliquot of the collected sample was kept and the enterohepatic circulation was maintained by reinfusion of the collected bile viathe distal t-tube port. Glucagon increased bile flow and decreased cholesterol and phospholipid output during stable bile acid output. Furthermore high-performance liquid Chromatographie analysis of bile acid profiles revealed no significant changes in bile salt species or conjugation after glucagon infusion. Glucagon is probably important in the physiologic regulation of biliary secretion in humans.