Biomedical subjects

J V Sitzmann

Publications and source records attributed to J V Sitzmann.

At least 91 records · Page 5Linked to original sources

PubMed1991

Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer.

Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival.

Adult↗

PubMed1991

Angiotensin II increases portosystemic collateral resistance in portal hypertension.

The decreased vasoconstrictive response of the splanchnic vasculature in portal hypertension (PHT) to angiotensin II (ANGII) is newly established. This could explain the limited ability of PHT patients to compensate in hypovolemic shock. However, the effect of ANGII upon portosystemic collateral resistance (Rc) is not known. We hypothesized that ANGII could directly effect Rc and thus change portal venous pressure (PVP). Chronic PHT was induced in New Zealand white rabbits by partial portal vein ligation 3 weeks prior to study. Splanchnic blood flow and portosystemic shunt (PSS) were measured simultaneously in six normal rabbits and then in six PHT rabbits at baseline and during intravenous ANGII infusion at 1.0 microgram/kg/min. Flow and resistance were standardized to 100 g small intestine weight. Superior mesenteric artery flow (Qsma) in normal rabbits was 64.9 +/- 3.6 ml/min, increased to 134.6 +/- 13.5 ml/min in the PHT animals (P less than 0.001) and was reduced 30% (P less than 0.05 vs PHT baseline) with ANGII. Concomitantly, PVP in the PHT animals was twice normal, 7.0 +/- 0.32 vs 14.4 +/- 0.55 mm Hg (P less than 0.001) and rose slightly with ANGII. The high PSS in PHT (84 +/- 6.0%, P less than 0.001 vs normal) was not affected significantly by ANGII infusion. Rc in the PHT rabbits rose 50% from 0.06 +/- 0.001 to 0.09 +/- 0.01 mm Hg/ml/min (P less than 0.001) with ANGII. This is the first evidence for a vasoconstrictive response in portosystemic collaterals during ANGII infusion. This change in collateral resistance causes both PVP and PSS to remain pathologically elevated in PHT despite a fall in portal inflow, thus predisposing to repeat variceal bleeding.

Angiotensin II↗

PubMed1991

Transduodenal exploration of the common bile duct in patients with nondilated ducts.

Exploration of the small common bile duct can be technically difficult and is associated with a significant risk of ductal injury or late stricture, or both. Transduodenal common duct exploration after sphincteroplasty (TCDE/S) is an alternative method of duct exploration that avoids choledochotomy. Cholecystectomy followed by TCDE/S was performed upon 28 patients with nondilated ducts and suspected choledocholithiasis. Common duct stones were retrieved in 17 patients. Failure to retrieve stones in the remaining 11 patients was attributed to either false-positive results of cholangiography, forceful passage of stones into the duodenum during the initial insertion of a Fogarty catheter through the cystic duct or a false-negative finding at duct exploration. There was no perioperative mortality. Two patients had asymptomatic postoperative hyperamylasemia. One patient had postoperative pancreatitis, hyperbilirubinemia and cholangitis that resolved with antibiotic therapy by the eighth postoperative day. Other complications included wound infection, delayed gastric emptying, pneumonia and otitis media. The over-all morbidity rate was 28.6 per cent. Long term follow-up was obtained in all 28 patients. All patients in the follow-up group are free of recurrent biliary tract disease. TCDE/S appears to be a safe and effective method of exploring the nondilated common bile duct.

Adult↗

PubMed1991

Modulation of splanchnic vascular sensitivity to angiotensin II.

We studied whether the diminished splanchnic vascular response to angiotensin II infusion in portal hypertension could be related to elevated levels of prostacyclin (PGI2). The changes in superior mesenteric artery resistance (RSMA) and systemic vascular resistance (RSYS) during angiotensin II infusion were measured by Doppler flow probe in normal rabbits (NL) and portal hypertensive rabbits (PHT), and in NL and PHT after cyclooxygenase blockade (CO) and after CO and during continuous PGI2 infusion at 300 ng/kg/min. Angiotensin II infusion in NL caused a disproportionately greater increase in RSMA than in RSYS (p less than 0.01). In PHT, angiotensin II response of RSMA was reduced from NL (p less than 0.05). CO dramatically improved the splanchnic response to angiotensin II in PHT animals, but did not significantly alter the RSMA response in NL. PGI2 in NL, NL + CO, and PHT + CO quantitatively established the splanchnic vascular hyporesponsiveness to angiotensin II seen in PHT. We conclude that PGI2 will directly diminish splanchnic response to angiotensin II in NL, and CO will ablate differences in splanchnic response between NL and PHT to angiotensin II. This strongly implies that much of the observed decrease in angiotensin II response in PHT is mediated by PGI2 and that the differences between NL and PHT vascular response is in part the result of circulating vasodilatory substances.

Angiotensin II↗

PubMed1991

Evidence for role of prostacyclin as a systemic hormone in portal hypertension.

The possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein. In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1 alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in all vascular beds (systemic arterial, systemic venous, and portal venous) when compared with levels in control animals. In PHT rabbits, exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial, systemic venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics. These hemodynamic changes were of equal magnitude irrespective of site of infusion in PHT. In controls there was no significant change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion. We conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

Favorable response to parenteral nutrition and medical therapy in Crohn's colitis. A report of 38 patients comparing severe Crohn's and ulcerative colitis.

The courses of 38 patients with severe, uncomplicated acute colitis (16 with Crohn's colitis and 22 with ulcerative colitis) were analyzed retrospectively. The patients were placed on total parenteral nutrition and treated concomitantly with corticosteroids, antibiotics (often metronidazole), sulfasalazine, and/or azathioprine. Fifteen of the 16 Crohn's colitis patients were initially managed without surgery. Four patients subsequently relapsed, two responded to reinstituted medical therapy, and two underwent colon resection 2 and 4 years later. Of 22 ulcerative colitis patients, 16 required surgery during the initial hospitalization, one patient subsequently had surgery, and one died after refusing surgery. Three of the other four continue in remission on medical therapy. Thus, there were significant differences in this series between the clinical courses of severe ulcerative colitis and severe Crohn's colitis. While most of the ulcerative colitis patients with severe disease underwent colectomy, most of the patients with severe but uncomplicated Crohn's colitis responded to aggressive medical therapy, of which total parenteral nutrition and perhaps bowel rest seemed to be an important part. Afterwards, the majority remained in remission on long-term medical therapy.

Catheterization↗

PubMed1990

Decreased mesenteric vascular response to angiotensin II in portal hypertension.

We studied the mesenteric and systemic vascular response to angiotensin II in normotensive and portal hypertensive (PHT) rabbits, because of the documented poor tolerance of hemorrhagic shock in PHT. Normally, the hemodynamic response to angiotensin II (AII) is characterized by selective and disproportionate splanchnic vasoconstriction. We postulated that the response to AII could be diminished in PHT. Chronic PHT was induced by partial portal vein ligation 3 weeks prior to graded angiotensin II infusion. Baseline hemodynamic measurements showed markedly elevated portal pressure (PPV) and superior mesenteric artery blood flow (QSMA) compared with those of normotensive animals (P less than 0.01). Superior mesenteric artery resistance (RSMA) was markedly reduced in PHT compared to that in controls (P less than 0.05). Angiotensin II infusion in normals resulted in a marked selective rise in RSMA compared with the rise in systemic resistance (RSYS) (P less than 0.01). AII infusion in PHT resulted in a rise in RSMA and RSYS, but the disproportionate in RSMA was attenuated. Furthermore, in both normal and PHT, AII caused a significant rise in PPV (P less than 0.01). We conclude that the findings indicate that the splanchnic vasoconstrictive response to AII is substantially impaired in PHT, and that AII will paradoxically cause a rise in PPV, possibly aggravating the tendency to hemorrhage in PHT.

Angiotensin II↗

PubMed1990

In vivo 31P NMR spectroscopic changes during liver regeneration.

Liver regeneration following partial hepatectomy involves rapid cell division 24 to 72 hr postresection. This cell division would necessarily involve changes in intracellular energy stores and cell membrane phospholipid precursors. In tumor models 31P nuclear magnetic resonance (NMR) has been shown to identify intracellular substrate changes associated with cell growth. The ability to monitor early changes in adenosine triphosphate (ATP), inorganic orthophosphate (Pi), phosphomonoesters (PME), or phosphodiesters (PDE) after liver resection could indicate the intracellular changes necessary for hepatocellular regeneration. In vivo 31P NMR scans of the liver were performed in both normal rats and in rats at 24, 48, 72, and 120 hr after 70% hepatectomy. At 48 hr, total ATP fell to 18.9% (P less than 0.05) and both Pi/beta-ATP and PME/beta-ATP were significantly elevated (P less than 0.01) from controls. These changes correlate with the known mitotic peak in the rat following hepatectomy. We conclude that in vivo 31P NMR is a potentially valuable tool for studying hepatic regeneration. The data also suggest that hepatocellular regeneration may be critically dependent on cellular ATP stores.

Adenosine Triphosphate↗

PubMed1990

Preoperative assessment of malignant hepatic tumors.

Over a 31-month period, 100 patients with malignant hepatic tumors were preoperatively evaluated with three imaging techniques. The results of intravenously enhanced computed tomography (CT) scan, selective hepatic arterial contrast CT, and magnetic resonance imaging (MRI) were compared with operative findings. A total of 227 lesions were identified, with the sensitivity for tumor detection being arteriographically enhanced CT 94% (p less than 0.01), MRI 70%, and CT 66%. This advantage for arteriographically enhanced CT was most marked for lesions less than 1 cm in diameter (82% versus 20% for MRI and 5% for CT; p less than 0.01). Arteriographically enhanced CT was also most sensitive in assessing tumor margins. MRI was clearly superior to arteriographically enhanced CT or CT in detecting vascular involvement (85% versus 30% and 8%, respectively; p less than 0.01). No imaging technique was sensitive in determining extrahepatic involvement. Arteriographically enhanced CT was also best at predicting the operative procedure. The combination of arteriographically enhanced CT and MRI was the best predictor of true disease. We conclude that both arteriographically enhanced CT and MRI should be used for preoperative assessment of hepatic malignancies.

Adolescent↗

PubMed1990

Current management of the Budd-Chiari syndrome.

Twenty-six patients with the Budd-Chiari syndrome were treated surgically at the Johns Hopkins Hospital. Twenty-one of the patients were female and five were male, with a median age at diagnosis of 37 years. Nine patients had polycythemia vera, 6 were receiving estrogen therapy, 5 had a previous hepatitis A or B infection, and 4 had cirrhosis. There was one case each of hepatic malignancy, paroxysmal nocturnal hemoglobinuria, and idiopathic thrombocytopenic purpura. In five cases no etiologic factors or associated disorders were identified. Ascites was the most common presenting feature in this group of patients. Hepatic function at the time of diagnosis, as measured by standard serum chemistries, was only minimally abnormal. The diagnosis of the Budd-Chiari syndrome was confirmed in all 26 patients by hepatic vein catheterization. Inferior vena cavography was also performed and revealed caval occlusion in 4 patients, significant caval obstruction in 13 patients, and a normal vena cava in 9 patients. Interpretation of the vena cavogram was helpful in selecting the appropriate surgical procedure for each patient. Twenty-three of the twenty-six patients underwent percutaneous liver biopsy before operation, with no morbidity or mortality. Four patients had well-established cirrhosis noted on biopsy. Thirty mesenteric-systemic venous shunts were performed on the 26 patients. In 11 patients a mesocaval shunt was performed and in one instance conversion to a mesoatrial shunt was required as a second procedure. In 15 patients a mesoatrial shunt was performed as the initial procedure. Graft thrombosis occurring in 2 of these 15 patients prompted one revision in 1 patient and 2 revisions in the second patient. After mesenteric-systemic venous shunt, eight of the patients (31%) died before discharge from the hospital. The remaining 18 patients in this series were discharged from the hospital alive and well with patent shunts. Patients were followed for a median of 43 months (range, 9 months to 13 years). Five late deaths occurred between 5 and 84 months after the operation. Three- and five-year actuarial survival rates were 65% and 59%, respectively.

Adolescent↗

PubMed1990

Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans.

Long term total parenteral nutrition (TPN) induces biliary sludge and formation of gallstones. Cholecystectomy is hazardous in these patients because of the underlying medical problems. Therefore, a randomized, double-blind controlled study was designed to test the hypothesis that daily administration of cholecystokinin-octapeptide (CCK-OP) prevents the formation of biliary sludge in humans receiving long term TPN. Adult patients receiving TPN for more than 21 consecutive days were studied. After randomization of 15 patients, the study was concluded because statistical significance was achieved. Eight patients received saline solution (placebo) intravenously and seven received CCK-OP (50 nanograms per kilogram) intravenously over a ten minute period daily. The groups were similar with respect to age, sex, diagnosis, liver function tests, amylase levels, total TPN time and time of study. All of the patients underwent weekly ultrasound studies. Volume and emptying studies of the gallbladder in response to the study drug were performed after one week. None of the patients receiving CCK-OP had sludge whereas five of eight of the patients receiving placebo had sludge (p less than 0.02). The results of emptying studies showed significant contraction of the gallbladder in those in the CCK-OP group but not in the placebo group. These data suggest that CCK-OP given intravenously daily prevents TPN induced stasis and sludge of the gallbladder. We conclude that CCK-OP should be used as routine prophylaxis against biliary sludge and formation of gallstones in patients receiving long term TPN.

Adult↗

PubMed1990

Reversal by antrectomy of endocrine cell hyperplasia in the gastric body in pernicious anemia: a morphometric study.

Multifocal gastric carcinoid tumors occasionally develop in patients with pernicious anemia, associated with hyperplasia of endocrine cells in the atrophic and metaplastic gastric body mucosa. This constellation of findings probably requires a trophic drive from hypergastrinemia associated with antral G cell hyperplasia, a consequence of achlorhydria in these patients. We report a case in which antrectomy was performed on such a patient in order to abrogate the trophic stimulus. Antrectomy was followed by resolution of hypergastrinemia and a decrease in the size of polyps endoscopically. Nine months later, the gastric remnant was resected. Using morphometric techniques, endocrine cells in the initial antrectomy specimen (which included body mucosa at the resection line) were compared with those in the subsequently removed gastric body. Antrectomy resulted in striking decreases in number (137 versus 34/mm2; P = 0.0001) and size (93 versus 56 microns2; P = 0.0001) of endocrine cells of body mucosa. The findings suggest that antrectomy may be useful in the management of endocrine cell hyperplasia, and possibly also associated carcinoid tumors, in pernicious anemia.

Anemia, Pernicious↗

PubMed1989

Statement on guidelines for total parenteral nutrition. The Patient Care Committee of the American Gastroenterological Association.

This is one of a series of clinical guidelines. They represent a consensus statement dealing with optimum patient care in significant clinical areas. The statement has been prepared by the Patient Care Committee, with the advice of other experts and with peer review. As with all such guidelines, they should be interpreted in a nondogmatic manner, so as not to exclude other therapies or opinions in any particular situation. Based on present knowledge, limited at times, future modifications or other changes in these guidelines may be necessary.

Gastroenterology↗

PubMed1989

Prostacyclin mediates splanchnic vascular response to norepinephrine in portal hypertension.

Portal hypertension is characterized by increased splanchnic blood flow. This hyperemia may be related to the documented in vitro impaired sympathetic response in portal hypertension. Because prostacyclin (PGI2) has been shown to be elevated in portal hypertensive rabbits, we studied whether PGI2 could mediate the reduced sympathetic response. We measured the change in the superior mesenteric artery resistance (Rsma) to norepinephrine infusion in chronic portal vein ligated (PHT) and normotensive rabbits, in both portal hypertensives and normals following cyclooxygenase blockade with 8 mg/kg indomethacin, and finally in portal hypertensive, cyclooxygenase-blocked rabbits with a constant IV infusion of PGI2 at 200 or 300 ng/kg/min. Dose-response curves were obtained and statistical comparisons were based on the dose of norepinephrine producing 50% of maximal Rsma response (ED50). Portal hypertensive rabbits had significantly higher ED50 (310 +/- 4.1 mg/kg) than normotensive rabbits (150 +/- 4.1 mg/kg, P less than 0.01). Cyclooxygenase blockade resulted in marked reduction of the ED50 in both groups and ablated the difference between normotensive and PHT rabbits (20 +/- 2.4 and 20 +/- 2.8 mg/kg/min, respectively). Prostacyclin infusion at 200 ng/kg/min increased the ED50 (80 +/- 2.5 mg/kg) and PGI2 infusion at 300 ng/kg/min increased the ED50 further (160 +/- 7.5 mg/kg/min, P less than 0.01 vs cyclooxygenase-blocked only rabbits). These results provide the first in vivo evidence of reduced splanchnic sensitivity to norepinephrine in portal hypertension and demonstrate that PGI2 will cause a dose-related decrease in sympathetic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

A method for hepatic arterial perfusion studies in the rat.

The current model for selective hepatic arterial infusion therapy was evaluated for its suitability for short-term pharmacokinetic experiments. This preparation consists of selective cannulation of the common hepatic artery via the gastroduodenal artery of the rat. Radioactive microspheres were injected to determine hepatic or extrahepatic sites of perfusion. Radioactive microsphere determination of hepatic arterial flow and cardiac output were also performed. Our data indicate that at high flow rates (2 ml/min), significant loss of drug would occur due to retrograde flow. Modification of the model to include temporary proximal hepatic artery occlusion ensures hepatic delivery of greater than 95% of drug. Furthermore, temporary hepatic artery occlusion does not alter cardiac output or hepatic arterial blood flow. Selective hepatic arterial infusion in rats with synchronous temporary hepatic artery occlusion is an adequate model for short-term pharmacokinetic studies.

Animals↗

PubMed1989

Immunoradiotherapy for primary nonresectable hepatocellular carcinoma.

The ability to convert a nonrectable lesion into a resectable one offers significant palliation and possible cure for patients with hepatoma. With increasing effectiveness of radiolabeled immunoglobulin and multimodality treatment, more patients are expected to become candidates for definitive resection after presenting with unresectable disease.

Carcinoma, Hepatocellular↗

PubMed1989

Role of prostacyclin in the splanchnic hyperemia contributing to portal hypertension.

To determine the possible role of prostacyclin (PGI2) as a mediator of the splanchnic hyperemia seen with portal hypertension, the portal and mesenteric hemodynamics in normal and portal hypertensive rabbits were studied before and after cyclo-oxygenase blockade. Three weeks after partial portal vein ligation, splenic pulp pressure was elevated from 4.3 +/- 0.9 to 9.8 +/- 0.8 mmHg (p less than 0.01). Mesenteric blood flow increased from 77.0 +/- 4.7 ml.min-1.100 g-1 to 99.1 +/- 5.19 ml/min-1/100 g-1. Mesenteric vascular resistance fell from 0.82 +/- 0.6 mmHg/ml-1/min-1 to 0.49 +/- 0.07 mmHg/ml-1/min-1 (p less than 0.01). These hemodynamic changes were associated with a 27.3 +/- 0.2% rise in systemic arterial levels of PGI2 (p less than 0.01) and were substantially ameliorated by cyclo-oxygenase blockade with indomethacin. The effects of indomethacin blockade were reversed by exogenous PGI2. Moreover, in normotensive rabbits, infusion of PGI2 reproduced the splanchnic hyperemia and caused a very small but significant increase in portosystemic shunting. These findings support the previously proposed concept that splanchnic hyperemia may contribute to the maintenance of chronic portal hypertension. Furthermore, they suggest that this effect may be partially mediated by splanchnic PGI2 production.

Animals↗

PubMed1989

Total parenteral nutrition and alternate energy substrates in treatment of severe acute pancreatitis.

The use of total parenteral nutrition (TPN) in the treatment of 73 patients with acute severe pancreatitis was prospectively studied during a two year period. Patients were divided into three groups on the basis of calorie substrate used. Glucose and twice weekly lipid infusion (glucose based) were used in 60 per cent; 27 per cent required daily lipid infusion (lipid based), and 13 per cent received no lipid because of pre-existing hyperlipemia or thrombocytopenia (no lipid). Nutritional indices (albumin, transferrin and total lymphocyte count) were initially abnormal in more than 80 per cent of patients, and 50 per cent had three or more of Ranson's criteria. After TPN, 81 per cent had improved nutritional indices, and none had hypertriglyceridemia or aggravation of pancreatitis develop. Patients who received lipid based or no lipid had higher insulin requirements (p less than 0.01) than those receiving mainly glucose. Mortality was increased tenfold (2.5 versus 21.4 per cent, p less than 0.01) in patients who did not achieve positive nitrogen balance. We conclude that TPN, either lipid or glucose based, is a safe and effective therapy to reverse the malnutrition of acute pancreatitis and that failure to achieve positive nitrogen balance is associated with increased mortality.

Acute Disease↗