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Biomedical subjects

W S Helton

Publications and source records attributed to W S Helton.

At least 37 records · Page 2Linked to original sources
PubMed1993

Oral prostaglandin E2 prevents gut atrophy during intravenous feeding but not bacterial translocation.

The pathophysiologic changes in gut physiology that result in bacterial translocation during intravenous feeding are poorly defined, though believed to be related in part to intestinal atrophy, decreased mesenteric blood flow, and lack of intestinal secretions. This study investigated the hypothesis that pharmacologic preservation of intestinal structure and function by orally administered 16,16-dimethyl-prostaglandin E2 would prevent bacterial translocation in intravenously fed rats. Thirty-five rats were randomized to three groups: group 1 was fed rat chow ad libitum, group 2 received standard parenteral nutrition, and group 3 received parenteral nutrition plus oral 16,16-dimethyl-prostaglandin E2 (150 micrograms/kg twice a day). Rats were fed there respective diets for 5 days and killed. Mesenteric lymph nodes were procured for culture, and the intestine was assessed for weight, DNA, protein values, and histologic character. Results demonstrate that orally administered 16,16-dimethyl-prostaglandin E2 potently attenuates the intestinal atrophy associated with parenteral feeding but does not prevent bacterial translocation. Intestinal barrier dysfunction and bacterial translocation during intravenous feeding is related to factors other than the development of gut atrophy.

Administration, Oral↗
PubMed1993

Critical appraisal of the angiographic portacaval shunt (TIPS).

The transjugular intrahepatic portacaval shunt (TIPS) is a novel angiographic method for achieving portal decompression without operation. Fifty-nine consecutive patients underwent a total of 80 consecutive TIPS procedures. The procedure was unsuccessful in 4 patients (7%) and initially succeeded in 55 (93%). Eighteen patients (30%) underwent 2 or more TIPS procedures during the same hospitalization due to technical difficulties, early rebleeding, shunt stenosis, or thrombosis. Early TIPS occlusion occurred in seven patients (12%) and led to recurrent variceal hemorrhage in five. Forty-two percent of the cases of persisting or recurrent bleeding were nonvariceal. Procedure-related complications occurred in 10% of TIPS procedures or 14% of patients. Twenty-three patients (39%) were actively bleeding at the time of the procedure, and, in 6 of these (26%), bleeding was never controlled. In-hospital mortality (25%) was related only to the presence of bleeding at the time of TIPS (56% for emergent versus 5.5% for non-emergent, p < 0.0001). Mortality was not related to the Child-Pugh classification. Hemodynamic stabilization, vasoconstrictor therapy, balloon tamponade, and sclerotherapy were underutilized in 30% to 40% of patients prior to TIPS. Aggressive medical management should be used to stop variceal hemorrhage prior to TIPS in all patients, regardless of the Child-Pugh classification. Prospective trials comparing TIPS with sclerotherapy and surgical shunt are required to demonstrate the proper role of this procedure in the management of portal hypertension and variceal hemorrhage.

Adult↗
PubMed1992

Portal hypertension and bleeding esophageal varices.

Bleeding from esophageal varices exacts a high mortality and extraordinary societal costs. Prophylaxis--medication, sclerotherapy, or shunt surgery to prevent an initial bleeding episode--is ineffective. In patients who have bled from varices, endoscopic injection sclerotherapy can control acute bleeding in more than 90% of patients. Because recurrent bleeding frequently occurs and survival without definitive therapy is dismal, selection of a permanently effective treatment is mandatory once variceal bleeding has been controlled. Long-term injection sclerotherapy can be performed in compliant patients; it is relatively safe but is associated with a 30-50% rebleeding rate. Beta-blockers significantly reduce portal pressure and recurrent bleeding but have not been shown to diminish mortality from BEV. Portal decompressive surgery permanently halts bleeding in more than 90% of patients; the risk of operative mortality is high in decompensated cirrhotics, and long-term complications of encephalopathy and accelerated liver failure may limit indications for shunt surgery to good-risk cirrhotics who are not liver transplant candidates. Devascularization procedures have a low operative mortality and encephalopathy rate but unacceptably high rates of recurrent bleeding. Liver transplantation is curative therapy for bleeding esophageal varices and the associated underlying hepatic dysfunction; cost and availability of donor organs generally limit its use in this setting to variceal bleeders with end-stage liver disease not associated with active alcoholism.

Esophageal and Gastric Varices↗
PubMed1992

Glutamine preserves liver glutathione after lethal hepatic injury.

Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. Glutamine augments host defenses and may be important in GSH synthesis. Acetaminophen toxicity causes hepatic GSH depletion and hepatic necrosis. The authors hypothesized that glutamine-supplemented nutrition would enhance liver GSH stores and diminish hepatic injury and death after acetaminophen overdose. Wistar rats received either a standard total parenteral nutrition (TPN) solution (STD) or an isocaloric, isonitrogenous glutamine-supplemented solution (GLN). On the 5th day of feeding, animals were given acetaminophen (400 mg/kg intraperitoneally) and then killed at various time points. Standard TPN solution animals had a rapid depletion of hepatic glutathione, whereas GLN animals were resistant to this drop and rapidly repleted hepatic GSH stores. Glutamine-supplemented animals maintained higher plasma glutamine concentrations, had lesser elevations in hepatic enzymes, and sustained significantly fewer complications compared with STD animals. The authors conclude that glutamine-supplemented nutrition preserves hepatic glutathione, protects the liver, and improves survival during acetaminophen toxicity. Glutamine may augment host defenses by enhancing antioxidant protection.

Acetaminophen↗
PubMed1991

Impedance electrodes positioned on proximal portions of limbs quantify fluid compartments in dogs.

Body resistance and reactance to the conduction of an alternating electrical current were measured using electrodes attached to distal and proximal portions of limbs in anesthetized dogs. Body impedance was calculated from these measurements obtained at 30-min time intervals during a control period and after intravenous administration of 0.9% saline. Extracellular (ECW) and total body water (TBW) were determined by bromide and heavy water dilution techniques, respectively. Baseline impedance obtained from proximal electrodes was related to ECW (r = 0.95, P less than 0.001) and TBW (r = 0.80, P less than 0.02). After saline infusion, proximal electrodes detected a significant fall in impedance (P less than 0.001), whereas distal electrodes did not (P = 0.06). Furthermore, ECW and TBW could be estimated from the drop of proximal impedance after this bolus infusion (r = 0.82, P less than 0.02, and r = 0.86, P less than 0.01, respectively), but not from distal impedance measurements. Proximally placed impedance electrodes are superior to traditionally used distal electrodes for assessment of body fluid changes in the dog.

Animals↗
PubMed1990

Glutamine prevents pancreatic atrophy and fatty liver during elemental feeding.

Rats fed an elemental, enteral diet (STD) developed pancreatic atrophy and hepatic steatosis following 60% jejunoileal intestinal resection. An isonitrogenous, isocaloric 2 g/100 ml glutamine-supplemented diet (GLN) significantly attenuated the development of pancreatic atrophy and hepatic steatosis associated with elemental feeding. Pancreatic weight, DNA, and protein were 27, 22, and 40% increased, respectively, in GLN animals. The pancreata of all animals appeared normal by light and electron microscopic examination. GLN animals had 12% less total liver wet weight, 3% less hepatic water content, and 47% less hepatic fat relative to STD rats. Histologic examination of the liver revealed extensive centrilobular fatty vacuolization in STD animals whereas GLN rats had normal looking hepatic parenchyma. Glutamine should be viewed as an important nutrient in elemental diets with trophic effects on the pancreas and protective effects against the development of hepatic steatosis.

Animals↗
PubMed1990

CGRP stimulates the release of pro-somatostatin-derived peptides from the gastric fundus.

Calcitonin gene-related peptide (CGRP) stimulates release of peptides derived from pro-somatostatin (Pro-S) into the general circulation. The purpose of this investigation was to elucidate the origin and molecular heterogeneity of Pro-S-derived peptides secreted in response to CGRP. Catheters were placed into the vena cava and veins draining the gastric fundus and corpus, antrum, and small intestine of anesthetized pigs. Human CGRP I was infused into the descending aorta at 0.2, 0.4, 0.8, and 1.6 micrograms.kg-1.h-1 for consecutive 30-min intervals. Blood was collected from the venous catheters after each period. S-28 was separated from Pro-S, S-14, and S-13 by immunoaffinity chromatography and peptides were quantified by radioimmunoassay. CGRP primarily evoked release of peptides measured collectively as Pro-S, S-14, and S-13 into venous blood draining the fundus and corpus, and concentrations were significantly elevated above basal at 0.8 and 1.6 micrograms.kg-1.h-1 CGRP (P less than 0.05). Basal concentrations of S-28, Pro-S, S-14, and S-13 in blood from the antrum and small intestine were not significantly elevated by CGRP. In conclusion, CGRP stimulated release of Pro-S-derived peptides from the gastric fundus and corpus but not from the antrum or small intestine.

Animals↗
PubMed1989

Inhibition of gastric and pancreatic secretion in dogs by CGRP: role of somatostatin.

The coexistence of calcitonin gene-related peptide (CGRP) and somatostatin (SS) within the stomach and pancreas and the potent inhibitory effects of both peptides on exocrine secretions from these organs suggest that they are functionally related. To assess the potential role of SS in the mediation of CGRP action, the effects of intravenous human CGRP (64, 132, and 264 pmol.kg-1.h-1) and somatostatin-14 (SS-14; 100, 400, and 800 pmol.kg-1.h-1) on plasma levels of SS immunoreactivity (SS-IR) and on pentagastrin-stimulated gastric and pancreatic secretion were compared in conscious dogs. CGRP caused significant inhibition of gastric acid (85-102%), pancreatic protein (63-86%), and pancreatic bicarbonate (74-89%) outputs and a simultaneous dose-related rise (40-102 fmol/ml) in plasma SS-IR. Cessation of CGRP infusion resulted in prompt return of plasma SS-IR to basal levels and an increase in gastric and pancreatic secretion. Although CGRP is a potent releasor of SS into the circulation, its inhibitory action on gastric acid secretion cannot be explained solely by a rise in plasma SS-IR. In the pancreas, in contrast to the stomach, inhibition appears to be more closely related to a rise in circulating level of SS-IR.

Animals↗
PubMed1988

Duplex ultrasound measurement of postprandial intestinal blood flow: effect of meal composition.

Duplex ultrasound was used to evaluate the effects of 350-cal, 300-ml protein, fat, carbohydrate, and mixed (Ensure-Plus) liquid meals on celiac, superior mesenteric, and femoral artery blood flow in 7 healthy volunteers. Ingestion of separate water and mannitol solutions served as controls for volume and osmolarity. Duplex parameters of peak systolic velocity, end-diastolic velocity, mean velocity, and volume flow were determined before, and serially for 90 min after, ingestion of each test meal. Maximal changes were compared with baseline values. There were no significant changes in any of the blood flow parameters derived from the celiac or femoral arteries after any test meal ingested. In contrast, maximal changes in all superior mesenteric artery parameters were increased significantly over baseline (p less than 0.05) after each of the test meals except water, with end-diastolic velocity showing proportionally the greatest increase. The study demonstrates that duplex ultrasound can provide a noninvasive means of studying the reactivity of the splanchnic arterial circulation to different stimuli and documents differing blood flow responses to variation of nutrients.

Adult↗
PubMed1988

Duplex sonography accurately assesses portacaval shunt patency.

Among 42 patients who had undergone portacaval shunt (PCS) to treat bleeding esophageal varices, shunt patency was assessed with duplex sonography 1 month to 5 years postoperatively. Patency was confirmed in all patients (100%). Correlative angiograms confirming the sonographic findings were obtained in 24 patients. Duplex scanning showed hepatofugal or stagnant flow in the distal portal vein in all 42 patients. Very low rates of liver-failure-related mortality (6%) and morbidity (6% incidence of encephaloparthy) in this series despite loss of portal perfusion of the liver in patients incriminate factors other than magnitude and direction of portal vein flow as the cause of complications occurring after PCS. Duplex sonography offers accurate and relevant clinical and physiologic data about shunt hemodynamics in patients who have undergone PCS.

Humans↗
PubMed1986

Diagnosis and treatment of splenic fungal abscesses in the immune-suppressed patient.

In an 18-month period candidal splenic abscesses were diagnosed and treated in eight patients. Predisposing factors consisted of recent exposure to cytotoxic chemotherapy, long-term use of prednisone, neutropenia, antibiotic therapy for greater than three weeks, and gastrointestinal tract colonization with Candida. The patients had a clinical profile of nontoxic appearance with a temperature of more than 38.5 degrees C that was unresponsive to antibiotics, pain and tenderness over the upper abdominal quadrants, focal defects visualized on ultrasound and/or computed tomographic scans, and an elevated alkaline phosphatase level. Candida infection was confirmed by histologic examination of the liver and/or spleen in all patients. Diagnosis was made by percutaneous biopsy in one patient and exploratory laparotomy in seven. Five patients had splenectomy and antifungal drugs. In three patients the fungal abscesses resolved with amphotericin B therapy alone. Seven of eight patients were cured of their splenic abscesses, and five of eight were long-term survivors.

Abscess↗
PubMedDate not supplied

Effects of transjugular intrahepatic portosystemic shunts on hepatic metabolic function determined with serial monitoring of arterial ketone bodies.

PURPOSE: To investigate the effects of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic metabolic function by measuring serial arterial ketone body ratio (acetoacetate/-hydroxybutyrate; AKBR). MATERIAL AND METHODS: The arterial blood of 30 TIPS patients was assayed before TIPS, 30 minutes after TIPS, and 24 hours after TIPS for acetoacetate, beta-hydroxybutyrate, and glucose. The authors compared the AKBR values to clinical outcome stratified by Child class, emergent versus elective TIPS, and before-TIPS AKBR value < or = 0.5 versus before-TIPS AKBR value > 0.5. RESULTS: A significant change was noted between the AKBR values obtained before TIPS and values 30 minutes after TIPS (0.76 +/- 0.09 vs 0.61 +/- 0.05, P < .05) and between 30 minutes and 24 hours after TIPS (0.81 +/- 0.10, P < .001), but not between the value obtained before TIPS and that obtained 24 hours after TIPS. The 30-day mortality rate in emergency TIPS patients was 50% compared to 7% in the elective TIPS patients (P < .01). The pre-TIPS AKBR values were significantly suppressed in the emergency TIPS patients compared to the elective TIPS patients (0.56 +/- 0.04 vs 0.99 +/- 0.17, P < .005). The 30-day mortality rate in patients with a pre-TIPS AKBR value < or = 0.5 was 75%, which was significantly higher than the 14% rate in patients with a pre-TIPS AKBR value > 0.5 (P < .01). CONCLUSION: A low pre-TIPS AKBR may be predictive of poor outcome after TIPS. Furthermore, AKBR may be of value in determining the timing for performing an elective TIPS.

Adolescent↗
PubMedDate not supplied

Omega-3 fatty acid supplementation reduces tumor growth and vascular endothelial growth factor expression in a model of progressive non-metastasizing malignancy.

BACKGROUND: Omega-3 fatty acids, the principal component of fish oil, have been demonstrated to have antiinflammatory properties. The role of eicosapentaenoic acid (EPA) supplementation for cancer patients is currently under investigation; however, the mechanisms of EPA activity have not been defined. The purpose of this study was to characterize tumor-specific and treatment-specific effects of supplemental dietary EPA in an animal model of progressive malignancy. METHODS: Fischer 344 rats (200-250 g) underwent flank implantation of the methycholanthrene (MCA)-induced fibrosarcoma on day 0. Rats were randomly divided into 3 treatment groups on day 13: EPA (1 mL, 5.0 g/kg per day) + 10 IU vitamin E; corn oil (1 mL) + 10 IU vitamin E, and saline (1 mL) + 10 IU vitamin E (vitamin E was used to prevent fatty acid oxidation). On day 14, gavage feeding was started and was continued through day 28. The animals were killed on day 29, and the tumors were removed. The tumors were weighed and divided by the tumor-free carcass weight to obtain percentage of tumor volume, and the livers were flash frozen. Vascular endothelial growth factor-alpha (VEGF-alpha) and cyclo-oxygenase 2 (COX-2) mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: EPA rats had significant reductions in tumor volume compared with isocaloric corn oil and control saline animals (25%, p < .01 and 33%, p < .01, respectively). Rats receiving EPA demonstrated decreased VEGF-alpha mRNA levels (0.023 +/- 0 0.001) compared with those receiving corn oil (0.129 +/- 0.047) or saline (0.150 +/- 0.026; p < .05). CONCLUSIONS: These data demonstrate that EPA supplementation inhibits tumor growth, potentially through alterations in the expression of the pro-angiogenic VEGF-alpha. The mechanism(s) of EPA as an inhibitor of tumor-related angiogenic growth factors may be associated with COX-2 enzyme fatty acid metabolism and merits further study.

Animals↗