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D L Jacobs

Publications and source records attributed to D L Jacobs.

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The effect of mesenteric venous hypertension on gut motility and absorption.

The effects of portal hypertension on gut function may be mediated by venous congestion and altered circulating levels of enteric hormones and neuropeptides. We designed this study to determine the effects of chronic intestinal venous hypertension (VHT), in isolation, on gut motility and absorption. In 10 dogs, a 20- to 25-cm loop of jejunum was isolated from the fecal stream, but myoneural continuity was maintained with the proximal bowel by a seromuscular bridge. In 5 dogs, VHT was created in the loop by a fixed stenosis of its venous drainage; a sham procedure was performed in a further 5 animals. Serosal monopolar electrodes were placed in all animals. Absorptive function and myoelectrical activity were studied over a 4-week period. Venous hypertension was achieved and sustained in the VHT animals; loop vein pressures for VHT vs control in cm H2O (means +/- SEM) are: initial--29.8 +/- 1.8 vs 7.5 +/- 0.4 (P less than 0.01), and at 4 weeks--17.6 +/- 6.88 vs 7.3 +/- 0.2 (P less than 0.01). Absorption of Na+, Cl-, glucose, and water was impaired in VHT loops. Normal patterns of fasting and postprandial myoelectrical activity were preserved in the VHT animals. We conclude that chronic VHT, in the absence of portosystemic shunting, results in impaired absorption of water, glucose, and electrolytes without any change in intestinal motility.

Animals

Indications and results of shunt operations in the treatment of patients with recurrent variceal hemorrhage.

None of the portasystemic shunts are ideal for all patients with recurrent variceal hemorrhage. Hemodynamic and clinical status should determine the type of shunt selected. Patients with a compatible anatomy, hepatopetal protal flow and controlled ascites are best served by a distal splenorenal shunt. Patients with variceal hemorrhage and medically resistant ascites are candidates for a side-to-side shunt, with consideration being given to an operation that avoids dissection of the porta hepatis. The end-to-side portacaval shunt should be used only in the emergency situation when other options are not available. However, due to the effectiveness of other therapies, such as sclerotherapy, in controlling bleeding, emergency shunts are rarely required. On the basis of the controlled trials of distal splenorenal shunt versus sclerotherapy, the latter is the initial treatment of choice with distal splenorenal shunt used promptly when sclerotherapy fails. Patients who live in remote areas, and noncompliant individuals may be best served with a distal splenorenal shunt as initial therapy.

Esophageal and Gastric Varices

Redox reactions associated with iron release from mammalian ferritin.

The early redox events involved in iron reduction and mobilization in mammalian ferritin have been investigated by several techniques. Sedimentation velocity measurements of ferritin samples with altered core sizes, prepared by partial reduction and Fe2+ chelation, suggest two different events occur during iron loss from the ferritin core. Reductive optical titrations confirm this biphasic behavior by showing that the first 20-30% of core reduction has different optical properties than the latter 70-80%. Proton uptake during initial core reduction is near zero, but as the percent core reduction increases, the proton uptake (H+/e) values increase to 2 H+/e (2 H+/Fe3+ reduced) as core reduction approaches 1 e/Fe3+. Coulometric reduction of ferritin by mediators of different redox potential and different cross-sectional areas show a two-phase sigmoidal reaction pattern in which initial core reduction occurs at a slower rate than later core reduction. The above experiments were all conducted in the absence of iron chelators so that the observed results were all attributed to core reduction rather than the combined effects of core reduction accompanied by Fe2+ chelation. The coulometric reduction of ferritin by various mediators shows a correlation more with reduction potential than with molecular cross-sectional area. The role of the ferritin channels in core reduction is considered in terms of the reported results.

Animals

Effects of enteral vs parenteral nutrition on reticuloendothelial function.

Previous investigations have shown that animals maintained with enteral nutrition are better able to survive an intraperitoneal bacterial challenge than animals receiving parenteral nutrition. The aim of this study was to assess the effects of enteral and parenteral nutrition on reticuloendothelial function. Eighteen enteral-fed male Sprague-Dawley rats had access to a standard hyperalimentation solution via a sipper tube ad libitum. Seventeen parenteral-fed animals received the same solution at an infusion rate determined by the volume ingested by the pair-fed enteral animals. All animals had central venous catheters. After 12 days, reticuloendothelial function was assessed by measuring the clearance rate (K) and the organ distribution of intravenous 51Cr-labeled sheep red blood cells and by plasma fibronectin levels. Nutritional status was assessed by body weight and nitrogen balance. K values in enteral and parenteral animals were similar (0.110 +/- 0.011 and 0.140 +/- 0.012, respectively, mean +/- SEM) as were plasma fibronectin levels (196 +/- 22 and 228 +/- 15 micrograms, respectively). Organ distribution of the 51Cr-labeled sheep red blood cells was the same in both groups. Nitrogen balance and body weights were also similar in both groups. These data demonstrate that in this experimental model enteral nutrition and parenteral nutrition were equally effective at maintaining reticuloendothelial function and nutritional status.

Animals

Solubilization of the iron molybdenum cofactor of Azotobacter vinelandii nitrogenase in dimethylformamide and acetonitrile.

The iron molybdenum cofactor of Azotobacter vinelandii nitrogenase has been solubilized for the first time in dimethylformamide and acetonitrile. These solutions have the ability to reconstitute the inactive nitrogenase of the UW 45 mutant of A. vinelandii and exhibit an S = 3/2 EPR signal similar to that for the cofactor in N-methylformamide. Our ability to obtain solutions of FeMoco in these solvents seemingly refutes a previous hypothesis concerning the necessity of solvents with a dissociable proton for iron molybdenum cofactor solubility and should facilitate the spectroscopic characterization of this important species.

Acetonitriles

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Accident Prevention

The effect of the route of nutrient delivery on gut structure and diamine oxidase levels.

Diamine oxidase (DAO) is an intestinal mucosal enzyme which serves as a marker of cellular maturity and integrity in ontogeny and after mucosal injury in the gastrointestinal tract. Since total parenteral nutrition is known to result in intestinal hypoplasia, this study was done to determine the effect of enteral and parenteral delivery of nutrients on gut structure and DAO levels. Central venous catheters were placed in 27 Sprague-Dawley rats (180-260 g), which received nutrients for 12 days via parenteral nutrition (GpI n = 10), oral intake of the parenteral solution (GpII n = 8), or standard rat chow (GpIII n = 9). Gross and microscopic measurements were made at sacrifice. Mucosal DAO levels were determined by metabolism of [3H] putrescine. Group III animals had a greater caloric intake than groups I and II, and were the only group with a significant increase in body weight. Gut weight, mucosal weight, and villous height were significantly less in group I vs groups II and III; group II values were less than group III (p less than 0.05). Both DAO specific activity and total gut DAO were significantly less in group I and group II. Mucosal DAO content correlated with total gut and mucosal weight. DAO mucosal levels decrease with parenteral nutrition, reflecting the intestinal hypoplasia that occurs. Mucosal DAO content may be dependent on both caloric intake and diet composition. Since serum DAO levels are known to correlate with mucosal DAO content, DAO activity may prove useful as a circulating marker of the effect of nutritional therapy on the intestinal mucosa.

Amine Oxidase (Copper-Containing)

Gastric compliance and motility in the portal hypertensive rat.

In an ex vivo rat model, we compared the intraluminal pressure response of both the whole stomach and the antrum to progressive intraluminal distension in portal hypertensive and sham-operated rats. In both groups, this response featured a biphasic change in tone with superimposed phasic pressure waves. While the tonic pressure response to distension (reflecting gastric compliance) was similar in both groups, the frequency and amplitude of antral phasic pressure waves (reflecting antral motility) were greater in the portal hypertensive animals. These studies indicate that portal hypertension does not alter gastric compliance but is associated with an exaggerated antral motor response to distension, suggesting that this latter mechanism, rather than impaired accommodation, may explain the accelerated gastric emptying described previously in the portal hypertensive rat.

Animals