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Biomedical subjects

J B Heneghan

Publications and source records attributed to J B Heneghan.

At least 19 recordsLinked to original sources

Jejunoileal bypass-induced liver dysfunction and bacterial translocation: effect of intraluminal glutamine-infusion.

We tested the effect of long-term intraluminal administration of glutamine on jejunoileal bypass (JIB) induced abnormalities in the plasma-liver profile in rats. Male Sprague Dawley rats (200-250 g) were subjected to an end to side JIB followed by daily intraluminal infusions of either 8 ml saline (n = 5), infused over a 4-hour period, or 8 ml saline containing 1g/Kg body weight glutamine (n = 7) for 3 weeks. Thirteen unoperated rats and four JIB rats without infusions served as controls. At the conclusion of the experiment, a cardiac blood sample was removed and analyzed for plasma cholesterol, albumin, total protein, gamma glutaril transferase, lactic dehydrogenase, glutamic-oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, and bilirubin. Tissue samples from various segments of bowel, liver, mesenteric lymph nodes, and spleen underwent histopathologic examination. Bacteriological cultures were prepared from jejunum, ileum, mesenteric lymph nodes, liver, and spleen. Bacterial translocation occurred in both JIB-saline and JIB-glutamine infused rats. Glutamine-infused rats developed a significant decrease in the plasma cholesterol levels. However, glutamine did not prevent the JIB-induced alterations in the plasma-liver profile and bowel histopathology. It is suggested that experimental JIB procedure can be used as a model of bacterial translocation consequent to mucosal permeability and intestinal inflammatory diseases.

Alanine Transaminase↗

Germfree animals and technics in surgical research.

Germfree animals have been reared to a size, weight, and age permitting the performance of major surgical procedures and the pursuit of a variety of surgical research problems. Germfree dogs have been maintained in the isolator system through three generations, indicating that life, reproduction, and growth are all possible in the absence of microbial contamination. The value of the germfree approach to surgical problems has been utilized in studies of a variety of gastrointestinal problems, shock, cancer, immunology, burns, wound healing, and in direct patient application. Patients have been maintained in isolator environments for prevention of infection, for operative procedures, for treatment of extensive burns, and for management of immune-suppressed individuals. We conclude that germfree animals and germfree technics provide a valuable addition to the armamentarium of the surgeon in both research and clinical applications.

Animals↗

A "treated" model for severe hemorrhagic shock: a comparison of conventional and germ-free animals.

In an unanesthetized "treated" model of severe hemorrhagic shock, a bacteremia originating from the animal's enteric flora was demonstrated by finding radiolabeled Escherichia coli in the blood as early as 2 hr after the onset of shock. In 50 patients admitted to our trauma unit, the observation was similar, with 56% positive blood cultures, when their mean arterial blood pressure was 80 mmHg or less. The relationship of bacterial translocation and the high post-shock mortality in our conventional (CV) animal model is being evaluated in germfree (GF) Sprague-Dawley rats. Preliminary observations in 15 GF animals showed 80% survival at 24 hr post-shock, 54% at 48 hr, and 42% at 72 hr compared with those of CV animals in previous experiments with survival at similar times of 73%, 20% and 7%, respectively.

Animals↗

Response of germfree animals to shock.

Many current models of septic shock in conventional (CV) rats utilize cecal ligation and perforation. That germfree (GF) status offered no increased protection in shock, compared with the effect on CV controls, was shown in early studies. Appropriate fluid therapy, however, did increase survival. Our laboratory's efforts to determine the influence of the GF rat's enlarged cecum on its early response to hemorrhagic shock can be summarized as follows. Ten litters of 8 GF rats each were randomly divided into four groups with two animals/group: CV control, GF control, CV cecectomized and GF cecectomized. Littermates were cecectomized at seven weeks and bled at 14 weeks. Under methoxyflurane anesthesia, the rats were cannulated (femoral artery), heparinized, restrained, and allowed to awaken. Blood pressure was maintained at 60 mmHg for 1 hr and at 50 mmHg for 3 hr by adjusting the height of a burette reservoir. In the GF cecectomized rats, 95% (19/20) survived, whereas only 50% (10/20) of the other three categories survived. Cecectomized GF rats required only 3% of their shed blood, whereas, the other three groups needed 10 to 15%. Cecum from the GF rat contains a 5-fold greater quantity of bioactive and vasoactive substances than the cecum of its CV control, and may cause these changes in basic cardiovascular parameters in GF control rats: decreased cardiac output, blood volume, heart weight, and vasoconstriction to epinephrine in mesenteric arterioles, plus increased hemoconcentration and blood viscosity. In cecectomised GF rats, these parameters return to the CV levels and help to protect the animal during the early hypovolemic trauma. Clearly, the rat's cecum produces significant cardiovascular effects that need to be considered when evaluating experimental models for trauma or stress.

Adaptation, Physiological↗

Does the bacteremia observed in hemorrhagic shock have clinical significance? A study in germ-free animals.

We have recently reported the rapid appearance of bacteria and endotoxin in the blood of rats and of trauma patients in the course of 30 minutes to 2 hours of hemorrhagic shock. The current study was designed to determine the effect of this bacteremia and endotoxemia on survival. Thirty-three conventional (C:group 1) and 36 germ-free (GF:group 2) Sprague Dawley rats were subjected to our previously described model of treated hemorrhagic shock. Survival in the GF group was significantly better than the C group at 24, 48, and 72 hours after shock. Endotoxin levels were elevated in 88% of C group during shock and in 28% of GF group. The gut of the GF animal contains endotoxin (26 ng/gm of stool) as does the sterile food supply (393 ng/gm of rat chow).

Animals↗

Glycosaminoglycan composition of germfree dog lungs.

Connective tissue of the lung is fundamentally important to pulmonary function. Exposure to foreign materials such as environmental toxins and microorganisms alters the connective tissue composition of pulmonary structures. In an effort to obtain information on the nature of complex carbohydrates in lungs unexposed to foreign materials, the composition of glycosaminoglycans from germfree dogs was studied. The total glycosaminoglycan concentration in germfree dog lungs was 47% greater than that in conventional dog lungs. Variations in individual glycosaminoglycan concentrations between germfree dog lungs and conventional dog lungs were noted. Heparan sulfate and heparin concentrations were lower in germfree dog lungs than in conventional dog lungs. Heparan sulfate fractions from germfree dog lungs had lower total sulfate content than heparan sulfate fractions from conventional dog lungs. The differences in glycosaminoglycan composition between germfree dog lungs and conventional dog lungs are likely due to exposure of conventional animals to a "normal" microbial flora and other environmental factors.

Animals↗

Intestinal obstruction in germ-free dogs.

Mechanical occlusions were created in the intestines of four germ-free dogs. At the time of the operation, a control loop of mid-intestine was perfused in vivo and then excised for examinations in vitro, which included the determination of the equilibrium uptake of phenylalanine and of beta-methyl-glucoside, the influx kinetics of phenylalanine and morphometric analysis of the mucosa by microdissection and stereological techniques. Seven days after establishment of the occlusion the abdomen was reopened, and loops above and below the occlusion were perfused, and then excised for the same tests in vitro. Unlike occluded loops of conventional dogs, the intestine of the germ-free animal above the occlusion does not secrete water and electrolytes into the lumen. Its transport properties in vitro do not differ from those of the control loop, and the morphometric analyses reveal only slight changes in villus structure. The loop below the obstruction undergoes marked atrophy, as has been observed in conventional dogs. The results suggest that the copious secretion that occurs above an intestinal obstruction in normal animals is due to the presence of an abundant bacterial population in the obstruction fluid.

Animals↗

Mast cell distribution in oral tissues of germ-free vs. conventional beagle dogs.

Light microscopic examination of the mast cell distribution in various oral tissues in germ-free and conventional beagle dogs revealed no differences between the two animals. Mast cells were observed in all tissues examined, with an increasing order of incidence as follows: cervical lymph node, parotid and submandibular glands, marginal gingivae, buccal mucosa and the middle one-third of the tongue. All four types (round, oval, elongated, and pseudopodial) of mast cells cell shapes previously described in the literature were observed. The marginal gingivae associated with the mandibular, second bicuspids was examined by light microscopy and was classified as to degree of inflammatory involvement. In a comparison of germ-free and conventional animals, the distribution of the degree of inflammation proved to be random. Correlation between mast cell densities and the degree of inflammatory infiltration was not statistically significant. However, mast cells tended to decrease as the inflammation became more severe. Electron microscopic examination of mast cells in the buccal mucosa revealed no difference in morphology of cells from germ-free or conventional animals. Cytoplasmic granules were of two basic types, one exhibited an amorphous matrix of uniform density and the other consisted of laminated coils of various sizes and densities.

Animals↗