Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide.

The aim of this study was to determine if nitric oxide (NO) is the non-adrenergic, non-cholinergic neurotransmitter, released by enteric inhibitory nerves, which mediates relaxation of the human internal anal sphincter. Isolated muscle strips were mounted for isometric tension recording in superfusion organ baths. Sodium nitroprusside, an exogenous donor of NO, relaxed the strips in a concentration dependent manner. In the presence of atropine and guanethidine, transmural field stimulation produced tetrodotoxin sensitive relaxations, which were inhibited in a dose dependent and enantiomer specific manner by antagonists of NO synthase; completely by L-nitroarginine and partially by L-N-monomethyl arginine. The effect of these antagonists was reversed by L-arginine but not D-arginine. Oxyhaemoglobin, a scavenger of nitric oxide, also abolished the relaxations but methaemoglobin had no such effect. These results strongly suggest that NO is, or is very closely associated with, the non-adrenergic, non-cholinergic neurotransmitter mediating neurogenic relaxation of the human internal anal sphincter.     

The Association Between Serum Calcium Levels and Short-Term Mortality in Patients with Chronic Heart Failure

Background

Patients with chronic heart failure have vulnerable myocardial function and are susceptible to electrolyte disturbances. In these patients, diuretic treatment is frequently prescribed, though it is known to cause electrolyte disturbances. Therefore, we investigated the association between altered calcium homeostasis and the risk of all-cause mortality in chronic heart failure patients.

Role of Klebsiella pneumoniae Type 1 and Type 3 Fimbriae in Colonizing Silicone Tubes Implanted into the Bladders of Mice as a Model of Catheter-Associated Urinary Tract Infections

Catheter-associated urinary tract infections are biofilm-mediated infections that cause a significant economic and health burden in nosocomial environments. Using a newly developed murine model of this type of infection, we investigated the role of fimbriae in implant-associated urinary tract infections by the Gram-negative bacterium Klebsiella pneumoniae, which is a proficient biofilm former and a commonly isolated nosocomial pathogen. Studies have shown that type 1 and type 3 fimbriae are involved in attachment and biofilm formation in vitro, and these fimbrial types are suspected to be important virulence factors during infection. To test this hypothesis, the virulence of fimbrial mutants was assessed in independent challenges in which mouse bladders were inoculated with the wild type or a fimbrial mutant and in coinfection studies in which the wild type and fimbrial mutants were inoculated together to assess the results of a direct competition in the urinary tract. Using these experiments, we were able to show that both fimbrial types serve to enhance colonization and persistence. Additionally, a double mutant had an additive colonization defect under some conditions, indicating that both fimbrial types have unique roles in the attachment and persistence in the bladder and on the implant itself. All of these mutants were outcompeted by the wild type in coinfection experiments. Using these methods, we are able to show that type 1 and type 3 fimbriae are important colonization factors in the murine urinary tract when an implanted silicone tube is present.     

New abnormalities in the morphology, cell surface receptors, and electrolyte metabolism of In(Lu) erythrocytes

The In(Lu) phenotype is inherited as an autosomal dominant trait and is characterized by suppression of the Lutheran, P1, i, and Aua erythrocyte blood group antigens. We have developed a monoclonal antibody (L21) that strongly agglutinates all erythrocytes except In(Lu), and we have identified eight In(Lu) individuals among 42,000 blood donors tested. Studies of two families confirmed the dominant mode of inheritance and revealed several new features of this phenotype. The erythrocytes of all five affected individuals from the two families exhibited diminished hemagglutination by the lectin concanavalin A, although they reacted normally with several other lectins. The erythrocytes of two affected individuals in one family exhibited marked acanthocytosis. The erythrocytes of the proposita of the other family exhibited a mild degree of poikilocytosis, but the cells of the other two affected individuals in this family had normal morphology. The osmotic fragility of fresh In(Lu) erythrocytes was normal, but after incubation for 24 hours at 37 degrees C in plasma the In(Lu) cells exhibited a marked increase in resistance to osmotic lysis. During the incubation period the erythrocytes lost K+ and their total cation content was diminished. These data indicate that in addition to the suppression of blood group antigens noted previously, the In(Lu) phenotype includes a variety of morphological abnormalities and a defect in electrolyte metabolism. The use of L21 and similar monoclonal antibodies provides a more sensitive means of detecting In(Lu) erythrocytes than typing with human anti-Lub antisera.     

Endomyocardial biopsy with a modified bioptome introducer sheath: focus on diagnostic yield and prevention of complications

With a focus directed on the potential diagnostic yield of tissue biopsy in suspected myocardial disease, transvascular endomyocardial biopsies were carried out prospectively in 130 patients. In 149 out of 153 consecutive procedures, where the number of associated major complications was less than 1%, King's bioptome and a specially designed radiopaque long introducer catheter were used. The rather thickwalled sheath had a conical tip which facilitated percutaneous entry and a preshaped distal bending which was particularly useful in the right ventricle for obtaining a steady and safe position in the direction of the interventricular septum. With respect to the histopathological information from an average of 4.2 biopsies per patient, a high clinical yield was gained in 28% of the patients, in the form of specific diagnoses and/or findings influencing subsequent therapy, and useful diagnostic information was gleaned from a further 53%. Thus, the procedure appears safe as a part of routine cardiac catheterization, and biopsy may contribute to a more accurate and clinically relevant classification of a substantial number of patients with suspected myocardial disease.     

Effect of low-dose exogenous secretin and somatostatin on pentagastrin-stimulated gastric acid secretion in man

The inhibitory effect of intravenous infusion of secretin (0.05 CU kg-1h-1) and somatostatin (60 pmol kg-1h-1), given alone or in combination, on pentagastrin-stimulated (100 ng kg-1 h-1) acid secretion was studied in 10 healthy subjects. Secretin inhibited acid secretion by 54% (p less than 0.05), and somatostatin inhibited by 70% (p less than 0.05). The combined infusion of secretin and somatostatin decreased acid output by 64% (p less than 0.05). The differences between the three groups were not significant (p greater than 0.05). Median plasma concentrations of secretin and somatostatin were of the same magnitude as seen after duodenal acidification. The present study did not demonstrate any interaction between secretin and somatostatin in the inhibition of gastric acid secretion.