Comparison of loop diuretics in patients with chronic renal insufficiency

Furosemide and bumetanide share a number of characteristics including reduced natriuretic effects in azotemic patients. It has been presumed that this condition affects each drug equally. Previous studies, however, suggest dissimilar pathways of delivery to their sites of action. Though not rigorously tested, this potential disparity might cause them to differ when used in azotemia. We, therefore, assessed the pharmacokinetic and pharmacodynamic characteristics of intravenously administered furosemide and bumetanide in ten adult patients with stable, chronic renal insufficiency (mean creatinine clearance = 14.1 +/- 2.0 ml/min/1.73 m2) in a randomized, cross-over study during controlled sodium intake. Our goals were to assess differences in diuretic effectiveness and in so doing to determine the dose required to produce a maximal response. The mean diuretic doses of 172 and 4.3 mg for furosemide and bumetanide, respectively (ratio = 40:1) were sufficient to produce a maximum response. Despite similarities in maximal fractional excretion of sodium (18.2 +/- 2.6% with furosemide vs. 19.4 +/- 4.5% with bumetanide, P = 0.687) demonstrating an equal tubular responsiveness to both drugs, overall response as quantified by cumulative natriuresis in the initial eight hour period was 52% greater with furosemide (108 +/- 17 vs. 71 +/- 7 mEq; P = 0.042). The difference in total excreted sodium was accounted for by a preserved nonrenal clearance of bumetanide (113 +/- 12 compared to 53 +/- 5 ml/min for furosemide, P = 0.001) which resulted in relatively less bumetanide in serum available to be delivered into the urine.(ABSTRACT TRUNCATED AT 250 WORDS)     

The management of preexcitation syndromes

The introduction of new techniques such as epicardial mapping and programmed stimulation of the heart has made it possible to unravel most of the mysteries surrounding ventricular preexcitation. They helped us to understand the mechanisms of the arrhythmias that frequently are found in these patients and led to better-directed therapeutic interventions. The purpose of this article is to review this information and to indicate how it can be used in the treatment of the patient with preexcitation.     

Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure

Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.     

Single-antibiotic use for penetrating abdominal trauma

A prospective randomized study compared the use of moxalactam disodium vs clindamycin phosphate and tobramycin sulfate for treatment of 190 patients with penetrating abdominal trauma. Twenty-seven patients were disqualified because of early death or failure to follow the protocol. The patients in each group were comparable regarding the cause and severity of injury. No significant difference was seen in the incidence of intra-abdominal infection between the moxalactam-treated group (13%) and the clindamycin- and tobramycin-treated group (9%). The intra-abdominal infection rate in patients with colon injuries (21%) was significantly increased when compared with the patients without colon injuries (6%), but the antibiotic regimen did not significantly change the infection rate. No evidence of bleeding problems from moxalactam were noted. Changes in prothrombin and partial thromboplastin times appeared to be related to shock rather than the use of moxalactam. The most severe coagulopathies occurred prior to moxalactam therapy and were seen only in those patients who had shock requiring 10 or more units of blood. Moxalactam is as effective as combination (clindamycin and tobramycin) antimicrobial therapy in patients with penetrating abdominal trauma.     

Innervation of the child urinary bladder

Muscle strips from the fundus, trigonum and distal ureters obtained from children at operations for vesico-ureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and despite a partial atropine resistance the neurophysiological experiments indicated that the transmitter causing contraction of the detrusor muscle is acetylcholine. Imipramine, which is used in the treatment of enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The adrenergic innervation was very sparse except around the ureter orifices. No contractile alpha-adrenoceptors could be detected but beta receptor mediated relaxation was found, which was neither of the beta 1 nor beta 2 type. A third type of beta receptor is postulated. Peptidergic nerves containing vasoactive intestinal peptide, VIP, were demonstrated in a few nerve terminals running along bundles of smooth muscle. No nerves containing enkephaline, somatostatine or substance P were found. VIP affected the detrusor muscle indicating a possible role as a modulator of transmitter action, while substance P had no effect. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, whether it was induced by nerve stimulation, cholinergic drugs or a potassium rich solution, making it suitable for treatment of diurnal enuresis.     

The presence and vector role of Culex bitaeniorhynchus in New Caledonia

Culex bitaeniorhynchus, reported from New Caledonia after a single collection of larvae in Noumea in 1952, has been found in two other localities, on the south-west and on the north-east coasts. The morphological features show some differences between the local population and the forms from the Oriental Region. Adults have been caught during the hot and rainy season, by light traps mainly. The females have been very rarely collected on human bait. Though found naturally infected by dengue 4 virus, that species is not likely to have an epidemiological importance in New Caledonia. It seems doubtful that it has been imported recently.     

The proliferative T-lymphocyte response to streptokinase

Purified streptokinase was found to initiate a proliferative T-lymphocyte response. The response was characterized by dose-response and kinetics investigations. Streptokinase did not initiate any response when tested on T lymphocytes from newborns, thus indicating that the proliferative T-lymphocyte response to streptokinase in vitro is an antigen stimulated activation of T lymphocytes from individuals previously sensitized in vivo. Of healthy individuals, 40% (16 out of 40 tested) showed a significant proliferative response to streptokinase. Methylprednisolone, cyclosporin A, theophyllamine and verapamil all inhibited the streptokinase-stimulated proliferative T-lymphocyte responses in a dose-dependent manner.