Role of nitric oxide-related mechanisms in renal function in ageing rats

BACKGROUND: The impaired renal function and vasodilatation that accompany age need to be re-addressed based upon the new knowledge concerning vascular nitric oxide (NO)-dependent systems. The present study examined the effects of age on the NO-related renal response. METHODS: The study was performed in euvolaemic, conscious Wistar rats, aged 5 and 18 months. Renal function and haemodynamic measurements with fluorescent microspheres were employed to assess differences between groups. RESULTS: A first set of experiments showed that ageing rats had a reduced natriuretic and diuretic response to acetylcholine, whereas the response to sodium nitroprusside was preserved. In the same regard, a reduction of the renal functional effects of L-arginine (L-Arg) and L-glycine (L-Gly) was found in the older rats. In the ageing rats, these responses were accompanied by an enhanced effect of the L-Arg competitive analogue, NwNLA, which provoked a marked reduction of renal function. This effect of NwNLA was blocked by the simultaneous administration of a small dose of L-Arg in the ageing but not in the young rats. Systemic haemodynamic studies revealed that in ageing rats, NwNLA reduced renal blood flow and increased renal vascular resistances in a significantly higher proportion than in younger animals. However, flow to other organs, namely, brain, spleen or liver, was affected in a similar manner in both young and old rats. Ultrastructural alterations were found in endothelial cells, which might constitute the anatomical basis for the observed functional derangements. CONCLUSIONS: The present experiments reveal that ageing is accompanied by significant differences in NO-related responses in the kidney which do not appear to affect blood flow to other organs. The response to L-Arg and L-Arg competitive analogues supports the existence of a marked dependency on NO-related mechanisms in the ageing rats, but not of a decreased baseline activity of the NO-dependent pathways.     

Extracorporeal membrane oxygenator support for cardiopulmonary failure. Experience in 28 cases

We have used extracorporeal membrane oxygenation (ECMO) for 28 patients (14 children and 14 adults) over a 5 year period. Nine patients improved on ECMO and 5 were long-term survivors. ECMO was used for pulmonary insufficiency in 24 patients. Initially, only moribund patients were treated, but recently the combination of open lung biopsy and pulmonary insufficiency index (PII) has been used to select patients. The best results have been obtained in newborn cases and the adult capillary leak syndromes; the major problem has been progression to fibrosis despite ECMO support. ECMO was used for cardiac failure in 4 patients. Children with postoperative cardiac failure did the best; profound shock was not reversed with venoarterial bypass. ECMO support is lifesaving in selected cases of pulmonary insufficiency. Initial trials in cardiac failure and the infant age group in this series suggest that ECMO will have an even greater role in those applications.     

Antimicrobial prophylaxis for catheter-associated bacteriuria

We evaluated short-term systemic antimicrobial prophylaxis for catheter-associated bacteriuria in women undergoing elective gynecological operations in a prospective, controlled, double-masked study. Nine of 100 placebo-treated patients acquired bacteriuria during catheterization compared with 3 of 96 of the drug-treated group. However, at the time of hospital discharge, clean-voided urine specimens were positive as frequently in the drug-treated group (8 of 82 patients cultured) as in the placebo group (8 of 75 patients cultured). No difference in febrile morbidity due to bacteriuria was noted between the prophylaxis and placebo groups. The incidence of catheter-associated bacteriuria may be reduced by antimicrobial prophylaxis. However, because the protective effect is transient and is associated with the selection of resistant organisms, prophylaxis is not indicated for patients at low risk for acquired bacteriuria and in whom the sequelae of catheter-associated infections are infrequent.     

Study of in vivo tumor state and response to therapy by analysis of DNA distribution

Comparative studies of cefamandole and cephalothin were carried out in 32 cancer patients. After rapid intravenous injection of 1 gm cefamandole or cephalothin, the peak mean serum concentrations in 11 patients achieved at 0.25 hr were 103.4 mcg/ml and 56.7 mcg/ml, respectively. Except at 6 hr, the serum concentration of cefamandole was higher (p less than 0.05) at all times. The terminal half-lives (t 1/2) were similar, being 1.2 hr for cefamandole and 1.0 hr for cephalothin. Cefamandole, 1 gm intramuscularly, induced a peak mean serum concentration of 26.6 mcg/ml at 1 hr, with a slow decay. Intermittent cefamandole (2 gm intravenously every 6 hr) induced very high mean serum concentrations (7 patients), but at 4 hr the concentrations were similar to those after 1 gm intravenously. Per cent of urinary excretion was similar for both drugs regardless of dose and mode of administration. Continuous-infusion cefamandole or cephalothin (2 gm loading followed by 2 gm every 6 hr) in 14 patients showed consistently higher serum concentrations for cefamandole (p less than 0.05) over a 5-day period. There was no evidence of drug accumulation in the multiple-dose studies. Both the single- and multiple-dose schedules were well tolerated.     

Effect of carboxylic acids on permeation of chlorpromazine through dimethyl polysiloxane membrane

The effect of carboxylic acids on the permeation of chlorpromazine was investigated through a dimethyl polysiloxane nonpolar membrane. The permeability of the diffusate, at pH 5.8, increases considerably in the presence of carboxylic acids or phosphate, probably due to an ion-pair formation between the relative anions and chlorpromazine.     

The continent ileostomy and the isolated ileal bladder

To study the mechanism of action by which droperidol exerts a negative chronotropic effect, 3 series of experiments were performed: a) on isolated right atria of rabbits, b) on the isolated vas deferens of guinea-pigs and c) by injecting the drug directly into the sinus node artery of anesthetized dogs. Isolated tissue results include: lack of cholinergic action or beta-adrenergic antagonism: a calcium ion flux interference could not be demonstrated. Alpha adrenergic antagonism of the drug (pA2) was ascertained in the vas deferens. Injections of droperidol in the sinus node artery caused a negative chrontropic effect proportional to the dose and arrest ensued with the largest dose followed by His escape rhythm. Droperidol could not inhibit isoproterenol or dopamine-induced tachycardia and showed similar negative chronotropism in vagotomized and atropinized dogs. Negative chronotropic effects of the drug appear to be caused by an exit blockade of sinus impulses.     

A new method of treatment for mallet finger. A preliminary report

An infant with a typical Edwards syndrome and a modal chromosome number of 46 is reported. In all cells analyzed one chromosome G was missing and an additional chromosome similar to a pair No. 16 was present. The phenotype of the child indicates that the extra element is a translocation between G and 18 chromosomes as in one case described previously.