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Biomedical subjects

R M Levin

Publications and source records attributed to R M Levin.

At least 289 records · Page 16Linked to original sources

The effects of heparin on the adherence of five species of urinary tract pathogens to urinary bladder mucosa.

Previous studies performed in our laboratory have indicated that the primary antibacterial defense mechanism of the rabbit urinary bladder is the antiadsorptive action of the surface mucopolysaccharide. Removal of this layer with an acid rinse increases bacterial adherence up to 100 fold. Exogenous mucopolysaccharide (heparin) has been shown to restore Escherichia coli adherence to control levels. To determine whether this antiadherence action of heparin is species specific, we compared the adherence of 5 common urinary tract pathogens (Escherichia coli, Klebsiella ozonae, Proteus mirabilis, Pseudomonas aeruginosa, and Streptococcus fecalis) to both mucin intact and mucin deficient rabbit bladders with and without prior heparin exposure. Bacteria were radiolabeled by addition of 3H-adenine to the culture broth so that the number of bacteria adhering to the bladder could be determined using liquid scintillation spectrophotometry. Results were as follows: Acid removal of the mucin layer significantly increased the adherence approximately 10 fold for all 5 species tested. Briefly exposing the mucin deficient bladders to heparin decreased the adherence of all species tested except Pseudomonas to mucin intact control levels. Heparin treatment of mucin intact bladders slightly decreased adherence of all species except Pseudomonas below mucin intact controls, however, results were not statistically significant. The magnitude of Klebsiella adherence was nearly 20 fold greater than all other species tested. While this non-species specific adherence inhibition of heparin may prove useful in the clinical setting, it appears to be less effective against Pseudomonas.

Animals↗

The effect of short-term obstruction on urinary bladder function in the rabbit.

The effect of short term partial obstruction on urinary bladder function was studied in rabbits. After 1 week of partial bladder obstruction, the bladders were significantly hypertrophied with a mass over 9 times that of control bladders. The obstruction resulted in a marked decrease in both intracellular ATP and muscarinic receptor density. In vitro response of isolated smooth muscle strips from the obstructed bladder body to cholinergic stimulation was only 50 per cent of the response of control bladders. The obstructed bladder was able to expel only 28 per cent of its volume whereas control bladders expelled 100 per cent of their volume. The results of these studies demonstrate the rapid nature of the response of the bladder to chronic obstruction. Within 1 week frank hypertrophy and significant defects in the contractile ability of the bladder were evident.

Adenosine Triphosphate↗

Analysis of the anticholinergic and musculotropic effects of desmethylimipramine on the rabbit urinary bladder.

The anticholinergic and musculotropic relaxant properties of desmethylimipramine (DMI) on smooth muscle were investigated utilizing cholinergic radioligand receptor binding and in-vitro muscle bath techniques. Receptor binding studies revealed the direct antimuscarinic potency of DMI to be 1/480th that of atropine. Muscle bath studies characterized discrete antimuscarinic and musculotropic actions. An initial, competitive antimuscarinic action could be separated from a delayed onset, noncompetitive musculotropic action by altering the time between the addition of DMI and the addition of bethanechol to the smooth muscle bath.

Animals↗

The contractile and metabolic effects of acute ischemia on the rabbit urinary bladder.

The present study determined the effect of 1 hour of in vivo ischemia on the response of the rabbit urinary bladder to specific autonomic agonists and on the intracellular adenosine triphosphate content. A 48 per cent decrease in the contractile response of the base to the alpha agonist methoxamine was noted. A 42 per cent decrease in the response of the bladder body to bethanechol was found. Neither tissue improved significantly after a 1-week recovery period. Ischemia caused an immediate 80 per cent decrease in the intracellular adenosine triphosphate content that improved to 50 per cent of control with a 1-week recovery period. Although the site of the defect is not definitely identified, acute ischemia resulted in a decreased contractile response that could result in bladder dysfunction.

Adenosine Triphosphate↗

Comparative pharmacological response of an in vitro whole bladder preparation (rabbit) with response of isolated smooth muscle strips.

Although much of our knowledge of the pharmacological response of the urinary bladder comes from in vitro muscle strip studies, it is not clear if these studies can be directly correlated with bladder function. We have compared the pharmacological response of an in vitro whole bladder model with the response of the standard muscle strip technique. The whole bladder model has the advantage of being able to measure both the isometric contractile response to drugs as well as a functional response in which the bladder can empty in the presence of a constant resistance. The results of these studies may be summarized as follows: 1) bethanechol was equipotent in contracting the muscle strips and in the closed whole bladder model; 2) at low and intermediate bladder volumes, the bladder fully emptied at concentrations of bethanechol significantly below the concentration required for maximal contraction; 3) isoproterenol, a potent beta-adrenergic agonist, stimulated a strong relaxation in muscle strips, whereas the whole bladder responded very poorly to isoproterenol; 4) in muscle strips isoproterenol strongly antagonized bethanechol contraction, whereas, in the whole bladder system, isoproterenol did not significantly antagonize bethanechol contraction; 5) methoxamine and adenosine triphosphate produced a moderate, equipotent contraction in both models.

Adenosine Triphosphate↗

Percutaneous ultrasonic lithotripsy: choice of irrigant.

Extravasation of glycine irrigant during percutaneous ultrasonic lithotripsy has caused a transurethral resection syndrome consisting of hypertension, confusion and hyponatremia. With a rabbit model this complication is recreated with the intraperitoneal instillation of 1.5 per cent glycine solution tagged with 14carbon-glycine. Significant quantitative absorption of glycine into blood and other organs is demonstrated. A review of the literature reveals few guidelines as to the choice of irrigant for intrarenal endoscopy. Since this procedure involves no electric current it is suggested that physiological saline rather than glycine be used for ultrasonic stone disintegration.

Animals↗

Intestinal parasites in immigrant children from Central America.

To begin to characterize the health needs of the growing number of refugees from Central America, we compiled the results of examinations for ova and parasites of a single stool specimen of each of 128 children of Central American and Mexican background who entered our health center during a four-month period. Among the 96 children who were born in Central America or Mexico, there was a 65% prevalence of parasitic infestation. Pathogens were found in 46% and multiple pathogens in 14%. Among the 32 American-born children there was a 13% prevalence of parasitic infection, but no pathogens were found. There was no correlation between symptoms and the presence of parasites. Screening Central American immigrant children for intestinal parasites is a high-yield procedure and should be part of their routine health care.

Adolescent↗

Penicillin-resistant Streptococcus constellatus as a cause of endocarditis.

Endocarditis in a 2-year-old child was caused by a penicillin-resistant Streptococcus constellatus. Viridans streptococci in general and those associated with endocarditis in particular are usually believed to be penicillin sensitive. Although the patient did not receive prophylactic antibiotics, the child had recently been treated with an oral penicillin. Penicillin-resistant viridans streptococci are usually sensitive to the synergistic effects of penicillin and an aminoglycoside, but this organism was not. Clindamycin was ultimately shown to demonstrate admirable bactericidal activity against this patient's S constellatus.

Clindamycin↗

Metabolic and contractile effects of anoxia on the rabbit urinary bladder.

The in vitro metabolic and contractile effects of anoxia and glucose deprivation on the rabbit urinary bladder were studied. The exposure of isolated strips of rabbit urinary bladder to a glucose deficient medium equilibrated with nitrogen rather than with oxygen resulted in 1) a rapid decrease in baseline tension, 2) a progressive decrease in the intracellular concentration of adenosine 5'-triphosphate (ATP) and progressive increases in the concentrations of adenosine 5'-monophosphate and adenosine 5'-diphosphate, 3) a rapid decrease in the ability of bethanechol to stimulate contractility, and 4) the inability of bethanechol to maintain a sustained increase in contractile force. Recovery from a 60-minute exposure of bladder strips to anoxia was characterized by a rapid recovery of the ability of the bladder to respond to bethanechol (50 per cent recovery occurring within 15 minutes) and a slightly slower recovery of the intracellular ATP level. Both the contractile response to bethanechol and the intracellular concentration of ATP returned to control levels within 60 minutes after the termination of anoxia.

Adenosine Diphosphate↗

Direct measurement of the anticholinergic activity of a series of pharmacological compounds on the canine and rabbit urinary bladder.

Antimuscarinic therapy is used widely in the treatment of urine storage failure. Examples of antimuscarinic agents used clinically include atropine, propantheline bromide and glycopyrrolate. Other agents used in clinical urology that are believed to act at least in part by antimuscarinic activity include oxybutynin, imipramine and dicyclomine, These studies were designed to determine the relative potency of a variety of agents to compete directly for muscarinic cholinergic receptors isolated from the canine and rabbit urinary bladder. Radio-ligand binding assays for muscarinic receptors were performed with 10 nM 3H-QNB and various concentrations of the drugs under study. Of the agents tested, propantheline bromide, atropine, and glycopyrrolate were the potent muscarinic antagonists/unit of concentration. Oxybutynin and dicyclomine hydrochloride were 30 to 50 times less potent than atropine. Chlorpromazine and desmethylimipramine were approximately 500 times less potent than atropine. As expected, agents such as guanethidine, tranylcypramine and hexamethonium possessed little antimuscarinic activity.

Animals↗

Phosphodiesterase activity of the lower urinary tract.

Cyclic AMP is believed to mediate the physiologic response of beta-receptor stimulation in the lower urinary tract. A possible novel therapy for specific dysfunctions might be via pharmacologic modification of cyclic AMP through regulation of phosphodiesterase, the enzyme responsible for metabolizing cyclic AMP. The present study characterizes the phosphodiesterase activity present in various sections of the lower urinary tract and determines the effect of calmodulin and the potency of a series of phosphodiesterase inhibitors. The results can be summarized as follows: the phosphodiesterase activity of all smooth muscle sections of the lower urinary tract were similar. They showed nonlinear kinetics with Vmax between 1.0 and 2.4 nmol./mg. protein/minute and apparent Km's around 100 microM. The external sphincter (skeletal muscle) displayed linear kinetics with a Vmax of 0.2 nmol./mg. protein/minute and a Km of 9 microM. Of the drugs tested, papaverine was the most potent inhibitor and theophylline was one of the weakest inhibitors. These studies also indicate that the major form of cyclic AMP phosphodiesterase is not sensitive to calmodulin.

Animals↗

Response of the in vitro whole bladder (rabbit) preparation to autonomic agonists.

Using an in vitro whole bladder preparation (rabbit), we studied both the volume-pressure relationship and the response of the bladder to specific autonomic agonists. We determined the response in: 1) an isovolumetric system in which the intravesical pressure was monitored in the absence of volume changes; 2) a system in which volume alterations were monitored in the presence of increasing pressure; and 3) a system in which the bladder emptied in the presence of a constant pressure. The results of these studies demonstrated: 1) volume-pressure studies generated a typical cystometric curve; 2) bethanechol produced a dose-dependent increase in intravesical pressure (decrease in bladder volume); 3) the whole bladder responded very poorly to isoproterenol; and 4) methoxamine and ATP both produced a modest increase in intravesical pressure. One advantage of the "whole bladder" in vitro preparation is that it can objectively measure a functional response of the bladder to pharmacological agents.

Adenosine Triphosphate↗

Susceptibility of Haemophilus influenzae type b to cefaclor and influence of inoculum size.

Cefaclor appeared to be an effective antibiotic against both beta-lactamase-positive and beta-lactamase-negative strains of Haemophilus influenzae type b when tested with 10(5) colony-forming units per ml. With inocula in excess of 10(6) colony-forming units per ml, these organisms were neither inhibited nor killed at concentrations of 400 micrograms/ml. This inoculum effect was also demonstrated in time-kill curve studies.

Cefaclor↗

Management of Candida peritonitis with intravenous amphotericin: Peritoneal fluid antibiotic levels.

The child presented in this report received intravenous amphotericin B 0.5 mg/kg every 36 hours, for dialysis-associated Candida peritonitis. Just prior to her third dose of amphotericin B, the peritoneal fluid concentration of this drug was 0.1 mcg/ml, and the simultaneous serum level was 0.2 mcg/ml. An hour following the third amphotericin B dose, the peritoneal fluid and serum concentrations were 0.2 and 0.4 mcg/ml respectively. The minimal inhibitory concentration (MIC) of amphotericin B for the C. albicans isolated from this patient was 0.05 mcg/ml, and the minimal lethal concentration (MLC) was 0.1 mcg/ml. Treatment included concurrent 5-fluorocytosine, and catheter removal. This is the first time that measurements of concentrations of amphotericin B in the peritoneal fluid have been reported in a child with peritonitis.

Amphotericin B↗

Effect of vasoactive intestinal peptide on the contractility of the rabbit urinary bladder.

Vasoactive intestinal peptide (V. I. P.) has been demonstrated in neuronal elements of smooth muscle organs including the urinary bladder, thus indicating that this peptide may be a neurohumoral transmitter. In isolated strips of rabbit urinary bladder we have demonstrated that V. I. P. causes relaxation. Unlike the relaxant effect of the beta agonist isoproterenol, the inhibition produced by V. I. P. could not be blocked by propranolol. These studies indicate that V. I. P. may play a role in the regulation of bladder contractility.U

Animals↗

Autonomic innervation of rabbit urinary bladder following estrogen administration.

The effects of estrogen administration on the autonomic innervation of the rabbit urinary bladder were studied. Immature female white rabbits were injected twice daily with estrogen (150 microgram./Kg.) for four consecutive days. Control animals received injections of vehicle alone. The adrenergic innervation was identified using the glyoxalic acid method of catecholamine histofluorescence. The cholinergic innervation was visualized utilizing specific acetylcholinesterase staining. Additionally, the effect of estrogen administration on the response of smooth muscle strips of urinary bladder to specific autonomic agonists was determined. Estrogen administration induced a moderate increase in the adrenergic innervation of the rabbit bladder detrusor, whereas no change could be observed in the cholinergic innervation. It should be noted, however, that whereas the adrenergic innervation in the bladder of the control animal was sparse, the cholinergic innervation in the bladder body was quite dense. Estrogen induced a marked increase in the response to alpha-adrenergic (methoxamine) and muscarinic cholinergic (bethanechol) agonists. No alterations were noted in the response to beta-adrenergic agonists (isoproterenol). These findings indicate that the urinary bladder responds as a target organ for estrogen-induced alterations in autonomic innervation.

Animals↗