Glycine-induced hyponatremia in the rat: a model of post-prostatectomy syndrome.

Post-prostatectomy syndrome (PPS) is characterized by hyponatremia after absorption of glycine irrigant. To study the pathogenesis of this syndrome, adult male rats with ligated ureters were infused over 15 minutes with 7.5 ml/100 g body weight of isosmotic glycine (N = 9) or mannitol (N = 9) and were compared to non-infused, ureter-ligated controls (N = 9). Immediately post-infusion, plasma sodium had decreased similarly in glycine- and mannitol-infused animals (111 +/- 2 vs. 106 +/- 1 mmol/liter), but plasma osmolality remained at control levels in both groups (285 +/- 1 vs. 288 +/- 1 mOsm/kg). Two hours post-infusion, hyponatremia was stable in the mannitol group (108 +/- 1 mmol/liter), but in the glycine group plasma sodium increased significantly (to 120 +/- 1 mmol/liter). Plasma osmolality two hours post-infusion was maintained in both the glycine (287 +/- 2) and mannitol (292 +/- 2) groups. Brain water in glycine-infused animals (3.90 +/- 0.01 liter/kg dry wt) was not significantly different from the mannitol-infused group (3.85 +/- 0.01) and only 1.8% higher than non-infused controls (3.83 +/- 0.02). Brain tissue glycine did not differ between the three groups. In contrast, muscle water two hours post-infusion in the glycine group was 6% higher than mannitol-infused and 13% higher than non-infused animals. Muscle glycine content in the glycine group (67 +/- 4 mM/kg dry tissue) was increased when compared to both mannitol-infused (25 +/- 1) and non-infused (20 +/- 1) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical application of otoacoustic emissions: what do we know about factors influencing measurement and analysis?

Three electrophysiologic audiologic procedures-aural immittance measurement, auditory brainstem response (ABR), and otoacoustic emissions (OAE)- were first described in the 1970's. Immittance measurement and ABR have contributed importantly for years to the assessment of auditory function in children and adults, whereas OAEs have not yet been incorporated into the everyday audiology test battery. In this article, we argue that the transition from OAE measurement by hearing scientists in laboratory settings to routine application by audiologists in the clinic will be greatly facilitated by (1) comprehensive, large-scale studies of the effects of subject characteristics, such as gender and age (from infancy to advancing adulthood), on both transient evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions; (2) clinical investigations of TEOAE and DPOAE in sizeable patient populations with specific neurotologic diagnoses; (3) guidelines for OAE test protocols in clinical environments; and (4) clear criteria for OAE analysis in clinical populations.

Dynamic sensorineural hearing loss: implications for audiologists: case reports.

Although many persons with sensorineural hearing loss (SNHL) seeking hearing care do not have active ear disease, audiologists must appreciate the potentially dynamic and treatable nature of some etiologies of SNHL. This is particularly important now as audiologists are increasingly employed in private practice or other clinical settings that may serve as the point of entry for hearing care. In this paper, we review a variety of clinical entities affecting newborn infants, children, and adults that are associated with dynamic SNHL. Using a case report format, we illustrate treatment-related changes in SNHL, emphasizing the audiologist's role in patient management.

Drug-induced modifications of the immune response. 12. 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids and derivatives as novel antiallergic agents.

The synthesis of a series of novel 4,5-dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids, salts, esters, and amides is described. The title compounds when tested in the mediator-induced dermal vascular permeability and active anaphylaxis assays in rats demonstrated moderate to potent antiallergic activity. The [2-trans-(4-methylphenyl)cyclopropyl]amino analogue 53 emerged as the most active derivative. Thus, when administered intraperitoneally to rats at a dose of 100 mg/kg, it inhibited the action of the mediators serotonin, histamine, and bradykinin by 100%. In the active anaphylaxis assay in rats, compound 30 suppressed the edema by 81% at a dose of 100 mg/kg, following intraperitoneal administration.

Ovary volume in young and premenopausal adults: US determination. Work in progress.

Normal adult ovary volume determined by ultrasonography (US) is often stated to be less than 6 cm3. This is based on data from teenagers and young adults aged 12-20 years. Recently, the mean normal volume determined by US was reported to be considerably higher. We measured the volumes of 28 ovaries from 15 healthy young adults and found them to range as high as 13.84 cm3, with an average of 6.48 cm3.

2-(Aminomethyl)phenols, a new class of saluretic agents. 4. Effects of oxygen and/or nitrogen substitution.

A series of oxygen and/or nitrogen substituted 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to demonstrate diuretic responses, or lack thereof, in a second species. In general, substitution on nitrogen with groups other than lower alkyl or substitution on nitrogen and/or oxygen with groups resistant to hydrolysis substantially diminished or ablated saluretic effects.

2-(Aminomethyl)phenols, a new class of saluretic agents. 3. Effects of functional group reorientation and modification.

A series of modified 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to show that the diuretic responses, or lack thereof, may be obtained in a second species. Reorientation of the 2-(aminomethyl) group either meta or para to the hydroxyl substituent resulted in loss of diuretic effects. Similarly, replacement of either the phenolic hydroxyl or the aminomethyl group with other functional moieties substantially diminished saluretic effects.

2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution.

A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.

Diflunisal renal clearance in anesthetized dogs: effect of probenecid, urine flow, and urine pH.

Using conventional clearance technique, the net renal clearance of diflunisal is very low, about 1% of glomerular filtration rate. Although net renal secretion is not demonstrable, probenecid significantly decreased renal clearance of the drug. Also, the renal clearance was increased by increases in urine flow or urinary pH. However, in contrast to acetylsalicylic acid, these effects would be expected to be minor, on the one hand to conserve drug or on the other hand in facilitating drug elimination in cases of overdosage.

Cambendazole and nondrug macromolecules in tissue residues.

The anthelmintic cambendazole is rapidly metabolized to at least 13 urinary metabolites. Radioactivity was found in liver for weeks after a single dose in cattle, but even at 3 days' withdrawal, cambendazole and metabolites previously identified in urine accounted for only a small fraction of liver radioactivity. The radioactivity was ubiquitously distributed in protein and nucleic acid fractions, and [14C] glutamic acid was identified, indicating incorporation of 14C into the endogenous pool. Part of the residual liver radioactivity at 7 days was convertible chemically to 5-nitrobenzimidazole, indicating a drug-related macromolecular residue. However, data from rats fed radiolabeled steer liver indicate that the residue is minimally bioavailable and therefore of substantially less toxicological concern than cambendazole itself.

Pharmacokinetics of methyldopa in man.

Single doses of methyldopa were administered orally and intravenously as aqueous solutions to 12 healthy volunteers in a crossover study. Serial plasma and urine samples were analyzed specifically for methyldopa and its O-sulfate conjugate. Kinetic analyses of the results indicated that methyldopa disposition could be adequately represented by a two-compartment open model. Renal excretion accounted for about two-thirds of the plasma clearance of methylodopa. Absorption profiles were constructed with the aid of the pharmacokinetic model and contrasted with estimates of absorption which were model-independent. The mean fraction reaching the systemic circulation as methyldopa was estimated to be 0.25 (range 0.08-0.62 for n = 11). Although most of the absorption occurred within the first 5 hours oral administration, a minor component, suggestive of limited enterohepatic circulation, persisted from 9 to 36 hours. O-sulfate conjugation was route-dependent and appeared to be derived predominantly, if not exclusively, as a first-pass effect of absorption and/or enterophepatic circulation.

3,5-disubstituted 1,2,3,4-triazoles, 1 new class of xanthine oxidase inhibitor.

3,5-Bis(4-pyridyl)-1,2,4-triazole (PPT), 3-(4-pyrimidinyl)-5-(4-pyridyl)-1,2,4-triazole (PMPT), and 3-(4-pyridazinyl)-5-(4-pyridyl)-1,2,4-triazole (PZPT) are among the most active competitive inhibitors of xanthine oxidase among a series of 3,5-disubstituted triazoles synthesized for this purpose, inhibition constants being less than 1 times 10(-7) M for each. ED50 values in squirrel monkeys derived from first-order rate constants for the first and rate-limiting step of the sequence, xanthine leads to uric acid leads to allantoin plus CO2, range from 0.04 to 0.08 mg kg-1 orally, with unusually long durations of action attributable to asymmetric distribution of inhibitor within liver and gut as a consequence of enterohepatic recirculation. Sensitivity of rats, dogs, and anthropoid species to these, as to other xanthine oxidase inhibitors, is markedly less than that of the squirrel monkey, but the triazoles are at least an order of magnitude more active than the representative purine analogs tested.