Effect of probenecid on dyphylline elimination.

Dyphylline is a methylxanthine bronchodilator with such a short a biologic t 1/2 that development of practical dosing regimens has been difficult. Because its rapid renal elimination suggests active secretion, the effect of 1 gm probenecid on single-dose elimination kinetics of dyphylline was determined. Twelve subjects (six male, six female) participated in a crossover design. Subjects were their own controls and received dyphylline, 20 mg/kg orally, alone and after probenecid. The dyphylline t 1/2 increased from 2.57 +/- 0.45 to 4.88 +/- 1.2 hr, whereas the elimination rate constant decreased from 0.276 +/- 0.056 to 0.150 +/- 0.037 hr-1 after probenecid. There was no significant change in the dyphylline apparent volume of distribution. Dyphylline total body clearance fell from 173 +/- 20 to 95 +/- 12 ml/kg . hr. The combined use of these drugs may lead to a practical dyphylline dosage schedule in aminophylline-hypersensitive patients or those incapacitated by theophylline gastrointestinal side effects.

Effects of cimetidine on caffeine disposition in smokers and nonsmokers.

The absorption, distribution, and elimination of caffeine, 2 mg/kg by mouth, were evaluated in six smokers and six nonsmokers before and on the fourth day of administration of cimetidine, 300 mg by mouth every 6 hr. Caffeine absorption, assessed by the maximal serum caffeine concentration (C max) and the time to reach Cmax (t max), was very rapid relative to elimination. The total body clearance (TBC) of caffeine was higher (2.49 +/- 0.35 and 1.59 +/- 0.19 ml/kg/min, P less than 0.05) and the elimination half-life (t1/2) shorter (190 +/- 15 and 276 +/- 30 min, P less than 0.05) in smokers than nonsmokers, but Cmax, tmax, and the apparent volume of distribution (Vd, app) did not differ (P greater than 0.05). Cimetidine decreased the TBC of caffeine by 31% (to 1.73 +/- 0.28 ml/kg/min, P less than 0.05) and by 42% (to 0.92 +/- 0.11 ml/kg/min, P less than 0.01) in smokers and nonsmokers. The increases in t1/2 were 45% (to 276 +/- 25 min, P less than 0.05) and 96% (to 542 +/- 123 min, P less than 0.05). Cmax, tmax, and Vd, app were unaffected by cimetidine. Caffeine induced similar slight increases in blood pressure and pulse rate in smokers and nonsmokers both before and during cimetidine dosing.

The effects of erythromycin on theophylline elimination in normal males.

The effects of three erythromycin preparations on theophylline elimination kinetics were examined in 23 male subjects. Subjects received 6 mg/kg of the theophylline elixir orally and elimination kinetics were determined. The population was then randomized to receive either a lactose placebo, erythromycin base, erythromycin stearate, or erythromycin ethylsuccinate. Each 250-mg preparation was given four times a day for six days. On day seven, a repeat kinetic study was performed. The mean theophylline half-life of controls was 7.8 +/- 2.6 hours. The half-life increased significantly in all erythromycin treatment groups. The increase for the base, stearate, and ethylsuccinate groups was 51.7, 21.3, and 60.3 per cent, respectively. The total body theophylline clearance decreased significantly in all treatment groups. This was not associated with biochemical evidence of hepatitis. Three of four smokers who received erythromycin manifested no increase in theophylline half-life, in contrast to one of 13 nonsmokers. There was no difference in the percentage theophylline bound to serum protein for any of the erythromycin treatment groups or controls as determined by ultracentrifugation.

Acute synovitis caused by an organism of the Rhodochrous taxon.

A 36-year-old man with systemic lupus erythematosus developed synovitis of the right wrist caused by an organism of the Rhodochrous taxon. The capacity of this pathogen to produce a granulomatous inflammatory reaction in human tissues is discussed. The isolate was sensitive to chloramphenicol, gentamicin, carbenicillin and colistin in in-vitro tests and the infection responded promptly to treatment with chloramphenicol.

A report of occupational deaths attributed to fluorocarbon-113.

This study reports two occupational deaths resulting from exposure to fluorocarbon-113 (1,1,2-trichloro-1,2,2-trifluoroethane; FC-113) in enclosed and confined spaces. One incident involved a worker who was exposed to FC-113 after entering a small degreasing tank to clean it. The second case involved a significant spill of FC-113 onboard a marine vessel. The incidents are compared to other fatal exposures.

Research on effects of color reversal on the visual perceptual and visuomotor performances of spastic cerebral palsied and other exceptional individuals.

Research pertaining to the effects of color-reversal (black and white) on the visual perceptual and visuomotor performances of spastic cerebral-palsied children and other exceptional individuals was examined. In general, evidence to date suggests that spastic cerebral-palsied children show significant improvement in visuomotor and visual perceptual performance with the color-reversal of the standard black-on-white figure-ground relationship in stimulus and response materials of standardized tests.

Effects of figure-ground reversal on the visual-perceptual and visuo-motor performances of cerebral palsied and normal children.

Individuals with brain damage often encounter visual perceptual and visuo-motor difficulties. Studies have indicated an improvement in exceptional individuals' performances when the colors of figure-ground materials were reversed. Effects of reversals were studied for spastic cerebral palsied and normal children's scores on the Developmental Test of Visual-motor Integration and the Motor-free Visual Perception Test. Normal children performed better than the cerebral palsied children on all tests; the cerebral palsied children performed best on the reversed-format Motor-free Visual Perception Test. Reversal affected neither group's scores on visual-motor integration.

Acute carbamazepine intoxication: clinical spectrum and management.

Carbamazepine is an anticonvulsant drug in widespread use for the treatment of tonic-clonic and temporal lobe seizure disorders. Acute intoxication with this agent results in both neurologic and cardiovascular dysfunction. Neurologic manifestations may range from mild ataxia to profound coma with respiratory failure and are correlated with the plasma drug level. Cardiovascular effects appear primarily as conduction system disturbances. Treatment of carbamazepine overdose consists of aggressive orogastric lavage followed by activated charcoal administration with catharsis. Continuous electrocardiographic monitoring and close observation are necessary until plasma carbamazepine levels fall to therapeutic anticonvulsant levels. In cases of severe intoxication with respiratory failure and prolonged intubation, charcoal hemoperfusion has been reported to result in rapid improvement.

Rapid binding of guanosine 5'-O-(3-thiotriphosphate) to an apparent complex of beta-adrenergic receptor and the GTP-binding regulatory protein Gs.

When reconstituted phospholipid vesicles that contain purified beta-adrenergic receptors and the GTP-binding regulatory protein Gs were preincubated with agonist before the addition of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), the typical receptor-stimulated GTP gamma S binding reaction was preceded by an even more rapid burst of GTP gamma S binding. This burst was studied in detail at 0 degree C. The rate of the burst was second order in nucleotide and Gs [k assoc approximately 2 X 10(7) (M.min)-1], consistent with diffusion-controlled binding. The magnitude of the burst was always less than the number of receptors present and was roughly linear with receptor number when similarly prepared vesicles were compared. There was no obvious quantitative correlation between the burst and the amount of Gs. The species that gave rise to the burst formed with t1/2 approximately 15 min at 0 degree C in the presence of agonist and decayed by approximately 3 min upon addition of antagonist or detergent. Formation and decay of this species was much faster at at 30 degrees C. The data suggest that a complex of agonist, receptor, and Gs that is primed for the rapid binding of guanine nucleotide can form and be analyzed in reconstituted vesicles.

Plastic surgeons' opinions of facial surgery for individuals with Down syndrome.

Plastic surgeons from Los Angeles and New York (N = 182) were surveyed on their opinions of facial plastic surgery for individuals with Down syndrome. Of the 100 respondents, 88 were familiar with the procedures, and 24 had performed the surgery. The surgeons indicated the circumstances for recommending the surgery, who would be required to give consent, the degree to which they thought individuals with Down syndrome could understand the nature of the surgery, and their opinion of the degree of discomfort associated with the surgery.

The effect of phosphonoacetic acid on the in vitro replication of varicella-zoster virus.

Phosphonoacetic acid (PAA) was found to inhibit in vitro varicella-zoster virus (VZV) replication. At 100 microng/ml, PAA blocked the development and spread of VZV cytopathology in both growing and contact-inhibited cultures. Formation of virus plaques by infected cells and cell-free virus was effectively blocked at concentrations as low as 25 microng/ml. The development of nuclear and cytoplasmic virus antigens was also inhibited by PAA. Inhibition by PAA suggests that VZV DNA replication, like that of other herpes-viruses, involves a virus-specific DNA polymerase.

Teenage partners' communication about sexual risk and condom use: the importance of parent-teenager discussions.

CONTEXT: Teenagers' communication with their partners about sex and their use of condoms may be influenced by the discussions teenagers have with their parents about sex. However, little is known about the process of parent-teenager communication on this topic. Understanding both what parents discuss with their children and how they discuss it may lead to a greater understanding of teenagers' sexual behavior. METHODS: Interviews were conducted with 372 sexually active black and Hispanic youth aged 14-17 from Alabama, New York and Puerto Rico. Regression analyses were used to examine parent-teenager discussions about sexuality and about sexual risk, and parental communication skills as predictors of teenagers' discussions about sexual risk with a partner and teenagers' condom use. RESULTS: Parent-teenager discussions about sexuality and sexual risk were associated with an increased likelihood of teenager-partner discussions about sexual risk and of teenagers' condom use, but only if parents were open, skilled and comfortable in having those discussions. Teenagers' communication with their partner about sexual risk also was associated with greater condom use, but the relationship between parent-teenager communication and teenagers' condom use was independent of this association. CONCLUSIONS: The influence on teenagers of parent-teenager discussions about sexuality and sexual risk depends on both what parents say and how they say it. Programs that foster parent-teenager communication about sexuality and sexual risk must emphasize both of these aspects.

PIP: Teenagers' communication with their partners about sex, an important factor in sexual risk reduction, has been shown to be influenced by discussions teens have with their parents about sex. The present study confirmed that parent-teen communication about sex does indeed promote teenagers' discussions with their partners about sex and condom use, but only when parents communicate in a skilled, comfortable, and open manner. Interviews were conducted during 1993-94 with 372 sexually active Black and Hispanic US high school students 14-17 years old from Alabama, New York, and Puerto Rico. On average, teens had first intercourse at age 13.7 years and had had 3.9 partners. The association between parent-teen discussions about sexuality and sexual risk and teenager-partner communication about sex was high when parental responsiveness (openness, skill, comfort) was rated high by the teenager, but this association was weaker and of only marginal significance when responsiveness was rated as low. Similarly, when parental responsiveness was high, sexuality and risk discussions were significantly associated with increased condom use during most recent intercourse and lifetime condom use. However, at low levels of parental responsiveness, sexuality discussions were negatively associated with most recent and lifetime condom use. The association between parent-teen communication and condom use was direct and independent. These findings highlight the importance of communication skills training for parents.

Reconstitution of catecholamine-stimulated adenylate cyclase activity using three purified proteins.

beta-Adrenergic receptors, the GTP-binding regulatory protein that stimulates adenylate cyclase (Gs), and adenylate cyclase were each purified and reconstituted into unilamellar vesicles composed of phosphatidylethanolamine and phosphatidylserine (3:2, w/w). The molar ratio of receptor:Gs:adenylate cyclase was estimated to be about 1:10:1. Adenylate cyclase activity in the vesicles was stimulated up to 2.6-fold by beta-adrenergic agonists. Stimulation was dependent on the presence of guanine nucleotide, displayed appropriate beta-adrenergic selectivity and stereoselectivity for agonists, and was blocked appropriately by beta-adrenergic antagonists. Therefore, while additional proteins may modulate adenylate cyclase activity in native membranes, these results show that these three proteins are sufficient for the expression of hormone-stimulated adenylate cyclase.

Evaluation of acute scrotum pain with testicular scanning.

Emergency room physicians frequently are faced with the evaluation of the patient with acute testicular pain. The rapid differentiation between testicular torsion and acute epididymitis is necessary although frequently difficult due to an atypical presentation. We describe four patients with testicular pain in whom testicular scanning provided useful adjunctive information regarding diagnosis. This technique clearly differentiates acute torsion, acute epididymitis, testicular rupture, and missed torsion with abscess formation, prompting appropriate therapy in each case. Testicular scanning provides a rapid, noninvasive method to assist in the evaluation of testicular pain.

Chronic sclerosing glomerulopathy (heroin-associated nephropathy) in intravenous T's and Blues abusers.

The intravenous (IV) use of pentazocine (Talwin) and tripelennamine (pyribenzamine) has become a major form of drug abuse seen in the midwestern United States. Complications of this abuse have included psychotic reactions, acute pulmonary insufficiency, convulsions, and various infections. We have observed three patients in whom the IV use of these agents was associated with the nephrotic syndrome and renal histopathologic findings similar to that reported in heroin addicts with the so-called "heroin-associated nephropathy." Percutaneous renal biopsy demonstrated focal to diffuse segmental or global glomerulosclerosis by light microscopy. Electron microscopy revealed glomerular visceral epithelial cell foot process effacement and microvillus formation. Immunofluorescent studies were negative in the two patients studied. One patient presented in renal failure, and two others progressed to renal failure within 3 years of diagnosis. We suggest the term opiate nephropathy for this lesion in narcotics users, indicating its potential occurrence in non-heroin-using drug addicts.