New therapy for impotence

In the not too distant past, the physician caring for the impotent patient had few therapeutic options. With the recent advances in penile pharmacotherapy, vascular surgery, and prosthetics, several possibilities for treatment are now available. Before a decision is made, however, numerous factors must be taken into consideration: age, manual dexterity, cause of erectile dysfunction, psychological attitude, and social considerations. Clearly, the choice of therapy for impotence must now be made on an individual basis after a careful diagnostic evaluation and in-depth consultation with the patient. Only then can the treatment that offers the highest likelihood of success, both functional and emotional, be chosen.     

Pyrolysis and volatilization of cocaine

The increasing popularity of inhaling cocaine vapor prompted the present study, to determine cocaine's fate during this process. The free base of [3H]cocaine (1 microCi/50 mg) was added to a glass pipe, which was then heated in a furnace to simulate freebasing. Negative pressure was used to draw the vapor through a series of glass wool, ethanol, acidic, and basic traps. Air flow rate and temperature were found to have profound effects on the volatilization and pyrolysis of cocaine. At a temperature of 260 degrees C and a flow rate of 400 mL/min, 37% of the radioactivity remained in the pipe, 39% was found in the glass wool trap, and less than 1% in the remainder of the volatilization apparatus after a 10-min volatilization. Reducing the air flow rate to 100 mL/min reduced the amount of radioactivity collected in the glass wool trap to less than 10% of the starting material and increased the amount that remained in the pipe to 58%. GC/MS analysis of the contents of the glass wool trap after volatilization at 260 degrees C and a flow rate of 400 mL/min revealed that 60% of the cocaine remained intact, while approximately 6 and 2% of the starting material was recovered as benzoic acid and methylecgonidine, respectively. As the temperature was increased to 650 degrees C, benzoic acid and methylecgonidine accounted for 83 and 89% of the starting material, respectively, whereas only 2% of the cocaine remained intact. Quantitation of cocaine in the vapor during the course of volatilization revealed high concentrations during the first two min and low concentrations for the remaining time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chlorpromazine alters outer hair cell electromotility.

OBJECTIVE: Outer hair cells (OHCs) of the inner ear rapidly convert electrical gradients into mechanical force, enhancing cochlear sensitivity and frequency selectivity. We investigated the effect of chlorpromazine, an antipsychotic medication that alters membrane biomechanics, on OHC electromotility. STUDY DESIGN: Isolated guinea pig outer hair cells were perfused with chlorpromazine under whole-cell patch-pipette recording conditions. Electromotile responses were measured. RESULTS: A dramatic, reversible, dose-dependent depolarization of voltage at peak capacitance (V(pkCm)) was seen with chlorpromazine treatment. The gain of the electromotile response was maximal near V(pkCm) both before and after chlorpromazine application. Unlike the 3 other agents that alter electromotility (salicylate, lanthanides, membrane tension), chlorpromazine did not change peak capacitance (Cm(pk)), which varies directly with maximal electromotile gain. CONCLUSION: Chlorpromazine changes the membrane voltage at which OHCs exhibit maximal electromotile gain, without changing the magnitude of electromotile responses. SIGNIFICANCE: Chlorpromazine may diminish hearing thresholds or otoacoustic emissions in large doses.     

Impairment of spermatogenesis in transgenic mice with selective overexpression of Bcl-2 in the somatic cells of the testis.

To explore the functional role of Bcl-2 in germ cell development, transgenic mice carrying 6 kilobases of the inhibin-alpha promoter were generated to express human bcl-2 gene product in the gonads. Although female transgenic mice demonstrated decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis, the adult males exhibited variable impairment of spermatogenesis. The degree of damage ranged from tubules with intraepithelial vacuoles of varying sizes to near atrophied tubules consisting of Sertoli cells and a few spermatogonia. Although there was no significant change in body weight, an approximately 34% decrease in testicular weights was noted in transgenic animals compared with wild-type mice. Gamete maturation, assessed by determining the percentage of tubules with advanced (steps 13-16) spermatids, was decreased to 44.4% of the values measured in the wild-type animals. The incidence of germ cell apoptosis increased 3.8-fold in the transgenic animals and was associated with a marked loss of germ cells. Electron microscopy of the testes further revealed large vacuoles in the Sertoli cell cytoplasm and dilations of the intracellular spaces between adjacent Sertoli cells, spermatid malformations, and increased germ cell apoptosis in the transgenic animals. There was no evidence of Sertoli cell death either by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay or electron microscopy. Leydig cell ultrastructure, cell size and numbers, and plasma levels of testosterone were not different between normal and the transgenic animals. Collectively, these results support the critical role of Bcl-2 in male germ cell development and are consistent with the gender-specific role of the Bcl-2 family members in reproduction.     

Clinical evaluation of psychiatric disorders among first-visit patients to a primary care unit

It is important for a primary care physician to know the most common psychiatric diagnoses, criteria for these diagnoses, and proper treatment. During a 4-month period from December 1987 to March 1988, the authors conducted this prospective study in a rural group practice center and investigated 189 first-visit patients aged from 16 to 60 years. Among them, 55 cases (29.1%) were diagnosed as having psychiatric disorders which included: psychological factors affecting physical condition, 29 cases; generalized anxiety disorder, 12 cases; adjustment disorder, 10 cases; and others, 4 cases. There were no significant differences in marital status, social class, or family structure between patients with and without psychiatric disorders. However, the patients with psychiatric disorders tended to have a longer duration of illness, to exhibit more salient features of introversion and neuroticism in their personalities, to show poorer family function and to experience more stressful life events. Although all the psychiatric patients presented somatic symptoms as their primary complaints, we also found that they reported significantly higher scores for psychiatric symptoms on a self-rating scale. This study demonstrates that in order to promote comprehensive primary health care, psychiatry and behavioral science are essential training curricula for family physicians.     

Effect of varying drop size on the efficacy and safety of a topical beta blocker

We studied the effects on efficacy and safety of varying the drop size of a topical solution of levobunolol 0.5%. In a double-masked, crossover acute study, we administered a single drop of either 35 microL of vehicle, or 20, 35, or 50 microL of levobunolol one hour before the subjects began a ten-minute treadmill challenge electrocardiogram. After exercise the mean heart rate was 111 beats per minute (bpm) in the vehicle group and 102 to 103 bpm in the three levobunolol groups, which were significantly different from the control group but not from each other. In a randomized double-masked, parallel, chronic study, 117 patients with elevated intraocular pressure (IOP) instilled one of the three drop sizes of levobunolol twice daily for three months. Mean decreases in IOP ranged from 5.1 to 6.0 mmHg in the three groups, not significantly different from each other in mean IOP, heart rate, or blood pressure. We conclude that drop size in the range tested had no clinically significant effect on either efficacy or safety of a beta blocker such as levobunolol.     

Pharmacological effects of adenosine on canine penile erection.

We investigated the pharmacological effects of adenosine on canine penile erection in vivo. Intracavernous injection of adenosine induced a full erection, which was unaffected by hexamethonium and atropine. The erectile response induced by adenosine was augmented by intracavernous pretreatment with dipyridamole and markedly depressed by theophylline. The erectile response induced by cavernous nerve stimulation was also enhanced by dipyridamole and reduced by theophylline. The combination of acetylcholine and adenosine, when injected intracavernously, induced a full erection, and the effect of these drugs was not additive but synergistic. These results suggest that penile erection induced by adenosine is due to a direct relaxing effect on cavernous smooth muscle. We propose that adenosine plays a cooperative role with acetylcholine and also has a physiological role as a neuromodulator in canine penile erection.     

Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis

BACKGROUND: Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens. METHODS: This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed with SAC and who had a positive reaction in a conjunctival allergen challenge were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1 drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine, respectively, for 8 weeks. The primary end point was ocular itching, and secondary end points included ocular hyperemia, chemosis, ocular mucous discharge (all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale), and tearing (present or absent). Efficacy analyses used assessments from the two 1-week periods with the highest pollen counts. For tolerability assessment slit-lamp biomicroscopy and visual acuity examinations were conducted at each study visit (weeks 0, 2, 4, 6, and 8). RESULTS: Two-hundred ninety-eight patients (159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years]) entered the study; 118 received epinastine, 118 received levocabastine, and 62 received vehicle. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P=0.045); scores for hyperemia were similar between these 2 groups. Ocular itching and hyperemia scores were similar between the epinastine and levocabastine groups. No clinically or statistically significant between-group differences were seen in slit-lamp biomicroscopy findings, changes in visual acuity from baseline, or the incidence of treatment-related adverse effects. CONCLUSIONS: In this study of patients with SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle for the control of ocular itching and was similar in efficacy to levocabastine for control of ocular itching and hyperemia. Epinastine was well tolerated.     

The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments.

The alpha and beta chains of spectrin are homologous, yet they have acquired different structural features that work in synergy to give the multimer its overall properties. The primary amino acid sequence of each spectrin subunit is dominated by tandemly repeated 106-residue motifs. By comparing the complete Drosophila beta-spectrin sequence with other spectrins we have discovered evidence that a higher-order, 848-amino acid supra-motif is tandemly repeated in both alpha- and beta-spectrin. These data argue that alpha- and beta-spectrin, rather than evolving independently from sequences encoding the ancestral 106-residue motifs, must have arisen after the establishment of a large supra-motif composed of eight of the 106-residue motifs. Our data suggest the segment structure of a progenitor gene that gave rise to both alpha- and beta-spectrin as well as dystrophin. The structural differences that evolved after the split between the alpha- and beta-spectrin genes confer the independent functions that exist in their products today.