Fertility issues and their management in men with testis cancer

Although a curable malignancy, testis cancer and its treatment have unique associated morbidities that largely affect reproductive dysfunction. In this focused review, the factors that contribute to infertility in men with testis cancer are outlined. The treatment-specific risks to fertility that accompany cancer management are also discussed. Contemporary methods of overcoming infertility in testis cancer patients are addressed, and several exciting and promising experimental approaches to the preservation or restoration of fertility for men with testis cancer are presented.     

Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity

Studies were carried out to examine the effects of long-term recombinant human growth hormone (GH) therapy on longevity in rodents. In the first study, 150 18-month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 microg GH/kg body weight three times per week; Group 3, 50 microg GH/kg body weight three times per week. GH and solvent vehicle therapies were started at 18 months of age and continued until all the animals died spontaneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decreased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical analysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice, even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were nephropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered by GH therapy. We conclude that long-term low-dose GH therapy that includes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no overt deleterious effects on longevity and pathology in aged rodents.     

The epidemic of gang-related homicides in Los Angeles County from 1979 through 1994

OBJECTIVE: To determine trends in gang homicides and the population at greatest risk for homicide by reviewing all gang-related homicides in Los Angeles County, California, from January 1979 to December 1994. DESIGN: Homicide files of the Los Angeles Police Department and the Los Angeles County Sheriff's Department from 1979 to 1994 involving violent street gang activity were reviewed. Gang files were reviewed for demographic data, weapons used, homicides by drive-by shootings, and times and geographic areas of occurrence. SETTING: Los Angeles County from January 1, 1979, to December 31, 1994. MAIN OUTCOME MEASURES: Age, race, and sex of gang-related homicide victims; frequency of weapon use; and the change in gang-related homicide rates during the study period. RESULTS: A total of 7288 gang-related homicides occurred in Los Angeles County from 1979 through 1994; 5541 of these homicides occurred in Los Angeles Police Department and Los Angeles County Sheriff's Department jurisdictions. During the study period, the proportion of all homicides that were gang related increased from 18.1% to 43.0% (P < .001). Of the 5541 gang-related homicide victims, 4580 (85.6%) were aged 15 to 34 years, 93.3% were African American or Hispanic, 5157 (93.2%) were male, 3559 (64.2%) were gang members, and 1408 (25.4%) occurred during drive-by shootings. Firearms were used in an increasing proportion of homicides, from 71.4% in 1979 to 94.5% in 1994. Homicides by semiautomatic handguns dramatically increased during the study period. Gang-related homicide rates for African-American males aged 15 to 19 years increased from 60.50 per 100,000 population per year in 1979 to 1981 to 192.41 per 100,000 population per year in 1989 to 1991. CONCLUSIONS: Gang-related homicides in Los Angeles County have reached epidemic proportions and are a major public health problem. To prevent gang violence, the root causes of violent street gang formation must be alleviated, the cycle of violent street gang involvement must be broken, and access to firearms must be limited.     

Evidence for opening of hair-cell transducer channels after tip-link loss

The mechanosensitive transducer channels of hair cells have long been proposed to be gated directly by tension in the tip links. These are thin, elastic extracellular elements connecting the tips of adjacent stereocilia located on the apical surface of the cell. If this hypothesis is true, the channels should close after destruction of tip links. The hypothesis was tested pharmacologically using receptor currents obtained in response to mechanical stimulation of the stereociliary bundle of outer hair cells isolated from the adult guinea pig cochlea. Application of elastase (20 U/ml) or 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetra-acetic acid (BAPTA; 5 mM), both of which are known to disrupt tip links in other hair-cell preparations, led to the expected irreversible loss of receptor currents. However, the cells then displayed a maintained inward current, implying that channels were left permanently open. This current was similar in magnitude to the receptor current before treatment and was reduced reversibly by known blockers of mechanosensitive channels, namely, dihydrostreptomycin (100 microM), amiloride (300 microM), and gadolinium ions (1 mM). These observations suggest that the maintained current flows through the mechanosensitive channels. Electron microscopical analysis of isolated hair cells, exposed to the same concentrations of elastase or BAPTA as in the electrophysiological experiments, demonstrated an almost total loss of tip links in hair bundles that showed no evidence of other mechanical damage. It is concluded that although the tip links are required for mechanoelectrical transduction, the channels are not gated directly by the tip links.     

A comparison of clustering solutions for cognitive heterogeneity in schizophrenia

This study investigated semantic priming for literal (stinging-mosquito) and metaphoric (stinging-insult) associates presented to either the left or right visual fields (RVF/LVF) across stimulus-onset-asynchronies (SOA) of 200 and 800 ms. For the short SOA condition, facilitation was found for metaphorically related targets in both visual fields (VFs) while literally related targets were facilitated only in the RVF. For the long SOA condition, metaphorically related targets were facilitated in the LVF whereas literally related targets were facilitated in the RVF. These results support previous findings indicating an enhanced role of the RH in metaphoric comprehension. In addition, the present results are in accordance with current models of hemispheric semantic processing.     

Role of neutrophil-endothelial cell adhesion in inflammatory disorders

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.     

Comparative evaluation of college football officials' attitudes toward NCAA mouthguard regulations and player compliance

A 12-item questionnaire addressing attitudes of football officials toward the 1990 National Collegiate Athletic Association (NCAA) mouthguard regulation was sent to all officials in the Southeastern Conference (N = 62). The response rate was 95% (59). Twenty-seven per cent of officials reported that all players were in compliance; 74% believed the new rule to be at least somewhat beneficial in determining player compliance, and 20% reported that the rule had resulted in more frequent player use. Twenty-two per cent reported they would ignore a mouthguard violation and none had charged a time-out or called a penalty during the 1991 season. Significant differences in the responses of Big East officials surveyed in a previous study were noted by the authors, when compared to the SEC, but both groups of officials strongly supported the idea that wearing mouthguards should be the responsibility of coaches rather than officials.     

Long-term treatment with abecarnil does not induce diazepam-like dependence in mice

Abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate) is a metabolically stable anxiolytic and anticonvulsant beta-carboline derivative with few sedative and muscle relaxant effects in rodents. Abecamil binds with high affinity to benzodiazepine receptors. Because long-term treatment with benzodiazepines leads to development of dependence, we evaluated in mice whether abecarnil also possesses a potential for producing dependence, using electroencephalographic and electromyographic monitoring, and behavioral assessment of anxiety to detect withdrawal responses after chronic treatment. Diazepam was used as a reference. Mice withdrawn from chronic treatment with diazepam (15 mg/kg/day for 12 days) showed a time-related evolution of anxiety, muscle rigidity and seizures between days 4 and 21 after discontinuation of the treatment. A period between withdrawal days 1 and 3 was symptom free. Mice withdrawn from chronic administration of abecarnil (6 mg/kg/day for 12 days) showed no anxiety and no changes in seizure susceptibility and muscle tone. The doses of diazepam and abecarnil used for chronic treatment were equivalent in terms of kinetics and binding to benzodiazepine receptors. These data indicate that long-term treatment with abecarnil does not induce benzodiazepine-like dependence in mice. Thus, it may be predicted that chronic treatment with abecarnil in humans may offer an important alternative to benzodiazepines in the treatment of anxiety.     

Phenotype of striatal cells expressing c-Fos following amphetamine treatment of rats with intrastriatal dopaminergic grafts

Activation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c-Fos expression in the striatum, mostly in the striatonigral substance P-ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c-Fos is greatly increased in the graft-bearing striatum compared with the normal striatum. We examined whether this increase in the number of c-Fos-expressing neurons corresponds to the recruitment of a new neuron population, or whether it reflects an increase in the proportion of substance P-ergic neurons exhibiting activation of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d-amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c-Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c-Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti-c-Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c-Fos following amphetamine treatment. The density of neurons expressing c-Fos following amphetamine treatment was three-fold higher in the graft-bearing striata than in the striata of control animals. Approximately 75% of the c-Fos expressing cells were substance P-ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic. Similar proportions were found in the graft-bearing striatum, signifying that the pattern of activation of c-fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c-Fos predominantly reflects a graft-induced increase in the proportion of neurons expressing c-Fos within the same population of neurons which normally expresses c-Fos in the striatum, i.e. the striatonigral substance P-ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P-ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine-induced stimulation of the implanted dopaminergic neurons.