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Biomedical subjects

M L Adams

Publications and source records attributed to M L Adams.

At least 19 recordsLinked to original sources

Interactions between alcohol- and opioid-induced suppression of rat testicular steroidogenesis in vivo.

To examine interactions between alcohol and endogenous opioids in their suppressive effects on rat testicular function, the opioid antagonist naltrexone or the opioid agonist morphine was administered to adult male rats alone or in combination with alcohol. Serum testosterone, testicular interstitial fluid (TIF) testosterone, and TIF volumes were measured to assess testicular function. Naltrexone induced dose-dependent increases in serum and TIF testosterone levels without changes in TIF volume. Alcohol (0.5 g/kg) inhibited naltrexone-induced stimulation of testosterone secretion and shifted the naltrexone dose-response curve to the right. Conversely, naltrexone (0.05 mg/kg) inhibited alcohol-induced suppression of testosterone secretion and shifted the alcohol dose-response curve to the right. Relatively high doses of naltrexone (5 to 30 mg/kg) were needed to stimulate testosterone secretion maximally in rats treated with a low dose of alcohol (0.5 g/kg) and to stimulate normal levels of testosterone secretion in rats treated with a high dose of alcohol (2 g/kg). In addition, combined treatment with 1 and 30 mg/kg of naltrexone and 0.5 to 2 g/kg of alcohol did not alter blood alcohol concentrations significantly, suggesting that the interactions between alcohol and naltrexone were unrelated to gross changes in alcohol metabolism or bioavailability factors. Simultaneous treatments with a low dose of alcohol (0.3 g/kg), near the threshold of efficacy, and low-moderate doses of morphine (0.3 to 3 mg/kg) were not additive in suppressing testosterone secretion, compared with either agent alone. These results support the hypothesis that opioid antagonists can reverse the suppressive effect of alcohol on testicular steroidogenesis, but the results also suggest that endogenous opioids do not exclusively mediate alcohol's effects on testosterone secretion.

Alcoholism

Effect of human adrenomedullin on vascular resistance of the canine tibia.

An ex vivo model of a perfused canine tibia was used to investigate the effect of human adrenomedullin, a novel peptide with known vasodilator properties, on the vascular resistance of bone. Human adrenomedullin has a potent and long-lasting vasodilator effect in the canine tibia following precontraction of vascular smooth muscle by infusion of prostaglandin F2 alpha. A 0.1 ml bolus injection of 10(-5) M human adrenomedullin suppressed the pressor response of the canine tibia preparation to an infusion of norepinephrine by 43-52% for a duration of 100 minutes. An injection of 10(-6) adrenomedullin suppressed the pressor response to an infusion of norepinephrine by 22-23% for a duration of 40 minutes. These data suggest that human adrenomedullin may be a potent and long-acting vascular smooth-muscle relaxant in bone.

Acetylcholine

Effects of nitric oxide-related agents on opioid regulation of rat testicular steroidogenesis.

These studies examined whether nitric oxide (NO) mediates opioid suppression of testicular steroidogenesis. Adult male rats were treated with various combinations of a NO synthase (NOS) inhibitor (NG-nitro-L-arginine methyl ester; NAME), a NO donor (isosorbide dinitrate; ISDN), an opioid agonist (morphine, and an opioid antagonist (naltrexone). Serum LH and testosterone and testicular interstitial fluid (TIF) testosterone concentrations were then measured. Inhibition of NO production by NAME reversed morphine-suppressed testosterone secretion; treatment with the NO donor, ISDN, reversed naltrexone-stimulated testosterone secretion. NAME did not alter morphine's effects on LH secretion and attenuated morphine's suppression of hCG-stimulated testosterone secretion, indicating that these effects occur directly in the testes and are not dependent on LH secretion. Even though these effects suggested possible interactions between NO and opioid systems, no additive or synergistic effects were found with suppressive combinations of morphine and ISDN, or with stimulatory combinations of naltrexone and NAME at does that had little effect on testosterone secretion when given alone. These results indicate that opioid and NO exert independent effects on testicular steroidogenesis through separate pathways or mechanisms and that NO does not mediate opioid-induced testicular suppression.

Animals

Is phototherapy safe for HIV-infected individuals?

Patients infected with human immunodeficiency virus (HIV) have a high prevalence of UV radiation-responsive skin diseases including psoriasis, pruritus, eosinophilic folliculitis and eczemas. On the other hand, UV has been shown to suppress T cell-mediated immune responses and to induce activation and replication of HIV. These developments have prompted clinicians and investigators to question whether phototherapy is safe for HIV-infected individuals. We have reviewed these issues and hereby provide a summary and critique of relevant laboratory and clinical evidence.

Clinical Trials as Topic

ADA is changing the way physicians practice medicine.

Although 5 years old, the Americans with Disabilities Act of 1990 is still considered a relatively new law. Physicians' practices are influenced daily by the Act--from office hiring practices to treating disabled patients. This article is in response to several questions that have been raised concerning the scope of the Act as it applies to a physician's office when treating hearing impaired patients.

Communication Methods, Total

A survey of sunbathing practices on three Connecticut State beaches.

In order to analyze sunbathing practices, a survey was conducted during the summer of 1995 on three Connecticut state beaches, with 1,003 interviews completed. The majority (65.8%) of respondents were women. Almost 70% of respondents were visiting the beach to get or maintain a tan. While the intended beach stay averaged four hours, only 55.7% of respondents were using sunscreen, 6.9% were sitting under shade, 12.7% were wearing hats, and 17.1% were wearing clothes other than a bathing suit. More than half (55%) of the sunscreen used had a sun protection factor of less than 15. Children were provided with greater protection than adults. The survey indicates the need for greater educational efforts to motivate protective behavior. Primary-care physicians could have an important role in these efforts.

Adolescent

Evaluation of influence of 24-hour cold preservation on endothelin production and on endothelin receptors in the bone vasculature.

Endothelin-1 is a vasoactive peptide produced by the vascular endothelium. It is one of the most potent endogenous vascular smooth muscle constrictors. Two subtypes of the endothelin receptor have been cloned and sequenced and denoted endothelin-A and endothelin-B. The aim of this study was to define the influence of cold ischemia on the production of endothelin-1 and on the endothelin receptors. Two different preservation techniques (cold storage only and cold storage with microperfusion with University of Wisconsin solution) also were compared. The study was performed in an in vitro bone perfusion model to isolate the vascular endothelium from blood components. The production of endothelin-1 by the bone vasculature was not altered after 24 hours of cold ischemia. No contractions were observed with S6c, a selective endothelin-B agonist, and this effect was not influenced by cold ischemia. The response mediated by the endothelin-A receptor was increased significantly, an effect that was not influenced by preservation with University of Wisconsin solution. This latter finding was the only significant alteration in the vascular function detected in the in vitro model after 24 hours of cold ischemia. With regard to the pharmacologic properties of endothelin-1, this mediated response could be implicated in the pathogenesis of vasospasm.

Animals

Nitric oxide-related agents alter alcohol withdrawal in male rats.

Evidence has been reported supporting the hypothesis that nitric oxide (NO) partially mediates the expression of morphine dependence. To examine whether NO-related agents also affect the expression of alcohol dependence, adult male rats were treated chronically with alcohol. Upon withdrawal of alcohol administration, abstinence signs were observed after treatment with a NO synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (NAME), or a NO donor, isosorbide dinitrate (ISDN). Withdrawal severity was based primarily on the presence and intensity of tremors, rigidity, hyperactivity, and spontaneous and audiogenic convulsions. The NOS inhibitor, NAME (10-100 mg/kg), injected during alcohol withdrawal significantly inhibited withdrawal severity decreasing the intensity of signs of hyperactivity, tremors, and rigidity, but not affecting the occurrence of convulsions. The NO donor, ISDN (30 mg/kg), administered during alcohol withdrawal significantly increased the severity of most withdrawal signs. These results suggest that NO mediates some aspects of the expression of alcohol dependence.

Alcohol Withdrawal Delirium

Outcome of carpal tunnel surgery in Washington State workers' compensation.

All cases of occupational carpal tunnel syndrome (OCTS) who received surgery for this condition in the Washington State workers' compensation system were identified using claim and physician billing databases. One hundred ninety-one incident surgical cases were identified between July 1, 1987 and December 31, 1987, and were followed up a mean of 3 years postoperatively for clinical, disability, and return to work outcomes. Medical record and claim file review was required for clinical and employment information. The mean age of all patients was 36.6 years, 48% were female, and 40% received bilateral surgery. The mean time from claim filing to surgery was 187 days. Ninety-eight percent of cases met the National Institute for Occupational Safety and Health (NIOSH) case definition for OCTS. Relief of pain was complete or modest in 86% (124/145) and only 14% of cases reported no improvement in symptoms. Mean duration of disability (time loss) postoperatively was nearly 4 months, and 8% of cases exceeded 1 year of time loss. The majority of cases returned to their same job (67%) or to a different job (15%). Workers in high risk occupations were less likely to return to the same job after CTS surgery compared to those in lower risk occupations (61% vs. 75%, p = 0.08). In this population, no association was seen between any outcome and age, gender, marital status, or baseline wage. Duration of disability was not significantly related to preoperative severity of OCTS or to more specific case criteria for this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Absenteeism

Acute alcohol exposure markedly influences male fertility and fetal outcome in the male rat.

Although it is recognized that drugs ingested by pregnant females produce marked cognitive and physiological deficits in their offspring, the possibility that paternal exposure to drugs prior to mating may have adverse effects on fertility and fetal outcome has not received much attention. The purpose of the present studies was to examine whether a single, acute exposure to alcohol influences the subsequent ability of adult male rats to mate and produce healthy and viable litters. Our results showed that a relatively large dose of alcohol 24 hours prior to breeding had little effect on the mating behavior of male rats, but there were markedly fewer pregnancies in females mated with alcohol-exposed male rats than in controls. Of equal importance, we found that, even when conception occurred and live births were produced, there were striking differences in fetal outcome. Alcohol-treated males sired many fewer pups than control males and there was a markedly enhanced mortality rate in their offspring. Collectively, these data suggest that acute paternal alcohol administration 24 hours prior to breeding does not affect mating behavior, but results in a greatly diminished fertility rate and fewer and less viable offspring. These studies suggest that paternal alcohol use may be as important as maternal alcohol abuse as a negative variable in pregnancy and fetal outcome.

Animals

Acute paternal alcohol exposure impairs fertility and fetal outcome.

An acute injection of an intoxicating dose of alcohol to male rats 24 hours prior to breeding with drug-naive females produced no discernible effect on copulatory activity, as reflected in vaginal plugs, but resulted in markedly (> 50%) reduced pregnancy rates. Fetal outcome was also markedly affected in offspring sired by alcohol-treated males: litter sizes were appreciably smaller (30%) and fetal mortality was more than 2 times higher than in controls. These results suggest that paternal alcohol use, like maternal alcohol abuse, may adversely affect fertility and fetal outcome.

Alcoholic Intoxication

Effects of nitric oxide-related agents on alcohol narcosis.

To examine whether nitric oxide (NO) affects alcohol (ethanol) narcosis, adult male rats were pretreated with a NO synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (NAME); a NOS substrate, l-arginine methyl ester (AME); or a NO donor, isosorbide dinitrate (ISDN); then treated with anesthetic doses (3-5 g/kg, ip) of alcohol. Pretreatment with NAME (30-100 mg/kg, sc) 40 min before alcohol treatment delayed the onset of alcohol-induced loss of the righting reflex (LORR) and increased the duration of the LORR. NAME (100 mg/kg) pretreatment combined with high doses of alcohol (4-5 g/kg) exerted significant lethal effects, even though treatment with either agent alone or NAME combined with lower doses of alcohol (3-3.5 g/kg) was not lethal. Simultaneous treatment with the NOS substrate AME (100 mg/kg, subcutaneous) blocked the effects of NAME on LORR duration times, but did not alter LORR onset times. The NO donor ISDN (30 mg/kg) given by oral gavage 2 hr before alcohol decreased LORR duration times without affecting the onset of LORR. In addition, ISDN dose-dependently inhibited NAME-induced LORR duration increases during alcohol narcosis without significantly altering LORR onset times. Neither ISDN nor NAME significantly altered blood alcohol concentrations. These results suggest that NOS inhibition and subsequent decreases in NO production enhance alcohol-induced narcosis and that increases in NO concentrations inhibit alcohol narcosis, supporting the hypothesis that inhibition of arginine-NOS-NO systems mediates part of the sedative-hypnotic effect of alcohol.

Amino Acid Oxidoreductases

Effects of nitric oxide-related agents on rat testicular function.

The effects of nitric oxide (NO)-related agents on testicular function were examined in male rats with measurements of serum luteinizing hormone, serum testosterone, testicular interstitial fluid (TIF) testosterone, and TIF volumes. Serum and TIF testosterone levels and luteinizing hormone secretion were significantly decreased by the NO donor, isosorbide dinitrate (ISDN), and the NO synthase (NOS) substrate, L-arginine methyl ester, a source for the endogenous production of NO. The effects of ISDN on TIF volumes were inconsistent, but L-arginine methyl ester decreased TIF formation in a dose-dependent manner. In addition, ISDN dose dependently suppressed testosterone secretion stimulated by human chorionic gonadotropin treatment, suggesting that the effects on testosterone secretion were independent of changes in secretion of the endogenous gonadotropin luteinizing hormone. ISDN, L-arginine methyl ester, and the endogenous NOS substrate L-arginine completely blocked testosterone secretion stimulated by the NOS inhibitor NG-nitro-L-arginine methyl ester (NAME), whereas the relatively inactive NOS substrate, D-arginine, only partially blocked NAME-stimulated testosterone secretion. Hydralazine and nicardipine, two vasodilators that do not exhibit prominent NO-related effects, also blocked basal testosterone secretion and testosterone secretion stimulated by the vasoconstrictor NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases

The public health impact and economic cost of smoking in Connecticut--1989.

Estimates of the smoking-attributable morbidity, mortality, and economic costs for Connecticut for 1989 were made using software distributed by the Centers for Disease Control and Prevention. The software calculations are based on relative risks for smoking-related diseases from major prospective studies. Using smoking prevalence, mortality, population, and health-care expenditure data for the state, 19.3% of all deaths in Connecticut in 1989 were estimated to be related to smoking. Cardiovascular disease and cancer accounted for the largest number of these estimated deaths. Men who died from smoking-related deaths lost an estimated 11.6 years of life while women died an estimated 12.8 years prematurely from smoking-related causes. The total cost, including direct and indirect smoking-related costs, was estimated to be $944 million, or $287 for each man, woman, and child in the state.

Adolescent

Reducing antipsychotic drug use in nursing homes. A controlled trial of provider education.

OBJECTIVE: In the United States, 20% or more of nursing home residents receive antipsychotic drugs, primarily for the behavioral manifestations of dementia. This high level of use of drugs with substantial toxicity has engendered a strong and persistent controversy and recently has led to explicit regulatory measures to curtail use (Omnibus Budget Reconciliation Act of 1987). We developed and tested a comprehensive program to reduce antipsychotic use through education of physicians, nurses, and other nursing home staff. The primary elements of the program were instruction in use of behavioral techniques to manage behavior problems and encouragement of a trial of gradual antipsychotic withdrawal. DESIGN: In a nonrandomized controlled trial, the program was implemented (beginning in August 1990) in two rural Tennessee community nursing homes with elevated antipsychotic use; two other comparable homes were selected as concurrent controls. PATIENTS: Throughout the study 194 residents were in the education homes and 184 were in the control homes. Residents in both groups of homes had comparable demographic characteristics and functional status, and each group had a baseline rate of 29 days of antipsychotic use per 100 days of nursing home residence. MAIN OUTCOME MEASURES: The primary end points were postintervention changes in administration of antipsychotics and other psychotropic drugs, use of physical restraints, and frequency of behavior problems. RESULTS: Days of antipsychotic use decreased by 72% in the education homes vs 13% in the control homes (P < .001). No significant changes were noted in the use of other psychotropic drugs in either group. Days of physical restraint use decreased 36% in the education homes vs 5% in the control homes (P < .001). Behavior problem frequency did not increase in either group, even among the 48% of baseline antipsychotic users in the education homes who had antipsychotic drug regimens discontinued for 3 or more months. CONCLUSIONS: The educational program led to a substantial reduction in antipsychotic use with no increase in the frequency of behavior problems. This suggests that for many antipsychotic drug users benefits may be marginal and that programs to reduce such drug use among the 250,000 US nursing home residents receiving these drugs should have high priority.

Aged

Preservation of bone graft vascularity with the University of Wisconsin cold storage solution.

The preservation of the microcirculation of bone has been evaluated with use of an in vitro canine tibia perfusion model. The production of relaxing factors by the osseous vascular endothelium was used as a metabolic marker for viability. This endothelial eccrine function was preserved for 5 days (120 h) by cold storage without continuous perfusion after a washout with the University of Wisconsin (UW) solution. This synthetic perfusate was superior to Krebs Ringer solution (p < 0.05), but storage without perfusion failed to prevent a significant rise in vascular resistance. Two techniques were effective for the preservation of bone vascularity for 24 h: washout with UW solution followed by nonperfusion cold (4 degrees C) storage, and vascular washout with mannitol solution followed by continuous hypothermic (5 degrees C) microperfusion (0.03 ml/min) with UW solution. The most consistent, and lowest, vascular resistance was produced by the microperfusion technique. However, UW solution does not consistently prevent an increase in vascular resistance with hypothermic ischemia. This technique may prove useful for the preservation of vascularized bone grafts, but it needs to be evaluated in a transplantation model.

Adenosine