Direct measurements of the optical cross sections and refractive indices of individual volatile and hygroscopic aerosol particles.

We present measurements of the evolving extinction cross sections of individual aerosol particles (spanning 700-2500 nm in radius) during the evaporation of volatile components or hygroscopic growth using a combination of a single particle trap formed from a Bessel light beam and cavity ring-down spectroscopy. For single component organic aerosol droplets of 1,2,6-hexanetriol, polyethylene glycol 400, and glycerol, the slow evaporation of the organic component (over time scales of 1000 to 10,000 s) leads to a time-varying size and extinction cross section that can be used to estimate the refractive index of the droplet. Measurements on binary aqueous-inorganic aerosol droplets containing one of the inorganic solutes ammonium bisulfate, ammonium sulfate, sodium nitrate, or sodium chloride (over time scales of 1000 to 15,000 s) under conditions of changing relative humidity show that extinction cross-section measurements are consistent with expectations from accepted models for the variation in droplet refractive index with hygroscopic growth. In addition, we use these systems to establish an experimental protocol for future single particle extinction measurements. The advantages of mapping out the evolving light extinction cross-section of an individual particle over extended time frames accompanied by hygroscopic cycling or component evaporation are discussed.

Cohort study examining long-term respiratory health, career duration and racing performance in racehorses that undergo left-sided prosthetic laryngoplasty and ventriculocordectomy surgery for treatment of left-sided laryngeal hemiplegia.

REASONS FOR PERFORMING STUDY: The risk of respiratory conditions, such as inflammatory airway disease (IAD) and exercise-induced pulmonary haemorrhage (EIPH), are thought to be higher in racehorses that undergo prosthetic laryngoplasty with ventriculocordectomy (PLVC) surgery to treat left-sided laryngeal hemiplegia (LLH) than in racehorses with normal laryngeal function. However, this has not been investigated formally owing to the difficulty of obtaining reliable follow-up data. OBJECTIVES: To determine the incidence of respiratory conditions (IAD and EIPH), duration of racing career, number of starts and number of starts for which stakes money was earned in racehorses that had undergone PLVC surgery to treat LLH, compared with racehorses that did not have LLH or undergo any laryngeal surgery. METHODS: A retrospective cohort study design was used, with surgical, clinical and race data of Thoroughbred racehorses obtained from the time of importation until retirement. The surgical cohort consisted of racehorses that had undergone PLVC for LLH and met specific inclusion criteria. Every surgical case was matched, according to trainer, year of import into Hong Kong and pre-import international handicap rating, to 2 unexposed racehorses. RESULTS: Respiratory conditions, such as excessive tracheal mucus and epistaxis due to severe EIPH, were significantly increased in the surgical cohort, compared with the matched unexposed cohort (P values <0.001 and <0.004, respectively). Racing career duration in the surgical cohort was significantly shorter than in the unexposed cohort, which was primarily due to retirement because of epistaxis. The number of race starts was fewer in the surgical than in the unexposed cohort after surgery/matching, but the number of starts for which stakes money was earned was not significantly different. CONCLUSIONS AND POTENTIAL RELEVANCE: Owners and trainers should be advised that racehorses with LLH that undergo PLVC surgery are at an increased risk of respiratory conditions (IAD and severe EIPH), which is likely to shorten their racing career compared to racehorses with normal laryngeal function. Racing performance in terms of race starts was significantly less in racehorses that had undergone PLVC surgery; however, the number of starts for which stakes money was earned was similar to those racehorses that were unexposed.

Costs and complications of equine castration: a UK practice-based study comparing 'standing nonsutured' and 'recumbent sutured' techniques.

REASONS FOR PERFORMING STUDY: Clinicians are often asked to guide owners and trainers over the relative advantages and disadvantages of equine castration performed in either the standing horse with an open unsutured scrotal wound with healing by second intention, or a recumbent horse under general anaesthesia in aseptic conditions, with sutured scrotal skin allowing primary wound closure. OBJECTIVES: To identify types and frequency of complications following the 2 differing approaches, and to compare the financial cost associated with each procedure, based on practice charges. METHODS: Veterinary expenses of 217 horses castrated by a Newmarket equine veterinary practice over an 18-month period were analysed. Of these, Group 1 (n = 121) were castrated standing and nonsutured by one of 2 ambulatory clinicians and Group 2 (n = 96) castrated in recumbency, in aseptic equine hospital conditions. RESULTS: Group 1 had a complication prevalence of 22% with no mortalities, and Group 2 a significantly lower complication prevalence of 6% (P = 0.001) with a mortality rate of 1%. The financial cost of Group 1, without complications, was approximately one-third of the cost of uncomplicated Group 2. However, the cost of Group 1 with complications increased to approximately two-thirds of the cost of an uncomplicated Group 2 castration. CONCLUSIONS: Even though the complication prevalence for Group 1 castrations leaving an open scrotal wound was significantly higher than for a recumbent horse with a sutured scrotal wound in a hospital, the average cost of Group 1 was still less, even taking into account the additional follow-up costs associated with treating such complications. POTENTIAL RELEVANCE: This report provides a benchmark for the outcome of 2 methods of castration based on a database obtained from particular circumstances within the practice involved. Further studies are required to corroborate and take into account future development in surgical and anaesthetic techniques.

Treatment of alcohol-dependent outpatients with acamprosate: a clinical review.

Acamprosate (calcium acetyl-homotaurine) is a synthetic compound whose chemical structure resembles that of homotaurine, a naturally occurring amino acid. Acamprosate acts centrally and appears to restore the normal activity of glutaminergic neurons, which become hyperexcited as a result of chronic alcohol exposure. Although not yet approved for use in the United States, acamprosate has been available by prescription in France since 1989 and is now available in many other countries throughout the world. This article reviews data from all published double-blind, placebo-controlled clinical trials of acamprosate among alcohol-dependent outpatients. Overall, patients treated with acamprosate exhibited a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treated with placebo. The drug's reliable effect on prolonging abstinence, in conjunction with an excellent safety profile, suggests that acamprosate may be useful for a broad range of patients with alcohol dependence.

Pharmacological relapse prevention in alcohol dependence: from animal models to clinical trials.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Jobst August-Ludwig Boening and Otto Michel Lesch. The presentations were (1) Pharmacological validation of a new animal model of alcoholism, by Rainer Spanagel; (2) Persisting loss of control as main criterion for alcohol addiction in rats and mice, by Jochen Wolffgramm; (3) Role of NMDA receptor subunits associated with protein kinase C in the prevention of alcohol dependence, by Minoru Narita; (4) Long-term follow up of continued naltrexone treatment, by David Sinclair; (5) Pharmacological treatment trials with dopaminergic and serotonergic substances: Myths or facts? by Gerhard A. Wiesbeck; and (6) Methodology and behavioral therapy of the U.S. acamprosate study, by Barbara J. Mason.

Natural control of Culex quinquefasciatus larvae in residential ditches by the copepod Macrocyclops albidus.

Natural populations of three larvivorous copepod species live in residential roadside ditches in Louisiana: Macrocyclops albidus, Acanthocyclops vernalis, and Megacyclops latipes. Macrocyclops is most common and killed an average of 27 first-instar Culex quinquefasciatus larvae/copepod/day in the laboratory. Although severe pollution from septic tank effluent in some parts of the ditches creates havens for Cx. quinquefasciatus production by excluding predatory copepods and fish (Gambusia affinis), Macrocyclops and the fish substantially reduce Cx. quinquefasciatus larval survival when present where pollution is not so severe. At natural abundance, Macrocyclops reduced the survival of Cx. quinquefasciatus larvae (during their first four days) to 2.6%, compared with 46% survival in controls without Macrocyclops. During one year of field observation, Macrocyclops was common in the spring but disappeared during the summer when fish (which prey on copepods) appeared in many ditches, reduced water flows led to more severe pollution, and water temperatures in very shallow water were sometimes higher than Macrocyclops could survive. Macrocyclops reappeared in many ditches during autumn and winter, when water temperatures and pollution declined and fish disappeared. Introduction of Macrocyclops to ditches in October accelerated its reappearance during autumn and winter and reduced the number of sites with Cx. quinquefasciatus larvae to one-quarter the number in control ditches. The most effective way to control Cx. quinquefasciatus is to eliminate pollution so predators like fish and copepods can live throughout the ditches, but timely introduction of fish and copepods could also contribute to control. More experience will be necessary to ascertain whether copepod introductions are cost effective.

Acamprosate for the treatment of alcohol dependence: a review of double-blind, placebo-controlled trials.

Acamprosate (calcium acetyl-homotaurine) is a synthetic compound that crosses the blood-brain barrier and has a chemical structure similar to that of the naturally occurring amino acid neuromediators, homotaurine and g-aminobutyric acid (GABA). Acamprosate appears to act primarily by restoring normal n-methyl-d-aspartate (NMDA) receptor tone in the glutamate system, and has been shown to have a specific dose-dependent effect on decreasing voluntary alcohol intake in animals with no effects on food and water consumption. The safety and efficacy of acamprosate in alcohol-dependent outpatients is currently under evaluation in the United States. Acamprosate has been available by prescription since 1989 in France and more recently in most European and Latin American coutries as well as Australia, South Africa, and Hong Kong. More than 4 million people have been treated with acamprosate since it became commercially available. The purpose of this article is to review all available double-blind, placebo-controlled clinical trials evaluating the safety and efficacy of acamprosate treatment of alcohol dependence. This work encompasses 16 controlled clinical trials conducted across 11 European countries and involves more than 4,500 outpatients with alcohol dependence. Fourteen of 16 studies found alcohol-dependent patients treated with acamprosate had a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treated with placebo. Additionally, a multinational open-label study of acamprosate in 1,281 patients with alcohol dependence found acamprosate to be equally effective across four major psychosocial concomitant treatment programs in maintaining abstinence and reducing consumption during any periods of relapse. An absence of known strong predictors of response to acamprosate, in conjunction with a modest but consistent effect on prolonging abstinence, and an excellent safety profile, lend support to the use of acamprosate across a broad range of patients with alcohol dependence.

A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence.

BACKGROUND: Nalmefene is a newer opioid antagonist that is structurally similar to naltrexone but with a number of potential pharmacological advantages for the treatment of alcohol dependence, including no dose-dependent association with toxic effects to the liver, greater oral bioavailability, longer duration of antagonist action, and more competitive binding with opioid receptor subtypes that are thought to reinforce drinking. METHODS: A double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of 2 doses of oral nalmefene for alcohol dependence. The 105 outpatient volunteers were abstinent for a mean of 2 weeks prior to random assignment to the placebo or 20- or 80-mg/d dose nalmefene groups for 12 weeks. Cognitive behavioral therapy was provided weekly during treatment. Self-reported drinking or abstinence was confirmed by determinations of breath alcohol concentration and by collateral informant reports. RESULTS: Outcomes did not differ between the 20- and 80-mg dose nalmefene groups. Significantly fewer patients treated with nalmefene than patients given placebo relapsed to heavy drinking through 12 weeks of treatment (P<.02), with a significant treatment effect at the first weekly study visit (P<.02). The odds ratio of relapsing to heavy drinking was 2.4 times greater with placebo compared with nalmefene (95% confidence interval, 1.05-5.59). Patients treated with nalmefene also had fewer subsequent relapses (P<.03) than patients given placebo. CONCLUSIONS: Treatment with nalmefene was effective in preventing relapse to heavy drinking relative to placebo in alcohol-dependent outpatients and was accompanied by acceptable side effects.

Occult fractures of the greater tuberosity of the humerus: radiographic and MR imaging findings.

OBJECTIVE: The purpose of this study is to discuss the clinical implications of diagnosing a one-part greater tuberosity fracture on radiography and to describe associated rotator cuff findings on MR imaging. CONCLUSION: One-part greater tuberosity fractures are traditionally treated conservatively. Because clinical findings simulate those of rotator cuff abnormalities, some patients with missed or nonvisible fractures may be referred for MR imaging for further examination. In our study, MR imaging revealed no associated cuff abnormalities that required early surgery. Diagnosis of such a fracture on radiography may obviate the need for unnecessary MR imaging and arthroscopic surgery.

Psychiatric comorbidity in methadone maintained patients.

Diagnosing comorbid psychiatric disorders in methadone maintained patients may help to identify subgroups with different outcomes and needs for treatment. In this study, 75 methadone maintenance clinic patients in treatment longer than 30 days were assessed with the Addiction Severity Index, Global Assessment Scale and Mini-Mental Status Exam, and were interviewed for DSM-III-R psychiatric diagnosis using the computerized Diagnostic Interview Schedule. Psychiatric diagnoses were prevalent in the sample with depression, phobic disorders, antisocial personality and generalized anxiety the most common. Both number of DSM-III-R diagnoses and severity of psychopathology were correlated with outcome measures such as concurrent drug abuse, family-social problems and employment status.

Pleural fluid: accuracy of computed tomography in differentiating exudates from transudates.

PURPOSE: To determine the accuracy of computed tomography in differentiating pleural exudates from transudates when reviewed subjectively by two experienced radiologists in a community hospital. METHODS: Computed tomography scans of 55 consecutive patients who had a thoracenteses within 10 days of the study were retrospectively reviewed independently by two experienced staff radiologists. They were asked to evaluate subjectively parietal pleural thickness (anterior, lateral, posterior), attenuation of extra-pleural fat, and categorize pleural fluid as loculated or free flowing. Radiographic findings were correlated with biochemical results of thoracentesis (Light's criteria) to assess the accuracy of computed tomography in differentiating pleural exudates from transudates. RESULTS: For the diagnosis of an exudate, pleural thickening alone had the best sensitivity and specificity (50%, 100%, respectively) with an accuracy of 55%. CONCLUSION: Subjective evaluations for increased pleural thickness have a high accuracy for diagnosing pleural exudates.

Possible serotonin syndrome associated with tramadol and sertraline coadministration.

OBJECTIVE: To report a possible case of serotonin syndrome associated with coadministration of tramadol hydrochloride and sertraline hydrochloride. CASE SUMMARY: A 42-year-old woman developed atypical chest pain, sinus tachycardia, confusion, psychosis, sundowning, agitation, diaphoresis, and tremor. She was taking multiple medications, including tramadol and sertraline. The tramadol dosage had recently been increased, resulting in what was believed to be serotonergic syndrome. DISCUSSION: Serotonin syndrome is a toxic hyperserotonergic state that develops soon after initiation or dosage increments of the offending agent. Patients may differ in their susceptibility to the development of serotonin syndrome. The (+) enantiomer of tramadol inhibits serotonin uptake. Tramadol is metabolized to an active metabolite, M1, by the CYP2D6 enzyme. If this metabolite has less serotonergic activity than tramadol, inhibition of CYP2D6 by sertraline could have been a factor in the interaction. CONCLUSIONS: Clinicians should be aware of the potential for serotonin syndrome with concomitant administration of sertraline and tramadol.

Ritanserin in the treatment of alcohol dependence--a multi-center clinical trial. Ritanserin Study Group.

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.

Dosing issues in the pharmacotherapy of alcoholism.

Pharmacological treatments for alcohol dependence have focused increasingly on agents that reduce alcohol craving and consumption or that treat psychiatric disorders associated with drinking relapse. Clinicians who treat alcohol-dependent patients must find the optimal dose of these agents to maximize response. Determining the best dosing strategy has been the goal of recent treatment studies with alcohol-dependent patients. One study, for example, showed that an opiate antagonist medication had a dose-dependent relationship with patient outcome and retention in treatment. Another dosing consideration involves the effect of long-term alcohol abuse on drug metabolism (e.g., when treating alcohol-dependent patients for comorbid psychiatric disorders). This was demonstrated in a study of recently abstinent patients who were taking the antidepressant desipramine for major depression. Alcohol-dependent patients had higher hepatic enzyme activities and lower plasma levels of desipramine relative to oral dose than did a comparison group of depressed patients without an alcohol use disorder.

A double-blind, placebo-controlled trial of desipramine for primary alcohol dependence stratified on the presence or absence of major depression.

OBJECTIVE: To assess the use of desipramine for secondary depression in primary alcohol dependence and its effect on abstinence. DESIGN: Randomized, double-blind, placebo-controlled trial, with stratification on the presence of secondary depression. SUBJECTS: Seventy-one volunteer and referred patients with primary alcohol dependence, abstinent a median of 8 days before randomization. A subset of 28 patients had major depression secondary to alcoholism. SETTING: The outpatient psychiatry departments of two urban medical centers. INTERVENTION: Six months of a clinically determined dose of desipramine. MAIN OUTCOME MEASURES: Hamilton Depression Rating Scale, and Time Line Follow Back Interview, with breath alcohol concentrations and collateral verification. RESULTS: Hamilton Depression scores of desipramine-treated depressed alcoholics decreased significantly, controlling for baseline Hamilton Depression scores (P=.04). Overall, patients were abstinent significantly longer when receiving desipramine (P=.03). Rates of relapse of depressed vs nondepressed patients, analyzed separately, were not significant, although the survival function approached significance for the depressed subgroup (P=.09). Desipramine-treated depressed patients were more satisfied and were rated as more improved. CONCLUSIONS: Major depression secondary to alcohol dependence that is diagnosed after at least 1 week of abstinence can remain stable in some placebo-treated alcoholics and can respond to desipramine. Treating depression secondary to alcoholism may reduce risk for drinking relapse in some patients. Use of desipramine to reduce relapse in nondepressed alcoholics is not supported.

Women and minorities representation in alcoholism treatment research.

Demographic and clinical information and referral outcome were systematically collected from 347 alcoholics who telephoned to inquire about treatment on alcoholism clinical research protocols over a 1-year period. The ratio of male to female callers was 7:3, with 2:1 scheduling appointments, 3:2 keeping appointments, and 3:2 actually enrolling in a treatment study. These data indicate that although a smaller ratio of female alcoholics initially called for treatment, those who did call were more likely to actually enter treatment than were male callers. A ratio of 2:1 non-minority to minority alcoholics called the clinic, with 7:3 scheduling appointments, 8:1.6 keeping appointments, and 8:1 actually entering the study. These data suggest that minority alcoholics were less likely than non-minority alcoholics to enter treatment protocols. However, discriminant function analysis found income to be a better predictor of entry into treatment than race, age, or gender, and analysis of covariance found non-minorities and minorities did not differ in rate of entry into treatment when income was used as covariate.

Assessment of sulfonylurea adherence and metabolic control.

This study was designed to compare sulfonylurea adherence assessment by providers, patients' self-report, pill counts, and a medication event monitoring system (MEMS-3) device, and correlate the estimates of metabolic control by provider, patient, and laboratory. Forty-seven outpatient veterans with fair to poor metabolic control of non-insulin-dependent diabetes mellitus were enrolled and received monthly refills of sulfonylurea in vials with a cap containing an electronic medication monitoring microprocessor. Pill counts and fasting plasma glucoses were measured monthly, and glycohemoglobin and a 24-hour diet recall were obtained at 0 and 60 days. Investigators then asked providers and patients to assess adherence and metabolic control. Forty-seven percent were nonadherent to medication using MEMS-3, 29% using pill counts, 29% using provider assessment, and 31% using self-report. Thirty-one percent of providers and 53% of patients assessed metabolic control differently than laboratory values. Assessment of medication adherence by provider, patient, and pill counts did not explain metabolic control as closely as assessment by MEMS-3.

A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence.

A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo-controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrexone in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol-dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse (p < or = 0.05), and a greater increase in the number of abstinent days/week (p < or = 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups (p < or = 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings.