Combined intranasal ipratropium bromide and oxymetazoline in experimental rhinovirus infection.

The topical anticholinergic ipratropium bromide and topical decongestant oxymetazoline were tested to determine whether oxymetazoline alone and the combination were well tolerated and reduced rhinorrhea and middle ear pressure abnormalities during experimental rhinovirus infection. The study was double-bind, placebo-controlled, and double dummy in design. Healthy volunteers (n = 109) with low serum neutralizing antibody titer (< or = 1:2) were. Treatments inoculated with rhinovirus (type 39 or Hank's strain) and randomized to treatment with ipra-tropium bromide 0.06% two sprays per nostril (84 micrograms per treatment) and oxymetazoline 0.05% two sprays per nostril, oxymetazoline alone, or placebo. Treatments were self administered twice daily for 5 days beginning 1 day after rhinovirus inoculation. The overall infection rate was 83% and of those infected, 88% felt that they had a cold. During the 3-hour period after dosing, the increase in nasal discharge was significantly lower in the combined ipratropium and oxymetazoline (0.13 +/- 0.17 gm/3 hr, mean +/- SE) than after oxymetazoline alone (0.60 +/- 0.18 gm/3 hr) or vehicle (0.73 +/- 0.18 gm/3 hr). Over the 5-day observation period, total daily nasal discharge also tended to be lower in the ipratropium plus oxymetazoline group (3.67 +/- 0.70 gm/24 hr, mean +/- SE) compared to oxymetazoline (5.61 +/- 0.73: 35% reduction) or the vehicle (5.04 +/- 0.73; 27% reduction) recipients, but the differences were not statistically significant. Subjective assessments of rhinorrhea indicated that the severity of rhinorrhea was significantly better among patients receiving oxymetazoline alone or with ipratropium compared to the vehicle. No significant difference in the cumulative frequencies of middle ear pressure abnormalities (27-31%) were found among the treatment groups. Oxymetazoline does not consistently stimulate or decrease nasal mucus production, and ipratropium added to oxymetazoline is well tolerated and reduces rhinorrhea during experimental rhinovirus infection.

Clinical evaluation of pramipexole in advanced Parkinson's disease: results of a double-blind, placebo-controlled, parallel-group study.

We compared the efficacy, safety, an tolerability of pramipexole, an aminobenzathiazol-derived dopamine agonist with novel properties, with those of placebo in advanced PD patients with motor fluctuations under levodopa treatment. Pramipexole improved motor function of patients during "on" and "off" periods, decreased the time spent in "off" periods, reduced the severity of "off" periods, decreased disability and PD severity during "on" and "off" periods, as assessed by the Unified Parkinson Disease Rating Scale, and permitted a reduction in levodopa dosage. Adverse effects related to the central nervous system were similar to those reported with other dopamine agonists, and the gastrointestinal and cardiovascular tolerability of the compound was satisfactory.

Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine the tolerability and clinical effectiveness of intranasal ipratropium bromide for the treatment of symptoms of common colds. DESIGN: Multicenter, double-blind, randomized trial. SETTING: 3 university student health services. PATIENTS: 411 previously healthy persons 14 to 56 years of age who had cold symptoms that had lasted for no more than 36 hours, rhinorrhea subjectively judged to be of at least moderate severity, and documented nasal discharge of at least 1.5 g over a 1-hour observation period. INTERVENTION: Either 1) ipratropium bromide nasal spray 0.06% in buffered salt solution, two 42-micrograms sprays per nostril administered by metered pump spray; 2) control nasal spray, which consisted of buffered salt solution; or 3) no treatment. Treatments were self-administered three or four times daily during waking hours for 4 days. After receiving their morning dose, patients stayed at the study center for 6 hours on study day 1 and 3 hours on study day 2; symptom severity was recorded and nasal mucus discharges were collected and weighed hourly during these periods. RESULTS: Ipratropium recipients had 26% less nasal discharge than controls (P = 0.0024) and 34% less nasal discharge than untreated patients (P = 0.0001). Severity of rhinorrhea as judged subjectively was reduced in ipratropium recipients by 31% compared with controls and by 78% compared with untreated patients (P = 0.0001 for both comparisons). In addition to being associated with reductions in daily assessments of the severity of rhinorrhea (P < or = 0.003), ipratropium was associated with reduced sneezing on study days 2 (20% difference; P = 0.03) and 4 (30% difference; P = 0.02) but not with reduced nasal congestion compared with the control spray. Ipratropium was generally well tolerated but was associated with higher rates of blood-tinged mucus (16.8% in the ipratropium group compared with 3.6% in the control group; P = 0.01) and nasal dryness (11.7% in the ipratropium group compared with 3.6% in the control group; P = 0.021) than the control spray. Patient assessments of the overall effectiveness of treatment were more favorable for ipratropium than for the control spray (P < or = 0.026) or for no treatment (P < or = 0.002) on each day of inquiry (study days 1, 2, and 5). CONCLUSIONS: Intranasal ipratropium bromide provides specific relief of rhinorrhea and sneezing associated with common colds.

Pramipexole in patients with early Parkinson's disease.

We evaluated the efficacy, safety, tolerability, and pharmacokinetics of pramipexole, a novel dopamine D2 receptor agonist, in early Parkinson's disease (PD). The study design was a parallel, placebo-controlled trial using an ascending dose of 4.5 mg/day pramipexole maximum. All subjects received selegiline (10 mg/day) but were not treated with levodopa. Of the 55 subjects who received at least one dose of the study medication, all but one, in the placebo group, completed the trial, which was 9 weeks in duration. The primary efficacy endpoints were changes in scores from baseline to final measurement on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. The pramipexole group had a significantly greater improvement (p = 0.002) than the placebo group on UPDRS Part II (Activities of Daily Living). The change in score from baseline to final measurement on UPDRS Part III (Motor Examination) was not significantly different (p = 0.10) between the pramipexole and placebo groups, although the trend favoured the pramipexole group. All subjects in both the pramipexole and the placebo groups experienced one or more episodes of asymptomatic orthostatic hypotension; there was no significant difference between the pramipexole and the placebo groups in the number of subjects experiencing symptomatic orthostatic hypotension. The adverse events profile of pramipexole was similar, in general, to that of other dopamine receptor agonists. Plasma pramipexole levels increased linearly with dose. Pramipexole appears to be promising agent in the treatment of early PD.

A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold.

Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold.

Is treatment for alcoholism effective in persons on methadone maintenance?

A randomized prospective study of 625 drug addicts on methadone maintenance revealed that 105 (17%) were active alcoholics, 47 (8%) were inactive alcoholics, and 473 (76%) were not alcoholics. The active alcoholics were randomly assigned to abstinence therapy, controlled drinking with behavior modification, or a control group receiving the usual clinic services. There were no differences between treatment and control groups at baseline and during follow-up of up to 2 1/2 years, and there was no relation between remission and treatment, suggesting that the effectiveness of currently employed specific interventions for alcoholism in active alcoholic addicts maintained on methadone cannot be demonstrated.

Alcoholism among narcotic addicts and patients on methadone maintenance.

There was no difference in prevalence of current alcoholism between new admissions to a methadone-maintenance treatment program (MMTP) and patients already in MMTP at least one year, by previous treatment for drug misuse, or between MMTP patients and the population of the surrounding community.

Opiate v CNS depressant therapy in neonatal drug abstinence syndrome.

Paregoric and phenobarbital, administered randomly in 153 passively addicted neonates, initially appeared to control neonatal abstinence signs equally well. However, seven of the 62 phenobarbital-treated newborns had abstinence-associated seizures within the first month of life, while none of 49 paregoric-treated neonates had seizures. Forty-two neonates initially requiring no specific pharmacotherapy for abstinence signs were born to mothers taking less methadone hydrochloride just before delivery. Five of those 42 neonates, however, had seizures within the first 14 days of life. Seizure occurrence could not be predicted from analysis of early abstinence patterns. We consider paregoric to be the treatment of choice for the neonatal abstinence syndrome. Phenobarbital use should be monitored with serum drug levels and modification of recommended dosage regimens considered.

Failure of mean red cell volume to serve as a biologic marker for alcoholism in narcotic dependence. A randomized control trial.

Mean red cell volume, mean red cell hemoglobin, and mean red cell hemoglobin concentration were measured in a prospective, longitudinal, single-bind study of alcoholism and its treatment in 625 patients receiving methadone. Mean red cell volume and mean red cell hemoglobin were significantly elevated in alcoholic as compared with nonalcoholic patients (p less than 0.001), with a sensitivity of 40 and 51 percent, respectively. The ability of an elevated mean red cell volume and mean red cell hemoglobin to exclude active alcoholism (specificity) was 86 and 76 percent, respectively. Development of excessive consumption of alcohol during the course of the study was not associated with significant elevations over baseline values of either mean red cell volume or mean red cell hemoglobin. Similarly, the mean red cell volume and mean red cell hemoglobin in the small number of patients whose consumption of alcohol markedly decreased did not significantly change from baseline values. These findings suggest that although the specificity of mean red cell volume may be helpful in eliminating those persons who are not actively alcoholic, its sensitivity does not permit its use as a biologic marker for alcoholism. The inclusion of an elevated mean red cell volume as a major criterion for the diagnosis of alcoholism should be reconsidered.

Alcoholism as a risk factor in methadone maintenance. A randomized controlled trial.

A randomized controlled trial of 625 addicts on methadone maintenance identified 105 (17 percent) as active alcoholics, 47 (8 percent) as inactive alcoholics, and 473 (75 percent) as nonalcoholics. Subjects were followed for up to 29 months (mean 53.7 weeks) to assess the influence of alcoholism on the rehabilitative process. During the study, alcohol consumption significantly decreased (p less than 0.001) in active alcoholics. Indexes of productive activity on entry or during follow-up revealed no significant differences between active alcoholics and other patients with the exception of alcohol-related hospitalizations (p less than 0.001). Behavioral indexes consistently improved with treatment in all patients, being greatest among active alcoholics (p less than 0.01). During the study, 28 (7 percent) of 399 nonalcoholics were recategorized as active alcoholics, and remission from alcoholism was noted in 28 (27 percent) of patients who were initially classified as alcoholic. These findings suggest that alcoholism does not significantly affect rehabilitation from narcotic use and therefore should not be cause for detoxification from methadone maintenance.

The relationship between hepatitis B surface antigen and antibody and continued drug use in narcotic dependency: a randomized controlled study.

Hepatitis B surface antigen (HBsAg) and antibody (antiHBs) were determined in 556 narcotic addicts entering a randomized prospective study of alcoholism in patients on methadone maintenance. Only 37% of patients were either negative for HBsAg or without detectable titers of antiHBs. No difference in reactivity existed between alcoholic as compared to nonalcoholic patients and the use of street heroin as compared to use of methadone upon entry to the study. At least a one year follow-up was obtained in 229 (41%) patients with 25 of 88 (28%) patients initially without titers to antiHBs developing detectable titers. No relationship existed between development of antiHBs titers and elevation of liver function tests or the subsequent use of parenteral heroin. These findings suggest that the development of titers to antiHBs in persons on methadone maintenance should not be used as an indication of parenteral drug use.

Alcohol consumption in persons on methadone maintenance therapy.

Alcohol use among methadone maintenance treatment program (MMTP) patients is substantial and a frequent impression is that addicts accelerate their consumption once in MMTP. This study reports an attempt to more clearly define alcohol consumption in opioid dependence as well as changes associated with methadone maintenance therapy. Two-day alcohol consumption (2-day EtOH) data were collected initially and quarterly on participants in a randomized controlled trial of intervention for alcoholism. Blood alcohol levels (BAL) were also determined. 17% of the participants were classified as active alcoholics (AA) and 8% as inactive alcoholics (IA). Two-day EtOH and BAL were significantly higher for AA than AI and nonalcoholics (NA, and AI higher than NA. Two-day EtOH decreased significantly over time for AA, AI, and NA. These findings indicate that AA among narcotic addicts and those on MMTP consume large quantities of EtOH but that consumption decreases with time on MMTP. The results, in confirmation of the work of others, suggest that entry and participation in MMTP has a broader effect than just on the use of narcotic drugs.

The effect of alcoholism in methadone-maintained persons on productive activity: a randomized control trial.

The effect of alcoholism on indices of productive activity was determined in a prospective, randomized, and controlled study of alcoholism in narcotic addicts undergoing methadone maintenance (MM) therapy. Indices of productive activity included: percentage of persons engaged in productive activities; number of days worked per quarter; number of arrests per quarter; number of hospitalizations; and days of hospitalizations per quarter. Baseline as well as longitudinal data were obtained on operative alcoholics (OA), inactive alcoholics (IA), and nonalcoholics (NA). OA patients were subsequently randomized to a control group or groups receiving either abstinence-oriented insight group therapy or controlled drinking-oriented behavioral modification group therapy. The retention rate in MM of OA versus NA during the 29-month clinical phase of the study did not differ significantly. Similarly, no significance was reported with respect to any index of productive activity. Indices of productive activity in OA undergoing treatment as compared to those randomized to the control group also did not reveal any significant differences. The compliance of OA in seeking and maintaining therapy for their alcoholism, however, was sufficiently poor so that any conclusions concerning the effectiveness of therapy on indices of productive activity should be viewed cautiously.

The ability of a Self-Administered Alcohol Screening Test (mSAAST) to detect future excessive alcohol consumption in persons on methadone maintenance.

A modified Self-Administered Alcoholism Screening Test (mSAAST) was prospectively administered to 625 narcotic addicts participating in a randomized clinical control trial to study its effectiveness in detecting future excessive alcohol consumption. At entry into the study, of 105 patients categorized as active alcoholics, 84 (80%) obtained a positive score on the mSAAST. Of 77 patients initially identified as being at risk for developing alcoholism (potential alcoholics) by mSAAST scores, 31 (40%) subsequently developed characteristics of excessive alcohol consumption. Of the 321 patients classified as nonalcoholic by history as well as mSAAST score, a significantly lesser proportion (15%) developed characteristics of excessive alcohol consumption (p less than 0.001). These findings suggest the mSAAST to be a useful adjunctive indicator of persons at risk of developing excessive consumption of alcohol. It is probable that the usefulness of the mSAAST extends beyond narcotic-dependent populations and may be of value in identifying the potential for excessive alcohol consumption in other populations.

Abnormal liver function tests as biological markers for alcoholism in narcotic addicts.

Liver Function Test (LFT) abnormalities are frequently observed in narcotic addicts. However, the role of alcohol in producing such changes remains unclear. In order to evaluate the effects of alcohol in producing LFT elevations as well as the use of routine LFTs to serve as biochemical markers for alcoholism in narcotic addicts, 612 addicts participating in a randomized control trial of intervention in alcoholism were studied. Baseline parameters including LFTs and history of alcohol use were obtained on entry into the study and subsequently periodically during follow-up which varied from 6 months to 2 1/2 years (mean 13.5 months). On entry to the study, 104 of 612 (17%) of addicts were classified as alcoholics. Mean values of LFTs (SGOT, SGPT, Alkaline phosphatase, GGTP) in the alcoholic cohort were significantly increased compared to those among nonalcoholics (p less than 0.01 to less than 0.001 for individual tests). Mean values of LFTs did not significantly change during methadone maintenance in either group. Although a greater proportion of alcoholic addicts had elevated LFTs, the predictive values for each test (18 to 35%) were sufficiently low to prevent them from being used as biochemical markers of alcoholism. These findings suggest that although elevations in LFTs are frequently present in narcotic addicts and are significantly greater among addicts who are also alcoholic, most elevations are not specifically due to alcohol. Conventional LFTs are therefore of limited value in assessing alcoholism among narcotic addicts.

Evaluation of a combination of self-administered fluoride procedures for the control of dental caries in a nonfluoride area: findings after four years.

Nearly all children who attend elementary school (grades K through 6) in a rural community have participated since 1972 in a school-based caries preventive program consisting of daily ingestion of a 1-mg fluoride tablet and weekly rinsing with a 0.2% sodium fluoride solution. 3they also regularly receive toothbrushes and a fluoride dentifrice for use at home. Examinations conducted after four years showed that the prevalence of dental caries among continuous participants, 7 through 12 years of age, was reduced by 35% compared with baseline findings; mean DMFS scores in 1972 and 1976 were 5.39 and 3.49, respectively. The preventive program inhibited decay in all three types of surfaces: approximal surfaces received about twice the relative protection against decay (70%) as buccolingual surfaces (34%) and more than three times as much as occlusal surfaces (22%). A comparison of estimates of four-year increments of decay taken from cross-sectional data at the baseline and actual increments from the 1972 and 1976 examinations showed that, for children ages 6 through 15, the incremental DMFS score was 41% lower during the period of the program than before its initiation. Findings in older children (ages 13 through 15) in 1976 who had stopped participation when they left elementary school at about age 12 showed evidence of strong posttreatment effects--as great as 31% fewer DMFS for 14-year-old children.

Effect of chewable fluoride tablets on dental caries in schoolchildren: results after six years of use.

Two groups of children, initially in the first and second grades, chewed, rinsed with, and swallowed an acidulated phosphate-fluoride tablet containing 1 mg of fluoride either once or twice a day in school. A control group of children followed the procedure once a day using a placebo tablet. An evaluation after six years of treatments showed that both the once-a-day and the twice-a-day procedures with fluoride tablets effectively reduced the incidence of dental caries.