The safety and efficacy of treatment with zolpidem for one month were assessed in an open evaluation by 335 general practitioners in 1219 insomniac patients aged ≤ 50 years. The physician evaluated safety by means of complaints of adverse events reported by the patient at the follow-up visit. Efficacy was assessed by means of changes in the severity of insomnia and the patient's well-being. The investigator evaluated each patient's insomnia using two criteria: lack of nocturnal sleep and its daytime consequences. Severity of lack of nocturnal sleep was assessed by means of an eleven-point scale ranging from 0 = absent to 10 = major. Patient's well-being was based on the assessment of the following parameters: wake-up and daytime condition, mood, and attitude to tasks. Mood and attitude to tasks were assessed in the morning, at midday and in the evening. The total number of adverse events reported was 106 (8.7%) and the most frequent were somnolence, headache, paroniria and vertigo. After one month of treatment with zolpidem, there was a marked and highly significant shift in the severity of the distribution of insomnia from higher to lower scores. Beneficial effects of zolpidem on wake-up/daytime condition, mood and attitude to tasks were also highly significant. This Post-Marketing Surveillance study supports the excellent efficacy and safety of zolpidem in a large sample of middle-aged and elderly subjects with insomnia, reported in previous placebo-controlled studies.
The effect of acute high-dose administration of absolute ethanol (6 ml/kg i.p.) on oxidized (GSSG) and reduced (GSH) glutathione levels in various organs of the rat (eye, liver, brain, heart, lung, stomach, testis, leg adductor muscle) was studied. GSH and GSSG levels are affected to different degrees depending on the organ concerned. The redox couple is also organ-specific: it does not change in muscle, becomes halved in the liver, doubled in the eye and brain, increased three times in the heart, eight times in the testis and eleven times in the lung. Lipid peroxidation evaluated by tissue accumulation of malondialdehyde (MDA) is present in liver, eye and brain. In the eye we found a correlation between a 60 % increase in GSSG levels related to MDA production (92.1 nmoles/g tissue).
The efficacy, tolerability and effect on quality of life of nisoldipine coat core (CC) and enalapril were compared in elderly patients with mild-to-moderate hypertension (JNC IV definition) in a four-centre, double-blind, double-dummy, randomised trial. Eighty patients, aged 65-93 years, with supine diastolic blood pressure (DBP) of 94-114 mmHg underwent a 4-week placebo run-in period, after which they were randomised to receive either nisoldipine CC, 10 mg once daily, plus enalapril placebo, or enalapril, 5 mg once daily, plus nisoldipine CC placebo. To achieve blood pressure control, the dose of nisoldipine CC could be increased to 20 mg and 40 mg, and the dose of enalapril to 10 mg and 20 mg over the following 4 weeks. The final dose was maintained for the remainder of the 10-week active treatment phase. Both drugs produced equivalent reductions in supine trough DBP and supine systolic blood pressure. The number of patients responding to treatment (reduction of DBP to <90 mmHg) was similar for the two treatments (87% for nisoldipine CC vs 91% for enalapril). Blood pressure was controlled in 62% of patients who received nisoldipine CC, 10 mg, and in 32% and 6% of patients whose dose was titrated to 20 mg and 40 mg, respectively. In the enalapril-treated group, blood pressure was controlled in 62% and 38% of patients whose dose was titrated to 5 mg and 10 mg once daily, respectively. Neither drug had any effect on heart rate. Adverse events were minor, and both drugs were well tolerated. Quality of life assessment using a modified Red Cross questionnaire revealed more favourable global scores in patients who had received nisoldipine CC than in those who had received enalapril. Nisoldipine CC also had more favourable effects on the individual dimensions of the quality-of-life scale, most notably in the daily activity dimension. In conclusion, nisoldipine CC has equivalent efficacy to enalapril in controlling blood pressure in elderly patients with mild-to-moderate hypertension. Moreover, it is well tolerated and does not appear to compromise quality of life in these patients.
Nisoldipine CC and amlodipine are both once-daily calcium channel blockers. Amlodipine has proven long action and efficacy in the treatment of mild to moderate hypertension. This study tests the equivalence in efficacy between nisoldipine CC and amlodipine in patients with mild to moderate essential hypertension (diastolic blood pressure (DBP) 95-114 mmHg) over a range of doses (nisoldipine CC, 10, 20, 40 mg od; amlodipine 5, 10 mg ed). Within the multicentre, randomized, double-blind, double-dummy, dose-titration study, 214 patients were randomized to receive either nisoldipine CC (10 mg od) or amlodipine (5 mg ed). Treatment was titrated at two-weekly intervals as necessary. The primary efficacy endpoint was reduction in sitting trough DBP; secondary efficacy endpoints were reductions in systolic blood pressure (SBP) and heart rate. Equivalence between nisoldipine CC and amlodipine was shown for the primary efficacy endpoint. Sitting DBP was reduced by 14.3+/-7.6 mmHg and 13.6+/-6.8 mmHg for nisoldipine CC and amlodipine, respectively. Response rates at the end of the study were 71% for nisoldipine CC and 75% for amlodipine. Reductions in the secondary efficacy endpoints were also similar for each drug. The numbers of total and drug-related adverse events were similar for both drugs, and were typical of those associated with calcium channel blockers. There were no dose-related adverse events for either drug. Nisoldipine CC provides equivalent reduction in DBP to amlodipine throughout the dose range. Furthermore, the three doses of nisoldipine CC tested in this study demonstrate the potential for enhanced flexibility in the control of mild to moderate hypertension.
To investigate the role of allergy in the appearance and persistence of otitis media with effusion (OME), 282 young people up to 15 years old were studied. Their selection was based on the presence of persistent OME, a positive personal or family history and evidence of allergy on physical examination. The diagnosis of OME was based upon otoscopic findings, as well as on a type-B flat tympanogram. All 282 patients underwent laboratory determination of total and specific IgE (Pharmacia Phadebas RAST) for inhalant and food allergens the results of which allowed division of the patients into allergic and non-allergic groups. The study lasted almost four years. The parameters studied included sex, age, place of residence, seasonal distribution of OME attacks, duration of morbidity, number of OME episodes and their duration, total and specific IgE for inhalant and food allergens. The results show that, in allergic patients, OME tends to recur, is more persistent and there is a greater incidence and a different seasonal distribution of OME attacks. Boys suffered more commonly from allergic OME than girls. Finally, cetirizine, a second generation anti-H1 agent with additional antiallergic properties, is proposed as a useful treatment for allergic OME.
Anxiety and panic are the most common psychiatric disorders. Anxiety usually becomes chronic and progressive. Symptoms of anxiety appear relatively early, as do depression and drug abuse, and often occur together with other disorders. Each year, at least 5 percent of the population presents with symptoms of anxiety severe enough to seek medical help. Sufferers from anxiety are big consumers of health care and make up 10-15 percent of the clientele of internists and cardiologists. The combination of psychotherapy and benzodiazepines is the therapy of choice, provided that it is correctly applied and that proper precautions are taken when (benzodiazepine) treatment is withdrawn.
Vigabatrin is an anticonvulsant drug which inhibits the catabolic enzyme GABA-transaminase (GABA-t), thereby increasing the action of synaptically released GABA. Psychiatric complications, somnolence, fatigue, confusion, headache, abdominal pain, anorexia and weight gain have been described as common adverse effects of vigabatrin. We examined the effect of vigabatrin on hair growth. In 5 of 52 patients who received vigabatrin for partial complex seizures, moderate hair loss or changes in hair structure developed. The complaints began after 3-7 weeks of vigabatrin treatment. Recovery of hair loss was seen in al patients after cessation of treatment. Because of its social relevance, hair loss must be taken into consideration during vigabatrin therapy, especially in young patients.
A double-blind cross-over placebo controlled pharmacodynamic trial was conducted in 24 healthy volunteers in whom the impact of the hepatic first pass effect on pharmacodynamic parameters of single doses of 10 mg of loratadine and 10 mg of cetirizine was determined using the histamine skin prick test. The volunteers were subjected to three single day study sessions where skin prick tests were conducted 20 minutes before and 2, 4 and 6 hours after drug intake, The impacts on the induced wheals were classified into 5 wheal and flare reduction groups defined as <20 %, 20-40 %, 40-60 %, 60-80 % and >80 %. The results indicate that strength and spread of the antihistaminic effect of loratadine varied widely from one time measure to the next and were mainly concentrated around the first three reduction categories, while strength and spread of the antihistaminic effect of cetirizine varied less and were mainly concentrated around the higher reduction categories, These results seem to indicate that the hepatic first pass effect, as well as the antihistaminic potency, influences the pharmacodynamic response on histamine cutaneous reactivity.
We evaluated the efficacy and tolerance of a single daily dose of quinapril in 10 patients with mild to moderate arterial hypertension. Patients were treated for 12 weeks after a 2-week placebo run-in period. 24-hour monitoring of arterial pressure was performed the day before inclusion and after treatment for 12 weeks. Standing and sitting blood pressures were measured at the end of the 4th, 8th and 12th weeks. Pressures recorded during 24-hour monitoring showed a significant reduction of systolic, diastolic and mean arterial pressures. A significant decrease in blood pressure was seen after 4 weeks' treatment and persisted until the end of the trial, Heart rate remained unchanged throughout the study. Biological parameters did not change. No adverse effects were reported and there were no changes in laboratory tests. Tolerance may be considered excellent.
The aims of the present study were to determine whether the imidazopyridine zolpidem and the benzodiazepine flunitrazepam differentially affect the sleep architecture, and whether zolpidem had any residual effects on driving performance or memory functions the morning after nightly drug administration. These effects were compared with flunitrazepam, partial sleep deprivation and placebo. Seventeen women who complained of chronic sleep disturbances underwent four experimental sessions on separate nights at weekly intervals - initially, during partial sleep deprivation, and after single doses of zolpidem 10 mg, flunitrazepam 2 mg and placebo administered in a double-blind, crossover design. Polysomnographic recordings were made each night, and verbal learning and driving tests were performed the following morning and subjective assessments of sleep quality, daytime sleepiness and activation, effort to perform the tests and driving quality determined by questionnaire. Polysomnographic recording showed that zolpidem and flunitrazepam significantly shortened sleep onset latency. Zolpidem respected the overall sleep architecture, without disturbance of NREM 3/4 sleep and REM sleep. Flunitrazepam significantly decreased REM sleep over the whole night. Zolpidem and flunitrazepam both enhanced deep NREM 3/4 sleep during the first two hours of sleep. Subjectively, flunitrazepam improved sleep quality and duration, but subjects reported feeling significantly more drowsy and less active during the day than after placebo. Both hypnotics significantly reduced the recalled frequency of nocturnal awakenings. Psychometric tests showed that flunitrazepam caused significant memory impairment the next morning, whereas zolpidem did not produce any disturbance of memory function. Driving performance was not disturbed by any drug treatment or partial sleep deprivation. We conclude that zolpidem 10 mg is an effective hypnotic which causes no psychometric dysfunction the next day. Sleep architecture remained unaffected by zolpidem and cyclicity was maintained without enhancement of duration.
For 40 years penicillin and erythromycin have been the most frequently used antibiotics for the treatment of streptococcal pharyngitis, especially caused by Streptococcus beta-hemolyticus. In recent years, several reports have suggested a loss of efficacy of these antibiotics due to progressively increasing resistance. What about Belgium? In order to answer this question, we asked over fifty paediatricians to treat 5 children each with exudative pharyngitis with erythromycin in a daily dose of 50 mg/kg for 10 days. A throat culture before and after treatment was requested. Between October 1993 and February 1994, 52 paediatricians included 278 children in this study, 147 boys and 131 girls, whose mean age was 4 +/- 3 years (mean +/- SD). Data from 16 children (6%) were not evaluable. In 19/262 children (7%) no pretreatment throat culture was obtained. In 109 of the remaining 243 children (45%), pre-treatment throat culture was positive for Streptococcus beta-hemolyticus. In 51 of these children (47%), a post-treatment throat culture was obtained; of these 48 (94%) were negative for Streptococcus beta-hemolyticus. The mean duration of treatment was 9 +/- 2 days. Clinical success, defined as absence of symptoms, occurred in 248 of the 262 evaluable patients (95%). The clinical success rate, in children with a positive throat culture for Streptococcus beta-hemolytius, was 95 % (104/109). Resolution of symptoms occurred within 3 +/- 2 days. These results show that the bacterial origin of the treated exudative pharyngitis was common and that both clinical success and bacterial eradication were remarkably high (95%). We may conclude that in view of its efficacy, the ecology and the cost of treatment, erythromycin remains in Belgium a drug of first choice for the treatment of exudative pharyngitis in children.
We assessed the preference, efficacy and tolerability of budesonide treatment with Turbuhaler(R) in 24 previously steroid-free asthmatic patients by comparing it to the delivery of budesonide by metered dose inhaler (MDI) with Nebuhaler(R). In an open randomized, cross-over study we tested the two delivery techniques over two four-week periods with a dose of 400 mu g budesonide administered twice daily. Compared to the findings in a two-week run-in period, lung function improved significantly with both active treatments, and there were no differences between the two delivery techniques; FEV(1) increased compared to baseline by 0.35 L with Turbuhaler (p<0.001) and 0.36 L (p<0.001) with Nebuhaler. Bronchial responsiveness to inhaled methacholine decreased significantly and equally with both budesonide treatments (Turbuhaler p<0.0001; Nebuhaler p<0.002). Budesonide Turbuhaler and Nebuhaler were also equally efficient in increasing morning and evening peak expiratory flow rate (PEFR) as well as in attenuating the symptoms of asthma. The overall incidence of oropharyngeal side effects was low with no significant differences between the two delivery systems: irritation in the mouth or airways occurred in three patients with Turbuhaler and five with Nebuhaler, coughing after inhalation one with Turbuhaler and three with Nebuhaler; three reported hoarseness with Turbuhaler and one with Nebuhaler. The differences between the delivery systems were not significant. Sixteen patients preferred Turbuhaler and eight Nebuhaler. These data indicate that the Turbuhaler technique is an efficient and safe alternative when inhaled steroid treatment is considered for an asthmatic patient.
In order to investigate experimentally possible synergism between a passiflora extract and a kava extract, both were tested individually and in combination in a controlled pharmacological study in the mouse. The effects on amphetamine-induced hypermotility and on barbiturate-sleeping-time were studied. The results show that both drugs exert statistically significant sedative effects. Their nature differed with each single extract. While the sedative effect of kava manifested itself as a pronounced reduction in amphetamine-induced hypermotility relatively greater than that of passiflora, the reverse was the case for prolongation of barbiturate-sleeping-time which was greater with passiflora than kava. Synergism between the two drugs was observed when the two extracts were administered simultaneously.
3,192 hospitalized patients with severe infections were treated with piperacillin alone (6-16 g daily) when urological, gynaecological or abdominal infections were diagnosed, or with a combination therapy of piperacillin and the preferred aminoglycoside within the hospital in case of pulmonary infections. The susceptibility to piperacillin of all Gram-negative bacteria as well as of anaerobic microorganisms isolated ranged between 85 % and 95 %. Overall, 90 % of the patients included in the study were considered as cured or improved. Piperacillin was well tolerated during this clinical trial: global tolerability was assessed as good in 90.1 % of patients, The most common side effect was thrombophlebitis, occurring in 7.5 % of patients. These data allow us to suggest the use of piperacillin as a first-choice antibiotic in monotherapy, or together with an aminoglycoside, in the treatment of severe infections in hospitalized patients including elderly patients and/or patients with underlying disorders.
Piracetam, a gamma aminobutyric acid (GABA) analogue and the prototype "nootropic" drug, has been widely used in the treatment of memory and cognitive deficits in several disease entities including Alzheimer's disease. Since 1978, case reports and clinical trials have shown the therapeutic efficacy of piracetam in patients with myoclonus of diverse aetiology, especially of cortical origin. Experimentally, piracetam seems to increase brain energy metabolism, hippocampal acetylcholine release and the firing of neurons in the locus coeruleus. Its effects are either additive to or antagonise the actions of glutamate, GABA and acetylcholine and are directed towards specific membrane sites. Published data support the view that cortical myoclonus represents a valid human model for demonstrating the modulatory effects of piracetam on neurotransmission.
Recent experimental data suggest that glycinergic drugs possessing a central action might potentiate the effect of neuroleptics and be useful in the treatment of memory disorders and Alzheimer's disease. An action of these glycinergic compounds on strychnine insensitive sites, potentiating the response of N-methyl-D-aspartate receptors, was proposed to explain these effects. However it has also been shown that serotonin (5-HT) and dopamine (DA) are involved in the mnemonic process and in the pathophysiology of psychosis, respectively. N-palmitoyl glycine (PG), a new glycinergic prodrug, demonstrated nootropic effects and potentiated the action of neuroleptics. Similar effects were recently obtained with D-cycloserine (DCS). We therefore investigated whether glycinergic drug-induced changes in brain 5-HT and DA levels, could be involved in the production of these effects. Wistar rats received PG in doses of 2, 10, 150 mg/kg i.p. An increase in 5-HT turnover in the cortex of rat brain was observed, a result similar to that seen after DCS administration (5, 50 mg/kg i.p.). A decrease in DA turnover was observed in the striatum after DCS treatment. Monoamine function might therefore be involved in these glycinergic drug-induced effects.
The use of cyclosporin A(CsA) has increased short and long term survival in organ transplanted patients and reduced the risk of rejection. It has also been used in primary biliary cirrhosis, autoimmune chronic hepatitis, primary sclerosing cholangitis, schistosomiasis, acute fulminant hepatitis and chronic granulomatous disease. We administered r-IFN alpha (3MU t.i.w.) to a 64 years old woman with chronic active hepatitis C. The patient presented with thrombocytopenia and anaemia after 4 weeks' treatment. IFN was suspended and concentrated platelet infusions were given together with steroid treatment for three months; however no great improvement occurred. Cortisone was then suspended and cyclosporin treatment initiated. The continuing improvement in transaminase, RBC and platelets induces us to recommend cyclosporin as an alternative treatment in virus or cytokine induced immune disorders.
Thirteen healthy adult women, suffering from long-standing chronic constipation, were enrolled into a trial of 8 weeks duration. They were first administered placebo powder for a laxative-free run-in period of 2 weeks, then lactitol at a flexible, individually adaptable dose for 4 weeks, followed by another two week follow-up period, again on placebo. Throughout the trial the participants kept a daily record of medication intake and bowel habits and collected isolated or 24-h stool samples at given intervals. The samples were analysed in terms of wet and dry weight, bacterial population, and volatile fatty acid concentration. Results in 11 participants showed that lactitol intake was followed by statistically significant improvements in stool characteristics (increase in wet & dry weight, softer consistency) as well as in microbiological variables (increase in total viable bacterial count and in anaerobic fermentative strains). In conclusion, it can be stated that the beneficial macroscopic changes observed in stool characteristics are the reflection of lactitol acting as an energy substrate for anaerobic fermenting commensal bacteria.
The authors have developed a questionnaire allowing overall evaluation of risk factors in hypertensive patients, The "Heart Smart Program" was, however, primarily designed to motivate patients to undertake life style improvement by making them aware of their shortcomings and assisting clinicians in achieving this objective.
We performed an open evaluation of alprazolam as a hypnotic agent given the night before operation and as a preoperative anxiolytic agent in 105 patients undergoing different types of surgery and anaesthesia. Five groups of patients were studied. The first group was treated using an empirical dosage schedule. Subsequent patients were treated using schedules based on the results of subjective (patient evaluation of the quality of sleep) and more objective measurements: effects on the cardiovascular system, respiratory rate, skin temperature, evaluation of sleep by the nurse, evaluation by the anaesthetist both of anxiolysis and the quality of recovery and recovery time. We found that the most effective dosage schedule takes into consideration both age and body weight: > 70 years old: hypnotic 0.5 mg preoperative anxiolytic 0.5 mg less than or equal to 70 years old and weighing less than or equal to 70 kg: hypnotic 0.5mg preoperative anxiolytic 0.5 mg less than or equal to 70 years old and weighing > 70 kg: hypnotic 1.0 mg preoperative anxiolytic 0.5 mg Our results indicate that alprazolam is an effective hypnotic and preoperative anxiolytic agent which was safe when used in these doses.
