A prospective study was carried out in 15 patients with peripheral obstructive arterial disease (Fontaine Stage II), with obstructions in the thigh region, to assess the effect of treatment with pentoxifylline on clinical and haemodynamically measurable factors, particularly changes in the post-ischaemic increase in peripheral blood pressure. After a 7-day wash-out period, patients were hospitalized for 1 week and received a daily infusion of 300 mg pentoxifylline plus a 600 mg tablet orally in the evening. They were then treated as out-patients for 2 weeks, receiving 1200 mg pentoxifylline orally per day. Pain-free and maximum possible walking ranges, using a treadmill ergometer, were determined on Days 7, 14, 21 and 28 of the study. Measurements were made at the same intervals, using Doppler ultrasound, and the peripheral resting blood pressure index and post-ischaemic blood pressure index calculated. The results showed significant improvement in both pain-free and maximum walking range after intravenous and oral therapy and this was particularly noticeable in those patients who, before treatment, had a walking range of less than 150 metres: their pain-free range doubled in the first week. There was a slight increase in the resting Doppler blood pressure indices during treatment and a clear, significant increase in the post-ischaemic pressure index 90 and 120 sec after the induced ischaemia ended.
A study was carried out in 68 otherwise healthy male naval crew members to assess the long-term effectiveness and side-effects of routine transdermal scopolamine administration for the prevention of seasickness. The transdermal patches were applied to the mastoid process before each sailing and the subjects generally used 2 patches a week. Check-ups were made every 3 months over a period of 3 years. The average reported seasickness severity (on a scale of 0 to 7) after 6 months at sea prior to the administration of transdermal scopolamine was 5.64 +/- 0.11 (mean +/- S.E.M.), in comparison with 3.14 +/- 0.23 post-administration (p less than 0.001). A significant improvement was found in the self-estimated performance at sea whilst receiving the drug: 65.7% +/- 3.38% (mean +/- S.E.M.), compared to 25% +/- 2.24% beforehand (p less than 0.001). Contact dermatitis precluded the use of transdermal scopolamine in 3 (4.4%) subjects. The only other significant side-effect was dryness of mucous membranes. In conclusion, transdermal scopolamine was found to be effective in the prevention of seasickness and improvement of performance at sea during 3 years of follow-up and routine administration of the drug was not complicated either by severe side-effects or by performance disturbances.
A prospective study was carried out in 43 hospitalized patients with respiratory or other serious bacterial infections requiring intravenous antibiotic therapy to assess the efficacy and tolerance of amoxycillin/clavulanic acid ('Augmentin'). After bacteriological and laboratory investigations patients were started on 1 g amoxycillin plus 200 mg clavulanic acid intravenously every 8 hours for the first 3 days and then were treated orally at the same dosage. Duration of treatment varied according to the type and severity of the infection, with a minimum of 10 days. Efficacy of treatment was evaluated by the clinical response, judged by the resolution of signs and symptoms of infection. The results showed that there was a clinical cure rate of 88.4%. Local tolerance was excellent and there were few side-effects reported. Six patients experienced vomiting which led to the withdrawal of treatment in 1 patient.
Apart from alcohol, various other substances with a psychotropic effect have been discussed recently in relation to their association with road traffic safety. There has been a general lack of hard facts, however, on how much drug use and abuse influence this. In the absence of data on the frequency of such effects, a representative random sample (approx. 8000 persons) of the Austrian population was interviewed and questioned on their drug intake. A smaller sample (2007 persons) was also questioned as to their behaviour regarding road traffic participation. The results showed that those drugs taken most frequently belong to the 'analgesic' group, whilst the frequency in use of substances to which greater importance is attached currently regarding road safety is relatively low (tranquillizers by 4%; strictly 'psychotropic' drugs by 0.3% to 0.6% of the population). These findings are similar to those reported in English-speaking countries. Data analysis showed that socio-cultural factors (age, sex, marital status and profession) influence the frequency and type of drug intake. The definition of drug abuse and addiction used (increase of dosage, inappropriate use, effect changes) proved somewhat unreliable and called into question the criteria used for diagnosis and categorization of persons at risk. In view of the results of previous studies and the importance attached by critics, an unexpected finding of this survey was the minor influence exerted by tranquillizers on road traffic safety. However, the number of cases for individual drug classes was relatively small and there is a need for more broadly based studies of a similar design before reaching firm conclusions.
A retrospective analysis was carried out of the results of 115 intensively-treated cancer inpatients receiving 91 treatment courses of amphotericin B given in an empirical fashion. Amphotericin B was administered over 1.5 to 2 hours at a dose of 0.6 to 0.7 mg/kg/day. Median duration of neutropenic fever before amphotericin B administration was 5 days (range 1 to 32 days) and median total amphotericin B dose was 480 mg (range 10 to 2450 mg). In 56 (61%) of 91 amphotericin B courses, neutropenic fevers resolved; this occurred a median of 3 days (range 1 to 15 days) after amphotericin B was begun and at a median dose of 120 mg (range 10 to 850 mg). Response to amphotericin was independent of positive cultures for fungus or sites of positive culture. Adverse reactions to amphotericin B included rigors (89% of courses), fever (23%), bronchospasm (9%), and transient hypotension (9%). Median increase above baseline serum creatinine in patients given amphotericin B was 0.5 mg/dl (range 0 to 2.6 mg/dl) compared to a median of 0.1 mg/dl (range 0 to 2.9 mg/dl) in a similar group of intensively-treated cancer patients who did not receive amphotericin B. Amphotericin B was well tolerated when given by rapid infusion and was associated with prompt resolution of neutropenic fever in the majority of patients.
In an open clinical multi-centre trial carried out in five Danish psychiatric departments, patients suffering from acute psychosis including mania or exacerbation of chronic psychosis were given injections of 5% zuclopenthixol acetate in 'Viscoleo'. The object of the trial was to evaluate the treatment by means of a global assessment of the severity of the psychosis, the therapeutic effect and the side-effects. The results showed that the treatment was rapidly effective in reducing the severity of psychotic symptoms combined with an advantageous unspecific sedation. The side-effect profile was similar to that after other neuroleptics. Special attention should be paid, however, to a possible occurrence of acute dystonia which was observed particularly in young men with acute psychosis.
The protective effect of xanthines against E. coli-induced and cytokine-induced lung injury in guinea-pigs has been demonstrated recently. In the present study, the possible protective effects were examined of an analogue of pentoxifylline, HWA-138, a xanthine derivative, on lung injury in septic guinea-pigs. Three groups of animals were studied over a period of 8 hours: Group I animals--saline control injected intravenously with 3 ml 2% lysine/normal saline followed by a continuous lysine/saline infusion (1 ml/kg/hr); Group II--septic control injected intravenously with 2 x 10(9)/kg Escherichia coli followed by a continuous lysine/saline infusion (1 ml/kg/hr); and Group III--E. coli septicaemia plus HWA-138 continuous infusion (HWA-138 dissolved in lysine/saline) began with a bolus (10 mg/kg) followed by a HWA-138 continuous infusion (3 mg/kg/hr) started 60 minutes before injection of E. coli. Arterial blood pressure and white blood cell counts were monitored serially for 8 hours. Lung water (wet-to-dry ratio) and the concentration ratio of 125I-labelled albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared to plasma (125I-albumin BAL/plasma, 125I-albumin lung/plasma) were examined. Results demonstrated that an intravenous injection of E. coli caused an increased W/D ratio (p less than 0.01) and an increased 125I-albumin lung/plasma ratio (p less than 0.01). In contrast, the HWA-138-treated group did not demonstrate significantly increased W/D lung ratios (p less than 0.01) and 125I-albumin lung/plasma ratios (p less than 0.05). The data suggest a possible role for HWA-138 in attenuating sepsis-induced lung injury.
A prospective, randomized comparative trial was carried out in 31 children suffering from lower respiratory tract infections, mainly bronchopneumonia or pneumonia. Twenty-one children received oral cefetamet pivoxil in a dose of 20 mg/kg/day (10 children) or 40 mg/kg/day (11 children), and 10 children 30 mg cefaclor/kg/day for 7 days. Clinical signs and symptoms, i.e. fever, dyspnoea, altered breath sounds and cough, subsided during treatment with both cefetamet pivoxil treatment doses in all patients. All X-ray findings and blood leucocytosis normalized, while 1 out of the 10 children to whom 30 mg cefaclor/kg/day was administered deteriorated from bronchopneumonia to pneumonitis during treatment. Treatment was stopped due to vomiting in 1 patient receiving the 40 mg cefetamet pivoxil/kg/day dose.
An open clinical trial was carried out in 21 chronic schizophrenics to assess the effectiveness and side-effects of treatment with depot neuroleptics. All patients had been stabilized on fluphenazine decanoate for at least 6 months and on entry to the study were given the choice of continuing with this treatment or changing over to flupenthixol decanoate. Sixteen patients chose to receive flupenthixol decanoate (40 mg) and the other 5 fluphenazine decanoate (25 mg). Doses were given every 4 weeks during the 12-week study period. Clinical assessments were carried out every 4 weeks (Weeks 0, 4, 8 and 12) using the Brief Psychiatric Rating Scale and a side-effects checklist, and the Hamilton Rating Scale for Depression, the Schedule for Affected Disorders and Schizophrenia--Change Version, and the Global Assessment Scale were completed on entry (Week 0) and at the end of the study (Week 12). The results indicated that symptoms of depression, withdrawal, worrying, and psychomotor retardation were improved significantly (p less than 0.05) more with flupenthixol than with fluphenazine. The frequency of side-effects decreased during treatment with flupenthixol and there was a tendency towards fewer side-effects in the flupenthixol group than in the fluphenazine group after 8 weeks of treatment. It is concluded that a group of schizophrenic patients characterized by depressive symptoms or side-effects attributable to a prescribed neuroleptic might benefit from a switch to flupenthixol treatment.
A single-blind, placebo-controlled study was carried out in 30 patients with chronic obstructive bronchopneumopathy to assess the effectiveness and tolerability of the theophylline derivative, bamyphylline. On entry, patients were allocated to receive twice daily oral doses of either 600 mg bamyphylline or placebo for a period of 60 days. Spirometric measurements, blood pressure and respiratory rate recordings and blood gas analyses were made at baseline and after 10, 30 and 60 days of treatment, as were assessments of clinical and objective signs, such as sibili, rales and vesicular murmurs. Plasma concentrations of bamyphylline 1 hour after the first dose of the day were monitored at the same intervals. The results showed that there was a highly significant progressive improvement in pulmonary function which was already apparent after 10 days and this was accompanied by a marked improvement in cardiac dynamics and clinical signs. Plasma concentrations of bamyphylline remained stable throughout the study period and there were no reports of side-effects or significant variations in blood chemistry.
A prospective, randomized controlled study was carried out in 104 patients to compare clavulanate-potentiated amoxycillin ('Augmentin') with a combination of cephalosporins (cefazoline and cefadroxil) supplemented with metronidazole in the treatment of abdominal septic states, suspected or proven after surgical intervention. Patients on 'Augmentin' received 1.2 g (1 g amoxycillin plus 200 mg clavulanic acid) intravenously 3-times daily for a mean of 6.6 days, then 375 mg (250 amoxycillin plus 125 mg clavulanic acid) orally for a further 6.4 days. Patients on the standard therapy received 1 g cefazoline intravenously 4-times daily plus 500 mg metronidazole intravenously 3-times daily for 7 days, then 500 mg cefadroxil orally 4-times daily for a mean of 6.6 days. Evaluation of the patients' condition was undertaken after 24 hours, 3 days and 7 days. The results showed a significantly better response to treatment in the 'Augmentin' group, as judged by the amelioration of clinical symptoms, bacteriological findings, and tolerance. All the patients treated with 'Augmentin' showed an excellent or satisfactory overall response at Day 7 compared with 76% of those receiving the standard therapy.
A randomized, multi-centre trial was carried out in 152 hospitalized women with pelvic inflammatory disease to evaluate the efficacy and tolerability of amoxycillin/clavulanic acid compared with that of a standard regimen using three antimicrobial agents (aminopenicillin, an aminoglycoside and metronidazole). Seventy patients initially received 3 to 4 intravenous doses per day of 1 g amoxycillin/200 mg clavulanic acid (mean 7.7 days) and then 4 to 6 tablets per day of 500 mg amoxycillin/125 mg clavulanic acid (mean 11.2 days). The other group of 82 patients initially received parenteral therapy daily (mean 7.7 days) with a combination of 3 to 4 g amoxycillin or ampicillin, 160 mg gentamicin (or 150 mg dibekacin or tobramycin) and 1.5 g metronidazole, and then oral therapy with 2 to 3 g amoxycillin or ampicillin and 1 to 1.5 g metronidazole daily (11.1 days). Clinical results, assessed at discharge from hospital (mean 10 days in both groups), were comparable in both groups, with 96% complete or partial response and no failures in the amoxycillin/clavulanic acid group, and 90% complete or partial successes and 5 failures with the triple therapy regimen. Both treatments were well tolerated and very few side-effects were reported.
Oral and/or parenteral amoxycillin was used to treat 52 young and adult patients suffering from moderately severe to severe bronchitis, bronchopneumonia or acute lobar pneumonia. The mean time between onset of disease and start of treatment was 3.8 days. Patients received doses of amoxycillin ranging from 375 mg to 1 g 2 to 3-times daily depending on the severity of the condition for a mean of 6.4 days. There was complete resolution of clinical symptoms such as fever, cough and pleural pain after 3 days in all but 3 of the patients. Response was considered excellent or good in 77% of patients and satisfactory in 14%. Mild to moderate side-effects such as urticaria and nausea were reported in 8 patients but were not severe enough to interrupt treatment. Overall, amoxycillin was considered to be effective in 82% and partially so in 11% of the patients treated.
A study was carried out in 8 patients with chronic stable bronchial asthma to compare the bronchodilator response with terbutaline, administered by a recently developed powder inhalation system ('Turbuhaler') and equipotent doses of salbutamol administered by a widely used powder inhaler ('Rotahaler'). Dose-effect relationships with usually applied clinical doses of the bronchodilators were estimated by maximal expiratory flow-volume analysis and airway resistance estimates from body plethysmography. There was no significant difference in clinical response using either inhaler. The equal and opposite changes in forced vital capacity and residual volume with increasing dose indicate an improvement in peripheral airway resistance and, therefore, adequate peripheral powder deposition of the bronchodilators. Only at the highest dose was a mild increase noted in pulse frequency and tremor score with both systems. It is suggested that, because of the multi-dose character, absence of additives, easy handling (no capsule loading) and low inspiratory flow needed for actuation, the 'Turbuhaler' system may be considered preferable for the application of a bronchodilator in children and severely obstructed adults.
A double-blind study was carried out in 48 hospitalized, elderly demented patients with key symptoms of aggressiveness and agitation to evaluate the efficacy and tolerability of zuclopenthixol compared with that of haloperidol/levomepromazine. Patients were allocated at random to receive initial doses of either 4 mg zuclopenthixol daily or 1 mg haloperidol in the morning and 5 mg levomepromazine in the evening over a period of 4 weeks. In Week 4, the mean daily dose was 4.8 mg zuclopenthixol and 1.6/7.6 mg haloperidol/levomepromazine, respectively. After 1 week, the severity of illness was already significantly reduced, and was further reduced after 2 and 4 weeks of treatment in both groups: the reduction, however, was most pronounced in the zuclopenthixol group and after 2 weeks this difference was significant. Side-effects were few. The results of the study indicate that, whilst both zuclopenthixol and haloperidol/levomepromazine were effective and well tolerated in these elderly patients with aggressiveness and agitation, onset of therapeutic effect appeared more rapidly with zuclopenthixol, which furthermore provides the practical advantage that it may be administered once a day.
In a double-blind, placebo-controlled crossover trial, the effects of ramipril, a long-acting non-sulphydryl angiotensin I converting enzyme inhibitor, on phenprocoumon steady-state pharmacodynamics were investigated in 8 healthy male volunteers taking individually fixed doses of phenprocoumon. The results showed that 5 mg ramipril or placebo once daily for 7 days did not alter the anticoagulant response (Quick values) to phenprocoumon after a stabilization phase of 2 weeks. Mean Quick values during the steady-state phase with ramipril and placebo were 67.5% and 69.3%, respectively. The clotting factors II, VII, IX and X as well as protein C decreased in the run-in phase and remained stable both during ramipril and placebo treatment. There were no differences between ramipril or placebo treatments. As the phenprocoumon dosage was kept unchanged during the double-blind phase, the results indicate that ramipril does not interfere with the vitamin K-dependent cascade.
A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) levels before and after exercise. Each subject underwent several bicycle ergometric exercises lasting 6 min before and after the application of test medications. Ergometric exercises were performed before medication, and at 2, 5, 9 and 24 hours after medication. Blood samples for ANP and ADH levels were drawn before, after 15 min, after 2 hours (immediately after ergometry) and 5, 7, 9, and 24 hours after medication (immediately before ergometry). Urine was collected as follows: -2 to 0, 0 to 2, 2 to 4, 4 to 7, 7 to 14 and 14 to 24 hours after medication, and the volume as well as sodium excretion were documented. Penbutolol caused suppression of the exercise-induced increase in ANP. The 2 to 4 hour fractional sodium excretion was significantly decreased from 12.1 +/- 4.9 mmol/fraction after placebo treatment to 7.8 +/- 3.0 mmol/fraction after penbutolol application (p less than 0.03). There were no differences in the urinary outputs between penbutolol and placebo until 4 hours after medication, but penbutolol caused the total urinary output to increase from 1390 +/- 388 ml/24 hr during placebo treatment to 1725 +/- 549 ml/24 hr (p less than 0.02) due to the last collection fraction. Blood pressure and pulse rate both decreased during exercise after penbutolol. As opposed to the suppressing influence of penbutolol on ANP, ADH plasma levels were increased after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Seventy-two depressed patients attending general practices were randomly allocated to treatment with either flupenthixol dihydrochloride (1 to 2 mg/day) or fluvoxamine maleate (100 to 200 mg/day) to assess efficacy and side-effects over a 4-week period. Clinical assessments were carried out before medication (Day 1) and on Days 8, 15 and 29 of treatment using the Hamilton Rating Scale for Depression, Clinical Global Impressions (CGI) and a patient self-assessment visual analogue scale for depression. Unwanted symptoms were also recorded. Reduction in mean total scores on the Hamilton scale at each assessment and therapeutic effect improvement on the CGI were greater for patients treated with flupenthixol (p less than 0.05). Reduction in unwanted symptoms was progressive in both groups, but more pronounced in patients receiving flupenthixol. Twice as many new symptoms arose in the fluvoxamine group compared to the flupenthixol group. Four patients were withdrawn in the fluvoxamine group due to untoward drug effects compared with none in the flupenthixol group.
An open, multi-centre, general practice study was carried out in 80 patients with acute diarrhoea to compare the effectiveness and tolerability of treatment with a liquid formulation of smectite, a hydrated aluminium-magnesium silicate (Liquid 'Diasorb'), and loperamide. Patients were allocated at random to receive one or other treatment for a maximum of 48 hours. Thirty-three of the patients on the smectite preparation and 30 of those on loperamide had acute diarrhoea of at least 24 hours but no longer than 48 hours in duration. Patients received a daily dose of 6 to 9 g smectite or 8 to 12 mg loperamide, depending on the symptoms. Details of red and white cell counts, serum electrolyte concentrations and stool culture for pathogens and parasites were recorded on entry and after 1 week. The results, judged in terms of resolution of symptoms after 2 and 7 days, doctor and patient assessment of response to therapy, and incidence of side-effects, showed that both treatments were equally effective and well-tolerated. Two patients were withdrawn, 1 patient (Liquid 'Diasorb') because of lack of response and the other (loperamide) because of dryness of the mouth and nausea. Laboratory parameters remained unchanged apart from a slight decrease in leucocytes in both groups.
