bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights Into The Mechanism of Action of Hypnotics
Authors: Doble A.
Published: January 2017

Between 1987 and 1989, the different protein subunits that make up the receptor for the inhibitory neurotransmitter γ-aminobutyric acid (GABA) were identified. These make up the α, β, γ and δ families, for each of which exist several subtypes. This receptor is the molecular target of modern hypnotic drugs (i.e. benzodiazepines, zopiclone, Zolpidem and zaleplon). In the 10 years that have followed this milestone, significant progress has been made in exploring the molecular mechanisms of hypnotic drug action. Receptor subtype specificity of hypnotics has been explained in terms of differential affinity for receptors containing different α subunits, which are expressed in different brain regions. Zolpidem and zaleplon bind preferentially to α1containing receptors, whereas benzodiazepines and zopiclone are aspecific. Different sets of subunits are encoded in contiguous ‘cassettes’ on the genome, and the transcription of each set appears to be regulated coherently. The predominant GABAA receptor composition found in the brain is α1β2γ2, which are all encoded on human chromosome 5. Targeted gene disruption has provided clues to the physiological functions served by GABAA receptors containing different subunits. Receptors containing γ2 appear to have a vital role in maintaining appropriate central inhibition, β3-containing receptors may also be important determinants of excitability in certain brain regions, whereas a clear role for α5-, α6- and γ3-containing receptors has not yet been established by these techniques. Site-directed mutagenesis has indicated that benzodiazepines bind to a cleft on the GABAA receptor surface at the interface between the α and γ subunits. Other drugs (flumazenil, zopiclone, Zolpidem) also bind to the a subunit, but interact with amino acids in different binding domains to the benzodiazepines. The molecular mechanism of hypnotic dependence has been explored, and seems to involve downregulation of transcription of the normally prevalent α1, β2 and γ2 subunits, and the reciprocal upregulation of the expression of rarer subunits. Chronic treatment with hypnotic drugs that may have less dependence potential, such as zopiclone and Zolpidem, appears to produce more limited change in GABAA receptor subunit expression. These ideas will be important both for designing new hypnotic drugs with a better safety/efficacy profile, and for evaluating more appropriate ways of using the drugs available today.
Brain Mechanisms of Sleep: Contribution of Neuroimaging Techniques
Authors: Maquet P.
Published: January 2017

Functional brain neuroimaging essentially relies on two basic principles:, functional segregation and functional interaction. Recent studies of the functional segregation of the human brain during sleep, using positron emission tomography and statistical parametric mapping, indicate that human brain function is organized in a very specific way in each state of vigilance. During slow wave sleep, the most deactivated areas are the upper brainstem, thalamic nuclei and basal forebrain; deactivation of the basal ganglia is also seen. In the cortex, the least active areas are the associative cortices of the frontal and parietal cortex. The anatomical extent of this deactivation remains uncertain. In rapid eye movement (REM) sleep there is significant activation of the dorsal tegmentum of the ponto-mesencephalic region and the thalamic nuclei. Within the cortex, the limbic areas (amygdala, hippocampus, orbito-frontal cortex and anterior cingulate cortex) are activated. In contrast, the associative areas of the frontal and parietal cortices are less active than other parts of the brain. The functional interactions between the amygdala and the temporal cortex during REM sleep differ markedly from those during other states of vigilance, and there is also an inverse relationship between the activities of the primary and secondary visual areas.
New Trends In Insomnia Management
Authors: Roth T.
Published: January 2017

Pharmacological management of insomnia is continually evolving. The introduction of non-benzodiazepine benzodiazepine receptor agonist hypnotics provides an opportunity to understand different patterns of pharmacological activity with mechanistic differences in receptor activity. The impact of insomnia on daytime functioning and long-term health and socioeconomic status has been recognized. Epidemiological studies indicate that insomnia is associated with increased absenteeism and healthcare costs (although the latter appear to be partly attributable to comorbid depression). It will thus be important to determine whether hypnotics, in addition to their effects on sleep, provide other benefits for the patient that are related to these parameters. The successful resolution of this issue will require the adoption of additional outcome measures, such as effects on quality of life and healthcare costs. Recognition that long-term hypnotic use is widespread among insomniacs has prompted proposals for alternative prescribing patterns. Although certain hypnotics appear to be free of tolerance on prolonged use, caution is required in the long-term use of any hypnotic because of the lack of systematic data on chronic efficacy and safety. Therefore, alternative administration schedules (e.g. intermittent and ‘as required’) are being investigated. These may have very different consequences in terms of abuse liability and patients' perceptions of efficacy, and thus permit a more effective and appropriate use of this drug class.
Treatment of Moderately Severe Essential Hypertension in General Practice with a Combination of Cyclopenthiazide with Potassium Chloride (Navidrex K) and Oxprenolol (Trasicor 80mg): A Report on 554 Patients
Authors: Forrest W A
Published: January 2017

Five hundred and fifty-four patients, with an initial mean diastolic pressure of 130 mm Hg, were treated with a combination of Navidrex K ( 0·5 mg daily) and up to 480 mg (six tablets daily) of Oxprenolol (Trasicor 80 mg).

In 69% of this group, good control of the blood pressure was achieved with a daily dose of four tablets ( 320 mg) of Oxprenolol.

In the remainder of patients significant reductions in blood pressure levels were noted, again with a mean dose of less than 320 mg daily of oxprenolol. There were indications in this group that better control of blood pressure levels might have been reached, had more of the patients been prescribed the maximum dose of 480 mg daily (six tablets) permitted in the study.

Tolerability of this regime was very good. More than 80% of patients reported no side-effects at all, and one patient in four reported ‘feeling better’ after treatment.
Lorazepam in Anxiety: A Controlled Study
Authors: Rickeis K , Csanalosi I , Pereira-Ogan J A , Parish L , Bell P J
Published: January 2017

Lorazepam ( 3 mg/day) was compared to placebo in a double-blind controlled study conducted with anxious neurotic out-patients. Sixty-eight patients were treated for at least two weeks. Significant main treatment effects were found with lorazepam producing more improvement than placebo in physician but not patient-completed measures. Lorazepam seemed to be most effective in the initially sicker patients. Its main side-effect was sedation.
Corticosteroids in Neurosurgical Practice
Authors: Boctor S M , Azab M G , Shawarby A , Narshy W K , Aref G E
Published: January 2017

Dexamethasone (Oradexon-Organon) was used in the treatment of forty-six patients with head injuries and sixty-four patients with brain tumours. Assessments were made based on clinical judgement, direct observations of the brain during surgery and repeated angiography. The results were compared with similar cases from previous years prior to the introduction of dexamethasone. A great improvement was seen with this corticosteroid therapy when combined with the appropriate resuscitation and intensive care techniques.
Psychometric Study of Praxilene
Authors: Bouvier J B , Passeron O , Chupin M P
Published: January 2017

Naftidrofuryl (Praxilene) has been shown experimentally to improve the metabolism of brain cells where this has been impaired by advancing ischaemia due to arteriosclerosis. It has been evaluated in warded chronic patients showing signs of impaired intellectual ability. The trial was performed double-blind involving an identical placebo and the results assessed using psychometric tests and analyzed statistically. The results confirm the effectiveness of Naftidrofuryl (Praxilene) in improving intellectual performance and this was particularly apparent in the less severely affected.
Effects of Placebo versus Guanabenz on Hypertensive Out-Patients
Authors: Walker Barry R , Schneider Bruce E , Rudnick Michael R , Gold Jerome A
Published: January 2017

The objectives of this study were two-fold: (1) a 4-week multicentre, randomized, double-blind efficacy comparison of placebo and guanabenz acetate, a new centrally acting antihypertensive drug, in 168 hypertensive out-patients and (2) a more accurate determination of the incidence of drug-related, non-specific side-effects. Both treatment groups were comparable: 68% female, 63% black, mean age 53 years; 57% mild, 32% moderate, 11% moderately severe hypertensives. Seventy-six placebo patients completed 4 weeks and had a mean supine diastolic blood pressure (SDBP) decrease from 105 to 101 mm Hg (p < 0.01). Seventy-nine guanabenz patients completing 4 weeks had a mean SDBP decrease from 104 to 92 mm Hg (p < 0.01). All of the placebo responses and 10/12 mm Hg of the guanabenz response occurred during Week 1. Clinically significant individual SDBP decreases occurred in thirty-one (41%) placebo and fifty-five (70%) guanabenz-treated patients (p < 0.01). Mean daily guanabenz dose was 24 mg. Drug-related biochemical or electrocardiographic abnormalities were absent. Side-effects of sedation and dry mouth were recorded two and three times more frequently, respectively, in guanabenz as compared to placebo patients. Side-effects usually occurred within Week 1 and diminished in incidence thereafter. Consequently, in these patients it appeared that: (1) guanabenz was an effective, well-tolerated drug, (2) placebo effects on efficacy were significant, occurred early and remained stable, and (3) placebo and guanabenz side effects were mainly sedation and dry mouth.
A Patient Compliance Comparative Study of Three Diuretics in the Treatment of Oedema
Authors: Wade A G
Published: January 2017

Diurexan® (xipamide*) 40 mg daily was substituted for Navidrex-K® (cyclopenthiazide 0.25 mg plus potassium 600 mg) or Moduretic® (amiloride hydrochloride 5 mg plus hydrochlorthiazide 50 mg) in nineteen patients with oedema of cardiac origin. Comparative efficacy and patient acceptability were examined over a 4-week treatment period. In six patients their oedema was resolved and in a further seven their oedema was markedly reduced (six patients had no overt oedema pre-trial). The body-weight of nine patients decreased by an average of 1.4 kg whilst in seven patients it remained static and in three patients it increased by an average of 1.8 kg. Thirteen of the patients preferred Diurexan at the end of the 4-week trial period, four patients had no preference and two patients preferred their previous treatment.
A Double-Blind Parallel-Group Comparison of Single Bedtime Doses of Halazepam and Placebo
Authors: McEvilly James P , Etemad Bijan
Published: January 2017

A single bedtime dose of 120 mg of halazepam was effective in the treatment of patients with mild to moderate anxiety. This dose was superior to both placebo and a 60 mg dose in this 2-week study, as shown by both physician and patient rating scales.

The safety of single bedtime doses of halazepam was confirmed. All the reported side-effects were known adverse experiences to benzodiazepines in general.
Quantitative Thermal Imaging to Assess Inositol Nicotinate Treatment for Raynaud's Syndrome
Authors: Ring E F J , Porto L O , Bacon P A
Published: January 2017

The objective assessment of thermography was used to quantify the response to cold stress in the hands of sufferers from Raynaud's Syndrome over a period of 36 weeks while on inositol nicotinate (Hexopal) in a dose of 4 g per day.

Objective improvement was observed in the thermal gradient of the hand after cold challenge (RTG) following this sustained treatment. Statistically significant improvements were noted on four of the five subjective assessments. No drug-related adverse reactions were noted.
Post-Marketing Surveillance: Drug Epidemiology
Authors: Borden E Keith
Published: January 2017

A description of the need for and appropriateness of a multi-component application of epidemiological methods to the post-marketing evaluation of drugs is presented. There is a need for the development of the art and science of Drug Epidemiology. The large number of drugs introduced over the last 40 years and the number of interventions constitute an issue of public health interest. It is appropriate that scientifically sound information be collected about medications. There has been considerable discussion about the methods to be used in any such systematic approach. The choice of method is obviously dependent upon the questions to be addressed and the functions to be satisfied. The proposal is presented for the appropriate content and functions of post-marketing drug evaluation, and a description of some currently employed approaches show how they differentially satisfy the functions. It is concluded that there is a need for the development and application of multiple complementary methods to satisfy the requirements of a meaningful system for post-marketing drug evaluation.
Rimactan Parenteral Formulation in Clinical Use
Authors: Kissling M , Xilinas M
Published: January 2017

One hundred and forty-nine mainly critically ill or comatose patients or patients with problems of gastro-intestinal tolerability and/or absorption have been treated during the last few years with a parenteral formulation of rifampicin made available for release in special cases, on humanitarian grounds.

The cases reported include ninety-seven tuberculous patients (eighteen of whom were suffering from tubercular meningitis) and fifty-two patients suffering from non-tuberculous infections, including twenty-two cases of sepsis (fifteen due to staphylococci), four cases of bacterial meningitis and four cases of Legionnaires' disease.

R ifampicin was administered in each case, together with at least one other suitable antibacterial agent, mainly by intravenous bolus injection (seventy-four cases) or intravenous drip infusion (forty-four cases), at daily doses ranging from 150 to 1800 mg. The duration of treatment ranged from 1 to 113 days.

Data allowing an assessment of effectiveness were made available for sixty-eight tuberculous patients, sixty-three of which (92.6%) showed favourable results, and for twenty-seven patients with non-tuberculous infections, nineteen of which (70.4%) had a favourable outcome. Especially favourable were the results in the cases of staphylococcal sepsis (78.6% of clinical and/or bacteriological cures).

Tolerability was good in most cases. Only fourteen of the 149 patients showed signs of local intolerability (thrombo-phlebitis), almost always occurring in patients treated for over 60 days. Fifteen patients (10%) complained of systemic unwanted effects, the relationship of which to the treatment was not always established. Treatment was finally withdrawn because of tolerability problems in only three of the 149 cases (2%).

Bearing in mind the very varied nature of the severe, life-threatening infections reported here, two comments may be made:

Intravenous rifampicin is useful and even life-saving in both severe tuberculous and non-tuberculous infections. It is safe even in long-term administration. However, treatments lasting over 30–60 days appear to involve a higher risk of venous thrombo-phlebitis.
The Treatment of Hypertension in Older Patients: A Double-Blind, Between-Patient Study in Previously Treated Patients Comparing a Diuretic, a Beta-Receptor Antagonist, and Their Fixed Combination
Authors: Forrest W A
Published: January 2017

Six hundred and forty-eight previously treated hypertensive patients, with a mean age of 64 years, were studied. In spite of treatment over a mean period of 18 months, their blood pressure was inadequately controlled, with an initial mean level of 180/108 mm Hg.

Previous treatment which had consisted of either a diuretic alone, a beta-receptor antagonist alone or these two drugs in combination was discontinued and Datients were randomly allocated, in a double-blind manner, to a 6-week treatment course of cyclopenthiazide (Navidrex®) or sustained release oxprenolol (Slow-Trasicor®) or a fixed combination of these two compounds (Trasidrex®) with the aim of lowering the diastolic pressure to < 100 mm Hg.

Blood pressure was substantially reduced in each treatment group, with the lowest final pressures in the group treated with the fixed combination, where 87% of the patients completing the study reached the target level of a diastolic pressure of < 100 mm Hg. Very few side-effects of treatment were reported with any of these compounds.

The results from this study suggest that these compounds in their standard dosage range are useful and safe antihypertensive agents in older patients. In those patients where blood pressure control with a single agent was proving difficult, the transfer to one or two tablets daily of the fixed combination (Trasidrex) produced a very satisfactory outcome in the large majority of cases.
A Double-Blind Comparison of Flurbiprofen and Indomethacin Suppositories in the Treatment of Osteoarthrosis and Rheumatoid Disease
Authors: De Moor M , Ooghe R
Published: January 2017

Forty patients with osteoarthrosis or rheumatoid arthritis were entered in a 4-week double-blind trial to compare the efficacy, safety and tolerance of a flurbiprofen 100 mg suppository formulation with indomethacin 100 mg suppositories. There were twenty patients each on indomethacin and flurbiprofen. Statistically significant improvements were reported for both treatments during the study with respect to morning stiffness, night pain and the overall progress of the patients.

Both treatments were equally effective with respect to the amount of improvement shown for the parameters.

No improvement was noted on either treatment with respect to grip-strength, functional capacity or the daily intake of analgesic therapy, while a marginally significant decrease in the erythrocyte sedimentation rate was noted on indomethacin.

Both treatments were well tolerated with only a few transient and mild side-effects being reported.

On the basis of this trial, flurbiprofen and indomethacin suppositories have equal therapeutic effects in the treatment of night pain and morning stiffness.
Driving Ability of Depressive Patients under Antidepressants
Authors: Hobi V , Gastpar M , Gastpar G , Gilsdorf U , Kielholz P , Schwarz E
Published: January 2017

A group of twenty depressive patients was compared during a 3–4 month course of antidepressant therapy (maprotiline: n = 6, age = 46·1; dibenzepin: n = 4, age = 43·0; lithium: n = 6, age = 44·5; ‘mixed’ (maprotiline, dibenzepin and trimeprimine): n = 4, age = 50·2) with a healthy control group (n = 32, age = 38·2) for subjective assessment of their depressive mood and performance as well as objective measurement of variables relating to driving behaviour. The measurements were taken 2–4 weeks after a pre-treatment period (day 1) and after 2–3 months of further therapy (day 2). During therapy, all patients felt ‘less depressive’ and ‘more capable’ in subjective terms. All patient groups made learning-progress in the objectively measured variables (psychomotor co-ordination and attentiveness tests). By day 2, the patient groups had almost reached the performance level of the control group, providing they received antidepressant therapy (regardless of the action profile) which was suitable for the basic disorder and the symptoms, and therapy was successful in the opinion of the physician. It may be concluded that depressive patients, assuming suitable antidepressant treatment and good response, are capable of driving while under maintenance therapy.
A Double-Blind Comparison of Meptazinol versus Distalgesic in Acute or Chronic Pain Presenting to the General Practitioner
Authors: Wade A G , Ward Peter J
Published: January 2017

The results of treating acute or chronic pain with Distalgesic were compared in a double-blind fashion with the new partial antagonist analgesic meptazinol. Both drugs had similar analgesic time effect profiles and both were acceptable to doctor and patients. However the side-effect profile was better for meptazinol than Distalgesic and so meptazinol may be a useful alternative to Distalgesic in the treatment of everyday pain states.
Analgesia following Adult Tonsillectomy: A Comparative Study of Solpadeine and a Soluble Form of Dextropropoxyphene Napsylate and Paracetamol
Authors: Mac Kay I S , Ananian V
Published: January 2017

A single-centre, single-blind, between-patient study was carried out to compare the effectiveness and tolerability of Solpadeine and a soluble form of dextropropoxyphene napsylate and paracetamol (DNP) in the alleviation of pain following bilateral tonsillectomy in adult patients. Patients were randomly allocated to receive either two Solpadeine or two DNP 6-hourly over a period of 3 days starting on the day after the operation.

The clinician assessed the patients' condition at the time of operation and again at the end of the 3-day treatment period. The patients determined the onset of analgesic action using visual analogue scales and also recorded the severity of their pain at various times during the day.

Seventy-four results were analyzed. Twenty per cent of those receiving Solpadeine were considered by the clinician to have excellent pain relief compared with only 8·8% on DNP. On Day 2, 51·3% of patients on Solpadeine described their pain relief as good or excellent in comparison with 37·5% on DNP. However, these differences were not statistically significant.

It is concluded that Solpadeine and DNP are both effective analgesics in relieving post-tonsillectomy pain, but that Solpadeine achieves a greater degree of good or excellent pain relief and is, therefore, to be preferred.
Effects of Therapeutic Doses of Cimetidine and Oxmetidine on the Parietal Cell Population, Gastric Mucosal Glycoproteins and Surface Gastric Epithelium, in Duodenal Ulcer Patients
Authors: Emmanouilidis Anastasios , Nicolopoulou-Stamati Polyxeni , Manousos Orestis
Published: January 2017

The histamine H2-receptor antagonists cimetidine and oxmetidine were administered in a dose of 1 g/day for 4 weeks to fifteen duodenal ulcer patients. Their effects on the parietal cell population, the intracellular mucosal glycoproteins and the surface gastric epithelium were investigated by comparing pre- and post-treatment fundic biopsies. It was found that treatment with either agent had no effect on any of the assessments made.
Single Dose Treatment of Trichomoniasis
Authors: Gabriel G , Robertson E , Thin R N T
Published: January 2017

Oral treatment for trichomonas vaginalis infection is now well established. In a previous paper, we established the value of a high single dose regimen of metronidazole for this condition by demonstrating its efficacy in a double-blind controlled study.

Tinidazole is another accepted trichomonacide. By means of a single-blind controlled trial, we demonstrate that a 2 g single dose of tinidazole is as effective as a 2 g single dose metronidazole in the treatment of vaginal trichomoniasis. The cure rate for tinidazole was 95% and for metronidazole it was 97·5%. No side-effects were reported with either regimen.
Report on a Double-Blind Comparison of Two Different Regimens of Dothiepin (Prothiaden)
Authors: Boening J
Published: January 2017

Thirty patients diagnosed as suffering from endogenous depression were entered into a 3-week double-blind trial comparing three times a day dosage of dothiepin with a single night-time dosage in a dosage range of 75 mg to 225 mg per day.

The trial was conducted on in-patients and assessments were made pretrial and after 1 and 3 weeks. The patients were assessed by clinician-rated scales for psychomotor and psychic symptoms and by Zung's self-rating scale.

Fifteen patients received dothiepin three times a day (day-time group) and fifteen received it as a single night-time dose (node group). There were two withdrawals in the day-time group and three in the node group. All withdrawals were due to lack of therapeutic effect.

Over the 3-week trial 67% of the day-time group and 47% of the node group showed a clinical improvement. It was found that there was no statistically significant difference between the two methods of treatment.

In the day-time group seven patients and in the night-time group nine patients suffered from side-effects. No particular pattern of side-effects emerged.

There were no drug-related changes in the laboratory results. It was concluded that the therapeutic effect of both dosage regimes should be regarded as equivalent. Advantages, due to the specific action of dothiepin, compared with classical antidepressants for reference, could, however, not be presumed by the clinical impression.
A Double-Blind Comparison in General Practice of a Combination Tablet Containing Orphenadrine Citrate and Paracetamol (‘Norgesic') with Paracetamol Alone
Authors: McGuinness B W
Published: January 2017

A double-blind trial of a combination tablet containing orphenadrine and paracetamol, ‘Norgesic', was carried out to assess the value of this product compared with paracetamol alone. All three symptomatic parameters which were measured: pain, spasm and impaired activity, showed a significantly quicker recovery when the combination product was used. Further studies are necessary to evaluate the combination product against orphenadrine citrate alone.
A Comparative Study of the Therapeutic Effect of Dithranol Cream 0·1% and 0·25% with That of Dithranol Stylus 0·1% and 0·2% in the Treatment of Psoriasis
Authors: Gisslèn H , Nordin P
Published: January 2017

In Dithranol cream the oily phase is emulsified with an aqueous phase to make the preparation more convenient to apply. The cream also contains ascorbic acid as an antioxidant, which protects dithranol against atmospheric oxidation, thus increasing its stability. A stylus containing dithranol, ol. cacao, paraffin and vaselinum has been used as a comparative drug. The stylus is routinely used in this clinic.

Sixty patients with stable psoriasis were pre-assigned into two treatment groups, receiving at random Dithranol cream 0·1%, 0·25% and Dithranol stylus 0·1%, 0·2%, respectively. Both groups started their treatment with the 0·1% preparation once a day for 2 weeks followed by the 0·2% or 0·25% preparations once a day for another 2 weeks. The following laboratory tests: Hb, WBC, Diff, S-ALAT, S-ASAT and S-creatinine were recorded before and after treatment. Staining of clothes was none to slight in 70% (21/30) of the patients using Dithranol stylus 0·2%, and 80% (24/30) in the patients using Dithranol cream 0·25%. The sensation of burning was none to slight in 83% (25/30) of the patients and skin discolouration was none to slight in approximately 80% (24/30) of the patients using the Dithranol stylus 0·2% and Dithranol cream 0·25% preparations. Both groups showed significant improvement in all effect-variables after 2 and 4 weeks' treatment compared to initial. The results are over all better after 4 weeks' treatment than after 2. No abnormal values due to dithranol treatment could be found in the laboratory tests.
A Crossover Comparative Study with Two Bulk Laxatives
Authors: Pers Mats , Pers Birgitta
Published: January 2017

Twenty elderly in-patients suffering from severe constipation were treated once daily for 2 weeks with each of two bulk laxatives. The preparations were allocated randomly as the first and second preparation. Agiolax, the new preparation, contained 15 mg senna glucosides, the old preparation, Lunelax comp., contained 25 mg senna glucoside A + B per dose. Both preparations worked well and no side-effects were seen.
Urinary Electrolyte Excretion and Orthostatic Response of Blood Pressure and Plasma Renin Activity in Children with Postural Hypotension before and after Treatment with Dihydergot®
Authors: Uchiyama Makoto , Sakai Kaoru
Published: January 2017

Na and K metabolism, and orthostatic response of blood pressure and plasma renin activity (PRA) were studied in six children, aged 10 to 15 years, with postural hypotension before and after treatment with Dihydergot®(DHE). All abnormal findings which we had already observed in children with postural hypotension (i.e. low fractional excretion of filtered Na in spite of low PRA, extremely high PRA on fainting, great postural fall in blood pressure, and so on) improved on treatment with DHE. This suggests that these abnormal physiological findings found in children with postural hypotension may result from increased venous pooling which can be reduced by DHE. Consequently, DHE seems an excellent drug to treat postural hypotension from the physiological point of view.
Treatment of HBeAg-Positive Chronic Hepatitis with a Streptococcal Preparation (OK-432)
Authors: Ichida F , Yoshikawa A , Yachi A , Goto Y , Furuta S , Hattori N , Kakumu S , Kosaka Y , Takino T , Nagashima H , Tsuji T , Ota Y
Published: January 2017

Forty-two patients with hepatitis Be antigen (HBeAg)-positive chronic hepatitis were treated by intramuscular injections with OK-432, an immunopotentiator possessing interferon-inducing activity. They were monitored with serial measurements of virological parameters to evaluate therapeutic effectiveness, and compared with a group of seventy-five untreated patients (natural course group).

In the group receiving OK-432 therapy, twenty-seven patients (64·3% of the forty-two patients) became negative for HBeAg in an average observation period of 20·1 months. Of these, fourteen patients (33·3% of the forty-two patients) underwent seroconversion from HBeAg to anti-HBe antibody (anti-HBe). In the natural course group, twenty-three patients (30·7% of the seventy-five patients) lost HBeAg reactivity in a mean follow-up period of 32·3 months, and thirteen patients (17·3% of the seventy-five patients) became seroconverted. Thus, the drug group showed significantly higher percentages of patients with disappearance of HBeAg and seroconversion, notwithstanding the shorter duration of the follow-up. Young males and females, females generally, or patients with high serum GPT levels were more likely to respond to the therapy. The serum GPT level tended to stabilize more inpatients receiving OK-432.
Comparison of Limbitrol (Chlordiazepoxide/Amitriptyline) and Amitriptyline Alone as a Single Night-Time Dose for the Treatment of Depression with Anxiety
Authors: James R T D , Dean B C
Published: January 2017

Four hundred and thirty-four patients suffering from mild to moderate depression were recruited into a double-blind multicentre general practice study and randomly received either Limbitrol (25 mg amitriptyline and 10 mg chlordiazepoxide) or amitriptyline 25 mg in matching white capsules given as a single night-time dose. The dose was titrated to a maximum of four capsules per night. Patients were assessed on entry and at 7-day intervals for depressive state (Hamilton Rating Scale for Depression), cardiovascular effect and side-effects for 28 days. Self-assessments of depression and anxiety using the Leeds Scale were made in the form of a patient questionnaire. Both groups showed significant improvement at each visit and significantly more patients improved after 7 days in the Limbitrol group. There was no significant difference in treatment over all between groups, in the incidence of side-effects, or in the effects on the heart.
Double-Blind Comparison of Astemizole, Terfenadine and Placebo in Hay Fever with Special Regard to Onset of Action
Authors: Girard J P , Sommacal-Schopf D , Bigliardi P , Henauer S A
Published: January 2017

In this double-blind study forty-seven patients with hay fever were treated for 8 days with either terfenadine 60 mg twice a day, astemizole 10 mg once a day or placebo.

On the second day of treatment terfenadine was statistically significantly superior to astemizole and placebo according to the ratings of symptomatology, efficacy and individual symptoms. The median onset of symptom alleviation was 3 hours for terfenadine and 2 days for astemizole.

On the eighth day both astemizole and terfenadine were statistically significantly more efficacious than placebo, but no significant differences were found between the two drugs. Both drugs were well tolerated.
Collagen Implantation in Patients Treated Previously with Silicone
Authors: Cooperman Linda , Mackinnon Victoria
Published: January 2017

This multicentric, open study evaluated the efficacy and safety of Zyderm® Collagen Implant (ZCI) in 158 patients with contour deficiencies of the dermis and a history of silicone fluid therapy. Following test implantation with ZCI, thirty-seven patients dropped out, including four patients who exhibited untoward responses to the implant material. Hence, 121 patients completed the course of therapy and were available for efficacy and safety evaluation. At 2-week intervals, ZCI was implanted intradermally in 327 sites; 186 (57%) were the identical sites that had been injected previously with silicone fluid. In 89% of patients, five injections or less of ZCI produced favourable clinical results. Moreover, of 176 sites injected five times or less, a consistent pattern of progressive improvement was observed with each additional injection, regardless of the aetiology of dermal lesions. Furthermore, no undesirable textural or pigmentary changes were apparent at any of the 327 treatment sites. An adverse effect consisting of localized swelling, induration and erythema at implantation sites occurred in one patient, but resolved spontaneously.
A Comparative Study of Two Dosage Levels of Ibuprofen Syrup in Children with Pyrexia
Authors: Kotob A
Published: January 2017

In a study of the antipyretic effect of two dosage levels of Ibuprofen syrup in children with fever due to a variety of causes, forty-four out of the fifty children admitted completed the 24-hour trial period, twenty-three receiving 20 mg ibuprofen/kg body-weight, twenty-one receiving 30 mg/kg ibuprofen. Both dosage levels gave highly significant (p < 0·001) reductions in rectal temperatures, with a statistically significant reduction, at the 5% level, in favour of the higher dose at 12 and 20 hours. No side-effects were reported at either dosage level, and the taste was acceptable to all the children. It is concluded that ibuprofen was a useful and effective antipyretic drug in the population studied, and that the higher dosage is preferable to the lower, being more effective, equally palatable, and giving rise to no side-effects in this study.
Predicting Severity of Liver Disease: Twelve Laboratory Tests Evaluated by Multiple Regression
Authors: Simko V , Kelley R E , Dincsoy H P
Published: January 2017

To determine the predictive value of laboratory procedures for severity of liver disease, twelve laboratory tests were evaluated in seventy-two patients with various liver disease and in nine non-liver disease hospitalized cases. A numerical score based on the number and extent of abnormal findings was developed for grading clinical and histological severity. Multiple linear regression, utilizing a forward stepwise selection procedure, was used to find the best combination of laboratory tests for prediction of disease severity. The best predictive model for both clinical and histological severity was found for lecithin cholesterol acyltransferase (LCAT), total plasma cholesterol, alkaline phosphatase and bile acids. Of the routine tests prothrombin time and albumin/globulin were useful if the four-test combination listed above was not used. There was a significant correlation (p <| 0·001) between the clinical and the histological score, confirming validity of clinical scoring. In conclusion, this study shows LCAT to rank as first in predicting severity of liver disease. Cholesterol metabolism appears to be affected by liver disease even more than prothrombin time, albumin and globulins. LCAT and bile acids have a place in routine testing of severity of liver disease.
A Double-Blind Crossover Evaluation of Naproxen and Piroxicam in Osteoarthritis of Hip or Knee
Authors: Björkenheim Jan-Magnus , Helland John , Peltonen Jari
Published: January 2017

Seventy-five patients participated in a randomized, double-blind, crossover study, the aim of which was to compare the efficacy and safety of naproxen 1000 mg once daily with Piroxicam 20 mg once daily for the treatment of osteoarthritis of hip or knee. Treatment periods of 4 weeks each were preceded by placebo wash-out periods of up to 1 week. The patients were examined clinically at every stage of the trial. Each treatment group exhibited significant improvement in weight-bearing and night pain, over-all disease severity, and the separate evaluations of patient response by physician and patient. There were no significant differences between the drugs in type, severity, or number of side-effects. Neither of the drugs influenced the patients' laboratory data. Night pain was less for patients using naproxen than for those taking Piroxicam, and patients indicated greater preference for naproxen than for Piroxicam. Naproxen was statistically superior to Piroxicam as measured by decreased weight-bearing pain and over-all disease severity, the separate physician and patient global assessments of patient response to therapy, and physician preference. In this study, naproxen 1000 mg once daily was more effective than Piroxicam 20 mg once daily for the treatment of osteoarthritis.
Pseudomonas Cepacia: The Sensitivity of Nosocomial Strains to New Antibiotics
Authors: Ferreira M O Santos , Canica M Manuela , Bacelar M Jesus
Published: January 2017

Pseudomonas cepacia, considered a phytopathogenic organism for many years, has been shown recently to be widely distributed geographically. The hospital environment has become an important source of this organism but the resistance of Ps. cepacia to most antibiotics has made the treatment of infections a problem.

One hundred per cent of the strains tested have proved to be sensitive to the sulphonamides and to novobiocin, 93·0% to the combination of trimethoprim and sulfamethoxazole (co-trimoxazole); 85·2% to minocycline; 77·8% to chloramphenicol and dibekacin and 44·4% to nalidixic acid. One hundred per cent of the strains exhibit resistance to ampicillin, cephalothin, cefamandole, cefoxitin, Colistin, cefuroxime, tetracycline and cefazolin; 88·9% to amikacin, tobramycin and sisomycin; 85·2% to carbenicillin. The new beta-lactams, apalcillin, ceftazidime, N-formimidoyl-thienamycin, piperacillin, cefotaxime and azlocillin proved to be the most potent of the molecules tested, inhibiting 90% of the strains, at concentrations of 4, 8, 8, 8, 32 and 16 mg/l and 100% of the strains at 8, 16, 16, 32, 32 and 64 mg/l, respectively.

In contrast to the usual sensitivity patterns of Pseudomonas spp, Ps. cepacia has been shown to be resistant to Colistin, cefsulodin and the aminoglycosides. However, unlike Ps. aeruginosa, Ps. cepacia has been shown, by the dilution method, to be sensitive to co-trimoxazole, 92·3% of the strains being inhibited by 16 mg/l.
The Effect of Alclometasone Dipropionate Cream 0·05% on the Hypothalamic-Pituitary-Adrenal Axis of Normal Volunteers
Authors: Thornfeldt Carl , Cornell Roger C , Stoughton Richard B
Published: January 2017

In an open study of ten evaluable normal volunteers, 30 g of alclometasone dipropionate cream 0·05% was applied to 80% of body surface each morning and evening for 21 days. A plastic body suit effectively occluded the treated area for 12 hours/day. As demonstrated by continued normal levels of 8 a.m. plasma cortisol and 24-hour urinary 17-hydroxysteroid and free cortisol, no suppression of the hypothalamic-pituitary-adrenal axis occurred. Local adverse reactions were mild and transient.
Comparative Study of the Efficacy, Tolerance and Side-Effects of Dexchlorpheniramine Maleate 6 Mg B.I.D. with Terfenadine 60 Mg B.I.D.
Authors: Gutkowski A , Carpio J Del , Gelinas B , Schulz J , Turenne Y
Published: January 2017

Dexchlorpheniramine maleate 6 mg b.i.d. was compared with Terfenadine 60 mg b.i.d. for efficacy in controlling Ragweed Hay Fever symptoms, as well as tolerance and occurrence of adverse reactions. The study was a randomized, multicentric, parallel group, blind evaluator design which involved 174 patients equally divided, eighty-seven receiving dexchlorpheniramine and eighty-seven terfenadine, for a period of 2 weeks during the latter half of August and the first half of September 1983. The study indicated that dexchlorpheniramine at the doses tested, was significantly more effective in controlling hay fever symptoms than terfenadine.
Tolerance of Carprofen in Patients with Asthma Caused by Non-Steroidal Anti-Inflammatory Drugs
Authors: Bianco S , Robuschi M , Simone P , Vaghi A , Pasargiklian M
Published: January 2017

Eight asthmatics with respiratory intolerance to NSAIDs and two subjects (one asthmatic, one healthy) only sensitive (asthma) to pyrazolone drugs were challenged under single-blind conditions with a new NSAID, carprofen.

No adverse effects were observed in patients sensitive to pyrazolones. Among the other patients, only three developed considerable bronchial obstruction which was rapidly reversed by inhalation of a β2-stimulant (fenoterol: 2 puffs). Two subjects developed nasal obstruction with rhinorrhoea: in conjunction with bronchoconstriction in one patient and alone in the other.

In conclusion, acute administration of carprofen in patients with respiratory intolerance to NSAIDs, in contrast to most other NSAIDs, never creates a situation of real danger even though in some patients it may considerably increase nasal and bronchial resistance.
Cefsulodin Treatment for Serious Pseudomonas aeruginosa Infections
Authors: Routman A , Van Manen W , Haddad R , Pollock B , Holmes B , Mogabgab W J
Published: January 2017

Cefsulodin, a narrow-spectrum cephalosporin with excellent antipseudomonal activity was used to treat 48 patients with 51 Pseudomonas aeruginosa infections. These included osteomyelitis, infected prostheses, post-operative and post-traumatic superficial wounds, decubitus and stasis ulcers, lower respiratory tract infections and infections of the urinary tract. Many of the patients were compromised by underlying debilitating conditions such as severe trauma, diabetes mellitus, vascular impairment, and abuse of alcohol and drugs. In cases of polymicrobial infections, a concomitant non-antipseudomonal antibiotic was sometimes administered. Cefsulodin was administered intravenously to 47 patients and by intramuscular injections to one individual. The dosage ranged from 0.5 to 2.0 g every six hr and duration of therapy was from 4 to 70 days. A satisfactory clinical response was observed in 88% of the patients. P. aeruginosa was eradicated from 76% of the infection sites. Failures, which included relapse within one year, were generally associated with prior severe trauma or vascular impairment in cases of osteomyelitis. Reinfections and superinfections developed in 12 individuals. Adverse reactions reported for two patients were nausea and vomiting. A third patient had transient increases in alkaline phosphatase and SGOT. These data indicate that cefsulodin is an effective and safe antibiotic in various types of P. aeruginosa infections.
A Comparative Study of Miraxid (Pivmecillinam plus Pivampicillin) and Augmentin (Amoxycillin plus Clavulanic Acid) in the Treatment of Lower Respiratory Tract Infections in General Practice
Authors: McGhie D , Kerfoot P , Talbot D J
Published: January 2017

Two treatments, a) pivmecillinam 200 mg plus pivampicillin 250 mg (Miraxid*) given twice-daily and b) amoxycillin 250 mg plus clavulanic acid 125 mg (Augmentin*) given three times daily were compared in two parallel groups of 388 general practice patients with acute bronchitis or acute exacerbations of chronic bronchitis. Patients with acute bronchitis (140 on Miraxid, 144 on Augmentin) received a 7-day course of treatment and those with acute exacerbations of chronic bronchitis (55 on Miraxid, 49 on Augmentin) a 10-day course of treatment. Both treatments were equally effective, with 99 (71%) patients with acute bronchitis being successfully treated with Miraxid and 107 (74%) with Augmentin. In acute exacerbations of chronic bronchitis, Miraxid was successful in 29 (53%) patients and Augmentin in 24 (49%) patients. Side-effects were reported by 26 (12%) of patients in both treatment groups. This single blind multicentre general practice study comparing twice-daily Miraxid with 3 times daily Augmentin demonstrated that both treatments were equally effective clinically and equally well tolerated.
Differential Dosing of Trazodone in Elderly Depressed Patients: A Study to Investigate Optimal Dosing
Authors: Mukherjee P K , Davey A
Published: January 2017

We investigated the comparative efficacy and tolerance of two initial starting doses of trazodone in 20 elderly inpatients suffering from depressive illness. The first 2-week phase was double-blind. Patients received either 25 mg trazodone tds or 50 mg tds. After this time the study was open, the dose of trazodone being titrated from the initial starting dose to maximise efficacy and tolerance. Patients received study medication for a total of 6 weeks.

Assessments for efficacy included the Hamilton Depression rating scale, Zung anxiety scale, visual analogue scales for depression, euphoria and tension, and global assesments of severity and improvement of condition. Tolerance was assessed by means of a checklist of symptoms and adverse effects. Assessments were performed at base line and at weekly or bi-weekly intervals thereafter.

A total of 18 patients were included in the analysis. The Zung and visual analogue scales indicated significant superiority for the high-dose group at Week 2. The Hamilton ratings indicated significant superiority for the high-dose group at Week 6 with a strong trend in favour of the high dose group at Week 2. Measures of severity of illness and improvement indicated more rapid improvement over time in the high-dose group. The treatment was generally well tolerated and at no time did adverse events outweigh therapeutic benefit. The incidence of headache and nausea was more frequent in the high-dose group in the first 2 weeks.

The group of elderly patients studied benefited from trazodone therapy initiated at a higher therapeutic dose. This dose (150 mg total daily) was well tolerated and proved effective over the course of 6 weeks' treatment.
Steroid Formation in Osteoblast-Like Cells
Authors: Saito H , Yanaihara T
Published: January 2017

For preventing the reduction of bone mass in post-menopausal women, oestrogen replacement is known to be useful and the importance of sex steroids in bone metabolism in both sexes is well established. The presence of steroid-converting-enzyme activities in various osteoblast and osteoblast-like cells has been demonstrated using in vitro culture systems. In the present study, we assessed the expression of messenger ribonucleic acid (mRNA) for aromatase, steroid sulphatase, 5α-reductase, 17β-hydroxysteroid dehydrogenase (17β-HSD) and 3β-HSD by reverse transcription-polymerase chain reaction in the human osteoblast-like cell lines, MG 63 and HOS. Oestrogen, androgen and progesterone receptor mRNAs were also measured. Expression of mRNA for these enzymes and receptors was found in both cell lines without induction. From these and previous findings, we conclude that osteoblast-like cells have the capacity to form biologically potent oestrogens and androgens from peripheral circulating steroids. This may indicate an important role of bone in facilitating hormonal action.