Changing patterns of bleeding in patients with severe haemophilia A.

Previous studies on the pattern of joint bleeding in patients with haemophilia have reported that the knee joint is most frequently affected. Home treatment data reporting bleeding frequency and location collected from 100 patients registered at six haemophilia centres in the UK have been analysed to determine current patterns of bleeding. Bleeding frequency has markedly decreased although bleeding into joints remains the main characteristic of haemophilia. However, the ankle joint has replaced the knee joint as the most common joint affected. Furthermore, it seems that the frequency of knee joint bleeding is also less than the elbow joint suggesting that the traditional pattern of joint bleeding in haemophilia has now changed significantly.

Distinctive microvillous brush border staining with HBME-1 distinguishes pleural mesotheliomas from pulmonary adenocarcinomas.

HBME-1 is an antimesothelial monoclonal antibody that recognises an unknown antigen on microvilli of mesothelioma cells. The aim of this study was to evaluate the staining pattern with respect to antibody dilution, cellular distribution and intensity of immunohistochemical staining with HBME-1 in pleural mesotheliomas compared with pulmonary adenocarcinomas. A total of 27 pulmonary adenocarcinomas and 26 mesotheliomas were stained with commercially available HBME-1 at various antibody dilutions and evaluated for the site (membranous, +/- microvillous brush border or cytoplasmic), intensity and percentage of cells staining. On light microscopy, 23 mesotheliomas showed distinctive microvillous brush border staining with HBME-1 (three mesotheliomas--two sarcomatoid and one poorly differentiated--were negative). Twenty-five adenocarcinomas showed membranous +/- cytoplasmic staining but lacked the distinctive microvillous brush border staining. In a subgroup of tumours studied by electron microscopy following immunogold labelling by HBME-1, all of 16 mesothelioma cases showed strong immunogold labelling in the membranes of the long microvilli. In contrast, the 12 cases of pulmonary adenocarcinomas showed minimal labelling in the membranes of the short microvilli, but staining was seen within vesicles, often near the surface of the cells. This study shows that the presence of a distinctive microvillous brush border by immunohistochemical staining with HBME-1 allows distinction between pleural mesotheliomas and pulmonary adenocarcinomas (sensitivity of 88%, specificity of 100%). The difference in the ultrastructural distribution of immunogold labelling with HBME-1 between mesotheliomas and adenocarcinomas underscores the light microscopy findings.

Efficacy and tolerability of sustained-release clomipramine (Anafranil SR) in the treatment of phobias: a comparison with the conventional formulation of clomipramine (Anafranil).

This multicentre double-blind trial in general practice compared the efficacy and tolerability of the sustained-release formulation of clomipramine (Anafranil SR) with its conventional formulation (Anafranil) in the treatment of phobias. Patients were allocated at random to receive clomipramine 75 mg once daily as either the sustained-release or conventional formulation for 11 weeks following a 1-week dosage build-up period. Analysis of results from forty-six patients showed that the sustained release formulation of clomipramine 75 mg was as effective as the conventional formulation of clomipramine 75 mg in improving symptoms of phobia as assessed by a phobia inventory and global evaluation. Unwanted effects attributable to therapy were similar in both treatment groups but there were fewer withdrawals due to unwanted effects of the sustained release formulation of clomipramine 75 mg. It was concluded that the sustained-release formulation of clomipramine does offer advantages for patients requiring 75 mg clomipramine daily.

Randomized crossover trial of isosorbide mononitrate (Elantan 20) and slow-release glyceryl trinitrate in the treatment of angina pectoris.

An open, randomized, comparative crossover clinical trial was carried out to compare the clinical efficacy of 20 mg isosorbide mononitrate 3-times daily and 6.4 mg sustained-release glyceryl trinitrate 3-times daily in the treatment of angina pectoris. Fifty patients entered the trial and 48 patients completed. Each treatment was given for 12 weeks followed by crossover to the alternative drug. Both treatments resulted in marked significant improvements relative to the pre-trial baseline, but isosorbide mononitrate was shown to be significantly (p less than 0.001) more efficacious than sustained-release glyceryl trinitrate in the reduction of the number of angina attacks and sub-lingual glyceryl trinitrate consumption. Angina frequency was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 33 (69%) of the patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 3 (6%) patients (p less than 0.001). Sub-lingual glyceryl trinitrate consumption was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 36 (75%) patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 5 (10%) patients. Examination of the effect of changing from isosorbide mononitrate to sustained-release glyceryl trinitrate therapy or vice versa confirmed the clinical superiority of isosorbide mononitrate. Physical exercise capacity was reported as improved in 20 (60%) patients with isosorbide mononitrate but in only 12 (25%) patients with sustained-release glyceryl trinitrate (p less than 0.02). Neither treatment showed any tendency for a reduction in effect during 12-weeks' continuous therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of phentermine and diethylpropion in the treatment of obese patients in general practice.

A study was carried out in general practice to compare the effectiveness and tolerance of phentermine and diethylpropion in helping patients more than 20% above their desirable weight to lose weight. Patients were allocated at random to receive either one 30 mg capsule of phentermine (50 patients) or one 75 mg tablet of diethylpropion (49 patients) daily over a period of 12 weeks. They were also asked to restrict their calorie intake to 1500 calories per day. The results showed that there was a significantly greater weight loss in patients treated with phentermine which was particularly marked during the last 4 weeks of the study. There were significant reductions in blood pressure and heart rate in the phentermine group and of heart rate in the diethylpropion group. These were almost certainly related to weight loss rather than to a direct effect of drug treatment. Side-effects were generally minor in nature and the incidence and nature of them were comparable in the two groups.

Doctor's versus patient's judgement in the assessment of mixed anxiety/depressive illness. Implications for measurement of therapeutic response.

The relationship of doctors' assessments to their patients' self-assessments was examined in a double-blind comparison of Motipress and Anafranil in patients suffering from mixed anxiety/depressive states. Significant differences between doctors' ratings were revealed which were largely parallelled by their patients' self-ratings done independently, suggesting differences between subgroups of patients within the whole population. Appropriate statistical analyses eliminated these factors in the data and showed that they did not affect the conclusions of a conventional statistical analysis of the two treatment groups as a whole; there were no significant differences between the major improvements associated with each treatment.

Bioluminescent assay of adenine nucleotides: rapid analysis of ATP and ADP in red cells and platelets using the LKB luminometer.

The assessment of both red cell and platelet function requires assay of adenine nucleotides. We describe the use of the new LKB luminometer to measure adenosine triphosphate (ATP) and adenosine diphosphate (ADP) by bioluminescence in both normal and abnormal red cells and platelets. ATP was measured a in a lysate of red cells suspended in buffer, pH 7.4, b in ethanol extracts of platelets from platelet-rich plasma (PRP) and c in ethanol extracts of supernatant platelet-poor plasma (PPP) following platelet aggregation by collagen. ADP was measured as ATP after phosphorylation by pyruvate kinase (PK) with phosphoenolpyruvate (PEP). Duplicate assays showed a variance of less than 3%. Red cell lysates and ethanol extracts of PRP and PPP stored at -40 degrees C were stable for 4 weeks. Duplicate assays of ATP and ADP in eight samples plus standards could be performed in 2 h. Normal values were: red cells (microM/ml red cells) (n = 20), ATP 1.15 +/- 0.17 (1 SD), ADP 0.22 +/- 0.07, ATP/ADP (mean ratio) 5.76:1, platelets (nm/10(9) platelets) (n = 20), ATP 53.3 +/- 7.6, ADP 27.8 +/- 5.8, ATP/ADP (mean ratio: 1.96:1). Abnormalities of red cell ATP and/or ADP could be demonstrated in chronic renal failure, hereditary glycolytic enzyme deficiencies and other haemolytic states. In myeloproliferative disorders defective platelet aggregation associated with storage pool deficiency and/or impaired release of ADP and ATP could be shown. We conclude that this is a reliable, rapid and economical technique for measuring red cell and platelet adenine nucleotides.

A double-blind study comparing cefaclor and amoxycillin in the treatment of respiratory tract infections in general practice.

A prospective double-blind study was carried out to compare the efficacy of intermittent versus continuous levels of beta-lactam antibiotics. Two hundred and ninety-eight patients attending their general practitioner and requiring treatment for respiratory tract infections were randomly allocated to receive either 250 mg cefaclor 3-times daily (intermittent) or 500 mg amoxycillin 3-times daily (continuous). By most of the parameters used to assess outcomes, the group on cefaclor did better than the group on amoxycillin, although in no case was the difference statistically significant. This result confirms previous studies which have shown that the maintenance of continuous levels of antibiotic is not a necessary objective when using beta-lactam antibiotics.

Anxiety states in family practice: an evaluation of the need for antidepressant as well as anxiolytic therapy.

Patients attending their family practitioner with emotional disturbance manifesting predominantly as anxiety were treated once daily for 4 weeks with either a pure anxiolytic, potassium clorazepate, or a formulation of a specific antidepressant together with an anxiolytic, fluphenazine/nortriptyline, in accordance with a double-blind, completely randomized design. After the first week the patients receiving fluphenazine/nortriptyline were showing a better response in terms of total symptomatology as well as anxiety, tension and depression taken separately, and after 4 weeks treatment this trend reached statistically significant levels on both the physicans' ratings and the patients' self-ratings for overall symptomatology (p less than 0-05) as well as anxiety and tension on the physicians' scale (p less than 0-01). Side-effects were infrequent, with the exception of drowsiness which was complained of by 42% of the patients receiving clorazepate. Although simple and convenient to take, a once daily benzodiazepine formulation of fixed dose is likely to be too inflexible to achieve optimal therapeutic effect in many patients. These results are in accord with accumulating evidence for the importance of a depressive aetiology underlying the majority of so-called anxiety states in family practice. Anxiolytic, in the absence of specific antidepressant, therapy is unlikely to be adequate for these patients, and may lead to long-term palliative use of benzodiazepines incurring a risk of dependence.

Once daily administration of a fluphenazine/nortriptyline preparation in the treatment of mixed anxiety/depressive states.

A study of 223 patients diagnosed as suffering from mixed anxiety/depressive states was carried out in general practice to compare the effectiveness of treatment with a once-daily tablet preparation containing 1.5 mg fluphenazine plus 30 mg nortriptyline, taken either at night or in the morning, with the same total daily dose taken as 1 tablet t.d.s. Patients were randomly assigned to 4-week's treatment with one of the three drug schemes, and patients' self-ratings as well as physicians's ratings were used to assess symptoms. Both rating assessments showed that there were highly significant improvements in each of the three treatment groups over the 4-week period. Although there were no clinically important differences between improvements in the night-time dose and t.d.s. groups, there was a higher incidence of drowsiness and tablet defaulting among patients taking the single morning dose.

Anxiety/depression in elderly patients. A double-blind comparative study of fluphenazine/nortriptyline and promazine.

A double-blind study involving sixty-two patients, aged 65 years or over, treated for twenty-eight days, showed that fluphenazine 0-5 mg/nortriptyline 10 mg three times daily was superior to promazine 50 mg three times daily in relieving symptoms of anxiety and was associated with a lower incidence of side-effects. The results are discussed in the light of the nature of anxiety/depression syndromes in the elderly and it is suggested that since symptoms of anxiety in these disorders are often manifestations of an underlying depressive illness, the antidepressant effect of the nortriptyline may have enhanced the 'anxiolytic' advantage of fluphenazine/nortriptyline.