A DOUBLE-BLIND,COMPARATIVE STUDY OF DOTHIEPIN AND CLOMIPRAMINE IN THE TREATMENT OF MAJOR DEPRESSIVE ILLNESS

Dothiepin, a well-established antidepressant, has been compared with clomipramine in a single-blind study which demonstrated that dothiepin was better tolerated but there was no difference in efficacy. The present study was performed to recent European guidelines on good clinical practice using a randomised, double-blind, parallel-group methodology. One hundred and one patients suffering from major depressive disorder as defined by DSM-III-R were randomised to receive either clomipramine (25-150 mg daily) or dothiepin (75-150 mg daily) for up to six weeks. The clomipramine group comprised 51 patients, the dothiepin group 50 patients. At baseline, both groups had a mean age of 41-43 years and gave similar mean scores on the Hamilton Depression Rating Scale (23.5 for clomipramine, 23.6 for dothiepin). At endpoint it was reduced in both groups but there were no significant differences between the groups (mean change from baseline for the clomipramine and dothiepin groups was -14.6 and -14.1 respectively). Thirty-one clomipramine patients and 41 dothiepin patients completed six weeks' treatment. Withdrawal from treatment (20 patients for clomipramine, nine for dothiepin) was significantly different (p=0.0105). When reasons for withdrawal were analysed, 13 clomipramine patients and two dothiepin patients withdrew because of adverse events, this difference being significant (p=0.002). Thus both treatments were effective in treating patients suffering from major depressive disorder, but patients receiving dothiepin suffered fewer adverse events and were more likely to complete their treatment.     

The management of traumatic brain injury

Traumatic brain injury (TBI) is a global problem with a huge socioeconomic impact. Current understanding of the pathophysiology of TBI has led to a systematic approach towards management in the pre-hospital, operating theatre and critical care settings. Early management is directed towards protecting the brain from secondary injury. TBI is a spectrum of diseases, and rapid radiological identification of the underlying pathology is paramount to determine appropriate surgical intervention. Perioperative management frequently requires neurocritical care, with most modern centres using intracranial pressure and cerebral perfusion pressure targeted therapies. Decompressive craniectomy can be a useful mechanism to control medically refractory intracranial hypertension and reduce mortality; however, it also results in a spectrum of outcome categories and remains a controversial topic. Finally, there is emerging evidence that TBI is a chronic illness, with increased incidence of cognitive and behavioural deficits, neurodegenerative disease and an increased mortality that extends well beyond the initial TBI stage.     

Posttransfusion hepatitis after induction chemotherapy in acute nonlymphoblastic leukemia: implications for long-term management and outcome

BACKGROUND: The purpose of this study was to evaluate 1) the incidence of hepatitis and its influence on the clinical management of and outcome in acute nonlymphoblastic leukemia (ANLL) patients in first complete remission and 2) the impact of routine hepatitis C virus screening on the incidence of hepatitis in these patients. STUDY DESIGN AND METHODS: Clinical and blood bank charts were reviewed for 65 consecutive ANLL patients between 1985 and 1993 who achieved complete remission after a course of daunomycin and cytarabine (cytarabine: 200 mg/m2/day × 7 days in continuous infusion; daunomycin: 60 mg/m2/day for the first 3 days of the 7, as a bolus). RESULTS: Only 43 percent of patients who developed hepatitis completed the scheduled therapy. Hepatitis did not decrease the probability of relapse (66 +/− 9% vs. 66 +/− 11%), but patients with changes in planned treatment, due to hepatitis or other causes, tended to have a higher relapse rate than patients without changes in consolidation therapy (56.5% vs. 40.4%; p = 0.10). This did not result in a decrease in disease-free survival, however, because of the higher number of treatment-related deaths in the patients without hepatitis (who completed the therapy). Over the period from 1985 through 1989, the 6-month actuarial probability of developing hepatitis was 42 percent. However, since 1989, when hepatitis C screening of blood donors was implemented, the incidence was reduced to 12.5 percent (p < 0.05), in spite of greater transfusion support (172 +/− 46 vs. 89 +/− 53, p < 0.01). No new cases of hepatitis were observed after the introduction of second-generation hepatitis C virus assays. CONCLUSION: Hepatitis precludes the use of consolidation therapy in about half of ANLL patients, resulting, in the experience described here, in a trend toward a higher rate of relapse. Hepatitis C virus screening of blood components reduces the incidence of hepatitis in ANLL patients.     

Safety and efficacy of hepatitis C virus antibody screening of blood donors with two sequential screening assays

BACKGROUND: Reactive samples in hepatitis C virus (HCV) antibody screening of blood donors are currently referred for a confirmatory assay. This scheme is not optimally efficient and is expensive because of the lack of specificity and cost of confirmatory tests, as well as the need to discard false-positive donations. As in some human immunodeficiency virus antibody-confirmatory schemes, the safety and efficacy of confirming anti-HCV with two sequential screening assays were evaluated. STUDY DESIGN AND METHODS: Three combinations of two anti-HCV screening assays were used to test 75,874 blood donors. Results were compared with the routine testing scheme and HCV RNA detection in any enzyme immunoassay-repeatably reactive samples. RESULTS: The use of an alternative screening assay for repeat testing decreased the proportion of enzyme immunoassay-positive donors from 0.28 to 0.05 percent. All samples that were "confirmed" as positive by the standard combination of immunoassays and all HCV RNA-positive samples were detected by the sequential screening assays. No samples that had discordant results on primary and secondary screening assays were confirmed by recombinant immunoblot assay or were found to contain detectable HCV RNA. CONCLUSION: The combination of screening assays for anti-HCV confirmation was as safe as, cheaper than, and nearly as efficient as the standard testing scheme.     

Relationship between structure and correcting activity of bovine high molecular weight kininogen upon the clotting time of fitzgerald-trait plasma

Bovine high molecular weight kininogen (bHMWK) partially corrects the activated plasma thromboplastin time (aPTT) of Fitzgerald trait plasma which is congenitally deficient in HMWK. The relationship between the structure and activity of HMWK was clarified by studying the effects of different fragments of bHMWK on the aPTT of Fitzgerald-trait plasma. The peptides studied were lys-bradykinin-free HMWK, bradykinin-fragment 1-2-free HMWK, heavy chain, fragment 1-2-light chain, and light chain. All fragments were tested in equimolar concentrations. Bradykinin-fragment 1-2-free HMWK, heavy chain, and light chain have little or no correcting activity upon Fitzgerald-trait plasma aPTr. Fragment 1-2 light chain has the same correcting activity as intact bHMWK, while that of lys-bradykinin-free HMWK appears to be higher. Both fragment 1-2 and fragment 2 inhibit the clotting time of normal human plasma. When compared on a molar basis, fragment 2 is a more active inhibitor than fragment 1-2. When the effects of bovine plasma kallikrein upon bHMWK and hHMWK were studied, it was found that it released kinins from both kininogens. However, while the correcting activity of bHMWK was completely destroyed after 60 min of incubation, that of hHMWK was fully retained. These data suggest that: (a) the active part of bHMWK is comprised of the fragment 1-2 light chain portion; (b) fragment 1-2 or fragment 2 is the binding site to negatively charged surfaces, while the light chain interacts with other components of the surface-mediated reactions; and (c) bovine plasma kallikrein releases kinins, but probably does not cause the release of fragment 1-2 from human HMWK.     

Self Chest Clapping: Patients'' Views and the Effects on Oxygen Saturation

The literature suggests that self chest clapping (SCC) does not enhance rate of sputum clearance if combined with the active cycle of breathing techniques (ACBT), but many patients find SCC beneficial and continue to use it. Previous studies have examined the effects of assisted chest clapping on oxygen saturation (SaO₂), but what would be the effects of SCC on SaO₂? It was important to establish any possible detrimental effects from its use and to explore the views of patients using it as part of their treatment.

The SaO₂ was measured in 20 clinically stable patients with cystic fibrosis during their physiotherapy (the ACBT with SCC in a gravity assisted position) and all patients completed a short anonymous questionnaire to obtain their views on SCC. Patient characteristics of lung function, arterial blood gases, response to bronchodilator therapy, 24-hour sputum weight and exercise ability were recorded, within 48 hours of participation within the study, to identify a possible relationship between these and a change in SaO₂.

In the group as a whole there was a statistically significant mean fall in SaO₂ with SCC (p = 0.026). However, this fall was never greater than 4.4%. In some patients a fall in SaO₂ was recorded with SCC, but in others there was an increase. There was no correlation between the variables measured and a fall in SaO₂ with SCC. The patients using SCC had strong views and beliefs about why they did so.     

The pathophysiology and clinical relevance of platelet heterogeneity

Recent studies on platelet heterogeneity support the hypothesis that platelet production is regulated to maintain a constant functional platelet mass. In concept this form of regulation is analogous to the manner by which RBC production is controlled to maintain the oxygen- carrying capacity of blood. The platelet mass appears to correlate more closely with platelet function than the platelet count alone, since several factors in addition to the platelet count have been shown to influence the platelets' hemostatic function. These factors include platelet size, density, age, and previous hemostatic interactions. Application of these concepts to clinical problems has provided important insights into platelet physiology and reactivity. Failure to account for differences in platelet heterogeneity among individuals may introduce significant errors in the interpretation of data from laboratory and clinical investigations. However, despite advances, a number of practical issues remain to be resolved before measurements of platelet heterogeneity become accepted as routine clinical tests and are used in the diagnosis of pathologic states.     

Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme

Background  

The relevance of angiogenesis inhibition in the treatment of glioblastoma multiforme (GBM) should be considered in the unique context of malignant brain tumours. Although patients benefit greatly from reduced cerebral oedema and intracranial pressure, this important clinical improvement on its own may not be considered as an anti-tumour effect.