Femoxetine and amitriptyline in general practice: a randomized double-blind group comparison

Patients with a depressive illness with 4 major symptoms of depression and a score of at least 17 on the Hamilton Depression Scale (1-17) (HDS) were allocated to a randomized double-blind group comparative study in general practice. After retrospective analysis, all 81 patients except one were characterized as suffering from a 'Definite Major Depressive Disorder', as defined by Spitzer et al. (1978). After 6 weeks of treatment with a daily dosage of 600 mg femoxetine or 150 mg amitriptyline, no statistically significant differences between the 2 treatment groups were observed, either when using the HDS or the clinical global assessment scale. Confidence limits of 95% for differences between therapeutic effect showed a non-significant tendency in favour of amitriptyline. During treatment, there were statistically significant differences in the reduction of HDS score between the 2 treatments in week 2. These differences were the result of amitriptyline's significantly greater effect on the 3 sleep items at week 2, as indicated by the results of single item analysis. Drop out rates due to side effects were between 14-15% in both treatment groups. Of the patients treated with femoxetine, 38% experienced no side effects, compared to 14% of patients treated with amitriptyline. Nausea was the side effect most commonly reported by patients treated with femoxetine, whereas a significantly greater frequency of anticholinergic side effects was recorded during treatment with amitriptyline (P less than 0.05). Unlike amitriptyline, femoxetine did not increase body weight. Treatment with the active drug was continued after the trial period in 14 and 18 patients in the femoxetine and amitriptyline groups respectively.     

Uptake of dehydroascorbic acid and ascorbic acid to isolated nerve terminals and secretory granules from ox neurohypophyses

When uptake of L-[14C]ascorbic acid ([14C]AA) to various organs in guinea-pigs was studied after intracardiac injection, the adenohypophysis, pars intermedia, and the neurohypophysis had an uptake per milligramme protein which was about half of the uptake to the adrenals. Adrenal uptake was 20 +/- 2.8 pmol mg-1 protein microCi-1 injected. The uptake to the different parts of the hypophysis was considerably higher than the uptake to pancreas, liver, kidney, spleen and other organs. When isolated nerve endings (neurosecretosomes) from ox neurohypophyses were incubated with a medium containing labelled dehydroascorbic acid ([14C]DHA), the uptake was much slower than when the medium contained labelled ascorbic acid. The uptake of [14C]DHA showed a linear dependence on concentration, and was not influenced by addition of Mg2+ and ATP. Addition of Mg2+ + ATP, omission of Ca2+ and Mg2+ or exchange of Na+ in the medium with K+ had no effect on the uptake of ascorbic acid. When isolated secretory granules from ox neurohypophyses were incubated with a medium containing [14C]DHA, uptake was considerably faster than the uptake when they were incubated in a medium containing [14C]AA. The uptake of dehydroascorbic acid was linear with the concentration in the medium and was not changed by addition of Mg2+ ATP. Addition of 10 mM NH4Cl or exchange of 120 mM K+ in the incubation medium with Na+ did not change the uptake of dehydroascorbic acid. The contents of copper, zinc, iron and cobalt were determined in isolated nerve endings (A) and membranes (B) as well as in lysate (C) from isolated neurosecretory granules. The results (in nmol mg-1 protein) were for Cu: (A): 0.25 +/- 0.01 (SEM), (B): 0.67 +/- 0.16, (C): 0.22 +/- 0.06; for Zn: (A): 0.53 +/- 0.13, (B): 6.97 +/- 0.75, (C): 1.8 +/- 0.53; and for Fe: (A): 15.6 +/- 1.9, (B): 6.92 +/- 0.32, (C): 3.15 +/- 0.43. In all preparations the cobalt content was below the detection limit (less than 5 pmol mg-1 protein).     

The longitudinal validity of proxy-reported CHU9D

Quality of Life Research - The Child Health Utility 9D (CHU9D) currently represents the only preference-based health-related quality-of-life instrument designed exclusively from its inception for...     

Statins and peripheral neuropathy

Within the past 3 years seven cases of reversible peripheral neuropathy apparently caused by statins have been reported. Here we report seven additional cases associated with long-term statin therapy, in which other causes of neuropathy were thoroughly excluded. The neuropathy was in all cases axonal and with affection of both thick and thin nerve fibers. The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to 1 year in four cases after statin treatment had been withdrawn. We suggest that long-term statin treatment may be associated with chronic peripheral neuropathy. Received: 6 July 1998 / Accepted in revised form: 1 October 1998     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma

Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.