A RANDOMISED,DOUBLE-BLIND,PARALLEL-GROUP COMPARISON OF VENLAFAXINE AND DOTHIEPIN IN GERIATRIC PATIENTS WITH MAJOR DEPRESSION

This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) from baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p=0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reason for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

Investigating employment following spinal cord injury: outcomes,methods, and population demographics

Purpose: The purpose of this review was to synthesize the literature about spinal cord injury and employment, focusing on sample demographics, indicators of employment outcome, and the methods used. The review included literature from the previous decade; 2006–2017.

Methods: A systematic quantitative literature review methodology was utilized, wherein papers’ characteristics were extracted and categorized in a database according to their topics, employment outcome indicators, populations, locations, and methods. Frequency tables were generated and cross-tabulated to yield conclusions about the outcomes of the studies and the methods and samples used to yield these outcomes.

Results: The review highlighted three key themes; the emergence of broader employment outcome measures that go beyond employment rate; a lack of consistency in the reporting of sample characteristics such as time since injury or ethnicity; and the relative lack of research focusing on people with newly acquired spinal cord injury.

Conclusions: The literature review identified a number of limitations in the existing research including the lack of standardized reporting of employment outcomes and a need for increased consistency in reporting sample characteristics. In addition, there are gaps in the research about people with newly acquired spinal cord injury, particularly regarding the timing of interventions.

• Implications for Rehabilitation

• Spinal cord injury has the potential to disrupt a person’s career across their lifespan.

• Employment rate is the gold standard for evaluating employment outcomes.

• Broader measures of employment, including job retention and hours worked, have potential in evaluating and improving the quality of employment outcomes for this population.

• Further research with people with newly acquired spinal cord injuries would better support the provision of vocational rehabilitation services earlier in a person’s rehabilitation, potentially preserving jobs.

     

Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey.

Programmed electrical stimulation was used to examine the ability of long-term dietary lipid modulation to influence myocardial vulnerability to the induction of ventricular fibrillation in adult marmoset monkeys (Callithrix jacchus). Marmosets fed diets supplemented (to a total of 28.5% of the energy as fat) with polyunsaturated fatty acid (PUFA)-rich tuna fish oil or sunflower seed oil had significantly elevated mean ventricular fibrillation threshold compared with those fed a saturated animal fat supplemented diet or a reference diet not supplemented with fat (11.2% of the energy as fat). Fibrillation threshold was reduced during acute myocardial ischemia induced by coronary artery occlusion but still remained higher in the PUFA-fed animals than either the control or the ischemic threshold in reference or saturated fat supplemented animals. Dietary tuna fish oil was associated with a low incidence of sustained fibrillation episodes and no fatalities. These results indicate that myocardial substrate vulnerability to arrhythmic stimuli is increased during ischemia in a nonhuman primate model but dietary PUFA can reduce vulnerability under both normal and ischemic conditions. Reduced dietary fat intake alone was without effect.     

Heparin and heparan sulphate are inhibitors of human leucocyte elastase.

1. Heparin and heparan sulphate strongly inhibited human leucocyte elastase activity in an automated assay using the soluble substrate, n-succinyl-(L-alanine)3-p-nitroanilide (50% inhibition of 250 microliters of 10 micrograms of human leucocyte elastase/ml was obtained with 80 microliters of 2.8 micrograms of heparin/ml and 8 micrograms of heparan sulphate/ml). Less significant inhibition at the same concentrations was seen with the other glycosaminoglycans tested: hyaluronic acid and chondroitin sulphates A-C. 2. Heparin and heparan sulphate also strongly inhibited human leucocyte elastase activity towards insoluble human lung elastin, as determined by an e.l.i.s.a. for soluble elastin-derived peptides released by elastolytic activity on the elastin. This inhibition was shown not to be due to a direct interference of the glycosaminoglycans in the e.l.i.s.a. nor to the inhibition causing a change in the size of the elastin-derived peptides. However, unlike the chromogenic assay with n-succinyl-(L-alanine)3-p-nitroanilide as substrate, where heparin was the more effective inhibitor, in this assay system heparan sulphate was the more effective inhibitor (50% inhibition of 100 microliters of 50 ng of human leucocyte elastase/ml was obtained with 100 microliters of 4.5 micrograms of heparin/ml and 0.8 microgram of heparan sulphate/ml). These results suggest that heparin and heparan sulphate, as components of cellular and basement membranes, are likely to have a role in protecting structural proteins, such as elastin, from the proteolytic activity of human leucocyte elastase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging

RATIONALE: Coughing in humans is typically preceded by a desire (or urge) to cough. The neural circuitry involved in sensing airway irritation and generating the urge-to-cough in humans is essentially unknown. OBJECTIVES: The aim of the present study was to use functional brain imaging to describe the supramedullary regions that are activated in humans during capsaicin inhalation. METHODS: Experiments were performed on 10 healthy subjects (5 males, 5 females). Capsaicin doses were individually tailored to evoke a transient and reversible urge-to-cough. Blood oxygen level-dependent (BOLD) functional magnetic resonance measures were collected during repeated 24-second challenges with capsaicin or saline inhalation and subjects were asked to rate the urge-to-cough intensity of each challenge. MEASUREMENTS AND MAIN RESULTS: Capsaicin inhalation reliably evoked an urge-to-cough, which was associated with activations in a variety of brain regions, including the insula cortex, anterior midcingulate cortex, primary sensory cortex, orbitofrontal cortex, supplementary motor area, and cerebellum. CONCLUSIONS: These data provide the first insights into the cortical neuronal network involved in sensing airway irritation and modulating coughing in humans.     

Is methoxyflurane a suitable battlefield analgesic?

Anecdotal reports of mechanical failure of morphine autojets have triggered a review of possible alternatives. Methoxyflurane is one such alternative already widely used by the Australian and New Zealand Defence Forces. The potential benefits and likely significant drawbacks of methoxyflurane are reviewed with the aim of stimulating discussion.     

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

Background  

Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting.     

Effects of L-histidine depletion and L-tyrosine/L-phenylalanine depletion on sensory and motor processes in healthy volunteers

Background and purpose:

Animal studies show that histamine plays a role in cognitive functioning and that histamine H₃-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H₁-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects.

Experimental approach:

Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed.

Key results:

Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency.

Conclusions and implications:

L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H₁-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies.