Binocular contrast detection with unequal monocular illuminance

Binocular summation was measured in eight normal subjects by means of psychometric functions for contrast detection. An average 47% increase in binocular over monocular performance was obtained. Our data agreed with the simple summation model of Signal Detection Theory (Legge, 1984). Binocular psychometric functions were also measured when the sensitivity of one eye was decreased by means of a 1.0 neutral density (ND) filter. We found that binocular detectability in this case was reduced to below that of the better eye. This binocular inhibition was seen in all subjects. The slope of a contrast detection function gives a measure of the rate of change in detectability with contrast. If the slopes of two functions are equal, then the difference in detectability between these functions remains constant for all the contrast values used. When the slopes of the measured functions were analysed, no significant differences were found under any of the testing conditions. This indicates that the magnitude of summation (with equal monocular sensitivities), and of inhibition (with unequal monocular sensitivities), remains constant across the range of stimulus contrasts. The clinical implications of binocular inhibition are discussed.     

Opioid receptor binding in parahippocampus of patients with temporal lobe epilepsy: its association with the antiepileptic effects of subacute electrical stimulation.

Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.     

The Specific Endothelin A Receptor Antagonist ZD4054: Preclinical and Clinical Results

ContextZD4054 is a specific endothelin A (ET_A) receptor antagonist being investigated for the treatment of hormone-resistant prostate cancer (HRPC). ZD4054 binds specifically to the ET_A receptor, with no detectable activity at the ET_B receptor. In preclinical studies, ZD4054 inhibited endothelin (ET-1)-mediated changes in cellular invasiveness in vitro, and inhibited angiogenesis and growth of tumour xenografts in vivo. Consistent with its specific binding profile, ZD4054 inhibited ET_A-receptor-mediated antiapoptotic events while allowing ET_B-receptor-mediated proapoptotic signalling.Evidence acquisitionThe preclinical and clinical activity of ZD4054 is reviewed.Evidence synthesisIn the clinical setting, stable levels of circulating ET-1 following single ZD4054 doses up to 240 mg demonstrated the absence of ZD4054 activity at the ET_B receptor. ZD4054 is cleared principally via the urine, with a terminal elimination half-life of approximately 8–12 hours and with little accumulation after once-daily oral dosing.In a Phase 2 trial, patients with metastatic HRPC who were pain free or mildly symptomatic for pain were randomized to once-daily oral tablets of ZD4054 10 mg (n = 107), or 15 mg (n = 98), or matched placebo (n = 107). ZD4054 was generally well tolerated in this population, with an adverse effect profile consistent with its known pharmacological activity. The most common adverse effects were headache, peripheral oedema and nasal congestion. At the primary analysis there was no statistically significant difference in time to progression between the ZD4054-treated groups and placebo (hazard ratio [HR]: ZD4054 10 mg, 0.88 [80% CI 0.71, 1.09]; ZD4054 15 mg, 0.83 [0.66, 1.03]). However, a promising signal for prolonged overall survival was observed, which was sustained at a subsequent analysis (HR versus placebo: ZD4054 10 mg, 0.55 [80% CI 0.41, 0.73]; ZD4054 15 mg, 0.65 [0.49, 0.86]).ConclusionsThese results support the strategy of targeting the ET_A receptor in prostate cancer, and mandate further investigation of ZD4054 in Phase 3 clinical trials.     

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.     

Respiratory syncytial virus

RSV is now understood to be the most significant viral respiratory pathogen of infants and is capable of causing both bronchiolitis and pneumonia. It is a particular risk to hospitalized infants as the virus is easily spread through close contact. The most vulnerable infants are those who suffer with either congenital heart disease or bronchopulmonary dysplasia who easily fall prey to pulmonary complications of infection. Strict environmental control and the use of protective clothing and eyewear should be implemented to decrease the nosocomial spread of RSV. Available diagnostic studies include viral isolation, fluorescent antibody stains, and enzyme immunoassays. Treatment of the disease is usually supportive but hospitalized patients frequently benefit from aerosolized ribavirin therapy. Hopefully, current vaccine trials will be successful and this pathogen will not only be treatable but will also be preventable.