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.     

Sustained use of insecticide-treated curtains is not associated with greater circulation of drug-resistant malaria parasites, or with higher risk of treatment failure among children with uncomplicated malaria in Burkina Faso

The impact of vector control measures on the evolution of antimalarial drug resistance is an important issue for malaria control programs. We investigated whether the in vivo efficacy of chloroquine (CQ) in children aged 6-59 months with uncomplicated malaria differed in 9 villages that had benefited from long-term use of insecticide-treated curtains (ITCs) and in 9 nearby non-ITC villages. We also compared the prevalence of genetic markers of resistance to CQ and sulfadoxine-pyrimethamine (SP) between the two groups of villages. The study enrolled 1,035 children with uncomplicated malaria and 231 infected but asymptomatic children. After taking account of re-infections, the proportions of children who experienced clinical failure after treatment with CQ were 14% and 19% in ITC and non-ITC villages, respectively (OR = 0.68; 95% CI: 0.39, 1.18). Parasitologic failure was observed in 49% of children in ITC villages and 58% of children in non-ITC villages (OR = 0.71 95%CI: 0.44, 1.13). The proportion of symptomatic children who harbored parasites carrying the pfcrt-76T allele was 43% in ITC villages and 40% in non-ITC villages (OR = 1.09; 95%CI: 0.80, 1.50). The pfmdr1-86Y allele was detected in 31% and 29% of children in the two groups of villages (OR = 1.14; 95%CI: 0.75, 1.72). Triple mutations in the dhfr gene were observed in 12% of children in both groups. No double mutations in the dhps gene were observed. Similar results were observed in asymptomatic children. In this setting, ITC use was not associated with increased circulation of parasites resistant to standard antimalarial drugs, or with a greater risk of treatment failure among children less than 5 years of age.     

Innate defenses in the liver during Listeria infection

Summary: The majority of pathogens entering the bloodstream are cleared by the liver. Listeria monocytogenes , an important natural pathogen of humans, is a useful tool for examining protective immune responses during systemic infections of mice. Innate immunity contributes to blood clearance and eventual sterilization of the liver subsequent to Listeria infections. Effector mechanisms expressed in the liver early after infections are orchestrated by complex interactions between resident populations, i.e. hepatocytes and Kupffer cells, with infiltrating monocytes, neutrophils, and natural killer cells. These interactions include cell to cell contact through adhesion molecules, as well as communication through secretion of cytokines and chemokines. The liver environment, as the interface between blood-borne pathogens and innate host defenses, is reviewed here.     

Visual field constriction as a cause of blindness or visual impairment.

Reported are the results of a study of onchocerciasis in communities mesoendemic for savanna onchocerciasis in Kaduna State, northern Nigeria. The study involved 6831 individuals aged > or = 5 years who underwent an extensive screening examination for visual function including Friedmann field analysis. A total of 185 (2.7%) were bilaterally blind by acuity and an additional 28 (0.4%) were blind by visual field constriction. Also 118 (1.7%) individuals were visually impaired by acuity criteria. No criteria for visual impairment by field constriction have been established, and we therefore investigated three potential criteria. As a result, a further 60 (0.9%) individuals were identified with significant visual impairment due to field loss by the various definitions. Small islands of remaining peripheral field occurred in 50 individuals, while 40 individuals had marked reduction of binocular visual field below the horizontal meridian. Concentric visual field constriction to < 20 degrees was found in seven individuals. The WHO definition of blindness currently includes visual field damage criteria for blindness but not for visual impairment. Visual field loss is recognized as a major disability. We hope that these findings stimulate international discussion leading to the development of satisfactory definitions for visual impairment by visual field constriction.     

Excreta disposal behaviour and latrine ownership in relation to the risk of childhood diarrhoea in Sri Lanka.

A case-control study of environmental and behavioural risk factors for childhood diarrhoea was conducted in Kurunegala district, Sri Lanka. From five hospitals, 2458 children aged less than 5 years and suffering from diarrhoea were recruited as clinic cases, and a further 4140 reporting with complaints other than diarrhoea were recruited as clinic controls. Community-based cross-sectional surveys were also conducted in three of the five areas served by these hospitals, and from these a further 1659 children were recruited as community controls. Children from households where excreta were reported to be disposed of in a latrine were less likely to have diarrhoea than children whose families improperly disposed of excreta. The results obtained from comparisons of cases with clinic controls (adjusted odds ratio [OR] 1.42, 95% confidence interval [CI] : 1.01-1.98), and of cases with community controls (OR 1.35, 95% CI : 0.85-2.13) were in agreement, suggesting that no important selection bias operated on this association. If the observed proportion (91%) of improper excreta disposal among the population could be reduced to 50%, 12% of childhood diarrhoea episodes would be prevented. Although latrine ownership may be a necessary condition for safe excreta disposal behaviour, diarrhoeal morbidity may only be reduced in Sri Lanka if behavioural changes take place concomitant with the construction of sanitation facilities.     

Altered neuronal excitability in cerebellar granule cells of mice lacking calretinin

Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mm of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore the calcium-buffering capacity. A proposed mathematical model demonstrates that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium-buffering capacity resulting from the absence of calretinin. This result suggests that calcium-binding proteins modulate intrinsic neuronal excitability and may therefore play a role in information processing in the CNS.