Potential risk factors for infection with Candida spp. in critically ill patients

The incidence, risk factors and prognostic factors for candidal infection were determined in a prospective study of 280 infected patients. Thirty-one (11%) patients were infected with Candida spp., sub-divided into 18 (58%) with C. albicans, and 13 (42%) with non-albicans spp. (six C. glabrata, three C. parapsilosis, and one each of C. krusei, C. tropicalis, C. guilliermondii and C. lusitaniae). Infection with Candida spp. was always associated with concurrent bacterial infection. By univariate logistic regression analysis, the degree of morbidity and the duration of mechanical ventilation were independent predictive factors for death, but infection with Candida spp., was not. Factors associated with Candida spp. infection were the degree of morbidity, intensive care unit length of stay, alterations of immune response, and the number of medical devices involved. By multivariate logistic regression analysis, the only independent risk factor for candidal infection was intensive care unit length of stay.     

The immune response of Drosophila melanogaster

Summary:  The response of the fruit fly Drosophila melanogaster to various microorganism infections relies on a multilayered defense. The epithelia constitute a first and efficient barrier. Innate immunity is activated when microorganisms succeed in entering the body cavity of the fly. Invading microorganisms are killed by the combined action of cellular and humoral processes. They are phagocytosed by specialized blood cells, surrounded by toxic melanin, or lysed by antibacterial peptides secreted into the hemolymph by fat body cells. During the last few years, research has focused on the mechanisms of microbial recognition by various pattern recognition receptors and of the subsequent induction of antimicrobial peptide expression. The cellular arm of the Drosophila innate immune system, which was somehow neglected, now constitutes the new frontier.     

Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)<50% or DTP before (log-rank test) and after adjustment using a Cox proportional hazard model for prespecified prognostic factors. Secondary endpoints were rates of change of various functional measures. In Study 1, primary outcome measures did not reach statistical significance. For the 2 mg group, for time to VC<50% analysis (without DTP) a significant 30% RRR was obtained (95% confidence interval [CI]: 8.46, P=0.009). In Study 2, no significant results were obtained. However, there was a trend in favour of add-on 1 mg dose xaliproden vs. placebo (RRR 15% [-6.31, ns] for time to VC<50%; RRR 12% [CI: -6.27, ns] for time to VC<50% or DTP). Adjusted RR ratios were consistently more favourable for the xaliproden groups. Tolerability was good, and dose-dependent side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.     

Ultrasound of soft tissue abnormalities of the extremities

Ultrasound may be the preferred initial diagnostic modality for the painful swollen extremity, the palpable extremity mass, and the injured extremity. The role of ultrasound in extremity soft tissue abnormalities, including muscle hemorrhage and injury, inflammatory processes, and soft tissue neoplasms, is the subject of this review.     

Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain

Neuroleptics influence a variety of putative neurotransmitters in the basal ganglia, including somatostatin and substance P. Most studies have been performed in animals after only 3 or 4 weeks of neuroleptic administration and have seldom examined the effects of withdrawal. To understand better the effects of haloperidol on neuropeptide systems, the effects of short-term (3 weeks) and long-term (8 months) administration, as well as withdrawal from long-term administration of haloperidol, on somatostatin and substance P concentrations were examined in the rat. Short-term haloperidol significantly decreased the concentrations of somatostatin in the caudate-putamen, nucleus accumbens, and ventral tegmental area, and decreased the concentration of substance P in the substantia nigra and the nucleus accumbens. However, long-term administration only decreased the concentration of somatostatin in the nucleus accumbens. In addition, a slight reduction in the concentration of substance P in the medial prefrontal cortex was detected after long-term treatment. After withdrawal from long-term haloperidol administration the concentrations of these peptides did not differ from control values in any of the brain regions examined. These results confirm that dopamine receptor blockade can affect the somatostatin and substance P systems in the basal ganglia and indicate that during long-term administration (8 months) tolerance develops to some of the effects that are observed after shorter (3 weeks) treatment periods.     

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin)

OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5-15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l (P<0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l (P> 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra-nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.     

Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy

Human Molecular     

Trans-perineal implantation of radio-opaque treatment verification markers into the prostate: an assessment of procedure related morbidity, patient acceptability and accuracy.

On-line imaging of prostate markers can be used to compensate for errors in radiation delivery. This study assessed the patient acceptability and morbidity associated with the trans-perineal route of implantation. A minority experienced acute pain or bleeding. Placement was accurate in all but one subject. An operator related learning curve exists. Although this is an invasive procedure most patients found it acceptable. Implementation for routine clinical practice is feasible.