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     

CEREBRAL BLOOD-FLOW VELOCITY AND INTERMITTENT INTRACRANIAL PRESSURE ELEVATION DURING SLEEP IN HYDROCEPHALIC CHILDREN

The clinical importance of intermittent intracranial pressure (ICP) elevations during sleep in hydrocephalic children is unclear. Eight studies of continuous ICP monitoring with simultaneous cerebral blood-flow velocity (CBFV) measurements were recorded during sleep in seven hydrocephalic children aged between one and 10 years. ICP was measured directly through a frontal reservoir. There were two main patterns of CBFV change in response to raised ICP: a progressive decrease in mean flow velocity and increase in resistance index, suggesting impaired haemodynamic compensation to ICP elevation due to reduced circulatory reserve in patients with limited intracranial compliance; and an increase in mean flow velocity with raised ICP, suggesting that appropriate haemodynamic compensation with increased blood-flow can occur to maintain adequate cerebral perfusion in those with sufficient circulatory reserve. Simultaneous CBFV and ICP measurements may help to identify those with reduced circulatory reserve who are at greater risk of ischaemic insult from episodic increases in ICP.     

Cholesterol reduction and death from noncoronary causes: evidence from randomised controlled trials*

An overview of randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction ?10%) provides clear evidence of a reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the observed reduction in CHD death (9%± 3) was only half as large as the reduction in non-fatal myocardial infarction (19%±4), although both were statistically significant (2p <0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 9%, the expected reduction in total deaths was about 5–6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases individually statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations suggest that the small excesses of noncoronary deaths observed in the cholesterol reduction trials may have occurred by chance. Evidence from ongoing longer-term studies of treatments producing larger cholesterol reductions will be useful in further delineating the effects, if any, of such treatments on non-coronary mortality.     

Agitation, cognition and attention during post-traumatic amnesia

During the early phases of recovery from traumatic head injury, the level of functional cognition and the presence of agitation in patients appear to co-vary. However, it has been observed that there appears to be some temporal dissasociation in the recovery of cognition and agitation. The purpose of this study was to investigate the degree to which attention accounts for the co-variation previously observed. Over a 1-year period, 130 patient-weeks of independent monitoring of cognition, agitation and attention were obtained from 20 head-injured patients in the acute phase of recovery. Weekly scores for measures of cognition, agitation and attention were each found to share approximately 50% of the variance when paired with one of the other two. When attention was extracted, only 7% of the variation in cognition was accounted for by agitation, and 40% of the variance could not be accounted for by either agitation or attention. These results support previous findings that cognition and agitation co-vary with most of the co-variance due to the effect of attention on each. Concomitantly, these results allow that significant portions of the variance in cognition and agitation may be temporally dissociated during the acute phases of recovery from traumatic head injury.     

Development of Resistance During Antimicrobial Therapy: A Review of Antibiotic Classes and Patient Characteristics in 173 Studies

The incidence of emergent resistance and clinical factors affecting its development were evaluated by retrospective review of 173 studies encompassing over 14,000 patients. Eight antibiotic classes and 225 individual treatment regimens were evaluated. Emergent resistance occurred among 4.0% of all organisms and 5.6% of all infections treated. It appeared to be significantly more frequent with penicillin and aminoglycoside monotherapy, with significantly lower rates associated with imipenem-cilastatin, aztreonam, and combination therapy. Clinical failure also appeared to be significantly more likely to occur after emergence of resistance among organisms treated with fluoroquinolones or aminoglycosides. Infections associated with higher resistance rates were cystic fibrosis, osteomyelitis, and lower respiratory tract infections. Resistance was most common in patients in intensive care units or receiving mechanical ventilation. It was also significantly frequent among studies performed in university or teaching hospitals. Organisms associated with high resistance rates were Pseudomonas aeruginosa, Serratia, Enterobacter, and Acinetobacter sp. Factors such as infection type, underlying diseases, type of institution, and specific pathogens warrant consideration when examining emergent resistance.