Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man

This is the first neuropsychological study using the S-enantiomer of the noncompetitive N-methyl-D-aspartate antagonist ketamine. In 2 randomized placebo-controlled trials we studied effects of two different doses of (S)-ketamine (low dose/high dose) on neuropsychological functions and psychopathology in 12 healthy male volunteers. Impairment was measured via standardized neuropsychological tests. Results indicate that both subanaesthetic doses produce only nonsignificant impairment in most of the tasks. Tasks involving divided and sustained attention as well as scores for objective and subjective psychopathology show significant impairment in a dose-dependent manner. Implications of these findings for the neuropsychology of attention and schizophrenia are discussed.     

Crossbow homicides

A total of eight cases of homicide by crossbow are reported, including six intentional, assault-like killings and one hired killer. The bolts showed a high penetration capacity despite the rather low kinetic energy (<100 J): a field-tip traversed one upper arm and the thorax (36 cm) and two broadheads caused perforating injuries of the thorax (25–26 cm). This was due to the high sectional density and the split-like penetration mechanism. Wound morphology was especially important if the perpetrator had extracted the bolt, which occurred in half of the cases. The shape of the entrance wound depended on the type of arrowhead: broadheads produced star-shaped to triangular wounds, field-tips caused circular, oval or slit-like injuries. Foreign material from the arrowhead was found inside two injuries. In assaults, the crossbow was used to hunt the victim down from a short distance which does not require practice but still has the advantage of a distance weapon. However, immediate incapacitation occurred rarely so that additional violence was frequently applied. The noiseless character of the weapon explains why many victims were taken by surprise and why the corpses initially remained unnoticed. Crossbows can therefore be considered ideal weapons for man hunting and some were bought for the very purpose of the killing.     

Occupational exposure and urological cancer

Occupational exposure is definitely a major cause of cancer. In the field of urology, the urinary bladder is the most important target. A classical cause of bladder cancer is exposure to carcinogenic aromatic amines, especially benzidine and beta-naphthylamine. Such exposures were related to work places in the chemical industry, implying production and processing of classical aromatic amines, and in the rubber industry. Occupational bladder cancer has also been observed in dyers, painters and hairdressers. Even some occupations with much lower exposures to carcinogenic aromatic amines, like coke oven workers or workers in the rubber industry after the ban on beta-naphthylamine, are at risk. In these occupations, exposure to complex mixtures of substances containing combustion products (e.g. polycyclic aromatic hydrocarbons) or nitrosamines is common. Renal cell cancer has been observed as an occupational disease in cases of very high exposure to trichloroethylene having led to narcotic or prenarcotic symptoms. Occupationally related cancers of the prostate or the testes appear currently not relevant.     

Structure-function relationships of multidrug resistance P-glycoprotein

The direct structure-function relationships of P-glycoprotein (P-gp) are presently unknown. In this paper two P-gp models are described: a homology model based on the Escherichia coli MsbA lipid transporter and a model based on the cross-linking results of Loo and Clarke. The pharmacophore pattern for the H-site (Hoechst 33342) is derived and binding sites on the transmembrane domains TM5 and TM11 are identified. Binding sites of rhodamines are also proposed on TM6 and TM12 in accordance with the published data. Location of the binding sites is opposite in both models, suggesting that TMs undergo rotation exposing the substrate bound from the membrane to the pore. It has been concluded that the models derived represent two different functional states of P-gp corresponding to nucleotide-free and nucleotide-bound P-gp. A qualitative correspondence to the P-gp crystallographic structure at 20 A resolution is found. A hypothesis is proposed about rearrangement of TMs upon state transition.     

Medical errors and the trainee: ethical concerns

How medical errors are handled by individual physicians and hospital systems is a topic of considerable interest. In teaching hospitals, medical students and house officers often observe and commit mistakes. Commission of a mistake is associated with serious emotional turmoil and uncertainty among trainees as well as experienced physicians. Although disclosure is the ethical standard, the consequences of disclosure are feared by many. This article focuses on the issues that surround medical errors as they pertain to medical students and residents. It is important that this group of future physicians has appropriate training, mentoring, and support when dealing with errors.     

Carbohydrate-deficient transferrin (CDT)--a biomarker for long-term alcohol consumption

Carbohydrate-deficient transferrin (CDT) is a biomarker for chronic alcohol intake of more than 60 g ethanol/d. It has been reported to be superior to conventional markers like gamma-glutamyltransferase (GGT) and mean corpuscular volume MCV). This review covers theoretical and analytical aspects, with data from controlled drinking experiments and from different population subgroups such as subjects with different liver diseases or different drinking patterns. CDT determinations are particularly indicated in (1) cases of chronic alcohol consumption and relapses after withdrawal, (2) license reapplication after driving under alcohol influence, (3) differentiating patients with enzyme-inducing medication from those with alcohol abuse, 4) congenital disorders of glycosylation such as carbohydrate-deficient glycoprotein syndrome Ia (CDGS Ia), and (5) patients treated for galactosemia. The main advantage of CDT is its high specificity, as evidenced in combination with increased alcohol consumption. CDT values are not markedly influenced by medication except in immunosuppressed patients, who may show low CDT values. In general, CDT values appear less elevated after alcohol intake in women. The main disadvantage is the relatively low sensitivity. Hence, this parameter is not suitable for screening for subjects with alcohol abuse in the general population. As CDT, GGT, and MCV are connected with chronic alcohol consumption by different pathophysiological mechanisms, a combination of these parameters will further improve the diagnostic value.     

Effect of partial left ventriculectomy on left and right ventricular volumes and function as assessed with electron beam tomography: preliminary results

Our objective was to determine if left ventricular reduction surgery affects left and right ventricular volumes and function. Twenty-three patients with end-stage heart failure underwent contrast-enhanced electron beam tomographic function studies before and twice after partial left ventriculectomy (PLV). The PLV was combined with other cardiosurgical procedures in 20 of 23 patients. Left and right ventricular enddiastolic volume (LVEDV, RVEDV), stroke volume (LVSV, RVSV), ejection fraction (LVEF, RVEF), and enddiastolic diameter (LVEDD, RVEDD) were determined by manual tracing of endo- and epicardial borders at enddiastole and endsystole. Patients were scanned 31 days (±34) before and 18 days (±13) and 8 months (±4) after PLV. Mean pre- and early and late postoperative values for LVEDV, LVSV, LVEF, and LVEDD were 387.9 ml (±125.5 ml), 255.6 ml (±79.3 ml; p<0.01), and 253.7 ml (±97.8 ml; p<0.05), 79.7 ml (±25.2 ml), 74.8 ml (±17.9; n.s.), and 79.1 ml (±26.5 ml; n.s.), 21.6% (±7.3%), 31.9% (±13.4%; p<0.05), and 34.1% (±14.1%; p<0.05), and 72.0 mm (±10.6 mm), 64.3 mm (±8.5 mm; p<0.05), and 63.5 mm (±9.4 mm; p<0.05), respectively. Mean pre- and postoperative values for RVEDV, RVSV, RVEF, and RVEDD were 177.7 ml (±72.8 ml), 172.4 ml (±59.2 ml; n.s.), and 178.9 ml (±60.8 ml; n.s.), 60.3 ml (±21.6 ml), 68.8 ml (±19.9 ml; n.s.), and 78.3 ml (±25.3 ml; n.s.), 38.1% (±15.4%), 43.7% (±16.3%; p<0.05), and 45.1% (±11.2%; n.s.), and 50.4 mm (±10.9 mm), 48.1 mm (±8.7 mm; n.s.), and 48.5 mm (±9.8 mm; n.s.), respectively. The PLV may induce a significant early reduction of left ventricular volumes and improvement of biventricular function; however, our results must be judged carefully as the majority of patients in this study underwent additional cardiosurgical procedures, the contributory effect of which on the overall outcome remains unclear. Electronic Publication     

Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by the degeneration of motor neurons in the spinal cord. The disease is caused by mutations of the survival of motor neuron 1 gene (SMN1), resulting in a reduced production of functional SMN protein. A major question unanswered thus far is why reduced amounts of ubiquitously expressed SMN protein specifically cause the degeneration of motor neurons without affecting other somatic cell types. In a first attempt to address this issue we have investigated the Smn interacting protein 1 (Sip1), with an emphasis on its developmental expression and subcellular distribution in spinal motor neurons in relation to Smn. By confocal immunofluorescence studies we provide evidence that a significant amount of Smn does not co-localize with Sip1 in neurites of motor neurons, indicating that Smn may exert motor neuron-specific functions that are not dependent on Sip1. Sip1 is highly expressed in the spinal cord during early development and expression decreases in parallel with Smn during postnatal development. Strikingly, reduced production of Smn as observed in cell lines derived from SMA patients or in a mouse model for SMA coincides with a simultaneous reduction of Sip1. The finding that expression of Sip1 and Smn is tightly co-regulated, together with the unique localization of Smn in neurites, may help in understanding the motor neuron-specific defects observed in SMA patients.