Comparison of ketamine, physical restraint, halothane and pentobarbital: lack of influence on serotonergic measures in monkeys and rats

The consequences of the use of ketamine for immobilization have been examined on the concentration of whole blood serotonin, concentrations of neurotransmitters and metabolites in CSF and brain, and specific binding of ligands related to neurotransmitters in brain. Vervet monkeys (Cercopithecus aethiops sabaeus) were examined under conditions which compared ketamine with physical restraint and with halothane. It was found that ketamine, used acutely in monkeys for restraint, had no influence on the concentration of serotonin in whole blood or the concentration of 5-hydroxyindoleacetic acid or homovanillic acid in the CSF. In rats, untreated animals were compared with those treated with ketamine alone, or in conjunction with pentobarbital. Treatment with ketamine had no influence on the specific binding of ketanserin, imipramine, prazosin or dihydroalprenolol in brain of rat, nor any influence on the concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, epinephrine, dopamine, or dihydroxyphenylacetic acid in brain. A moderately increased concentration of homovanillic acid was observed in several areas of the brain of the rat after ketamine alone or paired with pentobarbital.     

Present and projected consumption of hospital bed-days as a function of terminal days before death

In 1983 the bed-day consumption per year per 1,000 inhabitants was 1,571 for all subjects in the Copenhagen County, and 774, 1,239, and 4,918 for subjects 0-19 years, 20-64 years, and above 65 years of age, respectively. Extrapolating from these data the hospital bed-day consumption per inhabitant is predicted to increase by 20.6% in Denmark by the year 2025 as compared to 1986. The mean hospital bed-day consumption per subject during the last 150 days prior to death in hospital was 25.0 days for males and 29.7 for females. Making the conservative assumption that only subjects who die in hospital consume hospital bed-days during the last 150 days before death, the bed-day consumption during 1983 of 0-64 years old subjects being in the terminal 150-day phase was 5.87% of the total annual bed-day consumption of this age group. For subjects 65 years of age or older, it was 18.1%.     

Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study

BACKGROUND: Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing. OBJECTIVES: To map brain systems activated by sad facial affect processing in patients with depression and to identify brain functional correlates of antidepressant treatment and symptomatic response. DESIGN: Two groups underwent scanning twice using functional magnetic resonance imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed incidental affect recognition of facial stimuli morphed to express discriminable intensities of sadness. SETTING: Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients. PATIENTS AND OTHER PARTICIPANTS: We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers.Intervention After the baseline assessment, patients received fluoxetine hydrochloride, 20 mg/d, for 8 weeks. MAIN OUTCOME MEASURES: Average activation (capacity) and differential response to variable affective intensity (dynamic range) were estimated in each fMRI time series. We used analysis of variance to identify brain regions that demonstrated a main effect of group (depressed vs healthy subjects) and a group x time interaction (attributable to antidepressant treatment). Change in brain activation associated with reduction of depressive symptoms in the patient group was identified by means of regression analysis. Permutation tests were used for inference. RESULTS: Over time, depressed subjects showed reduced capacity for activation in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively correlated increase of dynamic range in the prefrontal cortex. Symptomatic improvement was associated with reduction of dynamic range in the pregenual cingulate cortex, ventral striatum, and cerebellum. CONCLUSIONS: Antidepressant treatment reduces left limbic, subcortical, and neocortical capacity for activation in depressed subjects and increases the dynamic range of the left prefrontal cortex. Changes in anterior cingulate function associated with symptomatic improvement indicate that fMRI may be a useful surrogate marker of antidepressant treatment response.     

Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder

CONTEXT: Obsessive-compulsive disorder (OCD) is clinically heterogeneous, yet most previous functional neuroimaging studies grouped together patients with mixed symptoms, thus potentially reducing the power and obscuring the findings of such studies. OBJECTIVE: To investigate the neural correlates of washing, checking, and hoarding symptom dimensions in OCD. DESIGN: Symptom provocation paradigm, functional magnetic resonance imaging, block design, and nonparametric brain mapping analyses. SETTING: University hospital. PARTICIPANTS: Sixteen patients with OCD (11 inpatients, 5 outpatients) with mixed symptoms and 17 healthy volunteers of both sexes.Intervention All subjects participated in 4 functional magnetic resonance imaging experiments. They were scanned while viewing alternating blocks of emotional (washing-related, checking-related, hoarding-related, or aversive, symptom-unrelated) and neutral pictures, and imagining scenarios related to the content of each picture type.Main Outcome Measure Blood oxygenation level-dependent response. RESULTS: Both patients and control subjects experienced increased subjective anxiety during symptom provocation (patients significantly more so) and activated neural regions previously linked to OCD. Analyses of covariance, controlling for depression, showed a distinct pattern of activation associated with each symptom dimension. Patients demonstrated significantly greater activation than controls in bilateral ventromedial prefrontal regions and right caudate nucleus (washing); putamen/globus pallidus, thalamus, and dorsal cortical areas (checking); left precentral gyrus and right orbitofrontal cortex (hoarding); and left occipitotemporal regions (aversive, symptom-unrelated). These results were further supported by correlation analyses within patients, which showed highly specific positive associations between subjective anxiety, questionnaire scores, and neural response in each experiment. There were no consistently significant differences between patients with (n = 9) and without (n = 7) comorbid diagnoses. CONCLUSIONS: The findings suggest that different obsessive-compulsive symptom dimensions are mediated by relatively distinct components of frontostriatothalamic circuits implicated in cognitive and emotion processing. Obsessive-compulsive disorder may be best conceptualized as a spectrum of multiple, potentially overlapping syndromes rather than a unitary nosologic entity.     

Molecular mechanisms of individual radiosensitivity studied in normal diploid human fibroblasts

The molecular mechanisms of individual radiosensitivity were studied in normal diploid human fibroblasts. For fibroblasts irradiated with X-rays in G1-phase the individual radiosensitivity was shown to be correlated with the extent of double-strand break (dsb) repair. The number of residual dsbs (including both non- and mis-rejoined dsbs) varied between 2 and 5% of the initial number induced and was low for resistant and high for sensitive strains. In the G1-phase dsbs are considered to be mostly repaired via the non-homologous end-joining pathway (NHEJ). However, so far none of the parameters tested for this pathway was found to be correlated with the number of residual dsbs. The parameters tested were mRNA expression, protein level and localisation and activity of the DNA-PK, which is the central complex of NHEJ. The dsb-repair capacity is also not regulated by the differentiation status, which varies substantially among fibroblast strains, whereas there is some indication that dsb repair might depend on the chromatin structure, with more efficient repair in cells with condensed DNA.Residual dsbs are converted into lethal chromosome aberrations finally leading to the loss of clonogenic activity, when cells pass through mitosis. Beside this so-called mitotic death, X-irradiated human fibroblasts are also inactivated via the TP53-dependent permanent G1-arrest, while apoptosis appears to be not important. On average, mitotic death and G1-arrest are equally effective, but there is a broad variation from one strain to the other, with a negative correlation between these two pathways. Fibroblast strains exhibiting only a moderate G1-arrest showed a high number of lethal aberrations and vice versa. This result points to a common regulator of both G1-arrest and dsb repair, which is presently under investigation.     

Endostatin expression in a pancreatic cell line is modulated by a TNFalpha-dependent elastase

Endostatin, an inhibitor of angiogenesis, is a 20 kDa fragment of the basement membrane protein, collagen XVIII. The formation of endostatin relies upon the action of proteases on collagen XVIII. TNFalpha, produced by activated macrophages, is a multifunctional proinflammatory cytokine with known effects on endothelial function. We postulated that TNFalpha may modulate the activities of proteases and thus regulate endostatin formation in pancreatic cells. Collagen XVIII/endostatin mRNA was expressed in one pancreatic cell line, SUIT-2, but not in BxPc-3. The 20 kDa endostatin was found in the cell-conditioned medium of SUIT-2 cells. Precursor forms only were found in the cells. Exogenous endostatin was degraded by cellular lysates of SUIT-2 cells. Elastase activity was found in cell extracts but not the cell-conditioned media of SUIT-2 cells. Incubation of SUIT-2 cells with TNFalpha increased intracellular elastase activity and also increased secretion of endostatin into the medium. We conclude that endostatin is released by SUIT-2 cells and that increases in intracellular elastase, induced by TNFalpha, are correlated with increased secretion. Endostatin is however susceptible to degradation by intracellular proteases and if tissue injury accompanies inflammation, endostatin may be degraded, allowing angiogenesis to occur.     

Serologic evidence of H1 swine Influenza virus infection in swine farm residents and employees

We evaluated seropositivity to swine and human H1 influenza viruses in 74 swine farm owners, employees, their family members, and veterinarians in rural south-central Wisconsin, compared with 114 urban Milwaukee, Wisconsin, residents. The number of swine farm participants with positive serum hemagglutination-inhibition (HI) antibody titers > or = 40 to swine influenza viruses (17/74) was significantly higher (p<0.001) than the number of seropositive urban control samples (1/114). The geometric mean serum HI antibody titers to swine influenza viruses were also significantly higher (p<0.001) among the farm participants. Swine virus seropositivity was significantly (p<0.05) associated with being a farm owner or a farm family member, living on a farm, or entering the swine barn > or = 4 days/week. Because pigs can play a role in generating genetically novel influenza viruses, swine farmers may represent an important sentinel population to evaluate the emergence of new pandemic influenza viruses.     

Anatomic-histologic survey of the sural nerve: implications for inferior alveolar nerve grafting

An anatomic and histologic study of the sural nerve was made as part of an effort to formulate a rationale governing selection of appropriate segments of the nerve as a donor graft for repair of the inferior alveolar nerve. Ten sural nerves were obtained by dissection at autopsy and their topography assessed. Hematoxylin and eosin stained transverse sections were prepared from samples taken at 32 locations along each nerve. Nerve diameter and shape, fascicle number, and fascicular arrangement were assessed at low power using light microscopy. It was concluded that technical objectives of graft repair can be better attained by selective sural nerve harvest.