Impact of a preceding striatal excitotoxic lesion and treatment with ciliary neurotrophic factor on striatal graft survival

The survival of grafted embryonic striatal tissue, dissected from the lateral ganglionic eminence, depends on the status of the host striatum. We found significantly larger volumes of surviving graft tissue and of striatal-like tissue (P-zone) within the graft, when the host striatum had been subjected to an excitotoxic lesion prior to transplantation surgery. Concomitantly the numbers of surviving grafted cells, assessed in both cresyl violet-stained sections and in sections stained with an immunohistochemical marker for striatal neurons, increased as compared to when graft tissue was placed in an intact unlesioned striatum. Finally, we examined the impact of treatment of the donor tissue with ciliary neurotrophic factor (CNTF) on graft survival. CNTF has previously been shown to protect striatal neurons against excitotoxic insults both in vitro and in vivo, but it did not improve striatal graft survival when added to the cell suspension prior to implantation.     

Prevalence, incidence and age at onset of psychiatric disorders in Norway

  Background: Increased demands for psychiatric services and increased rates of sickness absence for depression have raised the question of the occurrence of psychiatric disorders in Norway, and whether there is in fact a rising incidence rate. Methods: Between 1989–1991, 2015 and 617 persons participated in a two-phase population study. Phase I comprised screening by the Hopkins Symptom Check List 25 items (HSCL-25), and phase II a diagnostic interview by the Composite International Diagnostic Interview (CIDI), including report of date (year) of the first occurrence of any symptoms, and any consequent diagnosis: Results: A symptom score of 1.75 or more was found in 19.8% of the women and 9.3% of the men by the HSCL-25. Depression, anxiety or somatoform disorder by CIDI was found in 21.5% of the women and 11.5% of the men. The incidence rate increased significantly from 3.3 to 12.8 per 1000 person years from 1930 to 1991. The incidence rate in the year before the interview was 42.6 per 1000 person years. Age of onset became lower. More women became ill, but the illness seemed to last longer in men. A major problem in comparing results between studies is the different concepts and operationalisations of psychiatric illness, and the varying time periods given for estimates. Conclusion: The findings provide evidence of psychiatric illness being a rising and major health problem, but the role of recall bias must be further investigated. Accepted: 19 August 1999     

Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat

Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are mediated by influences on brain catecholamine concentrations. This study examined whether major changes in brain norepinephrine concentrations can alter outcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i. p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were left untreated (control). One week later, these rats were subjected to either 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusion and MABP=30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were also determined in brain homogenates from non-ischemic DSP-treated and control rats. A 95% depletion of norepinephrine was observed in brain homogenates from non-ischemic DSP-4-treated rats compared with control. During ischemia, microdialysate norepinephrine concentrations increased in control but not in DSP-4-treated rats (P=0.002). For plasma, intra-ischemic epinephrine concentrations increased 8-10-fold and returned to baseline values post-ischemia with no differences between groups. Plasma norepinephrine values remained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentrations on ischemic brain damage. These data indicate that peripheral catecholamine effects on near-complete forebrain ischemic outcome are unlikely to be mediated by effects on central catecholamine concentrations.     

Retrospective versus original information on physical and psychosocial exposure at work

OBJECTIVES: Retrospective exposure assessments are often performed in epidemiologic studies. The presence of an eventual misclassification, both nondifferential and differential, is debated but can rarely be investigated. The aim of this study was to compare self-reported information on the same physical and psychosocial work exposures with 25 years' difference. METHODS: In 1969-1970 a survey of randomly chosen men and women in Stockholm county, concerning, among other things, work exposures, was undertaken. During 1993-1994, 280 subjects participated in a reexamination, regarding psychosocial and physical factors at work and musculoskeletal disorders. The questions were all formulated in the same way as in 1969-1970. RESULTS: When self-reported information on work exposures, collected with a 25-year interval, was compared, acceptable, although not high, agreement was found for 3 out of 4 physical factors and for 4 out of 10 physical environmental factors. Questions measuring psychosocial load had somewhat lower agreement. Current exposure status influenced the memory of past exposures. Study subjects who reported low-back disorders at the reexamination tended to show a better agreement in their assessments of retrospective exposures than those without current symptoms. When relative risks from original and retrospective data were calculated, hardly any influence on the estimates due to that differential misclassification could be found. For persons with and without neck or shoulder symptoms no apparent differences in assessments were found. CONCLUSIONS: Retrospective assessments of exposures at the workplace showed misclassifications to a certain degree. However, the influence of the misclassifications on the risk estimates was limited.     

Decreased glutamate metabolism in cultured astrocytes in the presence of thiopental.

The effect of thiopental on glutamate metabolism was studied by 13C magnetic resonance spectroscopy. Cerebral cortical astrocytes were incubated with 0.5 mM [U-13C]glutamate for 2 hr in the presence of 0.5 or 1 mM thiopental. Labeled glutamate, glutamine, aspartate, and glutathione were observed in cell extracts, and glutamine, aspartate, and lactate in the medium. Not only present in the medium was uniformly labeled glutamate, but also glutamate derived from the tricarboxylic acid (TCA) cycle, and thus glutamate release could be detected. The amounts of [U-13C]glutamate and unlabeled glucose taken up by astrocytes were unchanged in the presence of 0.5 mM thiopental and decreased to about 50% and 80%, respectively when the concentration was increased to 1 mM. The amounts of most metabolites synthesized from [U-13C]glutamate were unchanged in the presence of 0.5 mM thiopental, but decreased [U-13C]glutamine, [U-13C]aspartate, and [U-13C]lactate were observed in the 1 mM group. Surprisingly, the amounts of [1,2,3-13C]glutamate, [2,3-13C]aspartate, and [3,4-13C]aspartate (2nd turn via the TCA cycle) were unchanged. However, this was not the case for [1,2-13C]lactate and [2,3-13C]lactate. Such variations indicate cellular compartmentation, possibly caused by a heterogeneous glutamate concentration within the cells affecting TCA cycle turnover rates differently.     

Takayasu''s aortitis with renovascular hypertension

We report a case of Takayasu's disease with severe renovascular hypertension in a girl from Eritrea. In the "burn-out" phase after the erythrocyte sedimentation rate had normalized, reconstructive vascular surgery was performed as further progression of the disease seemed unlikely. However, probably due to her growth, the graft rotated and a second operation was successfully performed.     

Coronary and systemic hemodynamic effects of clevidipine, an ultra-short-acting calcium antagonist, for treatment of hypertension after coronary artery surgery

BACKGROUND: The aim was to evaluate the use of clevidipine, a new vascular selective, ultra-short-acting calcium antagonist for blood pressure control after coronary artery bypass grafting (CABG). METHODS: The effects of clevidipine on central hemodynamics, myocardial blood flow and metabolism were studied at two different phases after CABG. In phase 1 (n=13), the hypertensive phase, the effects of clevidipine were compared to those of sodium nitroprusside (SNP) when used to control postoperative hypertension. In phase 2 (n=9), the normotensive phase, a clevidipine dose-response relationship was established. RESULTS: At a target mean arterial pressure (MAP) of 75 mmHg, systemic vascular resistance (SVR) and heart rate (HR) were lower, preload, stroke volume (SV) and pulmonary vascular resistance (PVR) were higher, while there were no differences in myocardial lactate metabolism or oxygen extraction with clevidipine compared to SNP. In the normotensive phase, clevidipine induced a dose-dependent decrease in MAP (-19%), SVR (-27%) and PVR (-15%), accompanied by an increase in SV (10%), but no reflex increase in HR or changes in cardiac preload. Clevidipine caused a direct coronary vasodilation, as indicated by a decrease in myocardial oxygen extraction from 54% to 45%. Myocardial lactate metabolism was unaffected by clevidipine. The blood clearance of clevidipine was 0.05 l x min(-1) x kg(-1), the volume of distribution at steady state was 0.08 l x kg(-1) and the initial and terminal half-lives were <1 min and 4 min, respectively. CONCLUSIONS: Clevidipine rapidly reduced MAP and induced a systemic, pulmonary and coronary vasodilation with no effect on venous capacitance vessels or HR. Clevidipine caused no adverse effects on myocardial lactate metabolism. Clevidipine thus appears suitable to control blood pressure after CABG.     

Satisfaction of caregivers of patients with schizophrenia in Finland

OBJECTIVE: The aims of the study were to determine whether the caregivers of discharged patients with schizophrenia were satisfied with their situation in general and with psychiatric services in particular and to examine the factors associated with caregiver satisfaction. METHODS: The data were drawn from a national project designed to study the treatment and life situation of deinstitutionalized schizophrenia patients in Finland. The patients were discharged from psychiatric hospitals in 1986, and both the patients (N=775) and their caregivers (N=545) were interviewed after a three-year follow-up. RESULTS: One-fifth of the caregivers were dissatisfied with the situation in general, and one-third were dissatisfied with the psychiatric services the patient received. Caregivers were more likely to be dissatisfied with the situation if they lived with the patient and if the patient's functional state was poor or the patient's use of services, particularly medication and rehabilitation, was low. Caregivers were likely to be dissatisfied with the psychiatric services if the patient had severe psychotic symptoms and poor "maintenance of grip on life" or if the patient was given less psychiatric care and rehabilitation or used more social services. CONCLUSIONS: The satisfaction of caregivers of persons with mental illness appears to have two dimensions. First, caregivers need to be accepted and treated as active partners in the patients' care and rehabilitation. Second, the burden on the families of persons with mental illness can be alleviated with long-term rehabilitation and care to help patients gain as high a functional state as possible.     

Sickness absence with psychiatric disorders – an increased risk for marginalisation among men?

  Background: Sickness absence with psychiatric disorders is a major public health problem with serious consequences for the individual, the employer and society. The aim was to assess the occurrence of psychiatric sickness absence with special focus on sex differences. Methods: A nationwide sickness insurance register was used. Population at risk was defined as all individuals entitled to sickness benefits in 1994 (N = 1,978,030). Those who were sick-listed for more than 14 consecutive days with a psychiatric diagnosis (n = 28,799) were selected as cases. Results: Of the population under study, 1.46% had at least one psychiatric sickness absence episode. Women had twice the male cumulative incidence of sickness absence for a psychiatric diagnosis. Cumulative incidence was highest among those aged 45–59 years. Men had more sickness absence days. Depression was the most common diagnosis among both women and men. Conclusion: Increased efforts are needed to recognise, treat and rehabilitate individuals with a lowered work capacity due to sickness absence. The increased risk of long sick-leave spells among men needs further attention. Accepted: 22 March 2000     

Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat

BACKGROUND: Although reduction of cerebral metabolic rate is thought to contribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evaluated in rats subjected to different durations of severe forebrain ischemia while anesthetized with volatile anesthetics that have substantially different effects on cerebral metabolic rate. METHODS: Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later. RESULTS: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0. 935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration. CONCLUSIONS: At 6.5 min ischemia, isoflurane provided improved outcome versus halothane. Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome became similar to that in halothane-N2O-anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain ischemia, but also suggest that such benefit is likely to be small.