A novel frozen brain tissue array technique: immunohistochemical detection of neuronal paraneoplastic autoantibodies

We introduce a modification of the tissue microarray technique in which several frozen brain tissue specimens are collected to a single frozen brain array block. In the present application, we use it for the detection of neuronal paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different brain regions were collected according to a standard neuropathological autopsy protocol. Cryostat sections from each block were cut and conventionally stained. From representative areas, cylinder tissue samples from each specimen were punched and then arrayed into a recipient array block. Using the cryostat sections of this brain array, autoantibodies from seven anti-Hu-positive patient sera (confirmed by immunoblotting) were screened by immunohistochemistry. Neuronal architecture was well preserved and immunohistochemical staining was comparable to that of conventional cryostat sections. Because of the variable staining pattern in different brain areas, two anti-Hu-positive sera could be detected immunohistochemically by the one brain array. With the present array technique, it is possible to characterize the variable staining patterns of neuronal paraneoplastic autoantibodies in different locations of the human brain. The frozen brain array also allows the detection of RNA and DNA targets involved in neurological diseases.     

Socioeconomic inequities in invasive cardiac procedures after first myocardial infarction in Finland in 1995

OBJECTIVE: We examined socioeconomic disparities in coronary procedure rates after first events among hospitalized myocardial infarction (MI) patients. STUDY DESIGN AND SETTING: Information on MI patients in 1995 in Finland was obtained from the Finnish Cardiovascular Disease Register Project. Data on comorbidity, invasive treatments, hospitalizations, mortality, and socioeconomic status were obtained by linking data from the Finnish Hospital Discharge Register, cause of death register, population census, and the health insurance register using personal identity numbers. RESULTS: In 1995, 5172 patients aged 40 to 74 years were hospitalized for first MI. This corresponds to age-standardized event rates of 354/100,000 for men and 152/100,000 for women. Within 2 years, 33% of men and 21% of women underwent an invasive coronary procedure. Men in the lowest income third underwent 25% (95% confidence interval [CI] 12-36) fewer procedures than men in the highest third. Among women, the corresponding difference was 43% (95% CI 24-57). These disparities persisted throughout the 2-year follow-up, and they were not reduced by adjustment for comorbidity or hospital district. CONCLUSION: Socioeconomic disparities were observed in receipt of invasive cardiac procedures. More attention should be paid to equitable distribution of scarce health care resources.     

Maternal midtrimester free beta-HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy-induced hypertension or obstetric cholestasis

OBJECTIVES: The present study aims at finding out whether a connection exists between altered serum free beta-hCG and/or alpha-fetoprotein (AFP) levels and the manifestation of specific pregnancy complications [i.e. gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH) or intrahepatic cholestasis of pregnancy (ICP)]. METHODS: We compared free beta-hCG and AFP multiples of median (MoM) values in singleton pregnancies. The study population consisted of 117 pregnancies with GDM, 107 with PIH and 24 with ICP. The control group consisted of 1148 singleton pregnancies without any pregnancy complications. All were spontaneously conceived. RESULTS: In the group with GDM, both the free beta-hCG (0.72 MoM) and AFP MoM values (0.93) were significantly lower than in controls (beta-hCG 0.97 MoM, p = 0.0063 and AFP 1.01 MoM, p = 0.01). No statistically significant differences in the marker levels were observed between the ICP pregnancies and the control group. CONCLUSIONS: GDM has an impact on maternal midtrimester free beta-hCG and AFP levels and may change the DS screening result.     

Alpha-adrenoceptor-mediated modulation of 5-HT2 receptor agonist induced impulsive responding in a 5-choice serial reaction time task

The activation of 5-HT2A receptors has been shown to enhance the probability of premature responding, regarded as a form of motor impulsive behaviour. At the behavioural level, the interaction of alpha-adrenoceptors and 5-HT2 receptors has been linked to head twitch behaviour, regarded as an experimental model of compulsive behaviour. The aim was to determine whether the probability of premature responding induced by an excess activation of 5-HT2A receptors can be modulated by the blockade of alpha1- or alpha2- adrenoceptors. In the experiments, the 5-choice serial reaction time task was used to measure attention and response control of the rats. The experiments assessed the effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) 0.1-0.2 mg/kg subcutaneously, a 5-HT2A/2C agonist, and prazosin, an alpha1-adrenoceptor antagonist, alone or in combination, on the performance of rats. In an additional experiment to examine the possible role of the alpha2-adrenoceptors, a potent, selective and specific alpha2-adrenoceptor antagonist, atipamezole, was given alone or in combination with DOI. Results showed that DOI increased the probability of premature responses, but it did not affect the choice accuracy. Prazosin (0.1 or 0.3 mg/kg, subcutaneously), given on its own had no effects on probability of responding prematurely, but prazosin (0.3 mg/kg.) was able to attenuate the DOI-induced responding. Atipamezole (0.1 mg/kg, s.c.) did not attenuate the effect of DOI on probability of premature responding. When given at lower doses, DOI (0.03 mg/kg) and atipamezole (0.03 mg/kg) synergistically increased the probability of premature responding, whereas a higher dose of atipamezole (0.3 mg/kg) on its own increased the probability of responding prematurely, but this effect was not additive to that of 0.1 mg/kg DOI. These data indicate that 5-HT2 receptor activation enhances impulsive responding and this effect can be diminished by the blockade of alpha1-adrenoceptors. Atipamezole, an alpha2-antagonist, enhances the probability of premature responding and shares the mechanism of action with the 5-HT2 agonist in this respect. These results provide evidence for an interaction between the serotonergic 5-HT2 receptors and alpha-adrenoceptors in the modulation of response control to the motor impulsivity type of behaviour (premature responding) in addition to that of compulsory behaviour (head shakes) found previously.     

Interrelationships between muscle structure,muscle strength,and running economy

PURPOSE: The present study was designed to investigate possible differences in running economy (RE) among elite middle-distance runners by examining muscle structure and maximal isometric force (MVC). METHODS: Ten young male runners ran at six different running speeds. During the running bouts, respiratory gases, and blood lactate were measured. Muscle biopsies were obtained from the vastus lateralis muscle for analyzing fiber type distribution, muscle fiber area, myosin heavy chain (MHC) composition, activities of a number of metabolic enzymes (citrate synthase, lactate dehydrogenase, phosphofruktokinase, and 3-hydroxyacyl-CoA-dehydrogenase), and titin isoforms. RESULTS: Energy expenditure (EE) increased linearly up to the speed of 6.0 m.s. The relative distribution of the MHC isoforms was MHC I: 67.0%, MHC IIA: 31.5%, and MHC IIX: 1.5%. The present results demonstrated that higher the area of Type II fibers, higher the MVC (r = 0.59, P< 0.05). The amount of MHC II correlated inversely with EE when running close to the competition speed (r = -0.61, P< 0.05). Enzyme activities did not correlate significantly with either RE or EE. Titin analysis revealed that a faster-mobility titin band was observed in all subjects, whereas a lower-mobility titin band was observed only in the most economical runner. CONCLUSION: Differences in RE among homogeneous group of middle-distance runners were observed at various running speeds. This may partly be explained by differences in muscle fiber distribution, MHC composition, and titin isoforms.     

Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition

The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.     

Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study

BACKGROUND: Although case reports and open studies have reported augmentation with buspirone to be beneficial in the treatment of depression refractory to treatment with a selective serotonin reuptake inhibitor (SSRI), a recently published randomized, placebo-controlled, double-blind study failed to show superiority of buspirone over placebo in this respect. METHOD: One hundred two outpatients who fulfilled DSM-IV criteria for a major depressive episode and who had failed to respond to a minimum of 6 weeks of treatment with either fluoxetine or citalopram were included in this double-blind, randomized, placebo-controlled study. After a single-blind placebo wash-in period of 2 weeks while continuing their SSRI, the patients were randomly assigned to adjunctive treatment with either buspirone, 10 to 30 mg b.i.d., or placebo for 6 weeks. Patients were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions scale (CGI), and visual analogue scales. RESULTS: After the first week of double-blind treatment, there was a significantly greater reduction in MADRS score (p = .034) in the buspirone group as compared with placebo. At endpoint, there was no significant difference between treatment groups as a whole, although patients with initially high MADRS scores (> 30) showed a significantly greater reduction in MADRS score (p = .026) in the buspirone group as compared with placebo. CONCLUSION: Patients with severe depressive symptoms may benefit from augmentation with buspirone. It cannot be excluded that augmentation with buspirone may speed up the antidepressive response of patients refractory to treatment with fluoxetine or citalopram.