Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort

Structural brain differences have been reported in many studies with schizophrenia, but few have involved a general population birth cohort. We investigated differences in volume, shape and laterality of hippocampus and amygdala in patients with schizophrenia, all psychoses and comparison subjects within a large general birth cohort sample, and explored effects of family history of psychosis, perinatal risk and age-at-onset of illness. All subjects with psychosis from the Northern Finland 1966 birth cohort were invited to a survey including MRI scan of the brain, conducted in 1999-2001. Comparison subjects not known to have psychosis were randomly selected from the same cohort. Volumes of hippocampus and amygdala were measured in 56 subjects with DSM-III-R schizophrenia, 26 patients with other psychoses and 104 comparison subjects. Small hippocampal volume reductions in schizophrenia (2%) and all psychoses (3%) were not significant when adjusted for total brain volume. The shape of hippocampus in schizophrenia did not differ significantly from comparison subjects. Right hippocampus and amygdala were significantly larger than the left in all groups. Mean amygdala volume in schizophrenia or all psychoses did not differ from comparison subjects. Patients with family history of psychosis had larger hippocampus than patients without. Neither perinatal risk nor age-at-onset of illness had any effect on hippocampal or amygdala volumes. Small hippocampal volume reduction in schizophrenia and all psychoses was not disproportionate to reduced whole brain volume in this population-based sample. Perinatal events that have been suggested as of etiological importance in structural pathology of psychosis had no effect.     

Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVE: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication. METHOD: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003. RESULTS: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms. CONCLUSION: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.     

Orthostatic hypotension predicts vascular death in older diabetic patients

Diastolic orthostatic hypotension measured 1 min after standing up (OH-D1), and systolic OH measured 3 min after standing up (OH-S3) increase vascular mortality risk among older adults. We hypothesized that the risk is especially high among diabetic patients. The orthostatic test was carried out in a standard way by a trained nurse in 868 subjects (79% of a representative population sample) and 98 of them were diabetic treated with oral hypoglycemic agents or insulin. OH-D1 occurred in 9 (9%) diabetic patients and in 43 (6%) other subjects of the cohort (Chi-Square; P = 0.157), and OH-S3, correspondingly, in 28 (29%) and 140 (18%) (P = 0.014). Absent patellar vibration sense, absent patellar reflex and resting heart rate was higher, and cardioacceleration early after active standing up was lower in the diabetic patients. According to Cox Proportional Hazards modelling, after adjustment for other baseline variables (age, sex, history of myocardial infarction, current smoking, chest pain and systolic blood pressure), the hazard ratio of vascular death as regards OH-D1 was 3.69 (95% confidence intervals 1.54-8.84), and that as regards OH-S3 was 2.70 (1.16-6.29). Among the persons free of diabetes treated with oral hypoglycaemic agents or insulin (N = 770), survival for vascular death did not differ in regard to presence and absence of OH-D1 and OH-S3. Our results suggest that diabetes patients with orthostatic hypotension carry a high risk of vascular death. Diabetic neuropathy is a plausible explanation to our findings.     

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.     

Time-sharing strategies in driving after various cerebral lesions

Primary objective: To analyse time-sharing strategies in patients with cerebral lesions when they performed everyday in-car tasks in real-life highway driving. Research design: A case-control study. Methods and procedures: Thirteen male patients with brain damage and 11 healthy controls participated. The frequency and duration of glances at the in-car tasks, total time of eyes-off the road during tasks, speed and lateral displacement of the car were recorded. Main outcomes and results: Long glances away from the road and consequent large lateral displacements were characteristic for patients with anterior damage, while the patients with more posterior lesions used frequent short glances at the in-car task. Conclusion: Two different time-sharing strategies that appeared to be related to different aetiology were found in the patients, indicating different control of the driving task. It is proposed that standardized on-road dual tasks should be used for detecting problems in allocation of attention during driving.     

Assessment of muscle strength and motor fatigue with a knee dynamometer in subjects with multiple sclerosis: a new fatigue index

OBJECTIVE: To measure muscle strength and motor fatigue with a knee dynamometer and to assess the intra-rater reliability of measurements for maximal isometric extensor and flexor torques and the reliability of a new fatigue index (FI) in patients with mild to moderate multiple sclerosis (MS). DESIGN: Repeated assessments with one-week intervals. SETTING: The Masku Neurological Rehabilitation Centre, Masku, and the Social Insurance Institution, Research Department, Turku, Finland. SUBJECTS: Twenty-eight MS patients. OUTCOME MEASURES: Maximal isometric torque during 5 s and fatigue of knee flexors and extensors during isometric contractions of 30 s were assessed. A new FI was established and compared with the two previously used indices (FI1 and FI2). All three indices are based on the calculated area under the force versus time curve (AUFC), with FI1 using the 30-s recording time in its entirety and F2 omitting the initial 5 s in the calculation. In the new fatigue index (FI3), the time point of maximum (TPM) torque achieved by the subject is used as the starting point in the calculation. The patient's subjective fatigue was measured by Fatigue Severity Scale (FSS). RESULTS: The intraclass correlation coefficient (ICC) was 0.97 in maximal isometric torque measurements. FI3 showed good intra-rater reliability (ICC =0.68-0.86). None of the fatigue indices correlated with FSS. CONCLUSIONS: Maximal isometric torque and motor fatigue of knee flexor and extensor muscles can be reliably measured using a knee dynamometer in MS patients. The new FI proved to be a reliable model for MS patients.     

Evaluation of exposure to man-made vitreous fibers by nasal lavage

The objectives of this study were to develop a biomonitoring method for the assessment of exposure to man-made vitreous fibers (MMVF), to examine the level of exposure to MMVF in the prefabricated house industry, and to study nasal inflammatory reactions and respiratory symptoms associated with MMVF among workers. Nasal lavage was performed on workers from two factories, and concentrations of MMVF were measured by electron microscopy. Cytokines (IL-6, IL-8, TNF-alpha, and IFN-gamma) were also assayed and inflammatory cells (lymphocytes, eosinophils, neutrophils, and macrophages) were counted microscopically. Concentrations of airborne fibers (longer than 5 microm) were measured for comparison. Moreover, the exposure to MMVF and the related symptoms were studied with a structured questionnaire. In nasal lavage samples, the mean concentration of MMVF (length >1.5 microm) was 3260 f/ mL in Factory 1, 1680 f/mL in Factory 2, and below 500 f/mL in the control group. About 52% of the retained fibers were longer than 100 microm. The group-specific mean concentrations of MMVF in nasal lavage samples correlated with production rates and airborne fiber levels in both plants. The airborne concentrations of MMVF both in the breathing zone and fixed-point samples were low (below 0.1 f/cm(3)). No significant differences in the biological response (inflammatory cells, cytokines) were found between the groups exposed and the control group. The workers complained of some irritation of the skin, eyes, and upper respiratory tract, which could be reduced by appropriate protective equipment. It is concluded that nasal lavage can be used as a biomonitoring method in the assessment of MMVF exposure.