Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder

OBJECTIVE: Ventriculomegaly has been reported in bipolar disorder, although whether it occurs at illness onset or progresses during the course of the disorder is unknown. In addition, it is unknown whether ventriculomegaly in bipolar disorder reflects acquired volume loss or underdevelopment of periventricular structures. METHOD: Magnetic resonance imaging was used to measure the volumes of the lateral and third ventricles and periventricular structures (caudate, putamen, thalamus, hippocampus). Patients with DSM-IV bipolar disorder, 18 who were having a first episode and 17 with multiple episodes, were compared with 32 healthy subjects. RESULTS: The lateral ventricles were significantly larger in the patients with multiple-episode bipolar disorder than in the first-episode patients or the healthy subjects, even after periventricular and total cerebral volumes were taken into account. Having larger lateral ventricles was associated with a higher number of prior manic episodes. The multiple-episode patients had a smaller total cerebral volume than the healthy subjects but not the first-episode patients. The putamen was significantly larger in the first-episode patients (and nearly so in the multiple-episode patients) than in the healthy subjects, although there was no difference between patient groups. CONCLUSIONS: Lateral ventriculomegaly was greater in bipolar disorder patients who had had repeated manic episodes, but it does not appear to be secondary to small critical periventricular structures. A larger than normal striatum, which has been reported in previous studies, was observed in first-episode patients. These results support the importance of prospectively studying neuroanatomic changes in bipolar disorder.     

Predicting motor decline and disability in Parkinson disease: a systematic review

CONTEXT: The clinical course of Parkinson disease (PD) varies from patient to patient. A number of studies investigating predictors of prognosis in patients with PD have been performed. OBJECTIVE: To summarize evidence on predicting the rate of motor decline and increasing disability in early PD. DATA SOURCES: English-language and French-language literature cited in the MEDLINE database (1966-2002). STUDY SELECTION: Cohort and case-control studies investigating associations between clinical features and subsequent motor impairment or disability were selected. DATA EXTRACTION: Study methods and results were abstracted by a single reviewer. DATA SYNTHESIS: The results of 13 studies were summarized qualitatively. Study methods were highly variable, particularly regarding the choice of outcome measure. Baseline motor impairment and cognitive impairment are probable predictors of more rapid motor decline and disability. A lack of tremor at onset and older age both appear to be predictive of increasing disability, but conflicting results exist for their association with the rate of change of motor impairment. Family history of PD does not appear to be prognostically important. The prognostic value of many other factors studied is uncertain owing to conflicting or unconfirmed results. CONCLUSIONS: Uncertainty remains about the prognostic importance of many baseline clinical features in PD. Greater baseline impairment, early cognitive disturbance, older age, and lack of tremor at onset appear to be adverse prognostic factors.     

Comparison of functional activity performance in normally developing children and children with cerebral palsy

OBJECTIVE: To compare the pattern of self-care performance in normal children and children with cerebral palsy (CP). METHOD: 142 normal children and 33 children with CP were evaluated by 22 items from the self-care scale of the PEDI functional test. Rasch methodology transformed scores into interval measures of difficulty from 0 to 100 (logit). Spearman rank correlation coefficient compared the order of logits in the two groups. RESULTS: Eleven items showed significant differences in the logit values received. Out of these, 7 items showed relative difficulty values greater in the group of children with CP and 4 items showed relative difficulty values greater among normal children. A significant correlation was observed in the order of the 22 items displayed in the two interval scales. CONCLUSION: The results suggest that the development of self-care functional activities may be influenced by the presence of CP. These results may support assessment and intervention strategies for children with neuromotor disorders.     

Schistosomiasis of the spinal cord: analysis of 80 cases

To outline through clinical-laboratorial analysis a profile of schistosomiasis of the spinal cord (SSC) that contributes to the diagnosis and treatment of this disease. 80 patients were studied (59 prospectively), and epidemiological, clinical,laboratorial, treatment and outcome data extracted. In 79 patients the diagnosis was presumptive and obeyed rigorous criteria. There was a predominance of male sex (68.7%), age group from 21 to 40 years (63.7%), Northeasterners (85%), building construction workers (31.2%), previous abdominal effort (57.5%), subacute beginning (61.2%), myeloradiculitis form and lesion in conus and cauda equina (72.5%). Cerebral spinal fluid showed lymphomononuclear pleocytosis and protein increase in 100% of the cases as well as gamma globulin in 76.5%, positiveness of immunofluorescence reaction and/or ELISA for schistosomiasis in 100% of the cases with average titles of 1/16 and 61 u/dl, respectively. Corticosteroids and antischistosomal drugs were given to all patients with a satisfactory outcome in 80% of the cases. We emphasize the importance of a precocious treatment to avoid irreversible deficits such as paraplegia or sexual impotence.     

Study of motor function development at 8 and 12 months of age in preterm and at term children

OBJECTIVE: To compare the development of motor function in children born preterm with those born at term, at 8 and 12 months of age. To investigate the relation of motor function quality at the age of 8 months with motor ability at 12 months. METHOD: Thirty-two children participated in this study: 16 were born preterm (risk group) and 16 were born at term (control group). The spontaneous movements of the children were assessed at 8 months and their mobility skills and independence were assessed at 12 months (corrected ages for the preterm group), using standardized developmental tests (AIMS and PEDI, respectively). Data were analysed using independent t-tests (between-group comparison) and Pearson correlation coefficients (within-group comparison). RESULTS: There was no significant difference in motor function, between those born preterm with those born at term, either at 8 or at 12 months of age. In the control group, there was significant association (r=0.67; p=0.004) between movement at 8 months and mobility skills at 12 months. In the risk group, there was significant relationship between skills and independence in mobility, at 12 months corrected age (r=0.80; p=0.0001). CONCLUSION: Preterm born children, without other disorders and with age correction, might show a similar motor development as those born at term. The path for the acquisition of motor abilities in preterm born children appears to differ among those infants.     

Brain-derived neurotrophic factor (BDNF) mRNA in rats with neonatal ibotenic acid lesions of the ventral hippocampus

Increasing evidence suggests that schizophrenia is a neurodevelopmental disorder with a progressive course characterized by worsening of symptoms and morphological alterations within the brain. This suggests that a neurodegenerative component may exist in schizophrenia. The role of brain-derived neurotrophic factor (BDNF) in neurodevelopment, cell viability and synaptic plasticity led to the investigation of BDNF as a potential candidate molecule in the pathophysiology of schizophrenia. BDNF mRNA was examined by in situ hybridization in the prefrontal cortex and hippocampus of animals with neonatal ibotenic acid lesions of the ventral hippocampus, a putative neurodevelopmental animal model of schizophrenia. Results demonstrate that animals with neonatal ibotenic acid lesions of the ventral hippocampus have reduced basal levels of BDNF mRNA. It is possible that alterations in this trophic factor render animals more susceptible to neurodegenerative insults.     

Hepatitis C viral load does not predict disease outcome: going beyond numbers

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.     

Residual effects of daytime administration of melatonin on performance relevant to flight

There is a general consensus that melatonin possesses time-dependent hypnotic effects, but there is no information yet whether it has residual effects on neurobehavioral performance, especially after daytime administration. In the present study we investigated the possible residual effects of 3 mg melatonin on performance relevant to flight and on subjective feelings of sleepiness, arousal, activation and affect after a daytime nap, as a function of nap length. Fifteen reserve pilots of the Israeli Air Force participated in the study. The experiment consisted of four sessions during which either melatonin or placebo was administered at 16:00 h. In two conditions, subjects were allowed to sleep for 2 h (17:00-19:00 h) whereas in the other two only a 0.5-h nap was allowed. After the naps they started performing a flight simulator task every 2 h. Sleep efficiency significantly increased and sleep latency significantly decreased in both melatonin conditions compared to placebo. Flight performance was only mildly affected in the 0.5-h nap condition. Subjective assessment of sleepiness significantly differed between the two treatment conditions, only in the 0.5-h nap condition. Subjects felt sleepier 2-4 h after melatonin administration. To conclude, our data suggest that administration of melatonin before a brief daytime nap (about 0.5 h) may be associated with mild residual effects on psychomotor performance and may significantly affect subjective feeling of sleepiness for 2-4 h.     

Behavioral effects of MK-801 on reserpine-treated mice

The effects of dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, were studied on dopamine-related behaviors induced by reserpine treatments. This study focuses on behavioral syndromes that may used as models for Parkinson's disease, or tardive dyskinesia, and its response after glutamatergic blockage. Reserpine (1 mg/kg), administered once every other day for 4 days, produced increases in orofacial dyskinesia, tongue protrusion and vacuous chewing in mice, which are signs indicative of tardive dyskinesia. Reserpine also produced tremor and catalepsy, which are signs suggestive of Parkinson's disease. MK-801 (0.1 mg/kg), administered 30 min before the observation test, prevented the vacuous chewing movements, tongue protrusions and catalepsy induced by reserpine. However, MK-801 injection produced a significant increase of tremor in reserpine-treated mice. Reserpine (1 mg/kg), administered 90 min before the test and followed by apomophine injection (0.1 mg/kg) 5 min before the test, did not produce oral dyskinesia in mice. On the other hand, reserpine induced increases in tremor and catalepsy compared to control mice. MK-801 (0.1 mg/kg) administration attenuated the catalepsy and tremor induced by reserpine. Pretreatment with reserpine (1 mg/kg) 24 h before the observation test produced increases in vacuous chewing movements and tongue protrusion, as well as increases in tremor and catalepsy, whereas MK-801 (0.1 mg/kg) injection 90 min before the test reversed the effects of reserpine. These results show that reserpine produces different and abnormal movements, which are related to dose and schedule employed and can be considered as parkinsonian-like and tardive dsykinesia signs. The glutamatergic blockage produced by NMDA can restore these signs, such as vacuous chewing movements, tongue protrusions, catalepsy and tremor according to the employed model.     

Monte Carlo simulation of an ethanol pharmacokinetic model

BACKGROUND: One challenge of using even relatively simple pharmacokinetic models is valuation of model parameters. Unknown model parameter values can be determined by fitting the model to measured data. Goals of the present study were to (1) obtain ethanol pharmacokinetic data from a cohort of dogs, (2) propose a physiologic ethanol pharmacokinetic model, (3) and perform Monte Carlo simulation to determine model parameter values. The rationale for the particular model proposed here was to account for the interrelationship between blood ethanol concentration and gastrointestinal physiology. METHODS: To each of five fasted dogs, 1 g of ethanol/kg body weight was administered as a gavage of 20% w/v ethanol solution. Developed was an ethanol pharmacokinetic model that comprised a gastric emptying mechanism, a body water compartment, ethanol diffusion through the stomach mucosa, gastric alcohol dehydrogenase (GADH) oxidation of ethanol, diffusion through the small intestine epithelia to the villi, a countercurrent exchanger model of the villi, and liver alcohol dehydrogenase oxidation of ethanol. Monte Carlo simulation was used to estimate model parameter values and standard deviations by minimization of the chi function. RESULTS: Fitting the experimental data to the model using Monte Carlo simulation yielded reasonable values for model parameters. The model predicted that the capacity for ethanol absorption in the intestine was 6.79-fold greater than the ethanol absorption capacity in the stomach. The model indicated that 23.8 +/- 8.3% of the ethanol dose was actually absorbed in the stomach, and an insignificant amount of ethanol was metabolized by GADH. CONCLUSIONS: Ethanol metabolism by GADH is insignificant in the present case. The blood ethanol profile was strongly determined by gastric emptying. Differences between experimental data and simulation results largely result from the gastric emptying model selected. Therefore, accuracy of the complete pharmacokinetic model can be improved significantly by improving the gastric emptying model.