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.     

Ultrasound for breast cancer screening and staging

The question then arises whether and for whom BWBS should be recommended. As yet there are no scientific criteria on which to base an answer, and the examination should not be considered the standard of care until its benefits can be established prospectively. We know that mass screening mammography will detect occult cancers in two to seven of every 1000 women screened, depending on patient age and whether the screens are prevalence or incidence examinations. Should we expect a similar yield for survey US? Kopans commented that Kolb's cancer detection rate was lower than would be expected from a mammographic prevalence screen. This was not a reasonable comparison. These women all had negative findings on screening mammography and would normally be told to have repeat screening mammography 1 year later. Kolb's cancer detection rate using US was comparable to a mammographic incidence screen, so the cancer diagnoses of these fortunate women were advanced by 1 year. To maximize the yield, it is obvious that US has little to offer over mammography in women with fatty breasts because mammography is less likely to be falsely negative. The group of patients in whom incidental cancers would be expected to be found more commonly are those with dense breasts who also are at higher-than-average risk either because of a previous personal history of breast cancer (Fig. 2) or a significant family history. Because it would be impractical to consider BWBS for all women with radiographically dense breasts, it would be useful to know what its potential yield would be in the relatively smaller group of high-risk patients. Annual mammography remains the standard of care for breast cancer screening. However, in our practice in Vancouver, I suggest that high-risk women undergo mammography and US annually, recognizing that this goes beyond the standard of care. Instead of having both examinations simultaneously, I recommend that they alternate the two modalities at 6-month intervals. Theoretically, this could increase lead-time in the detection of occult cancers. The usefulness of this approach remains to be determined. BWBS for staging in women known to have breast cancer has tremendous promise and should be considered for any breast cancer patient with dense breast tissue in whom the finding of additional unsuspected foci would change the planned management. The cost of implementation would be substantial but considerably less than staging MRI. A large-scale study comparing these two modalities is needed, including assessment of the impact of identifying additional mammographically occult lesions on breast cancer mortality.