According to the Autism Society of America, autism is now considered to be an epidemic. The increase in the rate of autism revealed by epidemiological studies and government reports implicates the importance of external or environmental factors that may be changing. This article discusses the evidence for the case that some children with autism may become autistic from neuronal cell death or brain damage sometime after birth as result of insult; and addresses the hypotheses that toxicity and oxidative stress may be a cause of neuronal insult in autism. The article first describes the Purkinje cell loss found in autism, Purkinje cell physiology and vulnerability, and the evidence for postnatal cell loss. Second, the article describes the increased brain volume in autism and how it may be related to the Purkinje cell loss. Third, the evidence for toxicity and oxidative stress is covered and the possible involvement of glutathione is discussed. Finally, the article discusses what may be happening over the course of development and the multiple factors that may interplay and make these children more vulnerable to toxicity, oxidative stress, and neuronal insult.
The Stroke Prevention Trial in Sickle Cell Anemia (STOP) was a randomized multicenter controlled trial comparing prophylactic blood transfusion with standard care in sickle cell anemia (SCA) children aged 2 to 16 years selected for high stroke risk by transcranial Doppler (TCD). More than 2000 children were screened with TCD to identify the 130 high-risk children who entered the randomized trial. A total of 5613 TCD studies from 2324 children were evaluated. We also collected information on stroke. We describe the changes in TCD with repeated testing and report the outcome without transfusion in the STOP screened cohort. Risk of stroke was higher with abnormal TCD than with normal or conditional TCD (P < .001) or inadequate TCD (P ؍ .002), and risk with conditional TCD was higher than with normal TCD (P < .001). Repeated TCD in 1215 children showed that the condition of 9.4% of children became abnormal during observation. Younger patients and those with higher initial flow velocities were most likely to convert to abnormal TCDs. Screening in STOP confirmed the predictive value of TCD for stroke. Substantial differences in the probability of conversion to abnormal TCD were observed, with younger children and those with higher velocity more likely to have an abnormal TCD with rescreening.
Objective-To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause.Design-Case-control study and segregation analysis.Setting-Two teaching hospitals in Leeds. Subjects-Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more childen recruited through vasectomy clinics or a maternity department.Main outcome measures-The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers.Results-Seventeen of the 148 (11.5a/.) brothers of probands but none ofthe 169 brothers ofcontrols had sought medical advice for childlessness (P< 0.0005).Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60"/! of subfertility in men. Seventeen ofthe 346 (4.9%/6) uncles ofprobands and 10 of420 (2.8"/!) uncles ofcontrols were reported to be involuntarily childless (P=0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families.Conclusion-Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.Insttute ofEpidemiology
The performance of Doppler ultrasound was highly variable. This suggests that Doppler performance is likely overstated in the literature, but specific devices may perform satisfactorily to detect individuals with hemodynamically significant stenosis. Because performance differs substantially among devices, local investigators are strongly urged to maintain local standardization series. With such standardization, ultrasound performance is sufficient for admission to clinical trials and as the is sufficient for admission to clinical trials and as the basis for carotid surgery. However, without quality control many ultrasound machines are not adequate to accurately predict the degree of carotid stenosis and should not be the only test to decide whether surgery is warranted.
The Stroke Prevention in Sickle Cell Disease (STOP) trial used transcranial Doppler (TCD) to screen children with sickle cell disease with no history of stroke. Children (who consented) who had time-averaged mean of the maximum (TAMM) velocities in the middle cerebral artery and/or distal internal carotid artery were randomized to transfusion or standard. Over a slightly more than 20-month average follow-up, there were 11 strokes in the standard care arm and 1 stroke in the transfusion arm. This study has caused a great deal of interest in using TCD to screen children with sickle cell disease. For the STOP TCD data to be applied appropriately, it is necessary for users of TCD to understand how the STOP TCD examinations were performed, how the TCD velocities were measured, and which velocities were used. This article will review the STOP TCD scanning protocol and the reading protocol and review the TAMM velocity and how it differs from other velocity measurements.
Velocities obtained by TCDI may be lower than TCD measurements, and these differences should be taken into consideration when performing screening for stroke risk and selection for prophylactic transfusion based on the STOP protocol.
Ultrasound (US) has become widely used in clinical medicine for the diagnosis of a variety of disease processes. The unique ability of US to provide accurate information through an efficacious, painless, portable, and nonionizing method has expanded its role and application in diverse medical settings. Given the current economic environment and the related interest in creating the greatest value for health care expenditures, US has been evaluated to compare its clinical accuracy/efficacy and cost-effectiveness versus other imaging modalities. The following literature review reports the results of research studies aimed at comparing the accuracy/efficacy and cost of US versus alternative imaging modalities, including magnetic resonance imaging, computed tomography, contrast angiography, and single-photon emission computed tomography.
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