Characterization of anti-myosin monoclonal antibodies.

The characterization of monoclonal antibodies (MAbs) with regard to reactivity and specificity is important for the successful application as a molecular probe and/or diagnostic reagent. Furthermore, it is recognized that some monoclonal reagents perform well in some assay systems but not others. In this study, the reactivity profiles of two anti-myosin MAbs (H1 and DH2, raised against human cardiac myosin) were evaluated in enzyme-linked immunosorbent assay (ELISA), slot-blotting, and immunocytochemistry. Both antibodies performed well in slot-blotting against myosin heavy chain preparations from cardiac and skeletal muscle and from non-human sources. In general, MAb H1 demonstrated strong to moderate reactivity in all assay systems, whilst MAb DH2 faired poorly in ELISA. MAb H1 also showed reactivity to synthetic peptides of myosin, one of which possessed a motif (ERRDA, single amino acid code) that was found in other human and nonhuman myosin protein sequences that could explain its cross-reactive profile. Intriguingly, this motif was found on viral and other pathogenic agents associated with myocarditis. Hence, it is speculated that this region could give some credence to the mechanism of molecular mimicry associated with some cardiac diseases. Overall, MAb H1 may serve as a useful probe of myosin structure.

Demystified...recombinant antibodies.

Recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic/therapeutic reagents. In this article, a background to humanized antibodies is given, together with details of the generation of antibody fragments--for example, single chain Fv fragments. Phage antibody fragments are fast becoming popular and can be generated by simple established methods of affinity enrichment from libraries derived from immune cells. Phage display methodology can also be used for the affinity enrichment of existing antibody fragments to provide a reagent with a higher affinity. Here, phage antibodies are demystified to provide a greater understanding of the potential of these reagents and to engage clinicians and biomedical scientists alike to think about potential applications in pathology and clinical settings.

Reactivity and isotype profiling of monoclonal antibodies using multiple antigenic peptides.

The characterisation of monoclonal antibodies (MAbs) is essential for the development of assay systems particularly where antigens have been developed using synthetic peptides. Indeed some peptide-carrier conjugates fail to induce immune responses and may not generate antibodies that bind to native protein. As an alternative to peptide-carrier conjugates, multiple antigenic peptides (MAPs) have been used for immunization strategies, but with little regard to the characteristics of the MAbs produced. In this study, we used 3 MAPs of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) to immunise BALB/c mice. Overall, the polyclonal antibody responses from tail bleeds showed that MAPs evoked B-cell responses. However, on screening 144 hybridomas, 24 MAb supernatants exhibited weak to moderate reactivity in enzyme-linked immunosorbant assay (ELISA) and against cell cytospin preparations (B95.8 and AG876 LCL), respectively. Isotype profiling of hybridoma supernatants also showed that 11 out of 24 were IgM. Further characterization of 6 MAbs in Western blotting showed reactivity to recombinant LMP1 and only one MAb (B28D) showed weak reactivity to the malignant cells (Hodgkin/Reed-Sternberg; HRS cells) of an EBV+ Hodgkin's lymphoma using paraffin-embedded tissue. It is probable that these MAPs failed to augment T-cell help and contributed to the production of low affinity (IgM) antibodies. These observations may be of importance to future immunization strategies, where MAPs are used in the production of monoclonal reagents.

Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction.

The purpose of this report is to demonstrate how to measure the magnitude of expression of the fetal alcohol syndrome (FAS) facial phenotype using the new 4-Digit Diagnostic Code and the previously developed D-score and to demonstrate how these two measures of the FAS facial phenotype correlate with brain function and structure; correlations that fail to be identified by the older gestalt method of facial measurement. The D-score and the facial component of the 4-Digit Diagnostic Code quantitatively measure the magnitude of expression of the FAS facial phenotype using three facial features (palpebral fissure length, philtrum smoothness, and upper lip thinness). These facial measurement systems were developed by the Washington State FAS Diagnostic and Prevention Network (FAS DPN) of clinics and are used to screen and diagnose the facial component of FAS for all patients evaluated in the network of clinics (1500 to date). The 4-Digit Diagnostic Code is a comprehensive diagnostic system developed by the FAS DPN in 1997 to diagnose the full spectrum of outcomes among patients with prenatal alcohol exposure. The four digits reflect the magnitude of expression of the four key diagnostic features of FAS in the following order: (1) growth deficiency; (2) the FAS facial phenotype; (3) brain dysfunction; (4) gestational alcohol exposure. The 4-Digit Diagnostic Code was developed to overcome the subjective, highly variable gestalt method of diagnosis that has been used as the standard to date, worldwide. Prior to the development of the 4-Digit Diagnostic Code, the first 445 patients evaluated in the FAS DPN were diagnosed using the gestalt method. For research purposes, their gestalt diagnoses were transformed into 4-Digit Diagnostic Codes, presenting a unique opportunity to directly compare the two diagnostic methods. When the facial phenotype was measured using the 4-Digit Diagnostic Code or D-score, the magnitude of expression of the FAS facial phenotype was significantly correlated with structural, neurologic, and functional measures of brain damage, and the phenotype of those receiving a 4-Digit Diagnosis of FAS showed little variability. When the gestalt method of diagnosis was used, the magnitude of expression of the FAS facial phenotype did not correlate with structural, neurologic and functional measures of brain damage, and the facial phenotype of those receiving a gestalt diagnosis of FAS was highly variable. The 4-Digit Diagnostic Code and D-score thus provide more precise and accurate measures of the FAS facial phenotype and reveal important correlations with brain structure and function, suggesting that intermediate expressions of the FAS facial phenotype may serve as important risk factors for brain damage caused by prenatal alcohol exposure.

Fetal alcohol syndrome (FAS) primary prevention through FAS diagnosis: I. Identification of high-risk birth mothers through the diagnosis of their children.

A 5-year, fetal alcohol syndrome (FAS) primary prevention study was conducted in Washington State to: (1) assess the feasibility of using a FAS diagnostic and prevention clinic as a centre for identifying and targeting primary prevention intervention to high-risk women (namely women who had given birth to a child with FAS); (2) generate a comprehensive, lifetime profile of these women; (3) identify factors that have enhanced and/or hindered their ability to achieve abstinence. The results of this study are presented in two parts: work on objective 1 is summarized in the present paper; whereas that on objectives 2 and 3 is summarized in the accompanying paper. This project demonstrated that a multidisciplinary FAS Diagnostic and Prevention Network (FAS DPN) clinic could successfully attract and meet the diagnostic and treatment planning needs of patients presenting with prenatal alcohol exposure. One out of every three patients evaluated in the FAS DPN clinics was diagnosed with FAS or static encephalopathy/alcohol exposed. The birth mothers of one out of every three of these children diagnosed with FAS or static encephalopathy/alcohol exposed could be located and directly contacted. Half of the birth mothers directly contacted were still at risk for producing more children damaged by prenatal alcohol exposure. Thus, one out of every 18 children evaluated in the FAS DPN clinics had a birth mother who could be found and was at risk of producing more children damaged by prenatal alcohol exposure. Primary prevention programmes targeted to this high-risk population could lead to measurable, cost-effective reductions in the incidence of FAS. Using this approach, the cost of raising a child with FAS would be roughly 30 times the cost of preventing FAS in the child. The benefit to the children, their mothers, and society would be immeasurable.

Fetal alcohol syndrome (FAS) primary prevention through fas diagnosis: II. A comprehensive profile of 80 birth mothers of children with FAS.

A 5-year, fetal alcohol syndrome (FAS) primary prevention study was conducted in Washington State to: (1) assess the feasibility of using a FAS diagnostic and prevention clinic as a centre for identifying and targeting primary prevention intervention to high-risk women; (2) generate a comprehensive, lifetime profile of these women; (3) identify factors that have enhanced and/or hindered their ability to achieve abstinence. The results of this study are presented in two parts. Objective 1 is summarized in the preceding paper and objectives 2 and 3 are summarized here. Comprehensive interviews were conducted with 80 women, who had given birth to a child diagnosed with FAS, to document their sociodemographics, reproductive and family planning history, social and healthcare utilization patterns, adverse social experiences, social support network, alcohol use and treatment history, mental health, and intelligence quotient (IQ). These high-risk women were diverse in racial, educational and economic backgrounds, were often victims of abuse, and challenged by mental health issues. Despite their rather harsh psychosocial profile, many demonstrated the ability to overcome their alcohol dependence over time. Relative to the women who had not achieved abstinence, the women who had achieved abstinence had significantly higher IQs, higher household incomes, larger more satisfactory social support networks, were more likely to report a religious affiliation, and were more likely to be receiving mental health treatment for their mental health disorders. The rate of unintended pregnancies and alcohol-exposed pregnancies was substantial. Key barriers to achieving effective family planning were maternal alcohol and drug use, lack of access to birth control and lack of support by their partner to use birth control. A FAS diagnostic and prevention clinic can be used to identify women at high risk for producing children damaged by prenatal alcohol exposure. Primary prevention programmes targeted to this population could lead to measurable reductions in the incidence of FAS.

Diagnosing the full spectrum of fetal alcohol-exposed individuals: introducing the 4-digit diagnostic code.

The medical/research records of 1014 patients diagnosed at the Washington State Fetal Alcohol Syndrome (FAS) Diagnostic and Prevention Network (DPN) of clinics were used to develop a new, comprehensive, reproducible method for diagnosing the full spectrum of outcomes among patients with prenatal alcohol exposure. This new diagnostic method, called the 4-Digit Diagnostic Code, was compared to the standard gestalt method of diagnosis on the first 454 patients who had received a gestalt diagnosis of FAS, atypical FAS (AFAS) or possible fetal alcohol effect (PFAE) prior to the development of the 4-Digit Diagnostic Code. The outcomes of the patients were more accurately and comprehensively documented by the 4-Digit Diagnostic Code, because of its use of quantitative, objective measurement scales and specific case definitions. The four digits in the code reflect the magnitude of expression of the four key diagnostic features of FAS in the following order: (1) growth deficiency; (2) the FAS facial phenotype; (3) central nervous system damage/dysfunction; (4) gestational alcohol exposure. The magnitude of expression of each feature is ranked independently on a four-point Likert scale with 1 reflecting complete absence of the FAS feature and 4 reflecting a strong 'classic' presence of the FAS feature. The 4-Digit Diagnostic Code is being used effectively for diagnosis, screening, and surveillance efforts in all Washington State FAS DPN clinics.

Fit of bicycle safety helmets and risk of head injuries in children.

BACKGROUND: Although bicycle helmets are effective in preventing head and brain injury, some helmeted individuals nevertheless sustain head injury. One of the possible reasons may be poor fit of the helmet on the head. This study was undertaken to examine the relationship between helmet fit and risk of injury. METHODS: 1718 individuals who were helmeted riders in a crash were queried on helmet fit and position. A sample of 28 children 2-14 years of age who sustained a head injury while wearing a bicycle helmet and 98 helmeted individuals of the same age treated in the same hospital emergency departments for injuries other than to the head, underwent anthropometric measurements of helmet fit. Measurements were made of the child's head, the helmet, and on a cast made of the child's head. RESULTS: Individuals whose helmets were reported to fit poorly had a 1.96-fold increased risk of head injury compared with those whose helmets fit well. Children with head injuries had helmets which were significantly wider than their heads compared with children without head injuries. Helmet fit was poorer among males and among younger children. CONCLUSIONS: Poor fit of helmets may be associated with an increased risk of head injury in children, especially in males. Helmets may not be designed to provide optimal protection.

Number of axons in the corpus callosum of the Mature macaca nemestrina: increases caused by prenatal exposure to ethanol.

The effects of prenatal exposure to ethanol on the number of callosal axons were examined. Pregnant Macaca nemestrina were treated with ethanol (1.8 g/kg b.wt.) 1 day per week during the first 6 weeks (Et6) or full 24 weeks (Et24) of gestation. Control macaques were intubated with an isocaloric amount of sucrose water (Ct). The mid-sagittal area of the corpus callosum in 4- to 5-year-old offspring was examined in magnetic resonance (MR) images and in fixed brains. The number of callosal axons was determined by using electron microscopy. In both MR images and fixed brains of macaques treated with ethanol, the corpus callosum was 26% larger than in the controls. The rostral portion was particularly affected by ethanol; it was 55% larger in Et6- and Et24-treated macaques. Axonal size and myelin thickness were unaffected by ethanol, but ethanol-treated macaques had more callosal axons (13.7 x 10(7)) than did controls (9.4 x 10(7) axons). The increase in the rostral corpus callosum suggests that parietal and frontal cortices are particularly susceptible to ethanol. The altered callosal connectivity may be a component of the structural abnormalities that underlie executive processing problems associated with fetal alcohol syndrome.

Outcomes of suction curettage and mifepristone abortion in the United States. A prospective comparison study.

A prospective, nonconcurrent cohort analysis of 178 mifepristone/misoprostol and 199 suction curettage abortion subjects, ages > or = 18 years, with intrauterine pregnancies < or = 63 days estimated gestational age, was conducted to compare the outcomes of suction curettage abortion to those of medical abortion. The medical abortion subjects received 600 mg of mifeprisone orally, followed by 400 micrograms of oral misoprostol 2 days later. Surgical abortion subjects underwent electronic vacuum aspiration. All subjects were followed for 2 weeks or until the absence of clinical bleeding. Outcome measures included a successful abortion (complete abortion without a surgical intervention), duration of bleeding, and morbidity. Overall, 18.3% medical and 4.7% surgical patients failed their primary procedure and received an unanticipated suction curettage (RR 3.93, 95% CI 1.87, 8.29). Four mifepristone subjects required curettage for acute bleeding, nine to manage ongoing pregnancy, and five for incomplete abortion. Fourteen mifepristone and eight surgical subjects required curettage for persistent bleeding. The median time delay for therapeutic curettage was significantly longer in the medical abortion group (35 versus 8 days; Mann-Whitney U = 17.0, p = 0.008). Medical subjects experienced significantly longer bleeding (mean difference = 9.6 days, 95% CI 6.8, 12.4). No significant change in hemoglobin occurred in either group. Mifepristone patients reported significantly greater pain (77.1% vs 10.5%; RR 7.4, 95% CI 4.7, 11.5), and nausea or vomiting (68.6% vs 0.6%; RR 117.9, 95% CI 16.7, 834.7). Women receiving mifepristone/misoprostol are more likely to require an unplanned surgical intervention than women who undergo suction curettage. They experience more discomfort with their procedure and in the follow-up interval, bleed for a longer period, and remain at risk for surgical completion curettage for several weeks.

PIP: A prospective, nonconcurrent cohort analysis was conducted to compare the outcomes of suction curettage abortion to those of medical abortion in the US. The study included 178 mifepristone/misoprostol and 199 curettage abortion subjects, ages 18 years or older, with intrauterine pregnancies of 63 or fewer days. Medical abortion subjects received 600 mg of mifepristone orally, followed by 400 mcg of oral misoprostol 2 days later. Surgical abortion subjects underwent electronic vacuum aspiration. Results showed that 18.3% of medical and 4.7% of surgical patients failed their primary procedure and received an unanticipated suction curettage. Medical subjects experienced significantly longer bleeding; however, no significant change in hemoglobin occurred in either group. While, mifepristone patients reported significantly greater pain, nausea or vomiting. Thus, women receiving mifepristone/misoprostol are more likely to require an unplanned surgical intervention than women who undergo curretage. Medical abortion patients have more discomfort, they bleed longer, and remain at risk for surgical completion curettage for several weeks.

Fetal alcohol syndrome: changes in craniofacial form with age, cognition, and timing of ethanol exposure in the macaque.

One component of the fetal alcohol syndrome (FAS) facial phenotype is a frontonasal anomaly characterized by a thin upper lip and a smooth philtrum. The expression of this anomaly can diminish with age and occurs infrequently in prenatal alcohol-exposed individuals. This study sought to explain these observations. Standardized craniofacial cephalograms of 18 nonhuman primates exposed weekly to ethanol or sucrose solution in utero were measured at ages 1, 6, 12, and 24 months to assess skeletal changes in craniofacial form with age, cognition, and timing of ethanol exposure. The data suggest that there may be a critical period for induction of alcohol-induced craniofacial alterations that occurs very early in gestation and is very short in duration (gestational days 19 or 20). The alterations were scarcely detectable at age 1 month, were most prominent at 6 months, and diminished progressively at 12 and 24 months in the macaque. The appearance and disappearance of the thin upper lip and smooth philtrum may be explained by underlying changes in skeletal structure with age. The infrequent occurrence of the FAS frontonasal anomaly may be explained, in part, by its short critical period of induction.

Selective dorsal rhizotomy: efficacy and safety in an investigator-masked randomized clinical trial.

The objective of this single-center investigator-masked randomized clinical trial was to investigate the efficacy and safety of selective dorsal rhizotomy (SDR) in children with spastic diplegia. Forty-three children with spastic diplegia were randomly assigned on an intention-to-treat basis to receive SDR plus physical therapy (PT), or PT alone. Thirty-eight children completed follow-up through 24 months. Twenty-one children received SDR (SDR+PT group) and 17 received PT (PT Only group). SDR was guided with electrophysiological monitoring and performed by one experienced neurosurgeon. All subjects received equivalent PT. Spasticity was quantified with an electromechanical torque measurement device (spasticity measurement system [SMS]). The Gross Motor Function Measure (GMFM) was used to document changes in functional mobility. Primary outcome measures were collected at baseline, 6, 12, and 24 months by evaluators masked to treatment. At 24 months, the SDR+PT group exceeded the PT Only group in mean reduction of spasticity by SMS measurement (-8.2 versus +5.1 newton meters/radian, P=0.02). The SDR+PT group and the PT Only group demonstrated similar improvements in independent mobility on the GMFM (7.0 versus 7.2 total percent score, P=0.94). Outcomes on secondary variables were consistent with primary outcomes. There were no serious adverse events. We conclude that SDR is safe and reduces spasticity in children with spastic diplegia. SDR plus PT and equivalent PT without SDR result in equal improvements in independent mobility at 24 months. SDR may not be an efficacious treatment for children with mild spastic diplegia.

Quantitative comparison of conventional spin echo and fast spin echo during brain myelination.

PURPOSE: Fast SE (FSE) sequences have largely replaced conventional SE (CSE) T2-weighted sequences in the brain and have been generally accepted as qualitatively comparable. The purpose of the present study was to subject these sequences to a quantitative comparative analysis in the brain. METHOD: A quantitative analysis of relative signal intensities of white and gray matter was performed comparing CSE and FSE T2-weighted sequences in brains of 20 children at varying stages of myelination. RESULTS AND CONCLUSION: At all ages in individual patients, white matter had less signal intensity (SI) relative to gray matter on FSE than CSE, though the relative difference in SI was small. This resulted in white matter appearing slightly more myelinated on FSE than CSE. This difference is attributed to differences in magnetization transfer. In myelinated brain (white matter hypointense to gray matter), contrast-to-noise was greater with FSE, while in unmyelinated brain, contrast-to-noise was greater with CSE.

A case definition and photographic screening tool for the facial phenotype of fetal alcohol syndrome.

OBJECTIVES: The purpose of this study was to demonstrate that a quantitative, multivariate case definition of the fetal alcohol syndrome (FAS) facial phenotype could be derived from photographs of individuals with FAS and to demonstrate how this case definition and photographic approach could be used to develop efficient, accurate, and precise screening tools, diagnostic aids, and possibly surveillance tools. STUDY DESIGN: Frontal facial photographs of 42 subjects (from birth to 27 years of age) with FAS were matched to 84 subjects without FAS. The study population was randomly divided in half. Group 1 was used to identify the facial features that best differentiated individuals with and without FAS. Group 2 was used for cross validation. RESULTS: In group 1, stepwise discriminant analysis identified three facial features (reduced palpebral fissure length/inner canthal distance ratio, smooth philtrum, and thin upper lip) as the cluster of features that differentiated individuals with and without FAS in groups 1 and 2 with 100% accuracy. Sensitivity and specificity were unaffected by race, gender, and age. CONCLUSIONS: The phenotypic case definition derived from photographs accurately distinguished between individuals with and without FAS, demonstrating the potential of this approach for developing screening, diagnostic, and surveillance tools. Further evaluation of the validity and generalizability of this method will be needed.

Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation.

The most serious features of fetal alcohol syndrome (FAS) are mental retardation and other behavioral problems resulting from alcohol-induced damage to the developing central nervous system (CNS). The mechanism by which alcohol induces its neuroteratogenic effects is unknown. One hypothesis is that gestational alcohol exposure results in a reduction in neuronal number. This study demonstrates that gestational exposure to ethanol in a non-human primate species induces permanent dose-related deficits in the number of cerebellar Purkinje cells. Ethanol was administered via nasogastric tube once per week to 15 gravid pigtailed macaques (Macaca nemistrina) in one of the following doses: 0.0 (intubated controls), 1.2, 1.8, 2.5, 3.3, and 4.1 g/kg/dose. Offspring were reared with parental surrogates and were sacrificed at 6 months of age; 8-microns-thick, parasagittal sections were cut through the paraffin-embedded cerebellar vermis. Purkinje cells were quantified, the length of the Purkinje cell line was determined stereologically, and Purkinje cell linear frequency was calculated. The number of Purkinje cells and their linear frequencies were significantly reduced in the alcohol-treated subjects, and the deficits were dose-dependent. The groups receiving 2.5 g/kg/dose and above were most severely affected and had an average deficit in Purkinje cell number of 11.8%, relative to controls. Alcohol had no effect on the length of the Purkinje cell line. The findings suggest that alcohol-induced reduction in neuronal number may be an important factor underlying the CNS dysfunction in FAS.

A fetal alcohol syndrome screening tool.

The purpose of this study was to derive a multivariate, quantitative case definition of the fetal alcohol syndrome (FAS) facial phenotype from a dysmorphologist-derived gold standard and use it to develop an effective screening tool for identification of children at risk for FAS. The facial and physical features of a racially mixed group of children (0.2-10.0 years of age), evaluated by a single dysmorphologist in the University of Washington FAS Clinic, were used to determine which feature or set of features best differentiated between children with and without a diagnosis of FAS. The study population was divided into two groups balanced on gender, age at examination, race, diagnosis, and date of examination. Group 1 was used to identify the most differentiating feature(s), and group 2 was used to validate the differentiating capability of the feature(s). Group 1 included 97 children (20 with FAS and 77 without FAS). Group 2 included 97 children (19 with FAS and 78 without FAS). Discriminant analysis identified smooth philtrum, thin upper lip, and short palpebral fissures as the cluster of features that best differentiated children with and without FAS based on the discriminant function [D = 1.7953086 + 0.8116083 (thin upper lip) + 2.6411562 (smooth philtrum)-3.4073780 (% predicted right palpebral fissure length)]. Patients with a D-score > or = 1.5 were classified as at-risk for FAS (screen positive). Using this cut-off value for the D-score, children in group 1 were classified with 100% sensitivity (20 of 20 true positives) and 90.0% specificity (70 of 77 true negatives). The children in group 2 were classified with 100% sensitivity (19 of 19 true positives) and 87.3% specificity (68 of 78 true negatives). Across all 194 patients, sensitivity was 100% [95% confidence interval (97-100)] and specificity was 89% [95% confidence interval (85 to 93)]. Seventy-one percent (n = 12) of the 17 false-positives had a true classification of possible fetal alcohol effects. Sensitivity and specificity were unaffected by race, gender, and age through 10 years. The screening tool is effective at differentiating children with and without FAS as diagnosed by a single dysmorphologist (S.K.C) at the University of Washington FAS Clinic. Assessment of diagnostic interrater agreement between trained dysmorphologists and testing in other clinic populations will be needed to assess the tool's external validity.

Magnetic resonance imaging and spectroscopy in fetal ethanol exposed Macaca nemestrina.

Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) offer noninvasive ways to observe structural and biochemical changes which might serve as valuable diagnostic markers for detecting brain damage from prenatal ethanol teratogenesis. Cranial MR imaging and spectroscopy were performed on 20 nonhuman primates (Macaca nemestrina) with known prenatal ethanol exposures and well-documented cognitive and behavioral levels of performance. The choline: creatine ratio detected by 1H-MRS in the brain increased significantly with increasing duration of in utero ethanol exposure. These signal alterations occurred in the absence of gross structural brain anomalies (detectable by MRI) and were significantly correlated with alcohol-related cognitive and behavioral dysfunction. These observations are consistent with reports of elevated choline: creatine ratios associated with various neurologic insults and disease states. The association observed between brain choline:creatine ratios and in utero ethanol exposure suggest a role for 1H-MRS in elucidating mechanisms of ethanol teratogenicity.

The role of selective dorsal rhizotomy in cerebral palsy: critical evaluation of a prospective clinical series.

This is a prospective observational study of a consecutive series of 34 children with spastic cerebral palsy treated at a single center. 10 had spastic quadriplegia and 24 had spastic diplegia. All were followed for at least one year. After selective dorsal rhizotomy (SDR), all children received one month of physical therapy at the center and were prescribed a program of physical therapy in their community. The children were assessed before and one year after SDR and physical therapy, using the Ashworth Scale, deep tendon reflex response, range of motion and the Gross Motor Function Measure. The results show that there is often a decrease in lower-extremity spasticity and functional improvement after SDR with physical therapy, but that there is considerable variability in outcome. Randomized prospective clinical trials with masked objective outcome measures are needed to determine the efficacy of SDR.

Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects.

Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF.