Relationship between fractional anisotropy of cerebral white matter and metabolite concentrations measured using (1)H magnetic resonance spectroscopy in healthy adults.

Fractional anisotropy (FA) of water diffusion in cerebral white matter (WM), derived from diffusion tensor imaging (DTI), is a sensitive index of microscopic WM integrity. Physiological and metabolic factors that explain intersubject variability in FA values were evaluated in two cohorts of healthy adults of different age spans (N=65, range: 28-50years; and N=25, age=66.6±6.2, range: 57-80years). Single voxel magnetic resonance spectroscopy (MRS) was used to measure N-acetylaspartate (NAA), total choline-containing compounds, and total creatine, bilaterally in an associative WM tract: anterior corona radiata (ACR). FA values were calculated for the underlying, proximal and two distal WM regions. Two-stage regression analysis was used to calculate the proportion of variability in FA values explained by spectroscopy measurements, at the first stage, and subject's age, at the second stage. WM NAA concentration explained 23% and 66% of intersubject variability (p<0.001) in the FA of the underlying WM in the younger and older cohorts, respectively. WM NAA concentration also explained a significant proportion of variability in FA of the genu of corpus callosum (CC), a proximal WM tract where some of the fibers contained within the spectroscopic voxel decussate. NAA concentrations also explained a significant proportion of variability in the FA values in the splenium of CC, a distal WM tract that also carries associative fibers, in both cohorts. These results suggest that MRS measurements explained a significant proportion of variability in FA values in both proximal and distal WM tracts that carry similar fiber-types.

Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings.

BACKGROUND: Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. METHODS: Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race. RESULTS: Both non-additive genetic and common environmental contributions were significant in our model (P-values<0.0001). No significant additive genetic contribution was found. In all, 63.6% (95% confidence interval (CI) 51.8-75.3%) of the total variance of BMI was explained by a non-additive genetic component, 25.7% (95% CI 13.8-37.5%) by a common environmental component and the remaining 10.7% by an unshared component. CONCLUSION: Our results suggest that genetic components play an essential role in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.

The swimbladder nematode Anguillicola crassus in American eels (Anguilla rostrata) from middle and upper regions of Chesapeake Bay.

The patterns of infection of American eels Anguilla rostrata, with the introduced swimbladder nematode Anguillicola crassus, in tributaries of middle and upper Chesapeake Bay are described. A total of 423 subadult eels was collected from 8 Bay tributaries from spring 1998 to fall 1999. Also, 30 elvers were collected from Ocean City, Maryland, in spring 1998. The numbers of juvenile and adult specimens of A. crassus in the swimbladder wall and lumen were counted. No elvers were infected. In subadult eels, prevalence of adult and juvenile stages combined ranged from 13% to 82%; mean intensity ranged from 2.6 to 9.0 worms per eel. Infection levels were highest for Susquehanna River eels (northernmost river) and lowest in the southernmost sites: St. Jerome's Creek and the Pocomoke River. Although eels from these 2 localities were larger, the low infection rates there are most likely due to reduced transmission in higher salinity water and not to eel size. Eels with both adult and juvenile stages of A. crassus were more common than expected by chance. This might be explained by inhibition of juveniles migrating into the swimbladder lumen when adults are already present there.

Cerebrospinal fluid and nerve conduction abnormalities in HIV positive individuals.

We studied whether there was an association between nerve conduction studies (NCS), CSF, and CD4-T lymphocyte parameters in a large cohort of HIV positive individuals. Two hundred and twenty-eight HIV positive individuals underwent motor and sensory nerve conduction studies, CSF evaluation, peripheral CD4-T lymphocyte count, and neurologic evaluation to determine the presence or absence of peripheral neuropathy. We compared NCS of HIV positive subjects with and without abnormal CSF parameters in the entire cohort. We also compared CSF parameters in a subset of CD4-matched patients with and without neuropathy. CSF abnormalities (in excess of laboratory norms) occurred frequently in the entire study group. There was no statistically significant relationship between NCS and CSF parameters. In addition, there was no significant difference in the CSF findings in the group of patients with clinical neuropathy compared to the group without neuropathy. However, there was an association (p < 0.05) between lower CD4 counts and NCS parameters. In general, abnormal CSF findings are not associated with deteriorating peripheral nerve function in HIV infected patients and are just as likely to be found in an HIV positive patient whether or not a peripheral neuropathy is present.

Congruence between mothers' and fathers' differential treatment of siblings: links with family relations and children's well-being.

We studied patterns of mothers' and fathers' differential treatment of firstborn (average age 10.5 years) and secondborn (average age 8 years) school-age siblings, and we examined the links between parents' differential treatment and children's well-being and dyadic family relationships. Mothers, fathers, and both siblings in 110 families were interviewed in their homes. For each dimension of parental behavior that we assessed (i.e., differential affection and discipline) we created groups of families that reflected mothers' and fathers' levels of differential treatment (e.g., discipline the firstborn more, equal treatment, discipline the secondborn more). Although we detected substantial correspondence between the 2 parents' differential treatment, we found a sizable group of families in which parents' reports were incongruent (i.e., 1 parent reported equal and the other differential treatment). Parental patterns were linked to differences between the siblings' well-being and both sibling and parent-child relationships, with younger siblings exhibiting greater vulnerability to differential treatment. Incongruence in differential warmth was associated with marital distress.

Peripheral nervous system involvement in a large cohort of human immunodeficiency virus-infected individuals.

OBJECTIVE: In individuals who were infected with the human immunodeficiency virus (HIV) we determined the prevalence of peripheral neuropathies (PNs) and explored the relationship between immunologic competence and nerve function. DESIGN: Cohort survey. SETTING: US Air Force medical center. PATIENTS: Population based. Seven hundred ninety-eight of 817 HIV-positive personnel identified by US Air Force HIV screening program from 1985 to 1989. Average age of cohort was 29.2 years. The majority were male with early-stage HIV disease. MAIN OUTCOME MEASURES: Neurologists examined all subjects for symptoms and signs of PN. We grouped patients by CD4 T-lymphocyte count. We further studied 300 HIV-infected volunteers without clinical evidene of PN by nervex

Cerebrospinal fluid neopterin levels in 159 neurologically asymptomatic persons infected with the human immunodeficiency virus (HIV-1): relationship to immune status.

Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurologic dysfunction associated with HIV-1 disease. Since neopterin is produced by monocytes-macrophages, we asked whether cerebrospinal fluid (CSF) neopterin levels increase before the onset of HIV-1 neurologic disease and whether they correlate with other CSF and peripheral blood immunologic parameters. In this study, CSF neopterin levels from 159 neurologically asymptomatic HIV-positive persons were found to increase as the blood CD4+ T-cell count decreased and as CSF IgG, IgG synthesis, IgG index, and beta 2-microglobulin increased. Neopterin levels in the CSF exceeded those in the serum in 32% of patients, while 25% had CSF levels > 13.5 nmol/liter. CSF neopterin levels vary with immune status, may reflect intrathecal production, and can be elevated in asymptomatic HIV-positive patients with normal neurologic examinations. Long-term follow-up of this patient population should be able to define the clinical correlation between CSF neopterin levels during the asymptomatic phase of HIV-1 disease and the risk of subsequent neurologic disease.

Autosomal recessive Duchenne-like muscular dystrophy: molecular and histochemical results.

An autosomal recessive disorder which mimics Duchenne muscular dystrophy has long been suspected as a cause of muscular dystrophy in karyotypically normal girls and in both boys and girls with consanguineous parents. Analysis of dystrophin now allows confirmation of the existence of this disorder. We report the results of this analysis in a brother and sister who have the typical clinical features of Duchenne muscular dystrophy, but no demonstrable abnormality in dystrophin or its gene.

Comparison of spinal fluid beta 2-microglobulin levels with CD4+ T cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the human immunodeficiency virus type 1.

Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.

Acute vincristine neurotoxicity in the presence of hereditary motor and sensory neuropathy type I.

Acute vincristine neurotoxicity leading to a severe motor and sensory neuropathy has been noted in patients with hereditary motor and sensory neuropathy type I (HMSN-I). The case of a 2-year-old boy with acute lymphocytic leukemia and HMSN-I is reported, and additional cases from the literature are reviewed. Severe vincristine neurotoxicity in patients with HMSN-I may be secondary to impairment of both slow and- fast axonal transport. Vincristine should be used with caution in patients with a family history of polyneuropathy.

Polyneuropathy following vincristine therapy in two patients with Charcot-Marie-Tooth syndrome.

The neurotoxicity of vincristine sulfate, a commonly used antineoplastic agent, has been well described. A literature review failed to reveal any absolute contraindications to the initial use of vincristine. We describe two patients with nodular sclerosing Hodgkin's disease in whom a rapidly progressive, but reversible, severe polyneuropathy developed when they were given a total of 4 mg of vincristine sulfate. Each was later shown to have the demyelinating form of Charcot-Marie-Tooth syndrome. This association suggests that the use of vincristine is contraindicated in patients with the demyelinating form of Charcot-Marie-Tooth syndrome.

Hereditary continuous muscle fiber activity.

We describe a family with classic features of continuous muscle fiber activity (Isaacs-Mertens syndrome) appearing in an autosomal dominant pattern. Both a mother and her son had muscle stiffness and rigidity in early childhood. Because the mother's condition was not immediately apparent, we recommend a thorough examination of family members.

Surgical treatment of anomalous left coronary artery from pulmonary artery: follow-up in teenagers and adults.

To determine which method of surgical therapy might be optimal for patients with anomalous left coronary artery from the pulmonary artery (ALCAPA), a follow-up study was performed. Twenty-nine teenagers and adults who had ALCAPA diagnosed during life at age 13 years or older were identified mainly by literature search. Recent follow-up was obtained on all. Thirteen treated by ALCAPA ligation alone (Group A), were followed a mean of 9.2 years postoperately (range 1 to 15 years). There was no operative mortality. Three Group A patients died suddenly; a mean of five years (range 2 to 7 years) postoperatively. Sixteen patients treated by simultaneous ALCAPA ligation and saphenous vein graft (SVG) from aorta to left coronary artery (Group B) were followed a mean of five years (range 0 to 11 years) with one intraoperative death and no late mortality. Using the generalized Wilcoxon test for single censored samples, there was no significant difference in survival at any postoperative year when comparing both Groups A and B. The late appearance of sudden death in three Group A patients and no late deaths in Group B patients suggests that ligation and SVG, or its equivalent, may be the therapy of choice.