Hypomelanosis of Ito with Sturge-Weber syndrome-like leptomeningeal angiomatosis

The term hypomelanosis of Ito (HI) is applied to individuals with skin hypopigmentation following the lines of Blaschko (type 1a of patterns indicative of somatic mosaicism as defined by Happle). Even though originally described as a purely cutaneous disease, subsequent reports of HI have included a 30-94% association with multiple extracutaneous manifestations. The frequency of extracutaneous associations has led many authors to consider HI to be neurocutaneous disorder. We report a male infant with cutaneous hypomelanosis along the lines of Blaschko distributed on the left half of the body who developed status epilepticus. Neuroimaging studies disclosed an angiomatous enlargement of the right choroid plexus and a gyral pattern of cortical and subcortical calcification in the right occipital region. Thus a diagnosis could be made of HI and associated Sturge-Weber syndrome-like leptomeningeal angiomatosis. This previously unreported association lends further support to the consideration of hypomelanosis of Ito as a marker of somatic mosaicism with frequently associated neurologic abnormalities. A relationship between HI and Sturge-Weber syndrome, two neuroectodermal disorders with a genetic mosaicism basis, might be possible due to nonallelic twin-spotting which in the embryologic period would define an abnormal development of neural, vascular, and cutaneous structures.     

Guanine and adenine nucleotidase activities in rat cerebrospinal fluid

Adenine and guanine nucleotides have been shown to exert multiple roles in central and peripheral nervous systems, and the sequential breakdown of these nucleotides by enzymatic systems is an important step in the modulation of their extracellular effects. The aim of this study was to investigate whether nucleotide hydrolysis also occurs in the cerebrospinal fluid (CSF) of rats. CSF was able to hydrolyze all guanine and adenine nucleotides investigated (2.0 mM): GDPADP=ATP=GTPAMP=GMP. More detailed studies with the diphosphate nucleotides showed that the hydrolysis of ADP and GDP was linear with incubation time and protein concentration. The apparent K_M (Henry–Michaelis–Menten constant) and V (maximal velocity) values for ADP and GDP were 164.3±54.7 μM and 12.2±3.8 nmol P_i/min per mg protein, and 841.0±90.2 μM and 22.8±8.0 nmol P_i/min per mg protein. The sum of ADP, GDP and UDP hydrolysis (2.0 mM) upon individual incubations with CSF was similar to the hydrolysis observed when all three nucleotides were incubated together. This pattern of hydrolysis strongly suggests the involvement of more than one enzyme activity. The higher maximum activity for GDP and UDP compared to ADP is compatible with presence of a soluble NTDPase5.     

Adams-Oliver Syndrome with Unusual Central Nervous System Alterations

Abstract: The association of aplasia cutis congenita of the scalp with distal malformations of the limbs is known as Adams-Oliver syndrome. Other reported associations include palatine or auricular malformations, cardiovascular alterations, and spina bifida. Multiple hereditary patterns have been described for this condition, and sporadic cases have also been reported. We report an infant with Adams-Oliver syndrome associated with intracranial calcifications in whom no evidence of intrauterine infection could be demonstrated.     

High correlation of human immunodeficiency virus type-1 viral load measured in dried-blood spot samples and in plasma under different storage conditions

BACKGROUND: To measure HIV-1 RNA concentration requires venous extraction of blood, use of RNAase-free materials, and transport in a cold chain, which makes difficult the management of samples in developing countries. We evaluated the utility of the determination of HIV-1 RNA concentration in blood samples dried on filter paper (DBS) and subjected to different conditions, as contrasted with determination in plasma. METHODS: HIV-1 RNA concentration was determined in HIV-infected patients in DBS and in plasma samples. Samples were subjected to the following: DBS were stored at 4, 22, and 37 degrees C for 1, 3, and 7 days; samples from patients from four regions of Mexico were mailed to a reference laboratory; DBS were sent under environmental conditions; and plasma samples were sent frozen. HIV-1 RNA concentrations were determined by NucliSens in DBS and by Amplicor test in plasma. RESULTS: HIV-1 RNA concentration determined in DBS subjected to different temperatures and times had a significant correlation (r=0.99) with those obtained in plasma. When compared with values in plasma, Kappa agreement coefficients of values in DBS stored for 7 days at 4, 22, and 37 degrees C were 0.98, 0.83, and 0.94, respectively. Quantification of HIV-1 RNA in 108 DBS mailed from remote areas with different climates demonstrated significant correlation with those obtained in plasma (r=0.95; p <0.001). CONCLUSIONS: DBS is a simple and reliable method to measure HIV-1 RNA concentration, especially when samples are mailed from remote areas to a reference center. This collection method is an economic and suitable alternative for use in developing countries.     

Competing risks of death and Hardy-Weinberg equilibrium in case-control studies of gene-disease association

OBJECTIVE: To study the impact of competing risks on Hardy-Weinberg equilibrium and their consequences in case-control studies of gene-late onset disease association. METHODS: Based on a population born in Hardy-Weinberg equilibrium for a particular gene, the genetic composition when the gene is associated with a lethal early-onset disease and its consequences on a late-onset disease can be deduced. Odds ratios estimates are unbiased in case-control studies when controls are sampled by density, even if the controls are in Hardy-Weinberg disequilibrium. RESULTS: An example in which a mutant gene is associated with early mortality is presented, producing a departure from Hardy-Weinberg equilibrium; as a result, controls in later ages are in disequilibrium, producing an odds ratio equal to 1.61. CONCLUSION: Although the main causes of Hardy-Weinberg disequilibrium in controls are selection bias or genotyping error, a competing risk of death associated with the mutant gene would also result in Hardy-Weinberg disequilibrium among controls.     

Efficacy of telephone and mail intervention in patient compliance with antihypertensive drugs in hypertension. ETECUM-HTA study

OBJECTIVE: To study the efficacy of telephone and mail intervention in therapeutic compliance among patients with mild to moderate hypertension. DESIGN: A prospective controlled multicenter clinical trial. SETTING: Eighty-five primary care centers in Spain, with a duration of 6 months. PATIENTS: A total of 636 patients with newly diagnosed or uncontrolled hypertension were included. Interventions. The patients were randomized and distributed between the following groups: (i) control (CG) - under routine clinical management; (ii) mail intervention (MIG) - received a mailed message reinforcing compliance and reminding of the visits (15 days, 2 and 4 months); (iii) telephone intervention (TIG) - received a telephone call at 15 days, then at 7 and 15 weeks. MAIN OUTCOME MEASURE: Five visits were scheduled, with the measurement of blood pressure and counting of tablets. Compliers were defined as subjects showing 80-110% drug consumption. Calculations were made of mean percentage compliance (MPC) and compliers, mean blood pressure and percentage controlled subjects. RESULTS: Five hundred and thirty-eight patients completed the study (261 males); 85.5% were compliers (CI = 82.5-88.5; n = 460). The MPC was 95.1+/-19.6% (CI = 93.28-96.92). The CG consisted of 182 individuals, MIG = 172 and TIG = 184. Compliers represented 69.2% of the CG (CI 62.5-75.9%), 91.3% (CI = 87.1-95.5) of the MIG (p = 0.0001) and 96.2% of the TIG (CI 93.5-98.9%); the final MPC was 89.6%+/-15 in CG, 96.6%+/-12 in MIG and 99.1+/-26.8 in TIG (p = 0.0001). The percentage of controlled subjects was 47.2% in CG (CI = 40-54.4), 61.3% in MIG (CI = 54.1-68.5%) and 63.3% in TIG (CI = 56.4-70.2%) (p<0.05). CONCLUSIONS: TIG and MIG are effective measures for improving patient compliance in hypertension.     

Genetic association of CYP46 and risk for Alzheimer's disease

An increasing number of studies suggest that cholesterol plays an important role in regulating beta-amyloid (Abeta) metabolism in Alzheimer's disease (AD). One of the most important mechanisms for the elimination of excess brain cholesterol is its conversion into the 24S-hydroxycholesterol catalyzed by cholesterol 24S-hydroxylase (CYP46). Preliminary evidence indicates that an intron 2 CYP46 T/C gene polymorphismis associated with increased brain Abeta load and higher risk of AD. A case-control study utilizing a clinically well-defined group of 321 sporadic AD patients and 315 control subjects was performed to test this association. Our results indicate that the intron 2 CYP46 C/C genotype may predispose to AD, and this association is independent of the apolipoprotein E genotype.     

Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadic Alzheimer's disease

Dyslexic subjects show a variety of mild sensory and motor deficits that have been assumed to reflect dysfunction of the large-diameter 'magnocells' in different parts of the brain. Hearing as a warning sense relies on rapidly-conducting fibers, and on the basis of the magnocellular deficit theory, we wondered whether auditory alerting would be weakened in dyslexic adults. We quantified the strength of sound-induced spinal facilitation in seven dyslexic and eight normal-reading adults by measuring the amplitudes of H-reflex, a monosynaptic spinal reflex, after loud binaural sounds. The audiospinal facilitation was of similar strength in dyslexic and control adults, indicating normal auditory alerting via cerebrospinal pathways. The slightly prolonged facilitation in dyslexics agrees with the dyslexics' general sluggishness of sensorimotor processing.