Linkage mapping of a nonspecific form of X‐linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X‐linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X‐linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2–26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. © 2001 Wiley‐Liss, Inc.     

Undertreatment of hypertension in community-dwelling older adults: a drug-utilization study in Dicomano, Italy

OBJECTIVE: To define: (1) the prevalence of and (2) factors associated with undertreatment of hypertension in older persons; and (3) the prevalence of specific drug regimens and reasons for their selection. PARTICIPANTS: Cross-sectional survey of persons aged > or =65 years living in Dicomano, Italy. MAIN OUTCOME MEASURES: Prevalence of untreated and uncontrolled hypertension, both defined on the basis of two blood pressure (BP) cut-off points (> or =140/90 and > or =160/90 mm Hg) and of the presence of pharmacological treatment Predictors of undertreatment were analysed for the higher BP cut-off only. RESULTS: Five hundred of 692 (72.3%) and 380/692 (54.9%) participants met the 140/90 and the 160/90 mm Hg BP criterion, respectively. Of the latter, 162 (42.6%) were untreated, 119 (31.3%) had uncontrolled and 99 (26.1%) controlled hypertension. Women [odds ratio (OR), 0.4; 95% confidence interval (CI), 0.2-0.7], participants with coronary artery disease (CAD) (OR, 0.2; 95% CI, 0.1-0.6), stroke (OR, 0.3; 95% CI, 0.1-0.7), and preserved cognitive status (Mini Mental State Examination score >21: 0.3; 95% CI, 0.2-0.7) were more frequently treated. Uncontrolled hypertension was less likely in women (OR, 0.5; 95% CI, 0.3-1.0) and CAD patients (OR, 0.3; 95% CI, 0.1-0.7). Angiotensin converting enzyme (ACE)-inhibitors (55%), calcium (Ca)-antagonists (31%) and diuretics (20%) were the drugs most commonly prescribed. ACE-inhibitors were preferred, and diuretics rarely used, in diabetic subjects. Ca-antagonists were used mostly in CAD participants. CONCLUSIONS: Hypertension is undertreated in the majority of noninstitutionalized older adults, especially in men with impaired cognition and no vascular disease. Drug regimens are mostly based on ACE-inhibitors and Ca-antagonists, as a result of associated clinical conditions, requiring individualized treatment.     

Clinical failure of vancomycin in a dialysis patient with methicillin-susceptible vancomycin-heteroresistant S. aureus

We report a case of recurrent Staphylococcus aureus bacteremia in a patient who failed vancomycin due to a vancomycin-heteroresistant strain lacking methicillin resistance. Although initial isolates were susceptible, isolates obtained after vancomycin chemotherapy were vancomycin heteroresistant. This case thus illustrates the clinical emergence of vancomycin heteroresistance.     

Placental and fetal effects of antenatal exposure to antidepressants or untreated maternal depression

Objective: To assess systematically the effects of antidepressants and untreated maternal depression on human placenta and the developing fetus.

Methods: Pertinent medical literature information was identified using MEDLINE/PubMed, SCOPUS and EMBASE. Electronic searches, limited to human studies published in English, provided 21 studies reporting primary data on placental and fetal effects of antidepressant exposure or untreated gestational depression.

Results: The impact of antidepressants and non-medicated maternal depression on placental functioning and fetal biochemical architecture seems to be demonstrated, although its clinical significance remains unclear. More robust data seem to indicate that exposure to either antidepressants or untreated maternal depression may induce epigenetic changes and interfere with the physiological fetal behavior. Two cases of iatrogenic fetal tachyarrhythmia have also been reported.

Conclusions: Future research should clarify the clinical relevance of the impact of antidepressant and untreated maternal depression exposure on placental functioning. Moreover, ultrasound studies investigating fetal responses to antidepressants or maternal depressive symptoms are mandatory. This assessment should be performed during the whole duration of gestational period, when different fetal behavioral patterns become progressively detectable. Analyses of biochemical and epigenetic modifications associated with maternal mood symptoms and antidepressant treatment should also be implemented.     

No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures

A missense mutation in the gene encoding the alpha(2) subunit of the Na(+),K(+) ATPase pump (ATP1A2) was found in a family with both familial hemiplegic migraine (FHM) and Benign Familial Infantile Seizures (BFIC). As it is still unclear whether ATP1A2 is responsible for pure BFIC syndromes, we checked mutations of the ATP1A2 gene in probands of 12 Italian multiplex families with pure BFIC, who were negative for mutations in the SCN2A gene. We screened the ATP1A2 gene by denaturing high performance liquid chromatography (D-HPLC) and direct sequencing of DNA fragments showing an aberrant elution pattern. We found one exonic variant and five intronic variants, none leading to significant amino acid changes or causing a modification of the physiological mRNA maturation. The ATP1A2 gene does not appear to be involved in the ethiopathogenesis of pure BFIC syndromes, at least in the explored Italian multiplex families. It could be either responsible of a minority of cases, or of complex syndromes where BFIC and FHM co-occur.     

Immunohistochemical localization of TRPC6 in the rat substantia nigra

Transient receptor potential channels (TRPC) are plasma membrane, nonselective cationic channels and have been proposed as candidates involved in the regulation of cellular Ca2+ influx [D.E. Clapham, L.W. Runnels, C., Strubing, The TRP ion channel family, Nat. Rev. Neurosci. 2 (2001) 387-396; A. Martorana, C. Giampa, Z. DeMarch, M.T. Viscomi, S. Patassini, G. Sancesario, G. Bernardi, F.R. Fusco, Distribution of TRPC1 receptors in dendrites of rat substantia nigra: a confocal and electron microscopy study, Eur. J. Neurosci. 24 (2006) 732-738]. Studies on regional localization patterns of TRPCs are necessary to provide helpful guidelines for correlating current types with particular channels. In this study, we examined the distribution of one particular member of TRPC superfamily, namely, TRPC6, in the substantia nigra of normal rat brain. Single and double label immunohistochemistry were employed to perform both light and confocal microscopy observations. Our single label studies showed that, in the substantia nigra, TRPC6 labeled the perikarya with a diffuse and intense immunoreaction product distributed throughout cell cytoplasm whereas only a light immunostaining was observed in the cell nuclei. No labeling of axon or terminals was observed, although TRPC6 was evenly distributed in the neuropil. Our dual label studies showed a TRPC6 immunoreactivity pattern that was localized into the proximal dendrites and axon hillock of the large dopaminergic neurons identified by TH immunoreaction. Furthermore, our double label immunofluorescence study for TRPC6 and mGluR1 showed a complete co-localization of the two markers in the substantia nigra. Moreover, TRPC6 did not co-localize with synaptophysin. Thus, our study shows the postsynaptic localization of TRPC6 and its association with mGluR1 in the midbrain dopamine neurons.     

Intracellular Human Papillomavirus E6, E7 mRNA Quantification Predicts CIN 2+ in Cervical Biopsies Better Than Papanicolaou Screening for Women Regardless of Age

Context.-Cervical cancer screening in women younger than 30?years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. Objectives.-To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30?years. Design.-We analyzed 3133 cytology specimens from a screening population of women aged 19-75?years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30?years. Test results were compared to histology in 246 cases. Results.-The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30?years and older. In women younger than 30?years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (≥ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30?years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of <10% for CIN 2+ and CIN 3+ in both groups. Conclusions.-HPV OncoTect demonstrates a performance that would be effective for ASCUS/LSIL triage in women including those younger than 30?years.