Cardiac features of Emery-Dreifuss muscular dystrophy caused by lamin A/C gene mutations.

AIMS: Retrospective studies have identified a mutation in the lamin A/C (LMNA) gene in patients selected on the basis of a phenotype characterized by dilated cardiomyopathy, atrioventricular conduction disturbances and sudden death. However, the features of cardiac abnormalities in patients with an initial diagnosis of Emery-Dreifuss muscular dystrophy (EDMD) are poorly known. Aim of the present study was to investigate the spectrum of cardiac disease in patients with an initial diagnosis of EDMD caused by a mutation in the LMNA gene. METHODS AND RESULTS: Ten consecutive patients with EDMD and a LMNA gene mutation were evaluated with structured medical interview, physical examination, ECG, echocardiogram and 24-h Holter monitoring. Electrophysiological testing and cardiac catheterization were performed if a class 1 or 2 American Heart Association guidelines indication was present. Cardiac disease was found in eight of 10 patients and consisted in the variable combination of supraventricular arrhythmias, disorders of atrioventricular conduction, ventricular arrhythmias, dilated cardiomyopathy, non-dilated cardiomyopathy, restrictive cardiomyopathy and sudden death despite pacemaker implant. CONCLUSIONS: Cardiac disease is common in patients with an initial diagnosis of EDMD caused by a mutation in the LMNA gene and consists of arrhythmias, disorders of atrioventricular conduction, cardiomyopathies and sudden death despite pacemaker implant.     

Epitaxial and large area Sb2Te3 thin films on silicon by MOCVD

Antimony telluride (Sb₂Te₃) thin films were prepared by a room temperature Metal–Organic Chemical Vapor Deposition (MOCVD) process using antimony chloride (SbCl₃) and bis(trimethylsilyl)telluride (Te(SiMe₃)₂) as precursors. Pre-growth and post-growth treatments were found to be pivotal in favoring out-of-plane and in-plane alignment of the crystallites composing the films. A comprehensive suite of characterization techniques were used to evaluate their composition, surface roughness, as well as to assess their morphology, crystallinity, and structural features, revealing that a quick post-growth annealing triggers the formation of epitaxial-quality Sb₂Te₃ films on Si(111).

Highly oriented antimony telluride thin films are prepared by room temperature metalorganic chemical vapor deposition on Si(111).     

Brassiere wearing and breast cancer risk: A systematic review and meta-analysis

AIM: To evaluate existing evidence for the association between different type of brassiere exposures and the risk of breast cancer. METHODS: Ovid Medline, CINAHL, Cochrane Data Base of Systematic Reviews, Pubmed, Scopus, Proquest, Sciencedirect, Wiley Online Library, WanFang Data, Hong Kong Index to Chinese Periodicals, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Text database, Taiwan Electronic Periodical Services and HyRead; reference lists of published studies; original research studies published in English or Chinese examining the association between type and duration of brassiere-wearing and breast cancer risk. Data were abstracted by a first reviewer and verified by a second. Study quality was rated according to predefined criteria. “Fair” or “good” quality studies were included. Results were summarised by meta-analysis whenever adequate material was available. RESULTS: Twelve case-control studies were included in the review. Meta-analysis showed brassiere wearing during sleep was associated with a two times of increased odds. CONCLUSION: The present review demonstrates insufficient evidence to establish a positive association between the duration and type of brassiere wearing and breast cancer. Further research is essential; specifically, a large-scale epidemiological study of a better design is needed to examine the association between various forms of brassiere exposure in detail and breast cancer risk, with adequate control of confounding variables.     

Domiciliary treatment of febrile episodes in cancer patients: a prospective randomized trial comparing oral versus parenteral empirical antibiotic treatment

Hospitalization and empirical broad-spectrum, intravenous antibiotics are the standard treatment for febrile cancer patients. Recent evidence supports the suggestion that febrile episodes in a low-risk population can be managed successfully in an outpatient setting, but the optimal drug regimen is unknown. In a prospective randomized clinical trial we compared ciprofloxacin 750 mg p.o. twice a day with ceftriaxone 2 g i.v. as a single daily dose for the empiric domiciliary treatment of febrile episodes in low-risk neutropenic and nonneutropenic cancer patients. A total of 173 patients, accounting for 183 febrile episodes, were enrolled in the study. Overall, successful outcomes were recorded for 76 of 93 (82%) febrile episodes in patients who were randomized to the oral regimen and for 68 of 90 (75%) febrile episodes in patients randomized to the i.v. regimen: this difference was not statistically significant. The success rate was similar in all subgroups of patients: neutropenic and nonneutropenic, with documented infection and with fever of unknown origin. There were 3 deaths in the group of patients treated with the parenteral regimen, and two of these were related to treatment failure. Both treatments were well tolerated, and the cost of the oral regimen was lower. This prospective study suggests that domiciliary antibiotic empiric monotherapy is feasible in febrile nonneutropenic or low-risk neutropenic outpatients in whom a bacterial infection is suspected, and that either an oral or a parenteral regimen can be used. A number of factors may influence the choice between an orally and an i.v.-administered antibiotic, but owing to the easier administration and lower cost, the oral regimen seems to be preferable. Published online: 5 March 1999     

Lack of nocturnal serum thyrotropin surge after surgery

The effects of surgery on TSH secretion, with particular regard to the nocturnal TSH surge, were evaluated in 10 consecutive patients followed for 6 days after surgery. Surgical trauma was associated in all patients with significant decreases in serum total and free T3 and a significant increase in serum rT3 levels, with no variations in serum total and free T4 concentrations. A marked increase in serum cortisol levels was observed, with higher values at night than in the morning. Serum cortisol levels and circadian rhythm normalized on the fifth day. Serum TSH values in the morning significantly decreased on the first day after surgery and returned to normal on the second day. Serum TSH values at night (2400-0200 h) were higher than in the morning preoperatively, but the nocturnal surge was abolished from days 1-5 after surgery and was restored only on the sixth day. Thus, surgery was associated with a prolonged loss of the nocturnal serum TSH surge. This effect on TSH secretion was more marked than predictable on the basis of serum TSH measurements in the morning alone. An inverse relationship was found between serum cortisol and serum TSH values at night, suggesting that the excessive endogenous cortisol secretion might play a role in the derangement of TSH secretion.     

A human immunodeficiency virus type 1 pol gene-derived sequence (cPPT/CTS) increases the efficiency of transduction of human nondividing monocytes and T lymphocytes by lentiviral vectors

We have investigated the capacity of two human immunodeficiency virus type 1-derived lentivectors, differing in the presence of a 118-bp pol fragment containing the cPPT/CTS element, to transduce human normal primary cells of different hematopoietic lineages. Infection of resting monocytes with a high multiplicity of infection (MOI > 10) revealed that the lentivirus carrying the pol fragment (cPPT) is effective, transducing 75% of cells compared with 36% for the no-cPPT vector. Even at low MOIs (< or =1) the cPPT vector still shows a better transduction efficiency than the no-cPPT vector. Moreover, transduction does not require dendritic cell differentiation. In contrast, infection of nonactivated T lymphocytes showed that both vectors, tested at high MOIs, can transduce a small, although measurable, percentage of cells (up to 10%), which may correspond to G(1a) "activated" cells as detected by simultaneous staining of DNA and RNA, in our cultures in the presence of medium alone. Furthermore, we show that the sole addition of interleukin 2 or interleukin 15 represents a full proliferative signal under our conditions and permits high transduction efficiency (up to 30% with the cPPT vector and 15% with the no-cPPT vector). Still higher transduction of T lymphocytes can be achieved after stimulation with phytohemagglutinin and interleukin 2 (up to 78% with the cPPT vector vs. 42% with the no-cPPT vector). Finally, both viruses do not transduce either resting or proliferating tonsillar B lymphocytes.     

Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy

Globoid cell leukodystrophy (GLD; also known as Krabbe disease) is an invariably fatal lysosomal storage disorder caused by mutations in the galactocerebrosidase (GALC) gene. Hematopoietic stem cell (HSC)-based gene therapy is being explored for GLD; however, we found that forced GALC expression was toxic to HSCs and early progenitors, highlighting the need for improved regulation of vector expression. We used a genetic reporter strategy based on lentiviral vectors to detect microRNA activity in hematopoietic cells at single-cell resolution. We report that miR-126 and miR-130a were expressed in HSCs and early progenitors from both mice and humans, but not in differentiated progeny. Moreover, repopulating HSCs could be purified solely on the basis of miRNA expression, providing a new method relevant for human HSC isolation. By incorporating miR-126 target sequences into a GALC-expressing vector, we suppressed GALC expression in HSCs while maintaining robust expression in mature hematopoietic cells. This approach protected HSCs from GALC toxicity and allowed successful treatment of a mouse GLD model, providing a rationale to explore HSC-based gene therapy for GLD.     

Assessment of sleep in women with night eating syndrome

STUDY OBJECTIVES: Evaluation of sleep in subjects with night eating syndrome (NES). DESIGN: Polysomnographic and questionnaire comparisons between subjects with NES and controls. SETTING AND PARTICIPANTS: Fifteen women with NES (mean +/- SD = 41 +/- 8 years) and 14 women (comparable age and weight) without NES (39 +/- 10 years) were studied in the laboratory for 3 days. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Subjects with NES did not differ from controls in timing of sleep onset or offset. They had less stage 2 sleep than controls (minutes, p = .012; percentage, p = .016) and less stage 3 sleep (p = .023), which contributed to their having a lower total sleep time (p = .05) and reduced sleep efficiency (p = .03). Subjects with NES did not have more awakenings than controls, but 93.3% of them ate on awakening during all 3 nights, while 92.9% of controls did not eat on any night. Logistic discriminant analyses identified a multiple sleep parameter model associated with increased likelihood of NES that had sensitivity of 84.6% and specificity of 76.9%. Patients with NES were more depressed than controls (p < .001) and reported greater sleep disturbance that included lower sleep quality (p < or = .001), reduced sleep duration (p < or = .001), and increased number of awakenings (p < or = .001). CONCLUSIONS: Patients with NES appear to have sleep maintenance insomnia rather than sleep-related eating disorder or a parasomnia. The maintenance of normal timing for sleep-wake behavior in the presence of a phase delay in the timing of caloric intake suggests this disorder reflects a state of internal circadian desynchrony associated with significant sleep complaints. It remains unknown whether the sleep disturbance precedes the abnormally timed eating.     

Tuberculosis infection and disease in immigrant children

From the second half of the eighties, the cases of tuberculosis (TBC) in Italy have been constantly increasing. The increase in TBC cases in developed countries is related to different factors, including HIV epidemic and increased number of immigrants from countries with high TBC incidence and important socio-economic problems. Compared with adults few children with TBC were homeless or coinfected with HIV, nonetheless the children lived frequently in low socioeconomic status and consequently high risk of being uninsured and with adults at risk for tuberculosis (immediate relative, household members, or recently immigrated). An epidemiologic study was carried out, in order to evaluate the impact of TBC infection in immigrant children. From January 2001 to December 2002, Mantoux test (5 IU) was performed in immigrant children hospitalized or followed in two children hospitals. They included 228 children: mean age 4 years (range 1 month to 15 years). The patients came from: South America (44%) (especially from Ecuador), from Africa (20%), from Eastern Europe (19%), (especially from Middle East and North Africa), from Far East (17%). In 30 cases (13,2%) Mantoux test was positive. Among these latter, 21 presented latent infection, whereas another 9 had tuberculous disease with pulmonary localization and one of them associated with cervical adenopathy. In the study period, among all children (4426) admitted the two Units, the prevalence of tuberculous disease was 2,5% in immigrant children compared 0.2% in native children. Accurate epidemiologic monitoring, further clinical studies aimed at highlighting TBC peculiar aspects in children, and adequate therapy can lead to TBC control in the immigrant children.