BACKGROUND—Rett syndrome is a neurodevelopmental disorder affecting only girls; 99.5% of Rett syndrome cases are sporadic, although several familial cases have been reported. Mutations in the MECP2 gene were identified in approximately 70-80% of sporadic Rett syndrome cases. METHODS—We have screened the MECP2 gene coding region for mutations in five familial cases of Rett syndrome and studied the patterns of X chromosome inactivation (XCI) in each girl. RESULTS—We found a mutation in MECP2 in only one family. In the four families without mutation in MECP2, we found that (1) all mothers exhibit a totally skewed pattern of XCI; (2) six out of eight affected girls also have a totally skewed pattern of XCI; and (3) it is the paternally inherited X chromosome which is active in the patients with a skewed pattern of XCI. Given that the skewing of XCI is inherited in our families, we genotyped the whole X chromosome using 32 polymorphic markers and we show that a locus potentially responsible for the skewed XCI in these families could be located on the short arm of the X chromosome. CONCLUSION—These data led us to propose a model for familial Rett syndrome transmission in which two traits are inherited, an X linked locus abnormally escaping X chromosome inactivation and the presence of a skewed XCI in carrier women.
Keywords: Rett syndrome; skewed X chromosome inactivation; X chromosome; MECP2相似文献
Background: Because protamine is administered to reverse heparin, a drug that might itself affect the pharmacologic properties of protamine, this study was designed to assess the properties of protamine alone and in the presence of heparin in conscious dogs.
Methods: Twelve dogs were instrumented to continuously record cardiac and regional hemodynamics. On separate occasions, a dose of protamine (0.5, 1, 3, 5, and 8 mg/kg) was randomly administered either alone or in the presence of heparin (ratio 100 IU/mg). Heparin (300 IU/kg) and protamine (3 mg/kg) were administered in the presence of N-methyl-l-arginine, a specific nitric oxide synthase inhibitor. Identical experiments were performed with protamine (8 mg/kg) in the absence of heparin on a separate occasion.
Results: Protamine alone produced limited cardiac and regional changes. In the presence of heparin, protamine produced hypotension at 3, 5, and 8 mg/kg, vasodilatation at 3 and 5 mg/kg, and a more pronounced dose-dependent increase in pulmonary pressure at 3, 5, and 8 mg/kg. Simultaneously, transient carotid vasodilatation at 3 and 5 mg/kg, coronary and hepatic vasodilatation at 3, 5, and 8 mg/kg, as well as a decrease in vertebral vascular resistance were recorded at 1, 3, and 8 mg/kg. Protamine produced an immediate increase followed by a secondary decrease in renal vascular resistance. Protamine-induced secondary pulmonary pressor effects were attenuated. In the presence of heparin, nitric oxide synthase blockade selectively attenuated protamine-induced immediate hypotension, systemic vasodilatation, and coronary, mesenteric, and hepatic vasodilations as well as the decrease in portal blood flow and accentuated the renal vasoconstriction. 相似文献
In pain clinical trials, the rescue analgesic medication such as patient-controlled analgesia morphine is often made available for patients for breakthrough pain. The patient-controlled analgesia morphine usage decreases the study agent's effect on pain relative to placebo and introduces greater variability in attainment of pain scores. For assessment of analgesic efficacy, the isolated statistical analysis of pain score or morphine consumption as a surrogate marker for pain not only loses statistical efficiency but also may incur increased false-positive findings because of multiple testing. The aim of this article is to review the research to date for choices of statistical tests for pain or morphine consumption outcome, with a focus on systematically evaluating a means for collective analgesic assessment of pain and morphine consumption using an integrated outcome. A case example is illustrated for data visualization, statistical comparison, and effect size estimation using the new endpoint. Some implications for clinical practice and further research are discussed.PerspectiveThis article provides statistical evidence to conclude that an integrated outcome of pain score and morphine consumption provides an efficient means for integrated analgesic assessment. 相似文献
Mutations in the MECP2 (Methyl-CpG-binding protein) gene have been reported to cause Rett syndrome (RTT), an X-linked progressive encephalopathy. Recent studies have identified large gene rearrangements that escape the common PCR-based mutation screening strategy and mutations in a novel MeCP2 isoform (named MECP2B). We have collected the results of MECP2 mutational analysis concerning 424 RTT patients conducted in eight laboratories in France. In total, 121 different MECP2 mutations were identified. R168X (11.5%) is the most common of MECP2 mutations, followed by R270X (9%), R255X (8.7%), T158 M (8.3%) and R306C (6.8%). Only eight mutations had relative frequency>3%. Large and complex rearrangements not previously detected using only a PCR-based strategy represent 5.8% of MECP2 mutations. On the contrary, mutation in exon 1 appears to be rare (less than 0.5%). These data demonstrate the high allelic heterogeneity of RTT in France and suggest that routine mutation screening in MECP2 should include quantitative analysis of the MECP2 gene. This study represents an important instrument for molecular diagnosis strategy and genetic counseling in RTT families. 相似文献
The synchronous development of epithelial tumours and lymphoma of gastrointestinal tract has been rarely reported in the literature. In this article, we report four cases having such synchronous association. Diagnosis was made based on the microscopic examination of surgical specimens along with immunohistochemistry. These observations further lead to the discussion of the pathogenesis of these tumours and the role of Helicobacter pylori in the development of gastric lymphoma and carcinoma. 相似文献
Hydatidosis is an endemic affection in Tunisia. Cerebral echinococcosis is a relatively rare entity accounting for only 1-2% of all hydatid cysts in humans. Extradural hydatid cyst of the posterior fossa is a very uncommon site for the disease. We report the case of a four-year-old child admitted for high intracranial pressure. Brain CT scan showed an extradural posterior fossa cyst without enhancement after contrast medium injection. Operative finding revealed a hydatid cyst. The histological examination of the tissue sample confirmed the diagnosis. The patient was given albendazole post operatively. She feels well six months later. 相似文献
AIM: Our aim was to study the susceptibility of Streptococcus pneumoniae to antibiotics in patients with pneumococcal meningitis and to search for the prognosis factors in those patients. METHODS: We have studied retrospectively 31 cases of pneumococcal meningitis. Comparaisons were performed with univariate analysis. RESULTS: The mean age was 36.7 +/- 20.5 years (ranged: 9 and 78 years). The sex ratio was 3,4. The susceptibility of Streptococcus pneumoniae to penicillin G was affected in 10 cases (33% of isolated pneumococcus. The MIC to penicillin G was > or =2 in only one case. The hospital mortality was 26% (8/31). With univariate analysis, factors associated with death were: age > or =55 years (Ss p= 0,006, OR: 17.2 IC95%: 2.3-134), albuminorachie > or = 7 g/l (p = 0.002, OR: 22; IC95%: 1.9-2.51), shock (p = 0.031, OR: 6.7; IC95%: 1.05-42) and Glasgow Coma Score (GCS) < or =8 (p = 0.001, OR: 20; IC95%: 2.68-149). CONCLUSION: No susceptibility to penicillin G is not associated with a worse outcome in patients with pneumococcal meningitis. An age > or =55 years, albuminorachie > or =7 g/l shock and Glasgow Coma Score < or =8 at admission were determinant of the prognosis in our study. 相似文献