Effects of prostaglandins and the autonomic nervous system on the vasodilatory properties of nitroglycerin in conscious dogs.

This study was designed to assess the respective roles of prostaglandins and the autonomic nervous system in the responses to nitroglycerin (NTG) in conscious dogs. In vivo, NTG (1, 10, and 100 micrograms/kg i.v.) induced dose-dependent decreases in blood pressure and increases in heart rate and cardiac output. Coronary and carotid blood flows increased simultaneously, whereas responses in renal blood flow were biphasic, i.e., an initial decrease was followed by an increase above control at 10 and 100 micrograms/kg. NTG responses were not changed by indomethacin but were affected by chlorisondamine alone or in combination with indomethacin; tachycardia was abolished, and increases in cardiac output after 10 and 100 micrograms/kg were reduced by 26 and 32%, respectively, after ganglionic blockade and by 19 and 32%, respectively, after chlorisondamine plus indomethacin. In addition, increases in carotid blood flow in doses of 100 micrograms/kg were reduced by 88% after chlorisondamine and 83% after chlorisondamine plus indomethacin. Finally, in the presence of chlorisondamine plus indomethacin, NTG induced a more pronounced hypotension associated with a more pronounced renal vasodilation at the highest dose. Independent of indomethacin pretreatment, NTG in vitro induced a dose-dependent relaxation of the carotid, coronary, and renal arteries. Depending on the vascular bed, the reflex and local controls of circulation are affected differently by NTG.     

Parental origin of de novo MECP2 mutations in Rett syndrome

Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases. Recently, DNA mutations in the MECP2 gene have been detected in approximately 70% of patients with RTT. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations occur exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analysed 19 families with RTT syndrome due to MECP2 molecular defects. In seven informative families we have found by DHPLC a nucleotide variant which could be used to differentiate between the maternal and the paternal allele. In each subject investigated from these families, we have amplified specifically each allele and sequenced allele-specific PCR products to identify the allele bearing the mutation as well as the parental origin of each X chromosome. This approach allowed us to determine the parental origin of de novo mutations in all informative families. In five cases, the de novo MECP2 mutations have a paternal origin and in the two other cases a maternal origin. In all transitions at CpG, the de novo mutation observed was of paternal origin. The high frequency of male germ-line transmission of the mutation (71% of RTT informative cases) is consistent with a predominant occurrence of the disease in females.     

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.      

Inv(X)(p21.1;q22.1) in a man with mental retardation,short stature,general muscle wasting,and facial dysmorphism: clinical study and mutation analysis of the NXF5 gene

We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel "Nuclear RNA export factor" (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended.     

Malignant granular cell tumor of the abdominal wall

The granular cell tumor is an uncommon tumor that usually appears as a solitary small nodular growth and runs a benign course. It occurs widely throughout the body, but is rarely described in the abdominal wall. The authors report a case of malignant granular cell tumor which was arising in anterior abdominal wall of a 67-year-old woman. Malignant variant is rare and the abdominal wall site is extremely uncommon. Regarding this clinical case and the literature the authors purpose to review the criteria of malignancy.     

Qualité des supports de communication de crise lors de la pandémie de la COVID-19 au Grand Maghreb

ObjectiveTo objectively assess the quality of “crisis communication” media, during the COVID-19 pandemic, in the three Greater Maghreb countries (Tunisia, Algeria, Morocco).MethodsA compliance audit for press releases and epidemiological bulletins was analyzed against a quality benchmark, which had been specifically designed by the authors. This framework, made up of five dimensions and 50 items, graded (0/1), was applied by two researchers in preventive medicine. Multiplying the scores by a coefficient of two resulted in a partial score of 20 points for each dimension and a total score of 100 points for the checklist taken as a whole. The quality of the communication media was considered to be good when exceeding the thresholds of 15/20 for the different dimensions and 75/100 for the entire grid.ResultsA total of 141 information media were included in this audit (Tunisia: 60; Algeria: 60; Morocco: 21). The overall median quality score for these media was only 56/100 (IIQ: [46–58]), without major variability between countries. The most appreciated dimension was “maintaining the confidence of the population”, with an overall median score of 14/20 (12/20 for epidemiological bulletins and 16/20 for press releases). The most poorly rated dimension was “strengthening community participation”, with a median score of only 4/20 (6/20 for epidemiological bulletins and 4/20 for press releases).ConclusionThe quality of the Maghreb crisis communication media during COVID-19 was insufficient in most of its dimensions and items, particularly from a psychosocial standpoint. Reinforcement of the capacities of communication officers to develop information material and supports during health crises is indispensable and should be considered as an urgent matter.