Higher frequency of uncommon 1.5-2 Mb deletions found in familial cases of 22q11.2 deletion syndrome

Familial 22q11.2 deletions have been reported as a 6%-28% of the total affected cases of 22q11.2 microdeletion syndrome (del22q11.2). Different deletion genotypes have been described for this disorder, with a predominant 3 Mb deletion present in 90% of the cases, a less common 1.5-2 Mb deletion in 8%, and atypical smaller deletions in 2%. We have studied 15 cases of del22q11.2 from 6 families (two of them three-generation families) that were previously diagnosed through FISH. We have sized the deleted region by allele genotyping of 12-16 polymorphic markers in all cases, and we have found three families affected with the 1.5-2 Mb deletion, two affected with the 3 Mb deletion, and one in which the deletion size could not be determined. This predominance of the smaller 1.5-2 Mb deletions in our familial cases differs from the minor frequency observed in sporadic cases of del22q11.2. This finding suggests that small deletions are more linked to familial inheritance than large ones, possibly due to psychosocial or biological factors associated with differences in the phenotype. Deletion sizing on routine diagnosis may help characterizing the inheritability of 22q11.2 microdeletion syndrome.     

How effective is surgical adrenalectomy in lowering steroid hormone concentrations?

Surgical adrenalectomy produces objective tumour regression in 50-60% of estrogen receptor-positive women with metastatic breast carcinoma. Additional responses to antiestrogens or further suppression of estrogens with aminoglutethimide after adrenalectomy suggest the possibility of continued adrenal steroid secretion even after surgical ablation. The use of sensitive and specific RIAs allows precise determination of the degree of hormone suppression after adrenalectomy and could provide documentation of nonsuppression or escape from suppression in individual patients. To evaluate the possibility of continued hormone secretion, we measured 14 hormones in 26 postmenopausal women with breast carcinoma before and after adrenalectomy. While the mean levels of androgens were markedly suppressed [dehydroepiandrosterone sulfate (DHEA-S), 99%, androstenedione, 94%; testosterone, 77%; dihydrotestosterone, 73%] after adrenalectomy, estrogen concentrations fell to a much lesser extent (plasma estrone, 73%; urinary estrone, 86%; plasma estradiol, 53%; urinary estradiol, 67%). Examination of data in individual patients revealed incomplete suppression in several women (less than 50% suppression of plasma estradiol in 14 of 25 patients, of urinary estradiol in 4 of 22, and of urinary estrone in 1 of 22). Androgen concentrations also fell incompletely after adrenalectomy in a few patients. Androstenedione concentrations were greater than 2 SD above the group mean in 2 of 23 patients, and in 2 of 25 patients, DHEA-S concentrations were also greater that 2 SD above the group mean. Serial measurements of hormones over a 1- to 3-yr period following surgery revealed escape from suppression over time (i.e. greater than 2-fold increase in hormone levels) in 7 of 26 women. The practical significance of the lack of suppression or of escape from inhibition was assessed by comparing estrogen levels in responders vs. nonresponders to surgical adrenalectomy. Of all steroids measured, greater suppression of only 1 hormone (urinary estrone) was observed in responders vs. nonresponders. These data indicate that adrenalectomy does not uniformly suppress circulating androgen and estrogen levels in postmenopausal patients. Women who initially suppress after adrenalectomy may show recovery of either androgen or estrogen levels with time.     

Genetic characterization of HIV-1 strains circulating in Kazakhstan

To determine the HIV-1 genetic diversity in Kazakhstan, 85 blood samples from HIV-seropositive donors were collected between 2001 and 2003. The study population consisted of 91.8% injecting drug users (IDUs); the remainder was infected sexually or iatrogenically. A genomic region that included part of the polymerase gene was sequenced for all 85 samples, and from these, 6 samples were randomly selected for nearly full genome sequencing. Subtype A was the most common genetic form (94.1%), followed by CRF02_AG (4.7%) and subtype C (1.2%). All subtype A sequences clustered closely with samples from countries of the former Soviet Union (FSU). From these sequences, 47 (58.8%) presented the secondary protease inhibitor mutation V77I that has been linked to a genetic lineage in the FSU epidemic. In addition, most had the other 2 mutations that characterize the "V77I haplotype." All 6 nearly full-length sequences were subtype A and clustered with other FSU strains. The CRF02_AG strains from this population clustered with strains from Uzbekistan, reflecting the spread of the CRF02_AG epidemic in Central Asia. The HIV epidemic in Kazakhstan is predominantly in IDUs and is indigenous to the geographic region, and most of the strains are genetically similar to those circulating in the FSU and other parts of Central Asia.     

Factors influencing citations to systematic reviews in skin diseases: a cross-sectional study through Web of Sciences and Scopus

BACKGROUND

Disseminating information derived from systematic reviews is a fundamental step for translating evidence into practice.

OBJECTIVE

To determine which features of dermatological SR are associated with systematic review dissemination, using citation rates as an indicator.

METHODS

Dermatological systematic reviews published between 2008 and 2012 were obtained from Scopus, the ISI Web of Sciences and the Cochrane Skin Group. Bibliometric data of every systematic review were collected and analyzed.

RESULTS

A total of 320 systematic reviews were analyzed. Univariable analysis showed that the journal impact factor, number of authors, and total references cited were positively associated with the number of citations. There was a significant difference in the median number of citations with regard to the corresponding author''s country, type of skin disease, type of funding, and presence of international collaboration. Cochrane reviews were significantly associated with a lower number of citations. Multivariable analysis found that the number of authors, number of references cited and the corresponding author from United Kingdom were independently correlated with many citations. Cochrane systematic reviews tended to be independently associated with a lower number of citations.

CONCLUSIONS

Citation number to systematic reviews may be improving by increasing the number of authors, especially collaborative authors, and the number of cited references. The reasons for the association of Cochrane SRs with fewer citations should be addressed in future studies.