Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions

BackgroundSubanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment.MethodsThirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report.ResultsTwenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37–0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η _p²=0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P < .001, d = 2.00; Quick Inventory of Depressive Symptoms Self-Report item 10, P < .001, d = 1.36).ConclusionA short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01945047","term_id":"NCT01945047"}}NCT01945047     

Efficacy of the FIFA 11+ Warm-Up Programme in Male Youth Football: A Cluster Randomised Controlled Trial

The FIFA 11+ is a structured warm-up programme specially designed to prevent injuries among football players from age 14 years and above. However, studies to prove its efficacy are generally few and it is yet to be tested in male youth footballers and among African players. The purpose of the study was to examine the efficacy of the FIFA 11+ programme in reducing the risk of injuries among male youth football players of the Lagos Junior League. A cluster randomised controlled trial was conducted. All the 20 teams (414 players aged 14 -19 years) in the Premier League division were block-randomised into either an intervention (INT) or a control (CON) group. The INT group performed the FIFA 11+ exercises as warm-up during training sessions and the CON group performed usual warm-up. Participating teams were prospectively followed through an entire league season of 6 months in which they were visited every week to assess injured players for time-loss injuries in both groups. The primary outcomes were any injury to the players, injuries by type of exposure and injuries specific to the lower extremities. The secondary outcomes were injuries reported by body location, aetiology, mechanism and severity. In total, 130 injuries were recorded affecting 104 (25%) of the 416 players. Team and player compliance with the INT was 60% and 74% respectively. Based on the primary outcome measures of the study, the FIFA 11+ programme significantly reduced the overall rate of injury in the INT group by 41% [RR = 0.59 (95% CI: 0.40 – 0.86; p = 0.006)] and all lower extremity injuries by 48% [RR = 0.52 (95% CI: 0.34 – 0.82; p = 0.004)]. However, the rate of injury reduction based on secondary outcomes mostly did not reach the level of statistical significance. The FIFA 11+ programme is effective in reducing the rates of injuries in male youth football players.

Key points

• The FIFA 11+ has only been tested in randomised controlled trials conducted on female youth football players; this study reports its efficacy in male youth football for the first time
• The FIFA 11+ programme significantly reduced the overall rate of injuries and lower extremity injuries in male youth football players
• Youth football administrators in Africa and other parts of the world should pursue the implementation of the FIFA 11+ in order to minimize the incidence of injuries among players

Key words: Injury prevention, neuromuscular training, FIFA, sports     

Cellular sensitization against spermatic and seminal plasma antigens in women after intrauterine insemination

Summary Using an indirect lymphokin-assay, the leucocyte-migration-inhibition-test (LMI-test), the cellular sensitization of fertile and infertile patients before and after homologous and heterologous intrauterine insemination (IUI) was investigated. In this assay several preparations of spermatozoa (“washed”-, “swim-up”- and “pellet”-spermatozoa) in different concentrations (1, 5 and 10×10⁶ sperms/ml culture medium) and seminal plasma were tested as antigen. In all investigated groups a cellular immune response against spermatic antigen was demonstrable and seemed to be dose dependent. In contrast to fertile women who reacted with an enhancement of the macrophage migration for low concentrations the same concentration of antigen induced an inhibition of macrophage migration in fertile patients. For high concentrations of spermatic antigens there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatic antigens as there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatozoa. The immunological response of infertile patients seems to be similar in those receiving husband and donor IUI.     

Indikation und Ergebnisse der Verkürzungsosteotomie der Ulna

A relatively or absolutely too long ulna leads always to pain in the wrist, so that a compensation in length of both forearmbones is achieved by shortening osteotomy. The gradual ulna shortening osteotomy, the stylectomy and the resection of the caput ulnae with or without radius transposition osteotomy are available as shortening operation. In 17 patients of the Gießener Unfallchirurgischen Klinik we performed in 14 cases a shortening osteotomy of the ulna and in 3 cases a resection of the caput ulnae. The shortening osteotomy lead in all cases to a reduction of complaints and to an improvement of the mobility of the wrist. Due to frequent arthropathy the resection of the caput ulnae should be taken more often into consideration in older people.     

Das Karzinom des Nierenparenchyms

Zusammenfassung Nach Aufgliederung der prim?ren epithelialen Nierenparenchymtumoren aus pathologisch-anatomischer Sicht in 1. hypernephroide Karzinome, 2. papill?re Adenokarzinome, 3. übergangsformen von 1 und 2, werden Nierenveneneinbruch und Einbruch in das Nierenholsystem im Hinblick auf überlebenszeit bzw. H?maturie untersucht. Altersverteilung, Inivialsymptome und Laboratoriumsbefunde werden in Tabellen aufgeführt. In der R?ntgendiagnostik wird die überragende Bedeutung der Aortographie hervorgehoben und ihre Grenzen besprochen. Schlie?lich erfolgt die Darstellung der überlebensrate nach verschiedenen Einteilungsprinzipien: Tumor auf die Niere beschr?nkt, perirenale Infiltration, Veneneinbruch, makroskopisch radikal operiert und die Ergebnisse aller operierten Patienten.

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Summary Classification of the primary epithelial tumors of the kidney parenchyma from a patho-anatomical standpoint in 1. hypernephroid carcinoma, 2. papillary adenocarcinoma, 3. transition of 1 to 2, invasion to renal vene and to calyx-pelvic system in relation to survival rate and haematuria is examinated. Age distribution, initial symptoms and laboratory findings are summarized in tables. The importance of aortography in the roentgenologic diagnostic of renal is emphasized. Discussion of survival rate according to: intraparenchymal tumor, perirenal and vene invasion, nephrectomy macroscopic radical and results of all operated patients.

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Mit Unterstützung aus dem Felix-Mandl-Fonds zur F?rderung wissenschaftlicher Arbeiten an den St?dtischen Krankenanstalten der Gemeinde Wien und aus der Ludwig-Boltzmann-Gesellschaft zur F?rderung der wissenschaftlichen Forschung in ?sterreich.