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.      

Psychiatric morbidity in stroke patients attending a neurology clinic in Nigeria

Back ground

Stroke produces a wide range of mental and emotional disorders. Neuropsychiatric complications associated with stroke may have negative effects on the social functioning, overall quality of life and the recovery of motor functioning of stroke survivors.

Objective

To determine the prevalence and nature of psychiatric morbidity among stroke patients attending neurology outpatient clinic of the University of Ilorin Teaching Hospital (UITH), Ilorin-Nigeria.

Methods

All patients with stroke aged 18 years and above at an outpatient neurology clinic in Ilorin, Nigeria were assessed for mental and emotional disorders using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) over one year (March 2009 to February 2010).

Results

Overall prevalence of psychiatric morbidity was 36.0% (30/83) among 83 patients who constituted the study population. Specific diagnoses recorded were depression (19.2%), generalised anxiety disorder (9.6%), harmful alcohol use (2.4%); dementia, somatoform disorder, phobia and delusional disorder each had a prevalence of 1.2%. Clinical and sociodemographic variables were not significantly associated with psychiatric morbidity.

Conclusion

Psychiatric disorders are often associated with stroke. Identifying and treating stroke patients with these psychiatric co-morbidities could thus help to improve the overall quality of life of these patients.     

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.     

Persistent systemic inflammatory response syndrome is predictive of nosocomial infection in trauma

BACKGROUND: Admission systemic inflammatory response syndrome (SIRS) score has been previously reported to be an accurate predictor of infection and outcome in trauma. However, these data were limited to only one SIRS score at admission. A prior study in surgical intensive care unit (ICU) patients reported that the SIRS score on ICU day 2 declined after completion of resuscitation, and was a more accurate predictor of outcome. Our objective in this follow-up study was to prospectively evaluate the utility of daily SIRS scores in prediction of nosocomial infection and outcome in high-risk trauma patients. METHODS: Prospective data were collected on 702 consecutive trauma patients admitted over a 12-month period to the ICU. SIRS scores were calculated daily. Centers for Disease Control and Prevention guidelines were used for the diagnosis of infection. Multivariate linear regression was used for statistical analysis. RESULTS: Five hundred seventy-three (82%) patients sustained blunt injuries and 129 (18%) sustained penetrating injuries. The mean age was 43 +/- 21 years, with an overall mortality of 11.4%. Two hundred ninety (41.3%) of the study patients acquired a nosocomial infection (respiratory site most common), with an associated mortality rate of 12.4%. SIRS (defined as SIRS score >/= 2) on hospital days 3 through 7 was a significant predictor of nosocomial infection and hospital length of stay. Persistent SIRS to hospital day 7 was associated with a significant risk for increased mortality (relative risk, 4.7; 95% confidence interval, 1.41-12.87; p = 0.047). CONCLUSION: Persistent SIRS is predictive of nosocomial infection in trauma. Daily monitoring of SIRS scores is easily accomplished and should be considered in all high-risk trauma patients. Persistent SIRS in trauma should initiate early diagnostic interventions for determination of source of infection, and consideration of early empiric antimicrobial therapy.