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.      

Association of C-reactive protein with coronary heart disease risk factors in patients with type 2 diabetes mellitus

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.     

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.     

Beneficial changes in serum apo A-1 and its ratio to apo B and HDL in stable hyperlipidaemic subjects after Ramadan fasting in Kuwait

BACKGROUND: In patients with metabolic and nutritional disorders such as diabetes and hyperlipidaemia, where strict compliance to advice on timing and composition of food intake is important, the prolonged daylight fasting during the month of Ramadan could produce undesirable biochemical consequences. AIM: The study aimed to compare pre- and post-Ramadan lipid and lipoprotein profiles in stable Kuwaiti hyperlipidaemic subjects attending a Lipid Clinic. SUBJECTS AND METHODS: The study population comprised 64 adult Kuwaitis (33 M, 31 F) who had been attending a Lipid Clinic for at least 12 months and were considered stable, without any acute systemic illness. At each clinic visit, the following parameters were measured: weight, total cholesterol (TC), triglycerides (TG), HDL, LDL, apo A-1, apo B, glucose and uric acid. These biochemical parameters were measured by routine automated analyzer techniques. The pre-Ramadan values comprised the means of two measurements taken at about 3 month and 1 month before commencement of Ramadan. Post-Ramadan values were obtained within 1 month of the end of the Ramadan fast. The parameters so obtained were compared in the whole group, and then according to gender, glycaemic status and modality of treatment (diet alone or with a fibrate or statin). RESULTS AND DISCUSSION: In the nondiabetic subjects, apo A-1 and apo A-1/apo B and apo A-1/HDL ratios were increased post-Ramadan (P<0.001). Weight did not change and the other lipid parameters-TC, TG, LDL, apo B-did not worsen. These observations, more consistent in the men than in the women, and in subjects treated with a fibrate or a statin rather than on diet alone, indicate a favorable coronary heart disease (CHD) risk profile. In the diabetic patients, these changes in the apo A-1 level and its ratio to HDL and apo B were also present, but TC and apo B levels increased, the latter significantly (P<0.05). These divergent effects in diabetic patients could variably influence CHD risk liability. Serum uric acid levels were also simultaneously reduced post-Ramadan in the non-diabetic subjects and those on statin treatment. CONCLUSION: When pre- and post-Ramadan lipid and lipoprotein profiles were compared in stable hyperlipidaemic subjects attending a Lipid Clinic in Kuwait, the most consistent changes post-Ramadan were increased levels of apo A-1 and apo A-1/apo B and apo A-1/HDL ratios and reduced uric acid levels. Body weight remained essentially unchanged and the other lipoprotein and lipid parameters were not worsened. These results suggest that Ramadan fasting in hyperlipidaemic subjects might favorably influence CHD risk.     

Immunoscintigraphy of ovarian endometriosis. A preliminary study

CA-125 is a membrane antigen detected in the serum of some women with gynaecological disease including endometriosis. We attempted to use a radioiodinated anti-CA-125 monoclonal antibody, OC-125, to image ovarian endometriosis using immunoscintigraphy. Two women with significant endometriosis and normal serum CA-125 levels had positive immunoscintigraphy. In one woman, all areas of endometriosis were imaged; in the other, endometriosis in one affected ovary was seen, but uptake in the other ovary was less than the extent of the disease.