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.      

Levels and specificity of antibody in bronchoalveolar lavage (BAL) and serum in an animal model of trimellitic anhydride-induced lung injury

A study was undertaken to characterize the antibody response in rats exposed to trimellitic anhydride (TMA) by inhalation. Total antibody levels directed to trimellitic rat serum albumin (TM-RSA) from TMA-exposed rats were assayed by an ammonium sulfate technique. Total antibody levels in bronchoalveolar lavage (BAL) and the matched serum were compared by correction for the albumin content of each. An ELISA was developed to detect IgG, IgA, and IgM directed toward TM-RSA in BAL and serum and to compare class-specific antibody levels in BAL and serum by normalizing for albumin content. The specificity of the rat IgG response was determined by ELISA inhibition with TM-RSA and TM-human serum albumin (TM-HSA) and compared with reciprocal inhibition studies with serum from TMA-exposed workers. The levels of total antibody in BAL were three to 15 times greater than the levels found in the matched serum pair. IgG, IgA, and IgM antibodies were detected in the BAL and the serum of TMA-exposed rats but not in control rats. In each of the four rats tested, all antibody classes were present in equal or greater amounts in the BAL than in the serum. Complete inhibition of the rat IgG binding in ELISA was observed when TM-RSA or TM-HSA were added as inhibitors. Human IgG was inhibited in ELISA only by TM-HSA. In an animal model of human lung disease, the levels of total antibody as well as class-specific antibodies directed against TM-RSA were greater in BAL than in serum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patient care contributions of clinical pharmacists in four ambulatory care clinics

This study investigates both cost-avoidance and improvement in the quality of care and patient outcome attributed to pharmacist intervention in four ambulatory care clinics. Four clinical pharmacists reported 199 interventions made in the pharmacotherapeutic management of 87 ambulatory clinic patients in 1 month. The majority of interventions were based on acceptable professional practices as ranked by peer reviewers. Positive impact of the interventions on patient outcome based on objective and subjective data was documented in 49% of the interventions. Forty-two percent of the interventions improved the process of care with no measurable impact on patient outcome. Cost avoidance was calculated according to interventions made at different steps of the drug use process. Net cost avoidance figures projected to 1 year amounted to $221,056.     

A Preliminary Study on the Usage of a Data-Driven Probabilistic Approach to Predict Valve Performance Under Different Physiological Conditions

Annals of Biomedical Engineering - Predicting potential complications after aortic valve replacement (AVR) is a crucial task that would help pre-planning procedures. The goal of this work is to...     

A serial immunologic and histopathologic study of lung injury induced by trimellitic anhydride

Trimellitic anhydride (TMA) can induce immunologic lung disease in exposed workers. We have developed a rat model of TMA lung injury characterized by lung hemorrhage and an immune response to trimellityl (TM) haptenized lung proteins. The model is similar to the pulmonary disease-anemia syndrome (PDA) seen in workers exposed to TMA fumes. Sprague-Dawley rats, 15 per exposure period, inhaled micronized TMA powder, 100 micrograms/m3, 6 h/day, for 2,6, or 10 days and were sacrificed. At each time period, total, IgG, IgA, and IgM antibody to TM-rat serum albumin (TM-RSA) were measured by radiolabeled antigen binding and enzyme-linked immunosorbent assay (ELISA) in serum and bronchoalveolar lavage fluid (BAL). Hemorrhagic lung foci, weight, and displacement volume were determined, and lungs were examined by light and electron microscopy. There was no lung injury or antibody response at 2 days. There was minimal lung injury at 6 days with low levels of antibody in BAL and serum. At 10 days, there was a marked increase in hemorrhagic foci and in BAL and serum antibody levels. BAL antibody levels at 6 and 10 days had higher correlations with measures of lung injury than corresponding serum levels. There was minimal ultrastructural change at 6 days. By Day 10, there was marked intraalveolar hemorrhage, alveolar septal inflammatory nodules, abundant alveolar macrophages, and evidence of endothelial and epithelial cell injury. These results indicate that the immune response to inhaled TMA occurs parallel with the development of lung lesions, and antibody levels in BAL and serum are highly correlated with lung injury.     

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.