Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease

Pulmonary hypertension with elevated pulmonary vascular resistance is a common cardiovascular complication associated with increased morbidity and mortality in preterm infants with chronic lung disease. Injury to the developing pulmonary circulation results in structural and functional abnormalities of the pulmonary vasculature. Animal studies have demonstrated that disruption of angiogenesis may contribute to the failure of normal alveolarisation in chronic lung disease. Levels of vascular endothelial growth factor in bronchoalveolar lavage fluid are lower in infants with chronic lung disease compared to preterm controls. Supplemental oxygen is commonly used to prevent and treat pulmonary hypertension, although optimal arterial oxygen saturation levels remain uncertain. Other vasodilators such as inhaled nitric oxide appear promising, but as yet have not been evaluated in the form of randomised controlled trials. Further studies are required to investigate the long-term effectiveness of pulmonary vasodilator therapy.     

Relationship of Quality of Life with Disability Grade in Obsessive Compulsive Disorder and Dysthymic Disorder

Background:

There is paucity of information on the relationship of quality of life (QOL) in obsessive compulsive disorder (OCD) and dysthymic disorder (DD) with disability grade in India.

Aim:

To assess the relation of QOL with disability level in OCD and DD.

Materials and Methods:

This hospital based study was conducted in a medical institution in Davanagere, Karnataka, India. Data was collected by using Diagnostic and Statistical Manual IV Text Revision (DSM IV TR) criteria, WHO QOL BREF and IDEAS. Relationship between disability grade and QOL was assessed by independent sample t test.

Results:

Mild disabled OCD patients had a significantly better QOL in the Q1 domain i.e. perception on quality of life as compared to moderately disabled patients (P < 0.05), while in other domains of QOL, there was no statistically significant difference (P > 0.05). But, QOL score in physical domain showed significant difference across disability grades (56.00, SD = 6.89; 48.50, SD = 12.28) in DD, but not in other domains.

Conclusion:

Perception of QOL is better in those with mild disability in OCD, but in DD, physical domain of QOL score is more in mild disability compared to moderate disability.     

Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas

AIM:To study the relationship between N-ras gene mutation and p53 gene expression in the carcinogenesis and the development of human hepatocellular carcinomas (HCC).METHODS:The N-ras gene mutation and the p53 gene expression were analyzed in 29 cases of HCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and immunohistochemistry.RESULTS:Thirteen cases of HCCs were p53 positive (44.8%), which showed a rather high Cpercen-tage of p53 gene mutation in Guangxi. The aberrations at N-ras codon 2-37 were found in 79.31% of HCCs and 80.77% of adjacent non-tumorous liver tissues. More than 2 point mutations of N-ras gene were observed in 22 cases (75.86%). Twelve cases (41.37%) of HCCs showed both N-ras gene mutation and p53 gene expression.CONCLUSION:N-ras gene and p53 gene may be involved in the carcinogenesis and the development of HCC.That 38% of HCCs with N-ras gene mutation did not express p53 protein indicates that some other genes or factors may participate in the carcinogenesis and the development of HCC.     

Nursing workforce. Skirting the issue

A study of part-time nurses in three London trusts found that they were concentrated in lower grades and less likely to be involved in management than full-time nurses. While senior managers in the trusts were fully committed to flexible working, managers lower in the organisation felt that part-time working presented problems for continuity of care, and that part-time nurses were unwilling to work unsocial hours. A more strategic approach is needed to ensure that part-time nurses are employed most effectively at a time of acute nursing shortages.     

Pharmacokinetics of enfuvirtide in pediatric human immunodeficiency virus 1-infected patients receiving combination therapy

BACKGROUND: Enfuvirtide is the first of a new class of antiretroviral agents, the fusion inhibitors. OBJECTIVES: The primary objective of this analysis was to evaluate the pharmacokinetics of 2.0 mg/kg enfuvirtide in human immunodeficiency virus 1 (HIV-1)-infected children and adolescents when administered in combination with at least 3 other antiretrovirals. METHODS: Twenty-five HIV-1-infected pediatric patients (5-16 years of age) enrolled in an ongoing phase I/II study were included in this analysis. Patients received enfuvirtide 2.0 mg/kg sc twice daily (bid) for at least 7 days. Blood samples were collected on day 7, and plasma concentrations of enfuvirtide and its metabolite were measured by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetics measures [Cmax, tmax, Ctrough, and area under the concentration time curve time 0 to 12 hours (AUC12 hours)] were calculated from plasma concentration-time data by standard noncompartmental methods. RESULTS: There was no significant difference between children and adolescents for enfuvirtide Cmax (6.43 versus 5.88 microg/mL), Ctrough (2.87 versus 2.98 microg/mL) and AUC12 hours (56.1 versus 52.7 hours . microg/mL). Similarly no significant differences were found when the pharmacokinetic measures were compared based on sexual maturity stages. A post hoc regression analysis based on AUC12 hours showed that body weight-adjusted dosing of enfuvirtide provides drug exposure that is independent of age group, body weight and body surface area. CONCLUSIONS: Body weight-adjusted dosing of enfuvirtide, at a dose of 2.0 mg/kg sc bid, in HIV-1-infected pediatric patients at least 5 years of age, provides drug exposure comparable with that previously observed in HIV-1-infected adults after 90 mg sc bid dosing. Drug exposure in children and adolescents is independent of age group, body weight, body surface area and sexual maturity stage.     

Excision of a recurrent mediastinal cyst through mid sternotomy with high thoracic epidural anesthesia as the sole anesthetic—A case report

Conclusion Our case report highlights the possibility of tackling mediastinal, pericardial and pleural problems with regional anesthesia alone even if the surgery requires opening of the pleura.     

Defining the pathogenic involvement of desmoglein 4 in pemphigus and staphylococcal scalded skin syndrome

Desmogleins (Dsgs), cadherin-type cell adhesion molecules, are targeted in skin-blistering diseases such as pemphigus and staphylococcal scalded skin syndrome (SSSS). The role of Dsg4, a new isoform, was investigated in these diseases. Dsg4 was recognized by 30 (77%) of 39 pemphigus sera containing anti-Dsg1 IgG but not by 16 pemphigus sera containing no anti-Dsg1 IgG or by 34 normal control sera. The Dsg4 immunoreactivity of these sera was abolished by removal of anti-Dsg1 IgG. Conversely, the removal of anti-Dsg4 IgG from pemphigus sera reduced the immunoreactivity against Dsg1 only 13.8% +/- 8.8% (n = 23) and did not affect its ability to induce blisters in neonatal mice. IgG that was affinity-purified on Dsg4 recognized Dsg1 but failed to induce blisters, while IgG purified on Dsg1 from the same pemphigus foliaceus sera induced blisters. Thus, pemphigus sera show Dsg4 reactivity due to cross-reactivity of a subset of anti-Dsg1 IgG, and the Dsg4/Dsg1-cross-reacting IgG has no demonstrable pathogenic effect. In addition, Dsg4 was not cleaved by exfoliative toxins that induce blisters in SSSS. These findings suggest that Dsg4 may play a role other than adhesion and that the cross-reactivity of desmoglein autoantibodies should be factored into the framework of future studies of autoimmune mechanisms in pemphigus.