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.     

Optimization and pharmacological characterization of receptor‐mediated Gi/o activation in postmortem human prefrontal cortex

The biochemical abnormalities in transmembrane signal transduction mediated through G protein‐coupled receptors (GPCRs) have been postulated as underlying pathophysiology of psychiatric diseases such as schizophrenia and mood disorders. In the present study, the experimental conditions of agonist‐induced [³⁵S]GTPγS binding in postmortem human brain membranes were optimized, and the responses induced by a series of agonists were pharmacologically characterized. The [³⁵S]GTPγS binding assay was performed in postmortem human prefrontal cortical membranes by means of filtration techniques, and standardized as to GDP concentration, membrane protein content, MgCl₂ and NaCl concentrations in assay buffer, incubation period and effect of white matter contamination. Under the standard assay conditions, the specific [³⁵S]GTPγS binding was stimulated by the addition of 15 compounds in a concentration‐dependent manner. Of these agonists, R(+)‐8‐OH‐DPAT, UK‐14,304, DAMGO and DPDPE showed apparently biphasic concentration‐response curves. As for these four responses, only higher‐potency site was pharmacologically characterized. The receptors involved in the responses investigated were 5‐HT_1A receptor (probed with R(+)‐8‐OH‐DPAT or 5‐HT), α_2A‐adrenoceptor (UK‐14,304 or (?)‐epinephrine), M₂/M₄ mAChRs (carbachol), adenosine A₁ receptor (adenosine), histamine H₃ receptor (histamine), group II mGlu (l ‐glutamate), GABA_B receptor (baclofen), μ‐opioid receptor (DAMGO or endomophin‐1), δ‐opioid receptor (DPDPE or SNC‐80) and NOP (nociceptin). Although dopamine also activated specific [³⁵S]GTPγS binding, this response was likely mediated via α_2A‐adrenoceptor, but not dopamine receptor subtypes. The present study provides us with fundamental aspects of the strategy for elucidation of probable abnormalities of neural signalling mediated by G proteins activated through multiple GPCRs in the brain of psychiatric patients.     

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.     

The regenerative potential of fibroblasts in a new diabetes‐induced delayed humanised wound healing model

Cutaneous diabetic wounds greatly affect the quality of life of patients, causing a substantial economic impact on the healthcare system. The limited clinical success of conventional treatments is mainly attributed to the lack of knowledge of the pathogenic mechanisms related to chronic ulceration. Therefore, management of diabetic ulcers remains a challenging clinical issue. Within this context, reliable animal models that recapitulate situations of impaired wound healing have become essential. In this study, we established a new in vivo humanised model of delayed wound healing in a diabetic context that reproduces the main features of the human disease. Diabetes was induced by multiple low doses of streptozotocin in bioengineered human‐skin‐engrafted immunodeficient mice. The significant delay in wound closure exhibited in diabetic wounds was mainly attributed to alterations in the granulation tissue formation and resolution, involving defects in wound bed maturation, vascularisation, inflammatory response and collagen deposition. In the new model, a cell‐based wound therapy consisting of the application of plasma‐derived fibrin dermal scaffolds containing fibroblasts consistently improved the healing response by triggering granulation tissue maturation and further providing a suitable matrix for migrating keratinocytes during wound re‐epithelialisation. The present preclinical wound healing model was able to shed light on the biological processes responsible for the improvement achieved, and these findings can be extended for designing new therapeutic approaches with clinical relevance.     

Perceived psychosocial outcomes of gastric bypass surgery: a qualitative study

Background: Attempts to understand postoperative psychosocial changes in the lives of individuals who have undergone gastric bypass surgery for morbid obesity have 1) been guided by constructs emanating from the assumptions of researchers, and 2) have resulted in fragmented conclusions that catalogue changes without theoretically integrating them. Materials and Methods: Using unstructured and semi-structured interviews and in-depth focus groups, 31 patients were asked in an open-ended fashion about the ways, if any, in which gastric bypass surgery had affected their lives. Grounded theory methodology was utilized in order to identify emergent themes and their interrelations, and build a meaningful, comprehensive theory of life after gastric bypass. Results: Patients' report of a rebirth/transformation was identified as the core process of the theory. The changes marking this process were clearly conceptualized in dichotomous terms comparing pre to postsurgical life. Patients reported changes that they regarded as unequivocally positive, a number of which had not been previously reported in the literature. Unique to this particular study was the finding of numerous life changes that generated tension and posed challenges in various aspects of patients' lives. Conclusion: The grounded theory proposes that the extent to which patients successfully negotiate tension-generating changes may be a major determinant in the long-term outcome of gastric bypass, both weight loss and psychosocial adjustment.     

Quantitative stoichiometry of G-proteins activated by mu-opioid receptors in postmortem human brain

Paradoxically, the potencies (EC(50)) of agonists stimulating [35S]GTPgammaS binding are several orders of magnitude lower than their affinities in receptor binding assays. We have investigated the quantitative stoichiometry of mu-opioid receptor-G-protein coupling in postmortem human brain. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO) displaced [3H]naloxone binding in a biphasic pattern. The ratio between K(i-low) and EC(50) of DAMGO stimulating [35S]GTPgammaS binding was lower than one. The K(A) of DAMGO was calculated following mu-opioid receptor alkylation by beta-funaltrexamine from [35S]GTPgammaS binding data using the "nested hyperbolic method", yielding K(A)/EC(50)>1. Thus, only 1.2 +/- 0.2% of mu-opioid receptors was needed to be occupied to achieve the half-maximal effect of DAMGO. The estimated ratio between the G-proteins activated by 10 microM DAMGO (determined by isotopic dilution curves) and the occupied-mu-opioid receptors was 1304. In conclusion, we have determined the stoichiometric and the kinetic parameters in the mu-opioid receptor-G-protein system.     

Men with prostate cancer: influence of psychological factors on informational needs and decision making

OBJECTIVES: Studies indicate that men with prostate cancer (MPC) adopt passive roles in cancer management; however, increasing public awareness of prostate cancer and advocacy by MPC and their allies suggest otherwise. This study looks at the information that is important to MPC; their preferred participation in decision making; and the influence of sociodemographic, disease, and psychological factors on information needs and decision preferences. METHOD: Consecutive men diagnosed with prostate cancer and attending two tertiary care cancer clinics completed questionnaires on information needs and decision preferences. Questions included demographic information, health and disease status, psychosocial functioning, optimism, and decisional preferences and information preferences for content, type, focus, format, and amount. RESULTS: Questionnaires were completed by 101 MPC. Their mean age was 70 years and most were married and well-educated. Over 70% wanted detailed information at all illness stages focusing on their disease, treatment, survival, self-care, and empowerment. Over 60% of MPC wanted shared decision making with their physician. Psychological variables were found to influence information needs but not involvement in decision making. CONCLUSION: These results represent a challenge to health-care providers for accomodating the informational needs and decision preferences of individual MPC.