Congenital generalized lipodystrophy: identification of novel variants and expansion of clinical spectrum

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder with two major subtypes. Variants in AGPAT2 result in CGL type 1 with milder manifestations, whereas BSCL2 variants cause CGL type 2 with more severe features. Muscle hypertrophy caused by lack of adipose tissue is present early in life in CGL patients. Our aim was to investigate 10 CGL patients from 7 different countries and report genotype–phenotype relationships. Genetic analysis identified disease‐causing variants in AGPAT2 (five patients) and in BSCL2 (five patients), including three novel variants; c.134C>A (p.Ser45*), c.216C>G (p.Tyr72*) in AGPAT2 and c.458C>A (p.Ser153*) in BSCL2. We also report possible novel clinical features such as anemia, breast enlargement, steatorrhea, intraventricular hemorrhage and nephrolithiasis in CGL patients. Generalized lipodystrophy and muscular hypertrophy were the only features in all of our patients. Hepatomegaly was the second common feature. Some manifestations were exclusively noticed in our CGL2 patients; hypertrichosis, high‐pitched voice and umbilical hernia. Bone cysts and history of seizures were noticed only in CGL1 patients. The findings of this study expand our knowledge of genotype–phenotype correlations in CGL patients. These results have important clinical applications in diagnosis and management of the CGL patients as well as in genetic counseling in families at‐risk.     

Epidemiology of rheumatic musculoskeletal disorders in the developing world

The epidemiology of rheumatic musculoskeletal (MSK) disorders in the developing world is much less well known than it is in the developed world. We expect ethnicity, traditions, socioeconomics and lifestyles to have an impact, but overall data are sparse. This report focuses on the WHO-ILAR COPCORD (community-oriented programme for control of rheumatic diseases). COPCORD was designed to collect community data on pain and disability in the developing economies. Several countries in Asia-Pacific and Central South America have completed COPCORD surveys. Despite some limitations in methodology, COPCORD provides a fair estimate of the spectrum and extent of rheumatic MSK disorders. We digress from a general overview to highlight the scenario for rheumatoid arthritis, and draw a few parallels with known statistics from the developed world. Overall, the emerging spectrum and severity are not very different, but in the developing countries the burden of disease, worsened by dismal rheumatology services, is likely to be staggering.     

Treatment of health-care-associated infections caused by Gram-negative bacteria: a consensus statement

This consensus statement presents the conclusions of a group of academic and industrial experts who met in London in September, 2006, to consider the issues associated with the treatment of hospital infections caused by Gram-negative bacteria. The group discussed the severe clinical problems arising from the emergence of antibiotic resistance in these bacteria and the lack of new antibacterial agents to challenge the threat. The discovery of new drugs active against hospital-acquired Gram-negative bacteria is essential to prevent a future medical and social catastrophe. An important strategy to promote drug discovery will be the development of focused cooperations between academic institutions and small pharmaceutical companies.     

30 years after Alma-Ata: has primary health care worked in countries?

We assessed progress for primary health care in countries since Alma-Ata. First we analysed life expectancy relative to national income and HIV prevalence to identify overachieving and underachieving countries. Then we focused on the 30 low-income and middle-income countries with the highest average yearly reduction of mortality among children less than 5 years of age, describing coverage and equity of primary health care as well as non-health sector actions. These 30 countries have scaled up selective primary health care (eg, immunisation, family planning), and 14 have progressed to comprehensive primary health care, marked by high coverage of skilled attendance at birth. Good governance and progress in non-health sectors are seen in almost all of the 14 countries identified with a comprehensive primary health care system. However, these 30 countries include those that are making progress despite very low income per person, political instability, and high HIV/AIDS prevalence. Thailand has the highest average yearly reduction in mortality among children less than 5 years of age (8.5%) and has achieved universal coverage of immunisation and skilled birth attendance, with low inequity. Lessons learned from all these countries include the need for a nationally agreed package of prioritised and phased primary health care that all stakeholders are committed to implementing, attention to district management systems, and consistent investment in primary health-care extension workers linked to the health system. More detailed analysis and evaluation within and across countries would be invaluable in guiding investments for primary health care, and expediting progress towards the Millennium Development Goals and "health for all".     

Alma-Ata 30 years on: revolutionary, relevant, and time to revitalise

In this paper, we revisit the revolutionary principles-equity, social justice, and health for all; community participation; health promotion; appropriate use of resources; and intersectoral action-raised by the 1978 Alma-Ata Declaration, a historic event for health and primary health care. Old health challenges remain and new priorities have emerged (eg, HIV/AIDS, chronic diseases, and mental health), ensuring that the tenets of Alma-Ata remain relevant. We examine 30 years of changes in global policy to identify the lessons learned that are of relevance today, particularly for accelerated scale-up of primary health-care services necessary to achieve the Millennium Development Goals, the modern iteration of the "health for all" goals. Health has moved from under-investment, to single disease focus, and now to increased funding and multiple new initiatives. For primary health care, the debate of the past two decades focused on selective (or vertical) versus comprehensive (horizontal) delivery, but is now shifting towards combining the strengths of both approaches in health systems. Debates of community versus facility-based health care are starting to shift towards building integrated health systems. Achievement of high and equitable coverage of integrated primary health-care services requires consistent political and financial commitment, incremental implementation based on local epidemiology, use of data to direct priorities and assess progress, especially at district level, and effective linkages with communities and non-health sectors. Community participation and intersectoral engagement seem to be the weakest strands in primary health care. Burgeoning task lists for primary health-care workers require long-term human resource planning and better training and supportive supervision. Essential drugs policies have made an important contribution to primary health care, but other appropriate technology lags behind. Revitalisng Alma-Ata and learning from three decades of experience is crucial to reach the ambitious goal of health for all in all countries, both rich and poor.     

Spectrum of haemoglobinopathies in a tertiary care hospital of armed forces

Background: Thalassaemia and other structural haemoglobinopathies are the major genetic disorders prevalent in certain parts of the world including India. This study presents the pattern of haemoglobinopathies amongst the referred patients of anaemia in a two-year period.     

Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a polymeric absorption enhancer: synthesis, characterization and applications

In recent years, researchers have been working extensively on various novel properties of polymers to develop increased efficiency of drug delivery and improve bioavailability of various drug molecules, especially macromolecules. Chitosan, a naturally occurring polysaccharide, because of its protonated/polymeric nature, provides effective and safe absorption of peptide and protein drugs. Its transmucosal absorption is, however, limited to acidic media because of its strong intermolecular hydrogen bonds. A new partially quaternized chitosan derivative, N-trimethyl chitosan chloride (TMC), has been synthesized with improved solubility, safety and effectiveness as an absorption enhancer at neutral pH and in aqueous environment. It enhances the absorption, especially of peptide drugs, by reversible opening of tight junctions in between epithelial cells, thereby facilitating the paracellular diffusion of peptide drugs. This derivative thus opens new perspectives as a biomaterial for various pharmaceutical applications/drug delivery systems. This review deals with the potential use of the quaternized chitosan derivative as a permeation enhancer for the mucosal delivery of macromolecular drugs along with its other biomedical applications.