Quaternary ammonium compounds and occupational asthma

Objective: Quaternary ammonium compounds, among which benzalkonium chloride is one of the best-known, are commonly used as antiseptics, disinfectants, detergents and preservatives. They can cause occupational asthma, which however, has been rarely reported so far, despite wide use of these products. We report three such cases. Possible mechanisms causing asthma are discussed, taking into account their characteristics. Methods and results: Our patients, all female nurses, manifested asthma symptoms upon handling disinfectant solutions containing benzalkonium chloride. Work-related fall in PEFR was observed in all of them. The diagnosis was confirmed by challenge tests where the patients were exposed, in a closed chamber, to suspected disinfectant contained in a tray. All of the women developed early or delayed symptoms upon exposure. Similar challenge tests to placebo or other disinfectants devoid of quaternary ammonium compound were negative. Conclusion: These three cases, in addition to others reported in the literature, point out an as yet poorly known etiology of occupational asthma to quaternary ammonium compounds in hospital employees. The exact mechanism of the action remains unexplained. Received: 20 October 1999 / Accepted: 25 March 2000     

The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours

2-Methoxyoestrogens are emerging as a new class of drug that can inhibit tumour growth and angiogenesis. As sulphamoylation of oestrogens enhances their potency and bioavailability we have synthesized 2-methoxyoestrone-3-O-sulphamate (2-MeOEMATE) and compared its ability to inhibit the proliferation of breast cancer cells with that of 2-methoxyoestrone (2-MeOE1). 2-MeOEMATE (1 microM) inhibited the growth of oestrogen receptor positive MCF-7 breast cancer cells by 52% whereas 2-MeOE1 had little effect at this concentration. 2-MeOEMATE also inhibited the growth of oestrogen receptor negative MDA-MB-231 breast cancer cells. Exposure of cells to 2-MeOEMATE caused them to round up and become detached suggesting that this compound may induce cells to undergo apoptosis. Cell cycle analysis revealed that 2-MeOEMATE caused cells to arrest in the G(2)/M phase with the increase in G(2)/M arrested cells being detectable by 12 hr. Exposure of MCF-7 cells to 2 L-MeOEMATE for 24 hr followed by culture in drug-free medium for 24 hr did not reverse the arrest of cells in the G(2)/M phase. TUNEL analysis confirmed that 2-MeOEMATE induced apoptosis in a significant proportion of treated MCF-7 cells. In an in vivo study, employing nitrosomethylurea-induced mammary tumours in intact rats, 2-MeOE1 (20mg/kg/d, p.o. for 11 days) had little effect on tumour growth. In contrast, the same dose of 2-MeOEMATE resulted in the almost complete regression of 2/3 tumours over an 11-day period. We conclude that 2-MeOEMATE should have considerable therapeutic potential for the treatment of breast tumours.     

Cerebral zygomycosis

Fifty-six patients with cerebral zygomycosis (mucormycosis) were seen during the period 1971-2001 in two tertiary care hospitals located in south India with tropical climate and catering to neurological diseases. Forty-four patients had rhinocerebral and twelve patients had isolated central nervous system (CNS) zygomycosis. Of these, ten were culture proven (Rhizopus oryzae in eight and Mucor in two); 30 were diagnosed as probable and 16 were diagnosed possible; mixed infections were seen in three patients. Diabetes mellitus was the predisposing condition in a majority (31/44) of patients with the rhinocerebral form of zygomycosis. The tissue obtained at biopsy/autopsy in either form showed necrotic/infarcted tissue with neutrophilic infiltration with broad non-septate hyphae showing irregular branching. The outcome was poor despite surgical excision and antifungal therapy. The high concentration of spores in a mouldy environment, the bird population and improper disposal of hospital waste may facilitate healthy hosts presenting with primary CNS disease.     

Cancer biology and necrotic changes in metastatic lymph nodes and survival of colon cancer patients

BACKGROUND: Identifying factors that can contribute to a better understanding of tumor progression in stage III colon cancer patients continues to be an important task. Necrotic changes in metastatic lymph nodes have not been previously analyzed in English literature. METHODS: The study included 48 consecutive colon and rectosigmoid cancer patients with stage III disease who underwent radical surgery. After reviewing the diagnostic slides, a pathologist developed a scale describing the extent of necrotic changes. Results were evaluated using Kaplan-Meier method and log-rank test. RESULTS: Thirty-four (70%) patients had necrotic changes in metastatic lymph nodes. Patients with necrotic changes in metastatic lymph nodes had more risk factors than patients without necrosis. The 5-year survival rate for patients with necrotic changes in metastatic lymph nodes was 85% and for patients without necrosis was 50% (P = 0.02). CONCLUSIONS: The survival of patients with necrotic changes in metastatic lymph nodes was higher (P = 0.02). These necrotic changes can help us to understand body-tumor relations.     

New anatomic repair of midline abdominal wall incisions extending to suprapubic region

This article describes a new technique to close infraumbilical midline abdominal wall incisions extending to the suprapubic region. This repair is technically easy to perform, saves time, reduces the risk of bowel and bladder injury and takes into consideration the anatomical landmarks of the peritoneum, the rectus sheath and the arcuate line. Abdominal wall closure with this repair is especially useful in obese patients. Furthermore, with this repair the pelvic cavity is lined with smooth peritoneum, which may reduce postoperative adhesions in the pelvis. Technically easy to perform and saves time Very useful technique for obese patients Reduced risk of bowel and bladder injury Anatomical in nature Potentially minimizes postoperative adhesions.     

Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children

OBJECTIVE: To study the association of Attention Deficit Hyperactivity Disorder (ADHD) and polymorphism in the dopamine beta hydroxylase (DBH) gene in Indian ADHD cases. SUBJECTS: Forty one ADHD cases were diagnosed as per the DSM-IV-TR criteria and evaluated by Conners Parents and Teachers Rating Scale and Wechslers Intelligence Scale for Children. METHODS: Genomic DNA was amplified for exon 2 *444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis. Haplotype-based haplotype relative risk (HHRR) was analyzed to ascertain the transmission pattern of these two polymorphisms in ADHD cases. Linkage disequilibrium (LD) between the two polymorphisms was calculated using EH+ and 2LD programs. RESULTS: In the limited number of samples analyzed, a slight increase in transmission of the 444a allele in ADHD subjects was observed for DBH 444g/a. The intron 5 (Taq I) polymorphism showed no significant association with ADHD in these cases. Strong disequilibrium was observed between DBH444g/a and intron 5 (Taq I) polymorphism. CONCLUSION: This is the first molecular genetic study on ADHD in Indian subjects exploring transmission of polymorphisms in the DBH gene. Preliminary investigation shows a trend towards association between the transmission of DBH444a allele and ADHD. No association was noticed between transmission of intron 5 (Taq I) polymorphism and ADHD in the Indian subjects. Presence of strong LD may point towards co-segregation of these two polymorphisms more often than expected.     

A new tool for measurement of process-based performance of multispecialty tertiary care hospitals

There is an increasing need of a model for the process-based performance measurement of multispecialty tertiary care hospitals for quality improvement. Analytic hierarchy process (AHP) is utilized in this study to evolve such a model. Each step in the model was derived by group-discussions and brainstorming sessions among experienced clinicians and managers. This tool was applied to two tertiary care teaching hospitals in Barbados and India. The model enabled identification of specific areas where neither hospital performed very well, and helped to suggest recommendations to improve those areas. AHP is recommended as a valuable tool to measure the process-based performance of multispecialty tertiary care hospitals.     

Inter-state disparities in health care and financial burden on the poor in India

Over five decades of independence, India has made rapid strides in various sectors. However, its performance in social sectors and particularly the healthcare sector has not been too rosy. Being the State's responsibility the healthcare has traditionally been influenced by individual State's budgetary allocation. Consequently inter-state disparity in availability and utilization of health services and health manpower are distinctly marked. This has implications for achievement of Health for All for the nation as a whole. Keeping in view the significance of studying inter-state variations in healthcare, this study focuses on the performance of healthcare sector in 15 major States in India. This is attempted through a comparative analysis of various parameters depicting availability of health services, their utilization and health outcomes. Our analysis depicts the prevalence of considerable inequity favoring high income group of States. In terms of healthcare resources, for instance, it indicates that the high income States hold a superior position in terms of: per capita government expenditure on medical and public health, total number of hospitals and dispensaries, per capita availability of beds in hospitals and dispensaries and health manpower in rural and urban areas. These parameters of availability have an impact on utilization levels and health outcomes in these States. A comparative profile of high and low income States as well as middle and low income States, both in rural and urban areas, reaffirms a greater financial burden in availing treatment at OPD and inpatient in low income States. In line with the higher financial burden and low per capita health expenditure, the health outcome indicators also depict a disconcerting situation in regard to low income States. These States are marked by lower life expectancy and higher incidence of diseases as well as high mortality rates. In this regard, demand as well as supply side constraints are observed which restrain the optimum utilization of existing health services. Among the low income States the main constraints on the demand side include illiteracy, malnutrition, and lack of infrastructure in accessing the facilities. Certain state specific supply side factors add significantly to under-utilization in low income States. In some of the States, however, corrective actions have been initiated to overcome the problem of the quality and low utilization of health facilities. In due course of time, it is likely that proper implementation of these measures may result in improved utilization level of existing health services, which may be useful to improve health status indicators. Nonetheless, overcoming the current levels of regional disparities in healthcare across three income groups of States may also require additional resources. The latter could be mobilized through assistance of donor agencies and appropriate mix of social and private insurance. Ultimately mitigating the problem of regional disparities in healthcare and protecting the poor and vulnerable from financial burden may require establishing and maintaining proper linkages between socio-economic development and healthcare planning.