Cost-effectiveness of a novel strategy of HIV/AIDS care in Armed Forces: A stochastic model with Monte Carlo simulation.

BACKGROUND: Despite the initial success of HIV/AIDS policy, an increasing number of patients are failing the first-line antiretroviral therapy (ART) each year and the failure rates are increasing. There is a need for identification of novel strategies to reduce failure rates. The aims of the study are (1) to design a novel strategy to reduce ART failure rates and (2) to create a stochastic model using Monte Carlo (MC) simulation comparing the novel strategy with existing strategy. METHODS: A novel strategy based on annual plasma viral load testing and resistance testing for HIV treatment at baseline and at the time of failure was designed. A cohort of 1000 patients each was created for the existing strategy and a novel strategy. Assumptions were included from Indian studies and own data. The two strategies were compared over 20 years of follow-up using stochastic modeling and MC simulation was done for death rates, failure rates, and cost-effectiveness analysis. SimVoi add-in software for MS Excel was used for simulations. Student's t-tests were performed for comparing continuous variables, and the cumulative rates for various outcomes were plotted using Kaplan-Meier analysis. RESULTS: The novel strategy resulted in lower mortality over a 20-year period (279.9 + 7.13 deaths vs 130.43 + 6.03 deaths) with incremental cost per life saved at Rs 32,925 per year. Incremental cost-effectiveness ratio cost per quality-adjusted life year was Rs 1.33 lakhs/annum at constant rate of discounting and just under Rs 90,000 per annum using differential discounting. CONCLUSION: Armed Forces are likely to benefit by adopting the novel strategy that is cost-effective with a significant mortality benefit.

Determination of lead and cadmium concentration limits in agricultural soil and municipal solid waste compost through an approach of zero tolerance to food contamination.

Cadmium and lead are important environmental pollutants with high toxicity to animals and human. Soils, though have considerable metal immobilizing capability, can contaminate food chain via plants grown upon them when their built-up occurs to a large extent. Present experiment was carried out with the objective of quantifying the limits of Pb and Cd loading in soil for the purpose of preventing food chain contamination beyond background concentration levels. Two separate sets of pot experiment were carried out for these two heavy metals with graded levels of application doses of Pb at 0.4-150 mg/kg and Cd at 0.02-20 mg/kg to an acidic light textured alluvial soil. Spinach crop was grown for 50 days on these treated soils after a stabilization period of 2 months. Upper limit of background concentration levels (C(ul)) of these metals were calculated through statistical approach from the heavy metals concentration values in leaves of spinach crop grown in farmers' fields. Lead and Cd concentration limits in soil were calculated by dividing C(ul) with uptake response slope obtained from the pot experiment. Cumulative loading limits (concentration limits in soil minus contents in uncontaminated soil) for the experimental soil were estimated to be 170 kg Pb/ha and 0.8 kg Cd/ha. Based on certain assumptions on application rate and computed cumulative loading limit values, maximum permissible Pb and Cd concentration values in municipal solid waste (MSW) compost were proposed as 170 mg Pb/kg and 0.8 mg Cd/kg, respectively. In view of these limiting values, about 56% and 47% of the MSW compost samples from different cities are found to contain Pb and Cd in the safe range.

An assessment of municipal solid waste compost quality produced in different cities of India in the perspective of developing quality control indices.

A study was conducted to investigate physico-chemical properties, fertilizing potential and heavy metal polluting potentials of municipal solid waste composts produced in 29 cities of the country. Results indicated that except a very few samples, all other samples have normal pH and EC. Organic matter as well as major nutrients N and P contents in MSW composts are generally low as compared to the composts prepared from rural wastes. Heavy metal contents in composts from bigger cities (>1 million population) were higher by about 86% for Zn, 155% for Cu, 194% for Cd, 105% for Pb, 43% for Ni and 132% for Cr as compared to those from smaller cities (<1 million population). Composts prepared from source separated biogenos wastes contained, on average, higher organic matter (by 57%), total N (by 77%) and total P (by 78%), but lower concentrations of heavy metals Zn (by 63%), Cu (by 78%), Cd (by 64%), Pb (by 84%), Ni (by 50%), and Cr (by 63%) as compared to those prepared from mixed wastes. Partial segregation at the site of composting did not improve quality of compost significantly in terms of fertilizing parameters and heavy metal contents. Majority of MSW composts did not conform to the quality control guideline of 'The Fertilizer (Control) Order 1985' in respect of total organic C, total P, total K as well as heavy metals Cu, Pb and Cr. In order to enable the relevant stakeholders to judge overall quality, a scheme has been proposed for the categorization of composts into different marketable classes (A, B, C, and D) and restricted use classes (RU-1, RU-2, and RU-3) on the basis their fertilizing potential and as well as potential for contaminating soil and food chain. Under the scheme, 'Fertilizing index' was calculated from the values of total organic C, N, P, K, C/N ratio and stability parameter, and 'Clean index' was calculated from the contents of heavy metals, taking the relative importance of each of the parameters into consideration. As per the scheme, majority of the compost samples did not belong to any classes and hence, have been found unsuitable for any kind of use. As per the regulatory limits of different countries, very few compost samples (prepared from source separated biogenos wastes) were found in marketable classes (A, B, C and D) and some samples (11-14) were found suitable only for some restricted use.

Does Down syndrome affect the outcome of congenital duodenal obstruction?

Congenital duodenal obstruction (DO) has a well-known association with Down syndrome (DS) and other congenital malformations. Previously reported series on DO have not examined the influence of DS on associated congenital malformations and postoperative morbidity and mortality. We report on a retrospective study of all children born with DO over an 11-year period to investigate this. A total of 79 patients with DO were studied: group 1 consisted of 51 (64.6%) children without DS, and group 2 consisted of 28 (35.4%) children with DS. There was no significant difference in mean gestational age and birth weight between groups 1 and 2. A coexisting congenital malformation was found in 68% of patients. Gastrointestinal malformations were the most common in group 1 (71.1%), and cardiac malformations were the most common in group 2 (81.5%). The mean time to reach full intragastric feeds was 12 days, with no significant difference between the two groups ( p=0.383). Seven (8.9%) patients developed a postoperative complication, with no significant difference between both groups ( p=0.853). A total of 11 patients died: six (12%) in group 1 and five (28%) in group 2, with no significant difference between the groups ( p=0.454). DS does not influence the morbidity and mortality of DO but does carry a higher incidence of congenital cardiac abnormalities. Delayed mortality was a result of coexisting congenital cardiac and respiratory disease.

Blood gases, hematology, and renal blood flow during prolonged mountain sojourns at 3500 and 5800 m.

BACKGROUND: This study mainly focused on renal blood flow, hematological parameters, blood gases, and blood pH, which are affected on exposure to moderate (3500 m) and extreme altitudes (5800 m) in sea level residents. HYPOTHESIS: Acute and prolonged exposure to high or extreme altitude may cause pathophysiological changes in kidney and renal plasma/blood flow, leading to retention of fluids in the tissues. Combined with the decreased availability of oxygen to the tissues, these may be responsible for high altitude maladies. METHOD: Fifteen male sea level (SL) volunteers, 22-25 yr old, were studied for blood gases, blood viscosity, hematocrit, hemoglobin concentration, and effective renal blood/plasma flow at Delhi (260 m), 3500 m (60 d stay), 5800 m (70 d stay), and 7 d after return to SL. RESULTS: Compared with SL, a significant increase from 7.34 to 7.43 (p < 0.01) in blood pH was observed at 3500 m that remained significantly increased at 5800 m. PO2 was about 39% less at 5800 m than at SL. PCO2 reduced significantly from 42.07 to 28.05 mm Hg on return from 5800 m to SL. The blood viscosity increased significantly (38%) at 5800 m and decreased significantly by 38% (p < 0.01) after return to SL. The effective renal plasma flow reduced significantly (p < 0.01) from 615.6 at SL to 381.5 ml x min(-1) x 1.73 m(-2) at 5800 m. CONCLUSION: The study suggests a crucial role of renal function in the acclimatization process; renal function also appears to be one factor by which the body protects itself against severe hypoxia.

Long-term effects of intercropping and bio-litter recycling on soil biological activity and fertility status of sub-tropical soils.

On-farm field experiments were carried out at two sites having 38- and 10-year-old orchard cropping systems under sub-tropical climatic regions to evaluate changes in organic carbon accumulation and chemical and microbiological properties of the soils. Under a system of different intercropped fruit trees, the cultivation of coconut (Cocos nucifera L.) intercropped with guava (Psidium guajava L.) enhanced the soil microbial activity approximately 2-fold after 38 yrs over 10 yrs of the same intercropped system. Soil organic carbon increased from 3.4 to 7.8 and 2.4 to 6.2 g kg-1 after 38 and 10 yrs, respectively, following the establishment of orchards. The increase was attributed to greater recycling of bio-litters. Levels of dehydrogenase, phosphatase and soil microbial biomass under field conditions generally depended more on the nature of the cropping system than on soil types. Similarly, average carbon inputs of bio-litter to the soil in monocrop (0.98 Mg ha-1 yr-1) was less than intercropped fruit trees (2.07 Mg ha-1 yr-1). The average level of soil microbial biomass carbon was 1158 kg ha-1 (0-0.15 m depth) and the organic carbon turnover rate was 8.5 yr-1 after 38 yrs of intercropped fruit trees, which resulted in a lower ratio (1.81) of carbon inputs to soil microbial biomass carbon.

Effect of time exposure to high altitude on zinc and copper concentrations in human plasma.

BACKGROUND: Research has focused mainly on the relationship of zinc and copper contents and physical stresses like running, cycling, etc. It has also been reported that other forms of stresses change the concentration of these trace elements in humans. However,there are no reports on the effects of high altitude induced hypoxic stress on the plasma levels of these metals. Since hypoxia is one of the important stresses, we considered it appropriate to observe the changes in the levels of zinc and copper concentrations and in certain related zinc and copper enzymes and hormones in the plasma of human volunteers on acute induction to high altitude. From these findings, we intended to ascertain whether supplementation of these trace elements would be required for optimal health under such conditions. HYPOTHESIS: On acute induction to hypoxia, contents of these trace elements may change as the requirements of stressed organs and tissue may increase. Hence, further supplementation may be beneficial under hypoxic stress for better adaptability. METHOD: Volunteers were divided into two groups: with and without zinc and copper salt supplementation. Blood samples were collected at sea level and on induction to acute hypoxia on days 3 and 10. Trace mineral contents and their related enzyme (alkaline phosphatase) and hormone (ceruloplasmin) levels were determined in plasma samples. RESULTS: Plasma zinc contents were significantly reduced upon induction to high altitude in the non-supplemented group, but not in the zinc-supplemented group. Alkaline phosphatase activity increased significantly upon induction to the high altitude stress. The enzyme activity remained elevated up to day 10 of the stress. Plasma copper contents and ceruloplasmin activity did not change upon induction to high altitude. CONCLUSION: Under hypoxic stress, circulating levels of zinc and alkaline phosphatase in plasma changed appreciably as plasma zinc was transported into the organs and tissues. However, circulating levels of copper and ceruloplasmin in plasma did not change, indicating no extra supplementation of copper is required under hypoxic stress.

Improved high altitude hypoxic tolerance and amelioration of anorexia and hypophagia in rats on oral glutamate supplementation.

BACKGROUND: The objective of this study is to evaluate the efficacy of oral glutamic acid supplementation in promoting hypoxic tolerance. METHODS: The experiments were conducted in albino rats by exposing them to three levels of hypoxia in a simulated environment for varying periods of time. The parameters studied include: gasping time at 35,000 ft (10,668 m), food and water intake, and heart to body weight (b.w.) ratio at 25,000 ft (7620 m), tolerance to composite stress at 15,000 ft (4572 m) and biodistribution of glutamate (glu). RESULTS: Supplementation of Glu (27 mg x kg(-1) b.w.) as glutamic acid dissolved in normal saline resulted in 4.8 times enhanced hypoxic tolerance (time taken for appearance of first gasp), 23% body weight gain and 24% increase in food consumption over control during hypoxia. When animals were subjected to composite stress of cold, hypoxia and restraint (CHR), the Glu fed animals showed higher resistance to fall in rectal temperature than the control group. Hypoxia significantly enhanced heart to body weight ratio compared with control, and Glu supplementation reduced and brought it down to that of control. CONCLUSION: The study reveals that Glu in optimal doses may be a conditionally essential amino acid resulting in enhanced tolerance to hypoxia and cold.

Nuclear factor 1 is essential for the expression of stearoyl-CoA desaturase 1 gene during preadipocyte differentiation.

Stearoyl CoA desaturase gene 1 (SCD1) is a delta 9 desaturase that is transcriptionally activated during the differentiation of 3T3-L1 preadipocytes into adipocytes. We have demonstrated that a SCD1/BP region in SCD1 proximal promoter (-114 to -86 bp) is essential for the transcriptional activation of this gene during differentiation. Mutation in this region abolished the basal activity of the proximal promoter of SCD1, and also failed to induce transcription in response to the differentiation cocktail in transfected cells. The SCD1/BP region contains a TGGCA sequence at -90 bp from the transcription start site. Using competitor oligonucleotides and nuclear factor 1 (NF1)-specific antibodies in gel shift assays, we have shown that in preadipocytes, a NF1 protein binds to this TGGCA sequence. On MDI-induced differentiation of preadipocyte into adipocyte, an additional DNA-protein complex appeared. The appearance of a new NF1 complex is related to the differentiation-specific transcriptional activation of the SCD1 gene. This is the first report to show a differentiation-related change in NF1 protein binding during preadipocyte differentiation.

Tyrosinase transfection produces melanin synthesis and growth retardation in glioma cells.

Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector. Stable transfectants were selected by their resistance to the antibiotic G418. More than a dozen G418-resistant clones were isolated and were screened for tyrosinase expression using dopa-oxidase activity. The clone with the highest tyrosinase activity was selected and expanded for further studies. Northern blot analyses of total RNA from cells showed that the transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human melanotic melanoma cells. The melanin content of the transfected cells was dependent on the concentration of L-tyrosine in the culture medium. In addition, the growth of transfected cells was inhibited when grown in a medium containing high concentrations of L-tyrosine. These results suggest that tyrosinase activity is cytotoxic in a substrate-dependent manner. This may have far reaching therapeutic use for glioma tumours.

Influence of vanadium on acclimatization of humans to high altitude.

The study was conducted on human volunteers as controls as well as after administration of vanadyl sulphate on induction to high altitude (HA) at 3500 m. The plasma vanadium contents were significantly reduced in the control group on abrupt induction to HA on days 3 and 10, indicating redistribution to other organs/tissues under the stressful situation. In the vanadium salt-treated group, plasma vanadium contents were similar to those obtained at sea-level. Administration of vanadyl sulphate did not act as a diuretic. Moreover the vanadium supplemented group drank more water and also excrete less urine than the control group.

Gap junctions in 9L and C6 glioma cells: correlation with growth characteristics.

The relationship between growth properties and gap junctional communication properties of two glioma cell lines, 9L and C6, was compared. Using microinjection of a gap junction permeable fluorescent dye, it was demonstrated that 9L cells were extensively dye coupled through gap junctions, whereas C6 cells had low levels of dye coupling between the cells. More gap junctions were observed between 9L cells than between C6 cells both by electron microscopy and immunofluorescent labelling with specific antibodies. Immunoblotting and immunofluorescence labelling of cellular proteins from 9L and C6 cells also showed differences in the Cx43 connexin contents of these cells, reflecting the differences in their gap junctional communication. Northern blot analyses confirmed that the level of Cx43 mRNA was higher in 9L than in C6 cells. In spite of these differences in gap junctions, the two cell lines did not differ in their growth rates in cultures. These results suggest a lack of direct correlation between gap junctional communication and cell growth regulation in these two glioma cell lines.

Inhibition of connexin 43 synthesis by antisense RNA in rat glioma cells.

The 9L rat glioma cells communicate via gap junctions which are formed of connexin 43. The gap junctional communication was inhibited in these cells by transfecting them with an antisense Cx43 DNA construct, and its effect on their growth rate was investigated. This construct was induced by a Zn(2+)-inducible metallothionein promoter. Results showed that the induction of antisense RNA expression in rat 9L glioma cells produced the loss of gap junctions which was reflected in the loss of gap junctional communication. By inducing the antisense construct with zinc acetate, and using specific antibodies to connexin 43, the synthesis of this connexin was inhibited in the transfected cells and gap junctions were lost on the cell-cell appositions. There was no such effect on the untransfected cells. The loss of gap junctions at cell-cell appositions also correlated with the loss of Lucifer yellow fluorescent dye transfer between the cells. The effect of loss of gap junctions on the growth rate of the cells was assessed. In spite of the drastic decrease in the number of gap junctions between cells, their growth rate was only approximately 20% less than that of the transfected but non-induced cells. Therefore, gap junction communication is not negatively related to the rate of growth of these cells.

A STUDY OF EPIDEMIOLOGICAL ASPECTS OF BURN INJURIES.

A study was conducted of the epidemiological aspects of 500 fresh cases of burns during the period February to August 1989. Women in the reproductive age group from the lower socioeconomic strata were the most frequently victims (52.8%). Four hundred and thirteen (82.5%) patients sustained accidental burns, 62 (12.4%) were suicidal and 25 (5%) homicidal. Majority (72%) of the accidents occurred as a consequence of garments catching fire. Though most of the subjects wore cotton garments, mortality was higher among those wearing synthetic fabric. Low socioeconomic conditions, overcrowding in the house, floor-level cooking, unsafe cooking appliances and the prevalent clothing pattern stand out prominently as risk factors for burn injury.

Rat glioma cell line as a model for astrogliosis.

In this investigation 9L rat glioma cells were grown on coverslips in culture, and when subjected to mechanical trauma, they were capable of mounting an astroglial response, without interaction with neurons, as evidenced by cell hypertrophy and increased immunostaining for glial fibrillary acidic protein and J1-31 antigen. It is of particular interest that this neoplastically transformed cell line is capable of mounting an astroglial response when subjected to mechanical trauma in vitro. The advantages of this model over in vivo models of central nervous system injury include the ease of reproducibility of results, and the ability to investigate molecular mechanisms under controlled conditions.

Effect of yogic exercises on thyroid function in subjects resident at sea level upon exposure to high altitude.

Using radioactive iodine, the effect of 1 month's yogic exercises has been investigated on the thyroid function of subjects resident at sea level (SL) specially after their exposure to high altitude (HA). The results have been compared with a group of SL subjects who underwent physical training (PT) exercises for the same duration. Ten healthy male volunteers in the age range of 20-30 years were used as test subjects in this study with each serving as his own control. The subjects were randomly divided into two groups of 5 each. One group practised hatha yogic exercises, while the other group performed the regular PT exercises. The thyroidal accumulation and release of radioactive iodine have been measured in each of the subjects of both groups before and after 1 month of their respective exercises at SL. One month of yogic exercises at SL has been observed to cause a significant reduction in the trans-thyroidal availability of radioiodine. The thyroid radioactivity in this group of subjects was always below normal levels with the exception of two peaks of radioactive iodine uptake, when the levels of radioactivity in the thyroid were similar to the control values of pre-yogic exercises. The release of radiolabel at 24-48 h was significantly increased after yogic exercises. In contrast, the subjects performing PT exercises for the same duration at SL showed significant thyroid uptake of radioactive iodine at 24 h. Subsequently their 131I uptake continued to rise slowly until 72 h without any demonstrable thyroidal release of radiolabel. This indicated that increased thyroid activity was induced by conventional PT exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in body fluid compartments during hypohydration and rehydration in heat-acclimated tropical subjects.

Body fluid compartments at different levels of graded hypohydration and partial rehydration were determined using radiotracers in 28 heat-acclimated, male volunteers from tropical regions of India, in hot dry conditions in a climatic chamber. These subjects were hypohydrated to varying degrees (i.e., 1%, 2%, 3%, and 4% body mass deficit) by moderate work in hot conditions in a climatic chamber maintained at 45 degrees C dry bulb temperature and 30% relative humidity. Rehydration study was carried out only in those subjects who were hypohydrated to 3% and 4% body mass and who were brought back to 2% level of hypohydration by receiving a calculated amount of water. Up to the 2% level of hypohydration, a major contribution towards sweat loss was observed from the interstitial fluid (ISF) compartment. At higher levels of hypohydration, no further significant loss from ISF was seen, though significant losses in intracellular fluid (ICF) and plasma volume (PV) were apparent. The present study also found that at the 4% hypohydration level, a maximum fluid contribution was met by the ICF compartment. Significant increases observed in sweat K+ at 3 and 4% also indicate the ICF mobilization, which is rich in K+ ions. On partial rehydration, the ISF compartment held the repletion fluid in excess, and was found to be enough to restore sweat rate to euhydration level. This study clearly indicates that sudorific gain is achieved with partial restoration alone in subjects hypohydrated to 3 and 4% levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroidal handling of radioiodine in sea level residents exposed to hypobaric hypoxia.

In the present investigation thyroidal accumulation of radioiodine and its release were assessed by direct testing of thyroid function using radioactive iodine, in vivo, in sea level residents intermittently exposed to hypobaric hypoxia. Thyroidal accumulation of radioiodine and its turnover were examined daily for 14 days. Twelve healthy human male volunteers were divided into three groups, with an equal number of individuals in each group. A decompression chamber was used to expose each group of subjects to hypoxic conditions at a simulated altitude of 3810 m for 8 h/day for 14 days. An oral dose of 25 mu Ci iodine-131 was administered to each individual of the first group immediately before the initiation of intermittent hypoxia. The second group of subjects received a tracer dose at the beginning of the 4th day of the 14 days, intermittent exposure to hypoxia, while the third group received the tracer dose 1 week after the completion of the exposure. Control studies were carried out on the subjects before they were subjected to the experimental conditions. Thyroidal accumulation of 131I in experimental subjects during the hypoxic state and in the post-hypoxic state was higher than in the control studies. The pattern of accumulation during exposure to hypoxia and in the post-hypoxic state showed multiple peaks of radioactive iodine uptake (PRAIU), a unique feature. The multiple PRAIU by the thyroid in experimental subjects were sharp and of short duration, reflecting an increased rate of 13I release from the thyroid. Control subjects had a single PRAIU by the thyroid 24 h after the administration of tracer.

Body fluid status on induction, reinduction and prolonged stay at high altitude of human volunteers.

Studies on adaptation to high altitude (HA) of 3500 m in the Himalayas were conducted in three phases, each including 10 normal and healthy males normally resident at sea-level. Phase I subjects had no previous experience of HA, phase II subjects after 4-6 months at HA were airlifted to sea-level and phase III subjects stayed continuously for 6 months at 3500 m. Body fluid compartments and blood gases were determined in all three groups. Plasma volume was highly elevated in the phase II subjects on reinduction to sea-level from HA. In comparison to phase I subjects, the retention of fluid in extracellular compartment was increased at HA leading to increased susceptibility to high altitude illness. Phase III subjects were hyperhydrated with decreased plasma volume and increased PO2 in comparison to the other two groups.