Health-related quality of life and perceived stress of informal caregivers of children and adolescents with intellectual disabilities and ADHD.

Introduction: Informal caregivers of children and adolescents with intellectual disabilities and attention deficit/hyperactivity disorder (ADHD) face numerous challenges. However, no study has yet compared the HRQoL of the caregivers of children and adolescents with these two conditions. We aimed to compare the HRQoL and perceived stress of caregivers of children and adolescents with intellectual disabilities and ADHD. Methods: The HRQoL and perceived stress of informal caregivers of children and adolescents with intellectual disabilities and ADHD (40 in each group) were compared using the perceived stress scale and the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form, respectively. Results: HRQoL was significantly worse in most dimensions in caregivers of children and adolescents with severe ADHD than in caregivers of children and adolescents with severe intellectual disabilities. However, perceived stress was similar. Conclusion: Differences in the impact of intellectual disability and ADHD on family members' HRQoL should be considered while developing educational programs for patients and their families.

An insight into anti-thyroid peroxidase (TPO) positive cognitive impairment: Analysis of four unusual cases and plea for pragmatism

Cognitive impairment and varied psychiatric manifestations are common in thyroid disorders. But autoimmune thyroid disorders masquerading as dementia or psychotic disorders without other overt systemic features of dysthyroidism are rare. Here we are presenting a detailed analysis of four heterogeneous cases of thyroid related cognitive impairments mimicking and fulfilling criteria of known psychiatric diagnosis for a brief period of time, requiring multiple psychotropic medications without any significant improvement. Cognitive impairment and behavioral abnormalities with a known psychiatric diagnosis, with unknown temporal profiling of anti-thyroid peroxidase (TPO) positivity, without encephalopathy and subsequent complete or partial responsiveness with levothyroxin, point towards a possible new entity not well explored so far.(AU)

Surface passivated and encapsulated ZnO atomic layers by high-κ ultrathin MgO layers.

Atomically transparent vertically aligned ZnO-based van der Waals materials have been developed by surface passivation and encapsulation with atomic layers of MgO using materials by design, and their physical properties have been investigated. The passivation and encapsulation led to a remarkable improvement in the optical and electronic properties. The valence-band offset ΔEv between MgO and ZnO, ZnO and MgO/ZnO, and ZnO and MgO/ZnO/MgO heterointerfaces is determined to be 0.37 ± 0.02, -0.05 ± 0.02, and -0.11 ± 0.02 eV, respectively, and the conduction-band offset ΔEc is deduced to be 0.97 ± 0.02, 0.46 ± 0.02, and 0.59 ± 0.02 eV, respectively, indicating straddling type-I in MgO and ZnO, and staggering type-II heterojunction band alignment in ZnO and the various heterostructures. The band-offsets and interfacial charge transfer are used to explain the origin of n-type conductivity in the superlattices. Enhanced optical absorption due to carrier confinement in the layers demonstrates that MgO is an excellent high-κ dielectric gate oxide for encapsulating ZnO-based optoelectronic devices.

Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section.

BACKGROUND: Phenylephrine, although considered the vasopressor of choice, can cause reflex bradycardia and a fall in cardiac output. Norepinephrine, due to its direct positive chronotropic and reflex negative chronotropic actions, is expected to overcome this problem. However, limited information about its effective dose for management of post-spinal hypotension, and its potency compared to phenylephrine, is available. METHODS: One hundred consecutive patients who developed post-spinal hypotension were treated with a predetermined dose of either phenylephrine or norepinephrine. Correction of hypotension after one minute was considered 'success'. The starting dose for the first patient and testing interval (the incremental or decremental dosing) were 100 µg and 10 µg in the phenylephrine group, and 6 µg and 0.5 µg in the norepinephrine group. Doses for subsequent patients were determined by the responses of previous patients according to the Narayana rule for up-down sequential allocation. ED95 and ED50 of phenylephrine and norepinephrine boluses and their potency ratio were calculated. RESULTS: Using Probit analysis, ED95 and ED50 values were 43.1 µg (95% CI 39.5 to 65.0 µg) and 33.2 µg (95% CI 5.1 to 37.0 µg) for phenylephrine, and 3.7 µg (95% CI 3.5 to 4.7 µg) and 3.2 µg (95% CI 1.8 to 3.4 µg) for norepinephrine. The relative potency ratio of norepinephrine and phenylephrine was 11.3 (95% CI 8.1 to 16.9). CONCLUSION: Based on the results of this study, norepinephrine is about 11 times more potent than phenylephrine. When used as bolus doses for treatment of hypotension, 100 µg phenylephrine should be approximately equivalent to 9 µg norepinephrine.

Engineering the Structural and Electronic Phases of MoTe2 through W Substitution.

MoTe2 is an exfoliable transition metal dichalcogenide (TMD) that crystallizes in three symmetries: the semiconducting trigonal-prismatic 2H- or α-phase, the semimetallic and monoclinic 1T'- or ß-phase, and the semimetallic orthorhombic γ-structure. The 2H-phase displays a band gap of ∼1 eV making it appealing for flexible and transparent optoelectronics. The γ-phase is predicted to possess unique topological properties that might lead to topologically protected nondissipative transport channels. Recently, it was argued that it is possible to locally induce phase-transformations in TMDs, through chemical doping, local heating, or electric-field to achieve ohmic contacts or to induce useful functionalities such as electronic phase-change memory elements. The combination of semiconducting and topological elements based upon the same compound might produce a new generation of high performance, low dissipation optoelectronic elements. Here, we show that it is possible to engineer the phases of MoTe2 through W substitution by unveiling the phase-diagram of the Mo1-xWxTe2 solid solution, which displays a semiconducting to semimetallic transition as a function of x. We find that a small critical W concentration xc ∼ 8% stabilizes the γ-phase at room temperature. This suggests that crystals with x close to xc might be particularly susceptible to phase transformations induced by an external perturbation, for example, an electric field. Photoemission spectroscopy, indicates that the γ-phase possesses a Fermi surface akin to that of WTe2.

Random blinded rechecking of AFB smears in a pilot project at an intermediate reference laboratory.

BACKGROUND: In most developing countries, sputum smear microscopy for acid-fast bacilli remains the front line and often the only diagnostic tool for the diagnosis of tuberculosis (TB), making quality assurance of smear microscopy an important activity. OBJECTIVE: To evaluate the results of a pilot study, where the random blinded rechecking for the entire state of Delhi was conducted at a reference laboratory. METHODOLOGY: Slides from 25 Revised National Tuberculosis Control Programme designated districts (200 peripheral microscopy centres) in Delhi were re-read after proper coding by all the Senior Tuberculosis Laboratory Supervisors (STLS) at an intermediate reference laboratory under proper supervision. RESULTS: Of 12,162 re-read slides, 204 discrepant results were found. Of these, 150 (73.5%) errors were attributed to the peripheral microscopy centres and 54 (26.5%) to STLS. High false-positive errors were observed at a frequency of 12/150 (8%), and high false-negative errors at a frequency of 38/150 (25%). Minor errors, i.e., low false-negative, low false-positive and quantification errors, were observed at frequencies of respectively 68/150 (45.3%), 17/150 (11.3%) and 15/150 (10.0%). CONCLUSION: Greater stringency in the supervision of random blinded rechecking at the district level is essential to make smear rechecking more efficient and effective.

Immunogenicity and protective efficacy of heparan sulphate binding proteins of Entamoeba histolytica in a guinea pig model of intestinal amoebiasis.

Entamoeba histolytica infection is associated with considerable morbidity and mortality in the form of intestinal and extraintestinal amoebiasis. No vaccine is yet available for amoebiasis. Heparan Sulphate Binding Proteins (HSBPs) from E. histolytica were evaluated for immunogenicity and protective efficacy in a Guinea pig model. Animals were immunized subcutaneously with 30µg of HSBP by three weekly inoculations. The immunogenicity of HSBP was determined by antibody response (IgG, IgM and IgA), splenocyte proliferation assay and in vitro direct amoebicidal assay with splenic lymphocytes and monocytes from vaccinated and control animals. The efficacy of the vaccine was evaluated by challenge infection to vaccinated and control animals by intra-caecal inoculation of E. histolytica trophozoites and comparing gross and histopathological findings in caeca of these animals. HSBP was found to induce specific anti-amoebic response as seen by specific antibody production and direct amoebicidal activity of splenocytes. The vaccine also showed partial protection against challenge infection in vaccinated animals as shown by mild/absent lesions and histopathological findings.

Genetic polymorphism in Plasmodium falciparum: differentiation of parasite isolates of high & low virulence by RAPD.

BACKGROUND & OBJECTIVES: The increase in Plasmodium falciparum infections which are associated with severe and complicated malaria and drug resistance has made control of malaria a difficult task. Extensive genetic polymorphism in P. falciparum has been reported from several parts of the world which affects the efficacy of sub-unit vaccines. The knowledge of genotypes of the parasite in a geographical region is therefore, important for effective management and control. The aim of the present study was to investigate the usefulness of random amplified polymorphic DNA (RAPD)-PCR technique for differentiation of P. falciparum isolates from patients presenting with severe (cerebral malaria) and mild malaria. METHODS: Genetic polymorphism in 21 P. falciparum isolates obtained from patients found positive for P. falciparum by light microscopy was studied by RAPD-PCR analysis. Eleven RAPD primers were used for analysis of 21 P. falciparum isolates obtained from cerebral and non-cerebral malaria patients. RESULTS: Of the 11 primers, only three (E-4, E-8, and R-8) produced useful polymorphic patterns. The cluster analysis based on UPGMA demonstrated that isolates causing cerebral malaria cluster separately from those causing uncomplicated malaria. However, the analysis of phylogenic tree showed that P. falciparum isolates causing non-cerebral and cerebral malaria clustered separately but showed relatedness. INTERPRETATION & CONCLUSIONS: The results of the present study showed that the RAPD-PCR was able to differentiate the isolates causing severe and mild malaria. The cluster analysis of the phylogenic tree suggested that the virulent strains evolved from less virulent strains as it clustered separately. RAPD technique may be useful in discriminating between the different isolates of the same species resulting in different clinical profiles.

Impact of aging mechanism on model simulated carbonaceous aerosols.

Carbonaceous aerosols including organic carbon and black carbon have significant implications for both climate and air quality. In the current global climate or chemical transport models, a fixed hydrophobic-to-hydrophilic conversion lifetime for carbonaceous aerosol (τ) is generally assumed, which is usually around one day. We have implemented a new detailed aging scheme for carbonaceous aerosols in a chemical transport model (GEOS-Chem) to account for both the chemical oxidation and the physical condensation-coagulation effects, where τ is affected by local atmospheric environment including atmospheric concentrations of water vapor, ozone, hydroxyl radical and sulfuric acid. The updated τ exhibits large spatial and temporal variations with the global average (up to 11 km altitude) calculated to be 2.6 days. The chemical aging effects are found to be strongest over the tropical regions driven by the low ozone concentrations and high humidity there. The τ resulted from chemical aging generally decreases with altitude due to increases in ozone concentration and decreases in humidity. The condensation-coagulation effects are found to be most important for the high-latitude areas, in particular the polar regions, where the τ values are calculated to be up to 15 days. When both the chemical aging and condensation-coagulation effects are considered, the total atmospheric burdens and global average lifetimes of BC, black carbon, (OC, organic carbon) are calculated to increase by 9% (3%) compared to the control simulation, with considerable enhancements of BC and OC concentrations in the Southern Hemisphere. Model evaluations against data from multiple datasets show that the updated aging scheme improves model simulations of carbonaceous aerosols for some regions, especially for the remote areas in the Northern Hemisphere. The improvement helps explain the persistent low model bias for carbonaceous aerosols in the Northern Hemisphere reported in literature. Further model sensitivity simulations focusing on the continental outflow of carbonaceous aerosols demonstrate that previous studies using the old aging scheme could have significantly underestimated the intercontinental transport of carbonaceous aerosols.

Immunodiagnosis of cystic echinocooccosis by antigen detection in serum, urine, and saliva samples.

BACKGROUND: Cystic echinococcosis (CE) being more common in rural areas, the collection of serum may not always be possible or may be hazardous in untrained hands. The alternative, noninvasive samples like saliva and urine which are non invasive and easy to collect need to be evaluated for diagnosis of CE. AIM: The aim of this study was to evaluate hydatid antigen detection by ELISA in urine and saliva samples by comparing them with antigen detection in serum for diagnosis of CE. MATERIALS AND METHODS: Serum, saliva and urine samples were collected from 25 clinically and radiologically diagnosed CE patients, 25 clinically suspected cases of CE, 15 other parasitic disease controls and 25 healthy controls. Hydatid antigen detection was done in these samples by Enzyme linked immunosorbent assay using hyperimmune serum raised in rabbits immunized with hydatid antigen. RESULTS AND CONCLUSIONS: The sensitivity of ELISA for antigen detection in serum, saliva and urine was found to be 40%, 24% and 52% respectively. Urine showed significantly higher (p<0.05) sensitivity than that of saliva samples but not significantly higher (p>0.05) than that of serum samples. The specificity was highest for serum (92.5%) followed by saliva (87.5%) and urine (80%). There was no significant difference in antigen detection in patients with single vs multiple cysts. There was no significant difference in antigen detection in patients with hepatic vs extrahepatic cysts in serum or saliva samples but antigen positivity in urine was significantly higher (p<0.05) in hepatic cysts than that in extrahepatic cysts. The results showed that biological fluids like urine and saliva may be used as an alternative or as an adjunct to serum samples by virtue of their noninvasive, easy collection and similar sensitivity and specificity.

Presumptive treatment for malaria is not justified in children receiving cancer chemotherapy.

BACKGROUND: Predominant etiologies of febrile neutropenia (FN) during the course of cancer chemotherapy include infections with bacteria, fungi, and viruses. Infection with malarial parasite is a possibility in regions that are endemic for malaria. Over-diagnosis and over-treatment of malaria is increasingly being recognized as a serious concern in malaria endemic regions. Aim was to determine the incidence of malarial infection in episodes of FN in children receiving chemotherapy for malignant disorders. METHODS: Children, with malignant disorders, on chemotherapy, who fulfilled the definition of FN were enrolled prospectively. Standard microscopy, quantitative buffy coat, and antigen detection (OptiMAL) were performed in each episode of FN. RESULTS: One hundred episodes of FN involving 82 children were investigated. The age ranged from 2 to 13 years (mean: 5.8 ± 2.8). Eighty-one episodes were in children with acute lymphoblastic leukemia, 15 in acute myeloid leukemia, and remaining 4 in other malignancies. Evidence for malaria was not found in any case by any of the three methods. CONCLUSIONS: Malaria was not found to be a causative agent for FN in children with various malignant disorders, in a region with low endemicity for malaria. Presumptive administration of antimalarials in children with FN is unjustified. Pediatric oncologists constantly face the challenge of managing febrile illnesses in immunocompromised patients. Those practicing in malaria endemic regions can effectively exploit diagnostic tools for malaria for a rational decision.

Concomitant intestinal parasitism and non-cholera vibrio infection.

Concomitant parasitism is not uncommon especially in tropical countries with low socioeconomic status. Here we report an unusual combination of intestinal infection due to Strongyloides stercoralis, Blastomyces hominis and non-cholera Vibrio in a patient suffering from acute gastroenteritis and hypoalbuminemia. Early recognition and accurate treatment of gastrointestinal infections and infestations before the patient develops complications is important.

Genetic polymorphism in msp-2, ama-1 and csp genes in Plasmodium falciparum field isolates from north and north-western India.

BACKGROUND & OBJECTIVES: Malaria is a major public health problem in tropical and sub-tropical countries. Malaria vaccine is highly desirable as an adjunct to existing malaria control measures. The polymorphism in vaccine candidate antigens might be a hurdle in developing an effective vaccine. Merozoite surface protein-2, apical membrane antigen-1 and circumsporozoite protein of Plasmodium falciparum are vaccine candidate antigens. The aim of this study was to detect extent of genetic polymorphism in potential vaccine candidate antigen genes, i.e. msp-2, ama-1 and csp of P. falciparum isolates prevalent in northern and north-western parts of India. METHODS: Overall 88 parasite isolates of P. falciparum were collected during July 1998-March 2002 from different parts of northern and north-western India. DNA was extracted and analyzed for genetic polymorphism by PCR-RFLP method. For msp-2 gene, family-specific (FC-27 and 3D7) nested PCR was also performed. RESULTS: PCR showed size polymorphism in all the target genes. Three alleles were observed in msp-2 and ama-1, while only two in csp. RFLP of ama-1 and csp with Dra-1 and Ssp-1 endonucleases respectively, failed to differentiate isolates in sub-allelic types, while Hinf-I digestion of msp-2 amplicons differentiated three alleles into two distinct allelic families, i.e. FC-27 and 3D7. The allelic family-specific PCR generally confirmed the results of PCR-RFLP except in a few isolates, which showed mixed (two) clones of msp-2 gene. INTERPRETATION & CONCLUSION: There was extensive polymorphism in msp-2 gene while ama-1 and csp genes showed low polymorphism which may be due to the functional constraints of these proteins. The low level transmission of malaria in the study area may also be a factor for low polymorphism.

Polymorphism in merozoite surface protein-1 gene in north & northwest Indian field isolates of Plasmodium vivax.

BACKGROUND & OBJECTIVE: Merozoite surface protein-1 of Plasmodium vivax (Pvmsp-1) is a strong vaccine candidate against asexual blood stages. Extensive polymorphism in msp-1 gene has been reported in P. vivax isolates from different geographical regions which is necessary before a field trial of any malaria vaccine based on msp-1 is undertaken. There are only a few reports available on polymorphism in msp-1 gene in Indian field isolates of P. vivax. The aim of the present study was therefore to investigate the polymorphism in Pvmsp-1 gene in 25 isolates of P. vivax collected from malaria patients from regions of north and northwest India. METHODS: DNA was extracted from whole blood samples collected in citrated anticoagulant. The polymorphic region-5, the most variable region of the Pvmsp-1 gene was amplified by PCR. The PCR products were further analyzed by restriction fragment length polymorphism (RFLP) using Mva-1 restriction enzyme. The DNA fragments obtained on PCR and RFLP were analyzed by agarose gel electrophoresis. RESULTS: On the basis of PCR, significant size polymorphism was seen and 4 allelic types were observed amongst the 25 isolates. Further analysis by RFLP discriminated these 4 allelic types into 9 sub-allelic types indicating that PCR-RFLP can be a good tool to study polymorphism in msp-1 gene of Plasmodium. INTERPRETATION & CONCLUSION: Marked genetic polymorphism was observed in msp-1 gene among the isolates of P. vivax. These observations stress the need to study larger numbers of isolates from different regions of India. The findings could have important implications on the vaccine development strategies for P. vivax.

Velocity-dependent fatigue crack paths in nanograined Pt films.

Studies of crack growth in nanograined films assert that mechanical damage accumulates at grain boundaries irrespective of the crack velocity and loading conditions. This work shows that crack advance in nanograined Pt films involves a dislocation-slip mechanism that is a function of the crack growth rate and mode of loading. Crack paths in Pt were initially intergranular, but transitioned to a transgranular mode that persisted until catastrophic failure. This research demonstrates that crack growth mechanisms modeled for nanograined Ni cannot be generalized to other pure, metallic systems.

Evaluation of direct agglutination test, rk39 Test, and ELISA for the diagnosis of visceral leishmaniasis.

The study reports an evaluation of the direct agglutination test (DAT) with use of promastigote/amastigote antigen, rk39 strip test, and ELISA for diagnosis of visceral leishmaniasis (VL). Out of 94 clinically suspected VL patients, 16 (17%) were seropositive by all the techniques; in addition, 6 were positive in rk39 strip test and ELISA. On retrospective analysis, out of 16 positive by all the techniques, 11 (69%) had demonstrable Leishmania donovani (LD) bodies in their bone marrow samples, while in 5 bone marrow was not examined. Out of 6 that were positive by ELISA and rk39 strip test, 2 had myelofibrosis and 4 had chronic myeloid leukemia. On the basis of bone marrow aspirate positivity, the sensitivity and specificity of DAT were 100% while those of rk39 strip test and ELISA were 100% and 87%, respectively. The study suggests that DAT appears to be the best technique for the serodiagnosis of VL.

Cysteine proteinase 30 (CP30) and antibody response to CP30 in serum and vaginal washes of symptomatic and asymptomatic Trichomonas vaginalis-infected women.

Infection with Trichomonas vaginalis may be asymptomatic or with symptoms suggestive of vaginitis. Because cysteine proteinase 30 (CP30) of T. vaginalis is known to be a virulence marker that plays a role in cytoadherence, the aim of this study was to analyse the presence of CP30 and antibody to CP30 in clinical samples of symptomatic and asymptomatic infected women. CP30 was detected in all the serum and vaginal washes (VWs) of symptomatic women and in 65% of the serum and 80% of the VWs of asymptomatic women. This suggested that the majority of asymptomatic women also exhibit CP30 in the serum and VWs. Antibody to CP30 was detected in all the serum samples of symptomatic and asymptomatic women and in the VWs of only 54.5% of the symptomatic and 35% of the asymptomatic women. Antibody to CP30 was also detected in 3/20 of the serum samples and in none of the VWs from uninfected women. Significantly higher amounts of antibody (mean OD values) were observed in serum and VWs of symptomatic as compared to asymptomatic and healthy women (P<0.001). These results indicate that besides CP30, other factors may also be playing a role in leading to symptomatic infection, because CP30 was detected in clinical samples from all the symptomatic and the majority of the asymptomatic women. Although anti-CP30 antibodies do not appear to be protective, detection of antibody to CP30 antigen in serum samples may be used as a diagnostic tool.

Cysteine proteinase 30 in clinical isolates of T. vaginalis from symptomatic and asymptomatic infected women.

A cysteine proteinase of 30 kDa (CP30) of Trichomonas vaginalis, is known to play a role in cytoadherence of the parasite to host cells. However, the CP30 activity in clinical isolates from symptomatic and asymptomatic patients has not been analyzed. In the present study, CP30 was detected in 20 fresh and long-term culture maintained T. vaginalis isolates each from symptomatic and asymptomatic women by substrate gel electrophoresis and immunoblotting. Though CP30 was detected in all the fresh isolates from 20 symptomatic and 20 asymptomatic women, the intensity of CP30 band was significantly higher in isolates from symptomatic as compared to asymptomatic women indicating higher expression in former. CP30 was found in all the 20 long-term cultured isolates from symptomatic whereas only in 70% of asymptomatic women indicating that CP30 expression is a more stable characteristic of symptomatic isolates. The isolates from symptomatic women, demonstrated significantly higher cytoadherence to VECs as compared to asymptomatic women. In both the types of isolates, this cytoadherence was inhibited significantly by CP30 specific hyperimmune serum. These results confirm that CP30 is an important virulence factor of T. vaginalis and has an important role in cytoadherence to VECs and thus has a role in pathogenesis of trichomoniasis.

Specific antibody detection in serum, urine and saliva samples for the diagnosis of cystic echinococcosis.

Serum, saliva and urine samples of 25 clinically and radiologically diagnosed cystic echinoccosis (CE) patients, 25 clinically suspected cases of CE, 15 other parasitic disease controls and 25 healthy controls were evaluated for anti-hydatid antibody response by ELISA. The sensitivity of serum, saliva and urine was found to be 72, 56 and 84%, respectively, while specificity was 76% in all the samples. Urine showed significantly higher (p<0.05) sensitivity than that of saliva samples but not significantly higher (p>0.05) than that of serum samples. There was no significant difference in the immune response of patients with hepatic versus extrahepatic cysts and single versus multiple cysts. Thus, biological fluid like urine may be used as an alternative or as an adjunct to serum samples by virtue of its non-invasive, easy collection and similar sensitivity and specificity.

Leishmania donovani: effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Indian clinical isolates to sodium stibogluconate.

Although pentavalent antimonials are the first-line drug for treatment of visceral leishmaniasis all over the world, yet, in India, increasing number of patients are being reported to be unresponsive to sodium stibogluconate. Verapamil, a calcium channel blocker, affects drug uptake by preventing its efflux and thereby accumulation within the cell. In the present study, effect of verapamil on in vitro susceptibility of both promastigote and amastigote stages of 15 clinical isolates and standard strain of Leishmania donovani to sodium stibogluconate was evaluated by detection of acid phosphatase. Amastigotes were found more susceptible to sodium stibogluconate than the promastigotes (p<0.05) and in the presence of verapamil, IC(50) value of sodium stibogluconate was reduced only for those isolates, which had a higher IC(50). Verapamil alone did not have any effect on the parasites. The results indicate that amastigotes are more susceptible to sodium stibogluconate than promastigotes and verapamil can reverse the in vitro drug resistance of L. donovani clinical isolates to sodium stibogluconate.