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V K Arora

Publications and source records attributed to V K Arora.

At least 19 recordsLinked to original sources
PubMed2003

Adherence to tuberculosis treatment: lessons from the urban setting of Delhi, India.

The Revised National Tuberculosis Control Programme (RNTCP), which incorporated the WHO DOTS strategy was introduced in India in the mid-1990s. An operational research project was conducted between 1996 and 1998 to assess the needs and perspectives of patients and providers in two chest clinics in Delhi, Moti Nagar and Nehru Nagar, during the introduction of the new strategy. This paper reports on the findings of the project, concentrating on information collected from 40 in-depth interviews with patient defaulters and from non-participant observations in clinics and directly observed treatment centres. In Moti Nagar chest clinic, 117 of 1786 (6.5%) patients and 195 of 1890 (10%) patients in Nehru Nagar left care before their treatment was complete. It was argued that the reasons for default stem from a poor correlation between patient and programme needs and priorities, and from particular characteristics of the disease and its treatment. Patient needs that were not met by the health system included convenient clinic timings, arrangements for the provision for treatment in the event of a family emergency and provision for complicated cases like alcoholics. The problems facing the provider were poor interpersonal communication with the health staff, lack of attention and support at the clinic, difficulty for patients to re-enter the system if they missed treatment and, in certain areas, long distances to the clinic. Problems related to diseases were inability of the staff to deal with drug side-effects, and patients' conception of equating well-being with cure. Simple, practical measures could improve the provision of tuberculosis (TB) treatment: more flexible hours, allowances for poor patients to reach the clinics and training health care staff for respectful communication and monitoring drug side-effects. The findings indicate a need to rethink the label of 'defaulter' often given to the patients. The important areas for future operational research is also highlighted.

Adolescent↗
PubMed2002

TB control, poverty, and vulnerability in Delhi, India.

The Revised National Tuberculosis Control Programme (RNTCP), based on the World Health Organization's DOTS strategy,* was introduced in India in the mid-1990s. This paper reports the findings from operational research studies in two pilot sites in New Delhi from 1996 to 1998. A variety of operational research methods were used, including semi-structured interviews, focus group discussions, non-participant observations and collection of data from the tuberculosis registers. The cure rates for the clinics were 71 and 75% with a default rate of 6 and 11%, respectively. An important finding was that health workers screened patients to determine their ability to conform to the direct observation of treatment element of the RNTCP. If the health worker was confident that the patient would comply and/or be easy to trace in the community in the event of 'default', they were provided with short-course treatment under the RNTCP. Other patients, largely those who were in absolute poverty, socially marginalized, itinerant labourers, poorly integrated in the city, were put on standard tuberculosis (TB) treatment as for the previous National TB Programme. The programme was evidently excluding the most vulnerable from the best available care. These findings demonstrate the potential dangers of target-driven programmes where there is an absence of support to both frontline health workers and patients. The paper also highlights the importance of operations research in helping to identify problems within TB programmes.

Antitubercular Agents↗
PubMed2001

Genetic and functional diversity of human immunodeficiency virus type 1 subtype B Nef primary isolates.

We have characterized the functional integrity of seven primary Nef isolates: five from a long-term nonprogressing human immunodeficiency virus (HIV)-infected individual and one each from two patients with AIDS. One of the seven Nefs was defective for CD4 downregulation, two others were defective for PAK-2 activation, and one Nef was defective for PAK-2 activation and major histocompatibility complex (MHC) class I downregulation. Five of the Nefs were tested and found to be functional for the enhancement of virus particle infectivity. The structural basis for each of the functional defects has been analyzed by constructing a consensus nef, followed by mutational analysis of the variant amino acid residues. Mutations A29V and F193I were deleterious to CD4 downregulation and PAK-2 activation, respectively, while S189R rendered Nef defective for both MHC class I downregulation and PAK-2 activation. A search of the literature identified HIVs from five patients with Nefs predominantly mutated at F193 and from one patient with Nefs predominantly mutated at A29. A29 is highly conserved in all HIV subtypes except for subtype E. F193 is conserved in subtype B (and possibly in the closely related subtype D), but none of the other HIV group M subtypes. Our results suggest that functional distinctions may exist between HIV subtypes.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Efficacy and safety of sparfloxacin in combination with kanamycin and ethionamide in multidrug-resistant pulmonary tuberculosis patients: preliminary results.

SETTING: Department of tuberculosis and chest diseases of a tertiary referral tuberculosis institute in New Delhi, India. OBJECTIVE: To study the efficacy and safety of sparfloxacin, in combination with kanamycin (for the initial 3-4 months) and ethionamide, in multidrug-resistant (MDR) pulmonary tuberculosis patients. DESIGN: Prospective, uncontrolled study of nine patients with pulmonary tuberculosis who had received adequate anti-tuberculosis treatment with first-line drugs, including supervised category II treatment regimen as per World Health Organization guidelines for 5 months, and were still sputum smear acid-fast bacilli positive. It was planned to give them kanamycin (initial 3-4 months), ethionamide and sparfloxacin for 2 years. RESULTS: All nine patients achieved sputum conversion within 6 months. Seven patients converted within 3.5 months, two of these within 1 month. All patients reported improvement in clinical symptoms, and chest X-ray improved in seven patients. Four patients developed mild to moderate phototoxicity. Eight patients have completed treatment for an average of 19 months (range 15-24 months), and are still under follow-up. One patient defaulted after 7 months of treatment. CONCLUSIONS: In MDR-TB patients, sparfloxacin, along with other anti-tuberculosis drugs, appears to be effective and safe. Mild to moderate phototoxicity is common. However, the long-term results, including relapses, are still awaited.

Adult↗
PubMed2000

Quantitative determination of SC-68328 in dog plasma using flow injection and tandem mass spectrometry.

A flow injection/tandem mass spectrometric assay was developed to quantitate SC-68328 in dog plasma using its stable isotopic analog [13C4]SC-68328 as an internal standard (IS). Since SC-68328, a manganese-based superoxide dismutase mimetic, is very unstable, very polar and adheres to silica-based high-performance liquid chromatographic columns, the analyte and IS were derivatized to their bis-isothiocyanate forms followed by a liquid-liquid extraction with methylene chloride and analyzed using positive ion electrospray mass spectrometric detection. SC-68328 was quantitated using the peak-height ratio of SC-68328 to its IS using MS/MS in the multiple reaction monitoring mode. The lower limit of quantitation of the assay was 0.25 microg ml(-1) SC-68328 in dog plasma with an inter-day precision of 11.8% and an accuracy of 113% (n = 12). Acceptable precision and accuracy were also obtained for concentrations in the calibration curve range (0.25-10 microg ml(-1) SC-68328 in dog plasma).

Animals↗
PubMed2000

Lentivirus Nef specifically activates Pak2.

Nef proteins from human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have been found to associate with an active cellular serine/threonine kinase designated Nef-associated kinase (Nak). The exact identity of Nak remains controversial, with two recent studies indicating that Nak may be either Pak1 or Pak2. In this study, we investigated the hypothesis that such discrepancies arise from the use of different Nef alleles or different cell types by individual investigators. We first confirm that Pak2 but not Pak1 is cleaved by caspase 3 in vitro and then demonstrate that Nak is caspase 3 sensitive, regardless of Nef allele or cell type used. We tested nef alleles from three lentiviruses (HIV-1 SF2, HIV-1 NL4-3, and SIVmac239) and used multiple cell lines of myeloid, lymphoid, and nonhematopoietic origin to evaluate the identity of Nak. We demonstrate that ectopically expressed Pak2 can substitute for Nak, while ectopically expressed Pak1 cannot. We then show that Nef specifically mediates the robust activation of ectopically expressed Pak2, directly demonstrating that Nef regulates Pak2 activity and does not merely associate with activated Pak2. We report that most of the active Pak2 is found bound to Nef, although a fraction is not. In contrast, only a small amount of Nef is found associated with Pak2. We conclude that Nak is Pak2 and that Nef specifically mediates Pak2 activation in a low-abundance complex. These results will facilitate both the elucidation of the role of Nef in pathogenesis and the development of specific inhibitors of this highly conserved function of Nef.

Alleles↗
PubMed2000

Malakoplakia of the appendix. An unusual association with eggs of Taenia species.

Malakoplakia of the appendix is an unusual condition that has been reported to occur in association with tumors, infections, and immunocompromised states. We describe a case of appendicular malakoplakia associated with eggs of Taenia species. The diagnosis was made on histopathologic examination of surgically resected tissue from an appendicular mass. To the best of our knowledge, this is the first time that helminths have been documented to be associated with malakoplakia. We also discuss the implications of helminthic infestation in the pathogenesis of the lesion.

Animals↗
PubMed2000

Histological assessment of dermal nerve damage occurring during multidrug therapy for leprosy.

This is a prospective histomorphological assessment of dermal innervation in biopsies taken before and after multidrug therapy (MDT) from 41 leprosy patients: 35 borderline tuberculoid (BT), 3 borderline lepromatous (BL), 3 lepromatous (LL). Biopsies of the same lesions taken before commencement (diagnostic therapy) and at the end of therapy (check biopsy) were compared. Hematoxylin and eosin, immunoperoxidase stain for S-100 protein, and the Holmes' silver impregnation method for nerve cells and fibers were used. Skin biopsies were classified as having detectable or undetectable nerves. Of 35 patients with BT leprosy, 17 had no detectable nerves in their diagnostic biopsies; in the check biopsies of 13 of these 17, dermal nerves remained undetectable, in 2 they were S-100 positive but were Holmes negative. Identifiable dermal nerves were present in diagnostic biopsies from 18 patients; in the check biopsies 5 of these 18 had no detectable nerves while in the remaining 13 nerve branches could be detected. The study provides histological documentation of complete damage to dermal innervation in 62.85% (22/35) of patients with BT leprosy, of which 14.28% (5/35) occurred during MDT. Of the patients with detectable dermal innervation at the onset of MDT, 27.7% (5/18) suffered continuing damage during MDT.

Biopsy↗
PubMed1999

Quantitative analysis of cimetidine in human plasma using LC/APCI/SRM/MS.

A quantitative method was developed and validated for rapid and sensitive analysis of cimetidine in human plasma. The method involved the use of liquid chromatography (LC) coupled with atmospheric pressure chemical ionization (APCI) and selected reaction monitoring (SRM) mass spectrometry (MS). A cimetidine analog, SKF92374, was used as the internal standard. Separation of cimetidine and the internal standard was accomplished using a reverse-phase HPLC column (C18). The eluted components were ionized by the APCI source and subsequently detected by a highly selective triple quadrupole mass spectrometer in the SRM mode. Linear standard curves were obtained from 5 ng/mL (lower limit of quantitation) to 10,000 ng/mL. The results demonstrated excellent precision (%RSD 1. 1-8.9%) and accuracy (94.7-108.0%) over this range. In addition, the amount of plasma sample needed for analysis was small (50 muL), and the plasma pretreatment (analyte recovery >94%) was simple and time saving. This assay was used to evaluate cimetidine levels in premature infants following intravenous infusion of cimetidine.

Child↗
PubMed1998

Nodular post-kala-azar dermal leishmaniasis: a distinct histopathological entity.

Post-kala-azar dermal leishmaniasis (PKDL) is an infrequently occurring sequel to treated visceral leishmaniasis. Diagnosis, particularly in non-endemic areas, is difficult because the clinical appearances may be subtle and simulate lepromatous leprosy. The histopathology of the condition has been a neglected subject. Nodular lesions constitute one of the large variety of lesions that can be seen in PKDL. This paper describes the histopathology of such lesions in 26 patients seen over a period of approximately 8 years in a non-endemic setting. All the biopsies had strikingly similar light microscopic features with characteristic findings: a dense lymphohistiocytic infiltrate beneath an atrophic epidermis, pronounced follicular plugging, vascular hyalinization and collagen changes and negative Fite stain. These allow a definite diagnosis of PKDL even in the absence of demonstrable Leishman-Donovan (L-D) bodies.

Biopsy↗
PubMed1998

Fine-needle aspiration cytology of lepromatous leprosy.

A prospective study correlating cytopathology with clinical morphology and histopathology in 22 patients with lepromatous leprosy was performed. Aspirates were taken from skin lesions in all patients. Lymph node aspirates were also performed in four patients with lymphadenopathy. Fine-needle aspirates yielded sufficient cellular material with excellent preservation of morphological detail. Diagnosis and correlation with bacillary index, clinical and histopathological findings was possible in all patients. In addition, the two patterns, partial and diffuse, of lymph node involvement could be recognized. Fine-needle aspiration cytology is a simple method for the laboratory assessment of leprosy.

Biopsy, Needle↗
PubMed1997

The cloning of a Caenorhabditis elegans guanylyl cyclase and the construction of a ligand-sensitive mammalian/nematode chimeric receptor.

Substantial guanylyl cyclase activity was detected in membrane fractions prepared from Caenorhabditis elegans (100 pmol cGMP/min/mg at 20 degrees C or 500 pmol cGMP/min/mg at 37 degrees C), suggesting the potential existence of orphan cyclase receptors in the nematode. Using degenerate primers, a cDNA clone encoding a putative membrane form of the enzyme (GCY-X1) was obtained. The apparent cyclase was most closely related to the mammalian natriuretic peptide receptor family, and retained cysteine residues conserved within the extracellular domain of the mammalian receptors. Expression of the cDNA in COS-7 cells resulted in low, but detectable guanylyl cyclase activity (about 2-fold above vector alone). The extracellular and protein kinase homology domain of the mammalian receptor (GC-B) for C-type natriuretic peptide (CNP) was fused to the catalytic domain of GCY-X1 and expressed in COS-7 cells to determine whether ligand-dependent regulation would now be obtained. The resulting chimeric protein (GC-BX1) was active, and CNP elevated cGMP in a concentration-dependent manner. Subsequently, a search of the genome data base demonstrated the existence of at least 29 different genes from C. elegans that align closely with the catalytic domain of GCY-X1, and thus an equally large number of different regulatory ligands may exist.

Amino Acid Sequence↗