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Biomedical subjects

V K Arora

Publications and source records attributed to V K Arora.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Nodular lepromatous leprosy: report of a case diagnosed by FNA.

Lepromatous leprosy can present with skin nodules which can be misdiagnosed as soft tissue tumors or infected cysts. FNA can be diagnostic if unstained, refractile, intracellular mycobacteria are recognized on Romanowsky stained smears. Fite stain for Mycobacterium leprae confirms the diagnosis. Awareness of the differential diagnosis of skin nodules yielding foamy histiocytes on FNA, briefly discussed, should help avoid error.

Axilla↗

Cytotoxic evaluation of some 3,5-diarylidene-4-piperidones and various related quaternary ammonium compounds and analogs.

A number of 3,5-diarylidene-4-piperidones (1) and some related quaternary ammonium salts (5) as well as closely related analogs were prepared principally as candidate cytotoxic agents in two screens. The first test system used an average of 54 human tumor cell lines from eight neoplastic diseases, namely leukemia, melanoma, colon, non-small-cell lung, small-cell lung, central nervous system, ovarian, and renal cancers. Selective toxicity was demonstrated by some of the compounds, especially toward leukemia. The second screen used L1210 lymphoid leukemia cells. In general, the compounds were less cytotoxic than the reference drug melphalan in both screens. Linear plots were made between the Hammett (sigma), fragment (f), and molar refractivity (MR) constants of the nuclear substituents in series 1 and 5 with the IC50 figures of both the human tumor cell lines and L1210 cells. Evaluation against the human tumor cell lines revealed that increases in the f values were correlated with elevation of cytotoxicity in both series 1 and 5; MR constants were also important in series 5. In the L1210 screen, sigma and MR constants were positively correlated with cytotoxicity. X-ray crystallography was undertaken on 3,5-bis-[[4'-(methylthio)phenyl]methylene]-1-methyl-4-piperidone methiodide (5d), which had significant cytotoxicity, and 3,5-bis(4-pyridylmethylene)-1-methyl-4-piperidone methiodide (6), which was virtually inactive in both screens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cytotoxic evaluation of some N-acyl and N-acyloxy analogues of 3,5-bis(arylidene)-4-piperidones.

The preparation of thirteen N-acyl and N-acyloxy analogues of two 3,5-bis(arylidene)-4-piperidones were prepared as potential prodrugs of the parent ketones. Approximately half of the compounds demonstrated antileukemic properties when evaluated against murine L1210 lymphoid leukemia cells. Three of the derivatives were more active than or equipotent with the reference drug melphalan. All of the compounds were examined against approximately 55 human tumours representing eight different neoplastic diseases. Not only were most of the compounds more cytotoxic than melphalan but 60% of the derivatives displayed selective toxicity to leukemia. A stability study of six of the candidate prodrugs using 1H NMR spectroscopy revealed that while some decomposition in solution occurred, the parent amine was not liberated.

Animals↗

An evaluation of the S-100 stain in the histological diagnosis of tuberculoid leprosy and other granulomatous dermatoses.

Forty biopsies of granulomatous dermatoses, 12 of which were tuberculoid leprosy (TL), were studied for patterns of nerve twig distribution using an immunoperoxidase technique for S-100 protein. Four distinct patterns of nerve twigs were identified: 1) within granulomas, 2) between granulomas, 3) within and between granulomas, and 4) undetectable nerve twigs in an adequate biopsy. Pattern 4 was seen exclusively in TL (p < 0.05). The other patterns occurred in nonleprosy dermatoses as well, suggesting that pattern 4 is the best indicator toward a diagnosis of TL. The granules of mycetoma and Mycobacterium leprae also stained positively with the S-100 stain.

Diagnosis, Differential↗