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P Aggarwal

Publications and source records attributed to P Aggarwal.

At least 19 recordsLinked to original sources
PubMed2006

Discovery and development of a type II collagen neoepitope (TIINE) biomarker for matrix metalloproteinase activity: from in vitro to in vivo.

Destruction of cartilage by matrix metalloproteinases (MMPs) plays a significant role in the pathology of osteoarthritis (OA). A translatable biomarker of MMP activity would enable development of MMP inhibitors for the treatment of OA and potentially the improved diagnosis of OA. A directed approach to identifying specific MMP cleavage products as potential biomarkers has been undertaken. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify peptides generated by MMP-driven degradation of human articular cartilage (HAC) in vivo. It was shown that a 45-mer peptide fragment of collagen type II with five hydroxyprolines (OH) can be selectively produced by the activity of collagenase, an enzyme purported to be involved in the pathology of OA. This 45-mer is the most abundant neoepitope peptide found in biological fluids such as urine and synovial fluid. An immunoaffinity LC-MS/MS assay has been developed to quantify collagen type II neoepitope peptides as biomarkers of collagenase modulation. The lower limit of quantification for this assay was established to be 0.035 nM. The assay was used to measure the levels of collagen type II peptides in the urine of both clinical (healthy human subjects) and preclinical species. The urinary levels of the most abundant peptides are reported for rat, rabbit, guinea pig, dog, and healthy human adult subjects. The utility of this peptide to monitor collagenase activity in vivo has been demonstrated through its detailed characterization in HAC explants as well as in the urine of human and other preclinical species.

Aged↗
PubMed2006

Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India.

OBJECTIVES: To define the genetic characteristics and resistance mechanisms of clinical isolates of Salmonella enterica serovar Typhi (S. Typhi) and S. enterica serovar Paratyphi A (S. Paratyphi A) exhibiting high-level fluoroquinolones resistance. METHODS: Three S. Typhi and two S. Paratyphi A ciprofloxacin-resistant isolates (MICs > 4 mg/L) were compared with isolates with reduced susceptibility to ciprofloxacin (MICs 0.125-1 mg/L) by PFGE, plasmid analysis, presence of integrons and nucleotide changes in topoisomerase genes. RESULTS: In S. Typhi and Paratyphi A, a single gyrA mutation (Ser-83-->Phe or Ser-83-->Tyr) was associated with reduced susceptibility to ciprofloxacin (MICs 0.125-1 mg/L); an additional mutation in parC (Ser-80-->Ile, Ser-80-->Arg, Asp-69-->Glu or Gly-78-->Asp) was accompanied by an increase in ciprofloxacin MIC (> or = 0.5 mg/L). Three mutations conferred ciprofloxacin resistance: two in gyrA (Ser-83-->Phe and Asp-87-->Asn or Asp-87-->Gly) and one in parC. This is the first report of parC mutations in S. Typhi. Ciprofloxacin-resistant S. Typhi and S. Paratyphi A differed in their MICs and mutations in gyrA and parC. Moreover S. Typhi harboured a 50 kb transferable plasmid carrying a class 1 integron (dfrA15/aadA1) that confers resistance to co-trimoxazole and tetracycline but not to ciprofloxacin. PFGE revealed undistinguishable XbaI fragment patterns in ciprofloxacin-resistant S. Typhi as well as in S. Paratyphi A isolates and showed that ciprofloxacin-resistant S. Typhi have emerged from a clonally related isolate with reduced susceptibility to ciprofloxacin after sequential acquisition of a second mutation in gyrA. CONCLUSIONS: To our knowledge this is the first report of molecular characterization of S. Typhi with full resistance to ciprofloxacin. Notably, the presence of a plasmid-borne integron in ciprofloxacin-resistant S. Typhi may lead to a situation of untreatable enteric fever.

Amino Acid Substitution↗
PubMed2006

Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma.

Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by overexpression of cyclin D1 due to the t(11;14) chromosomal translocation. While expression of cyclin D1 correlates with MCL development, expression of wild-type (WT) cyclin D1 transgene in murine lymphocytes is unable to drive B-cell lymphoma. As cyclin D1 mutants that are refractory to nuclear export display heighten oncogenicity in vitro compared with WT D1, we generated mice expressing FLAG-D1/T286A, a constitutively nuclear mutant, under the control of the immunoglobulin enhancer, Emu. D1/T286A transgenic mice universally develop a mature B-cell lymphoma. Expression of D1/T286A in B lymphocytes results in S phase entry in resting lymphocytes and increased apoptosis in spleens of young premalignant mice. Lymphoma onset correlates with perturbations in p53/MDM2/p19Arf expression and with BcL-2 overexpression suggesting that alterations in one or both of these pathways may contribute to lymphoma development. Our results describe a cyclin D1-driven model of B-cell lymphomagenesis and provide evidence that nuclear-retention of cyclin D1 is oncogenic in vivo.

Animals↗
PubMed2006

Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study.

OBJECTIVE: To test the hypothesis that combined administration of multiple doses of nebulised salbutamol and magnesium sulphate provides additional benefit compared with salbutamol alone in adult patients with acute asthma. DESIGN: Randomised, double blind, prospective study. METHODS: A total of 100 patients presenting to an emergency department with an acute attack of bronchial asthma were randomised to two groups: nebulisation with a combination of salbutamol and magnesium sulphate (group A) and nebulisation with salbutamol only (group B). Both groups received nebulisation thrice at intervals of 20 minutes. Salbutamol and magnesium sulphate were administered in doses of 0.5 mg and 500 mg, respectively, and the solutions were made isotonic to plasma osmolality. Pulse rate, blood pressure, and peak expiratory flow rate (PEFR) were measured at baseline and at 15, 60, 75, and 120 minutes. Serum magnesium levels and blood gases were measured at 0 and 120 minutes in both groups. RESULTS: All patients had either acute severe or life threatening asthma. The baseline characteristics were comparable in the two groups. Both groups showed significant rise in PEFR at all time intervals, however, there was no significant difference between the groups in rise in PEFR at any time point. Serum magnesium levels remained within normal limits, and there was no difference in requirement of additional medication during the study or hospital admission rates in both groups. No significant side effects were noted. CONCLUSION: This study suggests that there is no therapeutic benefit of adding magnesium sulphate to salbutamol nebulisation in the treatment of patients with acute severe or life threatening asthma.

Acute Disease↗
PubMed2005

Tumor necrosis factor-alpha levels in patients with HIV with wasting in South Asia.

Tumor necrosis factor (TNF)-alpha is thought to play an important role in wasting; but TNF-alpha levels have not been consistently found to be high in AIDS wasting. We conducted this study to determine any correlation between TNF-alpha levels and wasting in HIV-positive patients in a developing country. TNF-alpha levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative patients with tuberculosis with wasting (n = 25); and group 4, healthy controls (n = 25). Wasting was defined as a body bass index (BMI) </=16.0 kg/m(2). TNF-alpha was measured by a solid-phase sandwich enzyme linked immunosorbent assay (ELISA) kit. The mean BMI in HIV-positive patients with wasting (group 1) and without wasting (group 2) was 15.192 +/- 1.142 and 19.507 +/- 2.457, respectively, while group 3 and 4 had a BMI of 14.878 +/- 3.234 and 21.862 +/- 2.763 kg/m(2). The mean TNF-alpha level in group 1 was 50.864 +/- 99.13 pg/mL and 43.39 +/- 66.372 pg/mL in group 2. There was no significant difference between the two groups. TNF-alpha was significantly higher in the HIV/AIDS groups (group 1 and 2) compared to the tuberculosis group (10.74 +/- 7.854) and healthy controls (5.846 +/- 3.40) at p = 0.01. TNF-alpha was significantly (p = 0.002) higher in symptomatic patients compared to asymptomatic patients (16.03 +/- 7.61 versus 64.70 +/- 98.70). In conclusion, TNF-alpha levels were higher in HIV patients, regardless of the presence of wasting, compared to normal healthy controls of patients with tuberculosis with wasting.

Adolescent↗
PubMed2005

Characterization and changing minimum inhibitory concentration (MIC) of Acinetobacter species from a tertiary care setup.

128 isolates of Acinetobacter species from admitted and outdoor patients were subjected to biotyping and resistotyping. Resistance phenotype analysis included nine antibiotics and two betalactam inhibitor combination drugs. In 100 strains of Acinetobacter spp. ciprofloxacin, amikacin, cefotaxime and cefepime minimum inhibitory concentration (MIC) was done by agar dilution using NCCLS 2002 criteria. In forty-nine isolates MIC level was determined by E-strip also. Extended spectrum beta lactamase (ESBL) production was detected by double disc synergy technique. Inducible beta lactamases (IBL's) were detected by disc approximation method. The relationship between biotypes and resistance phenotype was analyzed. Majority of isolates (93.75%) were from admitted patients. The biotyping revealed Acinetobacter calcoaceticus-Acinetobacter baumannii complex (87.2%) to be the predominant species and they were isolated from tracheal aspirates of patients with ventilator associated pneumonia. By Kirby Bauer disc diffusion antimicrobial sensitivity testing Acinetobacter spp. were most sensitive to the combination of drug cefoperazone-sulbactam (95.6%) followed by meropenem (94.6%), piperacillin-tazobactam (92.6%). On screening incidence of Imipenem Nonsensitive Acinetobacter spp. (INSA) was (5.4%). Acinetobacter spp. were typable by six resistance phenotypes and six biotypes. Most common (66.6%) resistant phenotype of A. calcoaceticus-A. baumannii complex was susceptible to cefoperazone-sulbactam and or meropenem and or piperacillin-tazobactam. ESBL production was seen in 6% and IBL (Inducible Beta Lactamase) production was seen in 7% of Acinetobacter spp. The MIC90 for ciprofloxacin was =256 microg/ml, cefotaxime 512 microg/ml, cefepime 512 microg/ml, and amikacin 32 microg/ml. Multidrug resistance was seen in more than 90% of A. calcoaceticus-A. baumannii complex and 20% of Acinetobacter lwoffii. Acinetobacter spp. has other emerging novel mechanism of resistance that requires continuous research. Simpler, reproducible and reliable methods of biotyping and their subsequent correlation with resistotyping are more cost effective than molecular methods, which are available only in reference laboratories.

Acinetobacter↗
PubMed2004

Bleomycin-induced scleroderma.

Systemic sclerosis is a connective tissue disease, which can be triggered by environmental factors. We report one such case of bleomycin-induced scleroderma.

Antibiotics, Antineoplastic↗
PubMed2002

Clinical expression and EEG features of patients with juvenile myoclonic epilepsy (JME) from North India.

We aimed to characterize the clinical profile, EEG features and response to treatment of juvenile myoclonic epilepsy (JME) patients. We studied 103 JME probands with a standard protocol recording age of onset, type, frequency of seizures, EEG data, detailed family history and response to treatment in a superspeciality university hospital in New Delhi. The mean age of onset of disease was 14.01 +/- 3.14 years with a male to female ratio of 1.19 : 1. The myoclonic jerks were present in all the probands, generalized tonic-clonic seizures (GTCS) were present in 75.72% and 11.65% probands had absence seizures. The incidence of febrile convulsion (FC) was higher (9.7%) in our JME probands reflecting some ethnic variation or ascertainment bias. There was a considerable delay (of approximately 5.26 +/- 4.61 years) in the diagnosis of JME in our probands because most of the patients were referred from private physicians who were possibly not familiar with this epileptic syndrome in this part of the world or thought it was a milder variety of GTCS. The family history was positive in 25.24% JME probands among first- and second-degree relatives. An interictal EEG was found to be abnormal in 81 (78.64%) patients with the predominant abnormality being generalized polyspike and wave (PSW) discharges (39.80% probands). The majority of patients (80.58%) showed a good response to treatment with valproate alone. There was a subset of patients (11.65%) who required the addition of other antiepileptic drugs (AEDs) for control of GTCS: 7.76% of JME patients were diagnosed as cases of GTCS by private practitioners before they were registered in our study and their seizures were well controlled on other AEDs (without valproate) prescribed by the referring physicians (carbamazepine-4, phenytoin-2, clobazam-2). It is concluded that the clinical features and EEG data of JME probands were comparable to reports from other parts of the world except for the fact that the incidence of FC was higher in our JME patients. There was a delay in the diagnosis of JME due to unfamiliarity with the epileptic syndrome among private practitioners in this part of the world. There was a subset of JME patients who had complete seizure control on other AEDs besides valproate.

Adult↗
PubMed2002

Panniculitides--a clinicopathologic study.

OBJECTIVES: To describe the clinical and pathologic features of panniculitides, an uncommon group of diseases, where the available Indian literature is sparse. MATERIAL AND METHODS: Prospective four years study of patients presenting with panniculitis to a large teaching hospital in North India. RESULTS: Erythema nodosum (EN) was the commonest panniculitis (79.3% cases) in our cohort. Other causes included erythema induratum, Weber Christian disease, cutaneous polyarteritis nodosa and panniculitis associated with Takayasu's arteritis and dermatomyositis-lupus overlap. Elevated ESR and leukocytosis were the common laboratory abnormalities encountered. Septal panniculitis without vasculitis was the most frequent histopathologic pattern observed. Patients of EN did well on nonsteroidal anti-inflammatory drugs while corticosteroids with or without azathioprine were used to treat other panniculitides. CONCLUSIONS: Physician awareness, clinical pattern recognition and histopathological confirmation, all play a key role in the identification and management of panniculitis.

Adipose Tissue↗
PubMed2001

Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta.

Mitochondrial DNA (mtDNA) defects are associated with a number of human disorders. Although many occur sporadically, maternal transmission is the hallmark of diseases due to mtDNA point mutations. The same mutation may manifest strikingly different phenotypes; for example, the A to G substitution at np 3243 was first reported in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (the MELAS syndrome), but is also found in patients with diabetes and deafness. Here we present a case of gestational diabetes, deafness, premature greying, placenta accreta and Wolff-Parkinson-White (WPW) syndrome associated with a mtDNA mutation. Although this is the first report of such an association, study of 27 other patients with WPW syndrome failed to confirm that this mtDNA mutation is a common cause of such pre-excitation disorders.

Adult↗
PubMed2001

Classical polyarteritis nodosa and microscopic polyangiitis--a clinicopathologic study.

OBJECTIVE: To describe the clinical spectrum, laboratory features, histopathological findings and treatment outcome in patients with classical polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA). MATERIAL AND METHODS: Patients with PAN and MPA seen at a large teaching hospital in north India over a period of five years (1994-99) were included in the present study. RESULTS: We encountered five patients with PAN and six patients with MPA during the study period. Of the five patients with PAN, two had systemic disease while three had limited PAN. The patients with limited PAN included two with cutaneous PAN and one with PAN confined to the nerves. Constitutional symptoms, musculoskeletal complaints, peripheral neuropathy and skin lesions dominated the clinical picture. Fifty percent of the MPA patients presented as pulmonary renal syndrome. All the patients with PAN were HBsAg and ANCA negative and had normal urinalysis findings. In contrast, all patients with MPA demonstrated an active urine sediment and 83.3% were pANCA positive. Some of the rare features encountered by us were the presence of antiphospholipid syndrome and extensive interstitial lung disease in MPA, and spontaneous recovery in one patient with systemic PAN. Treatment outcome was better in PAN as compared with MPA. CONCLUSIONS: The clinical spectrum of PAN and MPA is quite varied. A good outcome is possible with the use of corticosteroids and cyclophosphamide.

Adolescent↗
PubMed2001

Seroepidemiology and active surveillance of dengue fever/dengue haemorrhagic fever in Delhi.

The aims of the present study were to carry out surveillance for dengue virus infection in adults with short-duration fever, and serological study of dengue virus infection in persons without fever. Patients were divided into two groups. Group 1 included patients above 12 years of age with fever of 2-12 days duration without any apparent cause. Of these, patients who presented with fever for 2-5 days were included for virus isolation (group 1a) while those who presented within 6-12 days of the onset of fever were included for the dengue-specific IgM serology (group 1b). Group 2 included a sample of population belonging to all age groups but without pyrexia and blood was collected for dengue-specific IgG serology. Twenty-six patients were enrolled in group 1a over a period of 4 months (September to December, 1997). Of these, DEN1 was isolated in 5 cases. Group 1b included 182 patients, out of which 34 (18.68%) were positive for dengue-specific IgM antibodies. Significantly, all the positive cases were detected during the months of September to November. Retro-orbital pain was present in a significantly more number of IgM-positive cases as compared to IgM-negative cases. Group 2 included 125 cases without fever. The overall positivity for dengue-specific IgG antibodies was 77.6%, with the highest positivity of 100% in the age group of 31-40 years. It was concluded that dengue virus infection is endemic in and around Delhi with peak incidence between September and Novemver. The prevalent serotype during September and December 1997 was DEN1. Since previous epidemic of DHF was due to DEN2 type, isolation of DEN1 serotype indicates changes of another epidemic of DHF due to DEN1 serotype. The stresses the urgent need for implementation of measures to control the transmission of dengue infection.

Adult↗
PubMed2001

A clinico-bacteriological study of peripheral tuberculous lymphadenitis.

OBJECTIVE: Tuberculous lymphadenitis is the commonest form of extra-pulmonary tuberculosis. It is most often caused by M. tuberculosis though several reports from other countries have shown mycobacteria other than tuberculosis (MOTT) to be responsible for a significant proportion of tuberculous lymphadenitis cases. The present study was conducted to find the prevalence of M. tuberculosis and MOTT as aetiological agents in patients with peripheral tuberculous lymphadenitis. METHODS: A total of 138 patients with tuberculous lymphadenitis were included in the study. Diagnosis of tuberculosis was established on the basis of fine needle aspiration cytology, histopathology, presence of mycobacteria on Ziehl Neelson stain or auramine rhodamine stain, or aspiration of pus with negative Gram's stain and pyogenic cultute with radiologic evidence of pulmonary tuberculosis. Mycobacterial cultures were performed on aspirated material and species identified using standard methods. RESULTS: Of 138 patients, single lymph nodal enlargement was found in 48.6% patients while others had more than one lymph nodes. Lymph nodes were matted in 26.8% cases while fluctuation could be elicited in 12.3% patients. Chest X-ray showed evidence of active pulmonary lesions or mediastinal lymphadenopathy in 28.3% cases. The fine needle aspiration cytology was positive for tuberculous lymphadenitis in 41.3% cases while it revealed granulomas or necrosis in another 13% cases. The Ziehl-Neelson and the auramine-rhodamine staining were positive in 19.6% and 26.8% patients, respectively. On culture, the lymph node aspirate was positive for Mycobacterium species in 40.6% patients. In all but two cases, the culture revealed presence of Mycobacterium tuberculosis. The other two cultures revealed growth of Mycobacterium fortuitum chelonae complex. Of the two HIV-positive patients, M. tuberculosis could be isolated in one case. CONCLUSION: Findings of this study suggest that M. tuberculosis is still the most common cause of tuberculous lymphadenitis and MOTT are responsible for very few cases. However, such studies need to be carried out frequently at various centres so as to see any periodic and geographic variations within India.

Adolescent↗