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A Jain

Publications and source records attributed to A Jain.

At least 73 records · Page 4Linked to original sources

Pseudotumor syndrome associated with antiphospholipid antibodies and cerebral venous sinus thrombosis.

Antiphospholipid antibodies have been recognized as a marker for an increased risk of thrombosis, including cerebral venous thrombosis. This is a clinical study of three patients who presented with features of raised intracranial tension. Investigations revealed normal CT of brain and CSF examination in two patients. MRI of brain revealed dural venous sinus thrombosis in all the patients and positive antiphospholipid antibodies in the blood. All patients recovered with anticoagulant therapy. Antiphospholipid antibodies should be considered in the differential diagnosis of pseudotumor syndrome related to cerebral venous thrombosis.

Adolescent↗

Treatment of new pulmonary tuberculosis patients: what do allopathic doctors do in India?

SETTING: Out- and in-patient services of the Department of Tuberculosis and Chest Diseases at King George's Medical College, Lucknow, India. OBJECTIVE: To analyse the prescribing patterns of allopathic doctors for treatment of new cases of pulmonary tuberculosis (PTB), and to compare their practices with the current national and World Health Organization (WHO) recommendations. DESIGN: A consecutive case series. Tuberculosis treatment practices of 449 primary doctors who had prescribed treatment for PTB to 218 patients were analysed. RESULTS: Thirty-three different drug combination regimens were prescribed by 449 primary doctors. Approximately 45% (95%CI 41.5-49.9) of doctors did not practise the current NTP/WHO recommended drug regimens. Overall 75% (95%C1 70.4-78.8) of doctors made prescription errors with respect to one or more aspects of treatment, including treatment duration (64.5%) and drug dosages (30%). The most frequent prescription error was treatment for longer than necessary (60.2%; 95%CI 55.5-64.8). Overall, both chest specialists and non-chest specialists made prescription errors with almost equal frequency (77.5% vs. 72.2%, P = 0.228). The majority of the doctors (70.2%; 95%CI 65.7-74.5) used fixed-dose formulations of two to four drugs. CONCLUSION: For effective tuberculosis control, strategies for targeted continuing medical education and auditing of the practices of all doctors need to be implemented without delay.

Adolescent↗

Anti-inflammatory effects of erythromycin and tetracycline on Propionibacterium acnes induced production of chemotactic factors and reactive oxygen species by human neutrophils.

Propionibacterium acnes (P. acnes), an anaerobic pathogen, plays an important role in the pathogenesis of acne and seems to initiate the inflammatory process by producing neutrophil chemotactic factors (NCF). Once neutrophils attracted by bacterial chemoattractants reach the inflamed site, they release inflammatory mediators such as lysosomal enzymes and reactive oxygen species (ROS). Previously, it has been shown that antibiotics may affect acne by means other than their anti-bacterial effects. Thus, we investigated the effect of subminimal inhibitory concentration (sub-MIC) of tetracycline and erythromycin on production of NCF and ROS. NCF was tested in vivo in a mouse model and ROS was estimated on human PMNL in vitro, by nitroblue tetrazolium dye reduction test (NBT) and cytochrome-C reduction test. Tetracycline (CS-T) and Erythromycin (CS-E) treated cultures showed a significant reduction of 35.8% and 58.3% in NCF production respectively, as compared to P. acnes stimulated cultures. Tetracycline and erythromycin at their sub-MIC also significantly inhibited release of ROS from human PMNL. Thus, tetracycline and erythromycin, besides having antibacterial activity, also have an anti-inflammatory action. These antibiotics reduce the capacity of P. acnes to produce NCF, as well decrease its ability to induce ROS from PMNL.

Acne Vulgaris↗

Evaluation of enzymes in serum and cerebrospinal fluid in cases of stroke.

Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) were estimated in serum and cerebrospinal fluid of 25 patients of stroke, and were correlated with severity of disease. 21 (84%) patients had ischemic stroke and four (16%) had hemorrhagic stroke. Serum and CSF AST levels were significantly elevated in the study group. The rise in CSF AST was more in the hemorrhagic subtype than in the ischemic subtype. Serum ALT and CSF LDH levels were also significantly elevated in patients with ischemic stroke. None of the enzyme levels were related to the severity of disease as assessed by the Glasgow coma scale.

Adult↗

Elevated levels of high-mobility-group chromosomal proteins, HMGA1, in murine skin carcinoma.

The high-mobility-group, HMGA1 (formerly HMGI(Y)) chromosomal proteins are known to be involved in gene regulation and their high expression is associated with neoplastic transformation of cells and metastatic tumor progression. Here, we present our results on the expression of HMGA1 in murine skin carcinoma as detected by acid-urea electrophoresis, reverse-phase high-performance liquid chromatography and Western blot. The enhanced expression of HMGA1 proteins directly correlates with the extent of cellular atypia and neoplastic changes noticed in the histopathology of tumor and suggest a potential use of these proteins as marker for determining the grade of skin tumor.

Acetic Acid↗

Histopathologic variability in usual and nonspecific interstitial pneumonias.

Findings of surgical lung biopsy (SLB) are important in categorizing patients with idiopathic interstitial pneumonia (IIP). We investigated whether histologic variability would be evident in SLB specimens from multiple lobes in patients with IIP. SLBs from 168 patients, 109 of whom had multiple lobes biopsied, were reviewed by three pathologists. A diagnosis was assigned to each lobe. A different diagnosis was found between lobes in 26% of the patients. Patients with usual interstitial pneumonia (UIP) in all lobes were categorized as concordant for UIP (n = 51) and those with UIP in at least one lobe were categorized as discordant for UIP (n = 28). Patients with nonspecific interstitial pneumonia (NSIP) in all lobes were categorized as having fibrotic (n = 25) or cellular NSIP (n = 5). No consistent distribution of lobar histology was noted. Patients concordant for UIP were older (63 +/- 9 [mean +/- SD] yr; p < 0.05 as compared with all other groups) than those discordant for UIP (57 +/- 12 yr) or with fibrotic NSIP (56 +/- 11 yr) or cellular NSIP (50 +/- 9 yr). Semiquantitative high-resolution computed tomography demonstrated a varied profusion of fibrosis (p < 0.05 for all group comparisons), with more fibrosis in concordant UIP (2.13 +/- 0.62) than in discordant UIP (1.42 +/- 0.73), fibrotic NSIP (0.83 +/- 0.58), or cellular NSIP (0.44 +/- 0.42). Survival was better for patients with NSIP than for those in both UIP groups (p < 0.001), although survival in the two UIP groups was comparable (p = 0.16). Lobar histologic variability is frequent in patients with IIP, patients with a histologic pattern of UIP in any lobe should be classified as having UIP.

Analysis of Variance↗

Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase II.

Intermolecular interactions of eleven different fluoroaromatic inhibitors are probed within the scaffolding of the crystal lattice of Phe-131-->Val carbonic anhydrase II. The degree and pattern of fluorine substitution on the inhibitor benzyl ring modulate its size, shape, and electronic character. In turn, these properties affect the geometry of intermolecular interactions between the fluoroaromatic rings of two different inhibitor molecules bound in the crystal lattice, as determined by X-ray crystallography. Depending on the degree and pattern of fluorine substitution, we observe a face-to-face (aromatic-aromatic) interaction, an atom-to-face (carbonyl-aromatic) interaction, or no interaction at all. These interaction geometries are analyzed with regard to van der Waals, electrostatic, and possible charge-transfer effects. For the aromatic-aromatic interactions investigated in this study, with aromatic ring quadrupoles specifically "tuned" by the degree and pattern of fluorination, the structural results suggest that London forces and charge-transfer complexation dominate over weakly polar electrostatic interactions in the association of aromatic ring pairs.

Binding, Competitive↗

A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone and mycophenolate mofetil in primary adult liver transplantation: a single center report.

BACKGROUND: Tacrolimus (TAC) and mycophenolate mofetil (MMF) are currently approved immunosuppressants for prevention of rejection in liver transplantation (LTx). They have different modes of action and toxicity profiles, but the efficacy and safety of MMF in primary liver transplantation with TAC has not been determined. METHODS: An Institutional Review Board-approved, open-label, single-center, prospective randomized trial was initiated to study the efficacy and toxicity of TAC and steroids (double-drug therapy (D)) versus TAC, steroids, and MMF (triple-drug therapy (T)) in primary adult LTx recipients. Both groups of patients were started on the same doses of TAC and steroids. Patients randomized to T also received 1 gm MMF twice a day. RESULTS: Between August 1995 and May 1998, 350 patients were enrolled at a single center-175 in the D and 175 in the T groups. All patients were followed until May 1998, with a mean follow-up of 33.8+/-9.1 months. Using an intention-to-treat analysis, the 1-, 2-, 3-, and 4-year patient survival was 85.1%, 81.6%, 78.6%, and 75.8%, respectively, for D and 87.4%, 85.4%, 81.3%, and 79.9%, respectively, for T. The 4-year graft survival was 70% for D and 72.1% for T. Although the rate of acute rejection in the first 3 months was significantly lower for T than for D (28% for triple vs. 38.9% for double, P=0.03), the overall rate of rejection for T at the end of 1 year was not significantly lower than for the D (38.9% triple vs. 45.2% double). The median time to the first episode of rejection was 14 days for D versus 24 days for T (P=0.008). During the study period, 38 of 175 patients in D received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 103 patients in the T discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. The need for corticosteroids was less after 6 months for T and the perioperative need for dialysis was lower with use of MMF. CONCLUSION: This final report confirms similar patient survival and graft survival up to 4 years with a trend towards fewer episodes of rejection, lower need for steroids, and better perioperative renal function. However, the complex nature of LTx patients and their posttransplantation course prevents the routine application of MMF.

Adult↗

Liver transplantation for alcoholic cirrhosis: long term follow-up and impact of disease recurrence.

BACKGROUND: Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse. METHODS: Retrospective cohort analysis of 123 alcoholic patients with a median of 7 years follow-up at one center. RESULTS: In addition to alcohol, 43 (35%) patients had another possible factor contributing to cirrhosis. Actuarial patient and graft survival rates were, respectively, 84% and 81% (1 year); 72% and 66% (5 years); and 63% and 59% (7 years). After transplantation, 18 patients (15%) manifested 21 noncutaneous de novo malignancies, which is significantly more than controls (P=0.0001); upper aerodigestive squamous carcinomas were overrepresented (P=0.03). Thirteen patients had definitely relapsed and three others were suspected to have relapsed. Relapse was predicted by daily ethanol consumption (P=0.0314), but not by duration of pretransplant sobriety or explant histology. No patient had alcoholic hepatitis after transplantation and neither late onset acute nor chronic rejection was significantly increased. Multiple regression analyses for predictors of graft failure identified major biliary/vascular complications (P=0.01), chronic bile duct injury on biopsy (P=0.002), and pericellular fibrosis on biopsy (P=0.05); graft viral hepatitis was marginally significant (P=0.07) on univariate analysis. CONCLUSIONS: Alcoholic liver disease is an excellent indication for liver transplantation in those without coexistent conditions. Recurrent alcoholic liver disease alone is not an important cause of graft pathology or failure. Potential recipients should be heavily screened before transplantation for coexistent conditions (e.g., hepatitis C, metabolic diseases) and other target-organ damage, especially aerodigestive malignancy, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease.

Adult↗

Reversal of steroid- and anti-lymphocyte antibody-resistant rejection using intravenous immunoglobulin (IVIG) in renal transplant recipients.

BACKGROUND: Despite the recent advances in immunosuppression, steroid-resistant rejection remains a difficult problem in renal transplant recipients. METHODS: We reviewed our experience with i.v. immunoglobulin (IVIG) in the treatment of steroid- and antilymphocyte antibody-resistant rejection in renal transplant patients. Between September 1996 and March 1999, 17 patients were treated with IVIG to reverse steroid- or antilymphocyte antibody-resistant rejection. A total of 2 g/kg of IVIG was administered to patients during each treatment course. RESULTS: With a mean follow-up of 21.5+/-9.5 months from the time of IVIG administration, patient and graft survival rates were 94% (16/17) and 71% (12/17), respectively. The baseline mean serum creatinine level prior to rejection was 2.2+/-0.7 mg/dl and peaked at 3.3+/-1.1 mg/dl at the time of the diagnosis of refractory rejection. IVIG therapy was associated with a fall in the mean creatinine to 2.8+/-1.1 mg/dl. The most recent serum creatinine in patients with functioning grafts was 2.8+/-1.6 mg/dl. In 82% of allograft biopsies after IVIG, reversal or reduction in the severity of rejection was demonstrated. In addition, IVIG therapy rescued three of four patients with antilymphocyte antibody-resistant rejection. CONCLUSIONS: IVIG rescue therapy for steroid- or antilymphocyte antibody-resistant rejection is associated with resolution or improvement of rejection severity, stable renal function, and reasonable graft survival.

Adult↗

Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeast.

Multicellular organisms must have means of preserving their genomic integrity or face catastrophic consequences such as uncontrolled cell proliferation or massive cell death. One response is a modification of nuclear proteins by the addition and removal of polymers of ADP-ribose that modulate the properties of DNA-binding proteins involved in DNA repair and metabolism. These ADP-ribose units are added by poly(ADP-ribose) polymerase (PARP) and removed by poly(ADP-ribose) glycohydrolase. Although budding yeast Saccharomyces cerevisiae does not possess proteins with significant sequence similarity to the human PARP family of proteins, we identified novel small molecule inhibitors against two family members, PARP1 and PARP2, using a cell-based assay in yeast. The assay was based on the reversal of growth inhibition caused by the heterologous expression of either PARP1 or PARP2. Validation of the assay was achieved by showing that the growth inhibition was relieved by a mutation in a single residue in the catalytic site of PARP1 or PARP2 or exposure of yeast to a known PARP1 inhibitor, 6(5H)-phenanthridinone. In separate experiments, when a putative protein regulator of PARP activity, human poly(ADP-ribose) glycohydrolase, was coexpressed with PARP1 or PARP2, yeast growth was restored. Finally, the inhibitors identified by screening the yeast assay are active in a mammalian PARP biochemical assay and inhibit PARP1 and PARP2 activity in yeast cell extracts. Thus, our data reflect the strength of using yeast to identify small molecule inhibitors of therapeutically relevant gene families, including those that are not found in yeast, such as PARP. The resultant inhibitors have two critical uses (a) as leads for drug development and (b) as tools to dissect cellular function.

ATP-Binding Cassette Transporters↗

Converted laparoscopic colorectal surgery.

BACKGROUND: Conversion rates following laparoscopic colorectal surgery vary widely between studies, and the outcome of converted patients remains controversial. METHODS: A comprehensive search of the English-language literature was updated until May 1999. RESULTS: Twenty-eight studies on 3232 patients were considered for analysis. The overall conversion rate was 15.38%. Seventy nine percent of the studies did not include a definition for conversion; in these studies, the conversion rate was significantly lower than in the series where a specific definition was considered (13.7% vs 18.9%, chi-square test, p < 0.001). Converted patients had a prolonged hospital stay (11.38 vs 7.41 days) and operative time (209 vs 189 min) in comparison with laparoscopically completed patients (95% confidence interval (CI), 1.70-4.00 and 35.90-37.10, respectively). The factors associated with an increased rate for conversion were left colectomy (Odds Ratio [OR] = 1.061), anterior resection of the rectum (OR = 1.088), diverticulitis (OR = 1.302), and cancer (OR = 2.944) (for each parameter, Wald chi-square value, p < 0.001). CONCLUSIONS: In nonrandomized studies, the rate of laparoscopically completed colorectal resections is close to 85%. Because converted patients have a distinct outcome, a clear definition of conversion is required to compare the results of randomized trials. Such trials should also consider a 20% rate of conversion when estimating the sample size for the desired power level. It is likely that converted patients will have a significant impact on the results of future clinical research in laparoscopic colorectal surgery.

Aged↗

Reasons for long-term use of steroid in primary adult liver transplantation under tacrolimus.

BACKGROUND: Tacrolimus is a potent immunosuppressive agent that provides higher freedom from acute and chronic rejection than cyclosporine after liver transplantation (LTx). Initially, a steroid-free state was observed in about 70% of patients at 1 year; this did not change over the next 5 years. The present study identifies the various reasons why the remaining 30% of adult patients still require steroids even after 5 years after successful LTx. METHOD: Eight hundred thirty-four consecutive patients who underwent LTx between August 1989 and December 1992 were included in this study. Four hundred ninety-nine patients were alive in January 1999 and were available for this study. The dose of steroid and the reason for steroid use were retrospectively determined from the clinical records. RESULTS: Three hundred sixty-five patients (73.1%) were off steroid, whereas 134 patients (26.9%) were receiving prednisone (mean dose was 6.4+/-3.7 mg/day) at the time of the study. Four hundred and eight-four patients (97%) were off prednisone at some time after LTx; however, in 119 (23.8%) patients, steroids were reintroduced. Fifteen patients (3%) continued to receive prednisone; eight receive prednisone due to reluctance of the local physician to withdraw the medication; in five patients, the prednisone was not withdrawn because these patients were on cyclosporine; in the remaining two patients, repeated attempts to withdraw steroid resulted in a rise in liver function test. In the 49 (36.6%) of 119 patients in whom the steroid was reintroduced, it was restarted secondary to pathologically proven or clinically suspected rejection (group I). In five patients steroid was reintroduced for abnormal liver function after being off immunosuppression for treatment of a posttransplantation lymphoproliferative disorder. Six patients were noncompliant with their immunosuppressive medication, and the steroid was reintroduced to control rejection. Steroids were reintroduced in 30 patients (22.4%) for recurrence of original disease: primary biliary cirrhosis (n= 19), sclerosing cholangitis (n=6), and autoimmune hepatitis (n=5) (group II). In 24 patients (20.2%), steroids were reintroduced to lower the dose of tacrolimus secondary to nephrotoxicity. Six of these patients received kidney transplantation (group III). In 16 patients (13.4%) the steroid was reintroduced for concomitant medical problems, consisting of ulcerative/Crohn's colitis (n=6), adrenal insufficiency (n=5), hematological disorders (n=3), dermatitis (n=1), and rheumatoid arthritis (n=1) (group IV). CONCLUSION: Ninety-seven percent of patients under tacrolimus were weaned off steroid; however, 23.8% required steroid reintroduction for late rejection, recurrence of autoimmune process(es), renal impairment, or the concomitant presence of other medical conditions. Although the use of other immunosuppressive agents may reduce the rate of reintroduction of steroid, long-term sustained freedom from steroid may not be possible in all patients under tacrolimus secondary to these conditions.

Adult↗

Novel Sp family-like transcription factors are present in adult insect cells and are involved in transcription from the polyhedrin gene initiator promoter.

We earlier documented the involvement of a cellular factor, polyhedrin (polh) promoter-binding protein, in transcription from the Autographa californica nuclear polyhedrosis virus polh gene promoter. Sequences upstream of the polh promoter were found to influence polh promoter-driven transcription. Analysis of one such region, which could partially compensate for the mutated polh promoter and also activate transcription from the wild-type promoter, revealed a sequence (AcSp) containing a CACCC motif and a loose GC box resembling the binding motifs of the transcription factor Sp1. AcSp and the consensus Sp1 sequence (cSp) specifically bound factor(s) in HeLa and Spodoptera frugiperda (Sf9) insect cell nuclear extracts to generate identical binding patterns, indicating the similar nature of the factor(s) interacting with these sequences. The AcSp and cSp oligonucleotides enhanced in vivo expression of a polh promoter-driven luciferase gene. In vivo mopping of these factor(s) significantly reduced transcription from the polh promoter. Recombinant viruses carrying deletions in the upstream AcSp sequence confirmed the requirement of these factor(s) in polh promoter-driven transcription in the viral context. We demonstrate for the first time DNA-protein interactions involving novel members of the Sp family of proteins in adult insect cells and their involvement in transcription from the polh promoter.

Animals↗

Polyotia.

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Child↗

Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium demonstrates its potential for tendon destruction in rheumatoid arthritis.

OBJECTIVE: To investigate the role of proinflammatory cytokines, vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the destruction of tendons by tenosynovium in rheumatoid arthritis (RA). METHODS: Synovial specimens were obtained from encapsulating tenosynovium (n = 17), invasive tenosynovium (n = 13), and wrist joints (n = 17) in 18 RA patients undergoing wrist extensor tenosynovectomy. Synovial membrane cells were dissociated from connective tissue by enzyme digestion and cultured in vitro for 48 hours, and harvested supernatants were assayed for the cytokines tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6), VEGF, MMPs 1, 2, 3, and 13, and TIMP-1 by enzyme-linked immunosorbent assay. Gelatin zymography was performed to demonstrate enzyme activity. Statistical analysis was performed using Student's paired 2-tailed t-tests for parametric data and the Wilcoxon signed rank test for nonparametric data. RESULTS: MMP-1 and MMP-13 levels were approximately 2.5-fold higher in invasive tenosynovium compared with encapsulating tenosynovium. Levels of MMP-2 were approximately 1.5-fold higher in invasive tenosynovium compared with both encapsulating tenosynovium and wrist joint synovium. MMP-13 (P = 0.009) and IL-6 (P = 0.03) levels were significantly lower in encapsulating tenosynovium compared with wrist joint synovium. Levels of VEGF, TIMP-1, TNFalpha, and MMP-3 were similar in all synovial sample groups. Zymography demonstrated enzyme activity in all synovium samples from all 9 patients assessed. CONCLUSION: Tenosynovium produces proinflammatory cytokines and proteolytic enzymes that are important in the tissue degradation seen in RA. Increased production of the enzymes MMP-1, MMP-2, and MMP-13 by invasive tenosynovium suggests a possible explanation for the worse prognosis and increased rupture rate associated with invasive tenosynovitis in RA. Production of VEGF by tenosynovium suggests that angiogenesis may have a role in tenosynovial proliferation and invasion of tendons.

Adult↗