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Biomedical subjects

P Arora

Publications and source records attributed to P Arora.

At least 19 recordsLinked to original sources
PubMed2006

Topical amiloride ointment accelerates healing of mechanical skin ulcers in albino rabbits and patients.

The present investigation was undertaken to explore the ulcer-healing property of 1% amiloride ointment on mechanically produced skin ulcers in albino rabbits and at donor site of patients requiring split skin graft. Four skin ulcers measuring 2 X 2 cm(2) (two on either side of the midline) were made 2 cm apart on the pre-shaved back of each anesthetized rabbit up to the depth of subcutaneous tissue. Ulcers on one side of the midline were treated with sterile soft paraffin and served as control, whereas those on the other side were treated with amiloride ointment. Each ulcer was observed for its size, slough formation, and any sign of irritation on alternate days, until healing was complete. Healing of ulcers was significantly (p<0.001) accelerated with amiloride ointment in terms of days required for complete healing, ulcer size, and area under the size-time curve. In each patient, the anterior thigh was used as donor site. Grafts were harvested from midline using Watson's modification of Humby's knife. Each site was divided into proximal and distal halves and was covered with either soft paraffin tulle serving as control or 1% amiloride tulle as test site and then dressed conventionally. Healing was evaluated visually on 10th postoperative day. Healing was significantly accelerated by amiloride tulle in terms of days required for complete healing (p<0.01), better quality of skin regenerated, leading to ease of removal of dressing with less of patient's discomfort, and hence more acceptability (p<0.01). No irritation or suppression of immunity was noticeable. Thus, topical amiloride may prove to be an inexpensive and better ulcer-healing agent with no apparent side effect. Inhibition of urokinase-type plasminogen activator and modulation of field strengths by amiloride seem to be responsible for this effect.

Administration, Cutaneous↗
PubMed2004

Transcriptional networks and cellular senescence in human mammary fibroblasts.

Senescence, the molecular program that limits the finite proliferative potential of a cell, acts as an important barrier to protect the body from cancer. Techniques for measuring transcriptome changes and for modulating their expression suggest that it may be possible to dissect the transcriptional networks underlying complex cellular processes. HMF3A cells are conditionally immortalized human mammary fibroblasts that can be induced to undergo coordinated senescence. Here, we used these cells in conjunction with microarrays, RNA interference, and in silico promoter analysis to promote the dissection of the transcriptional networks responsible for regulating cellular senescence. We first identified changes in the transcriptome when HMF3A cells undergo senescence and then compared them with those observed upon replicative senescence in primary human mammary fibroblasts. In addition to DUSP1 and known p53 and E2F targets, a number of genes such as PHLDA1, NR4A3, and a novel splice variant of STAC were implicated in senescence. Their role in senescence was then analyzed by RNA silencing followed by microarray analysis. In silico promoter analysis of all differential genes predicted that nuclear factor-kappaB and C/EBP transcription factors are activated upon senescence, and we confirmed this by electrophoretic mobility shift assay. The results suggest a putative signaling network for cellular senescence.

Cell Cycle Proteins↗
PubMed2004

Maternal and fetal outcome in valvular heart disease.

OBJECTIVES: To compare the pregnancy outcomes of women having valvular heart disease with the pregnancy outcomes of healthy women. METHODS: A retrospective comparison of the maternal and fetal pregnancy outcomes of 312 women with valvular heart disease and 321 healthy women cared for at a tertiary care hospital during the same period. Statistical analysis was done using the chi(2)-test, with significance fixed at 0.05. RESULTS: Women with valvular heart disease had a significantly higher incidence of surgical interventions during pregnancy than women in the control group [13.4% (balloon mitral valvotomy) vs. 0.6% (ovarian cystectomy)], congestive heart failure (5.1% vs. 0%, P<0.001), and mortality [0.64% (two women) vs. 0%]. Perinatal outcome was also more adverse in the valvular heart disease group than in the control group, with increased preterm delivery rate (48.3% vs. 20.5%), reduced birth weight (2434+/-599 g vs. 2653+/-542 g; P<0.001), and a higher incidence of APGAR scores less than 8 (8.3% vs. 4%; P<0.01). There was also a higher rate of instrumental delivery (9.9% vs. 3.4%). However, the rate of cesarean deliveries was similar in the two groups. CONCLUSIONS: Pregnancy in women with valvular heart disease is associated with significantly higher maternal morbidity and adverse fetal outcomes and requires a team approach for optimal management.

Anemia↗
PubMed2003

Chiari I malformation related syringomyelia: radionuclide cisternography as a predictor of outcome.

BACKGROUND: This prospective study, conducted in patients with Chiari I malformation (C I) related syringomyelia who underwent posterior decompression and duroplasty, utilizes radionuclide cisternography in order to study the cerebrospinal fluid (CSF) dynamics at the foramen magnum and to predict the clinical outcome following surgery. METHODS: 17 consecutive patients of C I with syringomyelia (but without hydrocephalus or fixed atlanto-axial dislocation), underwent a detailed neurological examination and were assigned a clinical disability score based on the modified Klekamp and Samii score. A radionuclide cisternography (using Tc99m-DTPA) was performed via the lumbar route and the ascent of the tracer was followed utilizing a gamma camera immediately after injection and then sequentially after 1, 2, 4, 6 and 24 hours. After posterior decompression and duroplasty, the modified Klekamp and Samii score was repeated at follow-up visits (range: 3 months to one year) along with radionuclide cisternography at 3 months, and MR imaging at 6 months. FINDINGS: Three patterns of tracer flow were observed: a). rapid flow (n=7); b). supratentorial subarachnoid delay (n=7); and, c). foramen magnum block (n=3). The patients having foramen magnum block had the poorest clinical scores on admission. At follow up, there was an improvement in the clinical scores so that the mean scores in all three categories reached nearly the same level. Following posterior decompression, the radionuclide cisternography performed in 10 patients showed a rapid flow of the tracer without any obstruction. The syrinx resolved in 4 of the 11 patients in whom an MRI was done. INTERPRETATION: The patients with C I with syringomyelia may often have a free flow of tracer across the FM. Posterior decompression and duroplasty provides maximum clinical relief in patients with a demonstrable foramen magnum block on radionuclide cisternography while those with a normal flow have less relief. The symptomatology related to brain-stem compression immediately responds to the surgical procedure but the syrinx-induced signs and symptoms of spinal cord dysfunction persist.

Adolescent↗
PubMed2003

Mitral valve surgery and maternal and fetal outcome in valvular heart disease.

OBJECTIVES: To compare maternal and fetal outcomes in patients with non-operated valvular heart disease and patients who had surgery before or during pregnancy. METHODS: The 308 women with valvular heart disease who delivered in this hospital in the last 8 years were divided into three groups. The 218 (70.7%) women in group 1 had no surgical intervention; the 42 (13.6%) women in group 2 underwent balloon mitral valvotomy during pregnancy; and the 48 (15.5%) women in group 3 had surgical intervention before pregnancy (35 had balloon mitral valvotomy, eight had mitral valve replacement, and five had mitral valve repair). Maternal and fetal outcomes were compared for these three groups. RESULTS: The antenatal events differed significantly: 175 (80.3%), 40 (94.2%), and 46 (95.8%) patients in groups 1, 2 and 3, respectively, had uneventful pregnancies. In group 1, 14 (6.4%) patients had congestive heart failure (P>0.05) and 24 (11%) patients had cardiac arrhythmias, which was statistically significant. The rate of preterm deliveries did not differ significantly among the three groups. The groups did not differ in mean birth weight, mode of delivery, low birth weight, Apgar scores less than 8, stillbirths, neonatal death, or congenital anomalies. CONCLUSIONS: Mitral valve surgery before or during pregnancy did not significantly improve maternal and fetal outcomes but decreased adverse events such as congestive heart failure and cardiac arrhythmias. It should be therefore performed only in selected cases.

Adult↗
PubMed2003

Discharge from triage: modelling the potential in different types of emergency department.

OBJECTIVE: To assess the potential for patients to be assessed and discharged directly from triage in an emergency department (ED). METHODS: Modelling was undertaken by collection of retrospective electronic data from four different EDs. Serial removal of groups was undertaken using data from coding systems related to patients details of admission/treatment/investigations and procedure undertaken. The final group left were analysed for ambulance usage, prior primary care consultation, and age group. RESULTS: 29.4% patients were discharged after clinical assessment but without any specific treatment or investigation. It was seen that of the patients who can be considered for discharge from triage, 15.5% were brought to the ED by ambulance, 3.5% were patients who had already consulted primary care, and 11% were children. CONCLUSIONS: This study suggests that a large percentage of patients seen in EDs may not require the extra facilities of that department. There is potential for a large number to be discharged within a few minutes of arrival if appropriate assessment skills are available at first contact. This may require more senior assessment than is currently used. This study has not assessed safety of such a system or the times of day when it is best deployed.

Adult↗
PubMed2001

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↗
PubMed2001

Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone.

OBJECTIVE: To analyze the efficacy of an IV combination of diltiazem and digoxin vs IV diltiazem alone for acute ventricular rate control in patients with atrial fibrillation. DESIGN: Prospective, randomized, open-label study. PATIENTS AND METHODS: Fifty-two patients with atrial fibrillation and uncontrolled ventricular rates were randomized to receive either an IV combination of diltiazem and digoxin or IV diltiazem alone and were observed for 12 h. The successful rate control was defined as a ventricular rate < 100 beats per minute (bpm) persisting for 1 h or conversion to sinus rhythm. The loss of rate control was defined as an increase in the ventricular rate to > 100 bpm persistently for > 30 min or rebound to atrial fibrillation. RESULTS: In both treatment arms (n = 26 each), all patients achieved successful and comparable ventricular rate control at 12 h. The mean (+/- SD) time taken to achieve successful rate control was shorter in the combination arm (15 +/- 16 vs. 22 +/- 22 min). Six patients in the combination arm and 11 in the diltiazem-alone arm experienced episodes of loss of rate control. This loss in the combination arm was less than that in the diltiazem-alone arm (14 vs 39 episodes; p = 0.05). The loss of rate control per patient in the combination arm was also less than that in the diltiazem-alone arm (2.0 +/- 1.0 vs. 3.5 +/- 1.9 episodes per patient; p = 0.04). CONCLUSIONS: This study demonstrates that in patients with atrial fibrillation who have a rapid ventricular response, the IV combination of diltiazem and digoxin results in a more efficacious ventricular rate control with fewer fluctuations than that achieved by therapy with IV diltiazem alone.

Adolescent↗
PubMed2001

A comparative evaluation of therapeutic effects of once a day dose of losartan potassium versus enalapril maleate in mild to moderate essential hypertension.

Hypertension is a major public health problem both in the developing and developed countries of the world and if untreated, can lead to various fatal complications like cerebral stroke, encephalopathy, ischaemic heart disease (IHD), renal failure and sudden cardiac death, etc. In the present study, a comparative evaluation was made between angiotensin-II receptor antagonists like losartan potassium (50 mg daily) and angiotensin converting enzyme (ACE) inhibitors like enalapril maleate (5 mg daily) in 100 patients (50 males and 50 females having 25-50 years of age) of mild to moderate essential hypertension with diastolic blood pressure (DBP) 90-109 mmHg. Both the drugs were tried as monotherapy for their clinical efficacy, safety, tolerability and adverse effect profile in this open trial. Losartan potassium lowered the DBP to <90 mmHg in 62% of the patients at the end of 8 weeks compared to 40% in the enalapril group. Percentage of side effects with losartan was 20 and 50 with enalapril. It is concluded that both the drugs are effective antihypertensive agents and cause significant and comparable fall in systolic blood pressure (SBP) and DBP in patients of mild to moderate essential hypertension. But losartan potassium has been found to be more effective with fewer side effects when compared to enalapril maleate.

Adult↗
PubMed2000

Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration.

Osteopontin (OPN) is a secreted glycoprotein with mineral- and cell-binding properties that can regulate cell activities through integrin receptors. Previously, we identified an intracellular form of osteopontin with a perimembranous distribution in migrating fetal fibroblasts (Zohar et al., J Cell Physiol 170:88-98, 1997). Since OPN and CD44 expression are increased in migrating cells, we analyzed the relationship of these proteins with immunofluorescence and confocal microscopy. A distinct co-localization of perimembranous OPN and cell-surface CD44 was observed in fetal fibroblasts, periodontal ligament cells, activated macrophages, and metastatic breast cancer cells. The co-localization of OPN and CD44 was prominent at the leading edge of migrating fibroblasts, where OPN also co-localized with the ezrin/radixin/moesin (ERM) protein ezrin, as well as in cell processes and at attachment sites of hyaluronan-coated beads. The subcortical location of OPN in these cells was verified by cell-surface biotinylation experiments in which biotinylated CD44 and non-biotinylated OPN were isolated from complexes formed with hyaluronan-coated beads and identified with immunoblotting. That perimembranous OPN represents secreted protein internalized by endocytosis or phagocytosis appeared to be unlikely since exogenous OPN that was added to cell cultures could not be detected inside the cells. A physical association with OPN, CD44, and ERM, but not with vinculin or alpha-actin, was indicated by immunoadsorption and immunoblotting of cell proteins in complexes extracted from hyaluronan-coated beads. The functional significance of OPN in this complex was demonstrated using OPN-/- and CD-/- mouse fibroblasts which displayed impaired migration and a reduced attachment to hyaluronan-coated beads. These studies indicate that OPN exists as an integral component of a hyaluronan-CD44-ERM attachment complex that is involved in the migration of embryonic fibroblasts, activated macrophages, and metastatic cells.

Animals↗
PubMed2000

Worsening of left ventricular diastolic dysfunction during exercise causes decreased exercise tolerance in hypertension.

BACKGROUND: Exercise tolerance is reduced in hypertension. Hypertension affects left ventricular (LV) diastolic filling by causing abnormal relaxation and decreasing compliance. HYPOTHESIS: This study was designed to determine whether worsening of LV diastolic dysfunction during exercise causes decreased exercise tolerance in hypertension. METHODS: Left ventricular diastolic filling parameters were examined at mitral valve by Doppler echocardiography at rest and at peak exercise in hypertensive patients and were compared with those of age- and gender-matched normotensive individuals. Treadmill exercise stress test was performed according to the Bruce protocol and the exercise time was recorded. RESULTS: Exercise time was significantly shorter in the hypertensive group than that in the normotensive group (320 +/- 29 vs. 446 +/- 38 s, p 0.03). The hypertensive group demonstrated abnormal relaxation pattern of diastolic mitral inflow at rest, which became pseudonormal at peak exercise (E/A velocity ratio, rest 0.86 +/- 0.06 vs. exercise 1.19 +/- 0.09, p < 0.001). The diastolic mitral inflow pattern remained normal at peak exercise in the normotensive group. The deceleration time and the pressure half time of early mitral inflow at peak exercise were significantly shorter in the hypertensive group than those in the normotensive group (deceleration time, 182 +/- 20 vs. 238 +/- 22 ms, p 0.02: pressure half time, 54 +/- 5 vs. 70 +/- 12 ms, p 0.01). CONCLUSIONS: This study demonstrates that reduced exercise tolerance in hypertension is associated with worsening of diastolic dysfunction during exercise consistent with an increase in left atrial pressure.

Compliance↗
PubMed2000

Etiology, prognosis, and outcome of post-operative acute renal failure.

A Multivariate analysis was done in all patients who developed post operative ARF, during the period 1990-1995 to determine the etiological spectrum and to identify various variables affecting the outcome. Of 140 patients (110 operated at SGPGI and 30 operated outside) 116 underwent elective surgery. The different types of surgery leading to ARF were urosurgery (3.5%), open heart surgery (32.9%), gastrosurgery (16.4%), pancreatic surgery (9.3%), obstetrical surgery (3.6%) and others (2.8%). The incidence of ARF in SGPGI patients was highest in pancreatic surgery group (8.2%) followed by open heart surgery (3%). The different etiological factors responsible for ARF were perioperative hypotension (67.1%), sepsis (63.6%) and exposure to nephrotoxic drugs (29.3%). Sixty-four patients (45.7%) required dialysis. The overall mortality was 45%. The mortality was highest in patients who underwent open heart surgery (89.1%) followed by pancreatic surgery (84.6%). The factors associated with high mortality, other than the type of surgery, were preoperative hypotension (p < 0.05), oliguria (p < 0.01), need for dialysis (p < 0.05) and multiorgan failure (p < 0.001). AM following emergency surgery had poor outcome, though not statistically significant. Perioperative sepsis (p < 0.05) and preoperative use of aminoglycoside (p < 0.05) were significantly higher in patients operated outside SGPGI. This was associated with higher incidence of ARF. Thus we conclude that presence of multiorgan failure, oligoanuria, preoperative hypotension and need far dialysis are poor prognostic markers in ARF following surgery.

Acute Kidney Injury↗
PubMed2000

Biochemical and functional characterization of intercellular adhesion and gap junctions in fibroblasts.

Despite their significance in wound healing, little is known about the molecular determinants of cell-to-cell adhesion and gap junctional communication in fibroblasts. We characterized intercellular adherens junctions and gap junctions in human gingival fibroblasts (HGFs) using a novel model. Calcein-labeled donor cells in suspension were added onto an established, Texas red dextran (10 kDa)-labeled acceptor cell monolayer. Cell-to-cell adhesion required Ca(2+) and was >30-fold stronger than cell-to-fibronectin adhesion at 15 min. Electron micrographs showed rapid formation of adherens junction-like structures at approximately 15 min that matured by approximately 2-3 h; distinct gap junctional complexes were evident by approximately 3 h. Immunoblotting showed that HGF expressed beta-catenin and that cadherins and connexin43 were recruited to the Triton-insoluble cytoskeletal fraction in confluent cultures. Confocal microscopy localized the same molecules to intercellular contacts of acceptor and donor cells. There was extensive calcein dye transfer in a cohort of Texas red dextran-labeled cells, but this was almost completely abolished by the gap junction inhibitor beta-glycyrrhetinic acid and the connexin43 mimetic peptide GAP 27. This donor-acceptor cell model allows large numbers (>10(5)) of cells to form synchronous cell-to-cell contacts, thereby enabling the simultaneous functional and molecular studies of adherens junctions and gap junctions.

Cadherins↗
PubMed1999

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population.

UNLABELLED: Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. BACKGROUND: More than 285,000 individuals in the United States suffer from end-stage renal disease (ESRD) and are treated predominantly by dialysis. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are few data about the level of renal function at the onset of ESRD and no established medical criteria for the initiation of dialysis. METHODS: We report the level of serum creatinine and glomerular filtration rate (GFR) in 90,897 patients who began dialysis in the U. S. between April 1995 through September 1997. Data were obtained from the U.S. Renal Data System. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. RESULTS: The mean (SD) serum creatinine was 8.5 (3.8) mg/dl. The mean (SD) predicted GFR was 7.1 (3.1) ml/min/1.73 m2, with a range from 1 to 42 ml/min/1.73 m2. The proportion of patients with predicted GFR of > 10, 5 to 10, and <5 ml/min/1.73 m2 was 14, 63, and 23%, respectively. The mean predicted GFR was significantly lower among younger patients, women, African Americans, patients with a higher body weight, patients with ESRD because of diseases other than diabetes, uninsured patients, patients who were employed, homemakers or students, and patients selecting hemodialysis. CONCLUSIONS: There is wide variation in renal function at the initiation of dialysis in the U.S. ESRD population, and a substantial fraction of patients start dialysis at very low levels of predicted GFR. Further analyses are needed to examine the factors associated with late initiation of dialysis and its impact on the cost and outcomes of ESRD.

Adult↗
PubMed1999

Prevalence, predictors, and consequences of late nephrology referral at a tertiary care center.

Despite improvements in dialysis care, mortality of patients with end-stage renal disease (ESRD) remains high. One factor that has thus far received little attention, but might contribute to morbidity and mortality, is the timing of referral to the nephrologist. This study examines the hypothesis that late referral of patients to the nephrologist might lead to suboptimal pre-ESRD care. Clinical and laboratory data were obtained from the patient records and electronic databases of New England Medical Center, its affiliated dialysis unit (Dialysis Clinics, Inc., Boston), and the office records of the outpatient nephrology clinic. Early (ER) and late (LR) referral were defined by the time of first nephrology encounter greater than or less than 4 mo, respectively, before initiation of dialysis. Multivariate models were built to explore factors associated with LR, and whether LR is associated with hypoalbuminemia or late initiation of dialysis. Of the 135 patients, 30 (22%) were referred late. There were no differences in age, gender, race, and cause of ESRD between ER and LR patients. However, there were significant differences in insurance coverage between these two groups. In the multivariate analysis, patients covered by health maintenance organizations were more likely to be referred late (odds ratio = 4.5) than patients covered by Medicare. Compared to ER, LR patients were more likely to have hypoalbuminemia (56% versus 80%), hematocrit <28% (33% versus 55%), and predicted GFR <5 ml/min per 1.73 m2 (17% versus 40%) at the start of dialysis, and less likely to have received erythropoietin (40% versus 17%) or have a functioning permanent vascular access for the first hemodialysis (40% versus 4%). It is concluded that late referral to the nephrologist is common in the United States and is associated with poor pre-ESRD care. Pre-ESRD care of patients treated by nephrologists was also less than ideal. The patient-, physician-, and system-related factors behind this observation are unclear. Meanwhile, pre-ESRD educational efforts need to target patients, generalists, and nephrologists.

Adult↗
PubMed1999

Prevalence of and factors associated with suboptimal care before initiation of dialysis in the United States.

Despite improvements in dialysis care, the mortality of patients with end-stage renal disease (ESRD) in the United States remains high. Factors that thus far have received scant attention, but could significantly affect morbidity and mortality in dialysis patients, are the timing and quality of care before the initiation of dialysis (pre-ESRD). Data from the new version of the Health Care Financing Administration (HCFA) 2728 Form were used to examine the prevalence of and factors associated with hypoalbuminemia, severe anemia, and erythropoietin (EPO) use among 155,076 incident chronic dialysis patients in the United States between April 1, 1995 and June 30, 1997. At initiation of dialysis, the median serum albumin and hematocrit were 3.3 g/dl and 28%, respectively. Sixty percent of patients had a serum albumin below the lower limit of normal and 51% had a hematocrit <28%. Overall, only 23% had received EPO pre-ESRD. Among patients with hematocrit <28%, only 20% were receiving EPO, compared to 27% among patients with hematocrit > or =28%. In a multivariate analysis that adjusted for diabetes, functional status, and demographic, socioeconomic, and geographic factors, the odds ratios for hypoalbuminemia, hematocrit <28%, and lack of EPO use were higher for African-Americans, patients with non-private insurance or no insurance, and patients who were started on hemodialysis. There were also significant differences in odds ratios for these outcomes between different geographic regions in the United States. The high prevalence of pre-ESRD hypoalbuminemia, hematocrit <28%, and lack of EPO use suggests that the quality of pre-ESRD care in the United States is suboptimal. Improvement in pre-ESRD care could potentially improve outcomes among ESRD patients.

Adolescent↗