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Biomedical subjects

N Agarwal

Publications and source records attributed to N Agarwal.

At least 37 records · Page 2Linked to original sources

A critical evaluation of laboratory tests in acute pancreatitis.

An ideal laboratory test in the evaluation of a patient with acute pancreatitis (AP) should, in addition to accurately establishing the diagnosis of AP, provide early assessment of its severity and identify the etiology. None of the tests available today meet all these criteria, and presently there is no biochemical test that can be considered the "gold standard" for the diagnosis and assessment of severity of AP. In the diagnosis of AP, serum amylase and lipase remain important tests. Advantages of amylase estimation are its technical simplicity, easy availability, and high sensitivity. However, its greatest disadvantage is its low specificity. A normal amylase would usually exclude the diagnosis of AP, with the exception of AP secondary to hyperlipidemia, acute exacerbation of chronic pancreatitis, and when the estimation of amylase is delayed in the course of the disease. The major advantage of lipase is an increased sensitivity in acute alcoholic pancreatitis and in patients who initially present to the emergency room days after the onset of the disease, as lipase remains elevated longer than amylase. Although once considered to be specific for AP, nonspecific elevations of lipase have been reported in almost as many disorders as amylase, thus decreasing its specificity. Simultaneous estimation of amylase and lipase does not improve the accuracy. Other enzymes for the diagnosis of AP--pancreatic isoamylase, immunoreactive trypsin, and elastase--are more cumbersome and expensive and have no clear role in the diagnosis of AP. No enzyme assay has a predictive role in determining the severity or etiology of AP. Once the diagnosis of AP is established, daily measurements of enzymes have no value in assessing the clinical progress of the patient or ultimate prognosis and should be discouraged. A host of new serological and urinary markers have been investigated in the last few years. Their main use is in predicting the severity of AP. At present, serum C-reactive protein at 48 h is the best available laboratory marker of severity. Urinary trypsinogen activation peptides within 12-24 h of onset of AP are able to predict the severity but are not widely available. Serum interleukins 6 and 8 seem promising but remain experimental.

Acute Disease↗

Impact of daily versus weekly hematinic supplementation on anemia in pregnant women.

OBJECTIVE: To compare the effectivity of weekly versus daily iron therapy in reducing maternal anemia and to evaluate the association of maternal hemoglobin and fetal growth. DESIGN: Prospective. SETTING: Tertiary care teaching hospital in an urban metropolis. METHOD: 40 pregnant women received daily and 40 pregnant women received weekly oral therapy (335 mg of ferrous sulphate and 500 g folic acid) for a period of 14 weeks. The age of each pregnant woman and their baseline anthropometric data (weight, height and body mass index) were estimated. Hemoglobin and hematocrit estimations were carried out during follow period at 4 wks, 8 wks and 14 weeks. Serum ferritin values as a marker of iron status were also calculated in both the groups initially, at 14 weeks and at the time of delivery. Fetal anthropometric indices of 137 full term neonates delivered to mothers included in either of the supplementation groups or admitted to the hospital were also studied in relation to maternal hemoglobin concentration. RESULTS: Forty subjects each were initially randomized into groups I and II. The age of pregnant women along with their baseline anthropometric data were similar in both groups. A total of 29 pregnant women in group I and 27 pregnant women in group II could be regularly followed up. The increase in hemoglobin and hematocrit values were similar in daily and weekly supplemented mothers. An intention to treat analysis also showed similar results. The ferritin values were similar at the start of supplementation and after 14 wks of weekly or daily iron therapy. Birth weight, crown heel length, head circumference of the neonate and placental weight increased significantly with rise in maternal hemoglobin levels. CONCLUSION: Weekly iron supplementation is an effective mode of treating anemia among pregnant women and maternal anemia during pregnancy is adversely associated with fetal growth.

Anemia↗

Expression pattern of sigma receptor 1 mRNA and protein in mammalian retina.

Sigma receptors are nonopiate and nonphencyclidine binding sites that are thought to be neuroprotective due to modulation of N-methyl-D-aspartate (NMDA) receptors. Sigma receptor 1 expression has been demonstrated in numerous tissues including brain. Recently, studies using binding assays have demonstrated sigma receptor 1 in neural retina, however these studies did not demonstrate in which retinal cell type(s) sigma receptor 1 was present nor did they establish unequivocally the molecular identity of the receptor. The present study was designed to address these issues. Reverse transcription-polymerase chain reaction (RT-PCR) analysis amplified sigma receptor 1 in neural retina, RPE-choroid complex, and lens isolated from mice. A similar RT-PCR product was amplified also in three cultured cell lines, rat Müller cells, rat ganglion cells and human ARPE-19 cells. In situ hybridization analysis revealed abundant sigma receptor 1 expression in ganglion cells, cells of the inner nuclear layer, inner segments of photoreceptor cells and retinal pigment epithelial (RPE) cells. Immunohistochemical studies detected the sigma receptor 1 protein in retinal ganglion, photoreceptor, RPE cells and surrounding the soma of cells in the inner nuclear layer. These data provide the first cellular localization of sigma receptor 1 in neural retina and establish the molecular identity of sigma receptor 1 in retinal cells. The demonstration that sigma receptor 1 is present in ganglion cells is particularly noteworthy given the well-documented susceptibility of these cells to glutamate toxicity. Our findings suggest that retinal ganglion cells may be amenable to the neuroprotective effects of sigma ligands under conditions of neurotoxicity such as occurs in diabetes.

Animals↗

High cholesterol diet down regulates the activity of activator protein-1 but not nuclear factor-kappa B in rabbit brain.

Cardiovascular risk factors and alterations in cholesterol metabolism are implicated in the pathogenesis of Alzheimer's dementia (AD). The hypercholesterolemic rabbit model of atheroslerosis and AD was utilized in this study to examine oxidative stress related changes in the brain. The high cholesterol diet induced dramatic increases in plasma and liver cholesterol concentrations, but brain cholesterol levels remained constant. Similar effects have been found regarding lipid oxidation products. The amounts of conjugated dienes, trienes and thiobarbituric acid reactive substances (TBARS) significantly increased in the plasma of cholesterol treated animals while the brain cortex showed no signs of increased lipid peroxidation. The oxidative damage sensitive nuclear transcription factor kappa B (NF-kappaB) and activator protein-1 (AP-1) diverged in their responses. Accordingly, the AP-1 DNA binding activity decreased by more than 50% in brain nuclear protein extracts while the NF-kappaB binding activity remained unaltered by the hypercholesterol diet. These results indicate that despite the relative resistance of the central nervous system to dietary manipulation of its lipid composition and lipid peroxidation products, chronic dietary intake of cholesterol can alter the function of certain proteins involved in regulation of gene expression in the brain.

Animals↗

Characterization of a transformed rat retinal ganglion cell line.

The purpose of the present study was to establish a rat retinal ganglion cell line by transformation of rat retinal cells. For this investigation, retinal cells were isolated from postnatal day 1 (PN1) rats and transformed with the psi2 E1A virus. In order to isolate retinal ganglion cells (RGC), single cell clones were chosen at random from the transformed cells. Expression of Thy-1 (a marker for RGC), glial fibrillary acidic protein (GFAP, a positive marker for Muller cells), HPC-1/syntaxin (a marker for amacrine cells), 8A1 (a marker for horizontal and ganglion cells) and neurotrophins was studied using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunocytochemistry. One of the retinal cell clones, designated RGC-5, was positive for Thy-1, Brn-3C, Neuritin, NMDA receptor, GABA-B receptor, and synaptophysin expression and negative for GFAP, HPC-1, and 8A1, suggesting that it represented a putative RGC clone. The results of RT-PCR analysis were confirmed by immunocytochemistry for Thy-1 and GFAP. Upon further characterization by immunoblotting, the RGC-5 clone was positive for Thy-1, negative for GFAP, 8A1 and syntaxin. RGC 5 cells were also positive for the expression of neurotrophins and their cognate receptors. To establish the physiological relevance of RGC-5, the effects of serum/trophic factor deprivation and glutamate toxicity were analyzed to determine if these cells would undergo apoptosis. The protective effects of neurotrophins on RGC-5 after serum deprivation was also investigated. Apoptosis was studied by terminal deoxynucleotidyl transferase-mediated fluoresceinated dUTP nick end labeling (TUNEL). Serum deprivation resulted in apoptosis and supplementation with both BDNF and NT-4 in the growth media, protected the RGC-5 cells from undergoing apoptosis. On differentiation with succinyl concanavalin A (sConA), RGC-5 cells became sensitive to glutamate toxicity, which could be reversed by inclusion of ciplizone (MK801). In conclusion, a transformed rat retinal cell line, RGC-5, has certain characteristics of retinal ganglion cells based on Thy-1 and Brn-3C expression and its sensitivity to glutamate excitotoxicity and neurotrophin withdrawal. These cells may be valuable in understanding of retinal ganglion cell biology and physiology including in vitro manipulations in experimental models of glaucoma.

Animals↗

Bcl-2 overexpression protects photooxidative stress-induced apoptosis of photoreceptor cells via NF-kappaB preservation.

We recently showed that photooxidative stress on cultured photoreceptor cells results in down-modulation of NF-kappaB activity which then leads to apoptosis of cultured 661W photoreceptor cells. In an effort to further delineate the mechanism of photoreceptor cell death, we sought to determine the effects of Bcl-2 overexpression on cell survivability. Wild-type 661W cells were transfected with the plasmid construct pSFFV-neo-Bcl-2 and several clones were isolated. All clones demonstrated increased Bcl-2 mRNA and protein levels, with the B4 clone exhibiting the greatest enhancement. On exposure to visible light the B4 cells were protected from undergoing apoptosis when compared with the mock transfected cells, as ascertained by TUNEL apoptosis assay and formazan based estimation of cell viability. The Bcl-2 overexpressing cells also maintained a higher Bcl-2/Bax ratio, suggesting that this ratio is important in protection from photooxidative stress. Electrophoretic mobility shift assays for NF-kappaB demonstrated higher activity in both nuclear and cytosolic fractions of the B4 photoreceptors compared with the 661W wild-type cells at all light exposure time points. Furthermore, the findings of the gel shift assays were further supported by immunocytochemistry for NF-kappaB which revealed that protein levels of the RelA subunit of NF-kappaB were protected in the nucleus as well as in the cytoplasm of Bcl-2 overexpressing B4 cells exposed to light compared to the 661W cells. These results suggest that Bcl-2 overexpression protects NF-kappaB protein levels and activity in the nucleus, indicating that preservation of NF-kappaB binding activity in the nucleus may be essential for photoreceptor cells to survive photooxidative damage induced apoptosis.

Animals↗

Laparoscopic ovarian drilling in clomiphene citrate-resistant women with polycystic ovary syndrome.

STUDY OBJECTIVE: To analyze the efficacy of laparoscopic ovarian drilling using monopolar diathermy in women with anovulatory infertility with clomiphene-resistant polycystic ovary syndrome (PCOS), and to determine factors influencing pregnancy rate and pregnancy outcomes. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: Infertility clinic in a tertiary referral teaching hospital. PATIENTS: Seventy women with clomiphene-resistant PCOS. INTERVENTION: Laparoscopic ovarian drilling, with follow-up for 4.5 years. MEASUREMENTS AND MAIN RESULTS: Follow-up data, which were available for 66 patients, showed a spontaneous ovulation rate of 81.8%, cumulative ovulation rate of 93.9%, and pregnancy rate of 54.5%. Successful pregnancies were commonly complicated by gestational diabetes mellitus and pregnancy-induced hypertension. Pregnancy rates (23.5%) were low in women with tuboperitoneal disease and those whose partners had subfertile male factors. Statistical evaluation using a proportion test (Z test) and multivariable logistical regression analysis showed that elevated luteinizing hormone levels (>10 IU/L), short duration of infertility (<3 yrs), and absence of preexisting tubal disease were associated with better outcomes. CONCLUSION: Laparoscopic ovarian drilling is an effective surgical procedure in women with clomiphene-resistant PCOS.

Adult↗

Laparoscopic management of Sertoli-Leydig cell tumors of the ovary. A report of two cases.

BACKGROUND: Sertoli-Leydig cell tumor is a rare ovarian tumor with an incidence of < .5% of all ovarian tumors. Laparotomy is the standard approach to these cases. CASES: Sertoli-Leydig cell tumors were diagnosed in two young, nulliparous, infertile women. Both presented with secondary amenorrhea. Virilization was found in one. Their testosterone levels were high, and sonography revealed a solid, echogenic mass in the fornix. Laparoscopic removal was performed. Both women achieved normal menstruation one month after the operation, and one became pregnant and gave birth to a healthy infant. CONCLUSION: There are very few case reports of laparoscopic removal of such tumors. Laparoscopic surgery, which is minimally invasive and cosmetically acceptable and has a speedy recovery, should be the approach of choice for these patients.

Adult↗

Successful pregnancy outcome in advanced chronic renal failure.

A 24 years female of advanced chronic renal failure due to lupus nephritis presented with pregnancy of eight weeks duration she continued the pregnancy against medical advice. At 29 weeks gestation further deterioration of renal function prompted weekly dialysis and hospitalisation for intensive maternal and fetal monitoring. At 35 weeks she was safely delivered by elective caesarian section. This is the first case of dialysis during pregnancy to be reported from India.

Adult↗

A study of autoimmune markers in hepatitis C infection.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV) infection is associated with several autoimmune markers. Despite HCV being common in India, no information on this aspect is available. This study was undertaken to ascertain the frequency and clinical significance of autoimmune markers like rheumatoid factor (RF), antinuclear antibodies (ANA), antibodies to double stranded deoxyribonucleic acid (dsDNA), anti neutrophil cytoplasmic antibody (ANCA), anti smooth muscle antibodies (ASMA), anti liver kidney microsomal 1 antibodies (anti LKM1), anti gastric parietal cell antibodies (anti GPCA), anti mitochondrial antibodies (AMA), anti cardiolipin antibodies (ACL) and cryoglobulins in HCV infection and to determine the effect of treatment on these markers. METHODS: Twenty five patients with chronic hepatitis C and 25 healthy controls were studied. Cryoglobulins were detected by cryoprecipitation, RF by latex agglutination, anti dsDNA and ACL by ELISA while indirect immunofluorescence was used to detect all other autoantibodies. RESULTS: Eighteen patients (72%) demonstrated autoimmune markers. RF, cryoglobulins and anti LKM1 antibodies were the most frequently detected markers (in 32% patients each). ASMA, perinuclear ANCA (pANCA), ANA and anti GPCA were seen in 24, 20, 12 and 4 per cent patients respectively. None of the patients exhibited ACL, AMA or antibodies to dsDNA. No antibodies were detected in healthy controls. Sixty per cent of the patients had rheumatological symptoms. Of the seven patients followed up after treatment with alpha interferon, only two exhibited persistence of RF, while symptoms and other markers disappeared. INTERPRETATION & CONCLUSION: Rheumatological symptoms and autoimmune markers are common in HCV infection and are usually overlooked. Patients with unexplained joint pains and/or palpable purpura should be screened for HCV. Further studies are needed to delineate fully the link between infection and autoimmunity.

Adult↗

Rupture uterus--changing Indian scenario.

A total of 60 cases of rupture uterus managed in last five years in the department of obstetrics and gynaecology at the University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi were reviewed. Of these 77% cases reported to the hospital with rupture uterus while in 23% cases rupture occurred after admission. The factor responsible for rupture in admitted patients was either oxytocin induction/augmentation in scarred uterus or obstetrical manipulation in unscarred uterus; 80% cases were totally unsupervised during antenatal period. Previous uterine scar was responsible for rupture in as high as 63.3% cases. The commonest previous surgery was caesarean section mostly for non-recurrent causes. Obstructed labour was responsible for rupture in 26.6% cases while traumatic rupture was seen in 10% cases. Repair of uterine rent was performed in 54% cases while rest required hysterectomy. Bladder injury was associated in 9 cases and was repaired at the time of laparotomy. Maternal mortality was 3.33% and foetal mortality was 78.66%. The changing trends observed in the present study are those of low maternal mortality and decreasing incidence of obstructed labour in the aetiology of rupture uterus.

Adolescent↗

Suitably functionalised pyrimidines as potential antimycotic agents.

Various suitably functionalized pyrimidine derivatives have been synthesized to explore their potential as antimycotic agents. Some of the synthesized compounds 4c, 4d, 8a-e have shown highly significant in vitro antifungal activity against five human pathogenic fungi.

Antifungal Agents↗

Upregulation of CD44 expression in the retina during the rds degeneration.

In adult mouse retinas the standard form of the cell surface adhesion/receptor molecule CD44 is localized to Müller cell apical microvilli. In the rds (retinal degeneration slow) mouse, however, CD44 immunolabel is increased and distributed throughout the retina by 3 months postnatal. At present, it is unclear if this labeling pattern is due to the increased expression of standard CD44, the expression of variant CD44 isoforms, or an unmasking of CD44 antigenic sites. To further characterize this response, we have studied the expression of CD44 mRNA and protein in rds retinas of different ages. RT-PCR analysis demonstrated one product which represented the message for standard CD44 in adult BALB/c mouse retina and in all ages of rds retinas studied. Upon Southern blotting, this major product was detected along with two minor bands of larger size in all samples. Northern blot analysis demonstrated a major transcript of approximately 4.0 kb and a minor one of 3.0 kb in all BALB/c and rds retinas. By 3 months postnatal in rds retinas, the expression of CD44 message was increased by at least two-fold. Western blot analysis demonstrated the presence of only the standard form of CD44 protein in all BALB/c and rds retinas. An increased amount of this standard CD44 protein was observed in 2, 3, and 6 month rds retinas. Thus, this study demonstrates that the inherited retinal degeneration exhibited by the rds mouse does not cause an altered expression of retinal CD44 isoforms, but does lead to an upregulation in the expression of mRNA and protein for standard CD44.

Aging↗