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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 163 records · Page 9Linked to original sources
PubMed2004

Arjunetin from Terminalia arjuna as an insect feeding-deterrent and growth inhibitor.

Crude ethanolic extract of the stem bark of Terminalia arjuna (Combretaceae) and its three compounds namely arjunic acid, arjungenin and arjunetin were evaluated for antifeedant, growth inhibitory and oviposition-deterrent activities against a lepidopterous insect Spilarctia obliqua. The compound arjunetin showed highest growth inhibitory and feeding-deterrent properties with a growth inhibition (GI(50)) and feeding-inhibition (FD(50)) of 188.5 and 287.1 micro g/g diet respectively. Oviposition bioassays indicated no oviposition-deterrence in any of the compounds tested. The structure-activity relationship study indicated the importance of a glycosidation linkage in arjunetin.

Animals↗
PubMed2004

A randomized comparison of sublingual and vaginal misoprostol for cervical priming before suction termination of first-trimester pregnancy.

This randomized trial compares the efficacy and side effects of sublingual and vaginal misoprostol for cervical priming before first-trimester pregnancy termination. One-hundred pregnant women between 6 and 12 weeks of gestation opting for termination of pregnancy by suction evacuation were included in this study. The women were randomly allocated into two groups. Group 1 received 400 microg of sublingual misoprostol and group 2 received 400 microg of vaginal misoprostol 2 h prior to suction evacuation. The abortion was carried out by suction evacuation using a Karman's cannula attached to an electrically operated suction machine under intravenous analgesia. Baseline cervical dilatation, duration of the procedure, operative blood loss, side effects and complications were noted in both groups. There was a significant difference between the sublingual and vaginal misoprostol groups with respect to mean cervical dilatation (8.6 mm vs. 6.8 mm, p < 0.05). However, the duration of the procedure (3.03 min vs. 3.16 min) and the amount of blood loss (29 mL vs. 31.2 mL) were not significantly different between the two groups. The women in the sublingual group experienced significantly more shivering and preoperative vaginal bleeding (68% vs. 56%, p < 0.05). None of the women in the two groups had either uterine perforation or excessive hemorrhage. In our study, sublingual misoprostol (400 microg) was significantly more effective in facilitating cervical dilation prior to surgical abortion than vaginal misoprostol.

Abortifacient Agents, Nonsteroidal↗
PubMed2004

A comparison of sonourethrography and retrograde urethrography in evaluation of anterior urethral strictures.

AIM: This prospective study was undertaken to evaluate the abnormalities of the male anterior urethra using high-resolution ultrasound (sonourethrography) and to compare the efficacy with that of retrograde urethrography (RGU) using operative findings as the gold standard. MATERIALS AND METHODS: Seventy patients with symptoms of lower urinary tract obstruction underwent RGU followed by sonourethrography. The sonologist was blinded to the findings of RGU. The parameters studied were compared with the intra-operative findings as gold standard, and the sensitivity, specificity and overall accuracy for the procedures were calculated. Chi-square test and kappa statistics were used where appropriate. RESULTS: All patients found to have urethral stricture disease by RGU were also detected by sonourethrography and confirmed intra-operatively. In the estimation of stricture length, RGU showed a lower sensitivity (60-80%) for lengths 1-4 cm, compared with sonourethrography (73.3-100%). Spongiofibrosis was detected by sonourethrography with a sensitivity of 77.3-83.3%. All the false tracts and calculi detected at sonourethrography were confirmed at surgery, whereas RGU showed a low sensitivity in their detection. The complications encountered during the procedures were pain, urethral bleeding and contrast intravasation. The frequency of pain during RGU was greater (p < 0.001); however, the difference in frequency of bleeding after the two procedures was not significant (p < 0.5). CONCLUSION: RGU and sonourethrography are equally efficacious in detection of anterior urethral strictures. Further characterization of strictures in terms of length, diameter and periurethral pathologies, like spongiofibrosis and false tracts, is done with greater sensitivity using sonourethrography as compared with RGU, with the added benefit of lower incidence of complications.

Hemorrhage↗
PubMed2004

The difference between ultrasound and computed tomography (CT) measurements of aortic diameter increases with aortic diameter: analysis of axial images of abdominal aortic and common iliac artery diameter in normal and aneurysmal aortas. The Tromsø Study, 1994-1995.

OBJECTIVE: To assess agreement between ultrasound and computed tomography (CT) measurements from axial images of normal and aneurysmatic aortic and common iliac artery diameter. DESIGN: Part of a population health screening for abdominal aortic aneurysm conducted in 1994-1995. MATERIALS AND METHODS: Three hundred and thirty-four subjects with and 221 subjects without ultrasound-detected aneurysm were scanned with CT. Three technicians and one radiologist measured ultrasonographic diameters and five radiologists measured CT diameters. The paired ultrasound-CT measurement differences were analyzed to assess agreement. RESULTS: Compared to CT measurements, ultrasound slightly underestimated the diameter in normal aortas and tended to overestimate the diameter in aneurysmal aortas. In 555 ultrasound-CT pairs of measurements, the absolute differences for measurements of maximal aortic diameter were 2 mm or less in 62, 60 and 77% in anterior-posterior, transverse and maximum diameter in any plane, respectively. The corresponding figures for an absolute difference of 5 mm or more were 14, 18 and 8%, respectively. Variability increased with increasing diameter. CONCLUSIONS: Both ultrasound and CT measurements of abdominal aortic diameter are liable to variability and neither of these methods can be considered to be 'gold standard'. Both methods can be used, while taking variability into consideration when making clinical decisions.

Aged↗
PubMed2004

Sublingual misoprostol versus methylergometrine for active management of the third stage of labor.

OBJECTIVE: To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor. METHOD: One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study. The women were randomized to receive either two tablets of misoprostol (200 microg/tablet) sublingually or 1 ml of methylergometrine (200 microg) intravenous injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were: need for additional oxytocic drugs, blood loss >or=500 ml, change in hemoglobin levels and side effects. RESULTS: Postpartum hemorrhage as defined by hemorrhage >or=500 ml occurred in 3.1% of the women in the sublingual misoprostol group but none of the women in the methylergometrine group (P > 0.05). There was a need for additional oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol, respectively (P > 0.05). The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 gm% in methylergometrine and misoprostol group, respectively(P > 0.05). In the misoprostol group, 6.6% women developed fever >or=38 degrees C and 21.6% had shivering while in methylergometrine group none experienced these side effects. However, the incidence of other side effects like nausea, vomiting, headache and giddiness were similar in both groups. CONCLUSION: Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage. However, larger randomized studies are needed to advocate its routine use.

Administration, Sublingual↗
PubMed2004

Metformin therapy in women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. METHOD: 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. RESULT: In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. CONCLUSION: A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.

Adolescent↗
PubMed2004

Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines.

Modest weight loss if maintained is associated with significant metabolic benefits and reduction in cardiovascular risk. Adipose tissue secretes cytokines believed to contribute to the pathogenesis of insulin resistance and cardiovascular risk. We therefore observed the effect of modest weight loss on serum adipocytokines and their relationship with changes in anthropometric and metabolic parameters within a period of 6 months in the setting of a routine obesity hospital clinic after various medical treatments. In this prospective, nonrandomized, nonblinded observational study, patients were first given treatment (sibutramine or orlistat) as decided by the treating clinician and then allocated into 1 of 2 groups according to the treatment prescribed. The first group included 21 Caucasian nondiabetic female subjects, with a mean (+/-SD) age of 43 +/- 11 years and a mean body mass index (BMI) of 46 +/- 8.6 kg/m(2); subjects were treated with sibutramine 10 or 15 mg/d for weight loss. The second group included 20 Caucasian nondiabetic female subjects, mean age 42 +/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced after 1 month on a low-fat (</=30%) diet in this group. Blood pressure and anthropometric measurements were performed before and after weight loss by a single observer. Serum glucose, insulin, lipid profile, C-reactive protein (CRP), resistin, leptin, and adiponectin were measured before and after weight loss on a fasting sample. After 6 months, the sibutramine group had a modest mean weight loss of 5.4% (P =.0001), and waist circumference was reduced by 4.5 +/- 1.4 cm. There was a decrease in serum resistin, leptin, and CRP levels, and a rise in serum adiponectin (P <.05). Change (%) (Delta) in BMI (DeltaBMI%) was associated with Deltainsulin(%) (P =.02, r = 0.53) and Deltaleptin(%) (P =.01, r = 0.58). Change in waist was associated with Deltainsulin(%) (P =.005, r = 0.75) and Deltaresistin(%) (P =.03, r = -0.55). The orlistat-treated group had a mean weight loss of 2.5%. Although this group did not show significant change in metabolic parameters, surprisingly there was a greater decrease of resistin (P =.02) associated with comparable (%) increase in adiponectin and (%) reduction of waist circumference and CRP. We conclude that modest weight loss (>5%) after medical treatment in a routine obesity hospital clinic is associated with improvements in insulin sensitivity and lipid profile. Modest weight loss is also associated with potentially favourably changes in serum adipocytokines, particularly in a rise of serum adiponectin. Reduction of waist circumference is associated with a change in serum resistin.

Abdomen↗
PubMed2004

Differential expression of CXCR4 receptor in early and term human placenta.

Chemokines and their receptors play a crucial role in regulation of T-cell migration and differentiation. Recent findings suggest that these proteins can also regulate cell functions such as angiogenesis and proliferation. Besides, CXCR4, a chemokine receptor, is one of the two major co-receptors for entry of the HIV virus during the late stages of HIV infection. We have studied the expression of CXCR4 in early (8-10 weeks) and term human placenta. Immunofluorescence staining and RT-PCR analysis revealed a differential expression of the CXCR4 receptor. Densitometric analysis revealed a two fold higher expression of the CXCR4 mRNA in early as compared to term placenta. This finding suggests that the expression of CXCR4 receptor may be developmentally regulated and its role in the early stages of pregnancy is implicated, when embryogenesis and organogenesis takes place. The fact that only 1-2 per cent of the placental transmission of the HIV virus takes place in the early placenta may also be correlated with our findings, suggesting that CXCR4 may not have a direct role in the transmission of HIV infection in the placenta.

Adult↗
PubMed2004

High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy.

Autologous stem cell transplant (SCT) improves survival in multiple myeloma (MM) and remains the standard of care for eligible patients. Nearly a third of patients with newly diagnosed MM fail initial therapy aimed at reducing tumor burden preceding SCT (primary refractory). It is unclear if an initial response is important for successful SCT. We evaluated our experience with SCT in 50 patients with primary refractory MM and compared it to 101 patients with chemosensitive disease receiving SCT. The study cohort had a median age of 56 years (range 29-72) consisting of 87 males (58%). A total of 46 patients (92%) in the refractory group and 100 (99%) in the chemosensitive group had a response to transplant (50% or greater reduction in the M-protein). In all, 10 refractory patients (20%) and 35 (35%) in the chemosensitive group achieved a CR (P=0.06). The 1-year estimated progression-free survival from the time of transplant for the refractory group was 70% compared to 83% for the chemosensitive group (P=0.65). The lack of response to initial induction therapy does not appear to preclude a good response to SCT. We recommend that patients with primary refractory MM be offered early SCT.

Adult↗
PubMed2004

Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy.

Bone marrow (BM) angiogenesis is increased in multiple myeloma and is an important prognostic factor. However, prior studies were mainly done on patients receiving conventional chemotherapy and there is limited data on its prognostic value in patients undergoing high-dose therapy (HDT) as initial therapy. We studied BM angiogenesis in terms of microvessel density (MVD) in 88 newly diagnosed patients, who were uniformly treated, with 3-4 cycles of induction chemotherapy followed by HDT. We examined if MVD at diagnosis was predictive of response to induction therapy or to subsequent HDT. In addition, we also examined its prognostic value in these patients. The median MVD for primary refractory patients was 28 (range, 2-84) compared to 27 (range, 2-99) for responding patients (P=0.7). The median progression-free survival (PFS) was 21 months for those with high-grade angiogenesis compared to 42 months for those with low-grade angiogenesis, P=0.017. The median overall-survival (OS) from diagnosis was 40 months for those with high-grade angiogenesis and not yet reached, for those with low-grade angiogenesis, P=0.007. BM MVD at the time of initial diagnosis is an important prognostic factor for OS and PFS in patients undergoing autologous transplantation as frontline therapy for myeloma.

Adult↗
PubMed2004

Single agent dexamethasone for pre-stem cell transplant induction therapy for multiple myeloma.

Given the survival advantage, high-dose therapy (HDT) remains the standard of care for patients with multiple myeloma eligible for the procedure. For those undergoing HDT, initial therapy aimed at reducing tumor burden is given prior to stem cell harvest. Various regimens, mostly variations of VAD (vincristine, doxorubicin, dexamethasone), are used for induction therapy. We retrospectively evaluated if single agent dexamethasone would be an effective induction therapy, given that it is the most active drug in these combinations. A total of 35 patients who received induction therapy with dexamethasone alone were compared to a similar group of 72 patients who received VAD as the initial therapy. We found a 63% response rate with dexamethasone compared to 74% with VAD (P=0.25). Including minimal responses, the overall response rate for Dex and VAD was 74 and 86%, respectively (P=0.13). The overall and complete response rates to transplant, respectively, were 97 and 26% for the dexamethasone group and 100 and 39% for the VAD group; P=0.33 and 0.18. No significant differences were observed in the progression-free and overall survival at 1 year post transplant. Single agent dexamethasone appears to be an effective alternative to VAD for induction therapy prior to HDT in myeloma.

Adult↗
PubMed2004

The biochemical mechanism of caspase-2 activation.

A unified model for initiator caspase activation has previously been proposed based on the biochemical analysis of caspase-8 and -9. Caspase-2 is structurally related to caspase-9, but its mechanism of activation is not known. Using an uncleavable mutant of caspase-2, we show that dimerization (and not processing) is the key event that drives initial procaspase-2 activation. Following dimerization, caspase-2 undergoes autocatalytic cleavage that promotes its stable dimerization and further enhances the catalytic activity of caspase-2. Although the caspase-2 zymogen does not require cleavage for the initial acquisition of activity, intersubunit cleavage is required to generate levels of activity required to induce cell death by overexpression. We also provide evidence that the reported disulfide bond linkage between two caspase-2 monomers is dispensable for caspase-2 dimerization. As caspase-2 does not require cleavage for its initial activation, our findings confirm caspase-2 to be a bona fide initiator caspase.

Animals↗
PubMed2004

Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF.

One potential benefit of DNA vaccines is the capacity to elicit antibody and T-cell responses against multiple antigens at the same time by mixing plasmids expressing different proteins. A possible negative effect of such mixing is interference among plasmids regarding immunogenicity. In preparation for a clinical trial, we assessed the immunogenicity of GMP-produced plasmids encoding five Plasmodium falciparum proteins, PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3, given as a mixture, or alone. The mixture induced higher levels of antibodies against whole parasites than did the individual plasmids, but was associated with a decrease in antibodies to individual P. falciparum proteins. T-cell responses were in general decreased by administration of the mixture. Immune responses to individual plasmids and mixtures were generally higher in inbred mice than in outbreds. In inbred BALB/c and C57BL/6 mice, coadministration of a plasmid expressing murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), increased antibody and T-cell responses, but in outbred CD-1 mice, coadministration of mGM-CSF was associated with a decrease in antibody responses. Such variability in data from studies in different strains of mice underscores the importance of genetic background on immune response and carefully considering the goals of any preclinical studies of vaccine mixtures planned for human trials.

Animals↗
PubMed2004

Reduced immunogenicity of DNA vaccine plasmids in mixtures.

We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-gamma responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-gamma responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-gamma responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously.

Animals↗
PubMed2004

Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma.

Bone marrow (BM) angiogenesis is increased in multiple myeloma and is an important prognostic factor for survival. Previous studies have shown that BM angiogenesis does not change following chemotherapy or stem cell transplant. Given its potential antiangiogenic effect, we evaluated if thalidomide therapy would affect the BM microvessel density (MVD). We studied BM angiogenesis in 81 patients with various disease stages treated with thalidomide with or without dexamethasone. MVD was determined as previously described. MVD was compared between pretreatment marrows and those obtained 4-6 months following therapy. The median (range) MVD pretherapy was 28 (2-116) and post-therapy was 15 (3-97). A partial or complete response was seen in 58% of patients, stable disease in 41% and progressive disease in one patient. MVD decreased significantly in responders (median decrease of 12, P<0.001). In contrast, no significant change in MVD was seen in those failing to respond to thalidomide. Unlike the lack of resolution of angiogenesis reported with other therapies, we demonstrate for the first time a significant decrease in microvessels with thalidomide therapy. Although not conclusive, this result lends further support to the hypothesis that angiogenesis is a relevant therapeutic target in myeloma.

Antineoplastic Combined Chemotherapy Protocols↗