Transcriptional status of HLA-G at the maternal-fetal interface in recurrent spontaneous abortion.
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Abortion, Spontaneous↗
Biomedical subjects
S Agrawal
Publications and source records attributed to S Agrawal.
Does the evidence support the use of concurrent chemoradiotherapy as a standard in the management of locally advanced cancer of the cervix, especially in developing countries?
Locally advanced cancer of the cervix (FIGO stages III and IVA) is one of the most common malignancies in developing countries. Conventional treatment has been a judicious combination of external radiotherapy and intracavitary brachytherapy. However, prompted by the results of five randomised-controlled trials (RCTs) published in close succession, The National Cancer Institute (NCI) alert in 1999, and two meta-analyses, the management of cancer of the cervix has gradually changed. Concurrent chemoradiotherapy with cisplatin alone, or in combination, is gradually being favoured for the treatment of cancer of the cervix. This overview examines whether the published evidence is sufficiently adequate to justify the use of chemoradiotherapy using cisplatin as standard care in the management of cancer of the cervix, especially in developing countries, where most women present with locally advanced cancer of the cervix. A critical review of the various phase III randomised trials and meta-analyses indicates that, although chemoradiotherapy could be a standard form of treatment for early cancer of the cervix, its role in advanced stages needs further exploration before this could be incorporated into routine clinical care.
Combined Modality Therapy↗
Metastatic lobular carcinoma of breast presenting on a routine cervical smear.
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Breast Neoplasms↗
HLA-E and immunobiology of pregnancy.
Recently, it has been suggested that non-classical antigens such as human leukocyte antigen (HLA)-G and HLA-E may interact with KIR receptors of NK cells which results into downregulation of immune response and helps in the maintenance of pregnancy. In the present study, we have investigated HLA-E polymorphism in normal fertile women and recurrent spontaneous aborters to assess the effect of HLA-E alleles on the success of pregnancy. Allele E*0101 was found to be significantly higher in patients with recurrent spontaneous abortion (chi(2) = 4.097 and P = 0.0430). Differential expression, peptide affinity, and stability of E*0101 may be one of the reasons.
Abortion, Habitual↗
SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells.
Cleavage of the hepatitis C virus (HCV) polyprotein by the viral NS3 protease releases functional viral proteins essential for viral replication. Recent studies by Foy and coworkers strongly suggest that NS3-mediated cleavage of host factors may abrogate cellular response to alpha interferon (IFN-alpha) (E. Foy, K. Li, R. Sumpter, Jr., Y.-M. Loo, C. L. Johnson, C. Wang, P. M. Fish, M. Yoneyama, T. Fujita, S. M. Lemon, and M. Gale, Jr., Proc. Natl. Acad. Sci. USA 102:2986-2991, 2005, and E. Foy, K. Li, C. Wang, R. Sumpter, Jr., M. Ikeda, S. M. Lemon, and M. Gale, Jr., Science 300:1145-1148, 2003). Blockage of NS3 protease activity therefore is expected to inhibit HCV replication by both direct suppression of viral protein production as well as by restoring host responsiveness to IFN. Using structure-assisted design, a ketoamide inhibitor, SCH 503034, was generated which demonstrated potent (overall inhibition constant, 14 nM) time-dependent inhibition of the NS3 protease in cell-free enzyme assays as well as robust in vitro activity in the HCV replicon system, as monitored by immunofluorescence and real-time PCR analysis. Continuous exposure of replicon-bearing cell lines to six times the 90% effective concentration of SCH 503034 for 15 days resulted in a greater than 4-log reduction in replicon RNA. The combination of SCH 503034 with IFN was more effective in suppressing replicon synthesis than either compound alone, supporting the suggestion of Foy and coworkers that combinations of IFN with protease inhibitors would lead to enhanced therapeutic efficacy.
Antiviral Agents↗
Primary bladder dermoid: a case report and review of the literature.
Bladder dermoid is a rare presentation. Diagnosis of this case was made cystoscopically and confirmed histopathologically. Complete excision was possible endoscopically. This is the 3rd case report from the Indian and Asian subcontinent.
Adult↗
Effect of placental-extract gel and cream on non-healing wounds.
OBJECTIVE: To compare the effects of topical placental-extract gel and cream in the treatment of chronic non-healing wounds with regard to wound healing and discomfort during dressing change. METHODS: A sample of 120 patients attending the wound clinic at University Hospital, Varanasi, India, with wounds of more than six weeks' duration were enrolled into the study. They were alternately allocated to group A (topical application of placental-extract gel) or group B (placental-extract cream). Wound biopsy was performed, and swab culture and sensitivity were taken. Wound size was measured, and visual analogue scale (VAS) scores for pain and discomfort at dressing change were recorded at weekly follow-up in both groups. Biopsy was repeated after two weeks of treatment and sent for histopathological examination for assessment of angiogenesis in 25 cases from each group. RESULTS: One hundred patients completed the study. More than 50% wound healing was observed after eight weeks in 72% of group A patients and 74% of group B patients (p = 0.75). Microscopic angiogenesis grading system (MAGS) scores were similar in both groups (not statistically significant, p = 0.92). The VAS scores for pain and discomfort were lower in group B (statistically significant, p < 0.02). CONCLUSION: Placental-extract gel and cream are both effective topical agents for chronic non-healing wounds. However, there is less pain and discomfort during dressing change with the placental-extract cream, which we thus recommend for topical application in chronic non-healing wounds.
Administration, Cutaneous↗
Dissolution testing of marketed rifampicin containing fixed dose combination formulations using a new discriminative media: a post marketing retrospective study.
Currently recommended compendial dissolution methods for quality control of orally administered solid dosage forms of rifampicin containing formulations are not found to be able to forecast the in vivo performance. A recently proposed dissolution method of 0.01 N HCl at 50 rpm using paddle apparatus for screening was found to be more appropriate and able to predict the in vivo performance of those formulations. The objective of this investigation was to validate the new method of dissolution testing for solid dosage forms of rifampicin containing formulations using a basket apparatus and to compare it with the frequently recommended pharmacopeial method. In the present study the newly proposed dissolution condition (0.01 N HCl) was validated using six formulations of two, three and four drug combinations from two different manufacturers by basket method and compared with the widely recommended compendial medium. In this investigation, the appropriateness of the proposed methodology was confirmed by the dissolution results of the two FDC formulations (a two-drug and a four-drug combinations) that had previously passed the bioequivalence tests. It was found that the recommended dissolution medium of 0.01 N HCl can be used for screening of rifampicin containing formulations using both paddle and basket dissolution apparatus at 50 rpm and 100 rpm, respectively.
Antitubercular Agents↗
Cortical localization of external urethral sphincter activation by transcranial electrical stimulation.
PURPOSE: Repetitive transcranial electrical stimulation (rTES) was used to activate descending output to the external urethral sphincter muscle. METHODS: Motor evoked potentials (MEPs) were recorded from external urethral sphincter (EUS), and anterior tibial (TA) muscles following high voltage rTES in 9 consecutive patients undergoing spine surgery. Anesthesia was achieved by continuous propofol/narcotic infusion without paralytic agents. Anodal cortical stimulation was delivered at C4/C3, C2/C1, and Cz/Fz locations in each patient. Latency and amplitude of the MEP was measured and compared for each bipolar stimulation montage. RESULTS: The mean latency was 20.24 +/- 1.3 msec. for Cz/Fz; 20.19 +/- 1.1 msec. for C4/C3 and 20.19 +/- 1.1 msec. for C2/C1. Statistical analysis showed no significant difference in latency between the three sites (F(2,15) = 0.004; p > 0.05). The mean amplitude was 37.14 +/- 24.3 microV for Cz/Fz; 113.33 +/- 100.6 microV for C4/C3; and 85 +/- 73.9 microV for C2/C1. A significant difference between the amplitudes at three sites was observed (F(2,8) = 5.2; p < 0.05). The amplitude at C4/C3 was significantly greater than amplitude at CzlFz (t (8) = 3.08; p < 0.05), but data did not give enough evidence to believe that difference between amplitudes for site C4/C3 & C2/C1 was significant (p > 0.05). CONCLUSIONS: This study shows that the intraoperative MEP monitoring of the EUS is a feasible method. Furthermore, activation of descending axonal outflow to the EUS muscle is best achieved by cortical stimulation directed from C4 to C3 or C2 to C1 points.
Adolescent↗
MUC 1 core protein as a marker of gallbladder malignancy.
AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.
Adenocarcinoma↗
The association between narcolepsy and REM behavior disorder (RBD).
BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep Behavior Disorder (RBD) is a movement disorder associated with loss of REM-related muscle atonia and is characterized by complex, vigorous and frequently violent dream-enacting behavior during REM sleep. RBD is usually idiopathic or secondary to neurological problems such as Parkinson's disease. This study looked at the association of RBD with another sleep disorder, narcolepsy. PATIENTS AND METHODS: Seventy-eight questionnaires were sent to known narcoleptics chosen at random from those with contact details available at the center. The questionnaire addressed current narcolepsy symptoms, medication use and symptoms of RBD. Positive questionnaire results were followed up with a telephone interview. Limited polysomnography (PSG) data was also analyzed. RESULTS: Fifty-five patients responded (response rate 71%). Of these, 20 (36%) had symptoms suggestive of RBD. The typical RBD patient is an older male (mean age of onset 60.9 years, 87% male); however, in this study, females were as likely to have RBD as males, and the mean age was 41 years. Sixty-eight percent of patients who regularly experienced cataplexy and the associated symptoms of narcolepsy (sleep paralysis, hypnogogic hallucinations and automatic behavior) had RBD, compared to 14% of those who never or rarely experienced these symptoms. CONCLUSION: This study implies a stronger relationship between these disorders than a previously published figure of 7-12% This is clinically significant as RBD is a potentially distressing but readily treatable disorder. It follows that narcoleptics, especially those with cataplexy and other associated symptoms, should be questioned about symptoms of RBD and treated accordingly. Similarly, anyone presenting with RBD should be assessed for symptoms of narcolepsy, particularly if female or of a younger age group than would otherwise be expected.
Adolescent↗
Structural and vibrational properties of small carbon clusters.
An ab-initio comprehensive study of the stability and structural and vibrational properties of small carbon clusters, CN for N = 1-10, has been made. We use a self-consistent pseudopotential method within density functional theory in the generalized gradient approximation considering spin polarization. The estimated values of binding energies for the various clusters are overestimated in the non-spin-polarized calculations. On the other hand, for the spin-polarized case, the computed binding energies are in very good agreement with the available experimental data. Also, the calculated vibrational frequencies for CN, N = 2-5, are in reasonable agreement with the available experimental values.
Binding Sites↗
Ab-initio study of the structural and electronic properties of very thin silver nanowires.
An ab initio study of the energetics, structural, and electronic properties of thin silver nanowires of Ag(n) with n = 1 to 6 has been made in density functional theory in local density approximation. The present study reveals that all of the wires are stable except the wire with 3 silver atoms per unit cell. The linear chain is comparatively less stable. The binding energies of the most stable wires lie in the range 2.60-3.18 eV/atom with maximum values for the 5-Ag pentagonal and the two 6-Ag (hexagonal and pyramidal) nanowires. The nearest neighbor Ag-Ag separations in all of the most stable wires up to n=6 is quite the same and is equal to 2.634 +/- 0.03 A. For the most stable 6-Ag pyramidal wire, the bond length increases to 2.75 or 2.81 A. The cross-sectional dimension of these wires are around 5.0 A. All of the studied silver wires are metallic. A majority of the sd mixed states cross the Fermi level. The density of state is maximum for the 5-Ag pentagonal and 6-Ag pyramidal nanowires, and so is the number of channels (5 or 6) crossing the E(F) which would be available for high electrical conduction.
Algorithms↗
Determination of rifampicin bioequivalence in a three-drug FDC by WHO and indian protocols: effect of sampling schedule and size.
SETTING: To promote the quality assurance of fixed-dose combination (FDC) formulations, the World Health Organization (WHO) has prepared a convenient simplified protocol for the determination of rifampicin (RMP) bioequivalence. During the development of this protocol, it was proved that sampling time up to 8 h can determine the rate and extent of RMP absorption. However, this protocol utilises 20 volunteers in contrast to other local regulatory requirements of a minimum of 12 volunteers. The different sample sizes utilised in these protocols may affect the sensitivity of the bioequivalence outcome. OBJECTIVE: To determine the effect of sampling size and schedule on RMP bioequivalence when two different protocols are used. DESIGN: A bioequivalence trial was conducted with a study design of 20 volunteers and 24 h sampling time, which fulfils the requirements of both the WHO and Indian regulatory protocols. Pharmacokinetic and statistical analysis was done by stepwise reduction in sample size and schedule. RESULT: Bioequivalence limits of RMP were unaffected by a reduced sample size of 12 volunteers and 8 h sampling time. CONCLUSION: Minimising sample size after validation for borderline and poor quality FDC formulations can further reduce the cost of conducting bioequivalence trials.
Absorption↗
Chitosan hydrochloride based microspheres of albendazole for colonic drug delivery.
Microspheres of chitosan hydrochloride (CH) were prepared in order to deliver albendazole specifically into the colon. Microspheres were prepared by an emulsion method using different ratios of drug and CH (1:1 to 1:5), agitation speeds (500 to 1500 rpm) and concentrations of glutaraldehyde in toluene as the cross-linking agent (0.25 to 1.0% w/v). The effect of polymer concentration, stirring rate and concentration of cross-linking agent on the particle size and drug loading was studied. With an increase in CH concentration, the average particle size was increased. Increased agitation speed reduced the size of the microspheres but higher agitation speed resulted in irregularly shaped microspheres. Increasing the concentration of cross-linking agent produced more regularly shaped microspheres of smaller size. The drug loading was highest at a drug: CH ratio of 1:3, stirring speed 1000 rpm and 0.75% w/v concentration of cross-linking agent. The effect of CH concentration on in vitro drug release from the microspheres was evaluated in simulated g.i.t fluids. A comparative in vitro drug release study of the optimized formulation was carried out in simulated colonic fluid, with and without 2% rat caecal content. The drug release in 24 h was 48.9% in colonic fluid without rat caecal content, and 76.5% in colonic fluid with rat caecal contents.
Albendazole↗
Angiotensin converting enzyme gene polymorphism in Indian children with steroid sensitive nephrotic syndrome.
CONTEXT: Nephrotic syndrome is one of the commonest renal problem encountered in children. It is difficult to predict at onset, the clinical course in terms of steroid responsiveness or resistance. Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been studied as a predictor of clinical course in common multi-factorial diseases including focal segmental glomerulosclerosis. There is no study available from our country till date to find out any correlation of the steroid response in idiopathic nephrotic syndrome and ACE gene polymorphism. AIM: To study distribution and correlation of ACE gene I/D polymorphism in idiopathic steroid sensitive nephrotic syndrome. SETTINGS & DESIGN: Case-control retrospective study. SUBJECTS & METHODS: We studied ACE gene polymorphism in 90 consecutive patients (82% males, 18% females) with steroid sensitive idiopathic nephrotic syndrome and 300 normal controls (NC). STATISTICAL ANALYSIS: Chi-square test and Fisher's exact test (for cases with insufficient expected cell frequencies). RESULTS: The mean age of onset was 5.3 +/- 4 years. Steroid sensitive (SS) patients showed II (SS-48%, NC-26%) genotype was more frequent than normal controls (p=0.002). There was no significant difference in genotype frequencies among steroid SS subgroups. CONCLUSIONS: In our study II genotype was more frequent in steroid sensitive nephrotic syndrome children in comparison to normal controls. Further functional studies with large number of children are required to investigate the role of II genotype in steroid sensitive nephrotic syndrome. Comparison of the genotypic frequency with steroid resistant patients may provide information, which might be useful in clinical practice.
Child, Preschool↗
Minimum sample size and sampling time requirements for assessment of rifampicin bioequivalence from FDC formulations.
SETTING: The WHO- and IUATLD-recommended protocol for rifampicin (RMP) bioequivalence utilises 20-22 volunteers and 8 h, whereas the requirement of other regulatory authorities is 12 volunteers with a 24 h sampling schedule. Differing sampling size and time requirements may change the outcome of RMP bioequivalence. OBJECTIVE: To determine the minimal sample size and time required to assess RMP bioequivalence from FDC formulations. DESIGN: Bioequivalence studies were conducted that fulfilled the criteria of the WHO and Indian regulatory protocols. From earlier studies, retrospective pharmacokinetic evaluation, power of the test and bioequivalence limits were also calculated using 8-22 volunteers and sampling points of 8-24 h. Pharmacokinetic and statistical evaluations from three representative studies showing low, moderate and high intra-subject variability are given to determine minimum requirements for RMP bioequivalence. RESULT: It was found that a sampling schedule up to 8 h was sufficient to compare the absorption process of RMP. There was no influence of reduced sample size on bioequivalence estimates of RMP that showed low or moderate variability. However, in a study showing higher variation, a sample size of 14-16 subjects was found to be optimal. CONCLUSION: It is possible to reduce the sample size requirement for determination of RMP bioequivalence using the WHO protocol.
Antibiotics, Antitubercular↗