Contraceptive coverage after medical termination of pregnancy

Abortion has become a popular method of prevention of unwanted births in India since the passage in 1972 of the Medical Termination of Pregnancy Act. About 6 million procedures are performed each year. Of concern, however, is the failure on the part of many of these abortion patients to begin contraceptive use after pregnancy termination. To determine the extent of this problem and its sociodemographic correlates, an analysis was performed of the records of the 1482 abortion patients at an Agra hospital in 1976-85. Overall, contraceptive coverage after abortion was 53%; however, this rate fluctuated from 82% in 1976-77 to 15% in 1980-81 to a high of 90% in 1984-85. The methods most often selected by these women were tubectomy (25%), Nirodh (14%), oral contraceptives (8), and the IUD (6%). Contraceptive coverage was significantly higher in the final quarter of each year, presumably as a result of the efforts of family planning personnel to meet annual targets. Contraceptive coverage after abortion showed significant, positive associations with maternal age (39% in the 15-19-year age group versus 59% among those 30-34 years old), maternal education (41% among illiterate women compared to 62% among women with a high school education), and parity (18% among women of parity versus 45% among those of parity 1 and 62% among those to parity 4). Urban women were somewhat more likely to become contraceptive acceptors after abortion; however, tubectomy acceptance was highest among older rural women. These findings suggest that young, uneducated women should be targeted for counseling about the importance of contraceptive use after the termination of an unplanned pregnancy to avoid the need for repeat abortion.     

β-Receptor responsiveness after desipramine treatment

To examine whether a tricyclic antidepressant affects the functional response to a -receptor agonist in man, the response of heart rate, blood pressure, and plasma cAMP to isoproterenol was measured in 14 normal controls taking 75 mg desipramine daily. Desipramine significantly increased the bolus dose of isoproterenol needed to increase heart rate by 25 bpm at 14–30 days but not at 3–8 days. During infusions of isoproterenol, the increase in systolic blood pressure was blunted at both 3–8 days and 14–30 days, while the decrease in diastolic blood pressure was unaffected. Blood pressure findings were not affected by preadministration of bethanechol. In ten controls, isoproterenol infusions increased plasma cAMP, but this was unaffected by desipramine treatment. These findings suggest a decrease in the functional response of ₁, but not ₂, receptors after treatment with desipramine.Presented in part at the 143rd Annual Meeting of the American Psychiatric Association, New York, NY, May 15, 1991.     

Influenza A Virus Infection Activates NLRP3 Inflammasome through Trans-Golgi Network Dispersion

The NLRP3 inflammasome consists of NLRP3, ASC, and pro-caspase-1 and is an important arm of the innate immune response against influenza A virus (IAV) infection. Upon infection, the inflammasome is activated, resulting in the production of IL-1β and IL-18, which recruits other immune cells to the site of infection. It has been suggested that in the presence of stress molecules such as nigericin, the trans-Golgi network (TGN) disperses into small puncta-like structures where NLRP3 is recruited and activated. Here, we investigated whether IAV infection could lead to TGN dispersion, whether dispersed TGN (dTGN) is responsible for NLRP3 inflammasome activation, and which viral protein is involved in this process. We showed that the IAV causes dTGN formation, which serves as one of the mechanisms of NLRP3 inflammasome activation in response to IAV infection. Furthermore, we generated a series of mutant IAVs that carry mutations in the M2 protein. We demonstrated the M2 proton channel activity, specifically His37 and Trp41 are pivotal for the dispersion of TGN, NLRP3 conformational change, and IL-1β induction. The results revealed a novel mechanism behind the activation and regulation of the NLRP3 inflammasome in IAV infection.     

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM–TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM–TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM–TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM–TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM–TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM–TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.     

Treatment Response and Drug Resistance Profiling of Genotype 6 of Hepatitis C Virus in HCV/HIV Co-Infected Patients: A Pilot Study from INDIA

Hepatitis C Virus (HCV) genotype (GT) 6 demonstrates maximum genomic diversity out of all the known genotypes of HCV, attributable to its inherent intra-genotype and inter-genotype recombination property. This is the most common genotype seen in HCV/HIV co-infected cases. HIV/HCV co-infection is linked with increased genetic diversity in HCV structural genes. The detailed information on the distribution of HCV GT6, its subtypes, and resistance to currently available antiviral drugs is limited in the Indian subcontinent. Therefore, in this single-center retrospective cross-sectional study, we aimed to map the occurrence of HCV GT6, its subtypes and resistance-associated substitution (RAS), and its correlation with antiviral treatment response in HCV-infected patients. From a cohort of 2052 HCV-infected patients, the overall prevalence of GT6 was 2.5% (n = 53), with a maximum of 81.1% (n = 43) seen in HCV/HIV co-infected patients. Nine different subtypes, 6a, 6b, 6f, 6i, 6n, 6u, 6v, 6w, and 6xa, were detected in the Indian population for the first time, with a predominance of 6xa (41.5%), a rare subtype, followed by 6n (39.6%). The phylogenetic analysis by the neighbor-joining method revealed three prominent viral clades, 6v, 6n, and 6xa–6u. The baseline (before treatment initiation) plasma samples of all GT6-infected patients were retrieved from −80 °C and a part of the NS5a and NS5b region of the viral genome was analyzed for the presence of RAS. No RASs were seen in the NS5b region, while in two patients (3.7%) RASs were seen at baseline in the NS5a region of the virus. Sustained viral response (SVR) was attained in 81% (n = 43) of patients. No difference in GT6 subtype distribution or occurrence of RAS was seen between mono-infected HCV and HIV/HCV co-infected cases. Our study revealed that RAS at baseline did not influence the attainment of SVR and the currently available antiviral therapy is effective against GT6 mono-infected and HIV/HCV co-infected patients.     

6 Year Prospective Clinical Trial of Primary Repair Versus Diversion Colostomy in Colonic Injury Cases

Management pathway of colonic injury has been evolving over last three decades. There has been general agreement that surgical methods dealing with colonic injury did not affect the outcome but there are certain independent risk factors for complications. These risk factors are still not clear and studies are going on to specify these risk factors. The primary objective of this study was to demonstrate that primary closure of colonic injury without colostomy in selective patient is safe. This was a prospective study of 6 year duration. All the colonic injuries operated and divided into two groups: primary repair and colostomy. The criteria for exclusion of primary repair taken were; injury time >8 hour, patient need >4 unit of blood transfusion till surgery, devascularization injury of colon, any pre existing disease of bowel, any severe co morbid disease like uncontrolled diabetes mellitus, tuberculosis, malignancy etc. Both groups are analyzed by assessing complications with special emphasis on leak rate. Patients died within 72 hours of admission were excluded from study. Total 55 colonic injury cases operated and primary repair was done in 35 cases and colostomy in 20 cases. There was 1 mortality in colostomy group and no major morbidity in both groups. The complications in primary repair group were; 1 leak (treated conservatively), 5 wound infections 1 incisional hernia and 1 intra abdominal abscess. In colostomy group 8 cases of wound infections, 2 incisional hernias and 2 intra abdominal abscesses occurred. Primary repair of colon injuries can be safely done in selected patient.     

Post-kala-azar dermal leishmaniasis (PKDL), HIV and pulmonary tuberculosis

Post-kala-azar dermal leishmaniasis is usually a sequel to visceral leishmaniasis. A 25-year-old woman presented with hypopigmented maculopapular lesions all over the body for the past 4 years without any previous history of visceral leishmaniasis. She was on treatment for leprosy and pulmonary tuberculosis for the past 2 months, but did not show any improvement. Investigations confirmed that she had post-kala-azar dermal leishmaniasis associated with pulmonary tuberculosis and HIV-1 infection. She was started on treatment for the triad of diseases, and showed improvement.     

Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion

Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation‐dependent probe amplification (MLPA), and methylation‐specific MLPA (MS‐MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH‐resistance remains unknown, but it seems unlikely that this disease variant is caused by heterozygous inherited or de novo mutations involving GNAS. © 2015 American Society for Bone and Mineral Research.