Ectopic pregnancy: reappraisal of risk factors and management strategies

Background: The incidence of ectopic pregnancy is increasing. The objective of this study was to analyze the risk factors, clinical characteristics, and management strategies in patients with ectopic pregnancy at a tertiary care referral centre in South India.  Methods: Retrospective observational study was done for a period of seven years from April 2006 to March 2014 where in case files of 87 cases of ectopic pregnancies were analyzed for clinical profile, sonological data, management strategies and outcome.Results: The incidence of ectopic pregnancy has increased from 8.3 in 2006 to 18.92/1000 live births in 2014. Risk factors associated were prior tubal ligation 21 (24.14%), history of pelvic inflammatory disease 11 (12.64%), prior ectopic 5 (5.75%), prior tubal surgery 4 (4.60%), infertility 13 (14.94%), prior pelvic surgery 22 (25.29%) and current use of Copper T - 3 (3.45%) cases. Common symptoms were lower abdominal pain in 80 (91.95%) and amenorrhea in 76 (87.35) cases. 9 cases presented in shock. Gray scale ultrasound showed complex adnexal mass in 42 (48.28%), tubal ring 19 (21.84%) and live fetus in 11 (12.64%). 72 cases were managed surgically, 11 medically and 4 by expectant management. Tubal rupture occurred in 30(41.67%). Among those managed surgically, laparotomy was done in 55 (76.39%), laparoscopy in 17 (23.61%) cases. Salpingectomy was done in 52 (72.22%), salpingostomy 9 (12.5%), salpingotomy 5 (6.94%), segmental resection 3 (4.17%), scar excision and repair 1 (1.39%), abdominal hysterectomy 1 (1.39%), and laparotomy for abdominal pregnancy in 1 (1.39%) case. There was no maternal death.  Conclusions: The incidence of ectopic has been increasing. Prior sterilization particularly done along with caesarean is the most common risk factor in our region. Surgical management by laparotomy and salpingectomy continues to be the preferred mode of management of ectopic pregnancy in our institution since two third of patients are referred from periphery and present with considerable intraperitoneal hemorrhage.

High risk scoring in pregnancy using modified Coopland’s scoring system and its association with perinatal outcome

Background: High-risk pregnancy is one in which the mother, foetus or the newborn has an elevated risk of experiencing an adverse outcome. These high-risk women form a special vulnerable cohort that can be identified in the antenatal period using a simple, easy to use, cost-effective tool- a maternal risk scoring system. Early identification of these high-risk mothers will facilitate effective intervention strategies to deal with the complications.Methods: This study was carried out on 300 pregnant women with gestational age more than 28 weeks. Detailed history, examination and necessary investigations were done and then using the Modified Coopland scoring system, each pregnant woman was assigned a risk score and stratified into 3 risk groups- low risk (0-3), moderate risk (4-6) and high risk (≥7) and followed up till delivery and 7 days postpartum. Subsequently, the maternal and perinatal outcomes were compared with their respective scores.Results: In this study, 14.66% patients belonged to the high-risk category. Statistically, a significant difference was noted in the number of low-birth-weight babies, in 5 minutes APGAR score <7 and in NICU admissions in the high-risk group compared to the low-risk group. Overall perinatal mortality was 13.33/1000 live births. In the high-risk group, a significant difference was seen in the occurrence of PPH and the need for operative delivery.Conclusions: Significant association between high-risk pregnancy and the poor maternal and perinatal outcome was noted. Therefore, a simple, cost-effective high-risk pregnancy scoring system such as the one proposed in this study can be used to identify potential high-risk pregnancies, provide them with tertiary care facilities and also corrective measures can be undertaken to prevent or minimize the complicating factors

Adnexal torsion: clinical, radiological and pathological characteristics in a tertiary care centre in Southern India

Background: Adnexal torsion accounts for 2.7% of gynecological emergencies. Early diagnosis can help prevent irreversible damage to ovary. Objective of this study was to analyze the clinical, radiological and pathological characteristics of surgically proven cases of ovarian torsion.Methods: Observational study was carried out from January 2006 to June 2014. Medical records of 38 cases of adnexal torsion were selected and analyzed retrospectively for age, parity, risk factors, clinical presentation, presence of leukocytosis, gray scale ultrasound and colour Doppler features, management, pathological results and post-operative outcome.Results: Adnexal torsion occurred most commonly in reproductive age group (mean 27.89 years) of whom 3 were pregnant. 42% had known risk factors commonly prior pelvic surgery (52.63%) and prior tubal ligation (31.58%). Symptoms include sudden abdominal or pelvic pain (94.74%), vomiting (60.53%) and fever (21.05%). Gray scale USG showed mixed echogenic mass (36.84%), homogenously echogenic cyst (34.21%) anechoic cyst (26.32%) and free fluid (23.68%). Doppler showed absent arterial and venous flow in 52.63%. Cases were managed by detorsion &amp; cystectomy (42.11%), unilateral salpingooophorectomy (47.37%), bilateral salpingooophorectomy (5.26%) and TAH with BSO (5.26%). Histopathology revealed benign serous epithelial tumors (31.58%), mucinous tumors (21.05%), mature teratoma (10.53%), corpus luteal cyst (5.26%), follicular cyst (2.63%) paraovarian cyst (13.16%), endometriotic cyst (2.63%) and ovarian hemangioma (2.63%).Conclusions: High index of suspicion &amp;prompt surgical intervention is necessary to preserve ovarian function even if Doppler shows vascularity. Though detorsion and cystectomy is the choice, salpingooophorectomy may be needed in infracted ovaries and older women. Higher incidence of serous &amp; mucinous tumors in our study suggests reappraisal of ovary sparing surgery for all patients as advocated by few

Marker‐Assisted Backcrossing to Introgress Resistance to Fusarium Wilt Race 1 and Ascochyta Blight in C 214, an Elite Cultivar of Chickpea

Fusarium wilt (FW) and Ascochyta blight (AB) are two major constraints to chickpea (Cicer arietinum L.) production. Therefore, two parallel marker-assisted backcrossing (MABC) programs by targeting foc1 locus and two quantitative trait loci (QTL) regions, ABQTL-I and ABQTL-II, were undertaken to introgress resistance to FW and AB, respectively, in C 214, an elite cultivar of chickpea. In the case of FW, foreground selection (FGS) was conducted with six markers (TR19, TA194, TAA60, GA16, TA110, and TS82) linked to foc1 in the cross C 214 × WR 315 (FW-resistant). On the other hand, eight markers (TA194, TR58, TS82, GA16, SCY17, TA130, TA2, and GAA47) linked with ABQTL-I and ABQTL-II were used in the case of AB by deploying C 214 × ILC 3279 (AB-resistant) cross. Background selection (BGS) in both crosses was employed with evenly distributed 40 (C 214 × WR 315) to 43 (C 214 × ILC 3279) SSR markers in the chickpea genome to select plant(s) with higher recurrent parent genome (RPG) recovery. By using three backcrosses and three rounds of selfing, 22 BC3F4 lines were generated for C 214 × WR 315 cross and 14 MABC lines for C 214 × ILC 3279 cross. Phenotyping of these lines has identified three resistant lines (with 92.7–95.2% RPG) to race 1 of FW, and seven resistant lines (with 81.7–85.40% RPG) to AB that may be tested for yield and other agronomic traits under multilocation trials for possible release and cultivation

TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSB mutations in predicting diabetes

<p>Abstract</p> <p>Background</p> <p>Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to developing countries in tropical regions and one of its important features is invariable progression to diabetes, a condition called fibro-calculous pancreatic diabetes (FCPD), but the nature of diabetes in TCP is controversial. We analysed the recently reported type 2 diabetes (T2D) associated polymorphisms in the <it>TCF7L2 </it>gene using a case-control approach, under the hypothesis that <it>TCF7L2 </it>variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the <it>TCF7L2 </it>variants and N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations, since they are strong predictors of risk for TCP.</p> <p>Methods</p> <p>Two polymorphisms rs7903146 and rs12255372 in the <it>TCF7L2 </it>gene were analyzed by direct sequencing in 478 well-characterized TCP patients and 661 healthy controls of Dravidian and Indo-European ethnicities. Their association with TCP with diabetes (FCPD) and without diabetes was tested in both populations independently using chi-square test. Finally, a meta analysis was performed on all the cases and controls for assessing the overall significance irrespective of ethnicity. We dichotomized the whole cohort based on the presence or absence of N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations and further subdivided them into TCP and FCPD patients and compared the distribution of <it>TCF7L2 </it>variants between them.</p> <p>Results</p> <p>The allelic and genotypic frequencies for both <it>TCF7L2 </it>polymorphisms, did not differ significantly between TCP patients and controls belonging to either of the ethnic groups or taken together. No statistically significant association of the SNPs was observed with TCP or FCPD or between carriers and non-carriers of N34S <it>SPINK1 </it>and L26V <it>CTSB </it>mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S <it>SPINK1 </it>variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93–2.70, P = 0.09), while, <it>TCF7L2</it><it/>variant showed a statistically significant association between TCP and FCPD patients carrying the 26V allele (OR = 1.69, 95% CI = 1.11–2.56, P = 0.013).</p> <p>Conclusion</p> <p>Type 2 diabetes associated <it>TCF7L2 </it>variants are not associated with diabetes in TCP. Since, <it>TCF7L2 </it>is a major susceptibility gene for T2D, it may be hypothesized that the diabetes in TCP patients may not be similar to T2D. Our data also suggests that co-existence of <it>TCF7L2 </it>variants and the <it>SPINK1 </it>and <it>CTSB </it>mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.</p

Marker-Assisted Backcrossing to Introgress Resistance to Fusarium Wilt Race 1 and Ascochyta Blight in C 214, an Elite Cultivar of Chickpea

Fusarium wilt (FW) and Ascochyta blight (AB) are two major constraints to chickpea (Cicer arietinum L.) production. Therefore, two parallel marker-assisted backcrossing (MABC) programs by targeting foc1 locus and two quantitative trait loci (QTL) regions, ABQTL-I and ABQTL-II, were undertaken to introgress resistance to FW and AB, respectively, in C 214, an elite cultivar of chickpea. In the case of FW, foreground selection (FGS) was conducted with six markers (TR19, TA194, TAA60, GA16, TA110, and TS82) linked to foc1 in the cross C 214 × WR 315 (FWresistant). On the other hand, eight markers (TA194, TR58, TS82, GA16, SCY17, TA130, TA2, and GAA47) linked with ABQTL-I and ABQTL-II were used in the case of AB by deploying C 214 × ILC 3279 (AB-resistant) cross. Background selection (BGS) in both crosses was employed with evenly distributed 40 (C 214 × WR 315) to 43 (C 214 × ILC 3279) SSR markers in the chickpea genome to select plant(s) with higher recurrent parent genome (RPG) recovery. By using three backcrosses and three rounds of selfing, 22 BC3F4 lines were generated for C 214 × WR 315 cross and 14 MABC lines for C 214 × ILC 3279 cross. Phenotyping of these lines has identified three resistant lines (with 92.7–95.2% RPG) to race 1 of FW, and seven resistant lines (with 81.7–85.40% RPG) to AB that may be tested for yield and other agronomic traits under multilocation trials for possible release and cultivation

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis

BACKGROUND: The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant. METHODS: We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects. RESULTS: We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients. CONCLUSION: We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes

Mammalian BTBD12 (SLX4) Protects against Genomic Instability during Mammalian Spermatogenesis

The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and also in genome stability prior to meiosis. Using a Btbd12 mutant mouse, we analyzed the role of BTBD12 in mammalian gametogenesis. BTBD12 localizes to pre-meiotic spermatogonia and to meiotic spermatocytes in wildtype males. Btbd12 mutant mice have less than 15% normal spermatozoa and are subfertile. Loss of BTBD12 during embryogenesis results in impaired primordial germ cell proliferation and increased apoptosis, which reduces the spermatogonial pool in the early postnatal testis. During prophase I, DSBs initiate normally in Btbd12 mutant animals. However, DSB repair is delayed or impeded, resulting in persistent γH2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond. Unlike yeast Slx4, therefore, BTBD12 appears to function in meiotic prophase I, possibly during the recombination events that lead to the production of crossovers. In line with its expected regulation by ATM kinase, BTBD12 protein is reduced in the testis of Atm−/− males, and Btbd12 mutant mice exhibit increased genomic instability in the form of elevated blood cell micronucleus formation similar to that seen in Atm−/− males. Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM

Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis

Gametogenesis is one of the most important biological processes in the life of an organism because it results in the production of gametes, haploid cells that pass on the organism's genetic material to its offspring. However, it a very complicated, intricate process that demands a very high level of regulation. This regulation is to ensure error free meiotic and post-meiotic divisions resulting in a haploid gamete. Errors during the meiotic process can result in defective embryos or fetal demise. Among mammals, humans exhibit a very high rate of gamete defects (~25%) leading to high rates of early embryo loss. Stage-specific cell signaling cascades such as the MAPK pathway regulate meiosis and germ-cell development. In addition to this, MAPKs specifically ERKs, are thought to be involved in cellular division, cytoskeletal reorganization and segregation of genetic material. So far pharmacological approaches have been used to study the action of ERKs in oocytes in vitro using inhibitors of the ERK pathway. However, these are not truly reflective of the physiological environment of the ovary. Hence, in order to better understand the mechanism of action of ERKs on oocyte division, I have generated an Erk2 conditional deletion system driven by an oocyte specific Cre on an Erk1 null background. I hypothesized that deregulation of the MAPK pathway in oocytes will produce drastic changes in the cytokinesis and in chromosome segregation. Mutant females were found to be infertile, with gross chromosome misalignment on metaphase spindles in oocytes, and severe early embryonic loss. This phenotype was accompanied by loss of phosphorylation of several downstream targets such as MSK1 and histone H3. Several possible new targets have also been identified in this study by comparing phosphrylation profiles of oocytes from various genotypes. Our results demonstrate that ERK activity specifically within the oocyte is essential for meiotic resumption and for normal pre-implantation development