Study of Surgical Emergencies of Tubercular Abdomen in Developing Countries

To study the various modes of presentation, diagnosis, and management of surgical emergencies of tubercular abdomen. This prospective study of surgical emergencies of tubercular abdomen was conducted in 50 patients who attended our surgical emergency from 2006 to 2008. Patients were evaluated thoroughly with history, physical examination, routine investigations, and special investigations such as ELISA, PCR, barium studies of gastrointestinal tract, and diagnostic laparoscopy as required and managed with medical and surgical treatment as necessary. The most of patients were from rural areas, in the third to sixth decades with slight male preponderance. Abdominal pain, vomiting, and constipation were commonest presenting symptoms. About 20 % patients had history of pulmonary tuberculosis and 16 % patients presented with ascites. PCR for blood and ascitic fluid was positive in 72 and 87.5 % patients, respectively. About 24 % patients were managed nonoperatively and responded to ATT. About 76 % patients needed surgery among which one-fifth of patients were operated in emergency. Procedures like adhesiolysis of gut (47.3 %), strictureplasty (10.5 %), resection anastomosis (5.2 %), right hemicolectomy (5.2 %), and ileotransverse anastomosis (7.8 %) were performed in 30 patients and peritoneal biopsy and lymph node biopsy in the remaining 8 patients. Both medically and surgically managed patients were put on antitubercular therapy. Abdominal tuberculosis is a disease of middle-aged rural people, presenting commonly with abdominal pain and vomiting with right lower abdominal tenderness. PCR (blood and ascites) for tuberculosis is much more sensitive than IgM ELISA (blood and ascites). The most of patients required surgical procedures and all patients responded dramatically to antitubercular therapy symptomatically with increase in the hemoglobin level and decrease in ESR.     

Additional Primary Malignancies in Patients with Gastrointestinal Stromal Tumor (GIST): A Clinicopathologic Study of 260 Patients with Molecular Analysis and Review of the Literature

Annals of Surgical Oncology - The incidence of other primary neoplasms in gastrointestinal stromal tumor (GIST) patients is relatively high. Our aim was to better characterize the clinicopathologic...     

Bilateral stress fractures of femoral neck in non-athletes: a report of four cases

Femoral neck stress fractures (FNSFs) are rare,constituting only 5％ of all stress fractures in young adults.These fractures are usually seen in athletes,military recruits and patients with underlying m...     

Prescribing conventional antipsychotics in the era of novel antipsychotics: informed consent issues

The goal of this study was to ascertain why patients are maintained on conventional antipsychotics and whether the risks/benefits and alternative treatments with novel antipsychotics are discussed with these patients. We reviewed the charts of 117 outpatients maintained on conventional antipsychotics at three New York hospitals: Hutchings Psychiatric Center (HPC), Syracuse Veterans Affairs Medical Center (SVA), and the Continuing Day Treatment Program (CDT). The major reasons for maintaining patients on conventional antipsychotics were good response (50%), patient choice (45%), and physician choice (36%). Despite the high incidence of tardive dyskinesia at all three hospitals (range: 12%-50%), physicians often did not discuss the risks/benefits of continuing conventional antipsychotics with the patients. The treating psychiatrist discussed alternative treatments with 37% of patients at SVA, 58% at HPC, and 68% at CDT (P = 0.066, df = 2, Pearson chi(2) test). For patients who are receiving any antipsychotic therapy, discussions about the risks/benefits of treatments are integral for optimal treatment and medicolegal purposes.     

Accuracy of diagnosis and relationship with quality of emergency medicine training program

An indicator for emergency room performance is the ability to establish the correct diagnosis within the emergency room over the years. The authors chose to examine the non-congruence of Emergency Room diagnoses to that established after hospital stay for three selected years. A total of 8488 records were reviewed and all disparate diagnosis were recorded and categorized. Retrospective chart reviews were done from July 2008 to February 2009 at the Aga Khan University Hospital, Karachi. A substantial reduction in the percentage of disparate diagnoses was seen over the years from 41% in the initial year to 14% in the last year evaluated. It was concluded that over the years there has been an improvement in the reliability of Emergency Room diagnoses at the Aga Khan University Hospital, Karachi.     

Continuation rates and reasons for discontinuation of intra-uterine device in three provinces of Pakistan: results of a 24-month prospective client follow-up

Background

Long-acting reversible contraceptives, such as the intrauterine device (IUD), remain underutilised in Pakistan with high discontinuation rates. Based on a 24-month prospective client follow-up (nested within a larger quasi-experimental study), this paper presents the comparison of two intervention models, one using private mid-level providers branded as “Suraj” and the other using community midwives (CMWs) of Maternal Newborn and Child Health Programme, for method continuation among IUD users. Moreover, determinants of IUD continuation and the reasons for discontinuation, and switching behaviour were studied within each arm.

Methods

A total of 1,163 IUD users, 824 from Suraj and 339 from the CMW model, were enrolled in this 24-month prospective client follow-up. Participants were followed-up by female community mobilisers physically every second month to ascertain continued IUD usage and to collect information on associated factors, switching behaviour, reasons for discontinuation, and pregnancy occurrence. The probabilities of IUD continuation and the risk factors for discontinuation were estimated by life table analysis and Cox proportional-hazard techniques, respectively.

Results

The cumulative probabilities of IUD continuation at 24 months in Suraj and CMW models were 82% and 80%, respectively. The difference between the two intervention areas was not significant. The probability distributions of IUD continuation were also similar in both interventions (Log rank test: χ² = 0.06, df = 1, P = 0.81; Breslow test: χ² = 0.6, df = 1, P = 0.44). Health concerns (Suraj = 57.1%, CMW = 38.7%) and pregnancy desire (Suraj = 29.3%, CMW = 40.3%) were reported as the most prominent reasons for IUD discontinuation in both intervention arms. IUD discontinuation was significantly associated with place of residence in Suraj and with age (15–25 years) in the CMW model.

Conclusion

CMWs and private providers are equally capable of providing quality IUD services and ensuring higher method continuation. Pakistan’s National Maternal Newborn and Child Health programme should consider training CMWs and providing IUDs through them. Moreover, private sector mid-level providers could be engaged in promoting the use of IUDs.

     

Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid‐type fibromatosis by whole‐exome sequencing and genomic analysis

CTNNB1 mutations or APC abnormalities have been observed in ～85% of desmoids examined by Sanger sequencing and are associated with Wnt/β‐catenin activation. We sought to identify molecular aberrations in “wild‐type” tumors (those without CTNNB1 or APC alteration) and to determine their prognostic relevance. CTNNB1 was examined by Sanger sequencing in 117 desmoids; a mutation was observed in 101 (86%) and 16 were wild type. Wild‐type status did not associate with tumor recurrence. Moreover, in unsupervised clustering based on U133A‐derived gene expression profiles, wild‐type and mutated tumors clustered together. Whole‐exome sequencing of eight of the wild‐type desmoids revealed that three had a CTNNB1 mutation that had been undetected by Sanger sequencing. The mutation was found in a mean 16% of reads (vs. 37% for mutations identified by Sanger). Of the other five wild‐type tumors sequenced, two had APC loss, two had chromosome 6 loss, and one had mutation of BMI1. The finding of low‐frequency CTNNB1 mutation or APC loss in wild‐type desmoids was validated in the remaining eight wild‐type desmoids; directed miSeq identified low‐frequency CTNNB1 mutation in four and comparative genomic hybridization identified APC loss in one. These results demonstrate that mutations affecting CTNNB1 or APC occur more frequently in desmoids than previously recognized (111 of 117; 95%), and designation of wild‐type genotype is largely determined by sensitivity of detection methods. Even true CTNNB1 wild‐type tumors (determined by next‐generation sequencing) may have genomic alterations associated with Wnt activation (chromosome 6 loss/BMI1 mutation), supporting Wnt/β‐catenin activation as the common pathway governing desmoid initiation. © 2015 Wiley Periodicals, Inc.     

Consistent copy number changes and recurrent PRKAR1A mutations distinguish Melanotic Schwannomas from Melanomas: SNP‐array and next generation sequencing analysis

Melanotic Schwannomas (MS) are rare tumors that share histological features with melanocytic tumors and schwannomas. However, their genetics are poorly understood. To elucidate the genetic characteristics of MS, we performed genome‐wide studies in a series of cases. Twelve MS cases were available for the study. Genomic DNAs extracted from formalin‐fixed paraffin embedded tumor tissues were subjected to copy number (CN) and allelic imbalance (AI) analysis by Single Nucleotide Polymorphism (SNP)‐array and screened for mutations in coding exons of 341 key cancer‐associated genes using a hybrid capture‐based next‐generation sequencing (NGS) assay. Sanger sequencing was used to further verify recurrent mutations detected by NGS study. SNP‐array analysis revealed remarkably stereotypic chromosomal abnormalities in MS. Hypodiploidy was common, typically involving monosomies of chromosomes 1, 2, and 17. All 12 samples showed mutations in PRKAR1A gene, including 2 cases with 2 mutations each. The 14 mutations were scattered across PRKAR1A, and most were inactivating mutations. AI on 17q, presenting as loss of heterozygosity with or without CN losses, combined with a PRKAR1A mutation was observed in 9/12 MS cases. The remaining 3 cases included the two samples harboring two mutations in PRKAR1A. MS exhibits a stereotypic pattern of chromosomal losses. In contrast, melanomas are typically characterized by the presence of multiple CN aberrations, without demonstrable differences in the frequency of losses and gains. Inactivation of both alleles of PRKAR1A by “two hits” observed in almost all cases underscores the central role of PRKAR1A in the pathogenesis of this neoplasm. © 2015 Wiley Periodicals, Inc.     

Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.