Gastric outlet obstruction caused by duodenal impaction of a large gallstone migrated through a cholecystoduodenal fistula has been referred to as Bouveret's syndrome. We present a case of gallstone-induced duodenal obstruction in an elderly female patient, diagnosed on a 64-slice MDCT scanner. One-stage surgery, that is, stone removal and cholecystectomy, was performed resulting in relief of obstruction and complete cure. Clinical features, multidetector computed tomography (MDCT) findings, and surgical management are discussed.
Cerebral venous sinus thrombosis (CVST) is an uncommon condition with severe consequences. Although we do not know the exact incidence and prevalence of CVST, it is an important diagnosis. Over the past decade, it has been diagnosed more frequently due to greater awareness and availability of noninvasive diagnostic techniques. Furthermore, routine diagnostic neuroimaging has been used to monitor the clinical progress of these patients, especially in deteriorating cases. In order to decrease morbidity and mortality, an understanding of CVST treatment options is important. Treatment of extensive intracranial venous sinus thrombosis with intrasinus infusion of recombinant tissue plasminogen activator (rt-PA) is relatively controversial as there are no clear guidelines in regards to appropriate therapeutic management. We report a case of successful intrasinus thrombolysis of deep cerebral sinus thrombosis (DCST) resulting in rapid radiographic improvement associated with complete clinical recovery.
We describe here a rare case of Idiopathic Bullous Emphysema/Vanishing Lung Syndrome (VLS) in a 33-year-old male patient with a history of marijuana abuse who presents to the hospital with pleuritic chest pain thought to be due to pneumothorax based on the chest radiograph. This case emphasizes the need to obtain chest computed tomography in a relatively stable patient suspected of VLS to reduce the potential risk of overseeing a bronchopleural fistula.
Pulmonary arteriovenous malformations (PAVMs), although most commonly congenital, are usually detected later in life. We present a case of a 25-year-old woman with no previous history of AVM or telangiectasia, who presented with life-threatening hypoxia, hypotension, and pleuritic chest pain in 36th week of gestation. Chest tube placement revealed 4 liters of blood. Patient was subsequently found to have bleeding pulmonary AVM as the source of hemothorax. Successful embolisation of the bleeding vessel followed by thoracoscopic evacuation of the organized clot relieved the hypoxia. Further screening for AVM revealed large splenic AVM for which patient underwent splenectomy in the coming months.
Ulcerative colitis is a chronic inflammatory disease of unknown etiology characterized by periods of remission and relapses. This study has been carried out in a group of North Indian patients, where the disease has shown an increasing prevalence and frequent relapses. Hence, there is a need to predict relapse for better management and to reduce morbidity. To assess the importance of biological and histological parameters in predicting relapse when the disease is in quiescent phase.
Materials and Methods:
A prospective study of twenty-six patients with quiescent ulcerative colitis was carried out in Dayanand Medical College and Hospital, Punjab. Only patients with clinical and endoscopic remission at the time of screening visit were included. Hemoglobin, erythrocyte sedimentation rate (ESR), C- reactive protein (CRP) and serum Interleukin-6 (IL-6) levels were measured. The baseline colonoscopic mucosal biopsies were retrieved and studied. Follow-up was conducted for one year at monthly interval or earlier if relapse occurred.
Fifteen out of twenty-six patients (57.69%) had evidence of clinical relapse during the follow-up. Hemoglobin, ESR, CRP and IL-6 levels were not found to be significant predictors of relapse. Increased number of eosinophils and neutrophils in the lamina propria were observed to be associated with significantly higher relapse rate.
A higher risk of relapse in patients with quiescent colitis can be predicted by the presence of increased number of eosinophils and neutrophils in the lamina propria.
Predictors; remission; relapse; quiescent phase; ulcerative colitis
We conducted a preliminary proof-of-concept study evaluating gabapentin for the treatment of tobacco dependence.
Subjects (N = 80) were randomized to gabapentin (600 mg three times per day or 900 mg three times per day) or placebo. After a 2-week dose titration, the target dose was maintained for 9 weeks and then tapered over 1 week. Follow-up was for 12 weeks after the medication phase.
The study had high dropout rates with more than one half of participants in each arm discontinuing study. Gabapentin-treated participants exhibited lower abstinence rates than placebo-treated participants; however, this difference was not significant. Smoking reduction was observed across all treatment arms compared with baseline (p < .01) but did not differ across treatment groups.
Although not definitive, our findings suggest that gabapentin administered at these doses with this dosing regimen holds little promise for the treatment of tobacco dependence in a population of smokers seeking treatment.
The Aboriginal population in Canada experiences high rates of end-stage renal disease and need for dialytic therapies. Our objective was to examine rates of mortality, technique failure and peritonitis among adult aboriginal patients receiving peritoneal dialysis in the province of Manitoba. We also aimed to explore whether differences in these rates may be accounted for by location of residence (i.e., urban versus rural).
We included all adult patients residing in the province of Manitoba who received peritoneal dialysis during the period from 1997–2007 (n = 727). We extracted data from a local administrative database and from the Canadian Organ Replacement Registry and the Peritonitis Organism Exit-sites/Tunnel infections (POET) database. We used Cox and logistic regression models to determine the relationship between outcomes and Aboriginal ethnicity. We performed Kaplan–Meier analyses to examine the relationship between outcomes and urban (i.e., 50 km or less from the primary dialysis centre in Winnipeg) versus rural (i.e., more than 50 km from the centre) residency among patients who were aboriginal.
One hundred sixty-one Aboriginal and 566 non-Aboriginal patients were included in the analyses. Adjusted hazard ratios for mortality (HR 1.476, CI 1.073–2.030) and adjusted time to peritonitis (HR 1.785, CI 1.352–2.357) were significantly higher among Aboriginal patients than among non-Aboriginal patients. We found no significant differences in mortality, technique failure or peritonitis between urban- or rural-residing Aboriginal patients.
Compared with non-Aboriginal patients receiving peritoneal dialysis, Aboriginal patients receiving peritoneal dialysis had higher mortality and faster time to peritonitis independent of comorbidities and demographic characteristics. This effect was not influenced by place of residence, whether rural or urban.
Introduction: Ulcerative colitis occurs worldwide. It is considered common in most of Europe and North America and uncommon in most of the developing Asian countries. The incidence/prevalence of ulcerative colitis varies not only according to geographical region but also with race and ethnicity. There are no reported data from India on the incidence of the disease and its prevalence.
Material and methods: A house to house survey was conducted by questionnaire, formulated to enquire about symptoms that are suggestive of ulcerative colitis. Those with prolonged diarrhoea with or without rectal bleeding were considered as suspected cases. These suspected cases were subjected to video sigmoidoscopy/colonoscopy and rectal biopsy. In addition, patients already diagnosed and receiving treatment for ulcerative colitis, encountered during the survey, were reviewed. Resurvey of the same areas was conducted after a one year interval to detect new cases. Using direct methods, standardised rates were calculated using world standard population weights 22, 18, 16, 12, 12, 9, 7, 3, and 1 for each 10 year age group. Standardised rates were also obtained separately for males, females, and combined populations, using the Punjab state 1991 population census data. Rates were also estimated according to UK 2000 population data. Ninety five per cent confidence intervals (95% CI) of prevalence and incidence rates of ulcerative colitis were estimated under the assumption that the distribution of cases followed a Poisson probability model.
Results: A total population of 51 910 were screened from January to March 1999. We identified 147 suspected cases and of these 23 were finally established as ulcerative colitis cases, giving a crude prevalence rate of 44.3 per 100 000 inhabitants (95% CI 29.4–66.6). A second visit to the same areas after one year identified 10 suspected cases in a population of 49 834. Of these, three were confirmed as “definite” ulcerative colitis giving a crude incidence rate of 6.02 cases per 100 000 inhabitants (95% CI 1.2–17.6).
Conclusions: This is the first population based study from India reporting on the incidence and prevalence of ulcerative colitis. The disease frequency is not much less than that reported from Europe and North America.
ulcerative colitis; ; epidemiology; India
Wnt/β-catenin signaling plays an important role in normal development. However, its aberrant activation is associated with several cancers. The aim of this study is to examine the Wnt/β-catenin pathway in patients with advanced pancreatic adenocarcinoma (n = 31). Paraffin sections from tumors (n = 16) and normal pancreata (n = 3) were used to determine the localization of β-catenin. An additional 15 frozen tumors, adjacent normal pancreata (n = 5), or normal pancreata (n = 4) were utilized for protein isolation. Tumors were also examined for mutations in exon 3 of the CTNNB1 gene. More than 65% of the tumors showed an increase in total β-catenin, consistent with its enhanced membranous, cytoplasmic, and nuclear localization, but only two showed mutations in CTNNB1. The majority of the remaining tumors demonstrated concurrent increases in Wnt-1 and frizzled-2 (positive regulators) and a decrease in Ser45/Thr41-phospho-β-catenin. Electrophoretic mobility shift assay demonstrated β-catenin-T-cell factor binding in tumors only. Adenomatous polyposis coli and axin, which are both negative regulators, remained unchanged. Unexpectedly, total glycogen synthase kinase-3β protein was elevated in these tumors. Elevated levels of E-cadherin were also observed, although E-cadherin-β-catenin association in tumors remained unaffected. Thus, Wnt/β-catenin activation was observed in 65% of pancreatic adenocarcinomas, independently of β-catenin gene mutations in most tumors.
Pancreas; tumors; mutation; patient; cancer
This prospective study was carried out in a service hospital, with the aim to study the prevalence and incidence of depression in pregnancy and postpartum period. Eighty Four consecutive patients attending the antenatal outpatient in the Obstetrics & Gynaecology department in their last trimester of pregnancy were recruited for the study. They were assessed on Beck Depression Inventory thrice viz. during third trimester of pregnancy, within 3 days of delivery (early postpartum period) & within 4-8 weeks of delivery (late postpartum period).The prevalence of depression was 8.3%, 20% and 12.8% respectively at three ratings. The incidence was 16% and 10% in the early & late postpartum period respectively. Further analysis revealed that depression in pregnancy correlated significantly with depression in early postpartum period, but not with late postpartum period. Depression in early postpartum period correlated with depression in late postpartum period.These findings have implications for early detection and care of women at risk for developing depression.
Depression; Pregnancy; Postpartum
Selection of physicians for fellowships in obstetrics and gynecology subspecialties has become increasingly competitive. The number and quality of research publications is an important factor in the selection process. We sought to estimate the incidence of unverifiable (“ghost”) publications among gynecologic oncology fellowship applicants.
We reviewed the applications to a single gynecologic oncology fellowship program during 2004–2008. Articles and book chapters reported as published, “in press”, “submitted”, or “in progress” were systematically searched for by three reviewers using PubMed and Google. Chi-square analysis was used to evaluate associations between demographic factors and unverifiable publications.
Two hundred forty-three applications met the inclusion criteria. Of the 35 applicants who listed membership in Alpha Omega Alpha, 4 (11%) were not listed on the organization’s website as inductees. Of the 464 articles reported as published or “in press”, only 387 (83%) could be verified. Of the 148 applicants who reported at least 1 published/“in press” article, 44 (30%) had at least 1 unverifiable publication. On multivariable analysis, only male gender increased the likelihood of unverifiable publications (OR 2.1, 95% CI 1.1–4.1). Of the 282 manuscripts reported as “submitted” or “in progress”, only 126 (44%) were published. Of the 124 applicants who reported at least 1 “submitted”/“in progress” manuscript, 88 (71%) had at least 1 unverifiable manuscript.
The proportion of unverifiable publications listed on gynecologic oncology fellowship applications is concerning. Stringent review of applications before interview invitations and match list submission is warranted.
The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer (PCa) tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in PCa cells. The junction of theTMPRSS2 and ERG derived portions of the fusion mRNA constitutes a cancer specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low toxicity treatment for PCa.
We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (Type III or Type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of PCa cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms.
The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed.
Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with PCa.
prostate cancer; siRNA; TMPRSS2/ERG; liposome; xenograft
OPCML, frequently inactivated in ovarian tumors, mediates its anti-tumor effect via binding to the extracellular domains of several important oncogenic receptor tyrosine kinases (RTKs). This, in turn, leads to the down-regulation of RTKs in tumor cells and results in significant inhibition of tumor growth.
Almost 3 billion people worldwide burn solid fuels indoors. These fuels include biomass and coal. Although indoor solid fuel smoke is likely a greater problem in developing countries, wood burning populations in developed countries may also be at risk from these exposures. Despite the large population at risk worldwide, the effect of exposure to indoor solid fuel smoke has not been adequately studied. Indoor air pollution from solid fuel use is strongly associated with COPD (both emphysema and chronic bronchitis), acute respiratory tract infections, and lung cancer (primarily coal use) and weakly associated with asthma, tuberculosis, and interstitial lung disease. Tobacco use further potentiates the development of respiratory disease among subjects exposed to solid fuel smoke. There is a need to perform additional interventional studies in this field. It is also important to increase awareness about the health effects of solid fuel smoke inhalation among physicians and patients as well as trigger preventive actions through education, research, and policy change in both developing and developed countries.
Biomass; Solid fuel; COPD; Asthma; Lung cancer; Respiratory tract infection
Aflibercept targets vascular endothelial growth factor and placental growth factor. We evaluated activity and toxicity of aflibercept in recurrent/persistent endometrial cancer patients. Biomarkers and association with clinical characteristics and outcome were explored.
Eligible patients had measurable disease; 1–2 prior cytotoxic regimens; performance status 0–2. Aflibercept 4 mg/kg IV q14 days (28-day cycles) was administered until disease progression or prohibitive toxicity. Primary endpoints were the proportion of patients with progression-free survival at six months (PFS6) and tumor response rate. A flexible two-stage group sequential design to detect 20% increases in the proportion of patients responding or enduring PFS6 with 90% power (α=10%) was employed.
Forty-nine patients were enrolled; five were excluded: wrong primary (2), second primary (1), wrong cell type (1); never treated (1). Median age was 64 (range 48–83). Eighteen patients (41%) had two prior regimens; 61%(27) had prior radiation. The PFS6 rate was 41%; three patients 7%, 90% CI:2–17) had partial response. Of note, 10 patients (23%) met the PFS6 endpoint without starting a subsequent therapy; the remaining eight patients discontinued therapy for toxicity and started another therapy before six months elapsed. Median PFS and overall survival were 2.9 months and 14.6 months, respectively. Significant grade 3/4 toxicities were: cardiovascular (23%/5%), constitutional (7%/0), hemorrhage (2%/5%), metabolic (7%/2%), pain (18%/0). Two treatment-related deaths were recorded: GI perforation (1), arterial rupture (1). FGF1 expression was associated with response.
Aflibercept met pretrial activity parameters, but was associated with significant toxicity at this dose and schedule in this population.
Aflibercept; endometrial cancer; VEGF Trap; Toxicity; Fibroblast growth factor
Varicella (chicken pox) is a highly contagious disease which is caused by Varicella Zoster Virus (VZV), a ubiquitous human α herpes virus. Nosocomial varicella in hospital employees can be costly to the hospital and disruptive to patient care. This case report describes an occupationally related outbreak of chickenpox in hospital staff and the lessons which were learnt by the hospital during this experience.
Occupational outbreak; Chicken-pox; Hospital
Whenever the treatment revolves around structural balance and aesthetic harmony, the crux remains to be the periodontal health of the existing dentition. In such scenarios where restorations and aesthetics are of concern, biologic width (BW) is the initial and final frontier. Considering attrition of teeth, the resistance which is offered by them is definitely at a lower level as compared to teeth with adequate height. Clinical crowns of worn out teeth are seriously handicapped when it comes to bearing the occlusal loads, which can be brought back to normalcy by crown lengthening . Crown lengthening includes the surgical removal of soft and hard periodontal architecture to gain (vertical dimension) a supracrestal tooth length, thus allowing a longer clinical crown reestablishment of BW. This paper has described the full mouth rehabilitation of severe fluorozed and attrited teeth in a 35–year male with the use of an interdisciplinary approach (6 Handed Dentistry).
Crown lengthening; Biologic width; Vertical dimension
This paper describes the pharmaceutical regulatory environment in 19 developed countries from 1992 to 2004 and examines how changes in regulatory policies affect pharmaceutical revenues. Several important findings emerge from our analysis. First, we document a trend towards increasing pharmaceutical regulation over this 13-year period. Second, we find that a majority of regulations reduce pharmaceutical revenues significantly. Third, we find that most countries that adopted new regulations since 1994 already had some regulations in place for controlling costs. We find that such additional regulation had a smaller impact on further controlling costs. However, we find that introducing new regulations in a largely unregulated market, for example the US, could reduce pharmaceutical revenues significantly. Finally, we show that the effects of price controls increase over time.
Chronic pain is a major clinical problem, yet the mechanisms underlying the transition from acute to chronic pain remain poorly understood. In mice, reduced expression of GPCR kinase 2 (GRK2) in nociceptors promotes cAMP signaling to the guanine nucleotide exchange factor EPAC1 and prolongs the PGE2-induced increase in pain sensitivity (hyperalgesia). Here we hypothesized that reduction of GRK2 or increased EPAC1 in dorsal root ganglion (DRG) neurons would promote the transition to chronic pain. We used 2 mouse models of hyperalgesic priming in which the transition from acute to chronic PGE2-induced hyperalgesia occurs. Hyperalgesic priming with carrageenan induced a sustained decrease in nociceptor GRK2, whereas priming with the PKCε agonist ΨεRACK increased DRG EPAC1. When either GRK2 was increased in vivo by viral-based gene transfer or EPAC1 was decreased in vivo, as was the case for mice heterozygous for Epac1 or mice treated with Epac1 antisense oligodeoxynucleotides, chronic PGE2-induced hyperalgesia development was prevented in the 2 priming models. Using the CFA model of chronic inflammatory pain, we found that increasing GRK2 or decreasing EPAC1 inhibited chronic hyperalgesia. Our data suggest that therapies targeted at balancing nociceptor GRK2 and EPAC1 levels have promise for the prevention and treatment of chronic pain.
Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer.
Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics.
The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer.
Angiogenesis has long been considered an important target for cancer therapy. Initial efforts have primarily focused on targeting of endothelial and tumor-derived vascular endothelial growth factor signaling. As evidence emerges that angiogenesis has significant mechanistic complexity, therapeutic resistance and escape have become practical limitations to drug development. Here, we review the mechanisms by which dynamic changes occur in the tumor microenvironment in response to antiangiogenic therapy, leading to drug resistance. These mechanisms include direct selection of clonal cell populations with the capacity to rapidly upregulate alternative proangiogenic pathways, increased invasive capacity, and intrinsic resistance to hypoxia. The implications of normalization of vasculature with subsequently improved vascular function as a result of antiangiogenic therapy are explored, as are the implications of the ability to incorporate and co-opt otherwise normal vasculature. Finally, we consider the extent to which a better understanding of the biology of hypoxia and reoxygenation, as well as the depth and breadth of systems invested in angiogenesis, may offer putative biomarkers and novel therapeutic targets. Insights gained through this work may offer solutions for personalizing antiangiogenesis approaches and improving the outcome of patients with cancer.
Chronic idiopathic constipation (CIC) and irritable bowel syndrome (IBS) are functional disorders of the lower gastrointestinal tract. Their prevalence in the general population is between 5% and 20%. Both disorders are chronic, with a relapsing and remitting natural history. The medical treatment of both conditions is unsatisfactory at present, and they represent a huge burden to the health service. Linaclotide is a first-in-class minimally adsorbed, 14-amino-acid peptide agonist of guanylate cyclase C. The drug acts on the intestinal enterocyte. As a consequence of this, intestinal fluid secretion is increased and intestinal transit is accelerated. The efficacy of linaclotide has been studied in both CIC and constipation-predominant IBS (IBS-C). Randomized controlled trials consistently demonstrate that the drug is effective in the treatment of CIC and IBS-C, across a wide range of continuous and dichotomous endpoints. The number needed to treat with linaclotide to prevent one patient with CIC or IBS-C failing to respond to therapy is between 5 and 8 in studies that have reported these data. Overall, in the majority of trials, total numbers of adverse events have been no more frequent with linaclotide, but rates of diarrhoea have been consistently higher. While the drug is clearly effective in the treatment of CIC, there are other evidence-based therapies available, and head-to-head efficacy and cost-effectiveness studies are therefore required to further delineate the role of linaclotide in the treatment of the condition. In IBS-C there are no other licensed therapies available, and linaclotide therefore represents a novel treatment with great promise.
abdominal pain; constipation; diarrhoea; irritable bowel syndrome; linaclotide