A case series of symptomatic intraluminal duodenal duplication cysts: presentation, endoscopic therapy, and long-term outcome (with video)

BACKGROUND: Duodenal duplication cysts are rare congenital anomalies. Symptomatic cases have classically been treated by surgical resection, which can be complex because of the close proximity of the cysts to the papilla. OBJECTIVE: To describe a series of 8 patients with symptomatic duodenal duplication cysts who were treated endoscopically, with a special focus on the long-term outcome. DESIGN: Retrospective case series. SETTING: Three tertiary-care European academic hospitals. PATIENTS: Eight patients, age 8 to 72 years, were treated endoscopically for symptomatic intraluminal duodenal duplication cysts between 1981 and 2006. Seven patients presented with acute pancreatitis, and one patient presented with jaundice. INTERVENTION: Endoscopic incision and marsupialization of the cysts was performed by using a variety of endoscopic tools (needle-knife and regular sphincterotomes, cystotomes, and polypectomy snares). MAIN OUTCOME MEASUREMENTS: Technical success of endoscopic intervention and long-term clinical recurrence of symptoms. RESULTS: No major complications occurred. All patients remained asymptomatic at a median follow-up of 7.3 years. LIMITATIONS: Retrospective study; the small number of patients. CONCLUSIONS: The endoscopic treatment of symptomatic intraluminal duodenal duplication cysts is a safe and effective technique, with excellent long-term results. It represents a minimally invasive alternative to surgical resection and might be considered the preferred therapeutic modality for these cases.     

Purified murine hematopoietic stem cells function longer on nonirradiated W41/Wv than on +/+ irradiated stroma

Mouse bone marrow (BM) was separated into low-density, lineage- negative, wheat germ agglutinin-positive (WGA+), Rhodamine-123 bright (Rhbright) or dim (Rhdim) cells to obtain populations that were highly enriched for committed progenitors (Rhbright cells) or for more primitive stem cells (Rhdim). When 2,500 Rhbright or Rhdim cells were seeded onto 6-week-old irradiated (20 Gy) long-term BM cultures (LTBMC), the nonadherent cell production from Rhbright cells was transient and ended after 5 weeks. Production from Rhdim cells did not begin until week 3, peaked at week 5, and ended at week 8, when the irradiated stroma seemed to fail. Termination of cell production from Rhdim cells did not occur in nonirradiated LTBMC from W41/Wv mice. During peak nonadherent cell production, 25% to 30% of the cells in the nonirradiated LTBMC from W41/Wv mice had donor cell markers. Two approaches were tested to try to enhance the proportion or number of donor cells. Addition of Origen-HGF at the time of seeding Rhdim cells caused a nonspecific increase in both host and donor cell production, but a specific increase in production of donor cells was obtained by seeding the cultures at 2 weeks rather than 6 weeks. Limiting dilution of Rhdim cells gave the same frequency of wells producing cells on both irradiated +/+ and nonirradiated W41/Wv or W/Wv cultures.     

Nanocarrier-based interventions for the management of MDR/XDR-TB

Emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB over the past decade presents an unprecedented public health challenge to which countries of concern are responding far too slowly. Global Tuberculosis Report 2014 marks the 20th anniversary of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance, indicating the highest global level of drug-resistance ever recorded detection of 97?000 patients with MDR-TB resulting in 170?000 deaths in 2013. Treatment of MDR-TB is expensive, complex, prolonged (18–24 months) and associated with a higher incidence of adverse events. In this context, nanocarrier delivery systems (NDSs) efficiently encapsulating considerable amounts of second-line anti tubercular drugs (^sATDs), eliciting controlled, sustained and more profound effect to trounce the need to administer ^sATDs at high and frequent doses, would assist in improving patient compliance and avoid hepatotoxicity and/or nephrotoxicity/ocular toxicity/ototoxicity associated with the prevalent ^sATDs. Besides, NDSs are also known to inhibit the P-glycoprotein efflux, reduce metabolism by gut cytochrome P-450 enzymes and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. This review first provides a holistic account on MDR-TB and discusses the molecular basis of Mycobacterium tuberculosis resistance to anti-tubercular drugs. It also provides an updated bird’s eye view on current treatment strategies and laboratory diagnostic test for MDR-TB. Furthermore, a relatively pithy view on patent studies on second-line chemotherapy using NDSs will be discussed.     

Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad District

BackgroundTreatment outcomes for Multidrug-Resistant Tuberculosis (MDR TB) is generally poor. The study aims to know about the treatment outcomes of MDR-TB under programmatic conditions in Hyderabad District and to analyze the factors influencing the treatment outcomes.MethodsThis is a retrospective study in which 377 patients of Hyderabad district, Telangana state who were diagnosed with MDR TB and registered at Drug Resistance TB Treatment site of Government General & Chest Hospital, Hyderabad from 4th quarter 2008 to 4th quarter 2013 were included in the study. Impact of Demographic factors (age, sex; Nutritional status (BMI); Co-morbid condition (Diabetes, HIV, Hypothyroidism); Programmatic factors (time delay in the initiation of treatment); Initial Resistance pattern on the outcomes were studied and analyzed.ResultsThe treatment outcomes of Multidrug-Resistant Tuberculosis under Programmatic Conditions were: 57% cured, 21.8% died, 19.6% defaulted, 1.1% failed and 0.5% switched to XDR. Age, Sex, BMI had a statistically significant impact on treatment outcomes. Hypothyroidism and Delay in the initiation of treatment >1 a month had an impact on the outcomes though not statistically significant. NO impact on treatment outcomes was found when Rifampicin resistance & INH sensitive patients were compared with those resistant to both INH and Rifampicin.ConclusionTo reduce MDR-TB transmission in the community, improvement of treatment outcomes, via ensuring adherence, paying special attention to elderly patients is required. The Programmatic Management of Drug Resistance Tuberculosis (PMDT) should seriously think of providing Nutritional support to patients with low BMI to improve outcomes. In the programmatic conditions if we could address the problems like delay in initiation of treatment and proper management of comorbidities like HIV, Diabetes, Hypothyroidism would definitely improve the treatment outcomes.     

Molecular basis of altered red blood cell membrane properties in Southeast Asian ovalocytosis: role of the mutant band 3 protein in band 3 oligomerization and retention by the membrane skeleton

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.     

Rifaximin,a pregnane X receptor (PXR) activator regulates apoptosis in a murine model of breast cancer

The present study was proposed to investigate the effect of rifaximin (RFX) on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized and divided among four groups of six animals each. Group I (control 0.9% normal saline, 3 ml kg⁻¹, p.o.); Group II (toxic control, MNU 47 mg kg⁻¹, i.v.); Group III (RFX, 25 mg kg⁻¹, p.o.); Group IV (RFX, 50 mg kg⁻¹, p.o.). Toxicity was induced by single i.v. injection of MNU. MNU treatment was evident with increased alveolar bud count, differentiation score, up-regulated inflammatory enzyme markers (COX, LOX, NO and H₂S) and oxidative stress markers (TBAR''s, protein carbonyl, SOD, catalase and Ach). The mammary gland surface architecture was studied using SEM, carmine staining and H&E staining. The treatment with RFX elicited noticeable restoration of the overall histological architecture in the experimental animals similar to the control. In the MNU treated toxic group, the levels of oxidative stress markers significantly increased in comparison to the control, which was subsequently restored after RFX treatment. Furthermore, RFX up regulated the levels of caspase 3 and caspase 8, when compared to the MNU treated animals. MNU associated toxicity was also ascertained, when determined for UCHL-1, COX, NF-κBp65, BAD, and BCL-xl expression, while RFX demonstrated modulation of the same.

The present study was proposed to investigate the effect of rifaximin (RFX) on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats.     

Probability Mapping to Determine the Spatial Risk Pattern of Acute Gastroenteritis in Coimbatore District,India, Using Geographic Information Systems (GIS)

Background:

Maps show well the spatial configuration of information. Considerable effort is devoted to the development of geographical information systems (GIS) that increase understanding of public health problems and in particular to collaborate efforts among clinicians, epidemiologists, ecologists, and geographers to map and forecast disease risk.

Objectives:

Small populations tend to give rise to the most extreme disease rates, even if the actual rates are similar across the areas. Such situations will follow the decision-maker''s attention on these areas when they scrutinize the map for decision making or resource allocation. As an alternative, maps can be prepared using P-values (probabilistic values).

Materials and Methods:

The statistical significance of rates rather than the rates themselves are used to map the results. The incidence rates calculated for each village from 2000 to 2009 is used to estimate λ, the expected number of cases in the study area. The obtained results are mapped using Arc GIS 10.0.

Results:

The likelihood of infections from low to high is depicted in the map and it is observed that five villages namely, Odanthurai, Coimbatore Corporation, Ikkaraiboluvampatti, Puliakulam, and Pollachi Corporation are more likely to have significantly high incidences.

Conclusion:

In the probability map, some of the areas with exceptionally high or low rates disappear. These are typically small unpopulated areas, whose rates are unstable due to the small numbers problem. The probability map shows more specific regions of relative risks and expected outcomes.     

Timing of Cholecystectomy in Acute Cholecystitis

Background

Cholecystitis is an inflammation of the gallbladder that most commonly occurs as a result of obstruction of the cystic duct by gallstones. The current standard of treatment for acute cholecystitis is cholecystectomy.