Outcome analysis of 71 clinical intestinal transplantations

Objective: The aim of the study was to determine risk factors associated with graft failure and mortality after transplantation of the intestine alone or as pad of an organ complex. Summary Background Data: Even with modern immunosuppressive therapies, clinical intestinal transplantation remains a difficult and unreliable procedure. Causes for this and solutions are needed. Methods: Between May 1990 and February 1995, 71 intestinal transplantations were performed in 66 patients using tacrolimus and low-dose steroids. The first 63 patients, all but one treated 1 to 5 years ago, received either isolated grafts (n = 22), liver and intestinal grafts (n = 30), or multivisceral grafts (n = 11). Three mere recipients of allografts who recently underwent surgery and one undergoing retransplantation were given unaltered donor bone marrow cells perioperatively as a biologic adjuvant. Results: Of the first 63 recipients, 32 are alive: 28 have functioning primary grafts and 4 have resumed total parenteral nutrition after graft enterectomy. Thirty-five primary grafts were lost to technical and management errors (n = 10), rejection (n = 6), and infection (n = 19). Regression analysis revealed that duration of surgery, positive donor cytomegalovirus (CMV) serology, inclusion of graft colon, OKT3 use, steroid recycle, and high tacrolimus blood levels contributed to graft loss. All four intestine and bone marrow recipients are alive for 2-3 months without evidence of graft- versus-host disease. Conclusion: To improve outcome after intestinal transplantation with previous management protocols, it will be necessary to avoid predictably difficult patients, CMV seropositive donors, and inclusion of the graft colon. Bone marrow transplantation may further improve outcome by ameliorating the biologic barriers of rejection and infection and allowing less restrictive selection criteria

CURBING ACTINOMYCETES AND THIDIAZURON ENHANCED MICROPROPAGATION IN THE RARE ALPINIA GALANGA - A MEDICINAL ZINGIBER

Objective: Elimination of endophytic actinomycetes before micropropagation using antibiotic pre-treatment in rhizome bud explants of Alpinia galanga. Then, the formulation of an operative protocol for Micropropagation of the same void of endophytic actinomycetes. Methods: A treatment of mercury chloride and carbendazim, alone and in combination was used as surface sterilants. A pre-treatment of rifampicin and fusidic acid was used against actinomycete endophyte disinfection of rhizome bud explants. Then, Murashige and Skoog (MS) medium supplemented with various concentrations of cytokinins were used for micropropagation of disinfected explants. Results: A treatment of 0.1% (w/v) mercury chloride and 0.1% (w/v) carbendazim, one after the other for 5 minutes gave the best sterility of 83.3%. A pre-treatment of Rifampicin 100 mg/l and fusidic acid 100 mg/l for 2 hrs gave the best disinfection of 70% against actinomycete endophytes. A combination of thidiazuron (TDZ) 0.45 μM and 6-benzyladenine 13.32 μM in MS medium resulted in 9.4 shoots per explant. MS medium fortified with 10.74 μMof 1-naphthaleneacetic acid gave the best rooting of 20 roots/shoot. inter simple sequence repeat marker genetic similarity of regenerants with the mother plant was confirmed. Conclusion: This study shows the potency of Rifampicin and Fusidic acid to disinfect explants from actinomycete endophytes and is significant as the first report on curbing actinomycetes endophytes in plant tissue culture of A. galanga. This is also the first report conferring the dissimilar regeneration capabilities of TDZ in comparison to other cytokinins in Zingiberaceae

Thermodynamics of a class of non-asymptotically flat black holes in Einstein-Maxwell-Dilaton theory

We analyse in detail the thermodynamics in the canonical and grand canonical ensembles of a class of non-asymptotically flat black holes of the Einstein-(anti) Maxwell-(anti) Dilaton theory in 4D with spherical symmetry. We present the first law of thermodynamics, the thermodynamic analysis of the system through the geometrothermodynamics methods, Weinhold, Ruppeiner, Liu-Lu-Luo-Shao and the most common, that made by the specific heat. The geometric methods show a curvature scalar identically zero, which is incompatible with the results of the analysis made by the non null specific heat, which shows that the system is thermodynamically interacting, does not possess extreme case nor phase transition. We also analyse the local and global stability of the thermodynamic system, and obtain a local and global stability for the normal case for 0<\gamma<1 and for other values of \gamma, an unstable system. The solution where \gamma=0 separates the class of locally and globally stable solutions from the unstable ones.Comment: 18 pages, version accepted for publication in General Relativity and Gravitatio

Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes

BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Adrenal Dysfunction in Hemodynamically Unstable Patients in the Emergency Department

Objective: Adrenal failure, a treatable condition, can have catastrophic consequences if unrecognized in critically ill ED patients. The authors' objective was to prospectively study adrenal function in a case series of hemodynamically unstable (high-risk) patients from a large, urban ED over a 12-month period. Methods: In a prospective manner, critically ill adult patients presenting to the ED were enrolled when presenting with a mean arterial blood pressure ≤60 mm Hg requiring vasopressor therapy for more than one hour after receiving fluid resuscitation (central venous pressure of 12-15 mm Hg or a minimum of 40 mL/kg of crystalloid). Patients were excluded if presenting with hemorrhage, trauma, or AIDS, or if steroids were used within the previous six months. An adrenocorticotropic hormone (ACTH) stimulation test was performed and serum cortisol was measured. Treatment for adrenal insufficiency was not instituted. Results: A total of 57 consecutive patients were studied. Of these, eight (14%) had baseline serum cortisol concentrations of <20 Μg/dL (<552 nmol/L), which was considered adrenal insufficiency (AI). Three additional patients (5%) had subnormal 60-minute post-ACTH-stimulation cortisol responses (<30 Μg/dL) and a delta cortisol ≤9 Μg/dL, which is the difference between the baseline and 60-minute levels. This is functional hypoadrenalism (FH). There were no laboratory abnormalities that distinguished patients with AI or FH from those with preserved adrenal function (PAF). Rates of survival to discharge did not differ between the AI group (7 of 8) and PAF patients (21 of 46; p = 0.052). Conclusions: Adrenal dysfunction is common in high-risk ED patients. Overall, it has a frequency of 19% among a homogeneous population of hemodynamically unstable vasopressor-dependent patients. The effect of physiologic glucocorticoid replacement in this setting remains to be determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71956/1/j.1553-2712.1999.tb00417.x.pd

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Bianchi Type-II String Cosmological Models in Normal Gauge for Lyra's Manifold with Constant Deceleration Parameter

The present study deals with a spatially homogeneous and anisotropic Bianchi-II cosmological models representing massive strings in normal gauge for Lyra's manifold by applying the variation law for generalized Hubble's parameter that yields a constant value of deceleration parameter. The variation law for Hubble's parameter generates two types of solutions for the average scale factor, one is of power-law type and other is of the exponential form. Using these two forms, Einstein's modified field equations are solved separately that correspond to expanding singular and non-singular models of the universe respectively. The energy-momentum tensor for such string as formulated by Letelier (1983) is used to construct massive string cosmological models for which we assume that the expansion ($\theta$) in the model is proportional to the component $\sigma^{1}_{~1}$ of the shear tensor $\sigma^{j}_{i}$. This condition leads to $A = (BC)^{m}$, where A, B and C are the metric coefficients and m is proportionality constant. Our models are in accelerating phase which is consistent to the recent observations. It has been found that the displacement vector $\beta$ behaves like cosmological term $\Lambda$ in the normal gauge treatment and the solutions are consistent with recent observations of SNe Ia. It has been found that massive strings dominate in the decelerating universe whereas strings dominate in the accelerating universe. Some physical and geometric behaviour of these models are also discussed.Comment: 24 pages, 10 figure

The impact of laxative use upon symptoms in patients with proven slow transit constipation

<p>Abstract</p> <p>Background</p> <p>Constipation severity is often defined by symptoms including feelings of complete evacuation, straining, stool frequency and consistency. These descriptors are mostly obtained in the absence of laxative use. For many constipated patients laxative usage is ubiquitous and long standing. Our aim was to determine the impact of laxative use upon the stereotypic constipation descriptors.</p> <p>Methods</p> <p>Patients with confirmed slow transit constipation completed 3-week stool diaries, detailing stool frequency and form, straining, laxative use and pain and bloating scores. Each diary day was classified as being under laxative affect (laxative affected days) or not (laxative unaffected days). Unconditional logistic regression was used to assess the affects of laxatives on constipation symptoms.</p> <p>Results</p> <p>Ninety four patients with scintigraphically confirmed slow transit constipation were enrolled in the study. These patients reported a stool frequency of 5.6 ± 4.3 bowel motions/week, only 21 patients reported <3 bowel motions/week. Similarly, 21 patients reported a predominant hard stool at defecation. The majority (90%) of patients reported regular straining. A regular feeling of complete evacuation was reported in just 7 patients. Daily pain and/or bloating were reported by 92% of patients. When compared with laxative unaffected days, on the laxative affected days patients had a higher stool frequency (OR 2.23; <it>P </it><0.001) and were more likely to report loose stools (OR 1.64; <it>P </it><0.009). Laxatives did not increase the number of bowel actions associated with a feeling of complete evacuation. Laxative use had no affect upon straining, pain or bloating scores</p> <p>Conclusions</p> <p>The reporting of frequent and loose stools with abdominal pain and/or bloating is common in patients with slow transit constipation. While laxative use is a significant contributor to altering stool frequency and form, laxatives have no apparent affect on pain or bloating or upon a patients feeling of complete evacuation. These factors need to be taken into account when using constipation symptoms to define this population.</p