Pharmacological therapy of vascular malformations of the gastrointestinal tract.

Vascular malformation (AVM) in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone) and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.     

The anesthetic management of ventricular septal defect (VSD) repair in a child with mitochondrial cytopathy

PURPOSE: To present the anesthetic management for the correction of a ventricular septal defect (VSD) in a patient with multiple acyl CoA dehydrogenase deficiency (glutaric aciduria type II; GAII). A review of the literature about anesthetic management of patients with mitochondrial diseases undergoing cardiopulmonary bypass (CPB) is also included. Clinical features: An 11-yr-old girl with GAII manifested as severe hypoglycemia since she was a newborn and generalized muscle weakness. She underwent open-heart surgery for VSD correction with CPB. The anesthetic management avoided inhalational anesthetics, maintained the blood sugar within normal limits and continued normothermia during CPB in order to avoid the stress of hypothermia for her abnormal mitochondria. The patient tolerated the procedure well and experienced a good recovery. CONCLUSION: The anesthetic management of patients with any mitochondrial disease requires normoglycemia, normothermia and the avoidance of metabolic stress in order to preserve energy production by the diseased mitochondria.     

Tissue Doppler assessment of left ventricular diastolic function in rheumatic mitral stenosis

BackgroundLeft ventricular systolic and diastolic functions are reported to be altered in mitral stenosis. Although conventional Doppler ultrasound recording of transmitral flow is used in the assessment of left ventricular diastolic function, yet, in patients with mitral stenosis, it is altered by mitral stenosis itself and thus precludes the proper assessment of LV diastolic function.Aim of the workThe aim of this work is to assess LV diastolic function using pulsed tissue Doppler interrogation of mitral annulus motion in patients with rheumatic mitral stenosis.Patients and methodsTwelve patients with established diagnosis of rheumatic mitral stenosis in normal sinus rhythm were obtained from outpatient clinic of Cardiology Department in Mansura specialized hospital. Thirteen age and sex matched controls with completely normal echo-Doppler study were taken for comparison. All patients were subjected to thorough history taking including dyspnea grading according to NYHA score, clinical examination, 12 lead surface electrocardiogram and most importantly echo-Doppler study.ResultsWe found statistically significant higher peak mitral annular E_a velocity from septal, anterior, inferior and lateral portions of the mitral annulus in controls compared with mitral stenosis patients as well as their averaged values. There is no statistically significant difference regarding peak mitral annular A_a velocity from septal, anterior, inferior and lateral portions of the mitral annulus between both groups as well as their averaged values. The ratio of early to late mitral annular velocities from all recorded sites was statistically significantly higher in the controls compared with mitral stenosis patients.ConclusionsTDI of mitral annulus may provide potential diagnostic role for assessment of LV diastolic function in patients with mitral stenosis.     

Congestive heart failure as a rare cause of unilateral breast edema: A case report & review of the literature

Reported cases encountered difficulty in differentiating between inflammatory carcinoma and breast edema caused by congestive heart failure especially if the breast edema is unilateral. Our presented case is an elderly woman with unilateral breast edema due to congestive heart failure that was initially suspected to have breast cancer based on clinical findings. However imaging studies showed breast edema pattern with no definite underlying mass. This edema was resolved with standard treatment of heart failure. Congestive heart failure may be a possible cause of unilateral breast edema especially in a patient with background of congestive heart failure.     

Geospatial blockchain: promises,challenges, and scenarios in health and healthcare

A PubMed query run in June 2018 using the keyword ‘blockchain’ retrieved 40 indexed papers, a reflection of the growing interest in blockchain among the medical and healthcare research and practice communities. Blockchain’s foundations of decentralisation, cryptographic security and immutability make it a strong contender in reshaping the healthcare landscape worldwide. Blockchain solutions are currently being explored for: (1) securing patient and provider identities; (2) managing pharmaceutical and medical device supply chains; (3) clinical research and data monetisation; (4) medical fraud detection; (5) public health surveillance; (6) enabling truly public and open geo-tagged data; (7) powering many Internet of Things-connected autonomous devices, wearables, drones and vehicles, via the distributed peer-to-peer apps they run, to deliver the full vision of smart healthy cities and regions; and (8) blockchain-enabled augmented reality in crisis mapping and recovery scenarios, including mechanisms for validating, crediting and rewarding crowdsourced geo-tagged data, among other emerging use cases. Geospatially-enabled blockchain solutions exist today that use a crypto-spatial coordinate system to add an immutable spatial context that regular blockchains lack. These geospatial blockchains do not just record an entry’s specific time, but also require and validate its associated proof of location, allowing accurate spatiotemporal mapping of physical world events. Blockchain and distributed ledger technology face similar challenges as any other technology threatening to disintermediate legacy processes and commercial interests, namely the challenges of blockchain interoperability, security and privacy, as well as the need to find suitable and sustainable business models of implementation. Nevertheless, we expect blockchain technologies to get increasingly powerful and robust, as they become coupled with artificial intelligence (AI) in various real-word healthcare solutions involving AI-mediated data exchange on blockchains.     

Relationship between HLA-DRB1*0101, DRB1*0301 alleles and interleukin-12 in haemophilic patients and hepatitis C virus positive hepatocellular carcinoma patients

The immune system can effectively eliminate hepatitis C virus (HCV) in 15 % of acute hepatitis cases. It is assumed that certain HLA-DR alleles present HCV epitopes more effectively to CD4 helper T cells than do others resulting in vigorous proliferative response to these epitopes and probably HCV recovery. So, we aimed at investigating the frequency of HLA-DRB1*0101 and DRB1*0301 alleles in child and adult haemophilics and in HCV positive hepatocellular carcinoma (HCC) patients in a trial to predict patients who require early therapeutic intervention. We also evaluated interleukin (IL)-12 levels in these patients since IL-12 induces interferon (IFN)-gamma production. This study was conducted on 50 antiHIV negative male patients subdivided into: 25 HCV negative haemophilics (group I), 10 HCV positive haemophilics (group II) and 15 HCV positive HCC (group III). Fifteen healthy persons of matched age and free of HCV and HIV infections were chosen as controls (group IV). All patients and controls were subjected to thorough history taking and clinical examination, routine and diagnostic investigations, viral markers, DRB1*0101 and DRB1*0301 amplification by polymerase chain reaction and plasma IL-12 quantitation by enzyme linked immunosorbent assay (ELISA). The frequencies of DRB1*0101 and DRB1*0301 were 20% and 30% respectively in HCV positive haemophilics and 13.3% and 40%, respectively in HCC. IL-12 levels were significantly lower in HCC cases than in HCV positive haemophilics. Among the haemophilics, IL-12 levels were non-significantly higher in children than in adults and were associated with the given number of blood product bags. DRB1*0101 and DRB1*0301 may have a role in HCV clearance and persistence in Egyptian patients with haemophilia and HCC. Low IL-12 levels encountered in HCV positive haemophilics suggest its relation to immunopathogenesis and outcome of HCV infection.     

Serum IL-2 and platelet-associated immunoglobulins are good prognostic markers in immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immunoglobulin, or splenectomy). This work was done to study the immunological difference between acute and chronic ITP, the effect of treatment on the studied immunological parameters, and to evaluate the role of prednisone therapy in chronic ITP. The study included 49 patients, twenty-three children with acute ITP, and twenty-six with chronic ITP. After taking the history, clinical examination was performed for all patients and control subjects. Laboratory investigations included complete blood count, bone marrow aspirate examination (patients), direct and indirect Coombs' test, antinuclear antibodies, lymphocyte phenotyping, cytokine (IL-2, IFN-gamma, and IL-6) measurement, and platelet antibodies by immunofluorescence. Results showed that acute ITP is more prevalent in preschool children and its relapse is lower when steroids are used for treatment. Platelet counts were significantly elevated in both acute and chronic ITP, especially with good response to steroids. Also, CD4 and CD4/CD8 were significantly reduced in chronic ITP with good response to therapy. Both IL-2 and IFN-gamma were significantly increased in chronic ITP when compared to acute ITP or control. Platelet associated IgM was detected more in acute than in chronic ITP, while IgG was equally detectable in both cases. This work shows that IL-2 is a good prognostic factor in chronic ITP and steroids are important for its treatment. It also shows that platelet associated IgG is a good monitoring parameter for response to treatment.     

Comparative Effectiveness of Commercial Bowel Preparations in Ambulatory Patients Presenting for Screening or Surveillance Colonoscopy

Digestive Diseases and Sciences - Inadequate bowel preparation (IBP) is associated with reduced adenoma detection. However, limited research has examined the impact of different commercial bowel...     

Blueprint for schistosomiasis vaccine development

A number of different schistosome antigens are capable of partially protecting experimental animals from challenge infection. More than 100 such antigens have been identified, about 15% of which are strongly protective and deemed promising though they do not reach the level close to sterile immunity seen after vaccination with irradiated cercariae. Studies of human correlate reactions, i.e. serological reactions and cytokine responses to schistosomiasis antigens, in individuals living in areas endemic for schistosomiasis have shown associations between certain antigen-specific immune responses and lack of re-infection over time. This approach was applied in Brazil and Egypt where it was possible to epidemiologically follow cohorts of individuals in endemic areas for extended periods of time correlating infection status with immune responses against a panel of well-researched, highly purified vaccine candidates. The immune correlates found were unique to each antigen and could be either positive or negative, i.e. associated with resistance or with susceptibility to re-infection. However, few antigens were clear-cut in this respect, i.e. the majority of them induced ambiguous responses. For example, a single antigen might have a significant positive correlation when antigen-driven interferon (INF)-gamma production is measured but also show a significant negative correlation with respect to the IgG1 titre induced. These observations suggest that there are desirable, antigen-specific immune responses that would be valuable in a vaccine but they also indicate that there are responses that must be avoided. The insights gained should be useful not only for antigen selection but also for vaccine formulation prior to Phase I/II trials in humans. It would be of great value if similar independent, long-term human correlate studies could also be undertaken in areas endemic for Schistosoma japonicum.     

Endothelin ETA receptor/lipid peroxides/COX-2/TGF-β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Background and Purpose

Cyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling.

Experimental Approach

The effects of a 10 day treatment with CSA (20 mg·kg⁻¹·day⁻¹), indomethacin (5 mg·kg⁻¹·day⁻¹) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ET_A receptor and COX-2 pathways in the interaction were evaluated.

Key Results

Oral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ET_A receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ET_A receptor and COX-2 expressions. Blockade of ET_A receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ET_A receptor and COX-2 protein.

Conclusions and Implications

The exaggerated oxidative insult and associated dysregulation of the ET_A receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ET_A receptor antagonism might be exploited therapeutically.Tables of Links