Combined short-term immunotherapy for experimental autoimmune myasthenia gravis

A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. "Memory" lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the "memory" cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar "curative" strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.     

Multiple mononeuropathy as the initial presentation of systemic lupus erythematosus — nerve biopsy and response to plasma exchange

Summary A total of 15 patients affected by idiopathic dystonia (7 with generalized and 8 with focal or segmental dystonia) were subjected to therapy with bromocriptine at low doses, pimozide and trihexyphenidyl. The symptoms were evaluated by giving a progressive score in relation to the intensity of the dystonic symptom to each of the body segments involved by the dystonia. Bromocriptine did not significantly modify the dystonia. Pimozide showed a slight nonsignificant improvement of the dystonic symptoms. Trihexyphenidyl was effective in the generalized dystonias, in agreement with previous reports in the literature. The variation in the pharmacological results could be due to the diversity of the dystonic syndromes, which comprise cases that are different in age at onset, site of dystonic symptoms, and evolution.

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Zusammenfassung Fünfzehn von idiopathischer — und zwar 7 von generalisierter und 8 von fokaler und segmentarischer — Dystonie befallenen Patienten unterzogen sich verschiedenen pharmakologischen Behandlungen mit kleinen Mengen Bromocriptine, Pymozide und Triesifenidile. Die Symptome wurden durch eine fortlaufende Punktzahl bezeichnet, so daß deren Schätzung von der Intensität des Symptoms Dystonie in jedem einzelnen befallenen Körperteil abhing. Die Dystonien wurden durch Bromocriptine nicht bedeutend geändert.Pymozide führte zu einer geringeren, doch unbedeutenden, Besserung der dystonischen Symptome.Triesifenidile wirkte auf die generalisierten Dystonien, in Übereinstimmung mit einigen Literaturangaben.Die Veränderlichkeit der pharmakologischen Ergebnisse wurde auf die Verschiedenheit der dystonischen Syndrome zurückgeführt, unter denen man Fälle versammelt, die sich durch Anfangsalter, Sitz der dystonischen Symptome und Entwicklungsart voneinander unterscheiden.

     

Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation

In tissue engineering and regenerative medicine, studies that utilize 3D scaffolds for generating voluminous tissues are mostly confined in the realm of in vitro research and preclinical animal model testing. Bioreactors offer an excellent platform to grow and develop 3D tissues by providing conditions that mimic their native microenvironment. Aligning the bioreactor development process with a focus on patient care will aid in the faster translation of the bioreactor technology to clinics. In this review, we discuss the various factors involved in the design of clinically relevant bioreactors in relation to their respective applications. We explore the functional relevance of tissue grafts generated by bioreactors that have been designed to provide physiologically relevant mechanical cues on the growing tissue. The review discusses the recent trends in non‐invasive sensing of the bioreactor culture conditions. It provides an insight to the current technological advancements that enable in situ, non‐invasive, qualitative and quantitative evaluation of the tissue grafts grown in a bioreactor system. We summarize the emerging trends in commercial bioreactor design followed by a short discussion on the aspects that hamper the ‘push’ of bioreactor systems into the commercial market as well as ‘pull’ factors for stakeholders to embrace and adopt widespread utility of bioreactors in the clinical setting. Copyright © 2017 John Wiley & Sons, Ltd.     

Case report and a review of the literature of two patients with gastric MALToma and pulmonary metastasis

Gastric mucosa‐associated lymphoid tissue lymphoma (or MALToma) is a relatively rare form of low‐grade B‐cell malignancy arising from the mucosal associated lymphoid tissue of the stomach. The majority of cases can be treated with Helicobacter pylori eradication with good prognosis. However, few reports have been published on the treatment of gastric MALToma with pulmonary metastasis. We report two such cases managed with systemic chemotherapy. At the time of writing, one of the cases was in static disease while the other had complete remission. In both patients, pulmonary metastases were detected upon staging thoracic computed tomography.     

Perceval Sutureless Valve – are Sutureless Valves Here?

With the advent of transcatheter aortic valve implantation (TAVI) techniques, a renewed interest has developed in sutureless aortic valve concepts in the last decade. The main feature of sutureless aortic valve implantation is the speed of insertion, thus making implantation easier for the surgeon. As a result, cross clamp times and myocardial ischemia may be reduced. The combined procedures (CABG with AVR in particular) can be done with a short cross clamp time. Perceval valve also provides an increased effective orifice area as compared with a stented bioprosthesis. Sutureless implantation of the Perceval valve is not only associated with shorter cross-clamp and cardiopulmonary bypass times but improved clinical outcomes too. This review covers the sutureless aortic valves and their evolution, with elaborate details on Perceval S valve in particular (which is the most widely used sutureless valve around the globe).     

Telemedicine to deliver diabetes care in low- and middle-income countries: a systematic review and meta-analysis

ObjectiveTo determine the effectiveness of telemedicine in the delivery of diabetes care in low- and middle-income countries.MethodsWe searched seven databases up to July 2020 for randomized controlled trials investigating the effectiveness of telemedicine in the delivery of diabetes care in low- and middle-income countries. We extracted data on the study characteristics, primary end-points and effect sizes of outcomes. Using random effects analyses, we ran a series of meta-analyses for both biochemical outcomes and related patient properties.FindingsWe included 31 interventions in our meta-analysis. We observed significant standardized mean differences of −0.38 for glycated haemoglobin (95% confidence interval, CI: −0.52 to −0.23; I² = 86.70%), −0.20 for fasting blood sugar (95% CI: −0.32 to −0.08; I² = 64.28%), 0.81 for adherence to treatment (95% CI: 0.19 to 1.42; I² = 93.75%), 0.55 for diabetes knowledge (95% CI: −0.10 to 1.20; I² = 92.65%) and 1.68 for self-efficacy (95% CI: 1.06 to 2.30; I² = 97.15%). We observed no significant treatment effects for other outcomes, with standardized mean differences of −0.04 for body mass index (95% CI: −0.13 to 0.05; I² = 35.94%), −0.06 for total cholesterol (95% CI: −0.16 to 0.04; I² = 59.93%) and −0.02 for triglycerides (95% CI: −0.12 to 0.09; I² = 0%). Interventions via telephone and short message service yielded the highest treatment effects compared with services based on telemetry and smartphone applications.ConclusionAlthough we determined that telemedicine is effective in improving several diabetes-related outcomes, the certainty of evidence was very low due to substantial heterogeneity and risk of bias.