Sequential Treatment of Guillain-Barré Syndrome with Extracorporeal Elimination and Intravenous Immunoglobulin

Abstract: Plasma exchange and administration of intravenous immunoglobulin (IgG) are established treatments for Guillain-Barré syndrome (GBS). Elimination of postulated pathogenetic factors by plasma exchange or selective adsorption treatment using affinity-type adsorption columns and subsequent immunomodulation by intravenous IgG may provide a more effective treatment. Forty-five patients with acute GBS were prospectively examined using a clinical score. We treated 11 patients by plasma exchange, 13 patients by selective adsorption using a tryptophan-linked polyvinyl alcohol gel adsorbent, and 21 patients by selective adsorption followed by intravenous IgG. The patients treated sequentially by selective adsorption and intravenous IgG improved significantly better than the patients who received plasma treatment only. The results suggest that sequential treatment of GBS may be superior to plasma treatment alone. The higher cost of combined treatment may be offset by lower overall expenditure.     

Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study.

OBJECTIVE: This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics. PATIENTS AND METHODS: The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period. RESULTS: The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate withdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volume (-9 +/- 33 vs. +24 +/- 47 ml; p < 0.01). CONCLUSION: The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.     

<Emphasis Type="Italic">Vegf-A</Emphasis> mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation

Aims/hypothesis

The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment.

Methods

Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice.

Results

At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA-transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean?±?SEM: 0.118?±?0.01 [n?=?3] in Vegf-A mRNA transfected group (VEGF) vs 0.056?±?0.01 [n?=?3] in no RNA [p?<?0.05] vs 0.063?±?0.02 [n?=?4] in Gfp mRNA transfected group (GFP) [p?<?0.05]); EndoC-bH3 grafts (2.85- and 2.48-fold. respectively) (0.085?±?0.02 [n?=?4] in VEGF vs 0.030?±?0.004 [n?=?4] in no RNA [p?<?0.05] vs 0.034?±?0.01 [n?=?5] in GFP [p?<?0.05]); and human islet grafts (3.17- and 3.80-fold, respectively) (0.048?±?0.013 [n?=?3] in VEGF vs 0.015?±?0.0051 [n?=?4] in no RNA [p?<?0.01] vs 0.013?±?0.0046 [n?=?4] in GFP [p?<?0.01]). At day 30 post transplantation, human islet grafts maintained a vascularisation benefit (1.70- and 1.82-fold, respectively) (0.049?±?0.0042 [n?=?8] in VEGF vs 0.029?±?0.0052 [n?=?5] in no RNA [p?<?0.05] vs 0.027?±?0.0056 [n?=?4] in GFP [p?<?0.05]) and a higher beta cell volume (1.64- and 2.26-fold, respectively) (0.0292?±?0.0032 μl [n?=?7] in VEGF vs 0.0178?±?0.0021 μl [n?=?5] in no RNA [p?<?0.01] vs 0.0129?±?0.0012 μl [n?=?4] in GFP [p?<?0.001]).

Conclusions/interpretation

Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants.

     

Development and first data of a customized short tracheal cannula based on digital data

Purpose

At the moment, there is an inadequate margin fit of commercially available stoma buttons. The aim of the present study was to develop a customized short tracheal cannula based on digital data. Furthermore, the applied material has to be evaluated considering germ colonization and appropriate cleaning procedures.

Methods

Computed tomographies of 53 patients who underwent laryngectomy were surveyed. Based on the digital data, a customized short tracheal cannula was created and manufactured from silicone. The new cannula was incorporated in ten patients and worn for 4 weeks. A clinical examination of an otolaryngologist and subjective assessment of the patients were carried out. Furthermore, microbiological test considering germ colonization was performed.

Results

The customized short tracheal cannula could be incorporated in all patients. The clinical results showed no irritation or mucosal lesions. The subjective individual evaluation by the patients was promising. The proposals for improvement could be considered. The microbiological examination revealed a higher contamination of the silicone compared to the silver cannulas. Both chemical and mechanical decontamination showed sufficient results.

Conclusion

A workflow for development and manufacturing of a customized short tracheal cannula from digital data could be established. The cannula is compatible to standard equipment and routine cleaning procedures. Clinical studies are required to evaluate the potential benefit for patients.