Reepithelialization of orthotopic tracheal allografts prevents rejection after withdrawal of immunosuppression

Prior work has demonstrated that immunosuppressed orthotopic tracheal allografts undergo progressive reepithelialization over a 48-day period with recipient-derived tracheal epithelium. We hypothesized that reepithelialization of tracheal allografts would prevent rejection after withdrawal of immunosuppression. BALB/c murine tracheal grafts were transplanted orthotopically into either syngeneic or allogeneic C57/BL6 recipients. The recipients were either not immunosuppressed, immunosuppressed with cyclosporine A (10 mg/kg per day) continuously, or immunosuppressed for 48 days and then withdrawn from immunosuppression. The grafts were assessed for acute and chronic rejection 10 days and 50 days after immunosuppression withdrawal. The immunosuppressed allograft recipients maintained a ciliated epithelium acutely and chronically after immunosuppression withdrawal. Ten days after immunosuppression withdrawal, there was a mild cellular infiltrate, which resolved 50 days after withdrawal. Electron microscopy, lymphocyte subpopulation assays, and lamina propria analysis demonstrated that immunosuppression withdrawal did not result in tracheal allograft rejection. In vitro and in vivo assessments did not demonstrate evidence of systemic or local immune tolerance. We conclude that reepithelialization of orthotopic tracheal allografts with recipient-derived mucosa prevents rejection of allograft segments. Tracheal transplantation may require only transient immunosuppression, which can be withdrawn after tracheal reepithelialization.     

Potentialities of cytoprotection in the treatment of chronic heart failure in patients with coronary heart disease

The study was undertaken to evaluate the effects of long-term (6-month) therapy with the selective beta-blocker bisoprolol, the cytoprotector trimetazidine and their combination on the clinical course of disease, the morphofunctional parameters of the left ventricle (LV) and life quality in 71 patients with coronary heart disease (CHD) concurrent with functional classes (FC) III-IV chronic heart failure (CHF) (ejection fraction (EF) < 35%, as evidenced by echoCG). In Groups 1, 2, and 3, basic therapy was supplemented by bisoprolol, trimetazidine, and bisoprolol plus trimetazidine, respectively. The initial dose of bisoprolol was 1.25 mg with its subsequent titration to an individually tolerable. Trimetazidine was given in a dose of 20 mg thrice daily. The patients' clinical status and echoCG were monthly assessed. There was a decrease in FC of CHD in all the groups, a reduction in LV end diastolic and systolic volumes, and an increase in shortening faction, LV EF, and an improvement of LV diastolic function. There was evidence that it should be expedient and safe to use the cytoprotector trimetazidine in the treatment of CHF in patients with CHD. In patients with CHD concurrent with CHF, therapy using a combination of bisoprolol and trimerazidine was found to have the most pronounced impact, which yielded the maximum clinical and hemodynamic effect (LV EF increased by 42.6% of the baseline values, the rate of early and late ventricular diastolic filling decreased by 59% of the baseline values). The revealed regularities of the positive effect on the clinical and hemodynamic parameters of long-use of bisoprolol, trimetazidine, and their combination in patients with CHD concurrent with FC III-IV CHF show it expedient to include these drugs and their combination into therapy for CHF that develops in the presence of CHD.     

The beneficial antispasticity effect of botulinum toxin type A is maintained after repeated treatment cycles

OBJECTIVE: To study the efficacy, safety, and incidence of BtxA antibody formation with repeated treatments with BtxA in post-stroke upper limb muscle spasticity. METHODS: The study was a prospective open label trial. Patients with established post-stroke upper limb spasticity received 1000 units of BtxA (Dysport) into five muscles of the affected arm on study entry. Treatment was repeated every 12, 16, or 20 weeks as clinically indicated. Each patient received a total of three treatment cycles. Efficacy of treatment was assessed using the Modified Ashworth Scale. Patients were assessed on study entry and on week 4 and 12 of each treatment cycle for all safety and efficacy parameters. Blood samples for BtxA antibody assay were taken at baseline and on completion of the trial. RESULTS: Fifty one patients were recruited and 41 of them completed the study. Improvement from the cycle one baseline was observed in all the outcome measures. Mild to moderately severe treatment related adverse events were reported in 24% of cases. There were no serious adverse events. No BtxA antibodies were detected. CONCLUSION: BtxA at a dose of 1000 units Dysport was efficacious in the symptomatic treatment of post-stroke upper limb spasticity. The study suggests that this effect can be maintained with repeated injections for up to at least three treatment cycles, with duration of effect per cycle of between 12 and 20 weeks. BtxA was safe in the dose used in this study and did not induce the formation of detectable levels of neutralising BtxA antibodies.     

Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis

AIM: To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. MATERIAL AND METHODS: The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). RESULTS: In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. CONCLUSION: Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.     

Experience in the use of polyosm in the treatment of edematous maculopathy

The efficiency and tolerability of using a new osmotic diuretic, i.e. polyosm (a solution of polyethylene oxide 400 for the intravenous administration), was studied in patients with edematous maculopathy of different geneses. The drop-by-drop introduction of polyosm, 200 ml (the dose amounted to 0.8-1 g/kg in terms of polyethylene oxide 400), one per day and during 3 days, proved the efficiency of the preparation as a corrector of edematous maculopathy, which was confirmed by an involution of the eye-tissue edema, reduced sizes of the central scotoma, and by an improved visual acuity. The tolerability of the course-based administration of polyosm by patients was found to be good and satisfactory. No negative impact produced by the preparation on the indices of central hemodynamics was detected; the hypotensive effect of polyosm was found, as a normalized level of the systolic and diastolic pressure, only in patients with an originally high arterial pressure. Hypokalemia was, after the course-based use of polyosm, of a moderate nature.