Haemopoietic Stem Cell Transplantation In The Treatment Of Severe AutoImmune Diseases 2000
Tyndall A, Passweg J, Gratwohl A
Ann Rheum Dis 2001 Jul;60(7):702-7
Univ Hospital, Dept of Rheumatology, Basel, Switzerland
PMID# 11406528; UI# 21298879
An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries.
With the aim of assessing the existing data on autologous Haemopoietic Stem Cell Transplantation (HSCT) in the treatment of severe AutoImmune Disease, and to decide on future trial planning.
Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others.
The major disease categories and number of patients receiving transplant were: Multiple Sclerosis (MS) 127, Systemic Sclerosis (SSc) 72, Rheumatoid Arthritis (RA) 70, Juvenile Idiopathic Arthritis (JIA) 36, Systemic Lupus Erythematosus (SLE) 34, Dermatomyositis/Polymyositis (DM/PM) 5, Idiopathic Thrombocytopenic Purpura (ITP) 7.
Single or several cases of other AutoImmune Diseases were reported.
Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA.
Treatment was associated with a significant morbidity and mortality.
In the EULAR/EBMT database (71 centers in 22 countries), a mobilization associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases.
The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA.
After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomized phase III trials are now appropriate in SSc, MS, and RA.
A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and Vasculitis.
The need for continuing collection of all cases after mobilization by the standardized EBMT and IBMTR data forms was emphasised.
During T, Gerst F, Hansel W, Wulff H, Koppenhofer E
Gen Physiol Biophys 2000 Dec;19(4):345-64
Univ of Kiel, Institute of Physiology, Kiel, Germany
PMID# 11409838; UI# 21302502
The effects of the PhotoToxic K+- channel blockers 8-MethoxyPsoralen (8-MOP) and 5-MethoxyPsoralen (5-MOP) on Ranvier Nodes were compared to those of 5,8-DiEthoxyPsoralen (5,8-EOP) by means of the Hodgkin-Huxley formalism.
When these test substances were added individually to the bathing solution (8-MOP: 100 micromol/l; 5-MOP: 50 micromol/l; 5,8-EOP: 10 micromol/l) the following completely reversible effects were observed:
- 8-MOP, caused a nearly potential-independent decrease of the Sodium permeability, P'Na, by ca. 17%. 5-MOP and 5,8-EOP merely decreased the maximal value of P'Na, by ca. 12 and 8% respectively, whereas with weak depolarizations P'Na was unchanged.
- In the tested potential range the Potassium permeability, P'K, was caused to decrease by ca. 9% by 8-MOP, ca. 21% by 5-MOP and ca. 19% by 5,8-EOP. 3.
The Potassium currents acquired a phasic time course previously described for 8-MOP and 5-MOP.
They reached a relative maximum and approached a lower steady-state value, kinfinity, with a time constant tauk at V = 120 mV of about 16 ms (8-MOP), 20 ms (5-MOP) and 94 ms (5,8-EOP).
To obtain dose-response relations the drug-induced effects on peak P'K and on the steady state value, kinfinity, were measured.
The corresponding apparent dissociation constants (in micromol/l) were 66.6 and 80.1 (for 8-MOP), 87.6 and 25.8 (for 5-MOP), and 13.5 and 6.5 (for 5,8-EOP).
In view of the similarity of the actions of 5-MOP and 5,8-EOP as well as the fact that 5,8-EOP is not PhotoToxic.
In future 5,8-EOP may well prove to be a particularly suitable K+-channel blocker for the symptomatic therapy of Multiple Sclerosis and other DeMyelinating Diseases.
Elderly Multiple Sclerosis Patients Reported Problems
Klewer J, Pohlau D, Nippert I, Haas J, Kugler J
J NeuroSci Nurs 2001 Jun;33(3):167-71
Univ of Dresden, Dresden Medical School, Institute of Medical Informatics, Biometry, and Public Health, IMIB-Fetscherstrasse 74, 01307 Dresden, Germany
PMID# 11413662; UI# 21307347
Multiple Sclerosis (MS) is one of the most common organic Neurological Diseases of the Central Nervous System.
Because of improved therapies, nurses are confronted with elderly MS patients, but little is known about the specific problems of these patients.
This survey analyzed problems in elderly MS patients. Fifty-three MS patients (44 female, 9 male; average age 73 years, average course of MS 25.3 years).
From the Berlin Section of the German Multiple Sclerosis Association were evaluated by using a standardized questionnaire.
Considering social situation, daily problems, disease course, and disabilities, and by using the Expanded Disability Status Scale (EDSS).
Elderly MS patients reported impaired mobility and inability to use public transportation; about 96% presented EDSS scores above 6.0.
Nearly 50% complained about Spasticity and Pain due to Spasticity. More than 70% suffered from Bladder Dysfunction.
Problems with Sleep and Fatigue were present in less than 20%, but Interrupted Sleep was common.
Selfcare impairments were reported by 50%-75% of the patients, and most of them required professional help.
Depressive moods and thoughts about committing suicide were mentioned by more than 30% of the patients. Elderly MS patients experience physical and PsychoSocial impairments.
Healthcare professionals should consider increasing independence and avoiding nursing home admissions in the management of elderly MS patients.
Beer M, Sandstede J, Weilbach F, Spindler M, Buchner S, Krug A, Kostler H, Pabst T, Kenn W, Landschutz W, von Kienlin M, Toyka KV, Ertl G, Gold R, Hahn D
Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2001 May;173(5):399-404
Universitat Wurzburg, Institut fur Rontgendiagnostik, Wurzburg, Germany
PMID# 11414146; UI# 21307840
Involvement of the Autonomic System in Multiple Sclerosis (MS) may concur with dysfunction of the CardioVascular System.
The introduction of potentially CardioToxic ImmunoSuppressive drugs like Mitoxantrone into the treatment of MS warrants proper assessment of pre-existing Heart Disease.
However, systematic analyzes of functional and metabolic derangements in MS are missing.
Using quantitative 31P-MR-Spectroscopy (MRS) and MR-imaging (MRI) metabolic and functional parameters were analyzed in patients with MS in comparison to healthy volunteers.
14/15 patients with MS could be included in the study, as the MRS examination of one patient had to be excluded from analysis due to movement during the examination.
Using Chemical Shift Imaging (CSI) and AMARES, PhosphoCreatine (PCr) to Adenosine TriPhosphate (ATP) ratios, characterizing MyoCardial high-energy Phosphate metabolism, were determined.
Additionally, absolute concentrations of PCr and ATP were calculated by SLOOP (Spatial Localization with Optimal Pointspread Function).
Analysis of functional changes was performed by Cine-MRI. 14 healthy volunteers matched for age and gender served as control.
A significant decrease of absolute PCr concentration was observed in patients with MS compared to matched volunteers (p < 0.05), whereas ATP concentrations showed no significant changes (p = 0.27).
Metabolite ratios calculated by SLOOP or AMARES showed a tendency to be reduced in patients, however, did not reach significance (p = 0.08, SLOOP; p = 0.47, AMARES).
Using volunteers' mean values +/- 2 x SD as cut off value revealed PCr changes in 5 of 14 patients, whereas only 2 also had pathologic PCr/ATP ratios.
Functional analysis by MRI depicted depressed Left Ventricular ejection fraction in 4 patients.
The reduction in Cardiac high-energy Phosphates in some patients with MS points to a subclinical involvement of the Heart.
This may be important for treatment with potentially CardioToxic drugs. Longitudinal studies are need to understand the clinical relevance of our findings.