Symptomatic therapies for multiple sclerosis

In spite of the proven efficacy of the newer immunomodulative pharmacologic treatments for multiple sclerosis, such as steroid pulse therapy for exacerbation and beta-interferon subcutaneous injections for prevention, those treatments have not yet satisfied the criteria for direct management of the disease. Thus, even now, patients with multiple sclerosis still need symptomatic therapy to improve their quality of life and ameliorate the impairments in their activities of daily living due to their various neurologic deficits. This article reviews the management of a wide range of neurologic symptoms of multiple sclerosis, including spasticity, bladder dysfunction, paroxysmal symptoms, and chronic pain.     

Varieties of right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy

We examined whether differences in the location of myocardial hypertrophy influence the right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy using cineangiography. Biplane right ventriculography was performed in 34 subjects (normal = 14, asymmetric septal hypertrophy = 9, apical hypertrophy = 11) during cardiac catheterization. In patients with asymmetric septal hypertrophy, compared with apical hypertrophy and normal groups, the indices of the right ventricular diastolic function including right ventricular peak filling rate and filling fraction of rapid filling phase were lower and the time to peak filling rate was prolonged. But in patients with apical hypertrophy, these indices were not significantly different compared with normal. There were no differences in right ventricular ejection fraction and cardiac index among the three groups. These data suggest that the location of the myocardial hypertrophy of the left ventricle is a significant factor affecting the right ventricular diastolic filling in non-obstructive hypertrophic cardiomyopathy.     

Evidence for nonclonal hematopoietic progenitor cell populations in bone marrow of patients with myelodysplastic syndromes

Clonality of marrow hematopoietic progenitor cells in myelodysplastic syndromes (MDS) was analyzed by X-chromosome inactivation pattern using polymerase chain reaction (PCR). Five female patients were included in this study; two with refractory anemia (RA) and three with RA with excess blasts (RAEB). They were heterozygous for BstXI restriction fragment length polymorphisms (RFLP) of the X-chromosome-linked phosphoglycerate kinase (PGK) gene. In each patient, erythroid and nonerythroid colonies, grown in the presence of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibited no remarkable difference in clonal constitution. Two patients showed only one methylation pattern, suggesting the monoclonal origin of hematopoietic progenitor cells. Colonies of two other patients exhibited predominant and minor methylation patterns in PGK gene, indicating that nonclonal progenitor cells remain a minor population. The bone marrow of one patient appeared to contain a greater proportion of nonclonal progenitors. Stem cell factor (SCF), a potent colony- stimulating factor, enhanced both erythroid and nonerythroid colony formation. However, it did not notably alter the clonal constitutions. We conclude that nonclonal hematopoietic progenitor cells can persist in a substantial number of MDS patients.     

Three-dimensional analysis of computed tomography-based navigation system for total knee arthroplasty: the accuracy of computed tomography-based navigation system

We evaluated the postoperative alignment of 37 primary total knee arthroplasties performed using a computed tomography–based navigation system (Vector Vision Knee 1.5; Brain Lab, Germany) with a new 3-dimensional analysis. The mean coronal femoral angle was 89.0° ± 1.4° (85.5°-92.8°), and the coronal tibial component was 89.2° ± 1.0° (87.4°-91.6°). The hip-knee-ankle angle was observed to be 178.2° ± 1.5° (173.9°-181.8°). The external rotational alignment of the femoral component relative to the surgical epicondylar axis was −0.5° ± 1.7° (−3.2° to 3.4°). The results demonstrated that a computed tomography–based navigation system provided a reasonably satisfactory component alignment. The discrepancy between the 2-dimensional and 3-dimensional evaluations was 1.0° ± 0.9° (0.1°-3.4°). Three-dimensional analysis is necessary to evaluate the accuracy of the navigation system.     

Combination therapy with telmisartan and spironolactone alleviates L-NAME exacerbated nephrosclerosis with an increase in PPAR-gamma and decrease in TGF-beta(1)

To investigate whether the receptor blockades of angiotensin II type 1 and aldosterone receptors can prevent renal tissue injury in relation to the renal tissue mRNA levels of peroxisome proliferation-activated receptors-gamma (PPAR-gamma) and transforming growth factor-beta (1) (TGF-beta(1)) in spontaneously hypertensive rats (SHR) given N(G)-nitro-L-arginine methyl ester (L-NAME), which is considered a model of malignant hypertension. This study was performed in 5 groups of 17-week-old male SHR treated for 3 weeks as follows: group 1, control; group 2, L-NAME (50 mg/L in drinking); group 3, L-NAME plus aldosterone antagonist, spironolactone (SPRL, 100 mg/kg/day); group 4, L-NAME plus angiotensin II type 1 receptor blocker, telmisartan (TELM, 3 mg/kg/day); group 5, L-NAME plus combination therapy (COMB) with low-dose TELM (1 mg/kg/day) and SPRL (100 mg/kg/day). Urinary protein excretion and the glomerular injury score were significantly reduced in the SPRL, TELM, and COMB groups as compared with the L-NAME group, while significant blood pressure reduction was observed only in the TELM group. In the TELM and COMB groups, the perivascular cell infiltration and fibrosis area were significantly reduced together with the PPAR-gamma mRNA increase and TGF- beta(1) mRNA decrease. The urinary excretion of nitric oxides was significantly recovered and the wall to lumen ratio of the interlobular artery was significantly reduced only in the COMB group compared with the L-NAME group. Combined administration of 1 mg/kg/day telmisartan and 100 mg/kg/day spironolactone is thought to be effective in alleviating hypertensive renal injuries independently of blood pressure changes. The anti-inflammatory and antifibrotic effects due to PPAR-gamma activation and TGF-beta(1) inhibition may participate in the renoprotection of this combination therapy.