Properties and outcomes of spinal rehabilitation units in four countries.

OBJECTIVE: Compare rehabilitation after spinal cord lesions (SCL) in different countries. DESIGN: Multicenter comparative study. SETTING: Four spinal rehabilitation units, in Denmark, Russia, Lithuania and Israel. SUBJECTS: 199 SCL patients. INTERVENTIONS: Information was collected about unit properties, rehabilitation objectives, American Spinal Injury Association (ASIA) scale and spinal cord independence measure (SCIM) assessments, and patient data. chi (2)-test, t-test, ANOVA and ANCOVA were used for statistical analysis. MAIN OUTCOME MEASURES: Time from lesion onset to admission for rehabilitation (TAR), length of stay in rehabilitation (LOS), SCIM and spinal cord ability realization measurement index (SCI-ARMI) scores, SCIM gain, SCI-ARMI gain and rehabilitation efficiency (RE). RESULTS: Differences were found between the units in rehabilitation objectives, facilities and special equipment for rehabilitation. Staff/bed ratio was 1.7 in Lithuania and Denmark, 1.1 in Israel and 0.9 in Russia. Russian patients were the youngest and had the most severe lesions among participating units. Admission SCIM and SCI-ARMI were the lowest in Israel: 25.1+/-17.2 and 34.3+/-17.3. TAR was highest in Russia (12.4 month) and lowest in Israel (2 weeks; P<0.01). LOS was longest in Denmark (176.9 days; P<0.001). SCIM score at the end of rehabilitation was highest in Denmark (67.3+/-23). SCIM gain and SCI ARMI gain were highest in Israel (36.9+/-18.3 and 38.5+/-19.4, respectively) and lowest in Russia (P<0.001). RE was highest in Lithuania and lowest in Denmark (P<0.001). CONCLUSIONS: In the participating units, SCL rehabilitation outcomes depend on SCL severity and unit-specific properties. A moderately delayed rehabilitation with long LOS achieved high functioning, and early or slightly delayed rehabilitation combined with shorter LOS achieved high functional gain or efficiency.

Characterization of mutations causing factor VII deficiency in 61 unrelated Israeli patients.

Inherited factor (F)VII deficiency is rare in most populations but relatively common in Israel. The aim of this study was to characterize the molecular and functional defect in unrelated Israeli patients with FVII deficiency. Mutations were identified by direct sequencing of PCR-amplified genomic DNA fragments. Selected mutations were expressed in baby hamster kidney (BHK) cells and tested for binding to tissue factor (TF), activation by FXa and activation of FX. In 61 patients with FVII deficiency, the causative mutation in the FVII gene was discerned. The predominant mutation found in this and a previously reported cohort of 27 unrelated patients in Israel was Ala244Val substitution; of 121 independent mutant alleles defined in all 88 patients ascertained in Israel, 102 (84%) bore this alteration. Eleven additional mutations were identified of which one, Cys22Arg, is novel. Expression of the mutations in BHK cells revealed that four (Ala244Val, 11128delC, Leu300Pro and Cys22Arg) were cross-reacting material (CRM)- negative, and three (Ala294Val, Cys310Phe and Phe24del) were CRM-positive. As predicted by modeling, we observed no binding to TF of FVII Phe24del, diminished binding of FVII Cys310Phe and normal binding of FVII Ala294Val. The main defect of FVII Ala294Val was its inability to activate FX in the presence of TF. Coexpression of Ala294Val and Arg353Gln, a polymorphism known to affect FVII secretion, did not reveal an additive effect on FVII secretion, while coexpression of Ala244Val and Arg353Gln did yield an additive effect.

Molecular characterization of four novel mutations causing factor VII deficiency.

INTRODUCTION: Hereditary deficiency of factor VII (FVII) is a rare coagulation defect. We previously studied the molecular basis of the FVII deficiency in Israeli patients and found that the majority of them bore the Ala244Val mutation. In the present study we further analysed FVII deficient patients. PATIENTS AND METHODS: Three patients with severe FVII deficiency (FVII activity < or =1%) and one with partial deficiency (25%) were studied. In all four patients, the FVII gene was amplified and sequenced. RESULTS: Four novel mutations have been identified: IVS 2+1G-->C Phe 24 deletion, Leu300Pro and Arg277His. Homozygosity for the IVS2+1G-->C mutation was lethal, whereas homozygosity for the Phe 24 deletion was accompanied by a severe bleeding tendency. FVII modeling showed that Phe 24 is located in the Gla domain. Both Arg 277 and Leu 300 are within the catalytic domain, although Arg 277 is also involved in tissue factor binding. CONCLUSION: We have analysed four mutations, two of which (IVS2+1G-->C, Phe 24 deletion) were associated with severe bleeding tendency in the homozygous state, facilitating prenatal diagnosis. Hypothetically, using FVII modeling, Arg 277 replacement by histidine may weaken the tissue factor, while deletion of Phe 24 and Leu300Pro mutation might be associated with abnormal folding of the Gla and catalytic domains, respectively.