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N Hasson

Publications and source records attributed to N Hasson.

9 recordsLinked to original sources
PubMed2004

Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine.

BACKGROUND: We have previously demonstrated that the copper chelator tetraethylenepentamine (TEPA) enables preferential expansion of early hematopoietic progenitor cells (CD34+CD38-, CD34+CD38-Lin-) in human umbilical cord blood (CB)-derived CD34+ cell cultures. This study extends our previous findings that copper chelation can modulate the balance between self-renewal and differentiation of hematopoietic progenitor cells. METHODS: In the present study we established a clinically applicative protocol for large-scale ex vivo expansion of CB-derived progenitors. Briefly, CD133+ cells, purified from CB using Miltenyi Biotec's (Bergisch Gladbach, Germany) CliniMACS separation device and the anti-CD133 reagent, were cultured for 3 weeks in a clinical-grade closed culture bag system, using the chelator-based technology in combination with early-acting cytokines (SCF, thrombopoietin, IL-6 and FLT-3 ligand). This protocol was evaluated using frozen units derived from accredited cord blood banks. RESULTS: Following 3 weeks of expansion under large-scale culture conditions that were suitable for clinical manufacturing, the median output value of CD34+ cells increase by 89-fold, CD34+CD38- increase by 30-fold and CFU cells (CFUc) by 172-fold over the input value. Transplantation into sublethally irradiated non-obese diabetic (NOD/SCID) mice indicated that the engraftment potential of the ex vivo expanded CD133+ cells was significantly superior to that of unexpanded cells: 60+/-5.5% vs. 21+/-3.5% CD45+ cells, P=0.001, and 11+/-1.8% vs. 4+/-0.68% CD45+CD34+ cells, P=0.012, n=32, respectively. DISCUSSION: Based on these large-scale experiments, the chelator-based ex vivo expansion technology is currently being tested in a phase 1 clinical trial in patients undergoing CB transplantation for hematological malignancies.

AC133 Antigen↗
PubMed2000

Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) can persist through adolescence and adulthood, resulting in significant disability. The use of low-dose oral methotrexate (MTX) for persistent polyarthritis has been shown to be effective by the USA/USSR collaborative study group. However, 2 of the most disabling subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in that study. The present study was therefore conducted to investigate the efficacy of MTX in these 2 subgroups. METHODS: Patients under the age of 16 years who fulfilled the International League of Associations for Rheumatology criteria for systemic or extended oligoarticular arthritis were eligible for this multicenter, double-blind, placebo-controlled crossover trial. Forty-five patients with systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2 months. Core outcome variables were considered as primary measures, giving a final score of "improved" or "not improved." Secondary measures included scores of systemic features and biochemical laboratory measures. Assessment of function was not included since there were no validated functional measures at the start of this trial in 1991. RESULTS: In the extended oligoarticular arthritis group, MTX treatment produced significant improvement in 3 of 5 core variables (erythrocyte sedimentation rate, physician's global assessment of disease activity, and parent's global assessment of disease activity). By the primary improvement criteria, there was significant overall improvement during MTX treatment. In the systemic arthritis group, only 2 of 5 core variables were significantly improved (physician's and parent's global assessment of disease activity). Systemic features were not part of the core variables, but the systemic feature score was not significantly different between MTX and placebo treatment. There was no significant overall improvement in this group during MTX treatment. However, no significant interaction between disease subgroup and treatment effect was demonstrated. When the data from both disease subgroups were combined, there was significant clinical improvement during MTX treatment (P = 0.006). CONCLUSION: MTX 15-20 mg/m2 given orally once a week was found to be an effective treatment for both extended oligoarticular and systemic JIA in this shortterm trial. Long-term efficacy needs to be addressed in future studies.

Adolescent↗
PubMed1996

Childhood-onset scleroderma: is it different from adult-onset disease.

OBJECTIVE: To distinguish childhood-onset scleroderma from adult-onset disease. METHODS: The clinical and serologic features of 58 patients with childhood-onset scleroderma (11 patients with diffuse cutaneous systemic sclerosis [SSc], 16 with linear SSc, 14 with linear morphea, and 17 with morphea) were examined in the largest cohort of such patients studied to date. These parameters were compared with data obtained from patients with adult-onset disease. RESULTS: Childhood-onset scleroderma resembled adult-onset disease with regard to the heterogeneity of clinical expression and subsets of disease, but it also differed from adult-onset disease in a number of clinical and laboratory parameters. The predominant childhood-onset disease presentation was the localized form of the disease, with limited and diffuse SSc being less notable. There was a significant association of trauma with childhood-onset scleroderma (P < 0.0001), which was not noted in adult-onset disease. Furthermore, in contrast to adult disease, patients with childhood-onset disease had normal levels of parameters of vascular activation (von Willebrand factor, angiotensin-converting enzyme, E-selectin, and endothelin-1), T cell activation (soluble interleukin-2 receptors), and collagen synthesis (carboxy-terminal type I and amino-terminal type III), a notable lack of anticentromere antibodies, and abnormal coagulation indices. CONCLUSION: A number of features distinguish childhood-onset scleroderma from adult-onset disease.

Adolescent↗
PubMed1996

Long term follow-up of children with mixed connective tissue disease.

Mixed connective tissue disease (MCTD) is characterized by features of more than one of the rheumatic disorders with antinuclear antibodies in a speckled pattern and with antibodies to nuclear ribonucleoprotein (nRNP). MCTD is uncommon in children and long-term follow-up studies in children are infrequently reported. A retrospective review of clinical experience at five pediatric rheumatology centers provided 11 patients who met the following inclusion criteria: (1) Kasukawa's criteria for MCTD1; (2) presentation younger than 18th birthday; (3) greater than five years of follow-up; (4) completion of data collection form. The widely varying outcomes of these 11 children with MCTD on long-term follow-up may lend doubt that this is a unique and distinctive rheumatologic disorder.

Adolescent↗
PubMed1993

Manifesting carriers of Xp21 muscular dystrophy; lack of correlation between dystrophin expression and clinical weakness.

Ten females presenting with muscle weakness and a raised serum creatine kinase revealed abnormalities in the expression of dystrophin in their muscle biopsies and were diagnosed as manifesting carriers of Xp21 Duchenne/Becker muscular dystrophy. Seven cases, aged 3-22 yr at the time of biopsy, had a variable proportion of dystrophin-deficient fibres and an abnormal expression on immunoblot. These were confidently diagnosed as manifesting carriers. Results in the remaining three cases, aged 8-10 yr, were less clear-cut. Dystrophin expression on immunoblots was slightly reduced and some unevenness and reduction of immunolabelling was seen on sections, but dystrophin-deficient fibres were not a feature of these cases. The weakness in the ten carriers ranged from minimal to severe and there was no correlation between the degree of weakness and the number of dystrophin-deficient fibres. Two minimally weak girls had a high proportion of dystrophin-deficient fibres. Our results show that analysis of dystrophin expression is useful for the differential diagnosis of carriers of Xp21 dystrophy and autosomal muscular dystrophy, but that dystrophin expression does not correlate directly with the degree of clinical weakness.

Adult↗
PubMed1991

Renal haemodynamics of cyclosporin A nephrotoxicity in children with juvenile dermatomyositis.

1. Renal haemodynamics were monitored over an average period of 19 months in 17 children being treated with cyclosporin A. Sixteen had juvenile dermatomyositis and one had chronic polyneuropathy. The dose of cyclosporin A ranged from 2.3 to 8.3 mg day-1 kg-1 (median 4.1 mg day-1 kg-1). 2. Glomerular filtration rate (expressed in terms of extracellular fluid volume), renal blood flow (expressed as a fraction of cardiac output) and filtration fraction were measured by using 99mTc-labelled diethylenetriamine-penta-acetate. They were compared with the dosage and trough blood levels of cyclosporin A, and, in 15 patients receiving prednisolone in addition to cyclosporin A, with steroid dosage. 3. All 17 children had a renogram performed 6 months after starting cyclosporin A treatment. Nine of them also had a renogram before starting cyclosporin A treatment (baseline study), while 13, in addition to their renogram 6 months after starting cyclosporin A treatment, also had at least one further renogram. 4. Glomerular filtration rate/extracellular fluid volume fell slightly but significantly from 0.009 (SD 0.0013) before starting cyclosporin A treatment to 0.0085 (0.002) min-1 (P less than 0.01) 6 months after cyclosporin A treatment in the nine children who underwent a baseline study. This was accompanied by a significant (P less than 0.001) fall in filtration fraction from 0.108 (0.015) to 0.088 (0.014). However, renal blood flow/cardiac output showed no change. 5. In the 13 children studied beyond 6 months after starting cyclosporin A treatment, there was no further significant overall change in any renal haemodynamic variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Cyclosporin in juvenile dermatomyositis.

Juvenile dermatomyositis in fourteen children who had not responded fully to steroids and other immunosuppressants and who had had chronic active disease for an average of 3 years was successfully treated with cyclosporin. Twelve patients had serious complications of the disease or of previous treatment. The response to cyclosporin included recovery of muscle strength and function and resolution of complications. It was possible to stop steroids or to reduce the steroid dose, which had previously been difficult, in all fourteen patients. In general, a low dose of cyclosporin (2.5-7.5 mg/kg daily) was sufficient and no serious side-effects were seen.

Child↗
PubMedDate not supplied

Septicemia following sinogram.

Contrast studies of draining sinus tracts can be of great assistance in defining the extent of an infection. Complications of this procedure must be quite rare. A 35-year-old paraplegic patient developed septicemia following a sinogram. An intraosseous venogram of the entire femoral shaft was visualized in addition to the sinus tract itself. The moderate pressure used to inject the dye may have contributed to the systemic spread of the infection and may be a hazard of sinography.

Adult↗