Biomedical subjects

H Qawi

Publications and source records attributed to H Qawi.

4 recordsLinked to original sources

PubMed1999

Biologic characteristics of patients with hypocellular myelodysplastic syndromes.

Rates of proliferation and apoptosis as well as expression of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and the number of macrophages were measured in bone marrow (BM) biopsies of 33 patients who presented with hypocellular (cellularity < 30%) myelodysplastic syndromes (MDS). Results showed that 2/3 of the patients had high apoptosis, high cytokine levels and large number of macrophages in their biopsies while 1/3 did not. Apoptosis and TNF-alpha levels were directly related (r = 0.583, P = 0.003, n = 24) as was apoptosis and the degree of anemia (P = 0.033, n = 18). A subgroup of patients with abnormalities of chromosomes 5 or 7 had higher platelets (P = 0.026) and higher apoptosis (P = 0.038) when compared with the rest of the group. Eight patients had no evidence of apoptosis and almost no detectable TNF-alpha in their biopsies. We conclude that within the hypocellular variant of MDS, there may be two distinct sub-groups of patients, one who present with high cytokine-mediated intramedullary apoptosis and the other who may be better characterized as having a stem-cell failure defect since they showed no evidence of apoptosis.

Adolescent↗

PubMed1999

Biological characteristics of myelodysplastic syndrome patients who demonstrated high versus no intramedullary apoptosis.

Spontaneous intramedullary apoptosis was measured in bone marrow (BM) biopsies of 175 patients with myelodysplastic syndromes (MDS) using in situ end-labeling (ISEL) of fragmented DNA. Two groups of high (n=71) versus low (n =43) levels of apoptosis were identified while 61 patients were ISEL-negative. Semiquantitative assessment of 3 cytokines, the number of macrophages and in vivo labeling indices (LI) were also determined from consecutive sections of the biopsy. Patients with high apoptosis levels tended to have a high LI (p=0.013), more macrophages in their BM biopsies (p=0.006) and higher tumor necrosis factor alpha (TNF-alpha) levels (not significant) compared to patients with no apoptosis. In addition, low risk MDS patients had significantly lower rates of apoptosis (p = 0.047) and lower levels of TNF-alpha (p = 0.055) compared to high-risk MDS patients. We conclude that the genesis of cytopenias in MDS is of multifactorial origin and that cytokine-associated apoptosis clearly identifies a distinct biological subgroup of patients who may benefit selectively by use of anti-cytokine therapies.

Aged↗

PubMed1999

Biologic characteristics of 164 patients with myelodysplastic syndromes.

Rates of proliferation, apoptosis and cytokine expression were measured in bone marrow (BM) biopsies of 164 myelodysplastic syndrome (MDS) patients. There were 107 males and 57 females. Median age was 69 years and 101 had refractory anemia (RA), 17 RA with ringed sideroblasts (RARS), 38 with RA and excess blasts (RAEB) and 8 with RAEB in transformation (RAEB-t). Apoptosis measured by in-situ end labeling (ISEL) was directly related to the number of macrophages (p = 0.028, n = 83). Mean tumor necrosis factor alpha (TNF-alpha) and ISEL positivity were higher in RAEB + RAEB-t patients (p = 0.0554 and p = 0.06 respectively) while hemoglobin was higher for RA + RARS group (p = 0.0472). Patients with high apoptosis had lower white blood cell counts (p = 0.0009), lower percentage of blasts (p = 0.0009) and higher number of macrophages (p = 0.0086). We conclude that measurements of apoptosis, proliferation and cytokine expression provide important biological information which helps to distinguish RA + RARS patients from RAEB + RAEB-t patients, and may be of additive prognostic significance.

Adolescent↗

PubMed1998

Tumor necrosis factor-alpha levels decrease with anticytokine therapy in patients with myelodysplastic syndromes.

Tumor necrosis factor-alpha (TNF-alpha) levels were measured in the serum (sTNF-alpha) or bone marrow (BM) biopsies of 43 patients with myelodysplastic syndromes (MDS) who subsequently received therapy with a combination of pentoxifylline and ciprofloxacin (PC) with or without dexamethasone (PCD). All 43 patients received only PC therapy for 12 weeks, after which 18 of 36 nonresponders received PCD. A total of 18 of 43 patients showed a hematologic or cytogenetic response or both. BM TNF-alpha levels were semiquantitatively assessed using immunohistochemistry on a scale of 0-8+ and in the serum using enzyme linked immunoassay. The median TNF-alpha for the entire group was 3.0 in BM and 6.9 pg/ml in the serum, and 14 patients had no detectable levels. Responders had higher BM levels (median 3.5 vs. 2.0) than nonresponders, although this was not statistically significant. During PC therapy, a decline in BM TNF-alpha level was seen in the entire group, which was significant at 2 weeks (p = 0.02), 8 weeks (p = 0.001), and 12 weeks (p = 0.0001). Both responders (p = 0.01) and nonresponders (p = 0.03) had a decline at 8 weeks, but at 12 weeks, only the responders continued to show a significant decline (p = 0.03). We conclude that MDS patients with high BM TNF-alpa levels have a better chance of responding to PCD therapy and that the therapy is quite successful in reducing the TNF-alpha levels in a sustained fashion. Future studies need to be directed at identifying agents that would be more potent suppressors of the proapoptotic cytokines in these patients.

Aged↗