Incidence and role of apoptosis in myelodysplastic syndrome: morphological and ultrastructural assessment.

By application of morphological and ultrastructural methods for identification of apoptosis, we analyzed the incidence of morphologically evident apoptosis in the bone marrow of 30 patients with myelodysplastic syndrome (MDS), and in the bone marrow of 12 healthy individuals. According to FAB classification, out of 30 patients, eight (26.6%) had refractory anemia, three (10%) had refractory anemia with ringed sideroblasts, 14 (46.6%) had refractory anemia with excess of blasts and two (6.8%) had refractory anemia with excess of blasts in transformation. Three patients (10%) had chronic myelomonocytic leukemia. Cells in apoptosis were examined on semithin slides and expressed as the apoptotic index (AI) (percent counted on at least 1000 cells). An overall increase in apoptosis in patients with MDS was found (median AI in patients vs controls, 3.13% vs 1.05%, P < 0.01 by Mann-Whitney U test). Also, negative correlation between AI and white blood cell count was found (linear r= -0.53, or Spearman rank R= -0.52, both P < 0.01). In patients with evident karyotype changes AI was not higher than in patients with normal karyotype. This suggests that discrete alterations in apoptosis are present even in karyotypically 'normal' clones. Our results strongly support the hypothesis that apoptosis has a role in ineffective hematopoiesis and may be a mechanism responsible for the paradox of hypercellular bone marrow and peripheral blood pancytopenia in MDS.

Influence of three-week fasting on gonadotropin pulsatility in obese menstruating women.

OBJECTIVE: To evaluate the influence of three-week fasting on gonadotropin pulsatility in extremely obese women of reproductive age. DESIGN: Prospective study of 21-day fasting (400 kcal/day), under medical supervision. SUBJECTS: 20 females, average age of 35.1 +/- 5.9 y, and average BMI of 41.19 +/- 8.39 kg/m2, with regular menstrual cycles (26-34 days). The mean weight loss was 12.5 +/- 3.23 kg. MEASUREMENTS: Blood samples for LH and FSH were taken between 4th and 7th day of the menstrual cycle, before and in the first cycle immediately after weight reduction, for 6 h, starting at 09.00 with 10 min intersample intervals. Pulsatility analysis was done using Pulsar program. Statistical analysis was done using Wilcoxon's matched pairs signed ranking test and McNemar's test. RESULTS: There was no statistically significant difference (p > 0.05) in LH and FSH pulsatile secretion before and after diet including the number of pulses, amplitudes, interpulse intervals and peak lengths. There were no disturbances of menstrual cycle during or after the diet. CONCLUSION: These results suggest that a 21-day fast, accompanied with significant weight loss, does not affect gonadotropin pulse pattern in follicular phase and normal menstrual cycle length in extremely obese females of reproductive age, compared with the pattern before diet.

Progression of refractory anaemia with ringed sideroblasts (RARS) to B-acute lymphoblastic leukaemia.

The study describes progression of refractory anaemia with ring sideroblasts (RARS) of 3 years' duration to B-acute lymphoblastic leukaemia (ALL). Development of ALL in this patient was preceded by the deterioration of dyserythropoiesis, leukopenia and an increase of blasts in the bone marrow. Our case may represent an additional evidence to the hypothesis that a primary pathogenetic lesion in myelodysplastic syndrome occurs at the level of the pluripotent stem cell.