Extensive apoptosis or programmed cell death (PCD) of both hematopoietic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic syndromes (MDS) cancels the high birth-rate resulting in ineffective hematopoiesis and has been demonstrated as the probable basis for peripheral cytopenias in MDS by our group. It is proposed that factors present in the microenvironment are inducing apoptosis in all the cells whether stromal or parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46 MDS patients and eight normal individuals were examined for the presence of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) and one cellular component, macrophages, by the use of monoclonal antibodies immunohistochemically. Results showed the presence of TNF-alpha and TGF-beta in 41/46 and 40/46 cases of MDS respectively, while only 15 cases showed the presence of GM-CSF. Further a significant direct relationship was found between the degree of TNF-alpha and the incidence of PCD (p= 0.0015). Patients who showed high PCD also had an elevated TNF-alpha level. Thus, the expression of high amounts of TNF-alpha and TGF-beta and low amounts of the viability factor GM-CSF may be responsible for the high incidence of PCD leading to ineffective hematopoiesis in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-alpha drugs such as pentoxifylline.

Apoptosis↗

PubMedDate not supplied

Difficult cases in heart failure: familial dilated cardiomyopathy.

While originally thought to be uncommon, familial dilated cardiomyopathy may occur quite often. Aside from symptoms of heart failure, these forms of dilated cardiomyopathy may be associated with arrhythmias and sudden death. The case detailed describes such a patient and emphasizes the importance of a careful family history. Also discussed is the importance of screening of first- and second-degree relatives of these patients. (c)2001 by CHF, Inc.

Journal Article↗

PubMedDate not supplied

Melphalan, vincristine, and 5-FU in advanced colonic carcinoma: results of a pilot study.

The results of treatment with melphalan, vincristine, and 5-FU (MVF) in 32 patients with advanced colonic carcinoma are reported. The objective response rate among 31 patients with measurable disease was 16% (five patients responded). The projected survival for all 32 patients was 277 days. Patients with objective response to MVF had a projected survival of 314 days, significantly longer than the survival of patients with no response to therapy, 84 days (P = 0.01). While toxic effects were mild with MVF, this regimen appears to have greater activity in advanced colonic carcinoma than therapy with 5-FU alone or in combination with nitrosoureas.

Aged↗