The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.

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A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol-paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre-and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which-even without overt malignant lymphoma-may occur in this group of disorders.

Incidence of the JAK2 mutation in their patients with chronic myeloproliferative neoplasia subgroups mainly corresponds to the literary data. Thrombosis ensued both in JAK positive polycythemia vera and essential thrombocythemia cases occurred nearly in the same number, but the incidence of thrombosis ensued in JAK2 negative cases did not differ significantly from the JAK2 positive patients. From these results it could be suggested that the presence or absence of JAK2 mutation in the development of thrombosis has no predictive value in patients with chronic myeloproliferative neoplasia.

Elevation of pressure in the pulmonary veins, with a consequent elevation of pressure in the pulmonary capillaries and pulmonary artery has for many years been invoked to explain pulmonary hypertension in both mitral stenosis and left ventricular failure. Ignoring the possibility of pulmonary vasoconstriction, this hypothesis was in complete accordance with the " mechanistic " concept of the regulation of pulmonary pressure, emphasized recently by Cournand (1947Cournand ( , 1950 and Hamilton (1951). It was based mainly on the relative refractoriness of the pulmonary circulation towards substances affecting the systemic circulation.It was soon established, however, that elevation of the pulmonary venous pressure is only partly responsible for the high pressure in the pulmonary artery that is observed in heart failure. Elevation of pulmonary " capillary " pressure beyond the colloid osmotic pressure of plasma causes an increase in the pulmonary pressure gradient (Dexter et al., 1950), as a result of an increase of the pulmonary arteriolar resistance. Lewis et al. (1952), emphasize that in mitral stenosis this increased arteriolar resistance is a physiological counterpart to the anatomical changes observed in the small pulmonary arteries by Parker and Weiss (1936) and Larrabee et al. (1949). In face of this " static " theory of increased pulmonary arteriolar resistance it seems hard to understand why the presence or absence of heart failure raises or lowers the pressure in the pulmonary artery, presumably without a change in the size of the stenosed orifice (Bloomfield et al., 1949;Bayliss et al., 1951), or in the lumen of the " statically" narrowed pulmonary arterioles. Not even an increase of the circulating blood volume explains this apparent contradiction. Nor does the decrease of pulmonary arteriolar resistance following mitral commissurotomy (Draper et al., 1951; favour this theory. On the other hand, no corresponding narrowing of the pulmonary vessels can be demonstrated in hypertensive heart failure despite a similar elevation of pulmonary arteriolar resistance (Borden et al., 1950). These data seem sufficient to support the view that anatomical factors alone cannot account for all the increase in pulmonary arterial pressure. The mechanism of this reversible elevation of pulmonary vascular resistance, therefore, needs further study.Anoxia, by producing widespread vasoconstriction in all parts of the circulation, elevates also pulmonary vascular resistance (Motley et al., 1947; LiUjestrand, 1948 ;Dirken and Heemstra, 1948; Doyle et al., 1951, etc.). Pulmonary hypertension following the administration of histamine was also observed in dogs by Dixon and Hoyle (1930). The vasomotor response to both these stimuli is a consequence of their direct chemical action on the pulmonary vessels. The significance of the nervous system as a source of vasomotor stimuli affecting the pulmonary circuit is generally underestimated. Kuntz (1946)