Continuous complete clinical and molecular remission in two patients with refractory lymphoid malignancies after autografting followed by allogeneic stem cell transplantation with reduced intensity conditioning

We present a 60-year-old patient with primary refractory non-Hodgkin's lymphoma and a 58-year-old patient with multiple myeloma with relapse after first autologous stem cell transplantation (ASCT), who underwent ASCT followed by allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning consisting of fludarabine and a single dose of total body irradiation. For graft-versus-host disease prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete donor chimaerism was observed on d 28 after SCT. Both patients achieved sustained complete haematological and molecular remission of the immunoglobulin kappa light chain (Igkappa) rearrangement and are alive and well 17 and 16 months after SCT respectively.     

The increasing supply of physicians in US urban and rural areas, 1975 to 1988.

BACKGROUND. Despite the rapid growth of the US physician supply since the mid-1970s, it remains unclear whether physicians have spread into the most rural areas of the country. This report examines the urban-rural distribution of physicians between 1975 and 1988. METHODS. A county-based typology of the urban-rural continuum was employed to examine trends in the supply of nonfederal primary care physicians, specialist physicians, and osteopaths. RESULTS. All urban and rural areas gained physicians during the late 1970s and 1980s. The supply of physicians increased most rapidly in metropolitan counties. Within nonmetropolitan areas, urbanized remote counties became more prominent centers of the physician supply. Osteopaths were more likely to locate in the most rural areas than allopaths. The physician supply in all areas also became more specialized over time. CONCLUSIONS. The rapid growth of the US physician supply was associated with the spread of more practitioners into all parts of the country. However, the supply of physicians increased most rapidly in urban areas, widening urban-rural differences in the availability of physicians.     

Extruded micronuclei induced by colchicine or acrylamide contain mostly lagging chromosomes identified in paintbrush smears by minor and major mouse DNA probes

In the mouse bone marrow micronucleus assay, it was studiedwhether micronuclei (MN) could be expelled from polychromaticerythrocytes (PCE) in a similar way to the main nucleus. Toavoid the disrupting centrifugation step of the conventionalbone marrow preparation procedure, the paintbrush techniquewas used in the present experiments. With May–Grünwald–Giemsastaining of paintbrush slides, 5% of the colchicine (COL)-inducedMN were found attached to the outside membranes of PCE and wereregarded as extruded. Of the acrylamide (AA)-induced MN, 22%were extruded. After fluorescence in situ hybridization (FISH)of a total of 300 MN per chemical treatment with the mouse minorand major satellite DNA probes, 9.7% MN were extruded in theCOL group and 8.3% MN were extruded in the AA group. FISH showedthat 76% of the retained COL-induced MN were signal-positive,indicating that they contained entire chromosomes. With A A,29% minor-positive and 28.3% major-positive retained MN werefound, confirming its known clastogenicity. However, the observedfrequency of signal-positive MN (1.7 MNPCE_pos/ 1000 PCE) inthe AA group was about three times higher than in the control(0.5 MNPCE_pos/1000 PCE) which indicates that AA has aneugenicpotential. FISH analysis of the extruded MN showed 72–100%major as well as minor signals. It is concluded that expelledMN contain mostly entire chromosomes. ³To whom correspondence should be addressed     

Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma.

PURPOSE: Although thalidomide (Thal) was introduced successfully in the treatment of multiple myeloma (MM), the optimal Thal dosage and schedule are still controversial. The aim of this study was to analyze whether the effect of Thal in MM is dose dependent and whether the outcome might be improved when the Thal dosage is adjusted to parameters reflecting body size. EXPERIMENTAL DESIGN: From December 1998 to March 2001, 83 patients with relapsed MM were enrolled in a clinical Phase II trial and treated with a maximum Thal dosage of 400 mg daily. We performed a retrospective analysis and studied the effect of the cumulative 3-month Thal dosage on progression-free survival and overall survival (OS) together with age and the pretreatment levels of beta2-microglobulin, C-reactive protein, albumin, and hemoglobin in a Cox regression model. RESULTS: After a median follow-up time of 17 months (range, 1-30 months), the estimated 12-month progression-free survival and OS were 45% (SE = 6%) and 86% (SE = 4%) for the whole patient group. After backward selection, hemoglobin (P = 0.002) and the cumulative 3-month Thal dosage (P = 0.002) were the remaining factors for OS. The effect on OS could not be improved when the cumulative 3-month Thal dosage was adjusted to parameters reflecting body size such as height, weight, body surface area, or body mass index in comparison with Thal alone. CONCLUSIONS: Our retrospective analysis demonstrates that the cumulative 3-month Thal dosage is one of the major prognostic factors for OS, supporting the hypothesis of a dose-dependent effect of Thal in relapsed MM.     

In vitro inhibition of adenosine deaminase by a group of steroid and Triterpenoid compounds

The effects of several sapogenins and saponins of the steroid and triterpenoid classes, as well as of a few common phytosterols, have been tested for their inhibitory action towards adenosine deaminase (ADA). It was found that the acidic sapogenins strongly inhibit the enzyme. The mean inhibitory concentration (IC₅₀) was in the range 10^?3 to 10^?2 mg/mL, while the inhibitor constants (K_i) have been estimated as about 10^?6 M. In contrast to this finding is the complete absence of any influence on the enzyme of the neutral sapo(ge)nins and the phytosterols. It is suggested that ADA is a worthwhile therapeutic target and that the (acidic) sapogenins, which are regular constituents of many medicinal plant species, presumably contribute their activity through an interaction with this enzyme.     

Health Insurance Coverage in U.S. Urban and Rural Areas

This study examines the health insurance coverage of the nonelderly population in U.S. urban and rural areas in 1989, using data from the March 1990 Current Population Survey conducted by the Bureau of the Census. Access to coverage was assessed by classifying all persons by family employment status and income. Rural residents had less access to coverage than urban residents but were only slightly less likely to be insured. In comparison to urban residents, fewer rural residents obtained coverage through employment, and more purchased private coverage outside the work place. The differences in coverage by family employment status and income were generally much greater than the differences by place of residence.     

Prostaglandin E1 induces vascular endothelial growth factor-1 in human adult cardiac myocytes but not in human adult cardiac fibroblasts via a cAMP-dependent mechanism

Prostaglandin E(1) (PGE(1)) has been used to treat pulmonary hypertension and peripheral artery occlusive disease and has been successfully employed for pharmacological bridging to transplantation in patients with chronic end-stage heart failure. In addition to its vasoactive effects PGE(1) was shown to stimulate angiogenesis in animal models. Recently we showed that PGE(1)-induced angiogenesis in hearts of patients with ischemic heart disease. We proposed that the angiogenic action of PGE(1) is mediated by vascular endothelial growth factor (VEGF). In the present paper we studied a possible effect of PGE(1) on the expression of VEGF-1 in cultured human adult cardiac myocytes (HACM) and cultured human adult cardiac fibroblasts (HACFB), respectively, to identify a cellular source of VEGF-1 in patients treated with PGE(1). We also aimed to delineate mechanisms involved in a possible regulation of VEGF-1 by PGE(1) in these cells. When HACM, isolated from human myocardial tissue, were treated with PGE(1), a significant up to 3-fold increase in VEGF-1 production could be observed. These results could be confirmed on the level of specific mRNA expression as determined by real-time polymerase chain reaction. The effect of PGE(1) on VEGF-1 expression could be blocked by H089, an inhibitor of cAMP-dependent protein kinase A. In HACFB, also isolated from human myocardial tissue, no effect of PGE(1) on VEGF-1 production was seen. If this effect of PGE(1) is also operative in the in vivo situation, one could speculate that cardiac myocytes could be a cellular source of PGE(1)-induced VEGF-1 expression in patients treated with this drug.