Sarcoidosis and lymphoma: case series and literature review.

This is a case series and literature review of patients with various types of hematologic disorders and sarcoidosis. The patients were treated in the hematologic day care unit at Shaare Zedek medical center and at the hematology department of Chaim Sheba Medical Center hospital from 1990 until 2008. We report eight cases from two centers where both diseases were diagnosed at different time points. We have shown that there might be coincidence of two rare conditions and emphasize the importance of tissues sampling of lesions suspected to be a relapse of a former biopsy-proven disease, even in the presence of positive PET results.

Hormonal response to Taekwondo fighting simulation in elite adolescent athletes.

Exercise training efficiency depends on the training load, as well as on the athlete's ability to tolerate it. The aim of the present study was to evaluate the effect of fighting simulation (3 fights, 6 min each, 30 min rest between fights) on anabolic (IGF-I, LH, FSH, estradiol, and testosterone) and catabolic hormones (cortisol) in elite, male (n = 10) and female (n = 10) adolescent (12-17 years) Taekwondo fighters. Blood samples were collected before the first and immediately after the third fight. The fighting simulation practice led to significant (p < 0.05) decreases in IGF-I (males -27.1 ± 25.6, females -22.4 ± 36.3 ng/ml), LH (males -0.7 ± 1.2, females -2.3 ± 3.3 U/L), and FSH (males -0.9 ± 0.5, females -1.5 ± 1.1 U/L), and to a significant increase (p < 0.05) in cortisol (males 141.9 ± 30.1, females 64.1 ± 30.6 mcg/dL) in both genders. Fighting simulation decreases in testosterone (males -1.9 ± 1.6, females -0.02 ± 0.06 ng/mL), and free androgen index (males -20.1 ± 21.5, females -0.3 ± 0.5) were significant (p < 0.05) only in male fighters. Exercise had no significant effect on estradiol, sex-hormone-binding globulins or thyroid function tests. Our data demonstrate that the physiologic and psychologic strain of a Taekwondo fighting simulation day led to a catabolic-type circulating hormonal response.

Anti-nuclear envelope antibodies: Clinical associations.

OBJECTIVES: Characterization of the clinical associations and clinical implications of antibodies reacting with antigens of the nuclear envelope. METHODS: Description of an illustrative case and a MEDLINE search-assisted literature review of relevant cases. RESULTS: With indirect immunofluorescence, autoantibodies directed against various antigens of the nuclear envelope stain the nucleus in a ring-like (rim) pattern. Autoantibodies against 5 antigenic components of the nuclear envelope have been described: anti-gp210, p62, lamina, lamina-associated polypeptides, and lamin B receptor. Antibodies to antigens of the nuclear pore complex, such as gp210 and p62, are highly specific (> 95%) for primary biliary cirrhosis and may aid in the serologic diagnosis of this condition, especially in cases in which antimitochondrial antibodies are not detectable. In contrast, antilamin antibodies are not disease-specific but seem to be associated with lupus anticoagulant or anticardiolipin antibodies, antiphospholipid syndrome, thrombocytopenia, autoimmune liver diseases, and arthralgia. High-titered antilamin antibodies help to define a subset of lupus patients with antiphospholipid antibodies who are at a lower risk of developing thrombotic events. In addition, preliminary data suggest that the presence of antilamin antibodies may be helpful in the diagnosis of chronic fatigue syndrome. CONCLUSIONS: Each of the antibodies reacting with nuclear membrane antigens has its own spectrum of disease associations. RELEVANCE: Determination of anti-nuclear envelope antibody pattern by indirect immunofluorescence, with subsequent determination of the specific antibody, carries important diagnostic and prognostic implications in various autoimmune conditions.

In vitro chemosensitivity testing of hematological cancers: immunohistochemical detection of ornithine decarboxylase.

A new method for in vitro chemosensitivity testing of human lymphoma and leukemia patients has been developed. The method is based on the use of ornithine decarboxylase (ODC), a universal marker of proliferation, which is expressed early during the cell cycle and has a short half-life. This marker was detected by a quantitative immunohistochemical analysis, using an ODC antibody and a FITC-linked second antibody. The in vitro chemosensitivity of lymphocytes from four normal individuals was tested by the immunohistochemical method. Lymphocytes from 25 cancer patients were also examined. In drug-sensitive cells, the intensity of the marker declined in the presence of the drug, whereas resistance to the drug was demonstrated by the presence of the marker. A good correlation was found between the predicted chemosensitivity and the outcome of the therapy. It has been suggested that this approach could be used for in vitro chemosensitivity testing of hematological cancers and most likely also for other malignancies.

Clinical implications of fluorescence in situ hybridization analysis in 13 chronic myeloid leukemia cases: Ph-negative and variant Ph-positive.

Thirteen chronic myeloid leukemia (CML) patients, 10 with variant Philadelphia (Ph) translocations and 3 Ph negative cases, were analyzed by fluorescence in situ hybridization (FISH) with the use of BCR and ABL cosmid probes and a chromosome 22 painting probe. In the variant Ph translocations, the BCR-ABL fusion gene was located on the Ph chromosome; in 1 CML Ph-negative patient, the BCR-ABL fusion gene was located on the Ph chromosome; and, in 2 patients, it was located on chromosome 9. The chromosome 22 painting probe was detected on the third-party chromosome of the variant translocation, and in none of the variant translocations was there any detectable signal on chromosome 9. In CML patients with clonal evolution of a simple Ph, a signal of the chromosome 22 painting probe was detected on the der(9) of the Ph translocation. It was concluded that the variant Ph translocations evolved simultaneously in a three-way rearrangement. The clinical parameters of the 13 patients were similar to those of a large group of CML patients with a simple Ph translocation. It is suggested that, to determine the prognosis of CML patients with a complex karyotype, FISH analysis with a chromosome 22 painting probe be performed.

Israel--a health system in transition.

Israeli health reform, implemented after many failed attempts throughout the years, represents an attempt to solve problems of politicization, dissatisfaction, unclear roles of government and public organizations, and lack of financial accountability, while maintaining a high quality and universally accessible health system. Despite many favorable aspects, including high quality medical care, near universal insurance coverage, and high availability of services, the health system has attracted criticism since its earliest days. Israel's experience with health reform, based on a version of managed competition, is of interest to other countries considering similar policy decisions.

Plasma cell dyscrasia with marrow fibrosis. A reversible syndrome mimicking agnogenic myeloid metaplasia.

BACKGROUND: The interrelation between plasma cell dyscrasia and myelofibrosis or agnogenic myeloid metaplasia (AMM) is unclear. The existence of two distinct syndromes has been proposed: (1) plasma cell dyscrasia associated with simple marrow fibrosis caused by the secretion of lymphokines and (2) myeloma coexisting with AMM representing two distinct clonal diseases. METHODS: The authors report the case of a 68 year-old man seen initially with severe anemia, massive splenomegaly, a leuko-erythroblastic blood morphology, and myelofibrosis coexisting with massive bone marrow infiltration with IgA lambda-producing plasmacytoid cells. RESULTS: Cyclic therapy with vincristine, carmustine, cyclophosphamide, melphalan, and prednisone resulted in clinical remission of the myeloma lasting for 2 years and complete resolution of all the clinical features resembling AMM. CONCLUSIONS: The authors' observations and the report of two other patients in whom remission of AMM has been observed after myeloma treatment underline the broad spectrum of secondary abnormalities ranging from moderate bone marrow fibrosis to the full clinical expression of a syndrome closely mimicking AMM. These secondary abnormalities are potentially reversible even in the presence of advanced bone marrow fibrosis and massive splenomegaly.

Optimal time interval between myeloablative whole body irradiation and reconstitution with syngeneic bone marrow graft.

The optimal time interval between termination of radiation therapy and marrow grafting has been studied in an animal model of syngeneic bone marrow transplantation, using a limiting number of bone marrow cells. Optimal survival was achieved when reconstitution took place 24 h following termination of radiation therapy at all cell doses studied, including 5 x 10(4), 2 x 10(5) and 1 x 10(6) cells/recipient. The worst results were observed when bone marrow cells were infused immediately after irradiation. These results suggest that reconstitution of lethally irradiated recipients requires migration of irradiated host marrow cells and establishment of adequate 'bone marrow space', which is optimal at 24 h following termination of whole body irradiation.

Two-stage separation of immature and mature T lymphocytes from myeloerythroid clonogenic bone marrow cells by apheresis and elutriation centrifugation.

Because graft-versus-host disease remains a major complication in allogeneic bone marrow transplantation, a number of techniques capable of removing mature T lymphocytes from bone marrow cells have been attempted. The authors describe a simple two-step procedure using counterflow centrifugation elutriation (CCE) that eliminated 95 to 98 percent of the mature T lymphocytes and greater than 97 percent of the T lymphocyte colony-forming units (CFU-T) while concentrating the bone marrow myeloid colony-forming cells. Viability was greater than 98 percent, and 72 to 98 percent of the total cells separated were recovered. Lymphocyte depletion was substantiated by both morphologic and phenotypic criteria using monoclonal antibodies to T lymphocytes, as well as by responsiveness in mixed-lymphocyte cultures and to mitogens. In addition, this technique separated the lymphoid colony-forming cells from the larger myeloid colony-forming cells. It was concluded that this simple two-step CCE procedure can be used to separate T lymphocytes and CFU-T from myeloid colony-forming cells and offers a means of purging T lymphocytes from large numbers of marrow cells that may be required for human allogeneic bone marrow transplantation.

Short-term outcome among patients with leukemia and lymphoma admitted to a medical intensive care unit.

We report here the short-term outcome of medical intensive care unit (MICU) admissions of patients with leukemia or lymphoma. We reviewed the charts of 29 such patients. Of 21 patients with acute leukemia admitted to the MICU, seven survived to leave the hospital; of eight patients with lymphoma, two survived to leave the hospital. The acute physiologic score (APS) (a system in which 0 to 4 points are given for the degree of deviation from normal for several organ systems) was used to score each patient on day 1 of their MICU stay. The APS for all patients with leukemia and lymphoma admitted to MICU was 28 +/- 11. The mortality was 69%, which is not significantly different from the predicted mortality of 56% for patients with the same APS but no underlying malignant disease. Among the survivors, young age and early stage of disease were predictors of favorable outcome.

T-cell phenotypic profile and colony formation during recovery from cytotoxic therapy-induced marrow aplasia.

Lymphocytes which appeared in the peripheral blood early (approximately 4 weeks) after complete bone marrow aplasia were studied in two groups of patients. Twenty-two allogeneic bone marrow transplant recipients and 12 acute nonlymphocytic leukemia patients (entering remission) were compared to 70 healthy control subjects studied during the same time interval. Studies performed included phenotyping T-cells using monoclonal antibodies and T-cell colony formation in response to phytohemagglutinin. The phenotypic profile for the two patient groups differed from each other and from that of the healthy controls. The total number of circulating cells reactive with OKT4 were significantly depressed in marrow graft recipients while only mildly, but significantly, depressed in leukemic patients. The number of circulating cells reactive with OKT8 were depressed in leukemic patients but were essentially normal in marrow graft recipients. The number of circulating cells reactive with OKla1 and OKT10 were significantly elevated in marrow graft recipients while significantly depressed in leukemic patients. The T4:T8 ratio was significantly depressed for marrow transplant recipients and significantly elevated for leukemic patients. T-cell colony formation in agarose without and with added interleukin-2 was decreased for both groups, more so for marrow graft recipients who virtually lacked the ability to make colonies without exogenous interleukin 2. These phenotypic and functional data suggest that T-cell reconstitution after bone marrow aplasia and profound lymphopenia takes quite different pathways for leukemic patients recovering from remission induction therapy and for recipients of bone marrow transplants. We were unable to correlate T-cell functional response in T-cell colony formation with the phenotypic profile of peripheral blood T-cells.

Blood leucocyte enzymes. III. Diurnal rhythm of activity in isolated lymphocytes of normal subjects and chronic lymphatic leukaemia patients.

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6 phosphate glucono dehydrogenase (6 phospho-D-gluconate: NADP oxidoreductase, 6PGD) lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH), glutamate oxaloacetate transaminase (L-aspartate: 2-oxo-glutarate aminotransferase, GOT) and hexokinase (ATP: D-hexo-6-phosphotrans-ferase, Hx) were measured over 24 h in isolated lymphocytes of normal subjects and in white cells of patients with chronic lymphatic leukaemia (CLL). The activitty patterns of all enzymes in the normal lymphocytes were similar. A computed pattern of all the results exhibited a circadian rhythm of activity with the highest level at 16.00 hours. The oscillations in the activities of the same enzymes in the CLL cells differed among the patients, although all the enzymes of the same individual showed a similar diurnal rhythmic pattern. All peaks in this group appeared between 20.00 and 08.00 hours. The possible importance of these observations in setting up therapeutic schedules was raised.

The diurnal rhythm of enzymes in human red cells.

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6-phosphogluconate dehydrogenase (6-phospho-d-gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP:D-hexose 6-phosphotransferase, HK), lactic dehydrogeanse (L-lactate: NAD oxidoreductase, LDH) and aspirate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, Asp.T) were determined in red blood cells of 11 healthy individuals. The determinations were carried out on samples drawn every 4 h over a 24 h period. The activities of G6PD, 6PGD, LDH and Asp.T exhibited a semi-circadian rhythm, namely, two peaks of activity during 24 h while HK activity demonstrated a true circadian rhythm. In addition a polymorphism of the G6PD and LDH activity patterns was observed. The implications of a biological clock in enucleated cells are discussed.

Blood leucocyte enzymes. II. Activities at 8-9 a.m. in cells of normal subjects, chronic lymphatic leukaemia and chronic myeloid leukaemia patients.

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP: D-hexose 6-phosphotransferase, Hx), lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH). glutamate oxaloacetate transaminase (L-aspartate: 2 oxoglutarate aminotransferase, GOT) and dihydrofolate reductase (DHFR) were measured at 8 a.m. in leucocytes of healthy individuals and patients with chronic myeloid leukaemia (CML), chronic lymphatic leukaemia (CLL), myelofibrosis with myeloid metaplasia and polycythaemia vera. In view of the heterogeneity of the leucocyte populations in these conditions, the enzyme activities were correlated to the number of immature cells in CML and to the percentage of lymphocytes in CLL. No differences in the enzyme activities were found between the white cells of healthy individuals, myelofibrosis with myeloid metaplasia and polycythaemia vera. In CML the activities of all enzymes except GOT correlated directly with the number of immature cells; an inverse correlation with the number of lymphocytes was observed in CLL. GOT was the only enzyme whose activity correlated with the number of lymphocytes in the cell suspension. Furthermore, a significantly higher activity of this enzyme was found in Ficoll-isolated CLL lymphocytes as compared to normal lymphocytes.