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Background: The influence of rapid and prolonged weight loss on body composition and muscle constituents in the obese patient is not well known. There are serious complications related to rapid and prolonged weight loss. It is of general interest to increase the understanding of the mechanisms and consequences of significant weight loss in man., Methods: In 40 obese patients, the body composition and muscle constituents were studied before and during 1 year of weight loss following gastroplasty. The study was undertaken in two groups (A and B) of obese patients, comprising 32 women and eight men, body weight 82-175 kg and aged 24-49 years. Mean BMI in group A and B was 45 (W/H(2)) and 43 (W/H(2)) respectively. Body composition was assessed by total body potassium measurements and muscle constituents were determined by analyses of muscle specimens obtained percutaneously., Results: The preoperative body composition was found to be equal parts of lean body mass and body fat. Preoperatively, muscle constituents revealed a higher protein content per cell and a lower potassium concentration related to fat-free solids. The loss of 18-28% body fat and lean body mass occurred in equal proportions during the first 3 postoperative months of rapid weight loss, followed by a continuous decrease of body fat but not of lean body mass. The concentrations of proteins and potassium per muscle cell revealed a reduction during the period of rapid weight loss. The RNA/DNA ratio 1 year after surgery was still reduced, indicating a low protein synthesis rate., Conclusions: Preoperatively mean body fat accounted for 50% of the body weight in obese patients. Following weight loss, body fat, lean body mass and concentrations of proteins were reduced compared to preoperative values. After the period of rapid weight loss, with reduction of lean body mass and body fat in parallel, a progressive reduction of body fat was observed whereas the lean body mass did not decrease further. Protein synthesis rate was still low 12 months after surgery.

The role of major histocompatibility complex (MHC) class I antigens and adhesion molecules (AM) in the resistance of leukemic B-cells to cell-mediated cytotoxicity was investigated using cells from eight patients with B-chronic lymphocytic leukemia (B-CLL) and six patients with immunocytoma (IC). Both CLL and IC cells were completely resistant to natural killer (NK) and lymphokine activated killer (LAK) cytotoxicity and no binding to effector cells was observed, irrespectively of AM expression. Blocking of MHC class I antigens with monoclonal antibodies or their temporary elimination from leukemic B-cell surface by acid treatment resulted in a significant (p < 0.005) increase in both conjugate formation and susceptibility to lysis, thus suggesting the relevance of MHC class I expression on leukemic B-cells for the NK/LAK resistance phenomenon.

Leukotrienes and lipoxins are bioactive lipoxygenase products formed by leukocytes alone or in collaboration with other cells. While the physiological role of lipoxins remains to be clarified, accumulating evidence shows that leukotrienes are important mediators in asthma and inflammation. Consequently, recent clinical trials with leukotriene D4 receptor antagonists and 5-lipoxygenase inhibitors have demonstrated marked reduction of airway symptoms in asthmatic patients. In addition, both leukotrienes and lipoxins have been indicated as modulators of cell proliferation. This article reviews recent findings suggesting that these compounds may also participate in the regulation of human myelopoiesis. Such a role is conceivable since leukotrienes and lipoxins can be produced by bone marrow cells and potently modulate GM-CSF-induced myeloid stem cell proliferation.

The incidence and mortality due to the major cancers such as lung, breast, colon-rectum, prostate, and ovary have changed very little over the past 20-30 years, in spite of the introduction of important new treatments and apparent prolongation of survival of patients with these cancers. The new strategies focus on earlier detection and primary prevention of cancer. Three approaches for prevention are receiving increasing prominence as an approach to reducing the incidence of cancer: (1) control of common source environmental carcinogens, (2) modification of personal health behavior believed to increase or decrease the risk of cancer, and (3) identification of specific genotypes that increase the risk of cancer. All of these approaches offer some hope of reducing cancer incidence and morbidity. All will be costly and, therefore, require careful evaluation. It is likely that the changes in personal health behaviors will have the greatest overall impact on cancer incidence. Identification of specific genotypes will be of importance for high risk families. At present, it is unlikely that control of environmental common sources will substantially reduce cancer incidence without better measures of exposure and risk of disease.

The possibility of using DNA image cytometry in hematological material was evaluated in 27 Feulgen stained normal bone marrow smears. The 95% normal limits of DNA index (DI) determined separately for each cell population in bone marrow were 0.89-1.15, 0.93-1.09 and 0.92-1.12 for blasts, granulocytes and lymphocytes, respectively. The mean DI for blasts, granulocytes and lymphocytes was 1.02, 1.01 and 1.02, respectively. In the blasts population the mean percentage of cells in S+G2/M phase was 38.1% (S.D. 12.9%, range 14.3-65.6%), whereas the corresponding values for granulocytes and lymphocytes were below 1%. Calculation of DI and G0/G1 C.V. obtained in bone marrow smears subjected to Feulgen hydrolysis (5 N HCl, 22 degrees C) for different periods of time revealed the presence of a plateau of results between 60 and 120 min for all of the cell types. The intraobserver and interobserver reproducibility was confirmed by duplicate measurements of each subpopulation (P > 0.05). A comparison of DI and G0/G1 C.V. using smears from the same donors stained with the Feulgen method either straight away or after destaining from May-Grunwald-Giemsa confirmed that destained smears can be used, provided applying appropriately prepared reference cells. We conclude that image cytometry can be used reliably to analyze DNA content in hematological material.

Conjugate formation by AML blasts with fresh peripheral blood lymphocytes (PBL) and lymphokine activated killer (LAK) effectors was studied by flow cytometry. Leukemic blasts formed very low numbers of conjugates with fresh PBL and were resistant to natural killer (NK) cytotoxicity. When LAK effectors were used a significant increase in conjugate formation was observed, which in the majority of cases was followed by an increased killing. There was a positive correlation between the percentages of conjugates formed by AML blasts with LAK effectors and the susceptibility to lysis. No significant difference in binding activity between the CD3+ and CD56+ LAK subpopulations was found. There was no correlation between the expression of ICAM-1, LFA-3 and Transferrin receptor (CD71) and the conjugate formation. The blocking of CD71 on the control K562 cell line reduced the conjugate formation with LAK effectors but no such effect could be observed with CD71+ AML blasts.

A variability in DNA content detected was found with image cytometry, in immature bone marrow cells from 13 healthy donors (median age 31 yr). The mean coefficient of variation (C.V.) of the DNA content was found to be significantly (P = 0.0002) higher in immature blasts and promyelocytes than in mature granulocytes, lymphocytes, and monocytes. The finding was not due to high DNA contents secondary to DNA-synthesis in immature cells, since the percentage of such cells with a reduced DNA content was also significantly (P = 0.0424-0.0002) increased. The error of the method expressed as the variance of multiple measurements has been found to be 0.0002-0.0004. A staining error has been found for some hydrolysis times, but not for times between 60 and 120 minutes. A measuring error was found for an average of 1.38 to 3.38% of the cells. If many normal cells with DNA-aneuploidy are sterile, this would explain the present findings as well as previous ones about intra-marrow cell death, and also the fact that the variability in DNA content could not be detected with cytogenetic or flow cytometric methods.

The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS-AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feulgen-stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS-AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; DI) in each cell population was determined using a digital video-based image-analyzing system (CAS-100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS-AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit DI was found both in immature and mature bone marrow cells. Patients with MDS-AML had those of DI values similar to normal controls. In consequence, a significantly reduced mean DI was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS-AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA-DR expression, these data suggest biological differences between the two diseases.

The relative intestinal absorption of heme- and non heme-iron in connection with a standardized test meal was studied in a group of fertile women given 16 mg Fe in the form of FeSO4 and 2 mg Fe in the form of hemoglobin. Both in normal subjects and in women with iron deficiency, the heme-iron was significantly better absorbed (16.13% +/- S.D. 8.0 vs 4.59 +/- 3.4, p < 0.01 and 22.03 +/- 8.9 vs 9.45 +/- 7.8, p < 0.05). For targeted prophylaxis of iron deficiency with small, side-effect-free doses, heme-iron is thus a valuable component which increases the absorption by about 40%. Heme-iron does not cause high concentrations in the intestinal lumen of free radical inducing, possibly harmful ferric iron.

The present results demonstrate leukotriene and lipoxin synthesis in human bone marrow and link these findings to biological effects in the same tissue. However, the mechanisms behind the described effects on myeloid progenitor cell growth are presently unknown. It is conceivable that both leukotrienes and lipoxins may act through modulation of endogenous cytokine production. However, it should be noted, that these lipoxygenase products totally failed to induce colony growth in the absence of GM-CSF. Moreover, the role of lipoxins in the bone marrow needs to be further clarified, since LXA4 induced both synergistic (with GM-CSF) and antagonistic (with LTC4) effects on progenitor cell growth. A possible pathophysiological role for leukotrienes and lipoxins may be suggested in chronic myelogenous leukemia. Thus, the capacity of hematological cells from CML patients to synthesize LTC4 was significantly increased. In addition, we have recently reported that CML platelets possessed a markedly decreased ability to participate in transcellular synthesis of the potential inhibitors of myelopoiesis, LXA4 and 5(S),12(S)-diHETE (Stenke et al., 1991b). Moreover, the production of these compounds was totally abolished in platelets obtained from CML patients in blastic crisis. Further studies should aim at defining the mechanisms behind the regulatory actions of leukotrienes and lipoxins in normal and leukemic human myelopoiesis.

Conjugate formation by natural killer (NK)-resistant and NK-sensitive leukaemic cell lines with fresh and IL-2-stimulated (lymphokine-activated killer, LAK) peripheral blood lymphocytes (PBL) was studied by a flow cytofluorometry method with double staining. A significant difference in binding of NK-resistant T-cell lymphoma (HuT 78) and NK-sensitive myeloid (K562) blasts to fresh PBL was observed (P < 0.01). Activation of lymphocytes with IL-2 resulted in a significant increase of binding and killing of both K562 and HuT 78. However, in the case of blasts from NK-resistant cell line Daudi a similar conjugate formation with fresh PBL and LAK effectors was observed, despite a significant increase in killing. Various subpopulations of LAK effectors (CD3, CD16 and CD56 positive) displayed similar binding activity towards myeloid (K562) and lymphoid (Raji) blasts, which shows that conjugate formation occurs not only with NK-cell-derived, but also with T-cell-derived LAK cells. The blocking of CD71 antigen (transferrin receptor) on K562 blasts inhibited binding of cytotoxic lymphocytes, which was mostly due to the blocking of binding of CD56+ subpopulation. Our results indicate that the resistance of leukaemic blasts to cell-mediated cytotoxicity may depend on different (and probably several) steps of this process.

DNA index (DI) and percentages of cells in S and G2/M phase were determined in Feulgen stained nuclei of blasts from 31 cases of childhood ALL at diagnosis. In 6 cases the results of DNA analysis and cytogenetics were concordant showing hyperdiploidy. Two other cases with normal karyotype were revealed as DNA aneuploid with image analysis. Cases with cytogenetic abnormalities like translocation, deletion or presence of single or double supernumerary chromosomes had DI within normal ranges. Nine ALL cases (29%) were found to be DNA aneuploid--8 hyperdiploid and 1 hypodiploid. The percentages of cells in S and G2/M phase for blasts from bone marrow (mean 17.6%) were significantly higher than those estimated in the peripheral blood (mean 1.57%). We conclude that analysis by image cytometry can detect aneuploid DNA content even in cases, which showed a normal karyotype and provides new information concerning the biological aspects of leukemic blasts.

The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4 or LTB4 to the cultures dose-dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean +/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)-diHETE did not affect the growth. LTD4 exerted a weak potentiating effect on progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P = .034), whereas LTE4 was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4 antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4 or LTC4. The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth.

An international committee (2) which has studied the health and environmental effects of the Chernobyl accident within the borders of the former Soviet Union does not expect that any increase in cancer frequency among adults can be demonstrated epidemiologically. However, the possibility of an observable increase in the incidence of thyroid cancer and increase in juvenile leukemia could not be excluded. The statistics in Sweden is more accurate, though the radiation doses were significantly lower. It would appear to be unlikely that any changes in cancer incidence (even among children), in mental development in children, in malformations or genetic changes ascribable to the Chernobyl accident will ever be demonstrated in Sweden.

By using a quantitative RNA-RNA solution hybridisation method, the average number of mdr1 RNA transcripts per cell was measured in total nucleic acid extracts of leukaemic cells from patients with acute leukaemia. The results in different types of leukaemia were (number of patients with detectable mdr1 RNA/total number of patients; median number of transcripts per cell in samples with detectable mdr1 RNA); de novo untreated acute myelocytic leukaemia (AML): 20/44; 0.7, secondary acute myelocytic leukaemia: 8/13; 1.1, acute lymphocytic (ALL) and undifferentiated leukaemia: 5/14; 0.6, relapsed leukaemia: 7/15; 0.7. Forty-six patients with de novo untreated acute leukaemia (AML: n = 34, ALL: n = 12) were evaluable for response to induction chemotherapy. Twelve of 18 patients (67%) with detectable mdr1 RNA levels achieved complete remission compared to 23 of 28 (82%) with undetectable levels (P = 0.40). The remission duration tended to be longer among patients with undetectable mdr1 RNA (P = 0.08). Leukaemic cells were analysed on consecutive occasions in 12 patients. The level of expression increased in four and decreased in two. In conclusion, expression of mdr1 RNA is common in acute untreated leukaemia. However, treatment with cytostatic drugs seems only rarely to increase the proportion of leukaemic cells that express mdr1 RNA. Expression of the mdr1 gene could be one of several equally important factors contributing to drug resistance in acute leukaemia.

The expression and function of neural cell adhesion molecule (NCAM, CD56, Leu19) on leukaemic blasts was investigated. The expression of NCAM was frequent (64%) in 14 studied cases of acute myeloid leukaemia (AML) but not in chronic lymphocytic leukaemia (CLL: 1/3 cases positive) or immunocytoma (IC: no positivity). No correlation with the expression of other AM (intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1). VLA beta chain) or with AML type, according to FAB classification, was observed. Blocking of NCAM with anti-Leu 19 MoAb on AML targets resulted in a significant decrease of their susceptibility to LAK killing and in inhibition of conjugate formation. In the case of B prolymphocytic leukaemia (B-PLL) which did not express ICAM-1 or LFA-1 but was NCAM+, a complete resistance to LAK activity and lack of conjugate formation was observed. Blocking of NCAM on LAK effectors did not decrease their cytotoxic activity. Our results suggest that NCAM, in the presence of other AM, may have a supportive role in adhesion of leukaemic targets to LAK effectors.

The bromodeoxyuridine (BRDU) labelling of bone marrow cells was studied in 46 subjects. The labelling in 14 patients, mostly untreated, with the myelodysplastic syndrome (MDS) and four lymphoma patients was significantly (p = 0.043) higher (11.38 +/- SE 2.3% S-phase cells) than that of marrow cells (7.18 +/- SE 1.04%) from 14 apparently healthy normal controls and from nine patients with non hematologic disease. Six iron deficiency had numerically but not significantly increased values. Bone marrow samples from MDS-patients showing the highest numbers of cells in the DNA-synthesis phase had the lowest numbers of colonies and clusters in the CFU-C assay (p < 0.03). The data suggest that the DNA-synthesis period is longer in MDS than in controls.

Lipoxins A4 and B4 together with the all-trans lipoxin (LX) isomers were produced by normal human bone marrow cell suspensions after incubation with ionophore A23187. Both LXA4 and LXB4 enhanced the growth of myeloid progenitor cells in semisolid agar in the presence of suboptimal concentrations of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lipoxin A4 at 10(-10) M stimulated the colony formation in 13 out of 15 tested human bone marrows with a mean (+/- SEM) increase of 47 +/- 11% (p = 0.001). A similar stimulatory effect was observed after addition of LXB4 (10(-10) M). The monohydroxyeicosatetraenoic acids 5-, 12- and 15-HETE did not affect colony growth. In addition, LXA4 (10(-8) M) efficiently counteracted the increased colony formation induced by leukotriene C4 (10(-10) M), suggesting an antagonistic relationship between these lipoxygenase products. The results support a role for lipoxins in the regulation of human myelopoiesis.

The expression of adhesion molecules on blasts from 14 patients with acute myeloid leukemia (AML) was investigated by immunofluorescence and flow cytofluorometry. All tested blast populations expressed CD18/CD11a complex [leukocyte function antigen-1 (LFA-1)] and CD29 (very-late antigen (VLA)) and the majority were positive for CD54 [intercellular adhesion molecule-1 (ICAM-1), 78.6%] and CD56 [neural cell adhesion molecule (NCAM), 64.3%]. The expression of two other alpha chains of CD18/CD11b and CD11c varied considerably (64.3% and 42.8% of positive cases, respectively). Only one case (AML-M4) showed a weak expression of the activated platelet antigen CD41b. None of the tested blasts expressed the vitronectin receptor (CD61/CD51). No significant correlation between the expression of adhesion molecules and the FAB type of leukemia could be found. All tested blast populations were completely resistant to NK-mediated cytotoxicity and relatively resistant to LAK-mediated cytotoxicity in the standard 51Cr release assay. While no statistically significant correlation of the results in cytotoxicity assays with the expression of adhesion molecules or the expression of HLA-DR antigen could be observed, 2 out of 3 completely resistant cases lacked ICAM-1. These results show that even leukemic blasts which express all of the tested adhesion molecules can still be resistant to LAK-mediated cytotoxicity.

Twenty-four obese patients were studied before and 3, 6, and 12 months after gastric banding to see if the excessive weight reduction caused any dysfunction of the peripheral or central nervous system or both. Postoperatively the patients were assumed to be able to keep their intake to 800-1000 kcal/day together with a multivitamin supplement. Electromyography, electroneurography and vibratory thresholds were used to assess the peripheral, somatosensory and visual evoked potentials to assess the central nervous and synaptic functions. Regular clinical and neurological assessments were made as well as laboratory examinations including total potassium estimations to calculate lean body mass. The mean weight loss and the mean lean body mass reduction amounted to 20.5% and 18.4% at 3 months, and to 30.3% and 10.2% at 12 months, respectively. Electromyography showed signs of acute denervation in the anterior tibial muscle in one patient 3 and 6 months after operation, but restitution after 12 months despite continuous weight loss. In the left peroneal nerve the electroneurography showed a trend with slight successive reduction of the conduction velocity in the postoperative period. No abnormalities of the vibratory thresholds were found postoperatively. Somatosensory and visual evoked potentials were normal in all patients and no significant changes were observed during the postoperative period. The present study did not reveal any significant dysfunction of the peripheral or central nervous system as a result of excessive weight loss in obese adults undergoing weight reducing surgery.

Autotransplants in leukemia are controversial; their rationale and results have been questioned. Here we consider several issues central to this debate: (1) Are there convincing data to suggest that more intensive therapy increases cures? (2) Are results post-autotransplant a consequence of the transplant, or do they reflect subject-selection and time-to-treatment (time censoring) biases? (3) Does leukemia relapse after an autotransplant develop from persisting leukemia cells in the subject or the graft? (4) Do autotransplants using hematopoietic stem cells from different sources have distinct outcomes? (5) Are immune-mediated anti-leukemia mechanisms likely to prevent relapse after autotransplants? and (6) Can comparably intensive therapy be given without an autotransplant?

Free radicals, intermediates in the tissue damage caused by radiation, are formed, inter alia, in interactions catalyzed by iron, which synergizes with radiation and some cytostatics (anthracyclins) in causing cell damage. Conversely, iron chelators can counteract cell damage. Similarly, antioxidants can slow atherogenesis, caused in part by oxidative stress and free radicals. Cell damage is also prevented by physiological defense systems like superoxide dismutase, against endogenous free radicals formed by granulocytes, monocytes, etc. Iron can thus induce free radicals which cause DNA double strand breaks and oncogene activation. This is suggested by four epidemiological studies suggesting a higher cancer risk in patients with larger iron stores than in those with small iron stores. In addition to its effect on carcinogenesis, iron can also maintain the growth of malignant cells as well as growth of pathogens. Breast cancer cells, for instance, display 5-15 times more transferrin receptors than normal breast tissue. Iron-carrying transferrin is in fact a growth factor. Hyposideremia in patients with cancer or infection is not a paraphenomenon but a functioning defense mechanism ('nutritional immunity'). If this immunity is broken by iron administration, relapses of diseases like tuberculosis, brucellosis, and malaria have been described. While iron-deficiency anemia should of course be diagnosed, treated and if possible prevented, there are good reasons to avoid over-utilization of medicamental iron.

Attitude studies of patients, their relatives, and sometimes even widows or widowers suggest that about 80 per cent of a small sample of Swedish in-patients are satisfied. However, the discontinuity of patient-staff relations in 69 per cent of out-patients is disturbing. There is a possibility that medical quality in the Swedish non-fee-for-service system is affected negatively by staff inactivity, which could explain slow diagnoses, long median durations of stay, and high cost. A tentative but comprehensive study indicates a theoretical efficiency increase in a large Swedish hospital of about 40, and a realistic increase of about 10 per cent. In the author's view, present attempts at cost reduction rarely achieve an efficiency increase, but they may reduce medical quality. The absence of quality assurance in parallel with cost reduction is criticized, and a WHO recommendation is proposed.

Intestinal absorption of calcium from three different labelled calcium preparations (all containing 500 mg elemental calcium) was determined using the whole body retention and urinary excretion of 47Ca in 14 normal subjects. Chewable calcium carbonate tablets showed a significantly (p less than 0.05) better mean minimum absorption of calcium (25.6% in exp. I, 22.8% in exp. II) than calcium given in the form of a lactogluconate/carbonate effervescent tablet, (17%), but similar to calcium in a chloride solution (24.7%). The minimum calcium absorption varied from 85 to 128 mg. All the preparations were taken with standardized low calcium test meals.

Verapamil (240 mg daily orally) was tested in a phase II trial to restore vincristine sensitivity in 9 patients with myeloma, chronic lymphatic leukemia and immunocytoma. These tumors were selected because treatment response and tumor progression can easily be ascertained with the help of electrophoresis and marrow studies, blood counts and lymph node examination. All patients were clinically refractory to vincristine-cytoxan-prednisolone combinations, to which adriamycin had been added in 2 patients. One patient was refractory to adriamycin, VM 26, and prednisone. In 2/9 patients a side effect-free second response lasting 5-10 months was observed, with a doubtful response in two additional patients. It is suggested that occasional clinical responses can be seen, despite the fact that in vitro the mean verapamil concentration required to affect vincristine efflux from malignant lymphocytes in 5 mumols/1 and the mean in vivo serum concentration only 1 mumole. Hypothetically, the clinical response can be explained by an overlapping in some patients of an unusually high serum concentration with an unusually low verapamil requirement.

Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML.

Results of five different methods (heme breakdown, mitotic indices, total marrow cellularity and different methods of labelling indices) to determine bone marrow cell growth are reviewed. Normal immature erythroblasts and myeloblasts have generation times of about 5-10 h. Erythroblasts in neoplastic conditions (the myelodysplastic syndrome and polycythemia vera) have generation times which are significantly prolonged, by 12-75 per cent, but this may not be true for myeloblasts, since total labelling indices are increased (from normal 3.9 to 11.2 per cent) in the myelodysplastic syndrome. In contrast, generation times in aplastic anemia are significantly shortened, by about 70-80 per cent. Normal mature erythroblasts and promyelocytes have generation times of about 24 h, and the malignant prolongation may be even greater.