[Impact of cancer in Catalonia: consequences for priorities in the prevention, diagnosis and treatment of cancer]. / Impacto del cáncer en Cataluña: consecuencias para las prioridades en prevención, diagnóstico y tratamiento.

BACKGROUND: The results of analysis of incidence, survival and mortality should be applied to set the priorities in cancer prevention and screening and improvement of cancer care in Catalonia. POPULATION AND METHODS: A review of the impact of cancer in Catalonia and its foreseeable tendencies, as well as the recent proposals made across Europe regarding cancer prevention and care, was carried out. RESULTS: The main priority in prevention continues to be smoking prevention in all age groups but especially among young women and people with a low socioeconomic position, together with overweight and obesity reduction, dietary improvements, and avoidance of excessive sun exposure. Colorectal cancer screening should cover all people aged 50 to 69 years old. Cancer care should be based on a multidisciplinary approach, with clinical practice guidelines, and should take into account the psychosocial and rehabilitation aspects of care. Areas that deserve greater efforts to improve oncology care are outcomes assessment among hospitals and improvements in coordination among centers and health professionals. CONCLUSIONS: The main priority should be to apply current knowledge to clinical practice, both in diagnosis and in treatment, within a multidisciplinary framework to improve outcomes. Other priorities aimed at reducing the impact of cancer in Catalonia are reducing the prevalence of smoking and obesity and extending the coverage of colorectal cancer screening to the target population.

Increased endothelial albumin permeability mediated by protein kinase C activation.

We examined the effects of activation of endothelial protein kinase C (PKC) of the endothelial barrier function. Exposure of confluent bovine pulmonary artery endothelial cell monolayers to phorbol 12-myristate 13-acetate (PMA) resulted in concentration-dependent (10(-8)-10(-6) M) increases in PKC activity and in the transendothelial flux of 125I-albumin. Exposure of the endothelium to 1-oleoyl 2-acetyl glycerol (OAG) also increased the transendothelial flux of 125I-albumin in a concentration-dependent manner. Neither 4 alpha-phorbol didecanoate nor 1-mono-oleoyl glycerol, which do not activate PKC, altered permeability. The increase in 125I-albumin permeability induced by PMA was inhibited by 25 microM H7 (a PKC inhibitor), but not by the control compound HA1004 (25 microM). After 16 h of exposure to PMA, 125I-albumin permeability returned to baseline and a significant reduction in cytosolic PKC activity was noted. Further challenge with PMA at this time resulted in no significant increase in PKC activity indicating downregulation of the enzyme; moreover, this PMA challenge did not increase endothelial permeability. Exposure of endothelial monolayers to phospholipase C (PLC), which increases membrane phosphatidylinositide turnover, or to alpha-thrombin also induced concentration-dependent activation of PKC and increases in 125I-albumin endothelial permeability. The thrombin- and PLC-induced permeability increases were inhibited by H7, but not by HA1004. The activation of endothelial PKC directly by PMA or OAG and by PLC and alpha-thrombin increases the transendothelial albumin permeability, indicating that PKC activation is an important signal transduction pathway by which extracellular mediators increase endothelial macromolecular transport.

Advanced breast cancer clinical nursing curriculum: review and recommendations.

PURPOSE: The needs and concerns of patients with advanced breast cancer are changing at every phase of the care intervention. Management and coordination of hospital resources and services are also steadily evolving. The objective of the present expert report is to define a new oncology nursing role specialising in advanced breast cancer, to help guide patients throughout the whole healthcare itinerary. METHODS: A group of eight experts in oncology nursing and medical oncology defined the content index of the curriculum document. A systematic review of bibliography was carried out, and the relevant contents were extracted. Based on these contents and the participants' experience, recommendations were formulated and validated through a Delphi questionnaire and a participative meeting. RESULTS: The advanced breast cancer clinical nurse (ABCCN) should develop a clinical, psychosocial role focused on coordinating patients in the healthcare network. The nurse would be in charge of evaluating and supervising the care administered and the healthcare resources used. The ABCCN should be aware and participate in the protocols and available resources, be able to solve conflicts, deal with burn-out signs and have clinical, coaching and team-working abilities. The proposed curriculum provides a specific process for the care of patients, as well as an implementation process. CONCLUSIONS: The ABCCN's role is crucial to assume the best care and the optimisation of available resources. This review and consensus document provides the required tools for the implementation in hospitals.

Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I).

The X region of the HTLV-I genome contains four major open reading frames (ORFs), two of which, termed x-I and x-II, are of still undefined biological significance. By indirect immunofluorescence and dual labeling with marker proteins, we demonstrate that p13II, an 87-amino acid protein coded by the x-II ORF, is selectively targeted to mitochondria. Mutational analysis revealed that mitochondrial targeting of p13II is directed by an atypical 10-amino acid signal sequence that is not cleaved upon import and is able to target the Green Fluorescent Protein to mitochondria. Expression of p13II results in specific alterations of mitochondrial morphology and distribution from a typical string-like, dispersed network to round-shaped clusters, suggesting that p13II might interfere with processes relying on an intact mitochondrial architecture. Functional studies of mitochondria with the cationic fluorochrome tetramethylrhodamine revealed that a subpopulation of the cells with p13II-positive mitochondria show a disruption in the mitochondrial inner membrane potential (Apsi), an early event observed in cells committed to apoptosis. Taken together, these results suggest novel virus-cell interactions that might be important in HTLV-I replication and/or pathogenicity.

Differential prostaglandin production by unfractionated and density-fractionated human monocytes and alveolar macrophages.

Mononuclear phagocyte elaboration of E series prostaglandins (PGE) may be important in the regulation of inflammatory and fibrotic reactions. Mononuclear phagocytes are morphologically and functionally heterogeneous cells. To further understand the processes controlling inflammation and fibrosis, in particular that in the human lung, we characterized the ability of unfractionated and density-fractionated human alveolar macrophages and blood monocytes to elaborate PGE. Alveolar macrophages and blood monocytes constitutively elaborated small amounts of PGE, and their elaboration of PGE was increased with lipopolysaccharide (LPS) stimulation. Monocytes elaborated more PGE than autologous alveolar macrophages. In addition, denser monocytes (specific gravity greater than 1.055) and denser alveolar macrophages (specific gravity greater than 1.044) elaborated more PGE than less dense monocytes and alveolar macrophages, respectively. When monocytes were incubated in vitro, their constitutive PGE elaboration decreased with time. However, in vitro incubation did not cause monocytes to lose their capacity to elaborate PGE in response to LPS. Thus, mononuclear phagocyte populations differ in their ability to elaborate PGE. These differences can be only partially attributed to differences in cell maturation.

Differential expression of menin in sporadic pituitary adenomas.

Pituitary adenomas represent one of the key features of multiple endocrine neoplasia type 1. The gene involved in this syndrome (MEN1) is a putative tumor suppressor, that codes for a 610-amino acid nuclear protein termed 'menin'. Analyses of sporadic pituitary adenomas have so far failed to reveal MEN1 mutations or defects in MEN1 transcription in these tumors. In the present study we detected menin protein expression in a panel of normal and tumoral pituitary tissues, using a monoclonal antibody against the carboxy-terminus of menin. In the normal human pituitary gland, strong nuclear staining for menin was detectable in the majority of the endocrine cells of the anterior lobe, without a clear association with a particular hormone-producing type. In sporadic pituitary adenomas, menin expression was variable, with a high percentage of cases demonstrating a significant decrease in menin immunoreactivity when compared with the normal pituitary. Interestingly, metastatic tissues derived from one pituitary carcinoma had no detectable menin levels. Altogether, our data provide the first information regarding the status of menin expression in human normal and neoplastic pituitary as determined by immunohistochemistry (IHC).

Screening for depression in mothers bringing their offspring for evaluation or treatment of depression.

OBJECTIVE: Numerous studies have shown that the highest risk for first onset of depression occurs in women of childbearing years and that there is a strong association between lifetime rates of depressive disorders in mothers and their offspring. This association is found regardless of whether the mother or child is the targeted patient. However, little is known about rates of current depression in mothers who bring their offspring to outpatient clinics for evaluation and/or treatment of depression. This information might be useful in developing intervention strategies. METHOD: One hundred seventeen mothers bringing their offspring for evaluation or treatment for depression were screened with the Patient Problem Questionnaire to determine current symptoms of depression, anxiety disorders, and substance abuse as well as current psychiatric treatment. RESULTS: Thirty-six (31%) of the mothers screened positive on the Patient Problem Questionnaire for a current psychiatric disorder. Sixteen (14%) screened positive for current major depression, 20 (17%) for panic disorder, 20 (17%) for generalized anxiety disorder, two (2%) for alcohol abuse, and one (1%) for drug abuse. In addition, 50 (43%) of the mothers had psychiatric symptoms that did not meet the diagnostic threshold for any of the above disorders. Twenty-six (22%) of mothers expressed suicidal ideation or intent. Only five (31%) of the 16 mothers diagnosed with major depression were currently receiving any psychiatric treatment. CONCLUSIONS: A substantial number of mothers bringing their offspring for evaluation or treatment of depression were themselves currently depressed and untreated. The treatment of depressed mothers may help both the mothers and their depressed offspring.

Test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders in a family study.

OBJECTIVE: The present study examined the test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders. METHOD: As part of a series of family studies of outpatients with depressive and personality disorders, best-estimate diagnoses of relatives were derived in team diagnostic conferences held regularly over 4 years. Diagnoses were based on all available information, including direct interviews, family history data, and treatment records, and explicit guidelines were developed to resolve discrepancies between data sources. To evaluate the reliability of the team best-estimate diagnoses, 92 relatives were independently rediagnosed after a 2-year interval. RESULTS: The reliability of both axis I and II disorders was good to excellent. The results were similar for cases in which diagnoses were based on direct interviews plus informant data and cases in which diagnoses were based on informant data alone. CONCLUSIONS: These data indicate that the team consensus best-estimate diagnostic method can be applied consistently, even over an interval of several years.

30-month stability of personality disorder diagnoses in depressed outpatients.

OBJECTIVE: This study examined the 30-month stability of axis II conditions. METHOD: One hundred eight depressed outpatients received comprehensive, semistructured personality disorder assessments at baseline and at follow-up. RESULTS: The diagnostic stability of personality disorders ranged from low to moderate at the categorical level and was generally moderate at the dimensional level. Most disorders exhibited good discriminant validity, in that the association between a disorder at baseline and at follow-up was greater than the associations between that disorder at baseline and the other 11 axis 11 disorders at follow-up. Two variables, sex and lifetime history of substance abuse or dependence, were significantly related to change in level of personality disorder features over time. CONCLUSIONS: Personality disorders have low to moderate stability over a 30-month period in depressed outpatients.

Understanding the comorbidity between early-onset dysthymia and cluster B personality disorders: a family study.

OBJECTIVE: A number of studies have documented significant comorbidity between dysthymia and axis II personality disorders, particularly those grouped in cluster B. However, the nature of this comorbidity is poorly understood. The purpose of this investigation was to use the family study method to test five competing models of the comorbidity between early-onset dysthymia and cluster B personality disorders. METHOD: Proband groups consisted of subjects with early-onset dysthymia and a co-occurring cluster B personality disorder (N = 28), subjects with early-onset dysthymia without a cluster B personality disorder (N = 69), and a comparison group of subjects who had never been psychiatrically ill (N = 45). The groups were compared on rates of dysthymia with a cluster B personality disorder, dysthymia without a cluster B personality disorder, and cluster B personality disorders without dysthymia in their first-degree relatives (N = 675). RESULTS: The relatives of both subgroups of dysthymic probands exhibited higher rates of dysthymia with a cluster B personality disorder, dysthymia without a cluster B personality disorder, and cluster B personality disorders without dysthymia than the relatives of the never ill probands. In addition, the relatives of probands with comorbid dysthymia exhibited higher rates of cluster B personality disorders without dysthymia than the relatives of probands with noncomorbid dysthymia. CONCLUSIONS: This pattern of results is consistent with the notion that dysthymia and cluster B personality disorders co-occur because of shared etiological factors. This was the only one of five models of the comorbidity between dysthymia and cluster B personality disorders that was supported by the family data.

Expression and functional properties of proteins encoded in the x-II ORF of HTLV-I.

With the aim of identifying viral proteins that contribute to the distinctive properties of HTLV-I biology and pathogenicity, several laboratories have investigated the coding potential of the X region of the genome, which includes five partially overlapping open reading frames (ORFs). We and others have shown that, in addition to the essential regulatory proteins Rex and Tax, a number of accessory proteins encoded in the X region can be produced by alternative splicing and multicistronic translation. One X region ORF, termed X-II, produces two protein isoforms named Tof/p30II and p13II, which are expressed from a doubly- and singly-spliced mRNA, respectively. Initial functional analyses demonstrated that Tof/p30II is a nucleolar/nuclear protein that possesses a region capable of binding to RNA, and p13II is a mitochondrial protein that alters the morphology and function of this organelle. Together with data from other laboratories demonstrating the production of antibodies and CTL against x-II ORF products in HTLV-I infected subjects and the requirement of this ORF for efficient viral replication in vivo, these findings suggest that further characterization of Tof/p30II and p13II will yield insight into remaining undefined aspects of HTLV-I pathogenicity and replication.

The p13II protein of HTLV type 1: comparison with mitochondrial proteins coded by other human viruses.

In addition to the essential regulatory proteins Rex and Tax, the HTLV-1 genome encodes several accessory proteins of yet undefined function. One of these "orphan" proteins, named p13(II), was recently shown to be selectively targeted to mitochondria and to induce specific changes in mitochondrial morphology suggestive of altered inner membrane permeability and swelling. This represented the first report of a retroviral gene product targeted to mitochondria, and suggested that p13(II)-induced alterations in the function of this organelle may play a role in HTLV-1 replication and/or pathogenesis. The more recent findings that both Vpr and Tat of HIV-1 are targeted to mitochondria reinforces the proposed relevance of mitochondrial metabolism to the life cycle of retroviruses. Thus, p13(II), Vpr, and Tat can be added to the growing list of mitochondrial proteins produced by clinically important human viruses, including Epstein-Barr virus, human cytomegalovirus, and hepatitis B virus. Mitochondria are known to play a critical role by providing an amplification loop required for the execution of signaling pathways leading to programmed cell death. The functional consequences of the interactions between viral proteins and mitochondria described so far have been attributed to either the positive or negative control of apoptotic responses mediated by this organelle. Further analysis of the effects of p13(II) on mitochondrial function is likely to add to our understanding of the mechanisms underlying the development of HTLV-1-associated diseases.

Chronic necrotizing pulmonary aspergillosis: approach to management.

OBJECTIVE: To describe our experience with 6 patients and to review the current literature to update the approach to the diagnosis and treatment of chronic necrotizing pulmonary aspergillosis. DESIGN: Patient reports and MEDLINE review of English-language literature published after 1980. RESULTS: Chronic necrotizing pulmonary aspergillosis (CNPA) is a subacute infection most commonly seen in patients with altered local defense from preexisting pulmonary disease or in patients with risk factors that alter systemic immune status. Delays in diagnosis are common. Although initial reports advocated intravenous amphotericin B, itraconazole has emerged as a better initial therapy because of its documented efficacy and minimal toxicity. The dose and duration of therapy should be based on clinical response. In patients who do not respond to medical therapy, pulmonary resection can be considered, but postoperative morbidity is high. Recurrent or relapsing infections occur; chronic maintenance therapy with itraconazole can be considered in patients with residual parenchymal scarring. A wide range of mortality rates has been reported for CNPA. Outcome is most likely influenced by severity of comorbid conditions, extent of underlying pulmonary disease, delays in diagnosis, and initiation of effective therapy.

Fractionated TBI and methotrexate-cyclosporin do not seem to increase relapses in BMT for first chronic phase CML patients: results of a single centre study.

Fractionated total body irradiation (FTBI) and methotrexate-cyclosporin A(MTX-CSA) have been found useful in reducing interstitial pneumonia (IP) and acute graft-versus-host-disease (GVHD) in bone marrow transplantation patients, but an increase in relapse rate has been observed by some authors when these strategies are used. To evaluate this relapse risk, we performed a retrospective analysis in 24 consecutive first chronic phase chronic myeloid leukemia patients who received an HLA-identical non-T cell-depleted graft in a single institution. All were conditioned with cyclophosphamide plus FTBI (12 Gy in six fractions delivered twice daily for 3 days) (CY-FTBI) and received MTX-CSA as GVHD prophylaxis. Serial hematologic and cytogenetic bone marrow analysis were performed at least three times (days +30, +100, +360) and at variable intervals thereafter in long-term survivors. Actuarial probabilities of developing IP and acute GVHD greater than or equal to II were respectively 5.9% and 44.2%, with a GVHD-associated mortality of 33%. Four-year actuarial relapse and disease-free survival rates were 7.7% and 48.2% respectively. No exclusively cytogenetic relapses were observed. Our results suggest that CY-FTBI and MTX-CSA are not associated with an increase in relapse rate in 1CP-CML patients.

TNF-alpha augments pulmonary vasoconstriction via the inhibition of nitrovasodilator activity.

We tested the hypothesis that tumor necrosis factor-alpha (TNF-alpha) increases pulmonary vasoconstriction by decreases in nitric oxide- (NO) dependent vasodilation. Lungs were isolated from guinea pigs 18 h after intraperitoneal injection of either TNF-alpha (1.60 x 10(5) U/kg) or control. U-46619 (365 mM/min) caused increases in pulmonary arterial and capillary pressures, pulmonary arterial and venous resistances, and lung weight. TNF-alpha augmented the U-46619-induced increases in pulmonary arterial and capillary pressures, pulmonary arterial and venous resistances, and lung weight. Methylene blue (1 microM), which inhibits the activation of soluble guanylate cyclase by NO, had an effect similar to TNF-alpha on the pulmonary response to U-46619 alone but was not additive to the effect of TNF-alpha. NG-monomethyl-L-arginine (270 microM), an inhibitor of NO generation, also enhanced the response to U-46619. Lung effluent levels of nitrite, the oxidation product of NO, were reduced after treatment with either TNF-alpha or NG-monomethyl-L-arginine compared with U-46619 alone. In addition, lungs isolated after TNF-alpha treatment showed decreased vasodilation in response to acetylcholine (10(-8)-10(-5) M) compared with control; however, vasodilation in response to L-arginine (10 mM) and nitroprusside (10(-6.3) and 10(-6) M), agents that promote NO release, was not decreased in TNF-alpha-treated lungs. The data indicate that TNF-alpha induces an increase in vascular constriction in response to U-46619 and a decrease in vasodilation in response to acetylcholine. The mechanism for the TNF-alpha-induced alteration in pulmonary vascular reactivity may be decreased generation of NO.

Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema.

We tested the hypothesis that nitrovasodilator repletion enhances tumor necrosis factor-alpha (TNF-alpha) -induced pulmonary edema. Lungs were isolated from control guinea pigs or 4 h after the intraperitoneal injection of TNF-alpha (1.60 x 10(5) U/kg). In the control and TNF-alpha-injected lungs, the thromboxane mimetic U-46619 (155 pmol/min) caused increases in pulmonary capillary pressure (Ppc) and lung weight (delta W). In control lungs, the nitrovasodilator agonist S-nitroso-N-acetyl-penicillamine (SNAP, 1 microM) attenuated the U-46619-induced increases in Ppc. In lungs injected with TNF-alpha, SNAP had no effect on Ppc and increased delta W. The peroxynitrite (ONOO-) scavenger urate (35 mM) prevented the TNF-alpha +SNAP-induced increases in Ppc and delta W. In addition, chemically synthesized ONOO- (4.0 mM) enhanced U-46619-induced increases in delta W. The data indicate that nitric oxide repletion enhances TNF-alpha-induced pulmonary edema, possibly via ONOO-.

Dextran sulfate inhibits PMN-dependent hydrostatic pulmonary edema induced by tumor necrosis factor.

We tested the hypothesis that neutrophil sequestration is required for the development of tumor necrosis factor- (TNF) induced neutrophil- (PMN) dependent pulmonary edema. TNF (3.2 X 10(5) U/kg ip) was injected into guinea pigs 18 h before lung isolation. After isolation, the lung was perfused with a phosphate-buffered Ringer solution. Dextran sulfate (mol wt 500,000) prevented the changes in pulmonary capillary pressure (Ppc; 8.5 +/- 0.8 vs. 12.8 +/- 0.8 cmH2O), lung weight gain (dW; +0.240 +/- 0.135 vs. +1.951 +/- 0.311 g), and pulmonary edema formation or wet-to-dry wt ratio [(W - D)/D; 6.6 +/- 0.2 vs. 8.3 +/- 0.5] at 60 min induced by PMN infusion into a TNF-pretreated lung. The unsulfated form of dextran had no protective effect [Ppc, dW, and (W - D)/D at 60 min: 11.9 +/- 0.9 cmH2O, +1.650 +/- 0.255 g, and 7.3 +/- 0.2, respectively], whereas the use of another anionic compound, heparin, inhibited the TNF + PMN response [Ppc, dW, and (W - D)/D at 60 min: 5.6 +/- 0.4 cmH2O, +0.168 +/- 0.0.052 g, and 6.4 +/- 0.2, respectively]. Isolated lungs showed increased PMN myeloperoxidase (MPO) activity compared with control in TNF-treated lungs at baseline and 60 min after PMN infusion. Dextran sulfate, dextran, and heparin inhibited the increase in MPO activity. The data indicate that inhibition of PMN sequestration alone is not sufficient for the inhibition of PMN-mediated TNF-induced hydrostatic pulmonary edema and that a charge-dependent mechanism mediates the protective effect of dextran sulfate.

Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema.

We tested the hypothesis that dextran sulfate and heparin sulfate inhibit platelet-activating factor- (PAF) induced pulmonary edema in the isolated perfused guinea pig lung via a charge-dependent mechanism. Dextran sulfate prevented the changes in pulmonary capillary pressure (Ppc, 7.8 +/- 0.9 vs. 14.0 +/- 0.7 cmH2O), lung weight gain (dW, +0.48 +/- 0.29 vs. +8.41 +/- 2.07 g), and pulmonary edema formation or wet-to-dry weight ratio [(W-D)/D, 6.5 +/- 0.3 vs. 13.2 +/- 2.6] occurring 60 min after PAF infusion (10(-11) M) into an isolated lung. The unsulfated form of dextran had no protective effect [Ppc, dW, and (W-D)/D, 11.9 +/- 1.4 cmH2O, +5.33 +/- 2.18 g, and 11.2 +/- 3.2, respectively]. The unrelated anionic compound, heparin sulfate, also inhibited the PAF response [Ppc, dW, and (W-D)/D, 7.0 +/- 0.5 cmH2O, +0.61 +/- 0.32 g, and 6.1 +/- 0.2, respectively], whereas the partially desulfated form of heparin was not effective in inhibiting PAF-induced edema [Ppc, dW, and (W-D)/D, 15.1 +/- 0.7 cmH2O, +6.07 +/- 1.58 g, and 10.0 +/- 1.2, respectively]. When the metachromatic dye crystal violet was used as an indicator of charge interactions, the sulfated compounds interacted with PAF in vitro. The data indicate that PAF-induced pulmonary edema is inhibited by sulfated polysaccharides, possibly via a charge interaction between negatively charged compounds and PAF.

Depressive disorders: distinctions in children.

OBJECTIVE: The present study examined the distinctions between major depression without dysthymia, dysthymia without major depression, and double depression in child psychiatry inpatients. METHOD: Sixty-two child inpatients, with current diagnoses of major depression and/or dysthymia, and their mothers were interviewed with the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version and the Social Adjustment Inventory for Children and Adolescents. RESULTS: Results suggest that the relationship between the three disorders is complex and varies according to the informant and the domain under examination. Externalizing disorders were present more often in the dysthymic group compared to the major depression and double depression groups. On the other hand, the major depression and double depression groups reported higher rates of depressive symptoms. Regarding social functioning, children with major depression appeared least impaired. Child report was found to be more sensitive to distinguishing between depressive syndromes, and parents reported the most depressive symptomatology. CONCLUSION: It appears that the presence of major depression plays an important role in the expression of depressive symptomatology and comorbidity, whereas chronicity seems to be the determining factor in social functioning.

Cytogenetic studies in 18 patients with secondary blood disorders.

Cytogenetic studies were carried out in 18 patients with secondary blood diseases; 15 patients had a history of prior malignancy, two had been professionally exposed to carcinogenic agents, and one patient had been treated with immunodepressors. The interval between initial therapy and secondary disease ranged from 13 to 123 months, with a mean of 57.8 months; the mean survival time from the diagnosis of secondary disease was 6 months. Cytogenetic abnormalities were present in 83% of cases, with a trend to hypodiploidy in 90%. The most often involved chromosomes were #5, #7, and 3p. A correlation between the cytogenetic abnormalities and etiologic factors has been analyzed; data from the present series and from the literature suggest a correlation between chromosome #7 and chemical agents, and chromosomes #11, #12, and #17 and physical agents.