Comprehensive clinical, molecular and histopathological analysis of bone marrow in chronic myeloproliferative neoplasia. / Análisis integrado clínico, molecular e histopatológico de la médula ósea en las neoplasias mieloproliferativas crónicas.

OBJECTIVES: To analyse the possible correlation between molecular changes in the JAK2, MPL and CALR genes, the morphological pattern of bone marrow and the clinical-haematologic profile of patients. PATIENTS AND METHODS: We conducted a retrospective study that included 140 patients diagnosed with Philadelphia-negative myeloproliferative neoplasia (Ph-MPN) in a single centre. RESULTS: In essential thrombocythaemia (ET), the patients with the JAK2 V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy. These findings support the fact that the mutational state in ET appears to define subtypes of patients with substantially different clinical courses and prognoses. In myelofibrosis, the mutational state appears to influence the histopathological changes found in the bone marrow biopsy, which did not occur in polycythaemia vera or ET.

Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients.

The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.

[Peritoneal tuberculosis as a complication in a case of unclassifiable myelodysplastic/myeloproliferative disease]. / Tuberculosis peritoneal como complicación en un caso de síndrome mielodisplásico/mieloproliferativo inclasificable.

We report the case of a 68-year-old male with a diagnosis of unclassifiable myelodysplatic/myeloproliferative disease (WHO classification), under prolonged steroid treatment and unsuccesful chemotherapy response, who developed progressive asthenia, thoracic pain, minimal efforts dyspnea, and abdominal distension, that initially was suspicious of splenic rupture. Exploratory laparotomy showed multiple peritoneal implants, and a diagnosis of peritoneal tuberculosis was obtained from local biopsy. Definitive diagnosis included a positive result to culture and PCR urine test, together with a possible pleural and splenic tuberculous affectation. Response to tuberculostatic treatment was successful. To the best of our knowledge, this is the first reported case with such characteristics.

AML with unusual chromosomal changes. Translocation (15;21) and 5q- in the presence of two normal chromosomes 5.

We performed serial cytogenetic studies of the bone marrow (BM) of a patient with acute myeloblastic leukemia (AML) and noted abnormal karyotypes 47,XY,+del(5)(q12q34),t(15;21)(q21;q22)/47,XY,+del(5)(q12q34 ) during the second relapse. Although a case of this t(15;21) was recently observed in a female patient with acute nonlymphocytic leukemia (ANLL) of subtype M4 of the French-American-British (FAB) classification, the present article constitutes the first report of its occurrence in association with ANLL of subtype M1-M2. Furthermore, the presence of the 5q- accompanied by two chromosomes 5 of normal appearance is very rare and of great interest.

Deletion of exon b3 of the BCR gene in CML: easy breakpoint mapping by a two-round PCR.

We have performed the molecular analysis for the detection of the BCR-ABL and ABL-BCR fusion genes in 50 patients with myeloproliferative disorders. All patients diagnosed with CML (13 out of 50) were positive for the BCR-ABL hybrid. Six CML patients (46%) showed ABL-BCR amplifications of the Ib-BCR type. All rearrangements but one were concordant. The aberrant case presented a deletion of exon b3, in addition to the alternative Ib-BCR and Ia-BCR. Its possible origin and relevance are briefly discussed.

Hepatocyte and nuclear areas in alcoholic liver cirrhosis: their relationship with the size of the nodules and the degree of fibrosis.

The aim of the study in alcoholic cirrhotic patients was to determine if a relationship exists between the areas of hepatocytes and their nuclei and the area of the nodules to which these cells belong as well as the thickness of the fibrous tracts which delimit these nodules. It was found that hepatocyte and nuclear areas were enlarged the smaller the nodules and the thicker the surrounding fibrous tracts. Considering that oxygen supply in liver cirrhosis decreases with increasing fibrosis, our results permit the hypothesis that a low oxygen supply causes an increase not only in liver cell size but also in nuclear size, which is an index of nuclear activity.

Evaluation of marrow cellularity in alcoholism and hepatic cirrhosis, by aspiration, biopsy and histomorphometric.

A study of bone marrow cell content was carried out in 23 non-cirrhotic alcoholics, 20 cirrhotic alcoholics and 19 cirrhotic non-alcoholics compared with a control group of 12 healthy subjects, by means of sternal aspiration and bone marrow biopsy with histomorphometric quantification of fat in the latter. Although in the three pathological groups the mean values of fat area were superior to those of the control group, the only statistical differences found were between non-alcoholic cirrhotic and control subjects. The differences disappeared under covariance analysis with age as the correcting factor, showing a correlation between age and bone marrow fat content. To conclude from the biopsy the bone marrow of the cirrhotic is not hypercellular, contrary to the so far accepted findings obtained through sternal aspiration. Moreover, between the subjective global cellularity evaluation by biopsy and aspiration there was an important disagreement in 23.8% and an absolute agreement only 28.6% of cases. The non-existence of a linear correlation between fat content in bone marrow and liver, suggests that the two phenomena do not develop simultaneously.

Alcohol-induced hypogonadism: reversal after ethanol withdrawal.

Serum testosterone, FSH, LH and prolactin levels have been determined in a group of 32 non-cirrhotic heavy drinkers at 9 and 21 h of the 1st, 3rd, 6th, 11th and 15th days after the onset of a florid ethanol withdrawal syndrome. In addition, serum steroid hormone binding globulin (SHBG) levels were determined at the 1st and 15th days. Serum levels of all these hormones were also determined in a control group of 15 healthy male volunteers. Serum testosterone levels, significantly lower in alcoholics at the beginning of the study, progressively increased along the observation period, recovering the circadian rhythm at the end of it. A significant increase was also observed in serum prolactin levels, in the low and upper limits of the normal range at the beginning and at the end of the study respectively. Serum FSH and LH levels were significantly higher in the alcoholics at the beginning of the study, with no significant variations during the observation period. There was a strong relationship between FSH and LH levels, but not between these hormones and testosterone. Thus, our data suggest that ethanol-induced hypogonadism is primary in origin, functional in nature and transient in its evolution.

[The beneficial effect of 1,25-dihydroxycholecalciferol on the excess of blasts and the myelofibrosis in 2 cases of chronic myeloproliferative syndrome]. / Efecto beneficioso del 1,25-dihidroxicolecalciferol sobre el exceso de blastos y la mielofibrosis en 2 casos de síndrome mieloproliferativo crónico.

The active metabolite of vitamin D3 1.25 dehydroxycholecalciferol (1.25DHCC) is a potent inducer of monocytic differentiation of the myeloid blasts "in vitro". Likewise the inhibiting role of vitamin D3 on bone marrow fibrosis by, among others, a stimulating effect of macrophagic activity is known. However, these actions have seldom been clinically demonstrated. Two cases of chronic myeloproliferative syndromes in which treatment with 1.25DHCC was effective are presented. In the first case, one patient with polycythemia vera with myelofibrosis and focal blastosis in the bone marrow achieved disappearance of the excess of blasts and a reduction in the fibrosis (grade III to grade I) upon treatment. In the second case, idiopathic myelofibrosis, also with focal blastosis in the bone marrow biopsy, there was no regression of the fibrosis but the blastosis did disappear. It was concluded that 1.25DHCC may constitute an interesting treatment in this group of diseases through the following two mechanisms: limitation of the fibrosis and delay of blast transformation.

[Neutrophil mobilization test with intravenous hydrocortisone in the study of chronic idiopathic neutropenias. Experience with 19 cases and usefulness of a new diagnostic index]. / Prueba de movilización de los neutrófilos con hidrocortisona intravenosa en el estudio de las neutropenias crónicas idiopáticas. Experiencia en 19 casos y utilidad de un nuevo índice diagnóstico.

BACKGROUND: Some patients with chronic benign neutropenia present granulocytes distribution disorders within their different physiologic pools, and this situation can be exposed by granulocyte mobilization tests. Stimulation with hydrocortisone is the best known test, but its performance and interpretation are not well standardized. Granulocyte mobilization test with hydrocortisone was performed in 19 patients with chronic peripheral idiopathic granulocytopenia, by applying homogeneous criteria. PATIENTS AND METHOD: The test included an injection of intravenous hydrocortisone 200 mg after a first basal blood neutrophil determination, and a second neutrophil count four hours after steroid administration. Following data were registered: basal blood neutrophil count (BNC), final blood neutrophil count (FNC), difference between both counts or increment (INCR), and the ratio = 60% of INCR/2.0 (109/1) BNC, which we name demargination index (DI). RESULTS: Three response patterns (three patient groups) were observed: pattern I, with FNC > 2.0 109/1 and DI >/= 1 (false neutropenia with hypermargination component); pattern II, with FNC > 2.0 (109/1) and DI < 1 (false neutropenia with pathogenic mechanisms others than hypermargination), and pattern III, with FNC < 2.0 (109/1) and DI < 1 (true neutropenia). There were no significant differences in BNC or INCR when groups I and II were compared, but we found differences in FNC (p = 0.026) and DI (p = 0.026). Comparison between groups I and III showed differences in all four parameters (BNC P = 0.07, FNC p < 0.001, INCR p = 0.02, and DI p < 0.001). No differences were found between groups II and III. CONCLUSIONS: Granulocyte mobilization test with intravenous hydrocortisone 200 mg and a four-hours interval between basal and final neutrophil counts, allows differentiation between false neutropenia with hypermargination component and true neutropenia.

[A study using nondecalcified bone biopsy of the incidence and presentation forms of renal osteodystrophy]. / Estudio con biopsia ósea sin descalcificar de la incidencia y formas de presentación de la osteodistrofia renal.

BACKGROUND: Renal osteodystrophy (ROD) is a common complication of chronic renal failure. Fibrous osteitis and, to a lesser extent, osteomalacia are the predominant lesions. The aim of the present study was to evaluate the prevalence of the different forms of ROD. METHODS: Nondecalcified bone biopsies were evaluated in 100 patients with end-stage renal disease (57 in pre-dialysis and 43 on hemodialysis) in whom biochemical (calcium, phosphorus, alkaline phosphatase, parathyroid hormone) and histomorphometric studies were carried out. Bone biopsies were classified in four histological groups: mild, fibrous osteitis (FO), osteomalacia (OM) and mixed type (FO + OM). RESULTS: 96% of patients had histological findings of ROD with the following distribution: 41% mild; 30% FO; 14% OM; and 11% mixed. The most advanced types of ROD were seen in interstitial renal diseases. Pre-dialysis OM was associated with metabolic acidosis, a low phosphocalcic product and relative hypophosphoremia. Chronic aluminium poisoning was uncommon (7%) and was basically associated with OM. No instance of aluminium poisoning with osteodystrophy and bone fractures was seen. CONCLUSIONS: The most severe histological forms of OM were found in hemodialysis patients with persistent hypophosphoremia and associated with osteosclerosis.

[Latent chronic constrictive pericarditis. Rapid filling overload for an accurate hemodynamic diagnosis (author's transl)]. / Pericarditis crónica constrictiva latente. Confirmación diagnóstica hemodinámica con sobrecarga volumétrica rápida.

Chest roentgenogram showed a pericardial calcification in a patient with inconspicuous signs of cardiac disease and normal basal pressures in the right cavities. A typical hemodynamic tracing of chronic constrictive pericarditis was obtained with rapid filling overload. The uncommeness of silent chronic constrictive pericarditis is mentioned and the usefulness of rapid filling overload for an accurate hemodynamic diagnosis of this condition is emphasized. Denomination of "latent" chronic constrictive pericarditis for similar cases to this reported is proposed.

[Ultrasound diagnosis of abdominal aortic aneurysm. Review of five cases (author's transl)]. / La ecografia abdominal en el diagnóstico del aneurisma aórtico. A propósito de cinco casos.

Five patients with aneurysms occuring in the abdominal aorta have been studied by means of arteriographic and echographic examinations. Suggestive clinical symptoms (pulsatile abdominal mass) were present in two cases, while the remaining three patients had doubtful symptomatology. Echography achieved and accurate diagnosis in all cases. Aortograms were useful in four cases, but a definite diagnosis was not obtained in the fifth case due to the presence of aortic fibrosis. Advantages of echographic procedure as a simple, useful, non-surgical and lower-cost method are mentioned.

[Chronic lymphoid leukemia. Survival in relation to clinical stages. Statistical analysis of 95 cases (author's transl)]. / Sobrevivencia de la leucemia linfoide crónica en relación con los estadios clínicos. Análisis estadístico de 95 casos.

The prognosis of patients with chronic lymphocytic leukemia is very difficult to evaluate. The classification system by stages, which at the present time is the most simple and useful method for the prognosis of this disease, recognizes five degrees of involvement: stage 0 (medullary and peripheral lymphocytosis); stage I (lymphocytosis + enlarged lymph nodes); stage II (lymphocyosis + hepato-and/or splenomegaly); stage III (lymphocytosis + anemia), and stage IV (lymphocytosis + thrombocytopenia). In the present report 95 controlled patients at the Farreras Valentí School of Hematology are analyzed using the classification by stages; there were 19 cases in stage 0; 16 in stage I; 30 in stage II; 21 in stage III, and 9 in stage IV. The mean survival rate in the global series was 63 months and the average 90.9 months. As in other series, it was observed that patients in stages 0 and I have a much better prognosis than those in stages III and IV. Stage II occupies an intermediate position in relation to prognosis, since the actuarial survival figure for this stage can practically be superimposed on that of the global series. The classification of chronic lymphocytic leukemia by stages permits the specification of the therapeutic indications for this condition; it also encourages the search for new modalities of treatment for stages with poor prognosis, since in these cases chronic lymphocytic leukemia behaves in the manner of an acute or subacute hemopathy.

[A-V conduction block at His bundle level; as the cause of syncopal crisis in patients with normal ECG (author's transl)]. / Bloqueos A-V completos intermitentes de localización intrahisiana, como causa de crisis sincopales con ECG de base normal.

The history, clinical evolution and complementary studies used to identify the diagnostic etiology of syncopal crisis in a series of 5 patients are presented. The crisis consisted of advanced disturbances of the A-V conduction at the level of the His bundle. It is pointed out that although the evolution of the disturbance was intermittent, the surface ECG was normal and neither A-V block nor broadening of the QRS complex were seen. The importance of continued monitorization, whether as out-patients (Holter system) or, in some cases in an Intensive Care Unit, as well as the need to practice electrophysiologic studies in all these cases as the only way of establishing a firm diagnosis, are underlined. The fact that these disturbances do not always lead to an advanced blockage of A-V conduction is discussed as being reminiscent of the prospective and retrospective studies in the similar case of bi-fascicle block.

[Spontaneous infection of ascitic fluid as a form of presentation of agnogenic myeloid metaplasia]. / Infección espontánea de líquido ascítico como forma de presentación de un caso de metaplasia mieloide agnogénica.

In most cases, the clinical manifestation of the agnogenic myeloid metaplasia is an anemic syndrome. Ascitis secondary to portal hypertension as the first manifestations is a rare clinical condition. Finally, the form of presentation of the idiopathic rare. We present a case of agnogenic myeloid metaplasia in a 64 years-old patient whose form of presentation was an spontaneous infection of the ascitic fluid. In our review of the literature we have not found any other case with similar characteristics.

HIV-associated primary body-cavity-based lymphoma: clinico-biologic features in three patients diagnosed at the same institution.

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/mL). Occasionally, it appears in others immunodepressive states (such as solid organs postransplant period) and even, although very rarelly, in immunocompetents patients. From a pathogenetic point of view, PEL has been related to Kaposi's sarcoma-associated herpes virus (also named human herpesvirus 8) and to the clinical antecedent of Kaposís sarcoma. Relative unfrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome, support the need of a deeper knowledge. We present here the clinical-biological findings of three patients that were diagnosed of pleural PEL in our institution in the last two years.

[Treatment of life threatening asthma with isoflurane]. / Tratamiento del "Life threatening asthma" con isofluorane.

Three patients, one adult, one adolescent and one child, with previous history of asthma difficult to treat and frequent acute crisis, were hospitalized with clinical signs of Life Threatening Asthma (LTA) refractory to intensive treatment, including intubation and mechanical ventilation, being treated with and inhaled anesthetic: Isoflurane. All patients responded satisfactorily to such treatment at a concentration varying from 0.5 to 1.5% and none of them suffered adverse reactions to the medication. The immediate therapeutic effect and the absence of intensive care are factors that indicate the use of Isoflurane.

[Atypical relapsing polychondritis]. / Policondritis recidivante atípica.

Relapsing polychondritis is a disease of unknown etiology whose main characteristic is the chronic inflammation and destruction of the different cartilaginous structures of the body. A rare case is presented, the rareness being the fact that ear cartilage was not affected and that the destructive arthropathy was similar to that produced by rheumatoid arthritis.

[Hepatic cirrhosis and alpha 1-antitrypsin deficit: a family study]. / Cirrosis hepática y déficit de alfa-1 antitripsina: estudio de una familia.

Hepatic cirrhosis secondary to deficit of alpha-1 antitrypsin is an entity rarely observed among the adult population. We describe the clinical and histological characteristics of a patient with PiZZ phenotype, affected by an hepatic cirrhosis of this etiology, as well as the analytical and phenotypical study of his close relatives, all of which presented a type-Z mutation.