Microirbe. Aproximación a la epidemiología de la microalbuminuria en las personas con diabetes e hipertensión de España / Microirbe. Approximation to epidemiology of microalbuminuria in patients with diabetes and hypertension in Spain

Objetivos: Análisis epidemiológico de la prevalencia de microalbuminuria en hipertensos y diabéticos tipo 2 de España. Averiguar la accesibilidad a la determinación del índice albúmina/creatinina en Atención Primaria Material y métodos: Estudio transversal epidemiológico anidado en un estudio de intervención. Participación voluntaria de 1.967 médicos de Atención Primaria que aportaron 7.592 pacientes hipertensos y diabéticos. Variables principales: hipertensión arterial, diabetes y excreción urinaria de albúmina (se recomienda el uso del índice albúmina/ creatinina, pero se aceptan otros métodos si no está disponible). Resultados: Muestra con edad media de 63,6 años (± 10,2) y con un 53,6% de mujeres. Las cifras promedio de la presión arterial fueron 155/92 mmHg (± 10,9/6,2) y de la HbA1c de 6,83% (± 1,07). El 34,4% de los hipertensos y el 21,5% de los diabéticos no utilizaban fármacos para éstas patologías. El 48,7% presentaban una hipercolesterolemia asociada. Globalmente el 38,8% de los pacientes presentaron cifras de excreción urinaria de albúmina dentro del rango de “microalbuminuria”. Se analizan modelos multivariados de predicción de la microalbuminuria. Se observó gran variabilidad interprovincial en la accesibilidad al índice albúmina/creatinina desde la Atención Primaria, con una media del 45,7% (rango: 0-84%). La determinación de microalbuminuria en orina matinal aislada fue el método más frecuente (47,1%)

Objectives: The trial main objective was the epidemiological analysis of microalbuminuria prevalence in patients with hypertension and type 2 diabetes mellitus in Spain. The secondary objective was to set the albumin/creatinine rate determination accessibility in Primary Care Centers. Material and methods: This trial was designed as transversal epidemiological study nested in an interventional study. A total number of 1,967 Primary Care physicians participated with a contribution of 7,592 patients with hypertension and type 2 diabetes mellitus. Main variables: High blood pressure, diabetes and albumin urinary excretion (the albumin/creatinine rate was recommended, but alternative methods were admitted when that rate was not available). Results: The sample average age was 63.6 years (± 10.2). A 53.6% of patients were female. The average blood pressure was 155/92 mmHg (± 10.9/6.2) and average HbA1c was 6.83% (± 1.07). The 34.4% of high blood pressure patients and a 21.5% of diabetic ones were not taking drugs for those pathologies. The 48.7% were having associated hypercholesterolemia. Globally, the 38.8% of patients presented albumin urinary excretion in the range of microalbuminuria. Multivariant models for microalbuminuria prediction were analyzed. A great interprovincial variability was detected relative to the albumin/creatinine rate accessibility in Primary Care Centers, with an average of 45.7% (range: 0-84%). The microalbuminuria determination in isoalted first-morning urine samples was the most frequent method (47.1%)

[Pathological characteristics of patients with diabetes mellitus type 2, in Spanish Primary Care]. / Perfil de los pacientes con diabetes mellitus tipo 2, en la Atención Primaria española.

CONTEXT: To know the characteristics, related risk factors, and degree of control in patients with diabetes mellitus type 2 (DM2) in our country. METHODS: Observational, unrandom, opened, and multicenter study. Anthropometric characteristics, substance abuse, medication, control of diabetes, cholesterol, and triglycerides were analyzed in 5,395 patients. The patients were classified according to the length of the diagnosis: recent diabetes (RD) and known diabetes (KD). The chi-square test was utilized in order to compare the categorical variables, and the Student's t test for compare the continuous variables. The relationship between these variables was analyzed through the Pearson's correlation coefficient, and an analysis of multiple correspondence was carried out. RESULTS: Median age, 63 years; obese, 34%; smokers, 11%; drinkers, 24%; hypertensives, 44%; lipemic, 42%. Control degree: HbA1c>6.5% in 79%, LDLc>115 mg/dl in 80%. Hypoglycemic treatment: sulfonylureas, 62.8%; antidiabetics combination, 5%; only insulin, 4.3%; insulin combined with antidiabetics, 20.6%. Control of diabetics, of lipids, and of weight was lower in the patients with KD that in the patients with RD (HbA1c, 7.6% versus 7%; LDLc 148 mg/dl versus 136 mg/dl; percentage of obese, 27.2% versus 38.62%). A relationship between the length of evolution of diabetes and the deterioration of the control of blood glucose and of lipids was detected. CONCLUSION: DM2 and its associated risk factors are insufficiently controlled in our country. The drug combination and insulin are utilized scarcely.

Perfil de los pacientes con diabetes mellitus tipo 2, en la Atención Primaria española / Pathological characteristics of patients with diabetes mellitus tipe 2, in Spanish Primary Care

Fundamento. Conocer las características, factores de riesgo asociados y el grado de control de los pacientes con diabetes mellitus tipo 2 (DM2) de nuestro país. Métodos. Estudio observacional, no aleatorizado, abierto y multicéntrico. Se analizó en 5.395 pacientes sus características antropométricas, hábitos tóxicos, medicación, control de la diabetes, colesterol y triglicéridos. Se dividieron según la antigüedad del diagnóstico en diabetes reciente (DR) y diabetes conocida (DC). Se utilizó la prueba de 2 para comparar las variables categóricas y la "t" de Student para comparar las variables continuas. La relación entre estas variables se analizó mediante el coeficiente de correlación de Pearson y se realizó un análisis de correspondencias múltiples. Resultados. Edad media, 63 años; obesos, 34 por ciento; fumadores, 11 por ciento; bebedores, 24 por ciento; hipertensos, 44 por ciento; hiperlipidémicos, 42 por ciento. Grado de control: HbA1c > 6,5 por ciento en el 79 por ciento, c-LDL>115 mg/dl en el 80 por ciento. Tratamiento hipoglucemiante: sulfonilurea, 62,8 por ciento; combinación de antidiabéticos, 5 por ciento; insulina sola 4,3 por ciento, y combinada con antidiabéticos, 20,6 por ciento. El control de la diabetes, de los lípidos y del peso fue peor en los pacientes con DC que en los DR (HbA1c, 7,6 por ciento frente al 7 por ciento; LDL, 148 mg/dl frente a 136 mg/dl; porcentaje de obesos, 27,2 por ciento frente al 38,62 por ciento). Encontramos relación entre el tiempo de evolución de la diabetes y el deterioro del control de la glucemia y de los lípidos. Conclusión. La DM2 y los factores de riesgo asociados están mal controlados en nuestro país. Se utiliza poco la combinación de fármacos y la insulina (AU)

Enhanced myeloid specificity of CD117 compared with CD13 and CD33.

The c-kit proto-oncogene encodes a 145 kd tyrosine kinase transmembrane receptor, which plays a key role in haemopoiesis. The c-kit has been classified as CD117 and is especially useful in the differential diagnosis of acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL). We analysed 104 consecutive cases (55 AML, 23 B-cell lineage ALL, three T-cell ALL, 11 blast crisis of chronic myeloproliferative disorders and 12 cases of myelodysplastic syndromes with more than 10% of blasts) referred to our Hospital for immunophenotypic diagnosis and compared the expression pattern of CD13, CD33 and CD117 using the same fluorochrome (phycoerythrin-PE). The recommendations of the EGIL group were followed in order to establish lineage involvement of the blastic population. The threshold used to assign positivity for CD117 was 10%. Bcr/abl, TEL/AML-1 and MLL rearrangements were assessed by molecular methods. CD117 expression was detected in 91% of AML and MDS. All the negative cases corresponded to acute monocytic leukemias. The calculated specificity for myeloid involvement was 0.86 for CD117, 0.36 for CD13 and 0.44 for CD33 (P < 0.005). CD117 was also positive in four cases of ALL. None of these cases showed bcr/abl or MLL rearrangements. In the light of these findings, CD117 expression should yield a higher score, at least one point, in the system currently applied for the diagnosis of biphenotypic acute leukemias (BAL) as its myeloid specificity is greater than that of CD13 and CD33. Moreover, its absence in AML could identify two subgroups of M5b cases. The coexpression of CD117 with cytoplasmic CD79a is often associated with CD7 reactivity, suggesting a stem cell disorder. CD117 should be included on a routine basis for the immunophenotypic diagnosis of acute leukemias.

cCD79a expression in a case of plasma cell leukemia.

In the present report we analyzed the immunophenotype of the neoplastic cells in a case of primary plasma cell leukemia (PCL). We performed simultaneous analysis of bone marrow and peripheral blood samples to investigate minor phenotypic variations that could explain the tendency of a population to leave medullary compartments. No major differences were observed between the two populations. The phenotype of the malignant clone was: CD38+, CD138+, CD19-, CD56+, CD117-, CD33+, CD44 , CD49e , cCD79a+ with positive cytoplasmic stain for kappa and IgG. Our findings expands the potential uses of cCD79a to cases of PCL with atypical morphology.

p53 mutation in a case of blastic transformation of follicular lymphoma with double bcl-2 rearrangement (MBR and VCR).

The bcl-2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters are found in two specific regions: mbr and mcr. Rearrangements of the immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl-2 protein. In cases of rearrangement of the light chains (variant translocations), a third breakpoint has been described at the 5' part of the bcl-2 locus (vcr). In the present case, we report the molecular analysis of an FL transformed into a blastic phase unresponsive to chemotherapy. Molecular studies revealed a typical bcl-2 rearrangement at the major locus (mbr). Vcr rearrangements was also observed with only a single restriction enzyme. At the same time, SSCP analysis of exon 5 of the p53 locus disclosed an abnormal conformer. Direct sequencing revealed a point mutation at codon 163 (A --> G). Immunohistochemical analysis of the affected sites disclosed overexpression of p53 and bcl-2. It is concluded that p53 mutation can contribute to blastic transformation in cases of follicular lymphomas with double rearrangement at the bcl-2 locus (mbr/vcr).

Aggressive natural killer cell leukemia: report of a case in a Caucasian boy.

We report a case of aggressive natural killer cell leukemia (ANKL) in a Caucasian boy diagnosed on clinical, cytologic, immunophenotypic and genotypic grounds. An anomalous karyotype and integration of Epstein-Barr virus (EBV) within the leukemic population were identified.

Concomitant chronic lymphocytic leukemia and acute myeloid leukemia with an uncommon immunophenotype.

We report a case of simultaneous diagnosis of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), in which the use of flow cytometry analysis allowed the demonstration of two different cell populations and the study of both immunophenotyping patterns with a large panel of monoclonal antibodies (MoAbs). CLL cells showed a typical immunophenotype with coexpression of B cell markers with CD5, CD23, CD43, and weak surface immunoglobulin light chain restriction expression, whereas the AML population had a very uncommon phenotype with expression of myeloid markers and CD56 and lack of expression of other natural killer (NK) antigens, CD34 and HLA-DR. After chemotherapeutic treatment of AML with two induction courses, the patient achieved complete remission of the AML with persistence of a CD19/CD5 positive population. After consolidation chemotherapy, this latter population was no longer detectable despite the presence of lymphoid nodules in a bone marrow biopsy. Six months after diagnosis, the patient relapsed with AML and died shortly afterwards.

[Informatics support to medical diagnosis. General information obtained from a first structured contact with the patient]. / Ayuda informática al diagnóstico médico. Información general obtenida en un primer contacto estructurado con el paciente.

BACKGROUND: The methods and characteristics of clinical data gathered at the initial steps of development of a computerized system to aid medical diagnosis are reported. The objectives of the study were as follows: to describe the overall method and to set a framework for developing an intellectual model of the medical diagnosis procedure. MATERIAL AND METHODS: A structured medical interview and physical examination using an informatic program on PC compatible portable computers were completed in a sample 1,238 patients attending the outpatient clinics of our institution. Data obtained were compared with information in the patient's medical record taking as reference pattern the record of physicians in charge of the patients. Diagnosis were codified according to WHO International Classification of Diseases (ICD-9-CM). RESULTS: The distribution of symptoms and signs corresponding to the different organs and systems was analyzed. Each subdivision afforded a range of 1.3 to 3.9 abnormal findings per patient. A total of 3,571 diagnoses were codified for the whole group 1,238 patients with a mean (standard deviation) of 3 (2) diagnoses per patient (range 0-12). The distribution of diagnostic groups varied depending on the consideration of the main diagnosis or the concomitant diagnoses that defined the patient's clinical context. The most frequent main diagnoses included tumors, cardiovascular diseases, gastrointestinal disorders, and genitourinary tract diseases. CONCLUSIONS: As shown by results obtained in a sample of 1,238 patients, there is a very complex situation in clinical practice due to the simultaneous occurrence of several clinical patterns. This finding should be taken into account when developing clinical decision making support systems. The use of a structured medical interview or a structured and standard medical visit may be an adequate tool to clarify this matter and to contribute to standardization of clinical concepts and situations.

Mutational analysis of p53 in 16 cases of acute lymphoblastic leukemia and Burkitt's lymphoma.

BACKGROUND AND OBJECTIVE: Improvements in therapy for patients with B-cell acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) depend on the identification of subsets of patients who require more intensive therapy. Abnormalities of the p53 gene are the most common molecular lesions in human cancer, and may be of prognostic significance in hematologic malignancies. In this study, we examined the p53 gene status in a group of patients with ALL/BL to determine whether some types of mutants were more frequent in this selected group of patients. METHODS: We selected a group of 16 patients with acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) in order to investigate the presence of p53 mutations. DNA obtained from affected organs (bone marrow, lymph node and a renal mass) was used for the molecular studies. Single-strand conformation polymorphism (SSCP) analysis of exons 5 to 9 of the gene was used to detect p53 mutants. After detecting an abnormal migration pattern on the SSCP, mutations were determined by direct sequencing. RESULTS: Point mutations were found in eight patients; a misense mutation in seven cases and a non-sense mutation in one case. The normal allele was also identified in 7 mutated samples. The same mutation at codon 282 was identified in three different patients, in whom an identical conformer was detected after SSCP analysis. Mutation at codon 282 was present in an extramedular relapse (renal) appearing after a BMT. No such alteration was present in the bone marrow analyzed at the same time. INTERPRETATION AND CONCLUSIONS: Our findings suggest that p53 mutations are quite frequent in recognized clinical groups. The criteria chosen in this study allowed us to identify a high percentage of the samples with mutation. Different malignant phenotypes could be determined by functional heterogeneity of p53 mutants.

Mutational analysis of RAG-1 in lymphoid malignancies.

Illegitimate recombinase activity promoted by the recombination activating RAG-1 and RAG-2 is assumed to be involved in the pathogenesis of the chromosomal translocations observed in lymphoid neoplasias. We analyzed the complete coding region of the RAG-1 gene in patients with lymphoid neoplasis using a multiple PCR-SSCP (single strand conformation polymorphism) strategy. Nine multiple myelomas, 17 non-Hodgkin's lymphomas, 18 acute lymphocytic leukemias, 37 chronic lymphocytic leukemias and 33 non-neoplastic controls were studied. To screen the entire RAG-1 gene we used primers overlapping genomic segments of the RAG-1 coding sequence (nucleotides 87 to 3311). Samples with an abnormal band pattern in the SSCP were cloned and sequenced. Successful amplification was achieved with our protocol. The multiple PCR-SSCP analysis proved to be a feasible and sensitive strategy for studying variations in the sequence of the RAG-1 gene. No mutations other than the three previously reported sequence variations were detected. Although mutations in this gene do not appear to be common in lymphoid neoplasias, it would be interesting to ascertain whether the different variant forms of RAG-1 protein have an abnormal recombinase activity.

Acute rhabdomyolysis complicating viridans streptococcal shock syndrome.

A 20-year-old male underwent an allogeneic bone marrow transplantation for acute myelogenous leukemia after conditioning with cyclophosphamide and total body irradiation. On day +6 of the procedure, he developed fever, chills and myalgias. Empiric treatment with ceftazidime and amikacin was begun, and blood cultures grew viridans streptococci. Biochemical changes suggestive of acute rhabdomyolysis were evident. Within 24 h, adult respiratory distress syndrome with multiorgan failure appeared, and he died 7 days later. At autopsy, the presence of rhabdomyolysis was confirmed.

Treatment of refractory and relapsed adult acute leukemia using a uniform chemotherapy protocol.

Twenty-nine adult patients with relapsed (21) or refractory (8) de novo acute leukemia (12 ALL and 17 ANLL) were treated with a remission-induction salvage chemotherapeutic protocol including vindesine, mitoxantrone, cyclophosphamide, intermediate-dose cytosine arabinoside, prednisolone and methotrexate. Ten of seventeen (59%) ANLL and 8/12 ALL (67%) achieved complete remission (CR). Seven of eight (86%) cases refractory to first-line remission-induction therapy (3/4 ANLL and 4/4 ALL) entered complete remission. The most frequent non-hematologic side effects were gastrointestinal. All patients experienced severe pancytopenia, with median times to recovery of granulocyte and platelet counts of 28 and 29 days, respectively. Nine of twenty-nine (31%) patients suffered febrile episodes of unknown origin and 13/29 (45%) suffered documented infections. Five patients (17%) died while aplastic, four from infection and one from cardiotoxicity. Four patients who entered CR were submitted to a bone marrow transplantation (BMT), two autologous and two allogeneic BMT. Sixteen of the 18 patients who entered CR relapsed, with a median remission duration of 3.5 +/- 2.9 months. Two patients remain in remission at 5+ and 17+ months. These results suggest that this protocol is an effective remission-induction salvage therapy for adult acute leukemias.