Prevalence of human herpesvirus-6 chromosomal integration (CIHHV-6) in Italian solid organ and allogeneic stem cell transplant patients.

The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5%) of 135 solid organ transplant (SOT) and 16 (22.8%) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9%) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6.

Urinary excretion of low molecular weight proteins in patients with pure monoclonal light chain proteinuria.

BACKGROUND: Because urinary low molecular weight protein (LMWP) measurement shows changes in renal integrity at an early stage, beta2-microglobulin (B2m), retinol-binding protein (RBP) and alpha1-microglobulin (A1m) were evaluated in 24-hour urine collection of 65 patients with pure monoclonal light chain (MLC) proteinuria and in 47 patients with different kidney diseases (DKDs) for comparison. METHODS AND RESULTS: Albumin, kappa, lambda, A1m and B2m were measured by immunonephelometry. RBP was determined by ELISA. The mean values of LMWP quantitation were significant for origin of the disease (MLC and DKD) (p<0.05) and renal failure (RF) (p<0.001) (MANOVA). Tukey HSD test only showed significant differences for LMWP between MLC patients with RF and DKD patients without RF. The mean value of A1m was different between patients with and without RF in each group (p<0.05 for MLC, and p<0.01 for DKD). In the group without RF, the frequency of A1m excretion above 12 mg/L differed between MLC patients and DKD patients (p<0.01). CONCLUSION: A tubular dysfunction occurred in a great number of patients excreting pure MLC even in those with well-preserved renal function, as it did in patients with DKDs. In patients with MLC without RF, A1m might be measured for the early recognition of tubular involvement.

IgG1-kappa biclonal gammopathy associated with multiple myeloma suggests a regulatory mechanism.

Multiclonal gammopathies associated with multiple myeloma may result either from a neoplastic transformation of a cell clone undergoing immunoglobulin class switching or from independent transforming events yielding proliferation of unrelated plasma cell clones. The simultaneous presence of more than one neoplastic clone may possess regulatory implications in terms of cell proliferation, clonal expansion, secretion of M-components or response to chemotherapy. We report a patient, diagnosed with multiple myeloma stage IIIa, who presented with two well-defined homogeneous IgG1-kappa components in the serum (designated WER-1 and WER-2) with striking differences in their plasma concentration and response to the classic melphalan/prednisone treatment. Immunochemical characterization and amino terminal sequence analysis of both the heavy and light chains of each M-component undoubtedly determined their biclonal origin. WER-1 was identified as IgG1(VHII)-kappaI while WER-2 was classified as IgG1(VHIII)-kappaIII. The plateau phase was characterized by very low or undetectable levels of WER-2, a high, almost constant, concentration of WER-1 and the absence of Bence Jones proteinuria, whereas these parameters were completely reversed during the escape phase with levels resembling those observed at the time of diagnosis. The statistically significant negative correlation between the biclonal components and the different susceptibility to the treatment clearly suggests regulatory interactions between the clones WER-1 and WER-2.

[Color Doppler echography in the diagnosis of deep venous thrombosis of the lower limbs]. / L'ecocolordoppler nella diagnosi della trombosi venosa profonda degli arti inferiori.

Deep venous thrombosis (DVT) is a common and severe disease which can produce a pulmonary embolism as an acute consequence and post-phlebitic syndrome as a late complication. Since DVT symptoms and clinical features are almost no sensitive and specific, its diagnosis is usually achieved by instrumental exams. Until few years ago phlebography was considered the "gold standard" diagnostic test, although its invasivity prevented it from becoming routinely used in symptomatic and non-symptomatic patients. The aim of our study was to emphasize the usefulness of echo color Doppler (ECD), a non-invasive method, as a first-choice exam to diagnose and manage the therapy of DVT symptomatic patients and to address an early diagnosis in high risk non-symptomatic patients. We studied 375 patients, aged from 13 months to 92 years. In most of the cases patients were seen because suffering from DVT symptoms, after surgery, or because suspected to have a pulmonary embolism. All the patients underwent a venous ECD of the lower limbs, whereas 16 of them had also a phlebography. ECD disclosed an acute DVT in 15% of the patients and a chronic DVT in 3% of them, whereas 17% of the cases were diagnosed as having other pathologies which can clinically mimic a DVT. ECD sensitivity and specificity is higher than that of other exams, both invasive and non invasive, as it allows a thorough assessment of both iliac and distal vessels, a better detection of non-occluding wall thrombi, and has been found to be very helpful in the evaluation of chronic DVT changes.

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL (AU)

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL

[Autoimmune hypoglycemia syndrome with specific anti-human insulin antibodies]. / Síndrome de hipoglucemia autoinmune con anticuerpos específicos anti-insulina humana.

A 33 year old woman with episodes of severe hypoglycemia is presented. The studies showed anti-insulin antibodies and variable C-peptide levels. Circulating insulin measured after acid-ethanol extraction, was of 1,600 uU/ml and shown to be human insulin after characterization by HLPC. Specific anti-human insulin antibodies were of high affinity (Ka1: 6.20 x 10(10) M-1; Ka2: 2.42 x 10(9) M-1). A small cross-reactive porcine and bovine antibody subpopulation was also detected (IgG, light k type chain). Plasmapheresis was undertaken when symptoms were spontaneously declining and turned antibody title negative. Prolonged follow-up showed no relapse of this syndrome.

[Diagnostic efficacy of albumin gradient in different causes of ascitis]. / Eficacia diagnóstica del gradiente de albumina en distintas causas de ascitis.

The aim of this study was to compare the serum-ascites albumin gradient (GS-A) to the transudate-exudate concept in the classification of ascites. The second objective was to analyze the predictive value and efficacy of GS-A, ascites total protein, LDH, Ratio and ascites cholesterol in patients with liver disease and malignant ascites. For this purpose we studied prospectively 98 patients (in prospective form). The transudate-exudate concept classified correctly the causes of ascites only in 65.6% of the patients. In contrast, the GS-A did it 95.7% of the patients. In differentiating ascites caused either by chronic liver disease or by malignancy, the tests with best efficacy were cholesterol (98%), (predictive value 97%) and GS-A efficacy 94% (predictive value 94%). We conclude that GS-A was better than the traditional transudate-exudate concept in classification of ascites. The test with the best efficcacy separating ascites caused by chronic liver disease or by malignancy was the ascites cholesterol.

Eficacia diagnóstica del gradiente de albumina en distintas causas de ascitis. / [Diagnostic efficacy of albumin gradient in different causes of ascitis]

The aim of this study was to compare the serum-ascites albumin gradient (GS-A) to the transudate-exudate concept in the classification of ascites. The second objective was to analyze the predictive value and efficacy of GS-A, ascites total protein, LDH, Ratio and ascites cholesterol in patients with liver disease and malignant ascites. For this purpose we studied prospectively 98 patients (in prospective form). The transudate-exudate concept classified correctly the causes of ascites only in 65.6

of the patients. In contrast, the GS-A did it 95.7

of the patients. In differentiating ascites caused either by chronic liver disease or by malignancy, the tests with best efficacy were cholesterol (98

), (predictive value 97

) and GS-A efficacy 94

(predictive value 94

). We conclude that GS-A was better than the traditional transudate-exudate concept in classification of ascites. The test with the best efficcacy separating ascites caused by chronic liver disease or by malignancy was the ascites cholesterol.

[Alteration of the erythrocyte membrane skeleton by oxidative damage]. / Alteración del esqueleto de la membrana eritrocitaria por daño oxidativo.

In order to assess the alterations mediated by oxidative agents in physiological and pathological conditions, polyacrylamide gel electrophoresis was performed with dodecyl sodium sulphate of red cell membranes previously subjected to oxidative stress with malonyl dialdehyde generation. The alterations of the normal proteic profile observed were related to the concentration and time of exposure to hydrogen peroxide. The red cell membranes were also treated with the following: (1) increasing doses of hydrogen peroxide with and without peroxidase, and (2) supernatant of neutrophils stimulated with digitonin or activated zymosan. No alterations of the membrane skeleton were appreciated under H2O2 treatment; on the contrary, severe alterations appeared after incubation with H2O2 + peroxidase, giving rise to several peptides with different molecular weight. Striking derangement of the proteic structure was induced by activated neutrophils, which was ascribed to release of proteolytic enzymes and activated oxygen compounds.