Nanostructured fluids from degradable nonionic surfactants for the cleaning of works of art from polymer contaminants.

Nanostructured fluids containing anionic surfactants are among the best performing systems for the cleaning of works of art. Though efficient, their application may result in the formation of a precipitate, due to the combination with divalent cations that might leach out from the artifact. We propose here two new aqueous formulations based on nonionic surfactants, which are non-toxic, readily biodegradable and insensitive to the presence of divalent ions. The cleaning properties of water-nonionic surfactant-2-butanone (MEK) were assessed both on model surfaces and on a XIII century fresco that could not be cleaned using conventional methods. Structural information on nanofluids has been gathered by means of small-angle neutron scattering, dynamic light scattering and nuclear magnetic resonance with diffusion monitoring. Beside the above-mentioned advantages, these formulations turned out to be considerably more efficient in the removal of polymer coatings than those based on anionic surfactants. Our results indicate that the cleaning process most likely consists of two steps: initially, the polymer film is swollen by the MEK dissolved in the continuous domain of the nanofluid; in the second stage, surfactant aggregates come into play by promoting the removal of the polymer film with a detergency-like mechanism. The efficiency can be tuned by the composition and nature of amphiphiles and is promoted by working as close as possible to the cloud point of the formulation, where the second step proceeds at maximum rate.

Activation of the NF-kappaB signalling pathway in diffuse large B-cell lymphoma: clinical implications.

AIM: To characterize the activation of the nuclear factor (NF)-kappaB pathway in diffuse large B-cell lymphoma (DLBCL) by immunohistochemistry. METHODS AND RESULTS: Sixty-six DLBCLs treated with anthracycline-containing chemotherapy were evaluated with antibodies against phosphorylated p65 (P-p65), p65, p50, p52, IKK alpha, and phosphorylated I kappaB (P-I kappaB). NF-kappaB activation was based on the expression of P-p65, P-I kappaB, and nuclear expression of p65 or p52 in the tumour cells. P-p65 and P-I kappaB were expressed in 13 (20%) and 17 cases (26%), respectively. p65, p52 and IKK alpha were found in the cytoplasm. A correlation was found between expression of P-p65 and P-I kappaB (P < 0.0001), but not between the two subtypes of DLBCL [germinal centre B cell and non-germinal centre (GC)]. P-p65+ tumours showed a better response to chemotherapy (P = 0.025) and a trend to increased event-free survival (P = 0.08). However, P-I kappaB expression was not associated with either clinical response or survival. Bcl-2 was not preferentially expressed on DLBCL tumours with NF-kappaB activation, as determined by expression of P-p65 and P-I kappaB proteins. CONCLUSIONS: NF-kappaB activation in DLBCL is preferentially mediated through the classical pathway and a novel mechanism involving phosphorylation of p65. Activation of NF-kappaB by P-p65 is associated with good prognosis. NF-kappaB activation is not confined to non-GC DLBCL exclusively.

Hematopoyesis extramedular cutánea en mielofibrosis idiopática: a propósito de un caso / A case of cutaneous extramedullary hematopoiesis associated with idiopathic myelofibrosis

La hematopoyesis extramedular cutánea es una manifestación infrecuente de los procesos mieloproliferativos crónicos, principalmente de la mielofibrosis crónica idiopática. En el adulto se manifiesta como máculas, pápulas, nódulos y úlceras en el tronco. La aparición suele darse poco después del diagnóstico y todavía es una cuestión debatida la posible relación entre la esplenectomía y la aparición de los focos de hematopoyesis extramedular. El diagnóstico se realiza mediante estudio histopatológico y la visualización de un infiltrado compuesto por diferentes combinaciones de precursores mieloides, eritroides y células megacariocíticas. El tratamiento es sintomático y el propio de la enfermedad de base. Aportamos un nuevo caso asociado a mielofibrosis crónica idiopática que a los 9 años del diagnóstico presentó focos de hematopoyesis extramedular cutánea. Dichas lesiones siguieron un curso progresivo, desarrollando posteriormente una leucemia mieloide aguda (AU)

Cutaneous extramedullary hematopoiesis is a rare manifestation of chronic myeloproliferative processes, mainly chronic idiopathic myelofibrosis. In adults, it manifests as macules, papules, nodules, and ulcers on the trunk. The lesions usually appear soon after diagnosis and the possibility of a relationship between splenectomy and the appearance of extramedullary foci of hematopoiesis is still debated. Diagnosis is based on histopathology showing an infiltrate with different combinations of myeloid and erythroid cell precursors and megakaryocytes. Symptomatic treatment is provided alongside treatment of the underlying disease. We report a new case associated with chronic idiopathic myelofibrosis in which foci of cutaneous extramedullary hematopoiesis were observed 9 years after initial diagnosis. The lesions were progressive and the patient went on to develop acute myeloid leukemia (AU)

[A case of cutaneous extramedullary hematopoiesis associated with idiopathic myelofibrosis]. / Hematopoyesis extramedular cutánea en mielofibrosis idiopática: a propósito de un caso.

Cutaneous extramedullary hematopoiesis is a rare manifestation of chronic myeloproliferative processes, mainly chronic idiopathic myelofibrosis. In adults, it manifests as macules, papules, nodules, and ulcers on the trunk. The lesions usually appear soon after diagnosis and the possibility of a relationship between splenectomy and the appearance of extramedullary foci of hematopoiesis is still debated. Diagnosis is based on histopathology showing an infiltrate with different combinations of myeloid and erythroid cell precursors and megakaryocytes. Symptomatic treatment is provided alongside treatment of the underlying disease. We report a new case associated with chronic idiopathic myelofibrosis in which foci of cutaneous extramedullary hematopoiesis were observed 9 years after initial diagnosis. The lesions were progressive and the patient went on to develop acute myeloid leukemia.

Clinical utility of bone marrow flow cytometry in B-cell non-Hodgkin lymphomas (B-NHL).

AIM: To determine the efficacy of flow cytometry (FC) in the assessment of bone marrow (BM) in B-cell non-Hodgkin lymphoma (B-NHL). FC is a common practice, but is far from being validated. METHODS AND RESULTS: Morphological analysis and FC immunophenotyping were performed on 421 samples. T-cell lymphomas, Hodgkin's disease, chronic lymphocytic leukaemia and hairy cell leukaemia were not included in the study. Clonality was assessed by the standard kappa/lambda/CD19 test. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. A double-step procedure was employed in all cases to increase the sensitivity of the FC procedure. Of 380 evaluable samples, 188 corresponded to follicular lymphoma (FL), 58 to diffuse large B-cell lymphoma (DLBCL), 57 to mantle cell lymphoma (MCL), seven to Burkitt's lymphoma and the remaining 70 samples to other low-grade lymphomas. Morphological marrow infiltration was found in 148 cases, and flow immunophenotyping identified 138 cases with BM involvement. A concordance between the two methods was detected in 298 cases (79%). There was a discordance in 82 cases (21%): morphology positive/FC negative in 46 cases and morphology negative/FC positive in 36 (61% of all cases with discordance were from FL). There was no difference in outcome when patients with discordances were compared with patients without discordances. CONCLUSIONS: Most samples showed concordance between morphological and FC results. FC identified BM involvement in the absence of morphological infiltration. Morphology/FC discordance seems to have no influence on the outcome of FL patients.

Insertion of the CCND1 gene into the IgH locus in a case of leukaemic small cell mantle lymphoma with normal chromosomes 11 and 14.

The t(11;14)(q13;q32) translocation is considered to be the cytogenetic hallmark of mantle cell lymphoma. This report describes a case of leukaemic mantle cell lymphoma in which conventional cytogenetics on stimulated peripheral blood cells showed a 46,XY, t(1;12)(p21;q23)/46,XY karyotype. Fluorescence in situ hybridisation analysis using a dual colour immunoglobulin heavy chain (IgH)/CCND1 probe showed a fusion hybridisation signal on one normal chromosome 14, indicating that an insertion of the CCND1 gene into the 14q32/IgH locus had taken place. Overexpression of the cyclin D1 protein was demonstrated on bone marrow trephine by immunohistochemical staining.

Sézary syndrome and related variants of classic cutaneous T-cell lymphoma. A descriptive and prognostic clinicopathologic study of 29 cases.

Large series of patients with Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), have been reported infrequently because of its low incidence. Here we recorded several clinical, histopathological and immunophenotypical features of 29 cases of leukemic CTCL patients from four Dermatology Departments of Catalonia, Spain, and analyzed their prognostic value. Clinical data included sex, age, delay of SS diagnosis, previous diagnosis of lymphoma, B-symptoms, type of skin lesions, peripheral adenopathy, histologic evaluation of lymph node biopsy, visceral involvement, percentage of circulating Sézary cells, serum LDH and beta-2-microglobulin levels, first treatment and response, disease-free interval, further therapies and survival. Histopathological data examined were epidermotropism, depth and thickness of the infiltrate, cell size, adnexal involvement, presence of granuloma, eosinophils and plasma cells, mitotic rate. The percentage of CD45Ro, CD43, CD20, CD30 and CD8 positive dermal cells were also recorded. Survival showed a mean actuarial risk of 57% at 3 years and 38% at 5 years, with a median survival of 48 months. Analysis of actuarial survival demonstrated as following as features linked with a bad prognosis: fast evolution of the disease (from symptoms onset up to diagnosis) (p = 0.0274) raised levels of serum lactate dehydrogenase (p = 0.0379) and beta-2-microglobulin (p = 0.0151), the latter being the most important prognostic factor. In conclusion although SS had been traditionally considered as a low-grade lymphoma, the present study agrees with the recent classification rating SS as an aggressive type of CTCL with a poor prognosis. Our results show that some simple clinical and blood test data can be useful as prognostic indicators in this disease.

Flow cytometry using the monoclonal antibody CD10-Pe/Cy5 is a useful tool to identify follicular lymphoma cells.

Follicular lymphoma (FL) is a specific entity defined by characteristic histology, phenotype and molecular rearrangements. Classically, reactivity for CD19, CD10, and strong positivity for the surface light chain immunoglobulin (SIg) are considered to be phenotypic signs typically expressed in FL. In practice, this pattern is difficult to identify since most neoplastic cells analysed by flow cytometry (FC) show weak intensity for CD19-Pe/Cy5 and for SIg and negativity for CD10-FITC. We used triple antigen combinations including two monoclonal antibodies (MoAbs) against CD10 (CD10-FITC and CD10-Pe/Cy5) and a long-distance polymerase chain reaction (PCR) approach to establish the phenotypic pattern of neoplastic cells carrying t(14;18)(q32;q21). Neoplastic cells showed the following immunophenotype: stronger reactivity against CD20 than against CD19, positivity for CD22 and SIg and negativity for CD5, CD11c and CD10-FITC. Characteristically, CD10-Pe/Cy5 was expressed in all the samples with positive bcl-2/JH rearrangements. In FL, there was a high correlation between histologic diagnosis and reactivity against CD10-Pe/Cy5 (96% cases). In diffuse large cell lymphomas (DLCL), CD10-Pe/Cy5 identified positive cases with t(14;18)(q32;q21) chromosomal translocation, whereas Burkitt lymphomas showed all cases reactivity against CD10-Pe/Cy5. In conclusion, CD10-Pe/Cy5 is a useful antibody for identifying neoplastic cells carrying t(14;18)(q32;q21) in FL and DLCL. In combination with other MoAbs, anti-CD10 (HI10a, Cy-Chrome) can be used to identify a characteristic phenotypic profile of FL against other lymphoproliferative disorders.

Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.

BACKGROUND: Because myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens. METHODS AND RESULTS: Forty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage. CONCLUSIONS: Apoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

Invisible mycosis fungoides: A diagnostic challenge.

We describe a 76-year-old woman who presented persistent generalized pruritus as the only cutaneous manifestation of a cutaneous T-cell lymphoma (mycosis fungoides). No cutaneous lesions were observed throughout the patient's course. Skin biopsies obtained from normal-looking pruritic skin revealed a discrete perivascular lymphocytic infiltrate in the upper dermis and focal intraepidermal clusters of atypical lymphoid cells (Pautrier's microabscesses). PCR analysis of TCR-gamma gene disclosed a monoclonal T-cell rearrangement. Sequencing of the PCR monoclonal product identified the J(8)V(2)C(2) TCR gene rearrangement. This observation illustrates the existence of a peculiar and exceedingly rare form of mycosis fungoides characterized only by persistent pruritus unresponsive to several therapeutic approaches. The diagnostic difficulties of this rare variant are stressed.

Semiinvasive pulmonary aspergillosis in chronic obstructive pulmonary disease: radiologic and pathologic findings in nine patients.

OBJECTIVE: The purpose of this study is to assess the radiographic, thin-section CT, and histologic findings of semiinvasive aspergillosis in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: The study included nine patients with COPD seen at the Hospital de Sant Pau during a 3-year period who had histopathologically proven aspergillosis with tissue invasion. Chest radiography and thin-section (2-mm collimation) CT of the chest were available in all cases. RESULTS: Nine patients had semiinvasive aspergillosis proven at autopsy (n = 7) or by thoracoscopically guided lung biopsy (n = 2). The radiologic findings consisted of parenchymal consolidation (n = 6) and nodules larger than 1 cm in diameter (n = 3). Parenchymal consolidation involved the upper lobes in five patients and was bilateral in four. Cavitation was present in two of the patients with consolidation and in two of the patients with nodular opacities. Adjacent pleural thickening was revealed by CT in four patients. Histologically, the areas of consolidation represented active inflammation and intraalveolar hemorrhage containing Aspergillus organisms. In the three patients with multiple cavitated nodules, a variable degree of central necrosis was observed. The inflammatory infiltrate extended into the surrounding lung parenchyma, and adjacent areas of hemorrhage were also seen. Aspergillus colonies were identified within the lung tissue. CONCLUSION: Upper lobe consolidation or multiple nodules in patients with COPD should raise the possibility of semiinvasive aspergillosis.

Hydatid pulmonary embolism from a ruptured mediastinal cyst: high-resolution computed tomography, angiographic, and pathologic findings.

Hydatid disease is a parasitic infestation caused by the larval stage of a tapeworm of the genus Echinococcus. This report describes an extremely rare complication of echinococcal disease in which severe pulmonary hypertension developed after massive hydatid pulmonary embolism.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation.

OBJECTIVES: The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND: Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS: In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS: Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS: The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

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).