Evaluation of right ventricular function performed by 3D-echocardiography in scleroderma patients.

The impairment of the right ventricle (RV) in systemic sclerosis (SSc) is usually related to pulmonary arterial hypertension (PAH). New echocardiographic techniques, such as 3-dimensional echocardiography (3DE) and 2-dimensional speckle tracking (2DSTE), allow an accurate evaluation of the RV function. The aim of this study was to evaluate the RV function using 3DE and 2DSTE in SSc patients with no history of heart disease and no PAH. Forty-five SSc patients, 42 females and 3 males, 28 with limited cutaneous SSc (lcSSc) and 17 with diffuse cutaneous SSc (dcSSc), were studied. Forty-three age- and gender-matched healthy subjects were enrolled as controls. All of them underwent a 3DE and 2DSTE ecocardiographic evaluation of the RV function. Systolic pulmonary arterial pressure (sPAP) and total pulmonary vascular resistance (tPVR) were also estimated by power doppler. RV echocardiographic parameters were compared in the different subsets of SSc patients. A statistical analysis was performed by t-test, ANOVA and multiple logistic regression. RV areas in 2DSTE and volumes in 3DE were higher and RV function parameters were reduced in SSc patients compared with controls. Also sPAP and tVPR were higher, but they did not reach pathological values. Echocardiographic alterations were more pronounced in patients with lcSSc. 3DE and 2DSTE echocardiography allowed us to detect morphological and functional alterations of the RV in a group of SSc patients with no clinical signs of heart disease and no PAH. These patients had significantly higher sPAP and tPVR than healthy controls without reporting values compatible with PAH. These data suggest that RV alterations are related to a pressure overload rather than to an intrinsic myocardial involvement in SSc.

Seasonal dynamics of megafauna on the deep West Antarctic Peninsula shelf in response to variable phytodetrital influx.

The deep West Antarctic Peninsula (WAP) shelf is characterized by intense deposition of phytodetritus during spring/summer months, while very little food material reaches the seafloor during winter. The response of the shelf benthic megafauna to this highly variable food supply is still poorly understood. In order to characterize the deposition of phytodetritus and the megabenthic community response, we deployed a seafloor time-lapse camera at approximately 590 m depth on the mid WAP shelf west of Anvers Island for 15 months. Seafloor photographs were taken at intervals of 12 or 24 h nearly continuously from 9 December 1999 (austral winter) to 20 March 2001 (summer) and analysed for phytodetritus deposition and megafaunal dynamics. Seafloor images indicated a marked seasonal arrival of greenish phytodetritus, with large interannual and seasonal variability in the coverage of depositing phytodetrital particles. The surface-deposit-feeding elasipod holothurians Protelpidia murrayi and Peniagone vignoni dominated the epibenthic megafauna throughout the year, frequently constituting more than 80% of the megafaunal abundance, attaining total densities of up to 2.4 individuals m(-2). Elasipod abundances were significantly higher in summer than winter. During summer periods of high phytodetrital flux, Pr. murrayi produced faecal casts at higher rates, indicating intensified population-level feeding activity. In March-June 2000, faecal casts lasted longest, suggesting lower horizontal bioturbation activity during autumn-winter. Our data indicate that the Pr. murrayi population increases its feeding rates in response to increasing amounts and/or lability of organic matter on the sediment surface. Assuming that this species feeds on the top millimetre of the sediment, we estimate that, during periods of high phytodetrital flux, the Pr. murrayi population reworks one square metre of sediment surface in approximately 287 days. We suggest that Pr. murrayi is an important species for organic-carbon recycling on the deep WAP shelf, controlling the availability of deposited labile phytodetritus to the broader shelf benthic community.

Erratum: Seasonal dynamics of megafauna on the deep West Antarctic Peninsula shelf in response to variable phytodetrital influx.

[This corrects the article DOI: 10.1098/rsos.140294.].

[Intravenous immunoglobulins in the treatment of glomerulopathies]. / Le immunoglobuline EV nella terapia delle glomerulopatie.

Intravenous high-dose immunoglobulin (IVIG) therapy is used in several antibody-mediated diseases including Guillain-Barré syndrome, idiopathic thrombocytopenic purpura, and autoimmune neuropathies. In the last decade, numerous studies have evaluated the application of IVIG therapy in autoimmune glomerulopathies such as lupus nephritis, membranous glomerulonephritis, and transplant-related chronic nephropathy. These studies were conducted on small numbers of patients and varied with respect to IVIG doses and duration of therapy cycles. Furthermore, many of the patients included in the studies did not respond to conventional therapies, were affected by complications, and had impaired renal function. IVIG therapy was able to reduce proteinuria and inflammation and improve renal function in some forms of glomerulonephritis, particularly LES-related forms. IVIG therapy was also tested in patients awaiting kidney transplantation and in patients affected by transplant-related chronic nephropathy: in both groups the results were controversial. Seventy-eight cases of IVIG-related nephrotoxicity have been reported in the literature. In most cases the toxic effect was reversible and observed in patients with pre-existing renal failure treated with IVIG formulations containing saccharose. IVIG could have beneficial effects in many glomerulopathies. Nevertheless, further trials are needed to clarify the potential and the limitations of this therapeutic approach.

Effects of fluvastatin treatment on lipid profile, C-reactive protein trend, and renal function in dyslipidemic patients with chronic renal failure.

The purpose of this trial was to evaluate the effects of fluvastatin on the lipid pro-file and on renal function, as measured by creatinine clearance, in dyslipidemic patients with chronic renal failure. In this 8-month prospective, open-label, randomized, parallel-group trial, 130 patients (70 men and 60 women), after a 2-month washout period following previous lipid-lowering treatments, were randomly assigned to fluvastatin XL 80 mg given once daily (80 patients) or to standard treatment (50 patients). Mean total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride values after 3 and 6 months of treatment with fluvastatin showed statistically significant improvement compared with standard treatment. Improved renal function, as measured by creatinine clearance, was observed at the end of the 6-month treatment period in approximately 65% of patients treated with fluvastatin. The increase in creatinine clearance consistently reached 10% to 15% of baseline values. A statistically significant reduction in C-reactive protein (CRP) over baseline values was observed in approximately 75% of patients treated with fluvastatin. Furthermore, mean values of CRP for the fluvastatin standard treatment groups, respectively, were 6.78 and 10.19 at 3 months and 4.47 and 11 at 6 months. Both treatments were well tolerated. No major adverse events were noted. Results of this study suggest that fluvastatin treatment in patients with chronic renal failure is effective in improving the lipid profile, and it demonstrates good safety and tolerability. Furthermore, fluvastatin may contribute to improved nephroprotection in this patient population.

Embryonal rhabdomyosarcoma with only numerical chromosome changes. Case report and review of the literature.

An embryonal rhabdomyosarcoma, presenting as a retroperitoneal mass in a 15-year-old girl, is reported. The histological and immunohistochemical picture was typical, except for the presence of focal chondroid differentiation. Interestingly, expression of the "muscle markers" desmin and alpha-sarcomeric actin was present in the latter areas. Cytogenetic analysis showed a hyperdiploid karyotype without structural chromosome changes. The pertinent literature on the subject is reviewed. Hyperdiploidy of the clonal type seems to occur frequently, but no characteristic karyotype is so far emerging.

Deletion of HMG17 in uterine leiomyomas with ring chromosome 1.

Uterine leiomyomas are characterized by several subgroups with characteristic chromosomal aberrations, mainly 12q14-15, 6p21, or interstitial deletions of chromosomes 3 and 7. For the first two subgroups, aberrations of the HMGIC and HMGIY genes have been described and are held responsible for tumor initiation. For other subgroups no molecular findings have been described as of yet. We focus here on a smaller subgroup of uterine leiomyomas with a ring chromosome 1 either as the only karyotypic deviation or occurring along with other abnormalities. In the p-arm of chromosome 1 HMG17, another member of the high-mobility group of proteins has been localized to the short arm of chromosome 1 (1p35) with two PAC clones on metaphase spreads of a uterine leiomyoma ring(1). Hybridization signals for these probes were not detected within the ring chromosome consistent with loss or deletion of HMG17. These findings suggest that HMG17 does not play a mechanistic role in leiomyoma similar to that observed with other high-mobility proteins.

Intracranial germ cell tumour (embryonal carcinoma with teratoma) with complex karyotype including isochromosome 12p.

We report the chromosomal characteristics of a malignant teratoma with embryonal carcinoma component located in the pineal region of a 15-year-old boy. Chromosome analysis showed a near-triploid complex karyotype (62 chromosomes), including two copies of an isochromosome 12p, confirmed by fluorescence in situ hybridization analysis. The present findings indicate that isochromosome 12p formation is probably associated with the development of malignant germ cell tumours.

Histology may depend on the presence of partial monosomy or partial trisomy 3 in renal cell carcinoma.

Rearrangements of 3q were found in 10% of a series of 230 cases of renal cell carcinoma (RCC). Together with observations from the literature, these structural changes can be concluded to involve two different regions, 3q21 and 3q11-12, and are usually present as unbalanced translocations. In some of these cases of RCC with the translocation, the normal chromosome 3 may reduplicate, giving rise to a partial trisomy 3q instead of a partial monosomy 3. In those cases, however, histology shows chromophilic-papillary RCC instead of clear cell-nonpapillary. Hence, besides the still unresolved underlying molecular changes causing RCC, histology may in part depend on the presence of partial monosomy or partial trisomy 3.

An important subgroup of phyllodes tumors of the breast is characterized by rearrangements of chromosomes 1q and 10q.

From a study of 10 cases of our own and 13 cases of the literature, anomalies of chromosome 1q and 10q emerge as consistently occurring changes in an important subgroup of phyllodes tumors of the breast. Anomalies of chromosome 1 were the most frequent ones, with a gain of 1q material, and histologically the tumors in which these anomalies were found were low grade malignancies. Structural changes of 10q emerged as the second most frequent chromosome change.

Lesions of 13q may occur independently of deletion of 16q in spindle cell/pleomorphic lipomas.

AIMS: Very recent multidisciplinary investigations have allowed for the definition among lipomas of a clinical and histological subtype called spindle cell and/or pleomorphic lipoma, possibly associated with partial monosomy 16 and anomalies of chromosome 13. In order to get nearer to the underlying critical molecular changes further multidisciplinary pathological and genetic research is indicated, to identify which chromosome(s) anomalies are crucial in the development of these tumours. METHODS AND RESULTS: In an ongoing multidisciplinary study of lipomatous tumours, including clinical findings, morphology, histochemistry and cytogenetics, two instances were found of spindle cell lipoma with clonal chromosome changes. In both cases chromosome 13 was involved, whereas only one showed a partial monosomy 16. CONCLUSIONS: Partial monosomy 16 is a characteristic lesion in spindle cell lipoma, usually associated with anomalies of chromosome 13. The present report confirming a previous single observation indicates, however, that lesions of 13 may occur independently from lesions of 16, suggesting different underlying molecular lesions in these otherwise very similar lipomas.

Hamartoma of the breast with involvement of 6p21 and rearrangement of HMGIY.

The first description of involvement of 6p21 and rearrangement of HMGIY in a hamartoma of the breast is in keeping with the emerging role of HMG genes in benign mesenchymal tumors.

Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia.

Human herpesvirus type-8 (HHV-8) is a lymphotropic herpesvirus originally identified in Kaposi's sarcoma. Among lymphoproliferative disorders, HHV-8 infection is restricted to body-cavity-based lymphoma (BCBL) and multicentric Castleman's disease (MCD). BCBL are B-cell lymphomas growing in liquid phase in the body cavities and most frequently associated with AIDS. BCBL express indeterminate phenotypes, in all cases are associated with HHV-8 infection, and frequently carry Epstein-Barr virus genomes in the absence of c-MYC rearrangements or other genetic lesions characteristic of B-cell lymphomas. The clinical outcome of BCBL is poor with a median survival of only few months. MCD is an atypical lymphoproliferative disorder which displays marked vascular hyperplasia and is commonly associated with Kaposi's sarcoma. HHV-8 infection occurs in 100% of AIDS-related MCD and in approximately 40% of AIDS-unrelated cases. Overall, the consistency of HHV-8 infection in BCBL and MCD, its selectivity throughout the spectrum of lymphoproliferative disorders and the high copy number of HHV-8 DNA sequences in infected cells suggest that the virus plays a pathogenetic role in these disorders.

AIDS-related Burkitt's lymphoma. Morphologic and immunophenotypic study of biopsy specimens.

In patients infected with HIV, high-grade B-cell non-Hodgkin's lymphomas (NHL), including the small noncleaved cell (SNCC) category, exhibit pleomorphic features, which makes precise definition difficult. Sixty-nine pathologic specimens with HIV-related systemic lymphomas, including 42 SNCC, 20 immunoblastic lymphomas (IBL), and 7 cases with features "intermediate" between SNCC and IBL were morphologically and immunophenotypically investigated. The host immune status was also analyzed in 57 of 69 patients. In 29 representative SNCC lymphomas, in 9 IBL cases, and an additional 3 intermediate lymphomas, both p53 protein overexpression and the association of Epstein-Barr virus (EBV) genetic information were assessed. Small noncleaved cell lymphomas included tumors exhibiting features of the 2 established subtypes (27 Burkitt's and 15 non-Burkitt's). In the seven intermediate cases, cells showed features intermediate between SNCC with plasmablastic differentiation and immunoblasts plasmacytoid. Immunoblast-like cells were also present. p53 protein overexpression and EBV association were found in a proportion of SNCC (14 of 29; 7 of 29) and intermediate (3 of 3; 2 of 3) lymphomas. Conversely, IBL cases were consistently p53 negative, but showed a high EBV association (7 of 9). All the evaluated patients with intermediate lymphomas had a considerably lower mean (76.6 per mm3 +/- 77.4 SD) and median (54 per mm3) number of CD4+ lymphocyte count than SNCC patients (mean 227.9 per mm3 +/- 186.9 SD, median 193 per mm3), thus mirroring IBL patients (mean 95.3 per mm3 +/- 82.8 SD, median 81 per mm3). All data provide evidence that lymphomas showing intermediate features constitute a distinct subgroup from either SNCC or IBL.