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D Rossi

Publications and source records attributed to D Rossi.

At least 73 records · Page 4Linked to original sources

Common-variable immunodeficiency-related lymphomas associate with mutations and rearrangements of BCL-6: pathogenetic and histogenetic implications.

Common-variable immunodeficiency (CVI) patients develop non-Hodgkin's lymphomas (NHL), mainly B-lineage diffuse large-cell lymphomas (DLCL), with a high relative risk. The molecular pathogenesis of CVI-related NHL (CVI-NHL) is unknown. Here we aimed at providing a detailed molecular characterization of CVI-NHL. Rearrangements of BCL-6 were detected in two thirds of CVI-NHL cases examined. All 3 CVI-NHL also harbored point mutations of the BCL-6 5' noncoding regions, which constitute a marker of B-cell transit through the germinal center (GC). The number and molecular pattern of BCL-6 mutations in CVI-NHL were similar to that detected in DLCL of immunocompetent hosts and in DLCL arising in other immunodeficiency settings. Microsatellite instability occurred in one CVI-NHL devoid of a BCL-6 rearrangement. All CVI-NHL scored negative for genetic lesions of BCL-2, p53, c-MYC, REL as well as for viral infection by EBV and HHV-8. Overall, these data indicate that: similarly to other immunodeficiency-related NHL, involvement of BCL6 occurs frequently also in CVI-NHL; and because BCL-6 mutations are acquired by B cells during GC transit, their occurrence in CVI-NHL suggest that these lymphomas are histogenetically related to GC B cells.

Adult↗

Steroid and cyclophosphamide in IgA nephropathy.

BACKGROUND: IgA nephropathy is associated with a wide spectrum of possible lesions. Therefore, different responses to anti-inflammatory or immunosuppressive therapies should be expected with acute inflammatory changes, which are predominantly reversible, and with prevalently sclerotic lesions. METHODS: The effects of a combined schedule of prednisone and cyclophosphamide was analysed in the specific subset of IgA nephropathy patients with acute inflammatory histologic changes associated with haematuria and proteinuria. Two groups of patients, with similar histologic lesions and clinical presentation, were considered. The first group (12 patients) was treated within 1 week after renal biopsy; starting with three pulses of methylprednisolone (1 g) followed by oral prednisone (0.8 mg/kg body weight for 2 weeks, 0.6 mg/kg for another 2 weeks, 0.4 mg/kg for an additional 4 weeks, then slowly tapered by 5 mg each month until discontinuation) and 1.5 mg/kg cyclophosphamide for 2 months. A second sample of eight untreated patients served as a control group. Treated and untreated patients had diffuse mesangial proliferation with florid crescents (8-60% in treated and 10-40% in untreated patients) with mild degree of glomerular sclerosis and interstitial changes. Basal creatinine (167 micromol/l, range 79-371 vs 132 micromol/l, range 79-256) and proteinuria (3.0 g/24 h, 1.0-4.9 vs 3.3 g/24 h, 1.0-13.7) were not statistically different between treated and untreated patients respectively. Nine treated and six untreated patients were hypertensive. Blood pressure treatment did not include ACE-inhibitors. RESULTS: Untreated patients' 5-year renal survival, as assessed by the Kaplan-Meier method, was found to be significantly lower than treated patients (37.5 vs 91.6%, log-rank P=0.01 and Breslow test P=0.008; relative risk to reach the endpoint of a 100% increase in serum creatinine=3.58, P=0.03). CONCLUSION: This short course of therapy with prednisone and cyclophosphamide has been effective in a subset of IgA nephropathy patients with florid glomerular changes and major urinary abnormalities, turning off phlogistic activity and preventing subsequent progression toward renal failure.

Adolescent↗

Effects of angiotensin II blockade on nitric oxide blood levels in IgA nephropathy.

BACKGROUND: The effects of renin-angiotensin system blockade on nitric oxide (NO), especially in pathological conditions, are far from being established. The influence of kinins and angiotensin type 2 receptor are largely speculative and based mainly on animal studies. This study was aimed to address these aspects in humans. METHODS: Eight IgA nephropathy patients with documented clinical and histological indicators of poor prognosis were given 50 mg of losartan, 10 mg of enalapril, and 40 mg of the NO donor isosorbide 5 mononitrate (as a control of NO generation) in randomized order for 7 days each. Treatment periods were separated by washout periods of 7 days each. Laboratory investigations were performed before and after each study period. Seven healthy controls received losartan and enalapril according to the same study design. RESULTS: Glomerular filtration rate remained stable while effective renal plasma flow increased with each treatment (P<0.05). Under losartan and enalapril, filtration fraction fell (P=0.02), plasma renin activity increased (P<0.05) and urinary aldosterone concentration decreased (P=0.02). Angiotensin-converting enzyme activity was reduced to the limit of detection under enalapril (P<0.001). Blood NO, detected as nitrosylhaemoglobin by a recently developed technique of spin-trap electron paramagnetic resonance, increased significantly, as expected, during treatment with isosorbide 5 mononitrate (P=0.01), with enalapril (P<0.05), and also with losartan (P<0.05). Unlike losartan, enalapril significantly reduced albuminuria (P=0.01) in this short-term period. In the seven healthy controls, neither enalapril nor losartan were able to increase blood NO levels significantly. CONCLUSIONS: Blood levels of nitrosylhaemoglobin, a surrogate marker of NO, increased under blockade of the renin-angiotensin system in patients with IgA nephropathy, but not in healthy volunteers. This increase could contribute to changes of effective renal plasma flow in renal disease states.

Adult↗

Switching from intracavernous prostaglandin E1 injections to oral sildenafil citrate in patients with erectile dysfunction: results of a multicenter European study. The Sildenafil Multicenter Study Group.

PURPOSE: Intracavernous injection is a well established medical therapy for erectile dysfunction. We assessed the rate of success when patients with erectile dysfunction who were effectively treated with intracavernous injections of prostaglandin E1 were changed to oral therapy with sildenafil citrate. MATERIALS AND METHODS: Only patients effectively managing erectile dysfunction by the intracavernous injection of 20 microg. or less prostaglandin E1 for more than 6 months were eligible for study enrollment. After a 4-week run-in phase while intracavernous prostaglandin E1 therapy continued and a 48-hour washout period 176 patients with erectile dysfunction received open label sildenafil orally for 12 weeks. Satisfaction with treatment was evaluated by the 11-item erectile dysfunction index of treatment satisfaction questionnaire. A successful change to sildenafil was prospectively defined as a questionnaire score of 0 to 100 after sildenafil that was greater than or equal to the score after intracavernous prostaglandin E1. RESULTS: Of the 176 patients 69% (95% confidence limit 62 to 76) successfully changed from intracavernous prostaglandin E1 injections to oral sildenafil and elected to continue oral treatment. Mean satisfaction score after sildenafil and prostaglandin E1 was 73.8 and 63.9, respectively (p <0.001). Only 3 patients (1.7%) discontinued therapy because of treatment related adverse events. CONCLUSIONS: More than two-thirds of the men with erectile dysfunction who were stable on intracavernous injections of 20 microg. or less prostaglandin E1 successfully changed to oral sildenafil, as determined by maintained or enhanced treatment satisfaction.

3',5'-Cyclic-GMP Phosphodiesterases↗

The biology of chemokines and their receptors.

During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection (1). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation (2), B (3), and T (4) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis (5). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines' biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.

Animals↗

Fine-needle percutaneous biopsy of renal masses with helical CT guidance.

PURPOSE: To evaluate the feasibility, accuracy, and clinical role of fine-needle percutaneous biopsy of renal masses, with helical computed tomographic (CT) guidance. MATERIALS AND METHODS: In 63 patients (mean age, 62 years), 73 biopsies were performed. The median tumor size was 4.0 cm. Tumor biopsy was performed with an 18-gauge needle by using helical CT guidance in an outpatient setting. Two to four cores per tumor were obtained. RESULTS: Biopsy material was insufficient for analysis in 15 (21%) procedures. The median tumor size of failed or successful biopsies was 3.0 or 4.8 cm, respectively (P =.03). A benign lesion was found at eight biopsies. Two samples were suspicious for renal cell carcinoma (RCC). RCC was found in 38 biopsy samples. The remainder were transitional cell carcinoma, metastasis, lymphoma, or sarcoma. Twenty-six patients underwent nephrectomy. The accuracies of biopsy for histopathologic and Fuhrman nuclear grade evaluation were 89% and 78%, respectively. For tumors of 3.0 cm or smaller or larger than 3.0 cm, 37% (11 of 30) or 9% (four of 43) had failure of biopsy, respectively (P =.006). No substantial morbidity occurred. CONCLUSION: Fine-needle biopsy with helical CT guidance is accurate for the histopathologic evaluation of renal masses without morbidity. Indications are renal lesions that do not have the typical radiologic features of RCC, Bosniak category III or IV cystic lesions, and locally advanced or metastatic RCC.

Adult↗

The role of cytokines in the pathogenesis and management of AIDS-related lymphomas.

AIDS-related non-Hodgkin lymphomas (AIDS-NHL) consistently derive from B-cells and are characterized by extreme clinical aggressiveness. At histological level, AIDS-NHL are classified as AIDS-related Burkitt's lymphoma (AIDS-BL), AIDS-related diffuse large cell lymphoma (AIDS-DLCL) and AIDS-related primary effusion lymphoma (AIDS-PEL). The role of cytokines in the pathogenesis and management of AIDS-NHL has been studied to a certain extent. Production of large quantities of human IL-10 occurs frequently in AIDS-BL and correlates with latent EBV infection of the tumor clone. Lesser amounts of the cytokine are released in EBV negative cases. The pathogenetic role of IL-10 in AIDS-BL is suggested by the observation that IL-10 antisense oligonucleotides inhibit proliferation of the lymphoma. A significant fraction of AIDS-BL cell lines produce TNFbeta. Among AIDS-NHL, the release of TNFbeta appears to be specific for AIDS-BL. The pathogenetic relevance of TNFbeta in lymphomagenesis is suggested by the observation that some BL cell lines use TNFbeta as an autocrine growth factor. Some cases of AIDS-BL, particularly those carrying EBV infection, also secrete IL-6, IL-7 and IL-12. With respect to AIDS-DLCL, many cases express the IL-6R, rendering these cells responsive to the paracrine stimulation by the IL-6 produced by nearby T-cells, macrophages and endothelial cells which are frequently abundant in these tumor samples. The tumor clone itself, however, generally fails to release IL-6. AIDS-PEL is characterized by secretion of large amounts of IL-6 and IL-10. Some PEL cases also release oncostatin M. Apart from human IL-6, PEL also express viral IL-6, which is encoded by the HHV-8 genome. The biological relevance of both IL-6 and IL-10 in PEL proliferation and growth has been recently clarified in vitro and in vivo. Overall, these data suggest that activation of different cytokine loops clusters with different clinico-pathologic categories of AIDS-NHL and may represent the potential target of novel therapeutic strategies.

B-Lymphocytes↗

[Patterns of use of terazosine in current medical practice in ambulatory patients with obstructive and irritative obstructive disorders of urination].

OBJECTIVES: To evaluate the efficacy and to describe the modalities of use of terazosin hydrochloride dihydrate, prescribed under conditions of routine clinical practice to a vast population of patients with benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: 1,624 patients suffering from BPH and requiring medical treatment were included in this multicentre open clinical trial performed by 983 general practitioners. After a one-week titration phase, terazosin was administered for 4 weeks at the dosage of 5 mg per day as a single dose in the evening at bedtime. The efficacy of treatment was assessed by the variation of the IPSS score between inclusion and the end of treatment, the treatment response rate (at least 3 point reduction of the IPSS score) and the course of the quality of life score. The safety of treatment was evaluated by clinical interview and physical examination at each visit and by analysis of all adverse events occurring during the trial. RESULTS: A mean 45.8% improvement of the IPSS score (corresponding to a mean decrease of 8.81 points) was demonstrated between D0 and D35 (p < 0.001). The treatment response rate was 91.8%. A mean improvement of 2.11 points (p < 0.001) of the quality of life score was obtained. Complementary subgroup analysis (moderate dysuria n = 775 and severe BPH n = 702) showed that the efficacy of treatment was independent of the initial severity of the voiding disorders. The clinical safety of treatment was considered to be good in 92.5% of cases by the investigators. The incidence of adverse events attributable to treatment and related to a fall in blood pressure was 2.6%. Less than half (20/43, i.e. 1.25% of the population) of the patients experiencing this type of adverse event had to discontinue treatment. The ease of use of treatment was considered to be good in 85.2% of cases. CONCLUSION: Terazosin constitutes an effective symptomatic treatment for BPH when surgery is not indicated, whether the initial disorders are moderate or severe. The safety of treatment appears to be perfectly satisfactory, in a patient series representative of the general practice outpatient population concerned by BPH (age, state of health, concomitant treatments). The one-week progressive dose regimen allows cautious introduction of treatment and generally does not raise any problems of acceptability.

Adrenergic alpha-Antagonists↗

[CT-guided percutaneous fine needle biopsy of solid tumors of the kidney].

OBJECTIVE: This study was designed to evaluate the reliability and the role of percutaneous needle biopsy in the diagnosis of renal masses. MATERIALS AND METHODS: 85 biopsies were performed in 74 patients (mean age: 62 +/- 14 years). The median tumour diameter was 4.44 +/- 2.53 cm. Biopsies were performed with an 18G ASAP* needle with CT guidance. 2 to 4 cores were obtained per patients. All biopsies were performed as an outpatient procedure. RESULTS: Biopsies were uninterpretable in 15 cases (17%) (13 with normal or no renal tissue and 2 necrotic samples). A benign lesion was detected in 8 cases (4 fibrous lesions, 4 infectious lesions). In 3 cases, biopsies were suspicious of cancer, which was confirmed on definitive histology. In 59 cases, biopsies were neoplastic: 6 benign tumours (4 oncocytomas, 1 angiomyolipoma, 1 cystadenoma), 42 renal cell carcinomas (RCC) (conventional: 32, chromophobe: 3, tubulopapillary: 7), 5 urothelial carcinomas, 3 metastases, 2 lymphomas and 1 sarcoma. The median Fürhman grade was 2. 30 RCC were operated. The correlation coefficient for the biopsy and pathology histological type was 0.90. The median pathological Fürhman grade was 2. The biopsy results modified therapeutic management in 38% of cases. There was no morbidity, post-biopsy medical management was never required. CONCLUSION: Biopsy of renal masses is reliable for evaluation of the histological type. The introduction of the CT scope should increase the accuracy of biopsies. The morbidity is low compared to that of diagnostic surgery.

Adult↗

Spatially segregated control of Ca2+ release in developing skeletal muscle of mice.

1. Confocal laser scanning microscopy was used to monitor Ca2+ signals in primary-cultured myotubes, prepared from forelimbs of wild-type or ryanodine receptor type 3 (RyR3) knockout mice. Myotubes loaded with the acetoxymethyl ester (AM) form of fluo-3 were imaged at rest or under whole-cell patch clamp. 2. Discrete Ca2+ release events were detected in intact wild-type and RyR3-knockout myotubes. They showed almost no difference in amplitude and width, but were substantially different in duration. In wild-type myotubes (660 events, 57 cells) the amplitude was 1.27 (0.85, 1.97) (median (25 %, 75 %)) units of resting fluorescence, the full width at half-magnitude (FWHM) was 1.4 (0.9, 2.3) microm, and the full duration at half-magnitude (FDHM) was 25.3 (9.6, 51.7) ms. In RyR3-knockout myotubes (655 events, 83 cells) the amplitude was 1.30 (0.84, 2.08), FWHM was 1.63 (1.02, 2.66) microm, and FDHM was 43.6 (23.6, 76.9) ms. 3. Depolarization under voltage clamp of both wild-type and RyR3-knockout myotubes produced substantial Ca2+ release devoid of discrete Ca2+ events. Discrete events were still present but occurred without correlation with the applied pulse, largely at locations where the pulse did not elicit release. 4. The local correspondence between voltage control and absence of discrete events implies that the functional interaction with voltage sensors suppresses the mechanism that activates discrete events. Because it applies whether RyR3 is present or not, it is this exclusion by voltage of other control mechanisms, rather than isoform composition, that primarily determines the absence of discrete Ca2+ events in adult mammalian muscle.

Animals↗

psi(SO2NH) transition state isosteres of peptides. Synthesis and bioactivity of sulfonamido pseudopeptides related to carnosine.

This paper reports the synthesis of tauryl dipeptides related to carnosine. In particular H-Tau-His-OH (5), H-Tau-His(pi-Me)-OH (6) and H-Tau-His(tau-Me)-OH (9) are described. The enzyme carnosinase has been isolated from pig kidney and after purification has been used to test the stability and the inhibitory activity of the three new analogues. H-Tau-His-OH (5) and H-Tau-His(tau-Me)-OH (9) were found to possess weak inhibitory properties towards carnosinase, while H-Tau-His(pi-Me)-OH (6) proved to be devoid of any significant activity. All the three sulfonamido pseudopeptides 5, 6 and 9 show stability to carnosinase activity.

Carnosine↗

[Urinary complications of Erdheim-Chester disease].

BACKGROUND: Erdeheim-Chester disease is an uncommon histiocytosis. Fifty-nine cases have been reported in the literature. Bone lesions are usually inaugural followed by multiorgan involvement combining bone disease, orbital infiltration, diabetes insipidis and retroperitoneal infiltration. CASE REPORT: A 53-year-old man had Erdheim-Chester disease which progressed over 11 years. The patient developed extrinsic obstruction of the upper urinary tract. This unusual complication of Erdheim-Chester disease raised a difficult therapeutic problem as percutaneous drainage was impossible. The patient was treated with an endoprothesis allowing urine derivation. Surgical ureterolysis was avoided. DISCUSSION: Data in the literature favor use of minimally invasive endourological treatment for patients with urinary tract complications of Erdheim-Chester disease.

Histiocytosis↗

Identification of a chicken "C" chemokine related to lymphotactin.

In this study we describe the isolation and characterization of a new chicken (Gallus gallus) chemokine. This molecule belongs to the C or gamma-chemokine family and is related to the mouse and human lymphotactin (Lptn). Mouse and human Lptn are distinguished from alpha and beta chemokines by the absence of two cysteines (Cys 1 and 3) that form a disulfide bridge; the novel chicken chemokine shows the same cysteine pattern, but replaces a long carboxy-terminal tail found in the other Lptn proteins with a short extension rich in Arg residues. The 1-kb mRNA is mainly expressed in spleen, although weaker signals have been detected in liver and colon. It is interesting to note that the chicken chemokine seems to preferentially induce the migration of spleen B cells over T cells or B cells from the bursa of Fabricius.

Amino Acid Sequence↗

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase II study.

BACKGROUND: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule. PATIENTS AND METHODS: Thirty-six untreated patients with stage IIIB IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on day 1,8, and 15, followed by one week of rest. RESULTS: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%-57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4-23) and the median survival time 11.8 months (range 1-24). World Health Organization (WHO) grade 3-4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity. CONCLUSIONS: This regimen appears to be active and to have a favourable toxicity profile.

Adult↗

[What is the role of the correspondence of free PSA/total PSA in the staging of local prostate cancer? Series of 50 radical prostatectomy cases].

OBJECTIVE: To refine the pretreatment staging of localized prostate cancers. MATERIAL AND METHOD: Prospective study on 50 total prostatectomy specimens from men with apparently prostate-confined adenocarcinoma. Preoperative assay of the free PSA/total PSA ratio and analysis of this ratio according to the presence of capsular effraction, capsular invasion and positive margins. RESULTS: Significant difference of this ratio according to the presence or absence of capsular effraction (13.2% versus 18.9%), capsular invasion (12.4% versus 17.5%) and positive margins (11.6% versus 16.3%). CONCLUSION: The free PSA/total PSA ratio can be useful for staging of prostate cancer, but this needs to be confirmed by a large-scale prospective study.

Adenocarcinoma↗

[Conformal radiotherapy].

Conformal radiotherapy is a new irradiation technique made possible by technological improvements, especially progress in imaging and 3D dosimetry. By conforming the volume irradiated as closely as possible to the clinical anatomical target volume, conformal radiotherapy is designed to deliver a higher dose to the tumour volume, while more effectively sparing the adjacent tissues from the adverse effects of irradiation. Conformal radiotherapy may therefore constitute a progress comparable to the contribution of high-energy radiotherapy in the 1960s or the impact of computer-assisted dosimetry in the 1970s. Evaluation of the results, definition of its indications, standardisation of practices, and study of the impact of dose escalation require further studies in the field of prostate cancer, as the superiority of this new technique over conventional radiotherapy has not been formally established due to the limited follow-up.

Humans↗

[The use of bronchial fibroscopy for difficult intubations in maxillofacial surgery].

BACKGROUND: Evaluation of difficulties and modalities of tracheal intubation in maxillofacial surgery. METHODS DESIGN: retrospective study. SETTING: maxillofacial operation room. 2152 patients who underwent elective maxillofacial surgery during a five-year time, from 1994 to 1998. Indications and alternative modalities of tracheal intubation through fiberoptic bronchoscope in eight patients (0.37%) with preoperatively evaluated difficult intubation due to temporomandibular ankylosis (3 patients), burns sequelae (1 patient), craniofacial congenital malformations (2 patients), unstables fractures of the cervical spine (2 patients), are discussed. Fiberoptic bronchoscope was used through nasotracheal route under topical nasal and laryngeal anaesthesia, combined with appropriate benzoanalgesia, in order to maintain spontaneous breathing. Proper positioning of tracheal tube was directly checked by fiberoptic bronchoscope, through visualization of the tracheal carina. RESULTS: In seven patients tracheal intubation was easily performed without complications in less than 20 minutes. In the eight patients the time spent was 35 minutes, due to important nasal bleeding, which caused a change of the nostril. CONCLUSION: Among the alternative methods of elective tracheal intubation, previously evaluated as difficult or impossible using conventional laryngoscopy, the use of fiberoptic bronchoscope seems to be safest and easiest to use, although not the cheapest.

Adult↗