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S Rota

Publications and source records attributed to S Rota.

At least 19 recordsLinked to original sources
PubMed2026

Lynch syndrome-associated urothelial carcinoma: clinical and molecular findings from a single-institution cohort.

Lynch syndrome-associated urothelial carcinoma (LS-UC) is a rare and undercharacterized clinical entity. While FGFR3 alterations are well described in sporadic urothelial carcinoma, their prevalence and clinical implications in LS-UC remain unclear. We aimed to provide a comprehensive clinical and molecular characterization of LS-UC. We conducted a retrospective single-center study including patients with Lynch syndrome (LS) and histologically confirmed urothelial carcinoma (UC). Clinical, pathological, treatment, and follow-up data were collected. Targeted next-generation sequencing was performed on available tumor samples to assess genomic alterations, with particular attention to FGFR3 mutations. A total of 27 patients with LS-UC were identified, with a predominance of upper urinary tract involvement (70%). Most tumors were diagnosed at an early stage and initially managed with local treatment. During a median follow-up of 92 months, 48% of patients experienced recurrence, with a median time to recurrence of 37 months. Recurrences were predominantly local and were mainly managed with additional surgical or intravesical treatments. No deaths were attributable to UC at last follow-up. Molecular analysis was feasible in 9 cases. FGFR3 mutations were detected in 67% of evaluable samples, with the recurrent p.Arg248Cys hotspot identified in 55% of cases. Additional alterations involved TP53, SWI/SNF complex genes, and PIK3CA, which co-occurred with FGFR3 p.Arg248Cys. No gene fusions were identified. This study expands the limited molecular and clinical evidence on Lynch syndrome-associated urothelial carcinoma. Beyond confirming the recurrent role of FGFR3 (notably p.Arg248Cys), our comprehensive multigene profiling enriches the current genomic knowledge for this rare population. Multi-center collaborative efforts remain essential to aggregate larger datasets and ultimately guide personalized patient management.

Humans↗
PubMed1998

Atherogenic lipoproteins support assembly of the prothrombinase complex and thrombin generation: modulation by oxidation and vitamin E.

The importance of lipoproteins in the etiology of atherosclerosis is well established. Evidence is now accumulating to implicate thrombin in the pathogenesis of atherosclerosis. We have investigated whether atherogenic lipoproteins can support thrombin generation. In the absence of platelets or endothelial cells, both very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (LDL) support assembly of the prothrombinase complex and generation of thrombin. Thrombin generation (per microgram of apolipoprotein) supported by VLDL was 19.4-fold greater than that supported by high-density lipoprotein (HDL), P < .00001, and 11.7-fold greater than that supported by LDL, P < .00001. Oxidation of LDL increased lipoprotein-supported thrombin generation 12-fold compared to unmodified LDL, P < .0001. We have shown that the phenomenon of lipoprotein-supported thrombin generation is mediated predominantly by specific phospholipids and is enhanced by oxidation of these phospholipids. The addition of vitamin E (alpha-tocopherol) markedly reduced the increase in thrombin generation observed after oxidation of LDL (822 +/- 57 v 138 +/- 47 nmol/L; P < .0001). These effects suggest that lipoproteins are important in the production of thrombin and that vitamin E may confer protection from the detrimental effects of lipoprotein oxidation by limiting thrombin formation. These results suggest that atherogenic lipoproteins are linked to the development of atherosclerosis in part by their capacity to support thrombin generation.

Adult↗
PubMed1998

The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis.

BACKGROUND: Several prognostic factors for stage I ovarian carcinoma have been analyzed. Some of them are biological and clinical in nature, but others such as the thoroughness of the staging procedure, the extent of the surgery and the philosophy of treatment, are defined by the human element. PATIENTS AND METHODS: We reviewed the records of 351 patients with Stage I ovarian cancer who had been treated from 1981 to 1991. For all patients the following information was available: age, size of the tumor, FIGO sub-stage, tumor grade, histologic type, rupture of the tumor, cytology, extent of the staging and of the surgery (hysterectomy and bilateral salpingo-oophorectomy vs. fertility-conserving surgery) and use of adjuvant treatments. The thoroughness of the staging was defined as: optimal staging: total abdominal hysterectomy and bilateral salpingo-oophorectomy or fertility-conserving surgery, peritoneal cytology or washing, omentectomy, multiple peritoneal biopsies, sampling of the retroperitoneal nodes or formal lymphadenectomy, peritoneal staging: all the criteria described above were met with the exception of retroperitoneal sampling, incomplete staging: lack of any of the previously-cited criteria. RESULTS: An optimal staging was performed in 100 patients, a peritoneal staging in 107 and an incomplete staging in 144. Radical surgery was performed in 295 women and fertility-conserving surgery in 56. With a median follow-up of 108 months (range 14-184) 64 patients had recurrence of the tumor. Fifty-three died of the disease, two are currently alive with disease and nine were salvaged by surgery and/or chemotherapy. In a multivariate analysis only the tumor grade and the type of staging were significant independent prognostic factors for both disease-free and overall survival. CONCLUSIONS: As described by other authors, we confirm that tumor grade is the single most important biological prognostic factor in early ovarian carcinoma. The thoroughness of the staging impacts significantly on survival, particularly in poorly differentiated carcinomas. Fertility-sparing surgery is not associated with a worse outcome than standard radical surgery.

Adolescent↗
PubMed1997

Effect of the sulfonylurea glyburide on superoxide dismutase in streptozotocin-induced diabetic rat muscle.

1. The effect of glyburide (glibenclamide) treatment on the muscle superoxide dismutase (SOD) activity of diabetic rats has been studied. 2. Four weeks of treatment with glyburide (5 mg/kg, orally) increased muscle SOD activity and decreased blood glucose levels. 3. The results of this study demonstrate that the sulfonylurea, glyburide, is capable of exerting direct insulin-like effects on muscle SOD activity in vivo.

Animals↗
PubMed1997

Individualized anticoagulation with dermatan sulphate for haemodialysis in chronic renal failure.

BACKGROUND: Dermatan sulphate (DS) is a selective thrombin inhibitor with antithrombotic properties and low bleeding potential. In preliminary studies it was reported to be effective for preventing clot formation in the haemodialysis circuit. METHODS: Ten patients on maintenance haemodialysis for chronic renal failure underwent three consecutive investigation phases. In phase 1 (individual dose titration), repeated dialyses were performed with increasing doses of DS until successful dialysis was obtained in two sessions at the same dose. In phase 2, individualized DS doses were validated by a randomized crossover comparison with the individual heparin dose of each patient. In phase 3, each patient underwent 24 consecutive dialyses with DS over 8 weeks. Successful dialysis was defined as completion of the procedure without visible clot formation in the bubble traps and lines or a greater than 20% decrease in dialyser capacity. Dialysis efficiency (decrease in serum urea and creatinine, Kt/V), APTT prolongation, bleeding time, and DS plasma concentrations were also assessed. RESULTS: Phase 1: successful dialysis was achieved in nine patients with 4 mg/kg DS as a predialysis intravenous bolus followed by continuous infusion of 0.65 mg/kg/h. One patient required 5 mg/kg plus 1.3 mg/kg/h. Phase 2: no statistically significant differences were found between DS and heparin in any of the investigated variables. Residual dialyser capacity and dialysis efficiency indexes indicated equivalent efficacy. Phase 3: residual dialyser capacity and dialysis efficiency did not change with time. There was no accumulation of DS in plasma. No bleeding or thrombocytopenia were observed. CONCLUSIONS: The dose of DS can be individually titrated to suppress clot formation during haemodialysis as efficiently as with individualized heparin. Such an individualized DS regimen maintains its anticoagulant efficacy and is safe in prolonged use.

Aged↗
PubMed1997

Conservative surgery for stage I ovarian carcinoma in women of childbearing age.

OBJECTIVE: To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas. DESIGN: Retrospective study. PARTICIPANTS: Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere. METHODS: Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery. CONCLUSION: After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage JC tumours.

Adolescent↗
PubMed1997

Neurotoxicity and ototoxicity of cisplatin plus paclitaxel in comparison to cisplatin plus cyclophosphamide in patients with epithelial ovarian cancer.

PURPOSE: To compare the neurotoxicity and ototoxicity of combination cisplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation. PATIENTS AND METHODS: Forty-six of 51 consecutive patients affected by-epithelial ovarian cancer seen in our institution between October 1994 and August 1995 entered the study. After randomization, they were assigned to receive cisplatin 75 mg/m2 every 3 weeks associated with cyclophosphamide 750 mg/m2 (CC group, n = 22) or paclitaxel 175 mg/m2 over a 3-hour infusion (CP group, n = 24). Treatment was repeated six times in 43 patients and nine times in 25. Before treatment and after three, six, and nine courses of chemotherapy, patients underwent clinical and instrumental neurologic and otologic examinations. RESULTS: Mild sensory impairment was evident even after only three courses of both treatments and signs and symptoms were more severe at the end of treatment. On clinical grounds only, it was possible to demonstrate after six and nine courses a difference between CC and CP treatment, due to the involvement in some CP patients of pain and thermal sensory modalities. However, the overall severity of the neuropathy was similar. Audiometric parameters demonstrated a more negative outcome after treatment in CC compared with CP patients. However, the different severity of the involvement was closely correlated to this initial difference in audiologic performance. CONCLUSION: Up to nine courses of chemotherapy, the CC and CP schedules are similar in terms of severity of neurotoxicity and ototoxicity when patients are evaluated during and immediately after treatment. With the doses used in our study, these toxicities are not dose-limiting. Our results suggest that most of the toxic effects observed during the treatment were due to cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Is platelet phospholipid-dependent thrombin generation altered by acute myocardial infarction or aspirin?

The ability of unactivated and calcium ionophore activated platelets to support thrombin generation in defibrinated plasma was measured by a chromogenic substrate assay in the absence of clot formation. Platelet phospholipid-dependent thrombin generation (Platelet-TG) could be measured using platelets isolated from blood collected into either sodium citrate or EDTA as anticoagulant. Measurements were stable in samples kept at room temperature for 24 hours after venesection. There was no significant difference in either the unactivated or activated platelet-TG with platelets collected into either anticoagulant (mean difference 10.12 nmol/min unactivated and 10.60 nmol/min activated). There was no correlation between unactivated and activated platelet-TG and patient age. Platelet-TG was 179 (153-237) nmol/min (median and inter quartile range) for unactivated and 489 (462-508) nmol/min for activated platelets from healthy volunteer subjects (median age 31, range 20-40 years). Platelet-TG was the same in subjects from a population-based cohort study (median age 58, range 45-70 years [162 (142-193) nmol/min and 527 (490-551) nmol/min, unactivated and activated platelets respectively] as compared to patients admitted with acute myocardial infarction (median age 68, range 36-85 years [179 (146-200) nmol/min and 473 (440-517) nmol/min unactivated and activated platelets respectively] (p = 0.497 for comparison between unactivated platelet-TGs and p = 0.487 for comparison between activated platelet-TGs in the two groups). Aspirin inhibited platelet aggregation but did not affect platelet-TG using either unactivated or activated platelets exposed to aspirin in vitro; or in vivo, using platelets obtained from individuals after ingestion of aspirin. In conclusion these results show that for measurement of platelet-TG, blood samples can be anticoagulated with EDTA as well as sodium citrate for up to 24 hours after venesection and that this measurement is not affected by subject age, aspirin treatment or the acute stage of myocardial infarction.

Adult↗
PubMed1996

[Brain metastases in patients with malignant ovarian epithelial tumors].

From September 1983 to September 1994, 23 patients with Central Nervous System (CNS) metastases from ovarian carcinoma were observed in our institution. The mean age at the time of CNS metastases diagnosis was 59 years, the mean interval between diagnosis of ovarian carcinoma and documentation of the CNS involvement was 35 months. All the patients presented neurological symptoms. One patient had meningeal carcinomatosis; 22 presented parenchymal lesions. Nine patients had a single CNS lesion and 13 had multiple metastatic sites. CNS was the only site of disease in 9 patients, while 8 had concomitant extraperitoneal dissemination. Four patients received hormonal treatment with a mean survival (MS) of 3 months; 14 received radiotherapy alone (MS 5.5 months), 5 underwent surgical resection of solitary lesion followed by radiotherapy (MS 17 months). Number of CNS lesions, extent of the disease at time of CNS metastases and the treatment were the factors which significantly affected survival. The prognosis of these patients appears poor, however, early diagnosis followed by multimodal treatment may result in significant palliation an improve overall survival in a selected group of patients.

Adult↗
PubMed1995

Limited invasiveness to assess retroperitoneal spread in stage I-II ovarian carcinoma.

OBJECTIVE: To evaluate the incidence of retroperitoneal metastases, survival rate and site of recurrence in early ovarian tumors undergoing limited retroperitoneal surgery. METHOD: Three hundred seventy-three consecutive patients underwent assessment of the retroperitoneum consisting of intraoperative palpation with or without biopsies. RESULTS: Retroperitoneal metastases were detected in 10 stage-I tumors (3.2%) and in 10 stage-II tumors (16%). The risk was inversely related to tumor differentiation. Palpation revealed metastases in 10 cases. During follow-up, none of the borderline tumors (1.9% of stage-I grade-1 node-negative, 2.7% of grade-2 and 7.0% of grade-3 tumors) recurred in the retroperitoneum. In stage II, two recurrences were observed in grade-2 tumors (11%) and one in grade 3 (4.5%). CONCLUSION: Limited retroperitoneal surgery enables satisfactory outcome in early ovarian cancers. Risk of retroperitoneal recurrence is minimal in grade 1 and non-existent in borderline tumors. Less differentiated tumors have low risk but further investigation of the therapeutic role of lymphadenectomy is justified.

Adult↗
PubMed1995

Humoral immune response in infants after BCG vaccination.

SETTING: Child welfare division of a university-based department of pediatrics in Turkey. OBJECTIVE: To determine specific IgM and IgG response after BCG vaccination. DESIGN: Prospective, randomized trial. METHODS: Serum samples of 66 infants were taken before and at 2, 4, 6 and 15 months after vaccination. 35 infants were vaccinated at the first month and 31 at the second month after delivery. An ELISA assay was performed using PPD antigen. RESULTS: IgM antibodies increased significantly (P < 0.05) during the post-vaccination period. On the other hand IgG antibodies decreased in the second month after vaccination. At the fourth month the IgG level began to rise continuously (P < 0.01). The infants who were vaccinated at the second month showed a higher IgM response at the second and fourth month than those vaccinated in the first month (P < 0.05), but the difference was not visible thereafter (P > 0.05). 52 infants (78%) were tuberculin positive 8 weeks after vaccination. CONCLUSION: Anti-PPD IgM and IgG levels rise progressively in BCG-vaccinated infants.

BCG Vaccine↗
PubMed1995

Sample adequacy in detecting Chlamydia trachomatis.

OBJECTIVE: Chlamydia trachomatis is an important etiological agent in female genital infection and may result in infertility. In recent years rapid diagnostic methods have become widely used as alternatives to cell culture. Our objective was to evaluate the technique of direct fluorescence assay (DFA) in estimating the presence of C. trachomatis. METHODS: Specimens taken from 40 infertile and 20 fertile women were examined by DFA for the presence of C. trachomatis. RESULTS: Six of forty (15%) infertile women were found to be positive whereas no positive specimens were detected in the control group. When the specimens were grouped into those which were adequate or inadequate, 19 and five specimens, respectively, were adequate in the infertile and healthy groups. If only adequate specimens are included in estimating the presence of Chlamydia, the percentage is 31.6%. CONCLUSIONS: In order to use DFA as a more reliable and rapid diagnostic test of C. trachomatis in female genital infection, false-negativity must be eliminated. Specimens must be collected adequately and concentrated in order to achieve optimal diagnostic success.

Cervix Uteri↗
PubMed1994

Humoral immune response against antigen 60 in BCG-vaccinated infants.

An ELISA assay based on the A-60 antigen complex from Mycobacterium bovis BCG cytoplasm was used to detect anti-mycobacterial antibodies of different classes in the sera of 63 BCG-vaccinated infants during the 6-month post-vaccination period. The mean IgM and IgA levels increased, whereas the mean IgG level decreased after BCG vaccination. However, in a minority of cases only Ig levels were above the cut-off line: this was true for IgM in 11/63 (17%) cases and for IgA in 14/63 (22%) of cases but none of the tested infants was anti-A60 IgG ELISA positive. Fifty-two infants (83%) were tuberculin-positive eight weeks after vaccination, and no significant difference in mean antibody levels of tuberculin-positive and negative cases was observed, except for IgG (p < 0.05).

Antibodies, Bacterial↗
PubMed1994

Seroprevalence of rubella virus in Turkish pregnant women.

OBJECTIVES: To assess the immune status of a group of Turkish pregnant women who had never been immunized. METHODS: Between June 1990 and April 1993, the seroprevelance of rubella was determined in the study group of 1351 women. RESULTS: A total of 242 (17.9%) pregnant women were found to be susceptible to rubella infection and the seropositivity rate related to prior infection was 82.1%. CONCLUSIONS: The importance of Rubella IgG determination in Turkish pregnant women is discussed and recommendations for prevention and control of congenital rubella syndrome (CRS) are suggested.

Antibodies, Viral↗
PubMed1993

The importance of 99mTc DMSA scanning in the localization of childhood urinary tract infections.

The use of 99mTechnetium dimercaptosuccinic acid (99mTc DMSA) scanning for the early diagnosis of upper urinary tract infections has been preferred for a few years. In this research we investigated the use of 99mTc DMSA scanning in the localization of renal parenchymal involvement in urinary tract infection. Twenty-four children presenting with first acute urinary tract infection were studied. Investigations included physical examination, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antibody-coated bacteria (ACB) and early 99mTc DMSA scanning. 99mTc DMSA scanning was taken as the gold standard method in determining renal parenchymal inflammation. According to the 99mTc DMSA scanning the sensitivity of clinical findings was 57.14%, WBC 23.80%, ESR 33.33%, CRP 14.28% and ACB 71.42% in the localization of urinary tract infection. We propose early 99mTc DMSA scanning performed around the time of infection as a good technique for localization of the level of infection in the urinary tract.

Bacterial Infections↗
PubMed1993

Clinical significance of antineutrophil cytoplasmic autoantibodies with specificity for lactoferrin in renal diseases.

The prevalence and clinical significance of antineutrophil cytoplasmic antibodies with specificity for lactoferrin was determined in patients with renal diseases. Antilactoferrin antibodies were found in only 12 of 920 patients (1.3%). These patients had either "pauci-immune" necrotizing crescentic glomerulonephritis (three cases) or lupus nephritis (nine cases). To verify whether antilactoferrin antibodies were specific for patients with systemic lupus erythematosus (SLE) and renal involvement, we studied 61 additional lupus patients, 40 with active lupus nephritis and 21 with active SLE and no renal involvement. Antilactoferrin antibodies were found in approximately 15% to 20% of patients with SLE, irrespective of the presence of renal involvement. We conclude that antineutrophil cytoplasmic antibodies with specificity for lactoferrin are only sporadically found in patients with renal diseases; these patients have either necrotizing crescentic glomerulonephritis or lupus nephritis. However, antilactoferrin antibodies are not a marker for renal involvement in SLE.

Adolescent↗
PubMed1993

Methylprednisolone normalizes superoxide anion production by polymorphs from patients with ANCA-positive vasculitides.

It has been convincingly documented that reactive oxygen species released from activated neutrophils mediate glomerular damage in experimental glomerulonephritis. Recent findings that antineutrophil cytoplasmic autoantibodies (ANCA) induce neutrophils to degranulate and produce oxygen radicals in vitro led us to explore whether neutrophils from patients with ANCA-positive vasculitides and necrotizing glomerulonephritis generated an increased amount of superoxide anion (O2-). Since glucocorticoids inhibit oxygen radicals generation in vitro we also evaluated the effect of intravenous pulses of methylprednisolone. Polymorphs were isolated from peripheral blood collected before (basal), 6 and 24 hours after the first infusion of methylprednisolone and 24 hours after the third one. O2- release by cells was assessed after 30 minute incubation without specific stimuli. Basal O2- release was significantly higher in patients than in controls (P < 0.01). Intravenous infusion of high doses of methylprednisolone markedly reduced O2- production with respect to the basal value, and the difference was statistically significant at various time interval considered after the steroid infusion. Besides reducing the excessive O2- formation, methylprednisolone induced an increase in polymorph expression of the gene encoding for manganese superoxide dismutase (Mn-SOD) enzyme. We conclude that polymorphs taken from patients with ANCA-positive vasculitides and necrotizing glomerulonephritis generate higher amounts of O2- than those from normal subjects. Methylprednisolone normalizes the abnormal generation of O2-, likely through its ability to up-regulate the gene for Mn-SOD, a potent antioxidant enzyme.

Adult↗