Real-time investigation of an influenza A(H3N2) virus outbreak in a refugee community, November 2022.

OBJECTIVES: To report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy. STUDY DESIGN: Outbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza. METHODS: An epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted. RESULTS: The outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9-14 years, 84.6% in those aged 15-24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period. CONCLUSIONS: The fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved.

Different variables predict the outcome of patients with synchronous versus metachronous metastases of colorectal cancer.

PURPOSE: Timing of metastasis is a controversial prognostic factor for patients with metastatic colorectal cancer (mCRC), as well as the performance of the common prognostic variables within patients with synchronous (SMs) or metachronous metastases (MMs). The aim of the current study is to evaluate outcome by the timing of metastases and to explore different tumor characteristics associated with SMs and MMs. METHODS: Data were collected from the clinical records of patients with mCRC, which were referred to the Department of Oncology of the Ospedale Civile di Sanremo from 2006 to 2011. A comparison of the characteristics of tumors of patients, overall and by the timing of metastases, and a Cox regression analysis have been performed to select the most relevant prognostic factors. Finally, the characteristics of the variables associated with the outcome were analyzed through a logistic regression. RESULTS: Two hundreds fifteen patients with SMs and two hundreds ten with MMs were included. Patients with SMs reported a poor prognosis (18.5 versus 62.8 months; p value < 0.001). Among patients with SMs there was a significant difference in overall survival between patients with a CEA-positive or negative disease, while no difference was present among patients with MMs. After multivariate analysis, only within the SMs group the occurrence of liver metastases was related to a CEA-positive disease. CONCLUSIONS: Within the cohort of SMs high CEA levels, occurrence of liver metastases and right-sided colon tumors were associated with a very poor prognosis, whereas no relationship was detectable in the group of patients with MMs.

Analysis of Clinical End Points of Randomised Trials Including Bevacizumab and Chemotherapy versus Chemotherapy as First-line Treatment of Metastatic Colorectal Cancer.

AIMS: Progression-free survival is recognised as an appropriate end point for randomised clinical trials of chemotherapy of patients with metastatic colorectal cancer, although it is not clear if it is reliable after chemotherapy plus bevacizumab. MATERIALS AND METHODS: A literature search of randomised trials of systemic treatment including chemotherapy plus bevacizumab versus chemotherapy in patients with metastatic colorectal cancer was undertaken. For each trial the differences in overall survival and in either time-to-event or response-related end points were calculated. A Spearman test was carried out between the difference in each end point and the difference in survival. For the end points with the higher relationships with overall survival a regression analysis was carried out and R(2) (proportion of variability explained) was reported. RESULTS: Progression-free survival is closely related to overall survival (r=0.817; R(2)=0.706) and this relationship does not seem to be changed by the discontinuation of bevacizumab. The response-related end points have a better overall performance than the other time-to-event end points, even when only phase III trials are considered. In phase III trials, the disease control rate seems to be strongly related to overall survival (r=0.975; R(2)=0.889) and the overall response rate reports a good performance (r=0.866; R(2)=0.484). An open-label design and the timing of disease radiological evaluation do not seem to interfere with the correlation of differences of progression-free survival and overall survival. CONCLUSIONS: A validation of the disease control rate and the overall response rate as a surrogate end point of survival at a patient level and a standardised definition of the timing for their measurement are strongly recommended in trials of chemotherapy plus bevacizumab.

[Immunologic effects of exposure to low levels of inorganic mercury]. / Effetti immunitari da esposizione a basse dosi di mercurio inorganico.

OBJECTIVE: The immune system is a target for the toxic effects of inorganic mercury, both in humans and animals. In humans it has been observed that occupational and environmental exposure to inorganic mercury may cause both clinical (autoimmunity, hypersensitivity) and subclinical effects (cellular and humoral immunologic variable modifications). To obtain a better definition of these effects with respect to the exposure levels, a multicentre study was performed on 117 workers exposed to very low doses of inorganic mercury and 172 subjects from the general population of the same geographical area with environmental exposure to mercury from dental amalgams and dietary fish intake. RESULTS: The white blood cell count was included in the normality range for all subjects and there was no difference between exposed and non exposed subjects. The immunologic variables studied showed an increase of the CD4+ and CD8+ number in exposed workers compared to non-exposed subjects, with a statistically significance only for CD4+, while no difference was observed regarding CD4+, CD8+, NK+ percentage and CD4+/CD8+ ratio. A significative decrease of serum IL-8 and an inverse correlation between serum levels of this cytokine and HgU were observed in exposed workers compared to non exposed subjects. No association between immunologic variables and both dental amalgams and dietary fish intake was found in subjects not occupationally exposed to inorganic mercury. DISCUSSION: The decrease in IL-8 serum levels observed in exposed workers might suggest an immunosuppressive effect of occupational exposure to very low doses of inorganic mercury. This result suggests the need to revise of current HgU BEI after further definition of its prognostic significance.

[Adaptation of the TriTEST TM for the investigation of blood samples for a multicenter study taken to a single laboratory]. / Adattamento del TriTEST TM per la raccolta di campioni ematici in studi multicentrici afferenti ad uno stesso laboratorio.

BACKGROUND: Immunotoxicological studies in humans are usually carried out via the determination of some selected immune parameters in subjects occupationally and/or environmentally exposed to immunotoxic substance. One of the most often measured parameters is the determination of lymphocyte subsets, which needs to be carried out in a very short time (a few hours) after blood collection. This is the major problem limiting the determination of lymphocyte subpopulations in field studies, where samples are usually collected directly at the workplace, and very often at the end of the workshift. Unfortunately, these collection modalities significantly prolong the time between collection and analysis. The problem is more evident in multicentric studies, where a further problem is represented by the time needed to send samples to the laboratory. OBJECTIVE: Since an immune evaluation was planned, including the determination of lymphocyte subpopulations CD4 (T-helper), CD8 (T-suppressor cytotoxic) and CD16/CD56 (natural killer) in the project "Assessing health effects in man from exposure to low doses of inorganic mercury in environmental and occupational settings", a method was developed for performing cytofluorimetric analysis in "field studies". METHODS: The method is based on commercially-available kits, and involves in loco treatment. Whole blood is labeled with monoclonal antibodies, and fixed samples immediately after collection. After the treatment, the samples are ready for flow cytometric analysis, which may be performed after a two-day period from sample collection. RESULTS AND CONCLUSION: The method described is adequate for immunotoxicity testing in field studies because it prolongs the maximum latency time from collection and cytofluorimetric analysis up to 48 hours. A second interesting characteristic of the method is the possibility of using whole blood, without any need of either complex manipulations or particular equipment.

Fetal and maternal white cells and B- and T-lymphocyte subpopulations in pregnant women with recent infection.

OBJECTIVE: To study maternal and fetal white cell counts, B- and T-lymphocyte subpopulations in pregnant women with evidence of recent infection. METHODS: Thirty-seven pregnant women with recent infection and 38 controls were studied. All were referred for fetal blood sampling to exclude congenital infection, or to perform fetal chromosome analysis. There were 16 infected fetuses: 9 cytomegalovirus (CMV), 4 rubella, and 3 toxoplasmosis. Maternal and fetal blood was taken and white cell counts, the percentage of CD3+, CD4+, CD8+, CD56+, HLADR+CD3+ T-lymphocyte subpopulations and CD19+ B lymphocytes were measured. RESULTS: The percentage of CD3+, CD8+, and HLADR+CD3+ lymphocytes were significantly higher in infected mothers compared to controls, while CD19+ and the CD4+/CD8+ ratio were lower. Infected mothers carrying infected fetuses had significantly lower white blood cell counts compared to those infected mothers without fetal infection. The percentage of HLADR+CD3+ T lymphocytes was significantly higher and the CD4+/CD8+ ratio lower in infected fetuses compared to controls and noninfected fetuses of infected mothers. Abnormal CD4+/CD8+ ratios and/or increased HLADR+CT3+ T lymphocytes were found in 8 of 10 fetuses with structural abnormalities and/or hematological/biochemical signs of systemic damage, and in 7 of 27 without (RR = 3.1, 95% CI = 1.5-6.3). CONCLUSION: Both infected fetuses and their mothers have significant identifiable changes in white cell counts and T-lymphocyte subpopulations compared to controls. These tests may help in diagnosing maternal and fetal infection.

Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group.

PURPOSE: To evaluate whether an accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) chemotherapy regimen with the support of granulocyte colony-stimulating factor (G-CSF) induces a higher activity and efficacy compared with standard CEF in metastatic breast cancer patients. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive as first-line chemotherapy either standard CEF (cyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 21 days (CEF21) or accelerated-intensified CEF (cyclophosphamide 1,000 mg/m(2), epirubicin 80 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 14 days (HD-CEF14) with the support of G-CSF. Treatment was administered for eight cycles. RESULTS: A total of 151 patients were randomized (74 patients on the CEF21 arm and 77 on the HD-CEF14 arm). In both arms, the median number of administered cycles was eight. The dose-intensity actually administered was 93% and 86% of that planned, in CEF21- and HD-CEF14-treated patients, respectively. Compared with the CEF21 arm, the dose-intensity increase in the HD-CEF14 arm was 80%. Both nonhematologic and hematologic toxicities were higher in the HD-CEF14 arm than in the CEF21 arm. During chemotherapy, four deaths occurred in the HD-CEF14 arm. No difference in overall response rate (complete plus partial responses) was observed: 49% and 51% in the CEF21 and HD-CEF14 arms, respectively (P =.94). A slightly non-statistically significant higher percentage of complete response was observed in the HD-CEF14 arm (20% v 15%). No difference in efficacy was observed. The median time to progression was 14.3 and 12.8 months in the CEF21 and HD-CEF14 arms, respectively (P =.69). Median overall survival was 32.7 and 27.2 months in the CEF21 and HD-CEF14 arms, respectively (P =.16). CONCLUSION: In metastatic breast cancer patients, an 80% increase in dose-intensity of the CEF regimen, obtained by both acceleration and dose intensification, does not improve the activity and the efficacy compared with a standard dose-intensity CEF regimen.

Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma.

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2-3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1-4 and fluorouracil, 200 mg/m2/day, days 1-4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2-3, 5-6, 8-9-10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2-3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III-IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies.

Paclitaxel plus ifosfamide in advanced ovarian cancer: a multicenter phase II study.

BACKGROUND: While ovarian cancer is one of the most sensitive cancers to cytotoxic drugs, with objective response rates of 60-80% routinely being reported in previously untreated patients, the majority of individuals with advanced disease ultimately relapse. Paclitaxel, a new and novel antimicrotubule agent, has shown activity as a salvage therapy in epithelial ovarian cancer. More importantly, in a prior study, it has been shown to be active in tumors that have displayed resistance to platinum compounds, with a reported response rate of 20%. Ifosfamide has shown activity in the treatment of patients who previously demonstrated clinical resistance to a platinum-cyclophosphamide combination. Recently, a synergistic activity of Taxol combined with ifosfamide has been reported in ovarian cell lines. Based on these data, a phase I/II study of a combination treatment with paclitaxel and ifosfamide was performed. PATIENTS AND METHODS: Thirty-one patients with recurrent ovarian cancer or ovarian cancer refractory to cisplatin (CDDP)-containing regimens were treated with paclitaxel at a dose of 135 mg/m2 on day 1; ifosfamide was administered at 1 g/m2 on days 2 and 3 for the first cycle and 1.5 and 2 g/m2 with the same schedule in cycles 2 and 3, respectively. In the absence of toxicity, the dose of ifosfamide was maintained at 2 g/m2 for the last three cycles. Cytotoxic therapy was repeated every 3 weeks. RESULTS: A 30% overall objective response rate was achieved in the 30 patients assessable for response. Among 21 platinum-resistant patients, 4 partial responses (19%) were observed, while in the 9 platinum-sensitive patients 2 complete responses and 3 partial responses (55%) were observed. Myelosuppression was the predominant toxicity. Leukopenia (WHO grade 3-4) occurred in 10% of patients who received ifosfamide at a dose of 1 g/m2 and in 18% of patients treated with ifosfamide at 1.5 g/m2. CONCLUSION: Our results confirmed a low activity of paclitaxel in platinum-resistant patients. The results of this combination treatment with paclitaxel-ifosfamide in our platinum-sensitive patients support further investigations in a randomized study of the combination regimen against paclitaxel alone or retreatment with organoplatinum compounds.

Partial inhibition of platelet aggregation by nebulized pentamidine in severe haemophiliacs.

The antiparasite agent pentamidine has been shown to inhibit human platelet aggregation in vitro at concentrations that (potentially) may be attained in patient plasma after the administration of the drug by nebulizer. We measured platelet aggregation in platelet-rich plasma (PRP) before and after the administration of 300 mg nebulized pentamidine to 10 HIV-positive patients with severe haemophilia on prophylaxis against Pneumocystis carinii pneumonia. All patients had normal platelet counts. PAF-acether, U46619, collagen and ADP at different concentrations were used as agonists. Platelet aggregation was lower in PRP samples taken at the end of pentamidine administration and 1 h thereafter than in samples taken at the same time points in control experiments (without the administration of pentamidine). The inhibition of platelet aggregation was mild and tended to be overcome by higher concentrations of platelet agonists. The bleeding time was prolonged from 5 to 15 min in one patient but did not change in the remaining nine patients. In conclusion, this controlled study shows that nebulized pentamidine inhibits platelet aggregation in HIV-positive haemophiliacs without significantly affecting their bleeding times. Although this mild inhibitory effect may not be clinically relevant in haemophiliacs with normal platelet counts despite their defect in intrinsic coagulation, patients with HIV-related thrombocytopenia should be monitored to detect any excessive prolongation of their bleeding times after nebulized pentamidine.

Human endometrial stromal cells as a source of soluble intercellular adhesion molecule (ICAM)-1 molecules.

Intercellular adhesion molecule (ICAM)-1-mediated cell-cell adhesion is essential for various immunological functions, including natural killer (NK) cell-mediated cytotoxicity against endometrium. The present study was designed to establish whether shedding of ICAM-1 from cultured endometrial stromal cells occurred and to characterize its potential functional significance in endometrial physiology and pathology. The shed sICAM-1 molecule was detected and quantified in supernatants from endometrial stromal cultures and in peritoneal fluid by a specific enzyme-linked immunosorbent assay. The results of this study indicate that cultured endometrial stromal cells constitutively shed ICAM-1 from their surface. This ability is regulated during the menstrual cycle, as it appears to be higher in the proliferative than in the secretory phase of the cycle (16.93 +/- 2.2 and 7.7 +/- 1.76 ng/ml respectively). In order to evaluate whether the release of sICAM-1 could interfere with cell-mediated lysis of endometrium we compared the determinations of sICAM-1 in endometrial supernatants with the ability of such supernatants to suppress NK cell-mediated cytotoxicity toward endometrial targets. A significant correlation (r = 0.6, P < 0.05) was found between the sICAM-1 concentration in endometrial supernatants and the percentage of inhibition of NK cell-mediated lysis exerted by the same supernatant samples. Finally, endometrial stromal shedding of sICAM-1 appears to be related to endometriosis since endometrial stromal cultures obtained from patients with advanced stages of the disease released significantly higher amounts of the soluble protein compared to the control group (P < 0.05). sICAM-1 is a soluble molecule which can interfere with immunological functions, and its shedding may be one of the mechanisms by which refluxed endometrial cells escape immunosurveillance.

Platelet activation in newborns detected by flow-cytometry.

Platelet function was investigated in full-term infants on the first, the fourth and tenth days of life and compared to normal adult controls. Platelet function was analyzed through a new cytofluorimetric technique with two murine monoclonal antibodies, PAC-1 and anti-GMP-140, directed against two membrane proteins expressed on the activated platelets' surface. The percentage of activated platelets detected with PAC-1 and anti-GMP-140 was evaluated at basal condition and after in vitro stimulation with a weak agonist (ADP) and a strong Txa2 analogue inducer (U 46619). At day 1 platelet activation at basal condition was negligible and similar to adult controls both with PAC-1 (1.2 vs 1.1%) and anti-GMP-140 (2.6 vs. 3.3%). On the contrary, after ADP stimulation the percentage of PAC-1-positive activated platelets was significantly reduced in neonates compared to adults (22 vs. 66%; p < 0.001) and even more after U 46619 (11 vs. 72%; p < 0.001). The percentage of anti-GMP-140-positive activated platelets behaved similarly after adding both ADP (26 vs. 46%; p < 0.01) and U 46619 (37 vs. 67%; p < 0.001). The reduced platelet activation after ADP and U 46619 persisted at day 4 both with PAC-1 and with anti-GMP-140. On the contrary, at day 10 newborn platelets analyzed with anti-GMP-140 behaved similarly to the adult ones both at basal condition and after stimulation with ADP or U 46619 (6 vs. 3% at basal state, 42 vs. 46% after ADP addition, and 55 vs. 67% after U 46619). These data demonstrate that the reduced platelet activation present in newborns is restored by the tenth day after birth.

Alternating chemo-radiotherapy in bladder cancer: a conservative approach.

PURPOSE: The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. METHODS AND MATERIALS: Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). RESULTS: A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. CONCLUSION: Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy.

R75251 in prostate cancer patients in progression after first-line hormonal treatment.

INTRODUCTION: The therapeutic potential of R75251, a ketoconazole derivative which has shown marked antitumor activity in animals and in men, was investigated in 16 patients with advanced prostatic cancer progressing after one or more lines of hormone therapy. PATIENTS AND METHODS: Patients were given the drug at 150 mg/b.i.d. for one month. After the first month of treatment, the dose was increased to 300 mg/b.i.d. In all patients, treatment was continued until disease progression or the development of sever toxicity. Clinical and biochemical assessments were performed on days 0, 14 and 28 and then repeated on a monthly basis. RESULTS: Of the 13 evaluable patients, 12 showed stable disease by strictly employing US-NPCP criteria. However, in 3 patients a clear effect was observed on the volume of their measurable lesions. In addition, 2 of them showed a more than 50% decrease of prostate-specific antigens (PSA). Overall, 50% of patients showed some decrease in PSA baseline levels. Overall tolerance to treatment was good. CONCLUSIONS: Our results, although achieved in a small number of patients, suggest that R75251 has a moderate but definite activity in patients with hormone-refractory prostate cancer and that the value of this drug as second-line treatment in these patients should be further investigated.

Carboplatin, methotrexate, and vinblastine in the treatment of patients with advanced urothelial cancer. A phase II trial.

BACKGROUND: A Phase II study with carboplatin, methotrexate, and vinblastine (CAMV) was conducted with patients who had advanced urothelial cancer to investigate the activity and toxicity of carboplatin when used in combination chemotherapy. METHODS: Thirty-six patients with advanced urothelial cancer were treated with carboplatin 300 mg/m2 (day 1), methotrexate 40 mg/m2 (days 1 and 8) and vinblastine 4 mg/m2 (days 1 and 8) every 4 weeks. Characteristics of the patients were as follows: men:women, 32:4; median age, 65 years (range, 42-76 years); and median Eastern Cooperative Oncology Group performance status, 0 (range, 0-2). Thirty-six patients were evaluable for toxicity and 33 for response. RESULTS: Objective responses (OR) were achieved in 13 patients: 2 were complete responses (CR) (6%) and 11 were partial responses (33.4%). Median duration of OR was 7 months (range, 3-27 months). Median duration of CR was 10 months (range, 4-27 months), and median survival time for patients achieving complete response was 30.5 months (range, 28-33 months). Patients with a pretreatment creatinine clearance greater than or equal to 50 ml/minute showed a higher response rate: 48% OR and 10% CR. Toxicity was evaluated (World Health Organization criteria) on 164 cycles and was generally mild. CONCLUSION: CAMV is an active and safe regimen in patients with advanced urothelial cancer, even in those with impaired renal function. It is recommended that future studies with this regimen be performed with pharmacokinetic modulation of carboplatin to improve the drug's tolerability and therapeutic activity.

Hemostatic parameters and platelet activation by flow-cytometry in normal pregnancy: a longitudinal study.

Nineteen pregnant women with uncomplicated pregnancies were studied during the first, second, and third trimesters. We measured the following hemostatic parameters: prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C, protein S, platelet number and volume. Platelet function was examined by a cytofluorimetric method, using an anti-GPM-140 antibody which is directed against a platelet alpha granule membrane protein. Activated platelets were expressed as a percentage of the GMP-140-positive platelets over total platelets. Fibrinogen levels showed a steady increase during pregnancy; conversely prothrombin time, activated partial thromboplastin time, protein C, and antithrombin III showed no significant modifications and remained within the reference range. There was a decrease of protein S activity throughout pregnancy, although protein S antigen did not follow this trend. The decrease occurred early in pregnancy and persisted during the second and third trimesters, reaching a stable plateau. We observed no platelet volume change or activation: the percentage of activated platelets was within the normal reference range, even in late pregnancy.

Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b: results of a multicentric Italian study.

PURPOSE: Interferons have shown a definite activity in the intravesical treatment of residual papillary bladder cancer or carcinoma in situ (CIS). The purpose of the present study was to investigate the efficacy of interferon alfa-2b (IFN) as prophylactic treatment of superficial bladder cancer. PATIENTS AND METHODS: Two hundred eighty-seven patients with primary pTa G2, pT1 G1 to G2 superficial bladder cancer, following complete transurethral resection (TUR), were randomly allocated to receive intravesical treatment, either with IFN (50 x 10(6) IU) or mitomycin (MIT-C; 40 mg). Drugs were instilled on a weekly basis for a total of 8 weeks. RESULTS: MIT-C was superior to IFN treatment with respect to time to recurrence, relative recurrence rate, recurrence rate per 100 patients per month, and recurrence tumor rate per 100 patients per month. This difference was particularly evident in patients with pTa G2 tumors. After multivariate analysis, the number of primary tumors and tumor grade were the best predictors of recurrence, while allocated treatment had only a moderate effect. Intravesical treatment was well tolerated in both arms. However, more local toxicity was experienced by patients treated with MIT-C. On the other hand, fever occurred significantly more frequently in patients treated with IFN. CONCLUSION: IFN was less effective, although locally better tolerated, than MIT-C as prophylactic treatment of primary superficial bladder cancer.

Maternal and fetal platelet activation in normal pregnancy.

OBJECTIVE: To study the platelet activation phase in normal pregnant women and their fetuses, both in vivo under basal conditions and in vitro after stimulation by adenosine diphosphate (ADP), a weak agonist, and U46619, a strong one. METHODS: Platelet function was investigated in 39 normal pregnant women and their fetuses undergoing fetal blood sampling at 18-37 weeks' gestation, using flow cytometry and the anti-GMP140 monoclonal antibody. This combined technique allows platelets to be investigated in small aliquots of whole blood, and it detects platelet secretion regardless of aggregation. In all cases, the percentage of activated platelets was determined under basal conditions and after addition of platelet agonists: ADP at concentrations of 10 and 50 mumol/L, and U46619, a stable analogue of thromboxane A2, at 1 mumol/L. RESULTS: Compared to nonpregnant controls, pregnant women had a significantly lower percentage of activated platelets after addition of U46619 (P = .02). Compared to their mothers, fetuses had significantly inferior platelet activation after addition of both platelet-activating factors at all concentrations used (ADP 10 mumol/L, P < .0001 and ADP 50 mumol/L, P < .0001; U46619, P < .0001). Maternal and fetal platelet activation did not change with duration of gestation. In the fetus, the percentage of activated platelets did not correlate with hematocrit, pH, or oxygen pressure, but it correlated significantly with platelet count after addition of U46619 (r = 0.45, P = .006). CONCLUSIONS: Decreased platelet activation in both pregnant women and fetuses suggests the action of a plasma factor that selectively inhibits prostaglandin-dependent activation. Prostacyclin, which is known to decrease platelet aggregation and release reactions caused by agonists, might have a greater inhibitory effect in the fetus than in the mother, or be present in larger amounts in the fetus.

Long-term endocrine effects of administration of either a non-steroidal antiandrogen or a luteinizing hormone-releasing hormone agonist in men with prostate cancer.

The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sought as a potential improvement in the palliative management of prostate cancer. A critical issue for the clinical use of these compounds is, however, the reported evidence in the rat of an excessive increase in testosterone concentrations as a consequence of the androgen negative feedback interruption. On the other hand, the recovery of testicular function after long-term inhibition by luteinizing hormone-releasing hormone (LHRH) analogs is also an important concern in view of the proposed use of these compounds for the treatment of several non-malignant conditions. We addressed these issues by studying the long-term endocrine effects induced by the administration of either the non-steroidal antiandrogen nilutamide or the depot preparation of D-Trp6-LHRH in men with prostate cancer. Treatment with the antiandrogen induced a marked increase in gonadotropin levels, LH concentrations rising from a mean (SEM) of 17.5 +/- 1.6 to a maximum of 56.6 +/- 6.9 kU/l (p < 0.001), while mean testosterone and 17 beta estradiol-concentrations rose only by about 50% and 70% over pretreatment values, testosterone levels reaching a plateau after 1 month of treatment. In the subjects treated with the LHRH agonist, 6 months after discontinuation of long-term administration the mean (+/- SEM) LH had risen to 36.9 +/- 6.8 IU/l while mean testosterone levels were still as low as 1.7 +/- 0.7 and rose only to a maximum of 4.2 +/- 1 nmol/l after high-dose human chorionic gonadotropin loadings.(ABSTRACT TRUNCATED AT 250 WORDS)