Incidental prostatic carcinoma: four-year follow-up after treatment with cyproterone acetate

This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.     

Multiple primary tumors: 17 cases of renal-cell carcinoma associated with primary tumors involving different steroid-hormone target tissues

The aim of this study was to analyze the characteristics of 17 women with renal-cell carcinoma (RCC) associated with other primary neoplasms occurring in steroid-hormone target tissues. The reproductive history of these patients and the use of exogenous hormones were taken into consideration. In all, 10 RCCs were associated with breast carcinoma; 4, with endometrial carcinoma; and 3, with ovarian carcinoma. The presentation of a second primary tumor was described as synchronous or metachronous by evaluation of the interval between the discovery of the two neoplasms. Hormone and surgical treatment as well as pathologic findings for each primary tumor were also reported. In these 17 RCCs the overall rate of disease-specific survival recorded after a mean follow-up period of 32.7 months (range 9–66 months) was 58.8%; 7 patients died of metastatic disease after surviving for a mean of 14.7 months. In terms of the pathologic stage of RCC, a significant difference in mean survival was found between pN0 (mean survival 22.1 ± 3.4 months) and pN 1 RCCs (mean survival 13.7 ± 3.5 months). A total of 13 (76.4%) women were postmenopausal at the time of diagnosis of the first primary tumor; the mean age of these women at menopause was 51.7 ± 1.2 years. No prior use of oral contraceptives was reported by 12 (70.5%) of the 17 patients. Plasma 17-beta-estradiol and estrone levels were determined in only 7 patients at the diagnosis of each of the primary tumors. High plasma estrogen levels were found in 4 women with RCC and breast carcinoma and in 1 patient with RCC and endometrial carcinoma; in the remaining 2 patients low-normal values were found. A relationship appears to exist between certain reproductive and hormone-related factors and the risk of developing these tumor associations. Data emerging from the present study do not provide strong support for the hypothesis of hormone dependency of RCC; however, a role for estrogens in cases in which RCC is associated with other primary tumors involving steroid-hormone target tissues can be hypothesized.     

Prophylactic chemotherapy with fosfomycin trometamol during transurethral surgery and urological man?uvres. Results of a multicentre study

The aim of the present open prospective study is to evaluate the efficacy and safety profile of fosfomycin trometamol in the chemoprophylaxis of urinary tract infections following transurethral diagnostic and/or therapeutic manuvres. 712 patients were enrolled in 72 urological surgical centres. All the enrolled patients received an initial dose of fosfomycin trometamol (Monuril® sachet containing 3 g of active drug in powder) 3 h before and a second dose 24 h after the transurethral manuvres. Clinical and microbiological examinations were carried out before the intervention, and then on the second and seventh days after the manuvres. 94 patients with positive baseline tests were excluded from the microbiological follow-up for noncompliance with the main inclusion criteria. Out of 618 patients with sterile urine or with bacteriuria <>⁵ ml on baseline screening, 20 (3.2%) developed UTI on the second day and 22 (3.6%) on the seventh day after treatment. Clinical follow-up is in agreement with these microbiological data. Overall, a total of 24 side effects were observed (3.3%), 16 of which were associated with Monuril® treatment. The results of this open study agree with the preliminary observations in the controlled studies.In der vorliegenden Studie wurde die Wirksamkeit und Sicherheit von Fosfomycin Trometamol in der Chemoprophylaxe bei diagnostischen und therapeutischen transurethralen Eingriffen geprüft. In 72 urologischen Zentren wurden 712 Patienten in die Studie aufgenommen. Alle Patienten erhielten drei Stunden vor dem Eingriff eine initiale Einzeldosis von 3 g Fosfomycin Trometamol (Monuril® Beutel mit 3 g Wirkstoff in Pulverform). Nach 24 Stunden wurde eine zweite Dosis verabreicht. Vor dem Eingriff sowie am zweiten und siebten Tag nach dem Eingriff wurden die Patienten klinisch untersucht und mikrobiologische Tests durchgeführt. Wegen Verletzung der Einschlußkriterien wurden 94 Patienten mit positiven Befunden zu Studienbeginn aus der mikrobiologischen Verlaufsbeurteilung ausgeschlossen. 20 der 618 Patienten, die vor dem Eingriff einen sterilen Urin oder eine Bakteriurie mit weniger als 10⁵ Keimen/ml hatten, wiesen am zweiten Tag eine Harnwegsinfektion auf (3,2%); am siebten Tag nach dem Eingriff waren 22 (3,6%) der Patienten an einer Harnwegsinfektion erkrankt. Diese mikrobiologischen Daten stimmen mit den klinischen Befunden bei den Verlaufskontrollen überein. Insgesamt traten in 24 Fällen unerwünschte Wirkungen auf (3,3%), davon wurden 16 mit Monuril® in Zusammenhang gebracht. Die Ergebnisse dieser offenen Studie stimmen mit vorläufigen Ergebnissen kontrollierter Studien überein.     

Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients

Cardiovascular Drugs and Therapy - The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of...     

Treatment with short-term,high-dose cyclosporin A in children with refractory chronic idiopathic thrombocytopenic purpura

We report on 14 children (seven boys, seven girls) with chronic idiopathic thrombocytopenic purpura (ITP) refractory to multiple treatments, who were given a short-term therapy (range between 6 and 10 weeks) with high doses of cyclosporin A (CyA) (median, 10 mg/kg/d). Six patients experienced adverse events and one developed severe systemic mycosis during therapy. A complete response (CR) was observed in four patients and a partial response (PR) in three patients. Only the four CR patients, who were all girls, had a sustained response. These data suggest that CyA may be effective in some children with chronic symptomatic ITP.     

Coexistence of hereditary spherocytosis (HS) due to band 3 deficiency and β-thalassaemia trait: partial correction of HS phenotype

Summary. A kindred with hereditary spherocytosis and β-thalassaemia trait was identified. Detailed studies of the red cell membrane proteins on polyacrylamide gels with sodium dodecyl sulphate (SDS-PAGE) demonstrated the presence of band 3 (anion transporter) deficiency in all HS subjects (20–25% reduction) whereas spectrin content was in the normal range. The molecular defect of β thalassaemia in this kindred was due to a β° codon 39 (C-T) mutation, as assessed by β globin gene amplification and ASO-probe hybridization. Seven subjects of this family were studied: two were normal, two had HS alone, two co-inherited HS and β-thalassaemia trait, and one had β-thalassaemia trait only. The two subjects with HS alone had a typical clinical form of spherocytosis with anaemia, reticulocytosis and increased red cell osmotic fragility. The two with both HS and β-thalassaemia trait were not anaemic and showed a small, well-compensated haemoIysis. Hence the finding of red cells with abnormalities of both HS and β-thalassaemia indicates that β-thalassaemic trait 'silences' HS caused by band 3 deficiency.     

A novel MEIS2 mutation explains the complex phenotype in a boy with a typical NF1 microdeletion syndrome

Concurrence of distinct genetic conditions in the same patient is not rare. Several cases involving neurofibromatosis type 1 (NF1) have recently been reported, indicating the need for more extensive molecular analysis when phenotypic features cannot be explained by a single gene mutation. Here, we describe the clinical presentation of a boy with a typical NF1 microdeletion syndrome complicated by cleft palate and other dysmorphic features, hypoplasia of corpus callosum, and partial bicoronal craniosynostosis caused by a novel 2bp deletion in exon 2 of Meis homeobox 2 gene (MEIS2) inherited from the mildly affected father. This is only the second case of an inherited MEIS2 intragenic mutation reported to date. MEIS2 is known to be associated with cleft palate, intellectual disability, heart defects, and dysmorphic features. Our clinical report suggests that this gene may also have a role in cranial morphogenesis in humans, as previously observed in animal models.     

Cytoskeletal behaviour in spectrin and in band 3 deficient spherocytic red cells: evidence for a differentiated splenic conditioning role

Based on quantitative analysis of red cell membrane proteins, hereditary spherocytosis (HS) can be divided into two main groups including isolated or ankyrin combined spectrin deficiency and band 3 reduction. Protein methyl esterification catalysed by protein carboxyl methyltransferase (PCMT type II; EC 2.1.1.77) is a post-biosynthetic modification which is involved in the metabolism of damaged membrane proteins. We utilized the evaluation of erythrocyte membrane protein methyl esterification as a marker of cytoskeletal disarray in seven HS subjects with spectrin reduction and in seven patients with HS due to band 3 deficiency. Our results support the notion that band 3 deficient erythrocytes are not affected by an extensive cytoskeletal derangement. On the contrary, we found a remarkable increase of membrane methylation in the unsplenectomized, spectrin-deficient, HS patients, suggesting a striking membrane skeleton disarray. This phenomenon was not observed in the spectrin-deficient red cells of splenectomized patients. Therefore in spectrin deficient erythrocytes the induction of cytoskeletal damage, specifically recognized by PCMT type II, could be one of the splenic steps producing conditioned spherocytes.