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Biomedical subjects

M Seveso

Publications and source records attributed to M Seveso.

At least 19 recordsLinked to original sources

Expression of CTLA-4 in nonhuman primate lymphocytes and its use as a potential target for specific immunotoxin-mediated apoptosis: results of in vitro studies.

T-cell-mediated immunoregulation is one of the main mechanisms implicated in induction and maintenance of transplantation tolerance. In this regard, deletion or modulation of xeno/alloantigen-specific T cells, as well as blocking of their interactions with other cell populations, are currently being pursued for tolerance induction in humans as well as nonhuman primates. In order to investigate whether cytotoxic T-lymphocyte antigen-4 (CTLA-4) may represent a suitable target for a T cell depletion approach in nonhuman primate models, we analysed CTLA-4 expression in peripheral blood mononuclear cells (PBMCs) from nonhuman primates and the potential role of two anti-CTLA-4 saporin-conjugated immunotoxins. The analysis was performed in PBMCs from 8 cynomolgus monkeys from Philippines and from Mauritius both at protein level by flow cytometry and at transcriptional level by RT-PCR. In addition, the apoptotic role of the immunotoxins was investigated. The results showed that CTLA-4 was expressed at variable levels depending on the origin of the cynomolgus monkeys and the resting or activated cell condition. CTLA-4 was not expressed on resting Mauritius PBMCs and showed a lower up-regulation upon PMA/PHA activation compared to the Philippines PBMCs that expressed CTLA-4 also before activation. Two CTLA-4 RNA transcripts (672 and 550 bp) were detected with levels variations after cell stimulation. Two anti-CTLA-4 immunotoxins induced in vitro apoptosis of activated PBMCs from both sources of cynomolgus monkeys. This is the first report that documents CTLA-4 expression both at protein and transcriptional level by nonhuman primate PBMCs and provides novel perspectives of xeno/allograft rejection immunotherapy based on CTLA-4 targeting.

Animals↗

Tetanus and botulinum neurotoxins: turning bad guys into good by research.

The neuroparalytic syndromes of tetanus and botulism are caused by neurotoxins produced by bacteria of the genus Clostridium. They are 150 kDa proteins consisting of three-domains, endowed with different functions: neurospecific binding, membrane translocation and specific proteolysis of three key components of the neuroexocytosis apparatus. After binding to the presynaptic membrane of motoneurons, tetanus neurotoxin (TeNT) is internalized and transported retroaxonally to the spinal cord, where it blocks neurotransmitter release from spinal inhibitory interneurons. In contrast, the seven botulinum neurotoxins (BoNT) act at the periphery and inhibit acetylcholine release from peripheral cholinergic nerve terminals. TeNT and BoNT-B, -D, -F and -G cleave specifically at single but different peptide bonds, VAMP/synaptobrevin, a membrane protein of small synaptic vesicles. BoNT types -A, -C and -E cleave SNAP-25 at different sites within the COOH-terminus, whereas BoNT-C also cleaves syntaxin. BoNTs are increasingly used in medicine for the treatment of human diseases characterized by hyperfunction of cholinergic terminals.

Animals↗

[Recovery of urinary incontinence after retropubic radical prostatectomy. Results in 100 patients].

AIM OF THE STUDY: To shorten the time to recovery of full urinary continence after radical retropubic prostatectomy and to increase the postoperative continence rate. MATERIALS AND METHODS: One hundred and five consecutive patients were submitted to radical retropubic prostatectomy for prostate cancer, with curative intent, focusing our attention on three steps of the operation. First, to achieve a complete control of bleeding from the dorsal vein complex and to perform a minimal touch dissection of the urethral stump; second, to perform a conservative dissection of the bladder neck, and, third, to implement a vascular type, watertight, vesico urethral anastomosis. Continence was assessed 24 hours after catheter removal and at monthly follow up visits until full recovery and graded as dry if no dropping was visible and the patient was able to interrupt the urinary stream during micturition; stress incontinence, if any dropping was observed during abdominal strain between micturitions; and wet, if uncontrollable dropping occurred, and the number of pads needed per day recorded. RESULTS: At a median follow-up time of 18 months, range 6 to 30, a total of 87 of 100 evaluable patients (87%) resulted as dry; 10 patients (10%) resulted as having a variable degree of stress incontinence needing one to three pads per day, and 3 patients (3%) resulted as wet. In 41 of the 87 dry patients (47.1%) continence was achieved within the first day from catheter removal, and in a median time of 4 weeks, range 2 to 16 in the remaining 46 patients (52.9%). CONCLUSIONS: The results of total continence rate of the present study seem to compare to the recent literature except for the time to full recovery which is shorter; it is difficult to identify the contribution of each single surgical step.

Aged↗

[Study of the diuretic efficacy and tolerability of therapy with Rocchetta mineral water in patients with recurrent calcium kidney stones].

The diluition of urine decreases the risk of stone formation by lowering the concentration of calcium, oxalate and uric acid, but involves a simultaneous decrease of the concentration of the inhibitors of crystallization. On the other hand the ion content of the drinking water used for stone prevention could by itself modify urine composition. We tested the effect of the administration of a mild-calcium high-bicarbonate content water on urine composition of a group of calcium renal stone formers. A group of 40 calcium renal stone formers was instructed to drink 3 l/day of a mild-calcium (57 mg/l) and high-bicarbonate (180 mg/l) content water (Rocchetta) for a 7 day period. A 24-h collection was obtained before and after water administration for analyses of calcium, magnesium, oxalate and citrate. Urine volume was significantly increased after water administration (1601 +/- 357 vs 1878 +/- 339). Daily urinary calcium, magnesium and citrate were significantly increased, whereas daily urinary oxalate was unchanged after water administration. In conclusion the mild-calcium high-bicarbonate content water administration seems suitable for stone prevention because of the increased excretion of urinary inhibitors counterbalancing increased urinary calcium excretion.

Diuretics↗

Renal stone fragments following shock wave lithotripsy.

PURPOSE: We describe a select group of asymptomatic patients with fragments and dust 3 months after extracorporeal treatment, who were followed to evaluate the long-term outcome and therapeutic implications. MATERIALS AND METHODS: A total of 129 patients with dust and residual fragments (less than 4 mm.) at 3 months was re-examined at 12 months, and 95 were also evaluated at 24 months. Followup examinations consisted of radiographic studies, renal ultrasonography and urine culture. Dust and residual fragments were sought, and patients were defined as free or as having persistent lithiasis or stone regrowth. At 24 months recurrences in the patients stone-free at 12 months also were considered. RESULTS: At the 12-month followup 60 patients (46.5%) were stone-free and 56 (43.5%) still had dust or residual fragments. The localization of the stones or fragments at 3 months and their sizes did not have a significant influence on the stone-free rate but regrowth was greater in patients with stones larger than 10 mm. (11 of 40 patients, 27.5% versus 2 of 89, 2.2%, p = 0.001). The probability of eliminating residual lithiasis at 12 months was significantly greater in patients with dust than in those with residual fragments (42 of 79 patients, 58% versus 18 of 50, 36%, p = 0.026). Regrowth of residual lithiasis was observed in 13 patients (10%). CONCLUSIONS: Based on our results, we do not believe that patients with fragments require systematic re-treatment in the short term but they may be followed long term and re-treated if symptoms persist or stones recur.

Adult↗

IL-12 synergizes with IL-2 and other stimuli in inducing IL-10 production by human T cells.

IL-12, a potent inducer of IFN-gamma production by T cells and NK cells, has been recently reported to exacerbate an established Th2 response in vivo. However, the effect of IL-12 on Th2-lymphokine production remains unclear. Since IL-10 is a lymphokine associated with Th2 responses which decreases both IL-12-induced IFN-gamma production and IL-12 production by macrophages, we have analyzed here, in an APC-free system, the ability of IL-12 to modulate the production of human IL-10 by established Th0, Th1, and Th2 T cell clones (TCC), T cell lines, and purified peripheral blood T cells. IL-12 synergized with anti-CD3 mAb, Con A, or IL-2 in inducing IL-10 production by Th0, Th1, and Th2 TCC and by T cell lines. This effect was dose dependent (from 0.1 to 50 U/ml) and associated with an increase of IL-10 mRNA transcription. As previously reported, IL-12 also enhanced IFN-gamma production by stimulated Th1 and Th0 TCC and, to a lesser extent, IL-4 production by stimulated Th0 and Th2 TCC. These observations were extended to peripheral blood T cells stimulated in the presence of exogenous IL-2. Moreover, using neutralizing anti-IL-2 Ab, we report that endogenous IL-2 produced by stimulated Th0 TCC could in part contribute to the effect of IL-12 on IL-10 and IL-4 production. In conclusion, IL-12 synergizes with IL-2 and other stimuli in inducing IL-4 and IL-10 production by T cells. This property may help to explain why IL-12 does not efficiently down-regulate an established Th2 response.

Adjuvants, Immunologic↗

[pT1G3 bladder carcinoma: parameters of a correct therapy].

Between 13.8% and 27% of all superficial bladder cancers are represented by pT1G3 neoplasm. In the Department of Urology of Policlinico S. Marco-Zingonia, between February 1988 and June 1994, we treated 22 patients suffering for pT1G3 bladder tumor. TUR-B has demonstrated to be a good approach for treatment of superficial bladder cancer, with low morbility; on the opposite side, we have to underline the high rate of recurrence and of progression of the urothelium disease. Now a day our best approach for the treatment of pT1G3 bladder tumor is represented by radical cystectomy supplied by chemotherapy.

BCG Vaccine↗

Extracorporeal shock wave lithotripsy.

The first clinical application of extracorporeal SWL dates back to 1980. Since then the use of this method has spread widely and its indications have been extended progressively so that it way now be considered the treatment of choice in 80-90% of cases of ureterorenal lithiasis. Treatments without anesthesia or analgesics have been associated with an increase of retreatments from 5-14% (original HM3) to 45-60% (lithotripters not requiring anesthesia or analgesia). However, almost all lithotripter succeed in fragmenting stones sufficiently. The stone free rate varies with different lithotripters in the different series: 90-56% for stones of maximum diameter < 1 cm, 78-30% for stones of maximum diameter of 1-2 cm. and 52.5-10% for stones of maximum diameter of 2-3 cm. (the last figure was obtained with a piezoelectric lithotripter). Extracorporeal lithotripsy as monotherapy of staghorn stones has yelded a stone free rate varying between 31% and 55% with high percentages of residual fragments in about 50% of case of the various series. The stone free rate after treatment varies according to stone site: it is between 75% and 84% of caliceal stones for upper caliceal calculi and falls to under 60% for lower caliceal ones. The frequency of recurrences, that is, of new stones in patients stone free after SWL, is between 4% and 10% annually. Adding the percentage of true recurrences reported by the various authors at 19 to 42 months of follow-up (6.2-13.8%) to the fragment regrowth rate (17.2-22.3%) gives a total new stone rate of 23.4% and 36%. These figures are not greatly different from those reported in a population of untreated stone formers (10-15% per year). Extracorporeal lithotripsy seems thus not to influence lithiasis recurrence significantly.

Equipment Design↗

Extracorporeal shock wave lithotripsy in the treatment of ureteral lithiasis: methodological controversies and therapeutic efficacy.

The treatment of ureteral stones has undergone a radical change in the last 15 years. First, the increased use of endoscopic procedures and then the introduction of extracorporeal lithotripsy relegated traditional surgery to a marginal role for this type of disorder. The best available treatment modality for ureteral lithiasis, particularly distal ureteral stones, is still a matter of great controversy among urologist. With the introduction in clinical use of second- and third generation lithotripters, which are even less invasive and require no anesthesia, interest has increased in treating patients by extracorporeal lithotripsy, reducing endoscopic monoeuvres to a minimum. The absolute contraindications to extracorporeal lithotripsy for ureteral stones are the same as those for renal stones: intractable hemostatic alterations, pregnancy, physical structure that limits positioning and altered patency of the urinary tract. From June 1990 to December 1994, 270 patients with ureteral stones were treated by extracorporeal lithotripsy at our center. The Dornier MPL 9000 lithotripter was used in 68 cases (25%) and the modified HM3 Dornier in 202 (75%). Pretreatment manoeuvres were performed in 130 patients (48%). Endoscopic manoeuvres were not performed in 140 patients treated in situ. 18 patients (13%) treated initially in situ subsequently underwent post-treatment manoeuvres which were required only in 3 patients who had undergone pretreatment. All patients were examined as outpatients 3 months after the treatment. A total of 241 patients (89%) were stone free, 121 who had undergone pretreatment manoeuvres and 119 who had been treated in situ. 29 patients (11%) were not stone free: 23 patients subsequently underwent endoscopic lithotripsy, 2 surgery and 4 stone removal by Dormia probe. The possibility of performing treatment without anesthesia, the absence of complications and the high proportion of successes make extracorporeal lithotripsy, particularly the in situ procedure, the treatment of choice for ureteral stones. Ureterorenoscopy has been proposed by some authors as the first treatment for mid and pelvic ureteral stones which are difficult to localize with the lithotripter. However, although this method is very efficacious and less expensive, the percentage of complications is greater and patient compliance is less.

Evaluation Studies as Topic↗

[Seminal obstructions of the inflammatory origin].

Presence of bacteria in the sperm is often associated to a reduction of fertility in relationship with a decrease in number and motility of spermatozoa and with an augmentation of the abnormal spermatic cells. In the most severe cases, chronic and complicated phlogosis may lead to obstruction of seminal pathways with consequent azoospermia. Clinical features of seminal phlogosis are extremely variable both in acute and chronic evolutions. In every case the first diagnostical step is sperm count and seminal complete analysis which can give evidence of phlogistic alteration in quantity and quality of spermatic cells with a typical presence of an excess in white blood cells (leukospermia) as consequence of infection. The great variety in clinical and bacteriological aspects and the particular biological features of the organs involved, as the prostate, makes treatment a difficult problem to solve with particular regard to the choice of an effective antibiotic which pharmacokinetic has to result suitable for the microorganism as well as for the tissue of the infection site. All those efforts are indispensable to reduce the too frequent therapeutical failures in the management of seminal phlogistic pathology with complications of organic but also physiological relevancy for the patient and the partner too, such as azoospermia.

Anti-Bacterial Agents↗

[Stress urinary incontinence after perineal radical prostatectomy].

22 pts treated by radical perineal prostatectomy have been submitted to pelvic floor training soon after catheter removal, in order to assess faster continence reappraisal than that normally described in literature. 18 pts resulted dry within 4 months from surgical care. 2 pts resulted with stabilized mild stress incontinence due to daytime activity within 6 months from prostatectomy. 2 pts complained strong stress urinary incontinence over a period of more 9 months from surgery, but none resulted affected from continuous leakage. In this pts we observed a maximum time of continence reappraisal of 6 months with a minimum of 1 and an average of 4. An high perineal test has been found statistically correlated in the first three months from surgery with nocturnal continence reappraisal and the begging of diurnal micturion events (p < 0.005). Pelvic floor exercises has been found useful in the treatment of post radical perineal prostatectomy stress urinary incontinence.

Aged↗

[Extracorporeal lithotripsy in patients with acquired or congenital coagulopathies].

Post ESWL haemorragic complications are frequent and most patients experience temporary haematuria and focal intrarenal bleeding or perirenal haematoma are detected by NMR or US imaging. By tradition coagulation troubles have been a contraindication for ESWL but literature describes cases of coagulopathic patients treated with ESWL. From January 1992 to July 1993, 4 of our patients with severe haemostatis troubles (severe haemophilia A in two cases, acquired deficit of coagulation factors and mild thrombocytopenia secondary to post-necrotic hepatitis in 1 case and Glanzmann's thrombasthenia in 1 case) underwent ESWL using Dornier HM3 mod. or MPL 9000. An extensive haematological and clinical evaluation pre and post-ESWL with an adequate haematological prophylaxis (transfusion of blood derivatives) has been performed depending on the coagulation disorder. In our patients we did not observe any haemorragic complication and we propose a reappraisal of the contraindications of ESWL in subjects with coagulation disorders: careful evaluation of haemorragic risk factors, by suitable correction measures and close clinical and instrumental monitoring, allows a reduction of the risk of haemorragic complications in coagulopathic patients who undergo ESWL treatment.

Adult↗

Molecular cloning of a recombinant retrovirus carrying a mutated envAKR-mycMH2 fusion gene immortalizing cells of the monocytic-macrophage lineage.

The VN-11 recombinant retroviruses, originally generated by co-transfection of the avian MH2 and AKRv viral genomes, were molecularly cloned from an infected mouse cell line named N11. The analysis of the proviral genome sequence from one of these recombinants showed a possible envAKR-mycMH2 fusion. Point mutations were also found in this envAKR-mycMH2 gene. The cloned viral genome was co-transfected with the neo gene into the psi 2 packaging cell line. Selected clones were shown to transcribe the viral genome and supernatants from these cultures, containing C-type particles, were used to infect primary cultures from mouse lymphoid tissues and brain. Proliferating macrophages and microglial cell clones were obtained, indicating that various types of cells of the mouse monocytic-macrophage lineage can be immortalized in spite of the absence of selection or special growth conditions.

Animals↗

[Treatment of urinary incontinence in the patient operated on for benign prostatic hyperplasia].

A potential complication of prostatic adenomectomy and TURP is urinary incontinence. The incidence of this problem ranges from 0.1 to 1%. we reviewed our experience with 15 patients who were incontinent between 10 to 24 months after prostatectomy. We treated these patients with bladder training. At first, patients were evaluated for the type and extent of incontinence. Perineal exercise were taught in detail, tested for their correct use via simultaneous and abdominal examination. Patients were evaluated weekly for compliance. No pharmaceutical agents were used. All the 15 patients improved in the number of incontinence episodes 5 patients achieved total continence, while only one showed a little change. We conclude that patients who are incontinent after prostatectomy can improve with a well-done behavioral training program.

Aged↗

[Treatment of prostatitis with a new laser probe with optic fiber].

The present treatment of the subacute abatteric prostatitis, prostatodinia, prostatosis (the most common prostatic flogistic diseases) is represented by the transrectal applications of infrared Laser. The concrete opportunity of applying such an energy directly to the prostate in cases of flogistic diseases--a very frequent pathology treated in many different and controversial ways--is a stimulating therapeutical method which we tested and that we presently use in our clinics. The thanks to the realization of an high technology equipment, easy to handle, cheap, safe, perfectly suitable, formed by a new infrared Laser probe, transrectal, atermical, made by a optical fibre, which we present. Micturition, ejaculation, fertility may draw a relevant improvement, provided that the same treatment is performed after a specific medical diagnosis and following a strict protocol.

Equipment Design↗

Perineal biofeedback versus pelvic floor training in the treatment of urinary incontinence.

Perineal floor training and perineal biofeedback allow to reach a good improvement of clinical discomfort in the treatment of stress and urge urinary incontinence. The aim of this study is the real evaluation of the benefit due to a 6 week perineal biofeedback and pelvic floor training (PFT) versus PFT alone. 8 female patients have been treated with a 6 week trial with perineal biofeedback plus PFT trial and 22 with a 3 month PFT alone one. PFT alone, permits a good improvement but 10% less than if associated to perineal biofeedback.

Biofeedback, Psychology↗

Extracorporeal shock-wave lithotripsy with MPL9000 for the treatment of urinary stones in pediatric patients.

Extracorporeal shock-wave lithotripsy (ESWL) is now applied as the treatment of choice in most cases of urinary stones. Its acceptance in pediatry, however has been only gradual despite numerous positive studies. We report on fourteen young patients (mean age: 9.7 years) who were all treated by ESWL with the MPL9000 lithotriptor for renal stones. Each patient received an average of 1440 shocks with generator energy set at 14.4 Kv. Six of these patients required either analgosedation or anesthesia. No observable complications of treatment occurred. At one-month follow up, the kidneys of twelve patients were found to be stone-free, while two still presented fragments that could pass spontaneously. At three-month follow-up, thirteen patients were stone-free and a single patient retained some fragments. From this data we infer that ESWL with the MPL9000 lithotriptor may be used safety and efficiently to treat urolithiasis in younger patients.

Adolescent↗