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Neurogenesis in the adult hippocampus can be up- or downregulated in response to a variety of physiological and pathological conditions. Among these, dysregulation of hippocampal neurogenesis has been recently implicated in the pathogenesis of depression. In addition, in animal models of depression, a variety of antidepressant treatments reverse that condition by increasing neurogenesis. As one night sleep deprivation is known to improve mood in depressed patients for at least 1 day, we investigated whether a comparable treatment may affect hippocampal neurogenesis in adult rats. Accordingly, rats were sleep-deprived by gentle handling for 12 h during their physiological period of rest, and were injected with bromodeoxyuridine 4 h and 2 h before the end of sleep deprivation. They were then perfused immediately thereafter, or after 15 days and 30 days. We found that 12 h sleep deprivation significantly increased cell proliferation and the total number of surviving cells in the hippocampal dentate gyrus soon after sleep deprivation, as well as 15 days and 30 days later, in comparison to control rats allowed to sleep. No changes were instead found in the subventricular zone of the lateral ventricles, indicating that 12 h sleep deprivation selectively triggers neurogenic signals to the hippocampus. The present data include acute sleep deprivation among the conditions which upregulate hippocampal neurogenesis and raise the possibility that such response could be implicated in the beneficial effects elicited in depressed patients by one night sleep deprivation. Thus, the findings could contribute to the understanding of the intriguing relationship between depression and neurogenesis in the adult brain.

We investigated the protective effect of subchronic treatment of the A2A receptor antagonist, SCH 58261 (0.01 mg/kg, i.p.), administered 5 min, 6 h and 15 h after permanent right middle cerebral artery occlusion (MCAo). Twenty-four hours after ischemia, an extensive pallid area, evaluated by cresyl violet staining, is evident in the vascular territories supplied by the MCA, the striatum and the sensory motor cortex. The pallid area reflects the extent of necrotic neurons. Soon after waking, rats showed a definite contralateral turning behavior which was significantly reduced by SCH 58261 treatment. Twenty-four hours after MCAo, SCH 58261 significantly improved the neurological deficit and reduced ischemic damage in the striatum and cortex. Phospho-p38 mitogen-activated protein kinase (MAPK), evaluated by Western Blot, increased by 500% in the ischemic striatum 24 h after MCAo. SCH 58261 treatment significantly reduced phospho-p38 MAPK by 70%. Microglia was immunostained using the OX-42 antibody. Phospho-p38 MAPK and OX-42-immunoreactive cells are localized in the ventral striatum and frontoparietal cortex. Furthermore, both OX-42 and phospho-p38 MAPK-immunoreactive cells have overlapping morphological features, typical of reactive microglia. SCH 58261 reduced phospho-p38 MAPK immunoreactivity in the striatum and in the cortex without changing the microglial cell morphology. These results indicate that the protective effect of the adenosine antagonist SCH 58261 during ischemia is not due to reduced microglial activation but involves inhibition of phospho-p38 MAPK and suggest that treatment with the A2A antagonist from the first hour to several hours after ischemia may be a useful therapeutic approach in cerebral ischemia.

Objective: To analyze the relationship between pain and presence, site, and type of adhesions in women with endometriosis., Methods: This was a multicenter, observational cross-sectional study. Eligible for the study were women with endometriosis and pelvic pain, consecutively observed during the study period at the collaborating centers. A total of 574 women entered the study., Results: Adhesions were observed in 81.9% of cases (470 women). The frequency was lower in women with endometriosis at stage I-II (65%) and higher in women with stage III-IV (88%); this difference was statistically significant (p < .01). The frequency of adhesions was lower in women with ovarian endometriosis (74%) and higher in those with ovarian and peritoneal endometriosis (87%) or other sites (96%) (p < .01). The presence of adhesions was associated with higher mean visual analog scale (VAS) scores and median multidimensional scale ratings in women with ovarian disease and with stage I-II disease. Women with ovarian adhesions reported higher VAS and multidimensional scale scores (p < .05) than women with peritoneal adhesions or adhesions in other sites., Conclusions: The results of this study suggest that there is no overall association between the presence of adhesions and the degree of pain in women with endometriosis. The data suggests that there may be an association between adhesions and pain in women with ovarian and Type I-II endometriosis. However, these associations were no longer significant after correction for multiple comparisons. Further research is indicated to test these associations.

Interest is growing in the role of adenosine triphosphate (ATP) on P2 receptors during hypoxic/ischemic events in the brain. However, there is no direct evidence of an increase in extracellular ATP levels during cerebral ischemia in vivo. The aim of the present study was to evaluate ATP outflow from the rat striatum by the microdialysis technique associated with focal cerebral ischemia in vivo by intraluminal occlusion of the right middle cerebral artery (MCA). Between 1 and 4h after ischemia, rats showed a clear turning behavior contralateral to the ischemic side. Twenty-four hour after MCA occlusion, ischemic rats had definite neurological deficit and striatal and cortical damage. The ATP concentration (mean+/-S.E.M.) in the striatum of normoxic rats (n = 8) was 3.10+/-0.34 nM. During 220 min after MCA occlusion, the extracellular ATP levels significantly increased two-fold, being 5.90+/-0.61 nM (p < 0.01 versus normoxic level). ATP outflow showed a tendency to increase over time during the 220 min of ischemia. Since extracellular ATP is rapidly metabolized to adenosine, we also assessed ATP outflow in the presence of the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene-adenosine diphosphate (AOPCP, 1 mM) directly perfused into the striatum. The ATP concentration in normoxic rats (n = 8) was increased three-fold in the presence of the ecto-5'-nucleotidase inhibitor (9.57+/-0.26 nM). During 220 min of ischemia, extracellular ATP levels significantly increased 1.3-fold in AOPCP-treated rats (12.62+/-0.65 nM, p < 0.01 versus normoxic level). The present study confirms that ATP is continuously released in the brain and demonstrates for the first time that ATP outflow increases during ischemia in vivo. These results confirm that ATP may be an important mediator in brain ischemia.

Objective: We evaluated the characteristics and determinants of 5-year survival in ovarian cancer patients with complete response after first line treatment who entered a randomised study comparing two different chemotherapeutic schedules., Methods: This analysis included 232 ovarian cancer patients with complete response after first line surgery and chemotherapy coming from a large randomised trial comparing the effect of different doses of paclitaxel combined with fixed doses of carboplatin., Results: The 5-year overall survival in patients was 57.3%. The difference in 5-year survival for age <52 years (65.1%), 53-62 (51.4%) and > or = 63 (51.2%) was statistically significant (P = 0.048). The 5-year overall survival rates were 64.6% for stage III and 57.9% for stage IV. Serous and clear cell histotypes had a worse 5-year overall survival (51.5% and 50.8% respectively), while the endometrioid and mucinous had 67.1% and 71.4%: these differences were statistically different (P = 0.04). Women with residual tumour of 1 cm or smaller after primary surgery had better 5-year survival rates: 71.2% for patients with residual tumour < or = 1 cm and 46.9% for residual tumour >1 cm: these differences were statistically significant (P < 0.006)., Conclusion: This study shows that in women with ovarian cancer and complete response after first line surgery and chemotherapy, age, histotype and residual tumour after surgery are determinants of 5-year overall survival.

Renal transplantation has become a well-established therapeutic option for end-stage renal disease, but infectious diseases remain a significant cause of morbidity and mortality. Although a wide variety of pathogens may cause infection, viral ones must be regarded as the single most important class of infections. Progress has been made both in the prevention and the early recognition treatment of infections that are closely linked to rejection. Immunosuppressive therapy is central to the pathogenesis of both. Because of the particular characteristics of transplant recipients, it is desirable to establish a close collaboration between nephrologists, surgeons, and infectious disease specialists for the management of these patients. In this article, we describe the different kinds of infectious disease that may affect patients with kidney transplant and the fundamental principles of clinical management, particularly our experience in Polyoma virus (BK) infection.

A 71-year-old-woman was admitted to the S. Eugenio Hospital for a history of progressively impaired standing and gait. Anamnesis revealed systemic hypertension, gastric polyposis and juvenile pulmonary tuberculosis. Neurological examination showed a severe truncal and gait ataxia, without any sensory-motor impairment. Motor and somato-sensory evoked potentials were normal. Brain Magnetic Resonance Imaging (MRI) showed minimal signs of chronic ischemia only at a supratentorial level. Cerebral Single Photon Emission Computed Tomography, spinal MRI, total body computed tomography, Esophagogastroduodenoscopy, and finally total body Positron Emission Tomography resulted negative for neoplasms. Oncological serum markers were negative. Serum antibody against Purkinje's cells (Anti-Yo) was detected and titer was 1:80, while normally it should be undetectable. Other autoantibodies (Anti-Hu, Anti-Ri) were undetectable. Two sessions of plasma exchange (PE) were thus performed, leading to a rapid, marked and durable improvement of standing and gait and to a reduction of the autoantibody, which became undetectable. No serious adverse effect was noted. Although no definite therapy for autoimmune cerebellar ataxia has been established, PE should be considered as one of the main therapeutic choices.

Purpose: Hemodiafiltration reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We devised a new technique, post-dilution HFR, aimed at increasing the purification efficiency, treatment tolerability and at reducing inflammatory state., Methods: We performed post-dilution HFR in six uremic patients during 18 months. Dialytic efficacy, filter blood rest and cytokine behavior were evaluated., Results: Neither pyrogenic reactions nor other adverse phenomena were recorded. The tolerance to the treatment was excellent. We observed a high rate of urea extraction and optimal Kt/V values, a high extraction of beta2 microglobulin (beta2-m) and a reduction in blood rest; in addition, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) significantly decreased. CONCLUSIONS. The inversion of the standard HFR configuration allowed us to improve the removal of both urea and beta2-m, and the blood rest, with an optimal tolerability. Moreover, the reduction in cytokine levels could attenuate the uremic microinflammatory state.

Objective: To evaluate whether a dietary protein restriction is useful for slowing the progression of chronic renal failure (CRF) in diabetic and nondiabetic patients and to analyze the possible risk of malnutrition after such a dietary regimen., Design: Prospective, randomized case-control clinical trial., Setting: Nephrology outpatients., Patients and Other Participants: A total of 169 patients, 89 affected with CRF and chronic hypertension and 80 affected with overt diabetic nephropathy (24 suffering from type 1 and 56 from type 2 diabetes) and chronic hypertension., Intervention: Diabetic patients and nondiabetic patients were randomly divided into 2 groups: 40 diabetic patients received a low-protein diet (0.8 g/kg/day) and 40 were maintained on a free protein diet; similarly, 44 nondiabetic patients received a low-protein diet (0.6 g/kg/day) and 45 were maintained on a free protein diet. The investigation lasted 1 year., Main Outcome Measure: Renal function and nutritional status., Results: At the end of the study, there were no statistically significant differences in renal function between treated and nontreated diabetic patients, whereas treated nondiabetic patients showed a lower decrease in renal function compared with the nontreated group. In both diabetic and nondiabetic patients, the mean body weight and obesity index decreased significantly in treated patients compared with nontreated ones. Serum albumin and prealbumin were stable in all patients during the whole study time, and there were no other signs of malnutrition., Conclusion: An adequate dietary protein restriction is accepted by patients, and it is well tolerated during a 12-month follow-up. Without any sign of malnutrition, it is possible to get near the ideal body weight and to reduce the obesity index and the body mass index, which are both well-established risk factors for developing cardiovascular pathology. In nondiabetic patients only, we observed a significant slowing of the progression of renal damage.

Background: To offer data on the relationship between diet and risk of pelvic endometriosis, we analysed data collected in the framework of two case-control studies., Methods: Data from two case-control studies conducted in Northern Italy between 1984 and 1999 were combined. Cases were 504 women aged < 65 years (median age 33 years, range 20-65) with a laparoscopically confirmed diagnosis of endometriosis, admitted to a network of obstetrics and gynaecology departments in Milan, Brescia and Pavia. Controls were 504 women (median age 34 years, range 20-61) admitted for acute non-gynaecological, non-hormonal, non-neoplastic conditions., Results: Compared to women in the lowest tertile of intake, a significant reduction in risk emerged for higher intake of green vegetables [odds ratio (OR) = 0.3 for the highest tertile of intake] and fresh fruit (OR = 0.6), whereas an increase in risk was associated with high intake of beef and other red meat (OR = 2.0) and ham (OR = 1.8). Consumption of milk, liver, carrots, cheese, fish and whole-grain foods, as well as coffee and alcohol consumption, were not significantly related to endometriosis., Conclusions: This study suggests a link between diet and risk of endometriosis., (Copyright 2004 European Society of Human Reproduction and Embryology)

The authors describe the first human renal transplantation and the first renal xenotransplant in Italy and the atmosphere at the University of Rome where these transplants were performed. Just a few months after those events, a state law was approved which allowed kidney donation.

Introduction: Reactivation of polyoma virus BK (BKV) is increasingly recognized as a cause of severe renal-allograft dysfunction. The aim of the present study was to evaluate prevalence of BKV infection and activity in a population of kidney (KT) and liver (LT) transplant patients and search for a possible correlation with renal dysfunction., Methods: We studied 118 patients for BKV viruria and, when present, for BKV viremia. We also assessed HCV status., Results: Among 16 patients with BKV viruria (5 LT and 11 KT), eight showed BKV viremia (one LT and seven KT). Among BKV viruria-positive patients, three LT recipients were HCV-positive. All LT BKV viruria-positive patients showed normal renal function with a mean serum creatinine (sCr) blood level of 0.9 mg% and a mean blood urea nitrogen (BUN) value of about 36 mg%. The mean transplant age was 2.5 years. In contrast, KT BKV viruria-positive patients showed impaired renal function which was slightly worse in patients who also displayed BKV viremia, namely, a mean sCr blood level 1.7 mg% and a mean BUN value about 80 mg%. The mean transplant age was 7 years., Conclusion: Based on these findings, it seems that BKV viruria in renal allograft recipients may be associated with viremia and related to nephropathy that may lead to allograft rejection. The study will be completed with a 2-year follow-up of positive patients to assess the possible relationship between BKV active infection and eventual decrease of renal function and loss of transplanted organ.

The availability of cadaveric donor organs is insufficient for actual needs. The organ demand increases by 20% per year. Living donor transplant (LDT) may be a valid therapeutical alternative provided one uses proper criteria. LDT provides many advantages, like improved patient and organ survival, short waiting time, and the possibility to carefully plan the procedure. Potential risks include perioperative mortality and renal dysfunction in the kidney donor. At present, kidney LDTs in Italy represent 8% of the total, with an organ survival rate of 97% after 1 year (vs 93% for cadaveric transplants) and donors mortality rate of almost null. Most LDTs are performed from kinsmen. Presently, law no. 458, 26 June 1967, is in force in Italy for kidney LDT and law no. 453, 16 December 1999, for liver LDT. The foundations of LDT are, of course, the recipient's condition, the donor's motivation, and the altruism of the donation. It is desirable that in the future an increasing number of LDT be performed, supported by a careful, widespread health education regarding organ donation from living subjects and by the possibility to obtain insurance for the donor, which has been considered but never provided by actual laws.

Purpose: To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer., Patients and Methods: Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study., Results: Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively., Conclusion: This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.

Background/aims: Hemofiltrate reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We set up a new technique, postdilution HFR (PD-HFR), aiming at increasing purification efficiency, treatment tolerance and at reducing inflammatory states., Methods: We performed PD-HFR in 6 uremic patients during 1 year. Dialysis efficacy, dialyzer blood loss and the behavior of cytokines were evaluated., Results: No pyrogenic reactions or other adverse events were recorded. Treatment tolerance was excellent. We observed high urea extraction rates and optimal Kt/V values, high beta2-microglobulin (beta2m) extraction rates and a decrease in dialyzer blood loss; also IL-6 and TNF-alpha decreased significantly., Conclusions: Inversion of the standard HFR configuration has allowed us to improve the removal of both urea and beta2m, and to decrease dialyzer blood loss, with an optimal tolerance. Moreover, the decrease in cytokine levels might attenuate the uremic microinflammatory state.

Nowadays artificial devices are not able to totally and undefinitely replace the loss of function of all vital organs and artificial organs can be used only to bridge the time to transplantation, which must be considered the first choice in the therapeutical approach for many chronic diseases. Since general population aging process is leading to an increase of organ demand, the gap between performed and requested transplantation is hard to fill. Xenotransplantation is nowadays only an experimental alternative solution and we have to do our best using available artificial organs to increase and improve the survival of patients waiting for transplantation. In this meeting we particularly dealt about organ function replacing therapy, especially regarding the kidney, heart, liver, pancreas and ear.

Background: Elevated serum cardiac troponin T (cTnT) levels are frequently observed in chronic dialysis patients and have been shown to be associated with increased morbidity and mortality. The aim of this study was to determine whether cardiac troponin I (cTnI), which is less frequently elevated, has similar clinical significance., Methods: We studied 101 asymptomatic patients with no clinical evidence of coronary artery disease who were undergoing chronic dialytic treatment. We measured their serum cTnI levels immediately before the start of their dialysis sessions by a second-generation assay (OPUS-DADE). Our study included a year-long follow-up with trimestrial cTnI assays as well as clinical, X-ray and echocardiographic surveillance. We considered patients with serum cTnI > or =0.15 ng/ml as positive and those with levels <0.15 ng/ml as negative., Results: Among the 14 patients with high serum cTnI levels, nine (64%) suffered acute cardiac events during the 12-month follow-up. In contrast, among the 72 patients with low cTnI levels only seven (9.7%) had acute events. In another group of 15 patients with variable cTnI levels, three patients (20%) had cardiac events., Conclusion: Based on these results, serum cTnI appears to be a valuable predictive marker of cardiovascular events in asymptomatic dialysis patients. For those patients who might benefit from thorough cardiac investigation and treatment, information on cTnI could be useful in preventing cardiac events.

Unlabelled: Myasthenia Gravis (MG) is a neuromuscular disease often associated with thymic pathology due to neuromuscular transmission impairment by circulating antibodies directed against the cholinergic postsynaptic receptor on the neuromuscular junction (Anti-AchR-Ab). The treatment of MG includes cholinesterase inhibitors, steroids and thymectomy. Plasmapheresis can remove Anti-AchR-Ab but more recently plasma-perfusion (PP), a more specific apheresis for selective removal of noxious plasma components, has been developed., Aim of the Study: To study the effect of PP treatment, performed by using specific immunocolumns for Anti-AchR-Ab, on the clinical outcome of MG patients non-responder to steroid therapy or thymectomy., Materials and Methods: We treated 8 patients suffering from severe MG by a cycle of 6 sessions of PP. We used columns containing triptophan as a specific ligand for Anti-AchR-Ab. In order to evaluate the effectiveness of treatment we used functional tests (muscular tests, respiratory function, electromyography) and laboratory tests (Anti-AchR-Ab; immunoglobulins, complement fractions, immunocomplexes)., Results: After one to three PP sessions, early clinical improvement in bulbar and respiratory symptoms were found in all patients and EMG showed improvement of neuromuscular transmission. Serum concentration of immunological markers decreased progressively and significantly during the treatment. Clinical improvements were progressive despite the tendency for Anti-AchR-Ab to reach initial values between one session and another. We observed no side effects due to the type of immunocolumns used., Conclusions: Triptophan columns appear to be able to remove large quantities of Anti-AchR-Ab and immunological markers from plasma. Our experience shows that PP performed using triptophan columns in patients suffering from severe MG provides good clinical results, improving patients' outcome, without any risk linked to the procedure.

An unusual case of acute intestinal obstruction following a PPH stapled haemorrhoidectomy is reported: the complication was due to an almost complete interruption of the rectal lumen tightened by a purse-string suture anchored by staples. The stricture was dilated and the suture released thus restoring intestinal continuity. Surgeons should be aware that such troublesome complication may occur and can be treated successfully by a transanal approach.

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD. Cases were 268 women with a histologically confirmed diagnosis of complete or partial mole referred to the participating Trophoblastic Disease Centers. A total of 268 subjects were interviewed; 79 cases were classified as partial and 159 as complete mole. Controls were randomly selected women who gave birth to healthy infants at term on randomly selected days in the same network of hospitals in which cases had been identified. A total of 104 cases and 130 controls reported ever OC use, and the corresponding odds ratio (OR) was 1.5 (95% CI, 1.1-2.1). The risk of GTD increases with duration of OC use: the OR was 1.7 (95% CI 1.2-2.6) for ever-users reporting >or=12 months of use. No consistent pattern of risk was observed with time since last OC use. We have analyzed separately the association between OC use and risk of complete and partial moles: no statistically significant difference emerged, but the OR for partial moles was higher (OR 3.0, 95% CI 1.6-8.4) than for complete mole (OR 1.0, 95% CI 1.8). In conclusion, we observed a weak association between OC use and GTD; such a weak association could be explained by factors other than causality.

The government of the Marche Region has approved an Act called the "Regional Health Plan" establishing rules for the organization and development of healthcare. The main aim of the general plan is to rationalize the activities of medical laboratories first by making up an inventory of existing facilities and tests performed, and by classifying laboratories on the basis of their specialization and the complexity of tests that they perform.Moreover, the possible role of point-of-care testing and the need for clinical advice by laboratory professionals has also been debated.

Aim: To examine the degree of agreement between the paediatrician's assessment and parental reporting of infants' development using a postal questionnaire., Methods: The developmental status of 241 infants in the charge of 9 community paediatricians or discharged from one Neonatal Intensive Care Unit (NICU) was assessed by their parents 18 mo after delivery, using a postal questionnaire regarding child's height, weight. respiratory, hearing and vision problems, and items taken mainly from the Griffiths' Developmental Scales. At this age, infants were seen by the community or NICU paediatricians, for a complete physical and neurodevelopmental examination., Results: The mean agreement on items regarding developmental areas between parents and paediatricians was 93.0%. In general, parents and professionals agreed on items describing gross motor behaviour (k from 0.39 to 0.83) and disagreed on individual questions describing language/relational behaviour (k from 0 to 0.38). A 97.9% level of agreement was found for hearing status (k = 0), and 96.2% for assessment of vision (k = 0.29), whereas the level of agreement ranged from 43.2% to 86.2% (k from 0 to 0.15) for the three questions describing respiratory problems. The mean weight and height assessments by paediatricians and parents of infants at 18 mo of age were similar., Conclusions: Further improvement of the questionnaire is needed, but our findings suggest that this methodology can be considered for use in comparing large cohorts of infants included in randomized clinical trials.

Background: The management of patients suffering from Amanita Phalloides poisoning (APP) may be very challenging. Furthermore, the treatment often includes depurative techniques and Orthotopic Liver Transplantation (OLTx) must be started timely to be effective. We report our experience in severe APP treatment., Patients and Methods: We retrospectively evaluated five patients suffering from APP and hospitalized within our Intensive Care Unit, assessing different kinds of treatment: two different dialytic techniques, namely Continuous Renal Replacement Therapy (CRRT), and Charcoal Plasmaperfusion (CRRT+CPP), and OLTx., Results: Two patients treated with CRRT+CPP, one patient treated with CRRT only and the patient treated by OLTx recovered. One patient, undergoing CRRT only, died after 14 days of treatment. During the CRRT+CPP treatment no relevant complication occurred. The transplanted patient received dialytic treatment for 7 days after transplantation in order to support renal function impairment and to enhance liver function recovery., Conclusions: Clinical management of patients suffering from APP requires multi-disciplinary intervention; therefore it is recommended to treat these patients in an Intensive Care Unit with specialized nephrological and toxicological consultancy, in collaboration with an organ transplantation team. In the near future we wish to associate dialytic treatment with a bioartificial liver device, which could bridge the time gap to liver transplantation.

We evaluated adherence to HIV treatments every 4 months during one year in 63 HIV-infected subjects using combination therapies including a protease inhibitor. A total of 18 subjects reported a high level of adherence, 14 in two evaluations, and eight a low level of adherence in all the three evaluations. The remaining 23 subjects (36.5%) reported different levels of adherence to treatment in the three evaluations. These findings suggest that the level of adherence to treatment changes markedly for each patient over time.

Objective: A large observational study was conducted to assess the frequency of urinary incontinence (UI) and overactive bladder (OAB) and to describe the diagnostic and therapeutic approach in General Medical Practice in Italy., Materials and Methods: Subjects eligible for the study were men aged > 50 years and women aged > 40 years, observed consecutively by their own General Practitioner (GP) for a check-up or medical prescription examination during the recruitment period, who agreed to participate in the study. All the subjects included in the study were interviewed by their GP using a common questionnaire that included information about their general characteristics and a specific medical history. The subject was also asked: "Have you had involuntary loss of urine during the last 3 months?"; "Do you urinate more than 8 times a day on average and/or Do you have to get up more than once a night?"; "Have you urgency problems?". If the subject answered yes to the first question or to both the second and third, a urinary problem was diagnosed, in particular UI if the anser was yes to the first and OAB if to the second and third. In these subjects the interview was continued in order to define the type of UI, using the diagnostic flow chart proposed by Wean., Results: On the whole, 9613 men (average age 64.8, range 50-98) and 13,365 women (average age 60.3 years, range 40-98) were interviewed by 774 GPs. A diagnosis of urinary problems was made in 1084 men (11.3%) and 1507 women (11.3%). Among the men the GP was already aware of the condition in 603 cases (55.6%) and a new diagnosis was made in 481 cases (44.4%). The corresponding figures for women were 560 (37.2%) and 947 (62.8%). The proportion of new diagnosis out of all the subjects with micturition problems tended to be greater in the younger age (chi square for trend p < 0.05). The presence of OAB without UI was found in 3.0% [95% Confidence Interval (CI) 1.7-3.5] of the men and 1.1% (95% CI 0.9-1.3) of the women. Over all, 8.3% (95% CI 7.7-8.9) of the men and 10.2% (95% CI 9.6-10.8) of the women reported UI. The frequency of OAB and UI conditions increased with age in both men and women. On the whole, a urine test was requested in 71.9% of the subjects with a new diagnosis of UI or OAB and the frequency of haematuria was equal to 15.7% of the cases, without marked differences by type of diagnosis of micturition problem. A urine culture was done in 60.7% of the cases and was positive in 17.7%. Further diagnostic investigations were prescribed in the majority of cases, 76.6%. This was observed in particular among the men (86.2% of the cases compared to 71.7% of the women) but with no substantial differences between the different diagnoses of UI. Pharmacological treatment was suggested to 68% of the men and 44.9% of the women. The condition for which pharmacological treatment was less often prescribed was stress UI, where it was suggested in 54.5% of the men and 27.3% of the women. For men, alpha-lytics were the drugs most often prescribed for all urinary problems, regardless of the type. For women, anticholinergics were the most commonly advised type of drug, followed by anti-infectives.

Acute renal failure is the most common complication of rhabdomyolysis, with an 8-20% reported incidence. In particular, rhabdomyolysis associated with acute renal failure is frequently observed in critically ill patients, with a 6-16% reported incidence in Intensive Care Units. Dialytic treatment is necessary to correct hydroelectrolytic imbalance and renal function alterations and it may be a pathogenetic therapy by myoglobin removal. In the present study we evaluated our experience on patients suffering from rhabdomyolysis and acute renal failure subjected to dialytic treatment. We retrospectively studied 28 patients, 17 admitted in our Intensive Care Unit (ICU-patients) and treated by continuous renal replacement therapy (particularly by continuous venovenous hemofiltration, continuous venovenous hemodialysis and continuous venovenous hemodiafiltration) and 11 admitted in our Nephrology Department (NICU-patients) and treated by high-efficiency daily hemodialysis. We excluded one ICU-patient from the study because she was affected with lung end-stage neoplasia and it would have been difficult to evaluate the effects of the dialytic treatment on RML biochemical index and on her final outcome. ICU-patients were older, with a mean age of 64 +/- 10 yrs, and were suffering from MODS and typical elderly diseases, such as cardiac and respiratory chronic failure, except from 3 patients with acute liver failure resulting from poisoning, who were relatively younger. In NICU-patients, instead, the mean age was 36 +/- 16 yrs and the causes of RML were narcotic drugs abuse, repetitive seizures and vigorous exercise, more frequently observed in young people. In three relatively older NICU-patients RML was due to lipid lowering drugs assumption. Before starting the dialytic treatment, in ICU-patients CPK plasma level was 2615 +/- 3586, while K+ was 5.10 +/- 1.08 and sCr was 5.69 +/- 4.06 In NICU-patients, on the other hand, CPK was 14273 +/- 9266, while K+ was 5.75 +/- 0.92 and sCr was 5.9 +/- 0.4. ICU-patients mortality rate was 50% (8/16 patients) in spite of the good recovery of renal function and the biochemical RML indexes improvement. In NICU-patients, instead, only one patient died for septic complications (he was a heroin-addict and suffered from overdose syndrome). Early dialytic treatment of RML allows not only to avoid life-threatening complications (first of all the acute renal failure) but moreover it's a pathogenetic treatment because it removes great amount of myoglobin from the plasma. Beside this, continuous renal replacement therapy allows a successful management of critically ill patients with severe hemodynamic conditions. Nevertheless, the final outcome may be very different between ICU- and NICU-patients, with a higher mortality rate in ICU-patients, suffering from MODS.

Continuous Renal Replacement Therapy (CRRT) indication is still discussed. We report our experience on 98 patients affected with Multiple Organ System Failure (MOSF) and renal failure (acute or chronic) requiring dialysis and timely treated by CRRT. Mortality after 5 days of ICU permanence was 60.2%; the remaining 39 patients were discharged within 21 days and received CRRT treatment for 6.36 +/- 5.59 days. APACHE II score was not able to predict the outcome of patients suffering from acute renal failure (ARF). On the contrary, Systemic Inflammatory Response Syndrome (SIRS) incidence was significantly higher in deceased patients compared to recovered patients. In conclusion, it is important to start dialytic treatment immediately when patients affected with MOSF show renal function damage, even if at an initial stage, in order to improve patients' survival. Moreover a multidisciplinary approach is preferable in ICU patients treatment for not underestimating the management of metabolic and infective complications, the nursing care, and nutritional support.

Purpose: To investigate long-term cardiac sequelae associated with anthracycline use in adjuvant chemotherapy of patients with early breast cancer., Patients and Methods: All 1,000 patients from three prospective trials of adjuvant chemotherapy containing doxorubicin (n = 637, median total dose of 294 mg/m(2)) or not containing the anthracycline (cyclophosphamide, methotrexate, and fluorouracil [CMF] regimen alone, n = 363) were analyzed for the relative incidence of congestive heart failure (CHF) and myocardial infarction (MI) during 14 years of follow-up. The 462 women continuously free of disease as of February 1996 were recalled, and 355 consented to undergo evaluation including 12-lead ECG and cardiac ultrasound with determination of left ventricular ejection fraction (LVEF) to assess the relative incidence of abnormalities in long-term survivors., Results: Among the 1,000 patients, there were six cases of CHF and three cases of MI. Cumulative cardiac mortality accounted for 0.4% (doxorubicin-treated = 0.6%; CMF-treated = 0). Eighteen (5%) of the 355 patients undergoing cardiac evaluation after median 11 years of follow-up presented systolic dysfunction as defined by pathologic (< 50%, n = 8) or borderline (50% to 55%, n = 10) LVEF. Systolic dysfunction was higher in doxorubicin-treated (15 of 192; 8%) than in CMF-treated patients (three of 150; 2%). Breast irradiation had a significant impact on the occurrence of early CHF (four of 116; 3%), but not on systolic dysfunctions., Conclusion: At longer than 10 years of follow-up, the use of doxorubicin at a total dose commonly applied in regimens of adjuvant chemotherapy does not lead to cardiac clinical sequelae that counter-balance the benefit of treatment in patients with operable breast cancer who may be cured of their disease.

At the Istituto Nazionale Tumori of Milan, a randomised adjuvant chemotherapy trial was carried out from 1982 to 1990 to compare alternating with sequential regimens of doxorubicin and CMF in 403 patients with more than 3 positive axillary nodes. Tumour proliferative activity was determined in 71% (285 cases) of women entering the clinical study. We investigated the relation between proliferative rate, determined as the [(3)H]thymidine labelling index (TLI) on tumour specimens obtained at diagnostic surgery, and clinical outcome following the 2 regimens, in which the same drugs were administered at the same dose intensity but with a different schedule. A high TLI was significantly associated with 12-year overall relapse (P = 0.009), distant metastasis (P = 0.001), and death (P = 0.002), even in the presence of information provided by tumour size, lymph node involvement, oestrogen receptors, and treatment regimen. The highest relapse-free survival (RFS) probability (45%, 95% CI 34-55%) was observed for patients with tumour TLI <5% and subjected to the sequential treatment. The lowest RFS probability (11%, 95% CI 0-26%) was observed for patients with tumour TLI >9% following the alternating regimen. Intermediate RFS probabilities, ranging from 23% to 34%, were observed for the other kinetic subgroups following the 2 treatment regimens. The benefit of sequential administration of doxorubicin and CMF was evident mainly in patients with tumours at low to intermediate proliferation., (Copyright 2000 Wiley-Liss, Inc.)

Histopathology has been suggested as a reliable method for tumour reduction evaluation of preoperatively treated breast cancer. Immunocytochemistry can be used to enhance the visibility of residual tumour cellularity and in the evaluation of its proliferative activity. We compared Image Analysis (IA) with Light Microscopy Analysis (LMA) on sections of breast carcinomas treated with preoperative chemo- or chemo/radiotherapy in the evaluation of the Neoplastic Cell Density (NCD) (69 cases) and the Proliferation Index (PI) (35 cases). NCD was expressed as the immunoreactive area to cytokeratin over the total original neoplastic area and PI was expressed as the number of immunostained tumoural nuclei with MIB 1 MoAb over the total of tumoural nuclei. The intraobserver agreement and that between IA and LMA for both indices were estimated by the common (kappa(w)) and the jackknife weighted kappa statistic (kappa(w)). The extent of agreement of each considered category was also assessed by means of the category-specific kappa statistics (kappa(cs)). The intraobserver agreement within LMA for NCD and PI and that between IA and LMA for PI were both satisfactory. Upon evaluation of the NCD, the agreement between IA and LMA showed unsatisfactory results, especially when the ratio between the residual tumour cells and the background was critical.

We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

An automated, fluid-based method for the preparation of cervical Papanicolaou smears/slides was compared to the conventional Papanicolaou smear (CPS) method used for the screening of neoplasia. We determined diagnostic agreement and sources of error for diagnostic disagreement. For 665 patients, one cervical sample was collected to make one CPS. The collection devices, a wooden Ayre spatula and endocervical brush, were rinsed into a vial with fluid medium to be processed in the automated device. All slides were distributed among five cytotechnologists in a blind fashion. Exact diagnostic agreement was 94.6%. The results were not statistically significant (P > or = .70, McNemar's test) but were clinically important, as evidenced by the detection of low grade lesions (LGL), during initial screening, on three slides prepared by the automated device but not on their matched-pair CPSs (0.5% of all specimens). After reevaluation, the three matched CPSs demonstrated LGL. Sources of diagnostic error on the CPSs were: air-drying artifact, obscuring blood/inflammation, crowding/overlapping of cells and/or absence of diagnostic cells. The only source of error in the automated-method smears was absence of diagnostic cells.

A total of 1292 sera, provided by different USLs (Local Health Centers) in the Marche Region (Italy), was tested by ELISA and Western Blot for the detection of anti-HTLV I/II ad HIV-1 antibodies. It was decided not to follow any particular criterion when collecting the sera, so no protocol of admission was established in advance. Of the 1292 sera tested, 12 were found antibody positive to HTLV I/II, 18 to HIV-1 and 4 to both viruses. Of the seropositives, for HTLV I/II and HIV-1, respectively, 2 and 3 were prisoners; 2 and 4 were IVDAs, 3 and 7 were hematological patients, 3 and 2 were hospitalized subjects (not for hematological disorders), and 2 and 2 were positives belonging to a healthy population group. These data suggest that the viruses may also be spreading among groups other than the high-risk ones (homosexuals, IVDAs, prisoners, blood-transfusion recipients, promiscuous heterosexuals).

This paper reports the results of a study carried out on 4614 samples of urine from inpatients and outpatients according to the sex. The positive monomicrobic urine specimens were examined and isolated strains were tested against various antimicrobial drugs. Our findings showed that 43.1% of urine specimens examined from inpatients and 38.4% from outpatients proved to be positive. Among the bacterial species more frequently isolated, significant differences among Enterobacter spp. in males and coagulase-negative Staphylococcus spp. in females from general practice, and Pseudomonas spp. in females from the hospital were observed. Statistical analysis reveals that: a) no significant differences were found in antibiotic-resistance among Escherichia coli, Proteus rettgeri, Streptococcus faecalis, Enterobacter spp. and Pseudomonas spp., isolated from inpatients and outpatients as regards males and females; b) Klebsiella spp., Proteus rettgeri and coagulase-negative Staphylococcus strains isolated from females inpatients are more chemo-resistant than those from females outpatients.

A colorimetric procedure is described for the determination of serum iron and TIBC, utilizing the action of the iron on the oxidation reaction of 4-aminophenazone with H2O2. The chromogen oxidized has maximum absorption at 540 nm. The method is interesting because it has important advantages over other methods: no deproteinization is needed, microsamples are used, it is simple, gives adequate precision, and the results correlate well with those obtained with the standard bathophenanthroline method.

The urinary proteins determination was carried out after purification by gel filtration over Sephadex rosin. The proteins eluaded react with Biuret-reagent to establish the coloured copper-proteins complex. If proteins concentrations is inferior, the proteins can be determinated by the copper-proteins complex isolation with second gel filtration and titrating Cu++ with reactives: dietildithiocarbamate or the PAR (4-(2pyridyl-azo)resorcinol monosodium salt).

We installed in our microbiology laboratory a new computerized management system with a dedicated software for the needs of the department. The system allow us to give to the clinician the reports of microbiological data in a shorter time and to store them permanently. The computer system doesn't modify the existing organization of work, samples acceptance, execution of microbiological and serological tests and the report of the results, but make them faster, safer and more efficient. The system also shows the possibilities of epidemiological researches and statistical studies. These data are very interesting and useful for the relationship between the laboratory and general wards.

The possibility to administer chemo-hormone- and immunotherapy on an out-patient basis has greatly increased because of the progress reached in the management of the out-patient departments. The improved knowledges on tossicological, pharmacodynamic and therapeutic data as well as the advent of the cyclic schedules determined the feasibility of medical treatments even when they are combined with surgical and/or radiotherapeutic modalities. To the patient, the possibility to be carefully and effectively treated on out-patient clinic, renders more acceptable, both from a psychologic and economic point of view, even a prolonged combined treatment. On the same time, also the Institutions have some advantages both on their organization (a shorter median stay in hospital and consequently a reduced waiting list) and for their scientific program (increased number of patients who can be treated according to a therapeutic program, possibilities to obtain statistically valuable information on the treatment program of a given disease and on the knowledge of its natural history). The last five year increasing activity of the Out-Patient Clinic for Medical Oncology Treatment of the Istituto Nazionale Tumori of Milan is illustrated in Text-figure 1, while Text-figure 2 represents its actual organization; this is obviously of a multidisciplinary type, both on its diagnostic and therapeutic phase. Table 1 shows the activity carried out in 1975; it is noteworthy that 2,570 patients have been followed, thus accounting for a total of 20,164 medical examinations and/or intravenous drug administrations. Table 2 presents the incidence of the different types of neoplasia followed in the out-patient department: the large majority was represented by breast cancer (40%); followed by malignant lymphomas (31.5%) and pediatric tumors (7.5%). During 1975, 22 therapeutic protocols have been applied, 10 of which (table 4) required an initial hospitalization and 12 (table 5) could be entirely carried out in the out-patient department. As shown in Table 6 chest x-rays accounted for 52% and skeletal survey for 18% of the 11.906 radiological examinations. Table 7 shows the number of off-hand required radiological reports carried out for patients not geographically accessible who, in one signle day, could have their radiological, and medical examinations as well as their hemogram and treatment performed. A total 467 scintiscans have been required, 86% of which of the liver (table 8). The hemato-pathology unit counted out about 16,000 hemograms with platelets (table 9). The hemograms were always performed within 1-2 hours with immediate communication of the counts to the out-patient department. In order to modify clinical situations which were deteriorated because either of the disease or of the treatment 358 blood units were transfused.

654 bacterial strains isolated from different biological materials have been tested either with "abac" automatic system or diffusion system on disks according to the Bauer-Kirby standardized method. The higher discrepancy has been observed to Co-trimoxazol antibiotic. Some other discrepancies, non significative, are shown in figures. The use of "abac" provides increased efficiency and convenience improving the quality of routine antimicrobic susceptibility results.