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Amylose and amylopectin were functionalized with an alkynyl derivative of spiropyran (SPCC) and/or propargyl alcohol by a two step procedure consisting in the derivatization of glucopyranose units with azide at the C6 position followed by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAc). Substitution degrees with spiropyran (DSSP) between 0.10 and 0.95 were achieved by simply modulating the molar ratio between alkyne species and polysaccharide in the CuAAc reaction, as it was confirmed by FT-IR and NMR spectroscopy characterizations. The UVeVis spectra of SPCC-modified amylose in DMF solution kept in the dark exhibited an absorbance band with maximum at ~346 nm, ascribed to spiropyran units. The intensity of the absorbance was found to increase linearly with DSSP. Upon irradiation with UV light, a band at ~560 nm appeared, due to the conversion of spiropyran to zwitterionic merocyanine, its intensity linearly increasing with DSSP too. ICP-MS analysis showed the presence of a small amount (

This paper investigates an original solution that can be used in the design of axial-flux permanent-magnet (AFPM) machines whenever a constrained shaft height requirement penalizes a standard design. A machine is tailored for electrical traction, but the ideas that are set forth are valid for any application with a constrained shaft height. Two design solutions that comply with a constrained shaft height are investigated, i.e., a standard Torus AFPM machine and an asymmetrically wound Torus machine, which is named “Ω AFPM” due to the shape of the stator winding. It is shown that the Ω AFPM machine has lower losses and higher efficiency. Finite-element simulations and experimental tests on a full-scale prototype confirm the validity of the proposed solution.

Background. Rituximab, a chimeric monoclonal antibody, has been successfully given in various diseases including HCV-associated mixed cryoglobulinemia. However, only preliminary data exists on its efficacy and safety after renal transplantation. Methods. We report on a renal transplant recipient with chronic hepatitis C who received rituximab therapy for gastric cancer. Four rituximab infusions of 375 mg/m2 were given. Results. Rituximab therapy was complicated by cholestatic hepatitis C with very high HCV RNA levels; liver insufficiency occurred. The patient developed bacterial pneumoniae and respiratory insufficiency was the cause of death. Although other mechanisms cannot be excluded, we found that rituximab therapy was implicated in the pathogenesis of cholestatic hepatitis C in our patient. Conclusions. We suggest that rituximab therapy may be associated with significant side effects. More experience has to be accumulated before any conclusions on efficacy and safety of rituximab therapy after RT can be drawn.

Background/Aims: Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination, including to hepatitis B vaccine. A recombinant HB vaccine containing a new adjuvant system AS04 (HBV-AS04) has been recently developed; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis. All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospectively included. Methods: Patients received four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 0,1,2, and 3. Anti-HB surface antibody concentrations were measured at intervals of 1, 2, 3, 4, and 12 months. Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine. Results: 102 patients were enrolled and 91 completed the study. At completion of the vaccination schedule, using per-protocol analysis, 76 of 91 (84%) had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations (GMCs) of 385.25 mIU/mL. The sero-protection rate at month 12 was 84% (48/57) with lower GMCs (62.74 mIU/mL, PPConclusions: HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present. Prospective studies with HBV-AS04 on larger study groups and with longer follow-ups are under way.

Background Dialysis and kidney transplantation represent two effective strategies in treating chronic uremia, albeit with different results. Our study compared the psychological aspects of two categories of patients: patients who faced kidney transplantation and have been on dialysis, and noncompliant patients treated with these therapies. Materials and Methods On 170 patients (120 hemodialysis and 50 peritoneal dialysis) we used a personality analysis (MMPI2) and the COPE, which assessed the ability of patients to cope under certain conditions that can be perceived as stressful or, in any case, unusual. The screening succeeded in 11 cases among the first group and 9 in the second. Three of the 20 patients were considered to be partially noncompliant: 1 on peritoneal and the other 2 on hemodialysis. We also tested a control group of 300 people of different ages, sexes, social and cultural status, dates and kinds of transplantation (cadaveric or living donors). Of the 36 feedbacks received, only 30 were considered valuable. Results The results of the research showed that patients with less than 2 years of dialysis treatment and patients with more than 2 years survival after transplantation time were inclined to deny their disease and the possible emotions about their clinical status, drawing an inadequate attention to the difficulties. This behavior was clearer among noncompliant patients. Family problems and couple malaise in everyday life can push more and more of these patients to be noncompliant with therapeutic prescriptions, as they do not feel adequate support. The result is an excessive foreboding, poor disposition, and nervousness. Conclusions Screening of patients’ social and psychological status is useful as is psychological intervention for those who miss emotional support from the family. This psychological support is advisable for uremics who have to enter a waiting list and for those who are subject to postoperative treatment in order to promote compliant behavior.

Only a few cases of acute post-infectious glomerulonephritis have been described in renal transplant patients. We report here three cases of acute post-bacterial glomerulonephritis in renal transplants. In contrast to the classic cases of post-streptococcal glomerulonephritis the type of infection was heterogeneous: respectively, Escherichia coli bacteremia, a skin abscess, and cholangitis. The clinical presentation was characterized by a deterioration of graft function in two of our three patients. Acute renal dysfunction recovered in both patients, but in the long term the outcome was severe; two of the three patients lost their graft function. It is difficult to ascertain whether progression was due to chronic allograft nephropathy, to glomerulonephritis, or both. It may be concluded that acute post-infectious glomerulonephritis is a possible, although rare, complication in renal transplant recipients. It has an unusual presentation and may have a poor outcome in the long term. The role of therapy, if any, is still undefined.

Background Little information is available about the role of oxidative stress in renal transplant patients. To evaluate the prevalence and severity of oxidative stress in renal transplantation, the authors conducted a cross-sectional study. Methods In 112 cadaver or living-donor kidney transplant recipients with a follow-up of at least 6 months and with plasma creatinine less than or equal to 2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC), serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured. Results The mean levels of Hcy (21.1 microM vs. 350 micromol/HclO/mL), were higher than the reference interval, whereas -SH groups, vitamin B12, s-F, and ery-F were within the normal range. In the multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and TAOC (P=0.0007) were independently associated with oxidative stress. At multiple regression analysis, -SH groups and ROS were directly and inversely related to hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between -SH groups and blood pressure levels (P=0.0095). Conclusions Renal transplant patients have a pattern of increased oxidant stress that is counterbalanced by an enhancement of the antioxidant mechanisms. Besides the well-known risk factors, the authors found that anemia is an independent risk factor for an increase of ROS. Further studies are needed to evaluate whether the correction of anemia might prevent or reduce the oxidative stress in renal transplant patients.

Risk factors for late kidney allograft failure. Background While graft survival rates in the short term have improved dramatically, only a modest improvement has been shown in long-term graft survival rates. We evaluated the causes of late failure in renal allograft recipients treated with cyclosporine A (CsA). Methods A total of 864 adults with a functioning graft at one year were evaluated. The end points were dialysis or death with a functioning graft. Results The 13-year patient and graft survival probabilities were 0.82 and 0.64, respectively. The graft half-life was 20.1 years and the pure graft half-life was 31.1 years. At multivariate analysis, plasma creatinine at one year ( P = 0.0006; RR 1.72), low-density lipoproteins (LDL) at one year ( P = 0.0014; RR 1.65), older age ( P = 0.0128; RR 1.50) and delayed graft function ( P = 0.0350; RR 1.45) were associated with the end point. Chronic allograft nephropathy was the cause of failure in 97 patients, death in 70, recurrence of glomerulonephritis in 24, other events in 6. Cardiovascular complications were the most frequent cause of death. Post-transplant cardiovascular events were associated with: pre-transplant cardiovascular events ( P = 0.0012; RR 2.65), older age ( P = 0.0001; RR 2.46), pre-transplant arterial hypertension ( P = 0.0249; RR 1.57), smoking ( P = 0.0235; RR 1.29), duration of dialysis ( P = 0.0229; RR 1.28). Mean serum cholesterol, LDL and triglycerides were each significantly associated post-transplant cardiovascular events. Conclusions The graft half-life was 20 years. Chronic allograft nephropathy was the leading cause of late failure, followed by death. If the data were censored by death, the projected pure graft half-life would be 31.1 years. Pre-transplant selection and preparation of the candidate as well as appropriate life style are recommended to improve life expectancy and extend graft survival.

Kidney transplantation in patients with IgA mesangial glomerulonephritis.BackgroundStrategies for treating IgA glomerulonephritis (IgAGN) are controversial, particularly with regards to the long-term results of kidney transplantation, including the risk of recurrence of IgAGN post-transplant and the impact of this recurrence on graft survival.MethodsThe outcomes of 106 adults transplanted because of a biopsy-proven IgAGN and of 212 patients without IgAGN transplanted during the same period were analyzed. To evaluate the risk of recurrence, patients with hematuria, proteinuria, or an increase in plasma creatinine were submitted to allograft biopsy. Factors influencing recurrence and the impact of recurrence on graft survival were analyzed.ResultsThe ten-year patient (0.93 vs. 0.92) and graft survival (0.75 vs. 0.82) probabilities were not significantly different between IgAGN patients and controls. Only plasma creatinine and proteinuria at six months were associated with an increased relative risk (RR) of graft failure (RR 2.79 and 5.94, respectively). Histological recurrence of IgA glomerulonephritis was diagnosed in 37 patients. Younger age (RR 2.63), increased plasma creatinine (RR 2.39), and proteinuria (RR 6.02) at six months were associated with the risk of recurrence. If proteinuria and plasma creatinine at six months were considered in the Cox model, IgA recurrence per se was not associated with an increased risk of graft failure (P = 0.181). The main causes of graft failure were glomerulonephritis in patients with recurrence of IgAGN and chronic rejection in patients without recurrence.ConclusionsThe ten-year graft survival rate was similar in patients with IgAGN or other renal diseases. At least 35% IgAGN patients had biopsy-proven recurrence, and younger patients were more prone to the risk of recurrence. Recurrence did not affect the ten-year graft survival.

This open, multicenter, randomized, parallel-group study evaluated the efficacy and safety of tacrolimus-based dual and triple therapy regimens. For this 3-month study (with 12-month follow up), 491 adult renal transplant patients were randomized and received either dual therapy (tacrolimus/corticosteroids; 246 patients) or triple therapy (tacrolimus/corticosteroids/azathioprine; 245 patients). Patient survival rates at months 3 and 12 were 99.2 (dual) vs 99.6 % (triple) and 97.8 vs 98.7 %, respectively. Graft survival rates at months 3 and 12 were 94.1 (dual) vs 95.4 % (triple) and 92.8 vs 93.3 %, respectively. After 3 months, the incidences of treated acute rejection were 28.8 (dual) and 29.7 % (triple); and 7.6 (dual) and 5.4 % (triple) for corticosteroid-resistant acute rejections. Between months 4 and 12, three new first rejections were reported, (dual: 2, triple: 1). For leukopenia (1.3 vs 11.7 %; P < 0.001) and anemia (14.8 vs 23.0 %, P = 0.026), significantly higher incidences were reported in the triple therapy group. The incidence of de novo insulin-dependent diabetes was 5.6 (dual) and 4.0 % (triple) at month 3. In terms of efficacy, no difference between the treatment groups was observed.

There is little information on the long-term outcome of patients initially assigned to cyclosporine (CsA) monotherapy and requiring the addition of steroid therapy during follow-up. The aim of this report is to describe our experience with 143 first renal transplant recipients (120 cadaver transplants, 23 living donor transplants) randomized to receive CsA monotherapy as a treatment arm of three consecutive controlled clinical trials. Median follow-up was 86 months. Thirty-four percent of the patients remained on the original CsA monotherapy, whereas the remaining 66% required the addition of steroid therapy. Cumulative patient and graft survivals at 11 years were 0.89 (95% confidence interval [CI], 0.83 to 0.95) and 0.62 (95% CI, 0.52 to 0.72), respectively. The 11-year graft survival for converted patients was 0.53 (95% CI, 0.39 to 0.67). Cumulative graft half-life was 19.9 +/- 3.47 (SE) years. According to the Cox model, variables at transplantation that correlated with a lower 11-year graft survival were yearly increases in age (relative risk [RR], 1. 04; P = 0.039), monthly increases in hemodialysis duration (RR, 1.01; P = 0.029), no blood transfusion before transplantation (RR, 1.99; P = 0.043), CsA administration in a double daily dose (RR, 2.35; P = 0.008), and a cadaver donor transplant (RR, 4.76; P = 0.039). Multivariate analysis of time-dependent variables showed that delayed graft function recovery (RR, 2.20; P = 0.019) and the need to add steroid and/or azathioprine therapy (RR, 5.28; P = 0.000) were also correlated with a lower graft survival. Patients who added steroid therapy developed infections (P < 0.001), cataracts (P < 0.001), cardiovascular complications (P = 0.004), and arterial hypertension (P = 0.024) more frequently than patients remaining on CsA monotherapy. Patients administered CsA in a single daily dose received significantly less CsA over the years (P = 0.0042) than patients administered CsA in two divided doses. They also showed a trend toward greater creatinine clearance levels, although not statistically significant. In conclusion, this analysis showed that in patients assigned to CsA therapy alone, good long-term patient and graft survival probabilities can be obtained. In approximately one third of the patients, the use of steroids could be avoided for up to 11 years, and these patients had a better long-term outcome than those who required the addition of steroid therapy. Finally, in patients administered CsA in a single daily dose, the possibility of reducing CsA dosage probably led to better intrarenal hemodynamics with improving creatinine clearances.

In this paper we assessed the clinical status of 150 cadaveric renal transplant patients who received cyclosporine without interruption for 10 yr. The mean creatinine clearance was 59.2 +/- 15.71 at 1 yr and 55.6 +/- 24.91 mL/min at 10 yr (p = 0.039). Patients were subdivided into four quartiles according to the mean creatinine clearance at 1 yr. The 14 patients with the lowest quartile showed a significant decrease of creatinine clearance from the 1st to 10th year (from 31.5 +/- 5.83 to 24.8 +/- 14.00 mL/min; p = 0.038) while no difference between the mean creatinine clearance at 1 and at 10 yr was found in the other three quartiles. At 10 yr, 84.6% patients needed antihypertensive therapy, a rate similar to that seen at 1 yr (81.4%). The mean plasma cholesterol (253 +/- 57.8 mg/dL) and triglyceride (197 +/- 113.1 mg/dL) at 10 yr were similar to those found at +/- yr (243 +/- 48.2 and 201 +/- 143.0 mg/dL, respectively). Most patients have a high degree of rehabilitation 10 yr after uninterrupted cyclosporine therapy and all patients but 3 were able to work.

Promising immunosuppressive drugs designed to prevent rejection have been developed recently. Two monoclonal antibodies directed against the interleukin-2 (IL-2) receptor, daclizumab and basiliximab, have been shown to significantly reduce the incidence of acute rejection without increasing adverse events. Sirolimus (rapamycin), an agent that inhibits T- and B-response at a later stage than cyclosporin, has been shown to be synergistic with cyclosporin in experimental and clinical studies. Ongoing clinical trials have reported that in renal transplantation high doses of sirolimus are as effective as cyclosporin. SDZ-RAD, a derivative of sirolimus, is also under investigation. FTY-720 another promising drug, prolonged the survival of allografts and synergised with cyclosporin and sirolimus in experimental models. Gusperimus (deoxyspergualin), which inhibits IL-1 synthesis, was useful in reversing early and late acute rejection in clinical trials. Antisense oligonucleotides which interfere with intercellular adhesion molecules which are important in rejection, gave encouraging results in primate renal allografts. The availability of these new drugs will be able to further abate the risk of rejection in organ transplantation. However, caution is warranted with their use in order to avoid the risks of over immunosuppression. Today excellent results can be obtained with the available drugs. Newer immunosuppressive schedules should be designed, not only to reduce the risk of rejection, but also to obtain a better therapeutic index that allows a further improvement of the graft survival while minimising the comorbidity and drug-related toxicity.

In patients who have not undergone transplantation, Guillain-Barré syndrome (GBS) is typically preceded by an acute infection often sustained by Campylobacter jejuni. Thus far, in renal transplant recipients, only eight cases of GBS have been reported. In seven patients GBS was attributed to cytomegalovirus infection and in the eighth patient to cyclosporin A neurotoxicity. We report here the case of a GBS in a renal transplant recipient following C. jejuni bacteremia. The infection quickly disappeared after erythromycin and methronidazole therapy. GBS progressively evolved into a paraparesis within 1 week. After reaching a plateau phase, the clinical status improved and the patient was able to walk unassisted after 3 weeks. At this last check-up, 54 months later, the patient was doing well with a functioning graft and only minimal weakness of the lower limbs.

The influence of three different immunosuppressive regimens with cyclosporine (CsA) on the development of osteopenia in renal transplant patients was assessed. Fifty-three adults with first kidney transplants participated in a randomized trial to analyze the efficacy of three different immunosuppressive regimens: CsA alone (group 1), CsA plus steroids (group 2), and CsA plus steroids plus azathioprine (group 3). Lumbar spine bone mineral density was assessed by dual energy x-ray absorptiometry every 6 months for 18 months. The values for trabecular mass were expressed as bone mineral density and as a fraction of the standard deviation of the mean of the normal value for patient's sex and decade of age (Z-score). Statistical analysis was performed on Z-score and "Z-score change" (value after 6 months minus the basal value at transplantation). At the 18th month, the Z-score increased significantly in treatment group 1 without steroids (P=0.006) and decreased significantly in steroid-treated groups 2 (P

This contribution investigates an original solution that can be used in the design of AFPM machines, whenever a constrained shaft height requirement penalizes a standard design. The machine is tailored for electrical traction, but the ideas that are set forth are valid for any application with constrained shaft height. Two design solutions are investigated that comply with the constrained shaft height: a standard Torus AFPM machine and an asymmetrically wound Torus machine, named “Ω AFPM” due to the shape of the stator. It is shown that the Ω AFPM machine has lower losses and a higher efficiency. FE simulations and experimental tests on a full-scale prototype confirm the validity of the proposed solution.

This study presents the 10-yr follow-up results of a multicenter controlled trial on 108 recipients of cadaveric renal transplantation, randomized to receive cyclosporine (N = 55) or azathioprine (N = 53), both in combination with steroids. The 10-yr patient survival rate was 89% in the cyclosporine group and 83% in the azathioprine group (P = not significant [NS]); the 10-yr graft survival was 56% and 35%, respectively (log-rank test, P = 0.009). The half-life of grafts functioning after 1 yr was 15.4 +/- 3.9 versus 10.6 +/- 3.6, P = NS). The rate of early rejection in the cyclosporine group was significantly lower than that in the azathioprine group (0.30 versus 1.4, P0.01). Although the mean creatinine clearance rate was always higher in the azathioprine group, the decline in graft function from the first to the tenth yr was not significantly different between the two groups (-13.0 +/- 16.4 versus -12.3 +/- 19 mL/min, P = NS). In cadaveric renal transplantation, cyclosporine allows better graft survival than azathioprine, not only in the short term but also in the long term, with similar attrition of graft function for up to 10 yr.

L'articolo (che nella sua prima parte è stato pubblicato su "Medicina e Morale" 1995,5:951-984) analizza quale etica sia confacente alla definizione dello statuto biologico dell'embrione. Dopo aver illustrato criticamente le varie posizioni filosofiche al riguardo, l'Autore ritiene decisivo per la riflessione il riconoscimento del rapporto fra ordine biologico ed ordine etico. Tale legame risponde all'esigenza di trovare dei punti fermi naturali ai quali ancorare il ragionamento e le norme che disciplinano la vita individuale e l'ordine civile in materia di tutela del diritto alla vita. Si tratta cioè di affermare che l'ordine insito nella natura umana può costituire il punto di orientamento della condotta della persona. Lo studio prosegue argomentando a favore della titolarità, da parte dell'embrione, di diritti essenziali rispetto alla madre, primo fra tutti quello alla vita, a partire dalla fecondazione. Il nascituro, quindi, va tutelato giuridicamente come persona umana. Dopo avere esaminato, alla luce di quanto precedentemente affermato, se esista un diritto della donna all'aborto volontario - arrivando ad una conclusione negativa - l'articolo si conclude auspicando che gli organi competenti nei vari Stati emanino una "Dichiarazione dei diritti del nascituro", nel rispetto di quanto affermato all'art. 3 della Dichia razione Universale dei Diritti dell'Uomo: "Ogni individuo ha diritto alla vita, alla libertà e alla sicurezza della propria persona".

Corticosteroids have played a key role in the immunosuppression of organ transplantation. Unfortunately, the extensive use of these agents has resulted in disabling and life-threatening adverse effects in many patients. The advent of concomitant corticosteroid/cyclosporin regimens has allowed a reduction in the dosages of steroids administered, yet steroid-induced morbidity is still a major problem in many cyclosporin-treated renal transplant patients. After favourable initial experiences with cyclosporin monotherapy, several attempts at steroid-free immunosuppression in renal transplant patients have been undertaken, either by not starting steroids after transplantation or by stopping steroids in patients with stable graft function. Most controlled and uncontrolled trials showed that with either strategy short term graft survival was similar with or without steroids, but acute rejection was more frequent in patients not taking steroids. The percentage of patients who could be maintained steroid-free ranged from 28 to 94%, and was higher in patients who stopped steroids later than in those never receiving them. Little information is available about long term follow-up of these patients. Some studies reported late attrition of renal function in patients not taking steroids, while others reported a favourable outcome even in the long term. Steroid-free immunosuppression is feasible in renal transplant patients, but it requires careful monitoring of renal function and cyclosporin dosage. This strategy is particularly indicated in patients at high risk of cardiovascular disease or steroid-related complications, and in children. Nevertheless, several issues need to be better elucidated by further studies, namely the long term outcome of steroid-free immunosuppression, the advantages and disadvantages of steroid avoidance versus steroid withdrawal, and the criteria for selecting patients.

Immunosuppression may favour the development of disseminated superficial porokeratosis (DSP). We report the clinical features and the outcome of DSP in 24 patients receiving immunosuppressive treatment (group A), and compare the characteristics of the disease with those of 13 immunocompetent patients with DSP (group B). The two groups were similar with regard to age, sex, area of skin involvement and mean follow-up. There was a family history of DSP in only two patients in group A, compared with five patients in group B (P = 0.03). The skin type, based on the tanning response to sunlight, was not significantly different between the two groups. Two of the 24 patients in group A had high sun exposure, compared with five of the 13 patients in group B (P = 0.03). Moreover, 10 patients in group A and 11 in group B (P = 0.01) exhibited worsening of the disease after exposure to sunlight, usually during the summertime. These observations appear to support the hypothesis that sun exposure is not always essential for the development of porokeratosis in immunosuppressed patients. None of our patients developed skin cancer in porokeratotic lesions during the follow-up period.

An abnormal vascular status is present in the transplanted kidney. To define whether vascular factors might influence kidney function of the graft, the renal volume, blood flow and vascular resistance of a group of healthy subjects were compared with those of a group of well functioning renal transplants by color Doppler ultrasonography. Sixty healthy subjects and 75 well functioning cadaver renal transplant recipients were compared by color Doppler ultrasonography. Subsequently, 15 couples of donors and recipients of a living related renal graft were compared to observe the differences between the two organs of the same subject in a different environment. The variables studied were: the diameters and the volume of the kindey, renal blood flow and renal resistance index (RI). The group of cadaver renal transplant patients showed higher mean blood pressure (P = 0.009), higher serum creatinine levels (P = 0.0001) and lower endogenous creatinine clearance (P < 0.0001) than healthy controls. The length (P < 0.00001) and volume (P < 0.001) of the kidneys of cadaver transplanted patients were significantly greater than those of healthy subjects, while the length and volume of the living donors kidneys were identical to those of the recipients. RI, measured on renal vessels, showed lower values in healthy subjects and in kidney donors than in transplantated patients (P < 0.00001). Well functioning transplanted kidneys showed increased renal arterial RI. This non-immunologic factor did not appear to be detrimental with renal function in time, at least until 50 months after successful grafting.

In 212 cyclosporine-treated renal transplant recipients with stable graft function at 1 year and with potential followup of 5 years the prevalence of arterial hypertension was 81.6% at 1 year and 81.2% at 5 years. The logistic regression analysis showed that the presence of hypertension before transplantation ( P = 0.0001; odds ratio 3.5), a plasma creatinine level higher than 2 mg/dL at 1 year ( P = 0.0001; odds ratio 3.8), and a maintenance therapy with corticosteroids ( P = 0.008; odds ratio 3.3) were positively associated with hypertension at 1 year after transplantation. The mean number of graft failures between 1 and 5 years was significantly higher and the mean reciprocal of plasma creatinine was significantly worse at 1 and 5 years in patients with noncontrolled hypertension than in normotensive patients or in patients with hypertension well controlled by drugs. We also investigated the potential protective role of nifedipine. The episodes of acute tubular necrosis (four versus three), of acute rejections (28 versus 29), the mean arterial pressure at 1 year (105 ± 9 versus 104 ± 9 mm Hg) and 5 years. (105 ± 10 versus 108 ± 12 mm Hg), and the mean plasma creatinine level at 1 year (1.4 ± 0.4 versus 1.6 ± 0.4 mg/dL) and 5 years (1.8 ± 1 versus 1.9 ± 1 mg/dL) were similar in 52 patients who were given nifedipine for at least 4 years and 58 hypertensive patients who never took calcium channel blockers. To evaluate whether an early administration of nifedipine might have a protective role on the graft we separated patients who started nifedipine within 3 days (17 patients) from those who were given the drug 4 or more days after transplantation (35 patients). No case of acute tubular necrosis was seen in patients treated early, while four cases occurred in the group receiving nifedipine later. The number of rejections (nine versus 19), mean arterial pressure at 1 year (105 ± 8 versus 105 ± 9 mm Hg) and 5 years (105 ± 11 versus 104 ± 9 mm Hg), and the mean plasma creatinine level at 1 year (1.5 ± 0.5 versus 1.5 ± 0.4 mg/dL) and 5 years (1.9 ± 1.5 versus 1.9 ± 0.9 mg/dL) were similar in the two groups.

Il problema dell'eutanasia nella società odierna non si caratterizza più per la sua natura eugenetica, ma trova il suo fondamento nell'ambito di un movimento ideologico, nella secolarizzazione, dove si afferma il diritto del malato ad essere protetto dalla sua malattia, dove ciò che si privilegia non è il diritto alla vita ma il diritto alla qualità della vita. L'autore, dopo aver affermato che il diritto del malato a essere protetto dalla sua malattia non può portare all'assurda conclusione del rifiuto della vita per evitare la sofferenza, in quanto la sofferenza e il dolore sono aspetti costitutivi dell'esistenza umana, conclude che soltanto nel rifiuto dell'eutanasia si attua il pieno rispetto dei diritti essenziali di ogni persona umana.

Introduction Mycobacterium gordonae is one of the least pathogenic of the mycobacteria. This pathogen may produce caseating or non-caseating granulomas, and skin lesions showing acute or chronic inflammation with scattered histiocytes and giant cells have been seen. The mortality rate is less than 0.1%. Mycobacterium gordonae may be a marker of severe immunosuppression in patients infected with human immunodeficiency virus. Case presentation We report a case of Mycobacterium gordonae infection in an 86-year-old woman and discuss the problems inherent to the identification and treatment of this emerging pathogen. Mycobacterium gordonae strain we isolated was resistant to trimethoprim-sulfamethoxazole but sensitive to ciprofloxacin, and long term administration (six months) induced complete healing of the cutaneous abscesses. Conclusion Advanced laboratory diagnostic techniques have improved the isolation and identification of nontuberculous mycobacteria. The diagnosis requires a high index of clinical suspicion, as detection by conventional methods is difficult. To our knowledge, this patient is the first documented case of cutaneous infection from this pathogen in Italy.

In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor-induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician.

renal vasculitis of small and medium-size vessels are Introduction frequent. In less severe cases, a mesangial lesion may be seen [2]. Mixed cryoglobulinaemia (MC) is a rare systemic disease characterized by circulating cold precipitable mixed immunoglobulins composed of monoclonal IgM rheumTreatment of MC nephritis atoid factor and polyclonal IgG. Purpura, weakness, arthralgias and glomerulonephritis are the principal clinical manifestations. Rarely gastrointestinal, cardiopGood blood-pressure control is of paramount importance in patients with MC nephritis. Arterial hypertenulmonary and neurological vasculitis may also occur. Liver disease is frequent. Some patients may remain sion is common and often severe in MC patients. As in any type of renal disease, hypertension contributes asymptomatic for years but in many cases the liver disease is progressive and this is a frequent cause of to progression and to cardiovascular disease. The latter represents the main cause of death among patients death. MC was called essential until recently because no aetiological factor could be identified. In 1990, with MC [3]. Therefore, every effort should be made to maintain blood pressure within the range of recomhowever, Pascual et al. [1] reported an association between MC and hepatitis C virus (HCV ) infection. mended values. A combination of antihypertensive agents is usually necessary to achieve this goal. Since then it has been recognized that the majority of patients with MC had anti-HCV antibodies and a Because of the frequent association of MC with HCV infection, treatment with the antiviral agent critical aetiological role has been attributed to HCV infection. a-interferon (aIFN ) is one therapeutic option which has been recommended in MC patients. In two randomized trials [4,5], doses ranging between 1.5×106 Cryoglobulinaemic nephritis and 3×106 Units were administered three times a week for 23–52 weeks. HCV RNA turned negative in about half of the 42 patients (53%). Most patients had only Kidney involvement is frequent in MC, but in many mild renal involvement and only a few had modercases renal disease is recognized only years or decades ate renal insufficiency. Improvement of systemic signs after HCV infection. In a few patients, however, renal and serological markers of disease activity such as and extrarenal signs and symptoms are present at the S-creatinine or circulating cryoglobulins, usually onset of the disease. The clinical presentation of renal occurred within the first month. Unfortunately, all the disease may be variable. A number of patients show patients who responded had a relapse of the disease proteinuria, microscopic haematuria and/or arterial upon discontinuation of aIFN. More recently a few hypertension. Moderate renal insufficiency is frequent. case reports have shown longer remission when higher In another 20% of cases renal involvement is heralded doses of aIFN, up to 10×106 Units three times a by a nephrotic syndrome. In some 20–30% of patients week, were given for a short period [6–9]. Anecdotal the first renal manifestation is an acute nephritic synobservations of reversal of membranoproliferative drome with microscopic or macroscopic haematuria, glomerulonephritis after aIFN have also been reported proteinuria and a rapidly progressive deterioration in [10]. From the available information it seems, however, renal function. A diffuse proliferative and exudathat the benefit of aIFN is transient and is confined to tive glomerulonephritis resembling a membranoprofew patients with mild and/or quiescent renal disease. liferative glomerulonephritis is the most common It remains unproven whether aIFN plays a favourhistological pattern observed. Intraluminal thrombi, able role at all in patients with flares of renal activity glomerular infiltration of monocytes, double-contour or with renal insufficiency. From a theoretical point of appearance of the glomerular basement membrane and view, aIFN may even be contraindicated in patients with active renal disease, as its immunostimulating Correspondence and offprint requests to: Mariarosaria Campise MD, activity might aggravate renal disease and vasculitic Divisione di Nefrologia e Dialisi, Ospedale Maggiore, IRCCS Via Commenda, 15, I-20122 Milan, Italy. lesions [11]. Furthermore, aIFN has myelosuppressive

Background. Little information is available about the long-term outcome of renal transplantation in adults with Henoch-Schonlein purpura (HSP). Methods. We compared the outcomes of 17 patients with HSP who received 19 renal transplants with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was109 ±99monthsforHSPpatientsand110 ±78months for controls. Results. The actuarial 15-year patient survival was 80% in HSP patients and 82% in controls, and the death-censored graft survival was 64% in HSP patients and in controls. The risks of acute rejection, chronic graft dysfunction, arterial hypertension and infection were not different between the twogroups.Ineightgrafts(42%)recurrenceofHSPnephritiswasfound(0.05/patient/year).Inspiteoftherapy,onepatient died and four eventually restarted dialysis respectively 10, 32, 35 and 143 months after renal transplant. Seventyone percent of grafts transplanted in patients with necrotizing/crescentic glomerulonephritis of the native kidney had HSP recurrence in comparison to 12% of recurrences in patients with mesangial nephritis (P = 0.05) Conclusions. Long-term patient and allograft survival of HSP patients was good. However, 42% of HSP patients, particularly those with necrotizing/crescentic glomerulonephritis of the native kidneys, developed a recurrence of HSP nephritis that eventually caused the loss of the graft function in half of them.

A cohort of 201 kidney transplant recipients (KTR) including 7 patients with evidence of renal function deterioration (as defined by creatinine levels >20% over baseline values) was analyzed for polyomavirus DNA in blood and urine samples by a new quantitative polymerase chain reaction method. Of 201 patients, 14 (6.9%) were positive for polyomavirus DNA in blood (median level, 500 copies per milliliter of blood) including all 7 patients with renal function deterioration. Polyomavirus DNA detection in blood for diagnosis of renal function deterioration in KTR showed a sensitivity of 100% and a specificity of 96%, whereas positive and negative predictive values were 50% and 100%, respectively. Diagnostic value of decoy cells detection and polyomavirus DNA quantification in urine samples was negligible.

Background Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. Methods Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. Results Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mκ [IgMκ]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 μmol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. Conclusion Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.

Background. In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available. Methods. In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation. Results. At enrollment in 1989 (5.5±4 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+,C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8),B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival. Conclusions. In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival.

BACKGROUND It is still unknown whether it is better to administer cyclosporine (CsA) once or twice a day to renal-transplant patients. METHODS Fifty-four patients were randomized to receive CsA once a day (OD group, 28 patients) or twice a day (BD group, 26 patients). Clinical parameters and pharmacokinetic studies were regularly monitored over the first year. RESULTS Two patients lost their grafts because of renal vascular thrombosis. A patient in the BD group died. The other 51 patients were alive with graft functioning after a minimum follow-up of 1 year. Five patients per group had reversible acute rejection. There was a not significant trend toward a lower mean serum creatinine in OD than in BD (1.38 +/- 0.38 and 1.7 +/- 0.80 mg/dL at 1 year posttransplant, respectively). In 47 patients, 319 pharmacokinetic studies were performed. We measured the area under the concentration-time curve during the first 4 hours (AUC0-4) and CsA blood levels at 0, 2, and 4 hours after dosing. C0 was significantly lower in OD than in BD (P=0.0011), whereas C2 (P

Nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) frequently recurs even after transplantation and may cause failure of the renal allograft. We report a case in which plasma exchange (PE) was used to treat a 32-year-old patient with biopsy-proven recurrence of FSGS in a second renal transplant after the first allograft had failed. One year after the second renal graft, the patient presented with proteinuria of 5 g/day and a creatinine level of 1.46 mg/dl. A course of 9 PE was performed over a 15-day period. Proteinuria improved rapidly, and 20 days after the last PE, it was already down to 0.8 g/day. This level continued to decrease progressively (0.5 g/day after 3 months) and reached zero after approximately 6 months. Eleven months after PE treatment, the patient had no proteinuria and his plasma creatinine level was normal. In our opinion PE should be instituted early in recurrent nephrotic syndrome after renal transplantation. The optimum frequency of such treatment still has to be established, especially with regard to its use as long-term maintenance therapy.

Little information is available about the role of oxidative stress in renal transplant patients. To evaluate the prevalence and severity of oxidative stress in renal transplantation, the authors conducted a cross-sectional study.In 112 cadaver or living-donor kidney transplant recipients with a follow-up of at least 6 months and with plasma creatinine less than or equal to 2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC), serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured.The mean levels of Hcy (21.1 microM vs.10 microM), ROS (302.7 U. Carr (Carratelli units) vs. 250-300 U. Carr), and TAOC (410.6 micromol/HclO/mL vs.350 micromol/HclO/mL), were higher than the reference interval, whereas -SH groups, vitamin B12, s-F, and ery-F were within the normal range. In the multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and TAOC (P=0.0007) were independently associated with oxidative stress. At multiple regression analysis, -SH groups and ROS were directly and inversely related to hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between -SH groups and blood pressure levels (P=0.0095).Renal transplant patients have a pattern of increased oxidant stress that is counterbalanced by an enhancement of the antioxidant mechanisms. Besides the well-known risk factors, the authors found that anemia is an independent risk factor for an increase of ROS. Further studies are needed to evaluate whether the correction of anemia might prevent or reduce the oxidative stress in renal transplant patients.

The occurrence of a rapidly progressive necrotizing glomerulonephritis after kidney transplantation is exceptional and usually leads to graft failure. We describe a case of necrotizing glomerulonephritis that developed 5 months after renal transplantation in a patient suffering from prolonged bowel paralysis and sepsis. After reinforcement of corticosteroid therapy and introduction of cyclophosphamide, glomerulonephritis recovered. Cyclophosphamide was stopped after 2 months and replaced by azatioprine while prednisone was progressively reduced. Three years after transplantation the patient has a stable serum creatinine of 1.7 mg/dL and mild proteinuria. To the best of our knowledge this is the first case of recovery from a necrotizing glomerulonephritis in a renal transplant recipient.

Background. Prevalence and pathogenicity of hepatitis G virus infection in long-term renal transplant recipients, are not fully known. Aim. To evaluate long-term impact of HGV infection on liver disease of renal transplanted patients. Patients and Methods. A total of 155 hepatitis B surface antigen negative kidney transplant recipients, followed for a mean of 11 years after renal transplantation, were studied. Of these 48 (31%] patients had persistently elevated serum aminotransferase values. Frozen serum samples were tested for HGV-RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent assay. Hepatitis C virus-RNA was typed by a line probe assay and quantified by a branched DNA signal amplification assay. Results. Hepatitis G virus-RNA was detected in 37 [24%) patients and anti-hepatitis G virus in another 26 (17%). Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients were similar in terms of age, sex, duration of dialysis, rate of transfusion, chronic liver disease, rate of hepatitis C virus infection and immunosuppressive therapy. Fifteen (41916) hepatitis G virus-RNA seropositive patients were hepatitis C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the 15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48 patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p=0.02). Only 3 hepatitis G virus carriers had persistently elevated alanine aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p

Whether it is better to treat renal transplant patients with cyclosporine alone, combined with steroids, or combined with steroids and azathioprine is still unclear. After initial therapy with cyclosporine and steroids, 354 cadaver renal transplant recipients were randomly assigned at the post-transplant day 5 to cyclosporine alone (monotherapy), cyclosporine plus steroids (double therapy), or cyclosporine plus steroids plus azathioprine (triple therapy). Monotherapy patients, after a second acute rejection, were switched to either of the two alternative therapies. According to intention-to-treat (ITT) analysis, the 4-year patient survival was 97% in monotherapy, 91% in double therapy, and 96% in triple therapy; the graft survival including death was 84%, 77%, and 88%, respectively; and the pure graft survival was 87%, 85% and 91%, respectively (P = not significant). Acute rejections were diagnosed in 79 patients in monotherapy, 58 in double therapy, and 59 in triple therapy (P < 0.01). Of the patients on monotherapy, 52% were switched to double or triple therapy. In these patients, the 4-year graft survival including death was 68%, and the pure graft survival was 72%, in comparison with 93% and 94%, respectively, for patients who continued on cyclosporine alone. Patients with renal polycystic disease as a cause of renal failure and with low plasma creatinine at the time of randomization (5 days after transplant) had a higher probability of remaining on monotherapy, wherease those with glomerulonephritis or systemic lupus erythematosus (SLE) and with high plasma creatinine levels at randomization had a higher probability of being switched to double or triple therapy. According to ITT analysis, there were fewer ocular (P < 0.0001), osteomuscular (P < 0.002) and cardiovascular complications (P = 0.05) and fewer patients with hypercholesterolemia (P < 0.0028) in the monotherapy group, with no difference between double and triple therapy. Creatinine clearance at 3 years was lower in monotherapy, but no attrition of renal function was seen over the years in any of the groups. Cyclosporine, however used, provided good results in cadaveric renal transplantation. Triple therapy and monotherapy offered a nonsignificantly better patient and graft survival than double therapy. Patients on monotherapy had a higher risk of acute rejection but had fewer adverse events than those on double or triple therapy. Patients maintained on cyclosporine alone had the best graft survival, whereas those who were assigned to monotherapy and had to add steroids because of multiple rejections had the worst outcome. Therefore, it seems reasonable to limit the choice of monotherapy to patients without immune-mediated renal diseases and with good graft function in the early post-transplant period.