Early and delayed orthotic treatment in congenital metatarsus varus: effectiveness of two types of orthoses.

AIM: The aim of this study was to evaluate the effectiveness of early or delayed orthotic treatment of congenital metatarsus varus and evaluate the efficacy of static vs dynamic anti-varus orthosis. METHODS: Twenty-five children (14 males, 11 females), of 81.3 days of age (range 1-189) (41 feet affected) were selected among 88 patients referred to our rehabilitation department for foot deformity. Children were assigned to 1 of 2 groups (dynamic or static orthosis) according to a simple randomization scheme. Patients were evaluated at diagnosis (T1), at the end of treatment (T2) and at a follow-up performed at least 2 years after the end of treatment (T3). Primary outcome was measured using the Bleck scale. The IOWA functional rating system questionnaire was performed at follow up evaluation. RESULTS: The Bleck scale showed that both static and dynamic orthoses were effective and that the best results were achieved with early treatment. The IOWA questionnaire showed that no child had residual deformities that interfered with daily activities. Nonetheless, the dynamic orthosis group had better scores in 4 sub-items related to parental satisfaction, foot function, heel position, and foot passive motion. CONCLUSIONS: Both static and dynamic orthoses are useful for correction of congenital metatarsus varus. Optimal results are achieved with early treatment.

Kidney, patient and new millennium nephrology.

The way nephrology develops in the new millennium is bound to be affected by changes in the nephrologist's clinical environment, as well as by the progress made in basic research which will need to find a clinical application. The nephrologist can expect to be more and more involved in renal substitution therapy, not just providing the treatment, but also managing the cost of the service. In the field of nephropathology, the highest expectations surround molecular biology and its application to both acquired and hereditary renal disease; the goal is to find an outlet for gene therapy in clinical practice. Artificial substitution therapy will focus chiefly on the project of 'intelligent dialysis', whereby biological and diagnostic components are combined according the specific needs of the individual patient. The ideal scenario for renal transplantation in the coming millennium would be one where donor supply matches the demand (xenotransplant?), where immunomodulation is perfected, and where diagnoses are based on precise biomolecular events observed in real time.

ELISA anti-HLA antibody screening identifies non-complement-fixing antibodies responsible for acute graft rejection. A case report.

We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.

Dialysis and transplant patients in the long term.

The history of renal replacement therapy is traced from the early days of dialysis and kidney transplantation through the era of miraculous technology and the alleged certainties of anti-rejection therapy. Attention is focused on the newly found or anomalous biotypes that are common to both dialysis and transplantation. In dialysis not only the patient but also uremia is maintained and either hyper- or hyporeactivity in different biological systems may occur with or without clinical symptoms. In transplantation, while the balance between immunomodulation and immunotolerance is far from ideal, extrarenal complications may occur with an atypical mode of presentation, serious immunological renal lesions may develop asymptomatically and clinical signs of rejection may appear without noticeable laboratory alterations.

Combined treatment in Wegener's granulomatosis with crescentic glomerulonephritis--clinical course and long-term outcome.

This study reports on 9 patients suffering from Wegener's granulomatosis (WG) with crescentic GN and severe systemic manifestations. On admission the mean serum creatinine was 10.9 +/- 5.1 mg/dl (4-20 mg/dl); 8 patients were oliguric and required dialysis treatment. Renal biopsy showed crescents in all cases, involving 66 to 100% of glomeruli. Patients were treated with a protocol including: a plasma exchange (PE) course; methylprednisolone; cyclophosphamide; and an antithrombotic agent (defibrotide). Clinical picture and renal function progressively improved in all patients within the first 4 weeks of treatment. After 1 month serum creatinine was 2.7 +/- 0.8 mg/dl and dialysis was no longer needed in any patient. Five relapses occurred in 3 patients 12-26 months after the onset of the disease, while they were still receiving immunosuppressive treatment. At follow-up (22 to 112 months: mean 71) all patients were alive with no clinical signs of disease activity. One patient was on regular dialysis while the others had a serum creatinine of 1.2-2.8 mg/dl (mean 1.9). Our results confirm that crescentic GN associated with WG can be successfully treated even when associated with severe clinical picture and suggest that PE can contribute to control the disease without increasing immunosuppression.

Plasma exchange treatment in rapidly progressive glomerulonephritis associated with anti-neutrophil cytoplasmic autoantibodies.

This study reports on 12 patients with acute renal failure due to biopsy-proven rapidly progressive glomerulonephritis and signs of systemic disease in whom antineutrophil cytoplasmic autoantibodies (ANCA) were detected by indirect immunofluorescence (IIF) on alcohol-fixed neutrophils and assessed in serial determinations by ELISA. The diagnosis was: Wegener's granulomatosis in nine patients who showed a diffuse cytoplasmic pattern at IIF (c-ANCA), and microscopic polyarteritis in three where a perinuclear pattern (p-ANCA) was seen. All patients underwent a course of plasma exchange - PE - (3-10 sessions per patient) associated with steroids and cyclophosphamide. The ANCA titer dropped steeply during PE in all cases and was followed by disappearance of systemic symptoms and renal function improvement within four weeks. After a follow-up period of 50 +/- 31.2 months all patients were alive without signs of disease activity; ten had stable renal function, with serum creatinine 1.8 +/- 0.7 mg/dl; two had entered regular dialysis treatment after 44 and 82 months. Our results suggest that the rapid removal of ANCA by means of PE can help control disease activity and reduce the risk of death or end-stage renal disease.

Flow cytometry evaluation of urinary sediment in renal transplantation.

The value of exfoliative urinary cytology for the diagnosis of different pathological conditions in renal transplantation is widely recognized. The method, however, has not yet gained full acceptance, mainly because identification of the different cells is not always possible by means of standard staining techniques. In view of its characteristics, flow cytometry (FC) seems to represent a consistently reliable, rapid and innovative approach for differentialing the various cells present in the urinary sediment and assessing their number. This study gives the examination result of 223 urinary specimens from 127 transplanted patients selected according to pathology. Sediment cells, collected from fresh urine samples, were washed, treated with a lysing solution, resuspended in saline solution and directly analysed in a FACSCAN cytometer. Morphological evaluation showed: a small number of cells in patients with stable renal function; a larger number of cells, with predominance of lymphocytes, during acute rejection episodes; an absolute predominance of neutrophils during bacterial infection; large-sized cellular debris in cases of post-transplant tubular necrosis; and small cell debris in cases of cyclosporine cytotoxicity. Lymphocyte surface-marker evaluation made it possible to differentiate lymphocyte populations observed during acute rejection episodes (cytotoxic T-cell, CD8 and HLA class II and NK cells) from those detected during bacterial infection (T-cell CD4 positive). These results suggest that urinary FC may be a reliable diagnostic tool in clinical renal transplantation.

Value of panel reactive antibodies (PRA) as a guide to the treatment of hyperimmunized patients in renal transplantation.

Patient presensitization represents a considerable problem in candidacy for renal transplantation. While it is well known that hyperimmunized patients--panel reactive antibody (PRA) higher than 60%--create difficulties in donor matching and have a worse outcome than non-hyperimmunized patients, less information is available on patients with an intermediate degree of sensitization (30-60%). In order to evaluate how graft outcome relates to such degrees of sensitization, 241 consecutive transplanted patients were divided into two groups on the basis of their previous year's PRA peak: group A, PRA 0-29%; group B, PRA 30-60%. Group A showed a significantly better survival both in the first year (90% vs 79%, P < 0.05) and in the third year (82% vs 64%, P < 0.01). However, detailed analysis of group B demonstrated that some parameters may significantly influence graft outcome: (1) better compatibility on locus DR; (2) a primary kidney transplant; (3) a dialysis duration of less than 6 months; and (4) the prophylactic use of antilymphocyte globulin (ALG).

Ten years experience with plasma exchange in renal transplantation.

Plasma exchange has been used in our renal transplantation programme for over ten years to treat 86 patients divided into four groups. Five patients had preformed cytotoxic antibodies before transplantation (group A); 13 sensitized patients (greater than 60% PRA) underwent prophylactic plasma exchange in the immediate post-operative period (group B); 62 patients were treated for acute vascular rejection (group C); six patients had chronic graft rejection (group D). Plasma exchange is a valid tool for the treatment of acute vascular rejection, provided that it is started before irreversible graft damage occurs: 75% rejection crises were reversed by plasma exchange and the actuarial graft survival from the rejection episode was 75% at one year, 66% at two and 50% at five years. Serum creatinine before treatment and glomerular thrombosis at graft biopsy correlated with the response to plasma exchange. In sensitized patients and in those with chronic rejection the results were disappointing and suggest that in these clinical conditions plasma exchange should be used only in selected cases.

Prevention of chronic glomerular uremia in steroid resistant glomerulonephritis. A clinical trial with a new antithrombotic agent.

To investigate the possibility of slowing down disease progression 27 patients with primary glomerular diseases unresponsive to steroids and cytotoxic drugs were treated with Defibrotide. This drug is a single stranded DNA fraction which has profibrinolytic and deaggregating properties and can promote the generation and release of prostacyclin from vascular tissue. Before treatment all patients showed proteinuria in excess of 1 g/day and 16 had a nephrotic syndrome (59%); 10 patients had serum creatinine above 1.6 mg/dl (37%) and 6 were hypertensive. After therapy a significant decrease in daily proteinuria was observed, although the reduction exceeded 50% of pre-treatment values in only 16 patients (59%). A progressive decrease in serum creatinine occurred in patients with abnormal renal function; serial measurement of renal plasma flow showed a progressive improvement with an average increase of 6 and 12%, after 1 and 3 months of treatment, respectively. These observations confirm the view that drugs improving endothelial function and renal hemodynamics can be of value in the treatment of chronic glomerular diseases and can contribute to the maintenance of renal function.

Glomerulonephritis in renal transplantation.

Recurrent glomerulonephritis and de novo glomerulonephritis may develop in the graft after renal transplantation. Among 59 patients with a pathological diagnosis of glomerulonephritis as original renal disease, 12 (20.3%) showed recurrence of the original lesions in the graft. Two patients with hereditary nephritis developed anti-GBM disease (one patients in two grafts). The disease rapidly progressed to graft loss. A de novo membranous nephropathy was diagnosed in four patients whose original renal disease was not a glomerulonephritis. One patient had been treated with antilymphocyte globulin, another with captopril.