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The ACCESS project, which is a project within the RACE (Research in Advanced Communication in Europe) program, is described. The scope of the project is to study the entire customer access connection, including the transmission, the multiplexing, and the passive optical network. The goal of the project is to perform an overall cost optimization, leading to one or more preferred implementations. Because the project is oriented toward the early phases of the integrated broadband network, the majority of the effort is spent on optimization and supplementation of present near-commercial technologies. The project involves 13 partners who share the work organized in three major areas, namely, the 622 Mb/s transmitter/receiver unit for bidirectional transmission on one single-mode (SM) fiber at 1330 and 1550 nm; the passive optical components, including mass splicing techniques, low-cost connectors, wavelength division multiplexing (WDM) devices, optical distribution frames, and optical cables; and system aspects of the frame structure and the interfaces to the customer premises network and to the exchange, with the associated functional units being the multiplexers and the broadband channel selector. >

Hereditary nephritis associated with hematologic abnormalities seems to be an exceptional occurrence. We have observed a family which nephritis was combined with May-Hegglin anomaly. A girl and her father suffered from proteinuria; a paternal uncle received kidney graft; a paternal grand aunt died on periodic hemodialysis. The girl, the father and the uncle presented macrothrombocytopenia (40-100 X 10(9)/l, size 4-8 mum) with prolonged bleeding time (which precluded renal biopsy) and cytoplasmic inclusions in neutrophils (Döhle bodies). These hematologic abnormalities characterize the May-Hegglin anomaly. This kind of association has not been reported so far.

The spontaneous sheep erythrocyte (E) rosette test was used on 340 occasions to measure T cell levels in 28 renal allograft recipients. The E rosette counts were reduced by high-dose steroids but usually returned towards normal under maintenance treatment with azathioprine and low-dose prednisone. Unexpectedly, rejection crises were more often associated with a decrease in E rosettes before steroid treatment (12 cases) than with an increase in E rosettes (5 cases). Our results show the need for caution in using the E rosette test and more generally B and T cell markers for monitoring anti-graft immunity in renal allograft recipients.

Experiments have been established in order to study the antagonistic effect of cyclophosphamid treatment on the antibiotic activity of gentamicin in vivo. An immunodepressive state in mice (50 % reduction of neutrophil polymorphonuclear) was obtained with a 5 day treatment of cyclophosphamid, at the dose of 15 mg/kg. The mice were inoculated intraperitoneally with 10 LD50 of Klebsiella pneumoniae. Antibiotherapy was applied in 2 ways differing with the dose of gentamicin given twice a day by subcutaneous route (either 2.5 or 25 mg/kg) and with the time at which treatment was started (either at 1 or at 2 h after bacterial challenge). The gentamicin activity decreases in immunosuppressed mice when antibiotic is applied with a low dose (2.5 mg/kg), 1 h after infection challenge. This effect disappears when gentamicin is given with high doses (20 mg/kg) or when antibiotherapy is delayed (2 h after infection challenge). In this case, mortality is important and close to non immunodepressed mice.

From June 1981 to June 1985, 22 patients with advanced chronic renal failure were treated with a preparation of ketoanalogues of essential amino acids (Ketosteril, 1 tablet/5 kg/day) combined with a protein supply of 0.4 g/kg/day. At the beginning of treatment, their mean plasma creatinine was 762 +/- 135 mumol/l and their creatinine clearance, 8.4 +/- 3.1 ml/min/1.73 m2. By the end of November, 1985, among the 20 assessable patients, 4 had been on ketoanalogues for 8 to 52 months, 9 had to be dialyzed after 4 to 20 months, 5 had died and 2 had abandoned treatment. A mean 28% decrease in plasma urea level and daily urinary urea output was observed after 1 month on ketoanalogues, and a sustained reduction in plasma creatinine was observed in 12 patients. Mean renal survival was 15.6 +/- 12 months (median: 12 months), and was longer in patients whose plasma creatinine was lower than 700 mumol/l at the beginning of treatment. The ketoanalogues were well tolerated, and no denutrition occurred. Our experience confirms the usefulness of this therapeutic approach in uremic patients and suggests that the best results would be obtained if ketoanalogues were introduced before end-stage renal failure.

Nine cases of urinary lithiasis following renal transplantation are reported. They differ from 15 cases in the literature in their development late after transplantation and in that no relation with hyperparathyroidism could be clearly demonstrated. We emphasise the difficulty of the clinical and radiological diagnosis of this little-known complication. The course is essentially similar to that in non-transplant patients with lithiasis.

We undertook two randomised studies in an effort to decrease the dosage of steroids in transplanted patients and to replace harmful steroid therapy by nonsteroid anti-inflammatory (NSAI) drugs. In the first study, 50 consecutive transplant recipients were randomly assigned to the treatment or the control group. In both groups, patients received azathioprine and prednisolone. ATG was added to this protocol in the experimental group. The number of renal failure episodes and consequently the amount of steroid necessary to control these episodes were significantly lower in the ATG group than in the other group. Two year post-transplantation kidney survival was 79% in the ATG group and 52% in the control group. In the second study, 15 consecutive transplant recipients were randomly assigned to two control groups and to one experimental group, where steroids were replaced by NSAI drugs. This preliminary, and very limited, pilot trial demonstrates the existence of early acute renal failure episodes, probably of immunological origin, which can improve spontaneously in the absence of steroid therapy.

Two hundred and forty end-stage kidneys removed during transplantation, were studied by immunofluorescence. Mesangial IgA glomerulonephritis was demonstrated in 24 cases. Since mesangial IgA glomerulonephritis accounts for 10% of the cases of terminal renal failure requiring transplantation, its prognosis is not as mild as it was initially believed. About one third of the patients must eventually develop renal insufficiency. Such an unfavourable course is even possible when the disease began during childhood.

Periarteritis nodosa was observed in three of 266 persistent hepatitis B antigen (HBsAg) carriers undergoing long-term hemodialysis; no cases of necrotizing vasculitis occurred among 384 other patients undergoing dialysis having either no or transient antigenemia. Circulating e antigen, but no e antibody, was found in two of these three patients. The serum level of the third component of complement (C3) was normal in two patients and low in the third. Circulating immune complexes were demonstrated in all three patients, using polyethylene-glycol (PEG) precipitation, PEG-C4, and solid phase C1q tests. HBsAg and anti-hepatitis B antibody (HBsAb) were identified in the PEG precipitates using radioimmunoassay and electron microscopy technics. Direct immunofluorescence performed on a muscle biopsy specimen from one patient was positive for HBsAg, but not for immunoglobulin G (IgG), immunoglobulin M (IgM), C3 or C1q. These data support the hypothesis that circulating immune complexes involving HBsAg may be involved in the pathogenesis of periarteritis nodosa.

Hypophosphataemia is a common finding among kidney transplanted patients [1,2]. In a previous study in kidney transplanted children with plasma creatinine below 1.1mg/dl, we demonstrated [3] a negative correlation between plasma phosphorus and 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), the renal hormonal form of vitamin D. No such correlation was apparent in children with minimal increase in plasma creatinine. The aim of the present investigation carried out in hypophosphataemic transplanted adults was two-fold: 1) to determine whether hypophosphataemia results from persisting hyperparathyroidism or from a renal phosphorus leak, or both, and 2) to study the relation between plasma phosphorus, iPTH and 1,25(OH)2D3 in these patients.

Bacterial infections were studied in 51 immunosuppression kidney transplant recipients. Eighty infectious episodes occured in the first six post-transplantation months. Forty percent of these episodes were nonfebrile, detected during the routine bacteriological follow-up examination. Out of these 80 bacterial infections, 59 were localized (47 in the urinary tract, nine in the surgical wound and three in the lungs) and 21 had spread. Neutopenia occured in 13 patients, in association with septicaemia in eight of them. Usually septicaemia appeared before neutropenia. In 12 cases, infectious episodes (10 septicaemias and two localized infections) and transplant failure were closely related. The bacterial strains responsible for these infections were essentially: Staphylococcus spp (39), Streptococcus spp (14), Klebsiella pneumoniae (9), Escherichia coli (9). Most of the localized infections cleared up when treated with a specific antibiotic. Seven failures of antibiotic treatment were observed in 21 cases of generalized infections. The importance of regular post-transplantation bacteriological check-up in detecting and treating infectious complications in graft recipients must be emphasized.

Infective complications are analysed in 100 transplanted patients all receiving corticosteroid and azathioprine. 170 infective episodes were noted, only 13 patients never had infection during the period of observation. Two complications were dominated by their gravity : pneumopathies (n equals 29) fatal in 20.6% of cases, and septicemia (n equals 21) fatal in 28.5% of cases. Alone they represented 75% of the overall mortality in this series. More than 50% of failures due to death or detransplantation, were directly due to infection. The results show that this type of complication represents the main limiting factor to renal grafts in patients submitted to immunosuppressor treatment which depresses non-specifically, the whole immune response.

Collins' solution is one of the world-wide methods used for kidney preservation. A long-term survey of transplanted kidneys thus preserved has never been reported. Clinical, biologic, radiologic, and pathologic data collected from 225 cadaver kidney transplantations were analyzed according to the total ischemic time (group 1: TIT less than or equal to 12 hr; group 2: TIT 12-30 hr). No differences could be demonstrated between the two groups, whether considering the percentage of immediate function, the serum creatinine level that was normal up to 2 years, the incidence of abnormal blood pressure, the pathologic changes on routine biopsies performed at 6 months and 2 years, or arteriographic features at 2 years. A better graft survival rate was consistently found at 6 months, 1 year, and 2 years when TIT was between 12 and 30 hr. This could be related to the higher incidence of well-matched kidneys in this group of patients, thereby emphasizing the efficiency of exchange programs for compatible kidneys.

Comparison between CDC and ADCC in a human allogeneic model using the same cytotoxicity marker, i.e. 51Cr release from labelled target cells, provided a better definition of the optimal technical conditions for revealing ADCC. Testing 229 sera from human renal allograft recipients after transplantation, we found that CDC is detected only during rejection (43% of cases) whereas ADCC can be found both in those recipients tolerating their grafts and in those undergoing rejection, more frequently in the former than in the latter (39% vs. 21%, p less than 0.05). These in vivo results and other in vitro experiments support the assumption that two distinct varieties of antibody can mediate the in vitro ADCC phenomenon, some directed against the A, B and C HLA loci and having a deleterious effect on the graft, and others capable of exerting a protective effect and which could be directed against D related HLA determinants.

In order to determine whether reinforced vaccinations improve the immune response among uremic patients, three vaccination schedules with hepatitis B surface antigen vaccine (Institut Pasteur Production) were compared. A total of 215 hemodialysis patients treated in HBV free units were randomly allocated to Group I (3 injections of 1 ml), Group II (3 injections of 2 ml) and Group III (4 injections of 1 ml). Immune response was evaluated in 204 patients. The percentages of responders within 12 months after the first injection (greater than = 10 mIU/ml on 2 successive blood specimens) were: 45.6%, 75.0% and 69.4% in Group I, Group II and Group III respectively. The geometric mean peak values of anti-HBs observed 6 months after the first injection among the responders were: 60, 192 and 268 mIU/ml respectively. One month after a booster dose given to 182 patients 14 months after the first injection, anti-HBs levels were 144, 1123, 524 mIU/ml respectively, and the frequency of patients with an anti-HBs titer greater than = 50 mIU/ml was 68%, 82% and 75% respectively. These results led us to discard the use of Protocol I for these immuno-depressed patients while it is quite satisfactory in healthy subjects; they also show that Protocol II and III give better results than Protocol I, but that they cannot be statistically differentiated. We conclude that response rates and anti HBs antibody titers can be significantly improved in chronic hemodialysis patients with reinforced vaccination protocols.

Since the first long term successful transplantation in the human in 1959, our group at the Necker Hospital has been concerned that a range of immunological tests, inspired by basic research into graft immunity, be introduced into clinical transplantation. We were thus the first in 1959 to concentrate our efforts on the immunologic selection of the donor and on discovering the means of assessing the degree of immunologic similarity between donor and recipient.

Among 500 patients on maintenance hemodialysis, 6 patients (5 young women and a 49-year-old man) developed bullous dermatosis, 2-54 months after initiating dialysis treatment. The skin lesions occurred mainly in sunlight-exposed areas, and 4 out of the 6 patients showed increased cutaneous fragility in response to trauma. Skin biopsy revealed subepidermal blisters for all of them, and skin immunofluorescence studies were negative for 2 patients. No increase in fecal or red cell coproporhyrin and protoporphyrin levels was found in any of the 6 patients. The syndrome was clinically and histologically indistinguishable from porphyria cutanea tarda.

The pharmacokinetics of the hypolipidemic agent, clofibrate have been studied in anuric patients on intermittent hemodialysis. In addition we have tried to determine whether the treatment of hyperlipidemia of chronic renal failure with clofibrate was safe and efficacious. Seven healthy volunteers and five uremic patients received a single dose of 25 mg/kg body weight of clofibrate. Mean peak plasma levels of clofibrate were comparable in both groups and were reached 3.5 hr after drug ingestion in the control subjects and after 6.5 hr in the uremic patients. The mean plasma half-life of clofibrate was 16.7 hr and 68.4 hr in the control subjects and in the patients, respectively (P less than 0.001). Following a short loading period a daily oral maintenance dose of 5 mg/kg body weight was given leading to a plasma clofibrate level of 75-100 microgram/100 ml. Five hyperlipidemic uremic patients received this dose for 3 months. Their plasma clofibrate and creatine kinase levels were constantly monitoried to detect clofibrate myotoxicity which we have observed in uremic patients at plasma levels generally considered safe in patients with normal renal function. Significant decreases in serum total lipid, triglyceride, and cholesterol levels were observed when compared to pretreatment values. In two of the 5 patients serum lipids remained decreased for 10 and 14 months. It is concluded that clofibrate treatment of hyperlipidemia in uremic patients, when carefully monitored, is safe and efficacious.

In a black man, recently receiving long-term hemodialysis, a severe, rapidly progressive polyradiculoneuritis (Guillain-Barre syndrome) developed. Routine virologic study revealed a high antimeasles virus antibody titer (1:1280 by hemagglutination-inhibition) which progressively decreased. There was no clinical evidence of measles. Discussed here is the possible relationship between the Guillain-Barre syndrome and clinically inapparent measles associated with and perhaps modified by the uremic state.

The response of the heart rate to intravenous isoproterenol was studied in seven chronic hemodialysis patients with severe hyperparathyroidism, before and after subtotal parathyroidectomy (PTX). Before PTX, significantly higher doses of isoproterenol were needed to achieve a standardized increase in heart rate when compared with the doses needed following PTX. A similar difference was observed before and after removal of a parathyroid adenoma in an additional nonuremic patient with primary hyperparathyroidism. This decreased cardiac responsiveness to a beta-adrenergic stimulus seemed to be related to the hyperparathyroid state.

Collins solution is one of the world methods used for kidney preservation. A long term survey of transplanted kidneys thus preserved has never been reported. Clinical, biological, radiological and pathological data collected from 225 cadaver kidney tranplantations were analysed according to the total ischemic time (T.I.T) groupe I: TIT less than or equal to 12 hours, groupe II: TIT from 12 to 30 hours). No difference could be demonstrated between the two groups whether considering the percentage of immediate function, the serum creatinine level which was normal up to two years, the incidence of abnormal blood pressure, the pathological changes on routine biopsies performed at 6 months and 2 years and arteriographic features at 2 years. A better graft survival rate was consistently found at 6 months one year and 2 years when TIT was between 12 and 30 hours. This could be related to the higher indicence of well matched kidneys in this group of patients. The efficiency of exchange programs for compatible kidneys is thus emphasized.

We report the case of a renal transplantation performed with the kidney of an asymptomatic female carrier of Fabry's disease. The recipient, her daughter, had normal alpha-galactosidase levels. Eight years after transplantation, the characteristic lesions of the glomerular epithelial cells, noted as early as 11 days after transplantation, are unchanged on the successive biopsies. This observation suggests that 1) some heterozygotes (perhaps all of them) have glomerular changes, 2) the glomerular changes are not modified if the kidney is placed in a normal enzymatic "environment".

Primary hyperoxaluria leading to calcium oxalate urinary stones and renal deposits occurs rarely in adults. We report three cases in whom end-stage renal failure was precipitated by urological surgery. In contrast, in one case renal stones were destroyed by extracorporeal shock-wave lithotripsy and renal function was not significantly altered. This emphasises the need for early diagnosis. This may not be easy in adult patients: urolithiasis may not be severe, radiological nephrocalcinosis may be lacking, and renal failure may develop late in life.

The authors report a case of acute lithium poisoning, of double interest by virtue of its accidental origin and the fact that the patient suffered from chronic uraemia treated by intermittent haemodialysis, without residual diuresis. Neurological involvement consisted of a succession of dysarthria, behaviour disturbance, extra-pyramidal hypertonia and finally coma with respiratory difficulties. A favourable outcome was obtained by daily haemodialysis which made possible the elimination of almost all the lithium introduced into the body.

Institut Pasteur Production vaccine, prepared from plasma of chronic carriers of HBsAg (ad + ay sub-types) negative for HBeAg, inactivated by formaldehyde, containing 5 microgram HBsAg per 1ml dose, with Al (OH)3 as adjuvant, was tested in a multicentric efficacy trial. After informed consent and exclusion of subjects positive for HBsAg, anti-HBc or anti-HBs, 367 permanent staff members and 138 chronic haemodialysis patients from 64 centres were enrolled in the trial. They received randomly, double-blind, 3 subcutaneous doses of either vaccine (V) or placebo (P) at one-month intervals and were followed monthly for one year. The incidence of HBV infections was significantly lower in V than in P recipients, in staff and in patients. In staff members, no HBV infections occurred in V recipients after the second injection, whereas they were distributed throughout the whole 12 month follow-up period in P recipients. Anti-HBs titres greater than or equal to 10mIU/ml were obtained in 94% of vaccinated subjects. Antibody peak (mean +/- 2 SE) reached 2433 +/- 1077mIU/ml two months after the third injection, with a further rise to about 30 times this value following a booster injection, 16 +/- 2 months after the first injection. These results demonstrate the immunogenicity and efficacy of Institut Pasteur Production hepatitis B vaccine.

Between 1967 and 1978, among more than 1 000 patients under haemodialysis, 66 who had severe secondary hyperparathyroidism, underwent parathyroidectomy (PTx). Subtotal PTx's were performed in 57 patients and total PTx's immediately followed by autotransplantation of parathyroid gland fragments in 9 patients. The patients operated upon by these two methods since 1976 were compared. Among the 10 patients who had undergone subtotal PTx recurrence of severe biological hyperparathyroidism was observed in four cases and permanent hypoparathyroidism in two cases. Among the 9 patients with total PTx and immediate autotransplantation only one was considered as suffering from recurrent hyperparathyroidism on account of increased plasma parathyroid hormone concentrations; none of the other patients in this group had hypoparathyroidism. On follow-up, the clinical and radiological findings were comparable in both groups. At the present moment, our choice of surgical method remains arbitrary. Total PTx with immediate autotransplantation is carried out in all cases of reexploration of the neck, in patients who do not comply with the proposed medical treatment and when surgery reveals grossly enlarged parathyroid glands. In all other cases we continue to perform subtotal PTx.