[Coronary artery disease and coronary angioplasty in chronic hemodialysis patients]. / Coronaropathie et angioplastie coronaire dans l'insuffisance rénale dialysée.

Chronic renal insufficiency leads to many cardiovascular complications and provide worst prognosis, especially when patients need hemodialysis. The atherosclerosis of chronic hemodialysis patients is qualified as "accelerated" by some authors, because of a very fast and large progression. To improve prognosis, it seems to be very important to detect and treat the frequent and serious underlying cardiovascular disease. Because of the high rate of diabetes mellitus, silent ischemia is a very frequent clinical situation. In the other hand, coronary artery disease in chronic hemodialysis patients is frequently complex, with a large coronary extension and high rate of coronary calcifications. Consequently, this disease needs a specific therapeutic approach. Even though, percutaneous coronary interventions (PCI) are more complex in this population, it provides good results, and improves patient's prognosis. However, the rate of complications of the vascular approach and the rate of restenosis is high. New devices, such as Drug Eluting Stents (DES) can critically decrease restenosis rate, and closure devices for trans-femoral approach, provides very encouraging results in this high risk population. Despite, good results of PCI with DES use, the mortality is still high in this population. To improve our efficiency, we have to progress in our therapeutic strategies and optimize medical approach to treat the important biological perturbations.

[Optimization of enoxaparin dose in the prevention of coagulation in the circuits of hemodialysis: results of a multicenter study]. / Optimisation de la dose d'énoxaparine (Lovenox) dans la prévention de la coagulation des circuits d'hémodialyse: résultats d'une étude multicentrique.

In order to define the optimal dosage of a low molecular weight enoxaparine (Lovenox) in the prevention of clotting in extracorporeal circulation during hemodialysis, a multicentre trial was conducted in 72 patients dialysed in seven hemodialysis units. During three weeks, these patients received as antithrombic treatment a single injection of enoxaparine at the beginning of the session. The initial dose fixed by previous data concerning dialysis with high hemorrhagic risks patients was 0.5 mg/kg (50 U1 Anti-Xa/kg). According to the evaluation of thrombotic manifestations during a 4 hour dialysis, the dosage was progressively increased if necessary for each patient. For 41% patients, the initial dose of 0.5 mg/kg was maintained along the whole study; 59% patients needed higher dose, between 0.6 and 0.9 mg/kg. The mean dose for the whole patient population at the end of the study was 0.62 +/- 0.16 mg/kg. No complication nor side effect was noted. The influence of blood flow, nature of dialysis membrane, level of hematocrit was studied. In conclusion, 0.5 mg/kg of enoxaparine can prevent thrombotic manifestations in almost half of chronic hemodialysed patients with good results. Further studies could precise the place of personal or technical parameters in the choice of the optimal dose for each patient.

Reversal effects of topical retinoic acid on the skin of kidney transplant recipients under systemic corticotherapy.

The systemic long-term corticosteroid treatment administered to kidney graft recipients (KGR) within the framework of the required immunosuppressive therapy induces an atrophy of the skin, from the sixth month onwards. We studied the effect of topical all-trans retinoic acid (0.05%; Galderma Labs.) applied to the forearms of 27 KGR (14 men, 13 women) over a 6-month period. Twenty-four subjects completed the trial. The following results were obtained in the treated forearm versus the untreated forearm (excipient alone): clinically, an increase in skin thickness; by noninvasive techniques, an increase in skin thickness, skin elasticity, skin conductance, and TEWL, and a reduction in the size of the corneocytes. No change in stratum corneum lipid content was observed. A sex-related difference was noted in the response to treatment under our experimental conditions, the female patients responding better. A punch biopsy (4 mm) was performed on both forearms of four patients after the 6-month period. Histologic and ultrastructural examination revealed epidermal and dermal changes evoking increased cellular metabolism in the retinoic acid-treated forearms.

Chronic hepatitis in kidney allograft recipients.

98 HBsAg-positive and 31 HBsAg-negative kidney recipients were compared to assess the effect of renal transplantation on chronic liver disease and vice versa. Diagnosis was based on analysis of liver biopsy specimens including semiquantitative evaluation of histological features of chronic hepatitis. Serial specimens were examined: chronic liver disease occurred in 88% of HBsAg-positive patients and 4% of HBsAg-negative patients with normal liver at the time of transplantation. Liver abnormalities in the former were chronic persistent hepatitis (32%), chronic active hepatitis (51%), and cirrhosis (17%). Actuarial patient survival was similar in HBsAg-positive (78%) and HBsAg-negative (87%) patients, as was allograft survival (64% and 71%, respectively). In both HBsAg-positive and HBsAg-negative patients chronic alcohol consumption was more frequent in those with chronic liver disease than those without. These data suggest that renal transplantation may be appropriate for haemodialysis patients with chronic hepatitis whatever their HBV status.

Molecular typing of nosocomial isolates of Legionella pneumophila serogroup 3.

In Paris, France, an outbreak of pneumonia due to Legionella pneumophila serogroup 3 was observed in Necker (four cases) and Pitié (six cases) hospitals. Neither the 10 clinical isolates nor 5 tap water isolates from Necker Hospital harbored plasmids. Clinical and environmental serogroup 3 isolates and serogroup 3 reference strain Bloomington 2 were analyzed by chromosomal probe fingerprinting. rRNA, 16S and 23S from Escherichia coli and a randomly cloned 15-kilobase-pair nucleotide sequence from L. pneumophila serogroup 3 were used as probes. All strains tested showed a single pattern after HindIII digestion of DNA and hybridization with the 32P-end-labeled rRNA probe, whereas three patterns were obtained after hybridization with the 32P-labeled 15-kilobase-pair DNA probe. One pattern was given by all clinical and tap water isolates from Necker Hospital, another one was given by all clinical isolates from Pitié Hospital, and a last one was given by reference strain Bloomington 2. Thus, molecular analysis showed that the two hospital outbreaks of legionellosis were unrelated and could link the outbreak in Necker Hospital to contaminated tap water.

Detection of human cytomegalovirus DNA in liver biopsies from patients with cytomegalovirus-related liver disease.

Infection with human cytomegalovirus (HCMV) has been associated with severe diseases in immunologically impaired patients. Cytomegalovirus hepatitis has been frequently described in this population, but this diagnosis is still difficult. Molecular hybridization with the V EcoRI restriction fragment of human cytomegalovirus strain AD 169 has been tested upon DNA extracted from liver samples to assess the usefulness of this technique for cytomegalovirus hepatitis diagnosis. This probe was shown by the Southern technique not to hybridize with DNA extracted from cells infected with other herpesviruses or with DNA of non-infected normal liver. The sensitivity was estimated to be 2 x 10(5) genomes. Twenty-five renal transplant recipients under immunosuppressive therapy and three patients having the acquired immunodeficiency syndrome were studied. In 9 out of 10 renal transplant recipients with normal liver, previous exposure to cytomegalovirus, as defined by serological tests, was not sufficient to allow positive detection by the probe. Out of 11 patients with abnormal liver, cytomegalovirus DNA sequences were shown in 5. In 2 patients with histological evidence of cytomegalovirus hepatitis, a very strong signal showed the presence of viral genomes. These results show that the Southern technique with the V EcoRI probe can be useful for the diagnosis of HCMV hepatitis and might be proposed for the detection of this viral genome in human tissues.

Lymphadenopathy in renal transplant patients treated with immunosuppressive antibodies (OKT3 and anti-thymocyte globulin). A report of nine cases.

A clinicopathological study of nine patients who developed systemic lymphadenopathy following renal transplantation and immunosuppressive therapy (OKT3 and anti-thymocyte globulin) showed a rapidity of onset and disappearance of lymphadenopathy (nine of nine cases), a frequent association of systemic signs (nine of nine cases), and a heterogeneity of histological patterns ranging from diffuse lymphoid hyperplasia to one incorrectly considered to be immunoblastic lymphoma. The coexpression of both light chains was useful in the exclusion of the diagnosis of B lymphoma. These posttransplant lymphoproliferative syndromes seem to represent an allergic reaction to the introduction of foreign protein resembling serum sickness rather than a viral infection favored by immunosuppression, although in one case (with pseudolymphomatous features) a virus was the likely mechanism.

[Comparison of the implantation and metabolic activity of human and rat fecal flora administered to axenic rats]. / Comparaison de l'implantation et de l'activité métabolique d'une flore fécale de rat et d'une flore fécale humaine inoculées chez le rat axénique.

Gnotobiotic rodents are increasingly used as a model for studying in vivo the characteristics of human colonic flora. However, the value of this model has been poorly assessed. In this study fecal bacterial flora provided either by a conventional rat (group RFR) or by man (group RFH) was administered orally to two groups of 6 germ-free rats. One month later, quantitative bacteriological analyses of feces revealed that bacterial populations were close to those of donors in both groups. The metabolic activity of the genuine flora was further compared in groups RFR and RFH with that of the implanted flora: a) concentrations of each fecal volatile fatty acid and of fecal bile acids were similar in conventional and RFR rats as well as the percentage of transformation of cholesterol into coprostanol (48 p. 100 and 54 +/- 5 p. 100 respectively; m +/- SD); b) similar concentrations of fecal volatile fatty acids were obtained from the human donor and RFH rats. Alpha, beta and omega muricholic acids absent in human donor's feces were found in RFH feces. Cholesterol transformation was lower in RFH rats (48 +/- 9 p. 100) than in man (85 p. 100); c) a single dose of lactulose (3 g/kg) increased breath hydrogen excretion in man but not in conventional or in RFR rats and RFH. Chronic lactulose ingestion (3 g/kg d.i.b. for 8 days) had no effect in conventional or RFR rats. Hydrogen excretion was decreased in man, whereas it was significantly increased in RFH rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Granulocyte-associated immunoglobulins in renal transplant recipients with cytomegalovirus infection.

Cytomegalovirus (CMV) infections in renal transplant recipients must be diagnosed rapidly, since they can be life-threatening unless chemotherapy is started early. Detection of granulocyte-associated immunoglobulins was compared with conventional virological methods for diagnosis of CMV infection in 71 renal transplant recipients. The granulocyte-associated immunoglobulin test (GAIT) was positive in 31 of 34 patients with proven CMV infections on the day of admission. By conventional virological criteria the diagnosis of active CMV infection could be made only 3-24 days later. The GAIT remained negative in 14 healthy transplant recipients, but it was positive in 9 of 23 patients with non-CMV-related post-transplantation complications. The GAIT, which is not a virological method, could be useful for rapid diagnosis of CMV infection; its sensitivity was 0.91 and specificity 0.82 (for patients without detectable immunoglobulins on erythrocytes or platelets) and the processing time is only 3 h.

Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients.

During a cumulated survey of 286 months, covering 11 gastroenterological patients under nocturnal-cyclic home parenteral nutrition, 24 cases of catheter-related sepsis were observed (one/11.9 months). None of these were associated with focus of infection at the cutaneous entry point or at the subcutaneous tunnel of the catheters. In this study attempt was made to control sepsis without removal of the surgically implanted siliconed lines (Vygon code 180-20 with an internal filling volume of 1 ml). The first two catheter-sepsis were conventionally treated with systemic antibiotics for 3 weeks which meant a 1-month hospital admission each time. Consequently, we used a new antibiotic therapy consisting of locking 12 hr/day 2 ml of highly concentrated antibiotic solution within the catheter. After identification of bacterial strains by blood cultures, the antibiotic lock-technique was daily applied either alone for 16 days (group I, n = 11) or for 12 days following a 3-day course of systemic antibiotics (group II, n = 11). After starting antibiotics via the infected line, the time taken for fever abatement and for obtaining negative in-line blood cultures were 2 and 4 days, respectively, and identical in group I and II. Failure of antibiotic treatment leading to catheter withdrawal was observed once in each group (9%) and was due to secondary candida catheter-sepsis. The time for hospital stay was shorter p less than 0.02 in group I (4 days) than in group II (7 days). Antibiotic-lock technique was then applied by trained patients at home.(ABSTRACT TRUNCATED AT 250 WORDS)

One-month prophylactic use of OKT3 in cadaver kidney transplant recipients.

Fifty-five recipients of first cadaveric renal allografts were randomly assigned to three treatment groups in order to compare the safety and efficacy of a mouse antihuman T cell monoclonal antibody (OKT3) given prophylactically for a one-month period. This long period of administration was made possible by concomitant administration of azathioprine. The immune response against the foreign immunoglobulin was thus delayed and decreased in both intensity and severity, and OKT3 treatment could be given during almost the entire month in the majority of patients. The 18 patients who were enrolled in this treatment group had significantly (P less than 0.01) fewer rejection episodes during the first month posttransplantation than the 19 patients allocated to the high-dose (HD) steroid control group or the 18 patients allocated to the low-dose (LD) control group. Actual 2-year as well as actuarial 4-year graft survival rates were 89% in the OKT3 group, whereas they were 70% and 67% respectively in the steroid control groups. Four-year serum creatinine levels were normal and doses of steroids and other immunosuppressive agents were lower in the OKT3 group as compared with the control groups. Tolerance to OKT3 was good, and while viral infections were more frequently observed in OKT3 treated patients, the total number and the severity of infectious episodes were similar in all groups. The combination of one-month OKT3 plus azathioprine prophylaxis followed by conventional azathioprine plus low-dose steroid maintenance produced very satisfactory long-term results comparable to the best results now being obtained with cyclosporine regimens.

Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipients. A prospective study of 90 patients.

Hepatitis B virus (HBV) infection may induce severe hepatitis and affect long-term survival of kidney transplant recipients. Persistent viral infection has been shown to occur despite the absence of usual serologic markers. The liver and serum HBV deoxyribonucleic acid (DNA) status of 90 patients were studied prospectively; recently transplanted patients, both hepatitis B virus surface antigen (HBsAg)-positive and negative, with and without liver disease, were investigated with HBV serology, serum HBV DNA, and liver histology. Thirty-four patients had detectable HBsAg, and 21 had viral multiplication at the time of transplantation. Serial HBV DNA determinations performed in 57 of 90 patients disclosed (a) reactivation of HBV replication in 11 of 12 HBsAg-positive patients, (b) increase of viral replication when positive on the initial sample in 6 of 11 patients, and (c) development of HBV replication in 7 of 35 of the HBsAg-negative patients. Moreover, liver HBV DNA studies showed a statistical correlation between the presence of integrated liver HBV DNA and chronic hepatitis in HBsAg-negative patients. This study demonstrates prospectively the significant association of HBsAg-positive as well as HBsAg-negative HBV infection with chronic hepatitis and suggests that immunosuppressive therapy may enhance the viral replication in both HBsAg-positive and negative subjects.

Toxoplasma antibody titers in renal transplant recipients. Pretransplant evaluation and posttransplant follow-up of 73 patients.

In 73 consecutive kidney transplant recipients, anti-Toxoplasma antibodies were determined before transplantation and during a 3-year follow-up after transplantation. In 9 patients, antibody titers increased significantly after transplantation. Antibody titers to various viral antigens determined in parallel remained unchanged, suggesting that the anti-Toxoplasma antibody increase was not due to polyclonal nonspecific stimulation. In 2 of the 24 pretransplant seronegative patients, acquired toxoplasmosis was diagnosed serologically after transplantation, with the observation of a strong IgM and IgG antibody response. The incidence of toxoplasmosis in this group of patients was not found to be significantly different from that in a normal population, suggesting that transmission of Toxoplasma from the transplanted kidney may not be a significant mode of contamination. Among the 49 patients who were seropositive before transplantation, reactivation of toxoplasmosis was suspected in 7 cases on the basis of a significant increase in IgG antibodies. Reactivation occurred more frequently in patients treated with azathioprine and antithymocyte globulin, and a direct relationship between administration of steroids and antibody increase was demonstrated in three patients. Although toxoplasmosis has occasionally been reported as a major infectious problem in kidney transplant recipients, our clinical and serological data show that the potential risk of developing Toxoplasma infection is low since none of the patients with either acquired or reactivated toxoplasmosis developed clinical disease.