The interaction between clarithromycin and cyclosporine in kidney transplant recipients.
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Biomedical subjects
Publications and source records attributed to E Goffin.
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The fate and significance of hepatitis C virus (HCV) infection after renal transplantation (TP) remain debated. We therefore evaluated the incidence and outcome of HCV infection in 120 kidney graft recipients both at the time of TP and 54 +/- 28 (13 to 123) months later using ELISA-II and RIBA-II immunoblot. Furthermore, the presence of anti-HCV antibodies at follow-up was correlated with HCV viremia, as detected by the nested polymerase chain reaction (PCR), and with chronically abnormal ALT levels. At the time of TP, 17 patients (14.2%) had anti-HCV antibodies. Compared to anti-HCV (-) patients, anti-HCV (+) patients had a longer duration of pre-TP dialysis (P < 0.001) and had received more pre-TP blood transfusions (P < 0.01). After an average follow-up of 48.5 +/- 24.7 (21 to 97) months, all these patients remained anti-HCV (+) but only 10 were still RIBA "reactive" due to the loss of reactivity against the 5-1-1, C100 and C33 (but not the C22) antigens. Five initially anti-HCV (-) patients had become (+) at follow-up. Among the 22 patients anti-HCV (+) at follow-up, 20 had HCV-RNA detectable by PCR but only 10 had elevated ALT. Ten out of 13 HBsAg (-) patients with elevated ALT were anti-HCV (+). Our study indicates that disappearance of ELISA-II anti-HCV antibodies is rare in kidney recipients and that HCV infection may also occur after TP. Anti-HCV antibodies are likely to reflect a persisting infection as suggested by the frequent detection of HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
The potential for neutrophils to obstruct microvessels was evaluated by measuring transit of individual neutrophils through 8-microns pores in an automated cell transit analyzer (CTA) or into micropipettes (4-8 microns ID). Stimulation in vitro by the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine. (fMLP), cigarette smoke, or purified antineutrophil cytoplasm antibodies greatly increased flow resistance, but the response varied in its dependence on time and pore diameter. Cigarette smoke or fMLP caused rapid loss of cellular deformability, although observations were complicated by changes in cell shape: progressive bipolar shape formation (after treatment with fMLP) could facilitate entry into larger pores (approximately 8 microns), whereas blebs induced by cigarette smoke caused bridging of these pores with cell immobilization. These processes led to an underestimation of the changes in deformability by the CTA. Neutrophils responded slowly to the antineutrophil cytoplasm antibodies (approximately 30 min), with a greater increase in flow resistance evaluated by a micro-pipette (4-6 microns ID) than by the CTA. We conclude that the effect of neutrophil stimulation on flow through capillary-sized vessels is potentially great (with resistance typically increased 10-fold or even complete blockage) but may depend on the vascular and cellular geometry and may be local or disseminated, depending on the rate of the rheological response.
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A syndrome of severe osteoarticular pain of lower limbs occurring early after renal transplantation (TP) has been recently identified. We describe its prevalence, clinical presentation and outcome. Symptomatic patients have been studied with conventional X-rays, magnetic resonance (MR) imaging, and 99mTechnetium scintigrams of the painful areas. Among 86 patients transplanted over a two-year period, nine (4 men, 5 women; mean age of 40.4 years; range 32 to 59) developed unexplained severe spontaneous osteoarticular pain of lower limbs 19 to 105 (mean 58) days after TP. Pain affected hip(s), knee(s), and/or ankle(s). Clinical examination was usually unremarkable. Favorable outcome was the rule; mean duration of pain was 86 (range 19 to 175) days. Radiographs were abnormal (joint swelling, patchy osteoporosis and/or periosteal reactions) in 41%, MR (epiphyseal fatty marrow replacement by edema and/or hemorrhages) in 83%, and bone scans (one to several epiphyseal foci of increased uptake) in 81% of the symptomatic examined areas. Among joints re-examined 9 to 12 months after resolution of the symptoms, X-rays showed periosteal reactions in 31%, and the bone scans disclosed persistent increased uptake in 53% of the joints, whereas epiphyseal MR abnormalities had completely disappeared in 86%. There was no difference in dialysis duration, post-TP weight gain, evidence of hyperparathyroidism, and steroid and cyclosporine doses between symptomatic and an appropriately selected group of asymptomatic patients. By contrast, serum alkaline phosphatase levels were transiently higher (at the onset of symptoms) in the symptomatic group.(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid function has been assessed in 36 clinically euthyroid patients undergoing regular haemodialysis. The influence of erythropoietin administration on the thyroid function tests has been determined. Thyroid-stimulating hormone (TSH) has been found to be elevated in 8% of the patients. Free tri-iodothyronine was below the normal range in 67% of the population. Free thyroxine (FT4) was low in 67% of the patients when tested by an analogue method. FT4 tested by a 2-stage method in a subgroup of 22 patients was abnormally low in only 23% of the patients. Erythropoietin did not seem to improve these thyroid abnormalities despite a partial correction of the anaemia. A rise in FT4 was also observed after haemodialysis without a concomitant change in TSH concentration. This FT4 elevation was attributed to the effect of heparin.
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Little clinical work has been performed using technetium-labelled lymphocytes due to the difficulty of effecting an imaging dose of technetium on the small number of lymphocytes available. We have successfully labelled lymphocytes using a high concentration and low volume of 99Tcm-exametazime. In eight readings from three patients and two volunteers, the labelling efficiency was 27% (4 S.D.). The radiolabel was stable in plasma in vitro up to 4 h. Viability of the lymphocytes as determined by trypan blue exclusion was greater than 95%.
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We tested the hypothesis that metabolism of individual cartilage samples, such as those which might be taken at arthroscopy, could reflect the overall intrinsic reparative response of the cartilaginous tissue of that joint. Full thickness samples of articular cartilage, removed from the anteromedial, anterolateral and posterolateral areas of the femoral condyles of 2 normal knees, were placed in tissue culture separately. The incorporation of 14C-glucosamine into matrix molecules, especially proteoglycan, was measured. Three slices of each area were removed after one, 3 or 6 weeks of in vitro culture. The extracted matrix molecules and the media were analyzed and the relative amount of radioactive proteoglycan and proteoglycan aggregates, as well as the total amount of radiolabelled proteoglycan/mg dry weight, were calculated. A progressive increase in these variables during the culture period was demonstrated, suggesting an attempt at repair of the articular cartilage in this in vitro condition. No differences in the incorporation dynamics were found between the anteromedial, anterolateral and posterolateral areas of both subjects.
Three main bone disorders may occur after organ transplantation: epiphyseal impactions, avascular bone necrosis, and osteoporosis. Their main clinical characteristics, causes, diagnostic approaches, and therapies are discussed in this review.
We report the case of a 29-year-old man with a 14-year history of type 1 diabetes, normal renal function, and mild diabetic retinopathy. The patient progressively developed a generalized allergic reaction to two insulin excipients--protamine and metacresol--with systemic manifestations of tremor, tachycardia, vertigo, shortness of breath, and short episodes of unconsciousness causing him to be out of work. In June 2003, he received a vascularized cadaveric pancreas transplant using induction with polyclonal antibodies along with tacrolimus and sirolimus but without steroids. A hyperglycemic episode following corticosteroid therapy for rejection treatment required reintroduction of insulin therapy with prompt reappearance of allergic manifestations. Now, the patient is euglycemic without insulin or allergic manifestations and a glycated hemoglobin of 6.4%.