T-cell gamma-delta lymphoproliferative disorders after renal transplantation.
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Biomedical subjects
Publications and source records attributed to D Durand.
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CHIME-Net is a state-wide community health information network project which uses a frame-relay approach to interfacility and internet connectivity. This is a collaborative effort among competitive institutions, which embraces technologies new to the health care industry. The experiences of implementation of the CHIME-Net pilot project are presented as a first milestone for the state-wide effort.
UNLABELLED: When early kidney transplant biopsies showed benign hypertensive nephrosclerosis, i.e. hyalin arteriosclerosis and/or interlobular arteries intimal thickening, they are thought to be of donor origin. Between 1987 and 1992, 439 cadaveric renal transplantations have been performed in our department: amongst them 97, i.e. 22% patients underwent a graft biopsy before the end of the first post transplant month (13 +/- 9.5 days). To ascertain if findings of early renal biopsy was predictive of eventual clinical outcome we analyzed renal function and blood pressure (BP) in the short and mid term. Nephrosclerosis lesions were found in 33 cases (group I) and were absent in the remaining 64 cases (group II). The 2 groups were not statistically different according to the time on dialysis, the recipient's age, the HLA matching, the cold ischemia time. The only statistically significant difference was the donor's age: 39.1 +/- 7 years in group I vs 26.9 +/- 8 years in group II (p = 0.0001). Delayed graft function was not different in the 2 groups (13 +/- 9 days group I vs 11 +/- 6 days group II). On the other hand, 30% of group I, patients required hemodialysis (9.8% in group II; p < 0.005). The incidence in graft rejection episodes was similar in both groups (50%) as well as surgical complications. Renal function was assessed by creatinine clearance at 1 and 2 years and at last follow-up visit (mean follow-up: 50.5 +/- 44 months in group I and 46.9 +/- 24 months in group II; p = Ns): it was similar in both groups (see table). The prevalence of hypertension (HTA) was significantly higher in group I than in group II at two years and last follow-up (*: p < 0.005). [table: see text] CONCLUSIONS: The age of donor is of importance in determining nephrosclerosis of the graft observed on early biopsies. Donor-related nephrosclerosis is a risk factor for the recipient of developing HTA without impairment of graft function in the mid term. In the context of early nephrosclerosis, the occurrence of acute rejection episode(s) is detrimental for the graft function.
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OBJECTIVE: To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN: Open randomised multicentre trial with three year follow up. SETTING: Outpatient departments of six French hospitals. PATIENTS: 100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS: Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS: 17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION: In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.
The Guillain-Barré syndrome associated with cytomegalovirus infection is a recognized entity of unknown pathogenesis. We observed two characteristic cases with acute polyradiculoneuropathy which occurred after renal transplantation. Both patients fulfilled the diagnostic criteria for Guillain-Barré syndrome: tetraparesis with diffuse areflexia and moderate sensorial signs, high protein level in cerebrospinal fluid without cellular reaction, slow or blocked nerve conduction and partial cure after several months delay. In two-thirds of such cases, the syndrome follows an episode of infection. Cytomegalovirus has been recognized as a possible association. The demyelinating polyradiculoneuropathy induced by cytomegalovirus has been reported essentially in immunodepressed patients infected with the human immunodeficiency virus in whom a pathogenic role for cytomegalovirus in peripheral nerves has been suggested. In our two cases, the cytomegalovirus infection occurred before onset of the acute polyradiculoneuropathy. In both cases, specific IgM antibodies and clear IgG positivization occurred before the first signs of neurological impairment even though neither the virus nor specific antibodies could be concomitantly detected in the cerebrospinal fluid. Despite the frequency of cytomegalovirus infections in transplant recipients, to our knowledge, only 9 cases of Guillain-Barré syndrome after transplantation have been reported and the exact mechanism remains to be ascertained. These two cases suggest that the onset of the Guillain-Barré syndrome after renal transplantation was closely related to cytomegalovirus infection. Adequate measures should be taken to quickly diagnose such cases in order to instore rapid treatment for the polyradiculoneuropathy. In addition, this particular situation of post-transplantation onset might help better understand the exact role of cytomegalovirus infection in the Guillain-Barré syndrome.
There has been renewed interest in determining the physicochemical properties of denatured states of proteins. In many denatured states there is evidence for the existence of nonrandom configurational distributions. Here we examine the small-angle neutron scattering profile of yeast phosphoglycerate kinase in the native state and in highly denaturing conditions. We show that the denatured protein scattering profile can be interpreted using a model developed for synthetic polymers in which the chain behaves as a random coil in a good solvent, i.e. with excluded volume interactions. The implications of this result for our appreciation of the protein folding process are discussed.
The aims of this study were to determine whether renal functional reserve (RFR) is still present in cyclosporin-treated renal transplant recipients, and to examine the relationship between RFR and proximal reabsorption. A serial study was carried out in 12 renal allograft recipients (R) with good renal graft function at 20 +/- 2.5 days (S1) and at 7.6 +/- 0.4 months (S2) post-transplantation, and the results were compared to those in eight subjects who had undergone unine-phrectomy (one-kidney controls: UNx.C) and in 12 healthy volunteers (two-kidney controls: 2K.C). R and C were in similar sodium and protein balance and with similar plasma renin and aldosterone levels. R had normal serum creatinine level on moderate doses of cyclosporin (whole blood cyclosporin concentration: 212 +/- 20 and 125 +/- 20 ng/ml at S1 and S2, respectively). Eight one-hour clearance periods were performed prior to, during and following a three-hour i.v. infusion of a mixture of 20 l-amino acids (Azonutril 25, 4.5 mg amino acids/kg/min). Baseline glomerular filtration rate (GFR) was lower in recipients at S1 and S2 (55 +/- 5 and 54 +/- 4 ml/min/1.73 m2, respectively) than in UNx.C and 2K.C (72 +/- 4 and 113 +/- 4 ml/min/1.73 m2, respectively, P < 0.05 and 0.001). Amino acid infusion elicited significant GFR increases in controls as well as in recipients in spite of higher renal vascular resistances (RVR). The greater measured increase in GFR, which represented RFR, was 18 +/- 3 and 28 +/- 2 ml/min/1.73 m2 in UNx.C and 2K.C, respectively (P < 0.001), and 17 +/- 3 ml/min/1.73 m2 in R at both S1 and S2 (P < 0.001). Contrary to both UNx and 2K controls, the acute hyperfiltration in R at S1 and S2 occurred with a significant increase in effective renal plasma flow, no alteration in filtration fraction and a large decrease (approximately 20 and 17%) in RVR while no correlation could be detected between the RFR and baseline GFR. Baseline lithium clearance, used as a marker of overall proximal fluid delivery (CLi), was significantly lower, whereas baseline fractional excretion of lithium (FELi) was significantly higher in R at S1 and S2 and in UNx.C (41 +/- 4, 40 +/- 3 and 38 +/- 3%, respectively) than in 2K.C (31 +/- 2%, P < 0.05). Consistent and significant increase in CLi, FELi and absolute proximal reabsorption occurred both in R at S1 and S2 and in UNx and 2K controls during elicitation of RFR.(ABSTRACT TRUNCATED AT 400 WORDS)
This paper reports on the first coherent neutron scattering measurements ever carried out on the vibrational spectrum of a nucleoside analog. Frequencies up to 3.5 Thz belonging to some half-dozen dispersion curves have been measured in a plane normal to the [1 10] direction in a triclinic crystal of 5-iodo-2'-deoxyuridine (5-iodouridine). The number of phonon branches observed suggests that the deoxyribose sugar and pyrimidine in this molecule are the vibrating entities at low frequencies. Comparisons, notably of elastic properties, are made with previous measurements on crystalline forms of DNA and various nucleic acid base derivatives. The observed frequencies are discussed with reference to a simple force constant model.
Cytomegalovirus (CMV) infections, either primoinfection or reactivation, remain an important problem in organ transplantation. We therefore designed a prospective study in which pre-transplant CMV-positive renal transplant (RT) patients were randomized to receive for 3 months starting immediately after transplantation either acyclovir or nothing. Between April 1992 and January 1993, 53 cadaveric renal transplantations were performed in our institution. The immunosuppressive regimen included anti-thymoglobulins (ATG), azathioprine, steroids and cyclosporine A. Patients randomized in the acyclovir arm received the drug from day 1 to day 90 (D90) intravenously as long as the creatinine clearance was not above 10 ml/min and per os afterwards (3200 mg/day if the creatinine clearance was above 50 ml/min). CMV viraemia tests were systematically performed every 2 weeks until day 90 or when febrile episodes occurred. The patients were 53 adults who received a RT during the study period; 37 were included in the study of which 19 received acyclovir prophylaxis (group A) and 18, no prophylaxis (group B). The two groups did not significantly differ according to sex ratio, recipient's age, number of CMV-negative donors and number of days on ATG (10.76+/-6.16 vs. 8.28+/-4.21 days). There were significantly fewer viraemia episodes in group A (n = 6) than in group B (n = 13, P < 0.05); nevertheless, the percentage of symptomatic CMV viraemia was the same in both groups (35% vs. 38.5%). The onset of CMV viraemia occurred in the same period in both groups (39+/-13.8 days vs. 34.3+/-15 days; P = NS). The number of rejection episodes in the study period was the same in both groups (8 in each). We conclude from this prospective study that post-RT acyclovir prophylaxis reduces significantly the number of CMV viraemia episodes but does not delay their onset. Furthermore, it has no effect upon the percentage of symptomatic viraemias.
In the present work we investigated a possible role of an alpha 1-noradrenergic (NA) pathway involving the hypothalamic paraventricular nucleus (PVN) in the central regulation of growth hormone (GH) release. A week after bilateral electrolytic lesions of the PVN, pulsatile GH-secretory patterns were monitored in unanesthetized, freely moving control or lesioned male rats. While the pulsatility of GH secretion was maintained, the amplitude of the pulses and the area under the curve during an 8-hour sampling period were twice as high in PVN-lesioned than in control rats. Trough levels of GH were similar in the two groups. Inactivation of PVN alpha 1-receptors by local infusion of an alpha 1-NA antagonist, prazosin (50 ng/rat), also induced an increase in GH release. In control animals, intravenous injection of the alpha 1-NA agonist methoxamine (0.02 mg/100 g body weight) elicited a decrease in GH release but was ineffective when administered to PVN-lesioned rats. These data show that alpha 1-NA receptors, mediating GH inhibition, are located in the PVN. In light of the analogous effects observed herein on PVN-lesioned animals and, previously, after locus coeruleus (LC) lesions it is suggested that GH inhibition by the LC is relayed by the PVN via a local alpha 1-receptor population.
We report the long-term follow-up of 5 patients (4 kidney, 1 heart recipients) having a pretransplant monoclonal gammopathy of undetermined significance (MGUS). The follow-up of MGUS before transplantation was 41.2 +/- 40.7 months (range 2-108). The monoclonal component isotype was IgG-kappa in 3 cases and IgA-lambda in 2. The pretransplant level of the monoclonal component was 11.1 +/- 4.8 g/l (range 4-15.6). The transplant recipients who had MGUS were older than our other transplant patients. All but one of them received ciclosporine A. They did not experience more rejection or infectious complications than the others. Their posttransplant follow-up ranged from 3 to 9 years. The monoclonal component level remained stable in 2 patients but increased in 3 (33-225%). This was not correlated with bone marrow plasmocytosis. Two patients developed smoldering myeloma indicated by bone marrow immunochemistry studies which showed monomorph monoclonal plasma cells; nevertheless, they did not have cytopenia or bone lytic lesions. This percentage is higher than in the Kyle study but we cannot assume that it is due to ciclosporine A since our study sample is too small. In conclusion, MGUS is not a contraindication to organ transplantation.
We report on 2 cases of renal oncocytoma occurring in a liver transplant patient and in a kidney allograft recipient, respectively, during the posttransplant period. This neoplasm has never been reported in transplant patients; its relationship with long-term immunosuppressive therapy is questioned.