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Biomedical subjects

J P Cosyns

Publications and source records attributed to J P Cosyns.

At least 37 records · Page 2Linked to original sources

Recurrent fulminant anti-glomerular basement membrane nephritis at a 7-year interval.

True recurrence of anti-glomerular basement membrane (anti-GBM) nephritis is very rare, both in native kidneys and after renal transplantation. We report the recurrence of fulminant anti-GBM nephritis in a kidney graft recipient after the spontaneous withdrawal of immunosuppressive treatment more than 5 years after renal transplantation. The initial episode of anti-GBM nephritis had destroyed the native kidneys 7 years earlier. Circulating anti-GBM antibodies had disappeared for 14 months at the time of transplantation and reappeared with recurrence. This observation challenges the concept of anti-GBM nephritis as a single-shot illness and emphasises the need to consider the possibility of recurrence, even in the long term, among patients who underwent transplantation for anti-GBM nephritis.

Adult↗

Glomerular thrombosis: an unusual cause of renal failure in systemic lupus erythematosus.

The authors report an unusual case of acute renal failure occurring in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Kidney biopsy revealed glomerular thrombosis, in the absence of glomerulonephritis. The authors stress the clinical and biological signs that suggest the thrombotic nature of kidney failure in lupus patients.

Acute Kidney Injury↗

Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum.

Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects (n = 5), uremic patients treated by hemodialysis (n = 7) or PD (n = 4), and nonuremic patients (n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35-50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever their origin, eNOS (135 kDa) is upregulated in the three patients with ascites and/or peritonitis (1 PD and 2 nonuremic patients). AQP-2, regulated by vasopressin, is not expressed at the protein level in human peritoneum. This study 1) supports AQP-1 as the molecular counterpart of the ultrasmall pore in the human peritoneum and 2) demonstrates that AQP-1 and eNOS are regulated independently of each other in clinical conditions characterized by peritoneal inflammation.

Adolescent↗

[Complete radical prostatectomy and positive lymph nodes (stages pT1 to 4, N1 to 3, M0, D1)].

Lymph node metastases are rarely detected during radical prostatectomy (55/647 patients in our series or 8.5%) and several authors consider that lymphadenectomy is unnecessary in most cases. Criteria based on clinical stage, PSA and tumor grade have been elaborated in order to avoid pelvic lymph node dissection in a low risk population. It is commonly admitted that patients with clinically localized prostate cancer, a PSA level < 10 ng/ml, and a Gleason score < 7 could be spared a pelvic lymphadenectomy. In our series, these patients account for 12% of positive nodes. The best treatment for prostate cancer patients with a nodal disease is controversial. We compare the evolution of two groups of patients: radical prostatectomy alone or combined with an immediate adjuvant hormonal treatment. We observe a difference between the two groups for biological progression (PSA failure) but not yet for clinical progression nor for survival as our mean follow-up in only 6 years.

Adenocarcinoma↗

Recurrence of membranous nephropathy after renal transplantation: probability, outcome and risk factors.

Recurrence of membranous nephropathy after renal transplantation has been reported either anecdotally or in a few series. In the present study, the potential risk factors as well as hitherto unreported actuarial risk for recurrence and graft loss due to recurrence were evaluated by combining data of a series of transplanted patients with MN at Louvain Medical School (n = 12) and at Lyon (n = 18; previously reported by Couchoud et al. 1995) giving a total of 30 patients. No risk factor for recurrence was identified as there was no statistical difference between the patients with and without recurrence for duration of MN in native kidneys or of pretransplant hemodialysis, presence of HLA-DR3, graft origin and use of cyclosporin. Actuarial risk for recurrence reached 29% at 3 years, plateauing up to 10 years. The outcome of recurrence was poor since the actual risk for graft loss among patients with recurrent MN was 38 and 52% at 5 and 10 years, respectively.

Actuarial Analysis↗

Splenic lymphoma presenting as necrotizing glomerulonephritis.

The authors report a case of necrotizing glomerulonephritis, with granular immune deposits, leading to the etiologic diagnosis of splenic non-Hodgkin's Lymphoma (NHL). The serum creatinine, initially markedly elevated, decreased under steroids and chlorambucil. Unfortunately, the patient died from septic complications. The importance of a careful search for a (localized) NHL in case of necrotizing glomerulonephritis with granular immune deposits is emphasized.

Aged↗

Allogeneic bone marrow transplantation for AL amyloidosis.

AL amyloidosis is an infiltrative disorder characterized by the extracellular deposition of insoluble fibrillar immunoglobulin light chains whose production results from a plasma cell dyscrasia. Treatment with melphalan has resulted in an improvement in a few patients. Recently, intensive chemotherapy followed by autologous or syngeneic stem cell support has been shown to offer potential benefit. Allogeneic stem cell support after intensive therapy would retain the benefits of autologous transplantation, with the additional advantages of a tumor-free graft and of a possible graft-versus-tumor effect. We report a patient with AL amyloidosis and significant proteinuria. She improved after an allogeneic bone marrow transplantation.

Amyloidosis↗

32P-post-labelling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy.

Recently, we reported that aristolochic acid (AA) a naturally occurring nephrotoxin and carcinogen is implicated in a unique type of renal fibrosis, designated Chinese herbs nephropathy (CHN). Indeed, we identified the principal aristolochic acid-DNA adduct in the kidney of five such patients. We now extend these observations and demonstrate the presence of additional AA-DNA adducts by the 32P-post-labelling method not only in the kidneys, but also in a ureter obtained after renal transplantation. Using the nuclease P1 version of the assay not only the major DNA adduct of aristolochic acid, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), but also the minor adducts, 7-(deoxyguanosin-N2-yl)-aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)-aristolactam II (dA-AAII) were detected, and identified by cochromatographic analyses with TLC and HPLC. Quantitative analyses of six kidneys revealed relative adduct levels from 0.7 to 5.3/10(7) for dA-AAI, from 0.02 to 0.12/10(7) for dG-AAI and 0.06 to 0.24/ 10(7) nucleotides for dA-AAII. The detection of the dA-AAII adduct is consistent with the occurrence of aristolochic acid II (AAII) in the herb powder imported under the name of Stephania tetrandra and confirms that the patients had indeed ingested the natural mixture of AAI and AAII. 32P-post-labelling analyses of further biopsy samples of one patient showed the known adduct pattern of AA exposure not only in the kidney, but also in the ureter, whereas in skin and muscle tissue no adduct spots were detectable. In an attempt to explain the higher level of the dA-AAI adduct compared to the dG-AAI adduct level in renal tissue even 44 months after the end of regimen, the persistence of these two purine adducts was investigated in the kidney of rats given a single oral dose of pure AAI. In contrast to the dG-AAI adduct, the dA-AAI adduct exhibited a lifelong persistence in the kidney of rats. Our data demonstrate that AA forms DNA adducts in human tissue by the same activation mechanism(s) reported from animal studies. Thus, the carcinogenic/mutagenic activity of AA observed in animals could also be responsible for the urothelial cancers observed in two of the CHN patients.

Adult↗

Treatment with dsDNA-anti-dsDNA antibody complexes extends survival, decreases anti-dsDNA antibody production and reduces severity of nephritis in MRLlpr mice.

Lupus nephritis results from the deposition on the glomerular basement membrane of antibodies cross-reacting with dsDNA. In an attempt to suppress the production of such antibodies in the MRLlpr mouse strain, mice were treated by injections of dsDNA-anti-dsDNA antibody complexes formed in an excess of syngeneic polyclonal antibodies to increase the immunogenicity of idiotypes. A first group of mice was treated after the onset of high-affinity anti-dsDNA IgG antibodies (3 months). We show here that fortnightly injections of dsDNA-anti-dsDNA antibody complexes significantly extend mouse survival over that of two control groups treated with either the carrier buffer or with sham complexes. Treated mice produced 5-fold less anti-dsDNA antibodies than control mice and presented a reduced nephritis activity index at the age of 7 months. Specific anti-idiotypic antibody levels were not modified in the treated group, while showing a sharp decrease in the control group between months 6 and 7. Mice of a second group were started on injections of dsDNA-anti-dsDNA complexes at the age of 4 months when nephritis was already ongoing, and were followed until death while receiving fortnightly injections. Forty percent of the treated mice were still alive after one year, while none of the control mice survived. dsDNA-anti-dsDNA complexes have therefore the potential of reducing the production of anti-dsDNA antibody production and the severity of nephritis in MRLlpr mice. These findings could be relevant for the treatment of human lupus.

Animals↗

[Recurrence following radical surgery for prostatic cancer. Analysis of clinical, biological and anatomo-pathological prognostic factors].

To better characterize risk factors of progression (or recurrence) of prostate cancer after radical surgery, we analysed clinical and biological preoperative characteristics and post-operative pathology results in a series of 179 patients who underwent radical prostatectomy between January 1, 1993 and December 31, 1994. The mean follow-up in the series is 36 months (24-36). 39 patients treated before radical prostatectomy by hormonotherapy or surgery (TURP, TULIP) were excluded from analysis. 28 patients treated with immediate adjuvant therapy were also excluded from the study on risk factors of recurrence. Clinical understaging is 37% (50/134 patients with stage T1-T2 have extracapsular extension or invasion of seminal vesicles). Preoperative PSA value is related to the pathologic stage. Extracapsular disease was found in 17% and 46% when PSA was < 4 ng/ml or > 10 ng/ml respectively, thereby confirming the poor staging value of preoperative PSA alone. Analysis of the surgical margins demonstrates a statistically significant difference (p = 0.018) between patients with a preoperative PSA < 10 ng/ml (22% of positive margins) and those with a PSA > 10 ng/ml (42% of positive margins). Predictive factors of recurrence were analyzed in the 112 patients who have not received pre- or postoperative treatment. The respective impact of clinical stage, preoperative PSA value, Gleason score, invasion of prostatic apex, capsular perforation, surgical margins, invasion of seminal vesicles or of pelvic lymph nodes, and invasion of intraprostatic, intracapsular or extraprostatic nerves were evaluated. In T3 cases, we observe 50% recurrence (but only 4 patients fall into this group) versus 14% in clinically localized tumors (T1c-T2c). No recurrence is detected when preoperative PSA is < 4 ng/ml; on the contrary 21% of patients with a PSA > 10 ng/ml recurred. Infiltration of the apex does not influence prognosis. In our experience, capsular perforation is a worse prognostic factor than positive surgical margins, the respective rate of failure being 25% and 17% respectively. Invasion of extraprostatic nerves increases the risk of failure compared to capsular perforation alone (31% vs 18%). Seminal vesicles invasion significantly worsens prognosis (50% vs 13% recurrence respectively; p = 0.024). All patients with positive lymph nodes recurred (p = 0.001).

Adenocarcinoma↗

Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy.

A unique type of rapidly progressive renal fibrosis, designated Chinese herbs nephropathy (CHN), has been described in young Belgian women who had followed a slimming regimen including recently introduced Chinese herbs (Stephania tetrandra and Magnolia officinalis). Aristolochic acid (AA), a known nephrotoxin and carcinogen, was suspected as its causal factor. To substantiate this hypothesis, renal tissue from five patients with CHN and six patients with other renal diseases was analyzed for the presence of AA-derived DNA adducts, a described biomarker of AA exposure associated with its carcinogenic and mutagenic activity. Using the 32P-postlabeling method, a major distinct DNA adduct spot was found in all five cases of CHN and identified by cochromatographic analyses with authentic markers as the deoxyadenosine adduct of AA-I [7-(deoxyadenosin-N6-yl)-aristolactam I], the major component of the plant extract AA. This DNA adduct was absent in the six control cases. The 7-(deoxyadenosin-N6-yl)-aristolactam I adduct levels in CHN ranged from 0.7 to 5.3/10(7) nucleotides. Our data demonstrate that AA is implicated in CHN. They suggest a mechanism for the urothelial atypia and cancers observed in this disease and raise the possibility that a DNA mutation is responsible for the kidney-destructive fibrotic process.

Adult↗

Hepatic angiomyo(myelo)lipoma: difficulties in radiological diagnosis and interest of fine needle aspiration biopsy.

We report the case of a patient admitted for acute heart failure associated with severe dilated cardiomyopathy in whom a large hepatic tumor of the right lobe of the liver was incidentally discovered. A fine needle biopsy was performed that led to the diagnosis of angiomyo(myelo)-lipoma (AMML). The difficulties in radiological diagnosis of these very rare heterogeneous benign tumors of the liver and the interest of fine needle aspiration biopsy are discussed.

Angiomyolipoma↗

[Percutaneous treatment of tumors of the upper urinary tract].

In our Institution, 23 patients were selected for percutaneous resection of tumors of the upper urinary tract. Two patients underwent a second procedure: the first for ipsilateral recur and the second for an heterolateral tumor. Among these 23 patients, 11 presented a benign tumor, 9 were treated for a transitional carcinoma of whom 2 invasive state. Both underwent a nephro-ureterectomy. For the 7 superficial transitional carcinomas, the mean follow-up period is 30.4 months. The ipsilateral local recurrencee is 14.3% (1/7), and concern a poorly differentiated tumor (G III). The advantage of the endoscopic techniques to explore and treat the upper urinary tract tumors is double. With these techniques, we can diagnose and treat adequately benign tumors which don't justify radical surgery. In the case of transitional tumors, the percutaneous way is an acceptable method of management when it appears better to avoid a radical treatment (solitary kidney, bilateral synchronous tumors, impairment of total renal function, general injuries). However, it must be performed only in selected cases, and patients should be carefully selected.

Aged↗

Course of Henoch-Schönlein nephritis after renal transplantation. Report on ten patients and review of the literature.

The frequency and the risk factors for clinical recurrence of Henoch-Schönlein nephritis following renal transplantation (TP) remain largely unknown. We report on 14 transplants performed at our center in 10 patients, detail the evolution of 2 of them with clinical recurrence, and review 64 other transplants reported in the literature. In our series, all patients are currently alive. Seven grafts are well-functioning 22-295 (mean, 97) months after TP without any sign of clinical recurrence. Five grafts were lost from rejection. Clinical recurrence occurred in 2 patients who were on cyclosporine/azathioprine/prednisone therapy. Pooling our series with that of Hasegawa et al., the actuarial risk for renal recurrence and for graft loss due to recurrence was 35 and 11% at 5 years after TP, respectively. In our series, duration of original disease was 2 and 28 months in the 2 patients with recurrence versus 31-144 months in the others without recurrence. In the literature, this duration was < or = 36 months in all 7 patients with recurrence. Recurrence occurred despite a > 12-month delay between disappearance of purpura and TP in our 2 patients and in 3 of 6 previously reported recurrences. We conclude that Henoch-Schönlein purpura nephritis frequently recurs after TP. Recurrence (1) seems to be associated with a shorter duration of the original disease, (2) can occur despite a delay of more than 1 year (as commonly advised) between disappearance of purpura and TP, and (3) is not prevented by a triple immunosuppressive regimen that includes cyclosporine.

Adolescent↗