Biomedical subjects
Publications and source records attributed to P Blanchet.
A case of leiomyosarcoma of the prostate is presented. Adult prostatic leiomyosarcoma is a rare tumor with a poor prognosis. US-CT and MRI findings are described.
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Using an antibody that recognizes the products of all known members of the fos family of immediate early genes, it was demonstrated that destruction of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle produces a prolonged (>3 months) elevation of Fos-like immunoreactivity in the striatum. Using retrograde tract tracing techniques, we have previously shown that this increase in Fos-like immunoreactivity is located predominantly in striatal neurons that project to the globus pallidus. In the present study, Western blots were performed on nuclear extracts from the intact and denervated striatum of 6-OHDA-lesioned rats to determine the nature of Fos-immunoreactive protein(s) responsible for this increase. Approximately 6 weeks after the 6-OHDA lesion, expression of two Fos-related antigens with apparent molecular masses of 43 and 45 kDa was enhanced in the denervated striatum. Chronic haloperidol administration also selectively elevated expression of these Fos-related antigens, suggesting that their induction after dopaminergic denervation is mediated by reduced activation of D2-like dopamine receptors. Western blot immunostaining using an antibody which recognizes the N-terminus of FosB indicated that the 43 and 45 kDa Fos-related antigens induced by dopaminergic denervation and chronic haloperidol administration may be related to a truncated form of FosB known as deltaFosB. Consistent with this proposal, retrograde tracing experiments confirmed that deltaFosB-like immunoreactivity in the deafferented striatum was located predominantly in striatopallidal neurons. Gel shift experiments demonstrated that elevated AP-1 binding activity in denervated striata contained FosB-like protein(s), suggesting that enhanced deltaFosB levels may mediate some of the effects of prolonged dopamine depletion on AP-1-regulated genes in striatopallidal neurons. In contrast, chronic administration of the D1-like receptor agonist CY 208243 to 6-OHDA-lesioned rats dramatically enhanced deltaFosB-like immunoreactivity in striatal neurons projecting to the substantia nigra. Western blot immunostaining revealed that deltaFosB and, to a lesser extent, FosB are elevated by chronic D1-like agonist administration. Both the quantitative reverse transcriptase-polymerase chain reaction and the ribonuclease protection assay demonstrated that deltafosB mRNA levels were substantially enhanced in the denervated striatum by chronic D1-like agonist administration. Lastly, we examined the effects of chronic administration ofD1-like and D2-like dopamine receptor agonists on striatal deltaFosB expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. In monkeys rendered Parkinsonian by MPTP, there was a modest increase in deltaFosB-like protein(s), while the development of dyskinesia produced by chronic D1-like agonist administration was accompanied by large increases in DeltaFosB-like protein(s). In contrast, administration of the long-acting D2-like agonist cabergoline, which alleviated Parkinsonian symptoms without producing dyskinesia reduced deltaFosB levels to near normal. Taken together, these results demonstrate that chronic alterations in dopaminergic neurotransmission produce a persistent elevation of deltaFosB-like protein(s) in both the rodent and primate striatum.
The binding of thyroid hormones and its regulation of NADPH and NADP+ were studied in human kidney cytosol, and a 38-kDa polypeptide (p38) was identified by photoaffinity labeling of cytosol with underivatized [125I]T3, SDS-PAGE, and autoradiography. The cytosolic thyroid hormone binding and p38 photolabeling were strongly activated by NADPH (maximum at 10(-7) M), whereas other nucleotides were less effective or ineffective. NADP+ did not activate T3 binding and p38 photolabeling, provided it was protected from conversion to NADPH by the addition of an exogenous oxidizing enzymatic system (oxidized glutathione plus glutathione reductase). Furthermore, NADP+ inhibited NADPH activation (half-maximum inhibitory effect at approximately 2 x 10(-5)M), and oxidation of NADPH to NADP+ induced dissociation of bound T3. The equilibrium dissociation constant (Kd) of the NADPH-activated cytosolic T3-binding sites was 0.3 nM, similar to the Kd of the nuclear T3 receptors. The kidney contained 200 times more cytosolic NADPH-activated thyroid hormone-binding sites than nuclear T3 receptors. Nonradioactive iodothyronines competed with [125I]T3 for both NADPH-activated binding and p38 photolabeling, with the following order of decreasing affinity: D-isomer of T3 > T3 > T4 > triiodothyroacetic acid > 3'-isopropyl-3,5-diiodothyronine > rT3. NADPH-activated T3 binding and photolabeled p38 were also detected in human heart and liver cytosols, but not in pancreas, cultured fibroblast and erythrocyte cytosols, or plasma. Rat kidney cytosol contained a 35-kDa photolabeled polypeptide homolog to human p38. The native molecular mass of the human photolabeled protein was 50 kDa, whereas that of the rat protein was 60 kDa, as determined by nondenaturing polyacrylamide gel electrophoresis. Two-dimensional PAGE of photolabeled p38 indicated an isoelectric point of 5.3. These findings describe the molecular properties of a NADPH/NADP+-regulated thyroid hormone-binding protein not previously identified in human and rat kidney cytosol.
Twenty five double kidney-pancreas transplantations were performed according to the total pancreas transplantation technique with drainage of exocrine secretions into the bladder via a vesicoduodenostomy. 72% of kidney-pancreas grafts were functional at one year and 59% were functional at four years. The authors observed a slightly higher rejection rate (0.56 versus 0.34) and a higher incidence of urinary tract infection (60% versus 35%) following double pancreas and renal transplantation than after isolated renal transplantation. Complications were rare: two venous thromboses and two cases of urethritis requiring of rediversion of the duodenum into the intestine. These good results, comparable to those reported in the international registry, reflect the value of the pancreatic and renal transplantation technique using a total pancreas drained into the bladder. It would probably be preferable to transplant patients earlier, when chronic renal failure secondary to insulin-dependent diabetes induces end-stage renal failure and the need for haemodialysis.
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In a series of 1500 patients transplanted between 1976 and 1992, 12 patients presented urinary calculi. The symptoms presented included obstructive anuria in 3 patients and abdominal pain in 1 patient. There were 8 asymptomatic patients. The risk factors were mainly hyperparathyroidism and non-absorbable sutures. The occurrence of renal graft calculi is now ten times less frequent than in the 1980s. In all, 5 of the patients were treated using incisional surgery, 5 with ESWL and 4 using ureteroscopy; a double J stent was inserted for the 3 cases of obstructive anuria. Nine patients are currently calculus-free and 2 have relapsed. One asymptomatic patient was not treated. The renal function of these 12 patient was not modified and no hypertension was noted after treatment. Calculi are generally asymptomatic when they are diagnosed by ultrasonography and in our experience they can be treated using ESWL or by ureteroscopy. In our opinion all patients can be treated successfully but with a high rate of relapse if the causal factors are not treated.
PURPOSE: Urologists successfully use ureteral stents to protect the ureterovesical anastomosis in nontransplant patients. MATERIALS AND METHODS: We determined the value of ureteral stents in transplant patients. The frequency of urological complications (leaks, obstructions and urinary tract infections) was compared in a prospective randomized series of 194 kidney transplantations (97 with and 97 without a double pigtail ureteral stent). RESULTS: In the stent group 1 patient had a urinary leak and 35 had urinary tract infections (including 2 cases of Corynebacterium cystitis). In the no stent group 6 patients had urinary leaks, 4 had obstructions and 32 had urinary tract infections. The 1-year patient and graft survival rates were similar in both groups, and renal function at 1 year was also similar (229 versus 208 mumol./l. creatinine in the stent and no stent groups, respectively). A small number of stent related complications occurred (2 stent breakages and 1 stent migration). No stones formed in any case. CONCLUSIONS: Ureteral stent insertion significantly decreases the rate of vesicoureteral leakage and obstruction in renal transplantation.
In a series of 731 kidneys taken from brain-dead donors for renal transplantation, 652 were grafted, and the renal function at 1 month is known for 490 of them. The results show that some donor-related factors influence the outcome of the transplant. In particular, haemodynamic instability refractory to medical treatment is responsible for a 50 mumol increase of serum creatinine one month after transplantation and the use of UW solution during organ collection is responsible for an improvement of serum creatinine compared to other preservation solutions. Haemodynamic instability is a criterion which must be added to those already demonstrated in donors, such as the cause of death, age and sex. The authors propose that donor-related factors be taken into account in the allocation of organs in the same way as immunological factors which, at the present time, constitute the only criterion for kidney allocation.
Multiple cystic clear cell renal tumors and in situ renal clear cell carcinoma occurred in a woman with von Hippel-Lindau disease. Kidney lesions in von Hippel-Lindau disease are one of the main features including renal cysts and renal cell carcinoma. In situ renal clear cell carcinoma has not yet been reported.
OBJECTIVE: The objective of this retrospective study was to determine whether the difference between the donor's weight (wd) and the recipient's dry weight (wr) could influence the function of renal transplants. METHODS: Between 1987 and 1994, 185 patients with a mean age of 43.3 years +/- 12 were transplanted with a locally harvested cadaver kidney, corresponding to 120 men (42.2 years +/- 1.4) and 65 women (45 years +/- 12.8). The weight variation between donors and recipients (wd - wr) was 0.06 for men and 0.22 for women. The serum creatinine of recipients at 1 year was 147 mumol +/- 41.7. We used analysis of variance for univariate statistical analysis and multiple linear regression for multivariate analysis. RESULTS: On univariate analysis, the serum creatinine at 1 and 2 years was significantly higher (p < 0.02 and p < 0.035 respectively) when the donor's weight was 10% lower than the recipient's weight. Multivariate analysis, taking into account the donor's age and sex and the recipient's serum creatinine, confirmed the influence of the donor-recipient weight difference on serum creatinine at 2 years (p0.03), but also the role of the donor's age at 1 and 2 years (p < 0.0001 and p < 0.0004, respectively). CONCLUSION: In our study, the donor-recipient weight difference was a factor influencing the recipient's serum creatinine at 2 years. The donor's age also influences the recipient's serum creatinine, 1 and 2 years after renal transplantation.
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Radical prostatectomy is one treatment for organ-confined prostatic adenocarcinoma. Dissemination of malignant prostatic cells after radical prostatectomy could be partly due to prostate manipulation during dissection. We confirmed by assay of prostate-specific membrane antigen by reverse-transcription nested PCR that prostate manipulation seeded prostatic epithelial cells in the general circulation in 12 of 14 consecutive patients operated on for organ-confined prostate adenocarcinoma. Our results suggest that surgeons should approach radical prostatectomy with care to avoid seeding from the prostate gland. Antiandrogen therapy might reduce the haematogenous spread of prostatic cells during radical prostatectomy.
OBJECTIVES: Neoplasic obstruction of the ureter is observed in patients with pelvic or extra-pelvic cancer. Indications of upper urinary tract drainage need to be clarified. METHODS: Percutaneous nephrostomy or double J catheter drainage was performed in 104 patients with ureteral obstruction due to pelvic cancer (bladder, prostate, uterus, ovary, rectum) or extra-pelvic cancer (usually breast and digestive cancers). Percutaneous nephrostomy or double J catheter was the first drainage procedure in 85 and 76 patients respectively. RESULTS: Success rate in first intention drainage was 74.5% with the double J catheter. When this procedure was impossible, percutaneous nephrostomy was always performed. In 52 cases we attempted to convert the nephrostomy to double J catheter drainage. Success rate was 68.8%. The main complications observed were ineffective drainage (12.5%) and infection (10.5%). CONCLUSION: These patients have a mean survival of 6.8 months despite the chemotherapy which is facilitated by the improved renal function.
A variety of renal diseases can be associated with end-stage liver diseases requiring orthotopic liver transplantation (OLT), including cirrhosis-associated glomerulonephritis (GN), and nephropathy unrelated to the liver disease. A retrospective survey showed that nine patients undergoing liver transplantation in our centre had histologically proven GN or interstitial nephritis with renal failure and/or nephrotic-range proteinuria, and experienced severe complications post-OLT since nephrotoxic immunosuppressive drugs (CsA and FK506) could not be adequately given. Four of the nine patients died. Therefore, combined liver-kidney transplantation has been suggested as first choice treatment in such patients. From January 1990 to February 1994, in patients with end-stage liver disease referred for OLT, and who presented with unexplained renal function impairment and/or significant proteinuria, severe nephropathy was confirmed by renal biopsy in nine: four mesangiocapillary GN with immune deposits, one membranous nephropathy, two diabetic glomerulosclerosis and two interstitial nephritis. All underwent liver transplantation immediately followed by kidney transplantation. The postoperative period was uneventful, and neither death nor renal failure were recorded. Combined transplantation resulted in all patients in the normalization of renal function, and in the disappearance of proteinuria within the first postoperative month. From 6 months to 4 years post-transplant, the renal function remained within normal ranges in all patients. Routine renal transplant biopsy was performed in two patients with pre-transplant cirrhosis-associated GN, and showed no evidence of recurrence of the original nephropathy. We conclude that combined liver-kidney transplantation is an adequate therapeutic option in patients with end-stage liver disease associated with advanced kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)
We report the development of a new sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) assay, using primers derived from the prostate-specific membrane antigen (PSM) cDNA sequence, to detect an hematogenous spread of prostate adenocarcinoma cells. In 60 patients with a biopsy-proven prostate cancer, PSM and PSA RT-PCR detected circulating prostate cells in 40 and 20 patients, respectively. In pT4 M+ and pT3 M+ disease patients, nested PSM primers detected cells in 28 of 33 patients (85%), whereas nested PSA primers detected cells in 17 of 33 (51%). In patients with organ-confined cancer spread (pT2a and pT2b patients) before radical prostatectomy, nested PSM RT-PCR detected circulating prostatic epithelial cells in 6 of 17 patients (35%), which suggests that an hematogenous spread of prostate cells may occur early in prostate cancer history. Altogether, these results suggest that the detection of PSM-expressing cells in blood may predict the development of cancer in patients without clinically apparent prostate cancer. Nevertheless, the potential application and the clinical significance of detection of hematogenous prostate cells through the use of nested PSM primers need an extensive longitudinal study.