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Biomedical subjects

Paul Meria

Publications and source records attributed to Paul Meria.

9 recordsLinked to original sources

Rapamycin inhibits human renal epithelial cell proliferation: effect on cyclin D3 mRNA expression and stability.

BACKGROUND: Recent data have suggested that rapamycin use during the initial period after transplantation is associated with prolonged delayed graft function (DGF). Because of the known effects of rapamycin in other cell types, we speculated that this action may be secondary to human renal epithelial cells (HRECs) inhibition of proliferation. METHODS: Primary cultures of HRECs were incubated with various concentrations of rapamycin. Cell proliferation was evaluated by cytotoxicity assays. The cell cycle was analyzed by flow cytometry. Protein expression levels were assessed by Western blot. Cyclin D3 mRNA levels were measured by quantitative real-time polymerase chain reaction (PCR). The transcriptional activity of the cyclin D3 gene was evaluated using transient transfection. RESULTS: Rapamycin exerted a significant concentration-dependent antiproliferative effect on growing HRECs by inhibiting the G(1) to S transition. The p70(S6) kinase pathway leading to cell cycle progression was found to be active, and low concentrations of rapamycin dramatically reduced p70(S6) kinase phosphorylation. Rapamycin completely inhibited the increase in cyclin D3 protein expression and mRNA accumulation induced by fetal calf serum, but did not affect cyclin E or cdk-inhibitor expression levels. This regulation of cyclin D3 protein expression is mainly due to a destabilization of its mRNA. Rapamycin reduced the mRNA half-life by 26% (4.8 +/- 1.3 hours vs. 6.5 +/- 1.0 hours, P < 0.001). CONCLUSION: Rapamycin inhibits the proliferative response of HRECs to mitogenic stimuli, and causes cell cycle arrest in the early G(1) phase, not only by a nonspecific process due to inhibition of the p70(S6k) pathway, but also by a direct effect on cyclin D3 mRNA stability.

Cell Proliferation↗

Management of pelvic stones larger than 20 mm: laparoscopic transperitoneal pyelolithotomy or percutaneous nephrolithotomy?

UNLABELLED: Large pelvic stones are frequently managed with percutaneous nephrolithotomy (PCNL) but laparoscopic transperitoneal pyelolithotomy (LTP) can be an alternative. We compared PCNL and LTP for the treatment of pelvic stones >20 mm in diameter. PATIENTS AND METHODS: Between November 1999 and November 2004, 16 consecutive patients, mean age 42, with a single pelvic stone >20 x 10 mm (group I), underwent LTP as first-line treatment or after shockwave lithotripsy failure. They were compared with a similar population of 16 consecutive patients, mean age 45 (group II), who underwent PCNL for the same indication and were assessed retrospectively. We evaluated operative characteristics, complications, and results for each technique. RESULTS: There was no difference between the two groups regarding the characteristics of patients and stones. Operative time duration was significantly longer in group I (129 vs. 75 min; p = 0.001) and conversion was required in 2 patients (12%). The main postoperative complications were urinary leakage (2 patients, 12%) in group I and bleeding (3 patients, 18%) in group II, but only 1 required blood transfusion. Mean hospital stay was respectively 6.5 and 5.6 days in groups I and II (p = 0.17). Stone-free rates were assessed at 3 months and were not different between group I and group II (88 vs. 82%). CONCLUSIONS: The operative time of LTP is longer and the results of both techniques are comparable but postoperative morbidity is different. Specific indications of each technique must be determined although PCNL remains the gold standard for most large pelvic stones.

Adult↗

[Renal cell carcinoma and trichloroethylene].

The authors report the case of a 51-year-old man with a history of trichloroethylene (TCE) poisoning. He was treated by radical nephrectomy after discovery ofa right renal mass corresponding to renal cell carcinoma. The objective of this study is to discuss the role of TCE abuse as a renal carcinogen. TCE is an excellent solvent used to degrease metal parts. It can enter the body by inhalation, ingestion or cutaneous contact, but the respiratory tract is the main route of absorption of TCE. Many epidemiological studies have been conducted on workers exposed to TCE, but they have not been able to clearly establish a link between exposure by inhalation to TCE and cancer. The International Agency for Research on Cancer has accumulated sufficient evidence to consider TCE to be carcinogenic to animals and considers that TCE is probably carcinogenic to humans. Toxic metabolites derived from TCE induce chronic renal tubular lesions and may exert a genotoxic effect on the proximal convoluted tubule. The initial genotoxic effect appears to be related to mutations of the VHL suppressor gene. The chronic toxic effects and the possible role of TCE in the development of cancer have not been specifically studied in the context of TCE abuse behaviour. To our knowledge, this is the first case of renal cell carcinoma reported in a TCE addict.

Carcinoma, Renal Cell↗

Encrusted cystitis and pyelitis in children: an unusual condition with potentially severe consequences.

OBJECTIVES: To report our experience with the management of encrusted cystitis and pyelitis (EC and EP) in the pediatric population. EC and EP are well-known entities in adults but are rarely identified in children. They consist of mucosal encrustations and are due to specific microorganisms. METHODS: Between 1996 and 2001, 4 children with a mean age of 9 years (range 4 to 13) were treated for EC (n = 2), EP (n = 1), and EC and EP (n = 1). The latter was a kidney transplant recipient. We retrospectively evaluated the clinical characteristics of the patients and the results of conservative management. RESULTS: The delay between the beginning of the symptoms and the diagnosis was longer than 1 month in all cases. The diagnosis of EC was not evoked and was made during cystoscopy in all cases. EP was diagnosed during pyelotomy in 1 patient because it was evoked and confirmed by computed tomography scan in the kidney transplant recipient. Corynebacterium urealyticum was identified in the urine of all patients. EC was treated by antibiotics and endoscopic debulking, and EP was treated by antibiotics and local acidification. The duration of antibiotic therapy was between 1 and 6 months. The tolerance to local acidification of the kidneys was poor. Cure was achieved in 3 cases, but the treatment of EP failed in the kidney transplant recipient and graft removal was decided after 6 months of failed management because intractable febrile urinary tract infections became life threatening for the patient. CONCLUSIONS: EC and EP are uncommon in children; however, these diseases must be considered. They must be diagnosed rapidly and require, if possible, conservative management. Nevertheless, kidney loss can occur in transplant recipients with EP.

Adolescent↗

[Percutaneous nephrolithotomy (PCNL) in subjects over the age of 70: a multicentre retrospective study of 210 cases].

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) in subjects over the age of 70 is considered to be associated with a higher risk than extracorporeal shock-wave lithotripsy (ESWL). However this technique is sometimes necessary for very large or complex stones in patients with several comorbidities. STUDY OBJECTIVE: To evaluate the predictive factors of success and operative risks likely to influence the results of PCNL in a population of patients over the age of 70. MATERIAL AND METHOD: Retrospective study of 203 patients (110 males, 97 females) over the age of 70, in whom a total of 210 PCNL were performed over a 12-year period in ten referral centres for the treatment of stones. 68.5% of cases presented a comorbidity and the median ASA score was 2. The median stone dimensions were 24 x 15 mm. There were 67 solitary pelvic stones, 7 infrapelvic ureteric stones, 31 solitary inferior caliceal stones, 40 complex stones and 13 staghorn calculi. A standard one-stage operative technique was performed in 92% of cases; the nephrostomy tract was easily performed by the urologists themselves in 71.8% of cases. RESULTS: The overall stone-free (SF) rate was 70.8%. The patient's weight and height (p=0.03 and p=0.01), stone dimensions and their solitary nature were significant factors of success (p<0.00001 and p=0.01) with SF rates of 81.1% for pelvic stones and 90.3%for solitary inferior caliceal stones (p<0.003); the SF rate for complete staghorn calculi was only 30.8%. A history of stones (p=0.04) and diabetes (p=0.03) influenced the stone-free rate, but the other comorbidities, body mass index, and age did not influence the stone-free rate. There were two deaths (0.9% and haemostasis nephrectomy was performed in 2 ASA 3 subjects in renal failure. In the other patients, there was no difference between preoperative and postoperative serum creatinine and haemoglobin levels. The ease of nephrostomy, the rapidity of PCNL, the day of removal of the drainage nephrostomy, the mean hospital stay (median stay: 6 days), sterility of postoperative urine and at the 1-month visit were significantly correlated with the SF rate. CONCLUSIONS: PCNL in subjects over the age of 70 years is a safe and reliable technique that achieved a stone-free rate of 70.8% for all types of stones combined. The best results were obtained for solitary stones larger than 20 mm in the renal pelvis or inferior calyx. Apart from diabetes, which remains a risk factor, well controlled comorbidities do not increase the operative risk. PCNL did not affect haemodynamic parameters or renal function.

Age Factors↗

Fatal septic shock caused by Corynebacterium D2.

BACKGROUND: Septic shock remains one of the leading causes of mortality in critically ill patients. Optimal management depends on prompt diagnosis with identification of the causative organisms to allow appropriate antibiotic therapy. PATIENT: We report the first case of septic shock caused by Corynebacterium D2, a micro-organism that can cause encrusted cystitis and pyelitis of transplanted kidneys or, more rarely, native kidneys. Diagnosis rests on identification of risk factors, positive urine cultures, and computed tomography results. Despite optimal treatment our patient died with persistent encrusted pyelitis. CONCLUSIONS: Corynebacterium D2 is known to cause chronic inflammation of the bladder and proximal urinary tract but can also cause severe septic shock in immunocompetent patients.

Aged↗

Laparoscopic management of primary hyperaldosteronism: clinical experience with 212 cases.

PURPOSE: Laparoscopy is now widely used to remove benign adrenal tumors. We assessed the value of transperitoneal partial or total adrenalectomy for primary hyperaldosteronism. MATERIALS AND METHODS: From September 1994 to October 2001, 212 consecutive patients with a mean age of 48 years who presented with primary hyperaldosteronism and related arterial hypertension underwent transperitoneal laparoscopic adrenalectomy (193) or tumor enucleation (20) performed by a single surgeon, including 1 who underwent bilateral adrenalectomy. In all cases preoperatively high plasma and urine aldosterone was associated with low plasma renin and hypokalemia. RESULTS: Mean followup was 44 months. Conversion to open surgery was necessary in 30 patients (14%) due to bleeding or adhesion and a procedure duration of greater than 3 hours. Mean operative time was 102 minutes (range 30 to 260). Six patients (2.8%) required blood transfusion. No deaths occurred. Postoperatively complications were observed in 10% of patients and the most frequent one was electrical myocardial ischemia without infarction. Mean postoperative pain medication was 17 mg. morphine sulfate equivalents (range 0 to 60). Mean and median hospital stay was 3.6 and 2.9 days, respectively (range 2 to 20). Postoperatively blood pressure was normal in 58% of patients without any drug, while treatment was decreased in the remainder. Kalemia was normalized in all cases. CONCLUSIONS: Although some complications can occur, mostly at the beginning of the learning curve, laparoscopic transperitoneal adrenalectomy is effective treatment for primary hyperaldosteronism.

Adrenal Gland Neoplasms↗