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P Saudan

Publications and source records attributed to P Saudan.

15 recordsLinked to original sources
PubMed2006

Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure.

Acute renal failure (ARF) in critically ill patients is associated with high mortality. Optimal method and dose of continuous renal replacement therapy could improve survival in these patients. We studied the hypothesis that an increase in dialysis dose obtained by continuous veno-venous hemodiafiltration (CVVHDF) is associated with a better survival than continuous veno-venous hemofiltration (CVVH) among critically ill patients with ARF. In a prospective randomized trial, these two methods were compared in patients undergoing renal replacement therapy in two intensive care units (ICUs). The patients had either CVVH (1-2.5 l/h replacement fluid) or continuous CVVHDF (1-2.5 l/h replacement fluid+1-1.5 l/h dialysate) according to their body weight. 28- and 90-day mortalities, renal recovery, and duration of ICU stay were the main outcome measures. Two hundred and six patients were randomized from October 2000 to December 2003. Twenty-eight-day survivals (%) were, respectively, 39 and 59 (P=0.03) in the CVVH and CVVHDF groups. Three months survivals (%) were, respectively, 34 and 59 (P=0.0005) in the CVVH and CVVHDF groups. Apache II score, age, baseline blood urea nitrogen, and hemodiafiltration (hazard ratio 0.59, 95% confidence interval 0.40-0.87; P=0.008) were independent predictors of survival at 90 days. Renal recovery rate among survivors (71 versus 78% in the CVVH and CVVHDF groups respectively, P=0.62) was not affected by the type of renal replacement therapy. These results suggest that increasing the dialysis dose especially for low molecular weight solutes confers a better survival in severely ill patients with ARF.

APACHE↗
PubMed2006

[Anticoagulation in patients with chronic renal failure].

Anticoagulation may be difficult to implement in patients suffering from chronic renal failure on account of platelet disorders and impaired clearance of some anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is necessary, more frequent testing of coagulation pathways may be required when these drugs are used in patients with renal failure. Long-term use of LMWH should be implemented cautiously with regular testing of anti-factor Xa activity and a half-dose may be advocated in patients with a creatinine clearance < 30 ml/mn. Danaparoid and thrombin inhibitors should be used mainly in patients suffering from renal failure and heparin-induced thrombocytopenia with regular monitoring of coagulation tests.

Anticoagulants↗
PubMed2006

[Nephrology].

Publications of relevance in nephrology during 2005 highlight the use of more specific molecules to treat glomerulonephritides and cast a doubt on the dogma: "the lower blood pressure, the better renal outcome". They report the effect of high dose Angiotensin 11 receptor blockers being used to lower proteinuria without any significant effect on blood pressure. In critically ill patients with acute renal failure, loop diuretics did not increase mortality. Should we treat end-stage renal failure patients with statins? probably not; with cinacalcet? definitely yes.

Blood Pressure↗
PubMed2005

Risk factors for early failure of native arteriovenous fistulas.

INTRODUCTION: Current guidelines recommend native arteriovenous fistulas (AVF) as the vascular access of choice for hemodialysis on account of the lower incidence of complications. However, this kind of vascular access has a high rate of early failure (early thrombosis or non-maturation). Our aim was to examine whether clear risk factors for early AVF failure could be identified in our patients. SUBJECTS AND METHODS: Data of all patients who underwent creation of an AVF at the Geneva University Hospital from January 1998 to December 2002 were reviewed. Early failure was defined as a non-functioning fistula (thrombosis or absence of fistula maturation). RESULTS: 119 patients underwent the creation of 148 native AVF, 88 (59.5%) in the forearm and 60 (40.5%) in the upper arm. 48 (32.4%) fistulae were created in diabetic patients. In a multiple logistic regression analysis, significant predictive factors of early failure were a distal location (adjusted odds ratio (aOR) = 8.21, 95% CI = 2.63-25.63, p < 0.001), female gender (aOR = 4.04, 95% CI = 1.44-11.30, p = 0.008), level of surgical expertise (aOR = 3.97, 95% CI = 1.39-11.32, p = 0.010) and diabetes mellitus (aOR = 3.19, 95% CI = 1.17-8.71, p = 0.024). CONCLUSION: Early failure of AVF occurs mainly in forearm sites among women and diabetic patients. Surgical expertise has also a significant influence. These results suggest that selection of a distal site for a native AVF has to be rigorously made for women and diabetic patients and that surgeon's dedication is of primary importance to avoid early AVF failure occurrence.

Adult↗
PubMed2005

[Prevention of contrast nephropathy: myth or reality?].

Prevention of Contrast Media induced acute renal failure is of importance, especially in patients with chronic renal failure. Vasodilatators such as fenoldopam and prophylactic hemodialysis have been reported to procure disappointing results. Hydratation prior to and post- exposure to contrast media remains the cornerstone of prevention. Urine alcalinisation with sodium bicarbonate may bring additional renoprotection. Use of a small quantity of contrast media and Acetylcysteine concomitantly to hydratation are also recommended.

Acute Kidney Injury↗
PubMed2001

Renal transplantation with donors aged over 50: a long-term, single centre experience.

BACKGROUND: Renal transplantation is now considered the best treatment for end-stage renal failure patients. In view of the worldwide growing waiting list, extending donor age is one of the strategies implemented to make more kidneys available for transplantation. METHODS: From October 1983 to February 2000, 324 renal transplantations were performed at Geneva University Hospital, 68 of which were done with kidneys from donors aged over 50 (mean donor age 55.3 + 4.8 years) The following data were analysed at 1, 5 and 10 years and compared between recipients with donors aged over 50 (> 50 years) and under 50 (< 50 years): actuarial patient and graft survival, serum creatinine, causes of graft loss. RESULTS: Patient survival at 10 years was 83% with donors < 50 years and 61% with donors > 50 years (non-significant). Graft survival at 10 years was 61% with donors < 50 years and 48% with donors > 50 years (non-significant). Graft survival at 10 years or death with functioning graft was 69% with donors < 50 years and 68% with donors > 50 years (non-significant). Overall, donor age was not a predictive factor for graft survival, as shown by multiple logistic regression. CONCLUSIONS: Kidneys obtained from donors > 50 years are suitable for renal transplantation and yield acceptable graft survival.

Adolescent↗
PubMed2001

Renal transplantation in the elderly: a long-term, single-centre experience.

BACKGROUND: End-stage renal failure increases with advancing age and renal transplantation should be considered in end-stage renal failure patients older than 60 years. However, there is a paucity of data on long-term patient and graft survival in this population. METHODS: From October 1983 to March 1999, 310 renal transplantations were performed at Geneva University Hospital in 283 patients, of which 49 were done in 48 patients older than 60 years (mean age 65.6+/-4.1 years). The following data were analysed at 1, 5, and 10 years, and compared between the patients >60 years and <60 years old: actuarial patient and graft survival, serum creatinine, causes of graft loss, and patient death. RESULTS: Patient survival at 10 years was 81% for patients <60 years and 44% for patients >60 years. Graft survival at 10 years was 59% for patients <60 years and 32% for patients >60 years. Graft survival at 10 years censored for death with functioning graft was 65% for patients <60 years and 81% for patients >60 years. Main causes of mortality in the older patients were related to cardiovascular events (47%), neoplasia (41%), and sepsis (18%). Overall, recipient and donor age were not predictive factors for graft survival, as shown by multiple logistic regression. CONCLUSIONS: Renal transplantation should be considered in patients older than 60 years, since graft survival is excellent in this population. Although these patients have a shorter life expectancy, they benefit from renal transplantation similarly to younger kidney transplant recipients.

Adolescent↗
PubMed2000

Inhibition of S-phase progression by adeno-associated virus Rep78 protein is mediated by hypophosphorylated pRb.

Adeno-associated virus (AAV) has an antiproliferative action on cells. We investigated the effect of the AAV replication proteins (Rep) on the cell division cycle using retroviral vectors. Rep78 and Rep68 inhibited the growth of primary, immortalized and transformed cells, while Rep52 and Rep40 did not. Rep68 induced cell cycle arrest in phases G(1) and G(2), with elevated CDK inhibitor p21 and reduced cyclin E-, A- and B1-associated kinase activity. Rep78-expressing cells were also impaired in S-phase progression and accumu lated almost exclusively with hypophosphorylated retinoblastoma protein (pRb). The differences between Rep78 and Rep68 were mapped to the C-terminal zinc finger domain of Rep78. Rep78-induced S-phase arrest could be bypassed by adenoviral E1A or papillomaviral E7 proteins but not by E1A or E7 mutants unable to bind pRb. Rb(-/-) primary mouse embryonic fibroblasts displayed a strongly reduced S-phase arrest when challenged with Rep78, compared with matched Rb(+/+) controls. These results suggest that physiological levels of active pRb can interfere with S-phase progression. We propose that the AAV Rep78 protein arrests cells within S-phase by a novel mechanism involving the ectopic accumulation of active pRb.

3T3 Cells↗
PubMed1999

Expression of human papillomavirus 16 E2 protein in Schizosaccharomyces pombe delays the initiation of mitosis.

Infection by some types of human papillomavirus (HPV) is associated with the development of cervical cancer. Analysis of viral DNA from cervical tumours shows that the E2 gene is frequently disrupted during integration into the host cell's DNA. It has therefore been suggested that loss of E2p is an important step in malignant transformation. Expression of E2p in the fission yeast Schizosaccharomyces pombe retards the G2-M transition, by delaying activation of Cdc2p kinase. In contrast, S phase progression, and commitment to cell division in late G1 are not affected. The delay is independent of the transcriptional trans-activation function of E2p, and does not result from E2p DNA binding mimicking DNA damage. Increased expression of E2p also delays mitotic initiation in mammalian cells. S. pombe may thus provide a simple model for the analysis of E2p function.

Adenosine Triphosphatases↗
PubMed1998

Does gestational hypertension become pre-eclampsia?

OBJECTIVE: To determine the likelihood of progression from gestational hypertension (GH) to pre-eclampsia (PE) in hypertensive pregnant women and whether this change can be identified in advance by available clinical and laboratory measures. DESIGN: A retrospective analysis and a prospective study. SETTING: St George Hospital, Sydney, a teaching hospital of the University of New South Wales delivering 2500 women per year. POPULATION: Eight hundred and forty-five women with new hypertension in the second half of pregnancy, managed by a uniform protocol (661 in the retrospective analysis, 184 in the prospective study). METHODS: Clinical and laboratory data at initial presentation were compared among women with GH who developed PE and those who remained with a diagnosis of GH until delivery. Data predictive for progression from GH to PE were analysed by logistic regression analysis. MAIN OUTCOME MEASURED: Progression from GH to PE. RESULTS: In the retrospective analysis, 416 women initially presented as having GH and 62 (15%) progressed to PE. In the prospective study, 112 women initially presented with GH and 29 (26%) progressed to PE, giving an overall progression of 17%. In both studies, women who developed PE from GH presented earlier than those who remained with GH until delivery. In multiple logistic regression analyses prior miscarriage and early gestation at presentation were associated with increased likelihood of progressing from GH to PE. CONCLUSION: Approximately 15-25% of women initially diagnosed with GH will develop PE and this is more likely with earlier presentation or if the woman has had a prior miscarriage. Women with gestational hypertension diagnosed after 36 weeks of gestation have only about 10% risk of developing PE. These data should help stratify the risks of mildly hypertensive pregnant women being managed as outpatients in their third trimester.

Abortion, Spontaneous↗
PubMed1997

High mobility group chromosomal protein 1 binds to the adeno-associated virus replication protein (Rep) and promotes Rep-mediated site-specific cleavage of DNA, ATPase activity and transcriptional repression.

High mobility group protein 1 (HMG1) is an abundant non-histone chromosomal protein which plays a role in several nuclear events involving DNA. Here we demonstrate that HMG1 physically interacts with the human adeno-associated virus (AAV) Rep protein. HMG1 promotes the formation of Rep-DNA complexes and stimulates the activity of Rep in site- and strand-specific cleavage of DNA and the hydrolysis of ATP, functions required for viral gene regulation, replication and site-specific integration of viral DNA into human chromosome 19. We show that HMG1 enhances Rep-mediated repression of the AAV p5 promoter in transfected cells, suggesting that HMG1 and Rep also interact in vivo. HMG1, Rep and DNA can be immunoprecipitated as a ternary complex. Kinetic studies indicate that complexes of Rep with DNA have similar stabilities in the presence and absence of HMG1. These results suggest that the effect of HMG1 on Rep binding is exerted at the step of complex formation and thereby may reflect an activity of HMG1 in promoting the assembly of complex cellular nucleoprotein structures.

Adenosine Triphosphatases↗
PubMed1996

Sex-peptide activates juvenile hormone biosynthesis in the Drosophila melanogaster corpus allatum.

Mating elicits two well-defined reactions in sexually matured females of many insects: reduction of receptivity and increased oviposition. These post-mating responses have been shown to be induced by factors synthesized in the reproductive tract of the adult male and transferred in the seminal fluid to the female during copulation. One of these factors, named sex-peptide (SP), has been identified in Drosophila melanogaster. Using an in vitro radiochemical assay, we show that synthetic sex-peptide considerably activates juvenile hormone III-bisepoxide (JHB3) synthesis in corpus allatum (CA) excised from Days 3 and 4 post-eclosion virgin females. Base levels are significantly lower at emergence (Day 0) than on subsequent days, and only weak stimulation is obtained on Day 1, while none is obtained on Day 2, where maximal basal synthesis occurs. The CA of mated females cannot be stimulated further for at least 7 days, but regain responsiveness by Day 10 after mating. Synthesis of JHB3 stimulated by SP in vitro persists for at least 4 h after removal of the peptide. Development of responsiveness of the CA to SP in vitro is compared with development of the post-mating reactions of sex-peptide injected virgin females. Our results suggest that the CA is a direct target for SP in vivo and that sexual maturity is established separately for the two post-mating reactions.

Animals↗
PubMed1990

Depletion of hypothalamic growth hormone-releasing hormone by neonatal monosodium glutamate treatment reveals an inhibitory effect of betamethasone on growth hormone secretion in adult rats.

Rats were treated with monosodium glutamate (MSG), 4 mg/g on alternate days for the first 10 days of life, to induce lesions of the arcuate nucleus and destroy the majority of growth hormone-releasing hormone (GHRH) neurones. At 10 weeks of age, control (n = 42) and MSG-treated (n = 36) male rats were used to test the effect of glucocorticoids on growth hormone (GH) secretion. Each treatment group was divided into six study groups to determine the effect of betamethasone (BM), administered either 3 or 20 h prior to sacrifice, alone and in combination with hypoglycaemia (insulin 0.1 U/100 g). BM treatment of male rats was without effect on plasma GH levels in control animals. In contrast, glucocorticoid administered either 3 h before sacrifice or the previous evening significantly reduced circulating GH (p less than 0.001) in MSG-treated animals. The difference in plasma GH response to BM pretreatment in control rats and those with lesions of the arcuate nucleus indicates a hypothalamic action of glucocorticoids, presumably on somatostatin and GHRH neurones. In control animals the effects appear to be counterbalancing, but following destruction of GHRH neurones an uncompensated inhibitory influence was observed. Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls. Female rats which had undergone the same neonatal MSG treatment (n = 40) when sacrificed 1 week after their male counterparts showed similar reductions in body weight (-15%), hypothalamic GHRH (-74%), and pituitary GH (-67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Dexamethasone treatment increases neuropeptide Y levels in rat hypothalamic neurones.

Immunoreactive glucocorticoid receptors (GR) have previously been demonstrated in neuropeptide Y (NPY) neurones of the rat hypothalamus. To determine whether NPY synthesis is influenced by glucocorticoids, the effect of dexamethasone (DEX) on the levels of immunoreactive NPY in rat hypothalamic neurones was investigated in vivo and in vitro. Daily injections of DEX (0.1 mg/day) for 5 days increased the NPY content of the mediobasal hypothalamus in female rats by 117% (p less than 0.002). Primary cultures of hypothalamic neurones were also sensitive to the effect of glucocorticoids. Intracellular NPY levels were significantly increased (p less than 0.001) compared to control values by 151%, 222% and 268% when cultures were maintained in a defined serum free medium containing DEX 10(-9), 10(-8) and 10(-7) M respectively.

Animals↗