Biomedical subjects

C Perret

Publications and source records attributed to C Perret.

At least 55 records · Page 3Linked to original sources

PubMed1998

Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas.

Hepatocellular carcinoma (HCC) is the major primary malignant tumor in the human liver, but the molecular changes leading to liver cell transformation remain largely unknown. The Wnt-beta-catenin pathway is activated in colon cancers and some melanoma cell lines, but has not yet been investigated in HCC. We have examined the status of the beta-catenin gene in different transgenic mouse lines of HCC obtained with the oncogenes c-myc or H-ras. Fifty percent of the hepatic tumors in these transgenic mice had activating somatic mutations within the beta-catenin gene similar to those found in colon cancers and melanomas. These alterations in the beta-catenin gene (point mutations or deletions) lead to a disregulation of the signaling function of beta-catenin and thus to carcinogenesis. We then analyzed human HCCs and found similar mutations in eight of 31 (26%) human liver tumors tested and in HepG2 and HuH6 hepatoma cells. The mutations led to the accumulation of beta-catenin in the nucleus. Thus alterations in the beta-catenin gene frequently are selected for during liver tumorigenesis and suggest that disregulation of the Wnt-beta-catenin pathway is a major event in the development of HCC in humans and mice.

Animals↗

PubMed1998

Extreme hypercapnia is not a long-term prognostic factor after near-fatal asthma: a 12-year follow-up study.

QUESTION OF THE STUDY: Some patients experiencing near-fatal asthma present with extreme hypercapnia (PaCO2 > or = 100 mm Hg), whereas others do not. The influence of this factor on short- and long-term outcome and quality of life in these patients is still unknown. PATIENTS AND METHODS: A series of 39 consecutive patients who had had an episode of near-fatal asthma between 1978 and 1992 were followed up. Long-term outcome and quality of life of the 12 patients who had experienced extreme hypercapnia were compared with those of the 27 patients who had not. RESULTS: Four patients died, but only 1 from asthma. Three patients were lost to follow-up. The remaining 32 patients had a median observation period of 12.7 years. The hypercapnic patients did not significantly differ from the others in past asthma history, subsequent hospitalizations, medication needs, pulmonary function tests, quality of life and impairment/disability. In the event of subsequent near-fatal asthma attacks, they tended to present with hypercapnia levels similar to those observed during the first episode. DISCUSSION: Extreme hypercapnia in near-fatal asthma tended to recur, but is not an aggravating long-term prognostic factor. Targeted surveillance of these high-risk patients should make it possible to reduce relapses and death rates from asthma.

Adult↗

PubMed1998

Epidemiology of sociodemographic characteristics, lifestyle, medical history, and colon cancer: a case-control study among French Canadians in Montreal.

Colon cancer is the second most common cancer in both men and women in North America and other developed countries. In a population-based case-control study of colon cancer among French Canadians in greater Montreal, a total of 402 cases and 668 controls were interviewed. The cancer cases were identified through the admission offices of five major Francophone teaching hospitals in Montreal from 1989 to 1993. The controls, matched by age, sex, place of residence, and language, were selected by a modified random digit dialing method. The results show that subjects who had ever been married had a lower risk for colon cancer (odds ratio [OR]: 0.58; 95% confidence interval [95% CI]: 0.48-0.84) than did individuals who had never been married. A significant association (OR: 1.90; p for trend = 0.003) was found between the height of subjects and the risk of colon cancer. The OR for individuals with a family history of colorectal cancer was 2.78 with a p value of 0.01. A direct and significant association (OR: 2.01) was found among constipation, use of laxatives (OR: 1.41), and the risk of colon cancer. Among women, a suggestive inverse association was detected between the number of full-term pregnancies and the risk of colon cancer in female subjects (the OR for five or more pregnancies was 0.58 with a p for trend of 0.08). There was also a suggestive linear trend (increased age-decreased risk) between age at menarche and the risk of colon cancer. No association was apparent between other sociodemographic characteristics and the risk of colon cancer. In conclusion, married individuals had lower risk for colon cancer, perhaps due to food habits or other characteristics of being single. Higher height and weight history 10 years before the diagnosis of cancer are risk factors for breast cancer, while both current weight and body mass index seem to be protective. Positive family history of colon cancer increased the risk of colon cancer significantly.

Adult↗

PubMed1998

Sociodemographic characteristics, smoking, medical and family history, and breast cancer.

The relationship between sociodemographic characteristics, lifestyle, family history of cancer, medical history, and reproductive factors and breast cancer was investigated in a population-based case-control study of French Canadians in Montreal. In this study, a total of 414 French-Canadian cases and 429 age- and language-matched population controls were interviewed. Ever-married women showed significantly lower risk (OR: 0.64 [0.45-0.92]) for breast cancer, as did smokers (OR: 0.73 [0.55-0.98]), particularly of nonfilter cigarettes (OR: 0.36 [0.17-0.72]). Weight history, both for the year before the diagnosis of breast cancer and 10 years previously, was associated with risk for the disease. A strong inverse relationship was found between the number of full-term pregnancies (OR: 0.48 [0.28-0.82]) and the risk of breast cancer, while the p trend for late age at first pregnancy (p = 0.02) and menopause (p = 0.004) was statistically significant. A history of breast problems (OR: 1.87 [1.34-2.60]) and a history of breast cancer in relatives (OR: 2.95 [1.63-5.34]) were strongly associated with risk. This study confirms the risk factors of late age at first full-term pregnancy, nulliparity, late age at menopause, and positive family history of breast cancer in the etiology of this disease. Perhaps the protective effect of smoking against breast cancer could be due to its antiestrogenic influence.

Adult↗

PubMed1998

Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock.

The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-gamma-L-arginine methyl ester (L-NAME, nonselective NOS inhibitor, 10-60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50-300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this setting.

Animals↗

PubMed1998

Is the pulmonary artery catheter misused? A European view.

OBJECTIVES: To review the problems associated with pulmonary artery catheter use in the intensive care unit; to discuss the need for clinical trials to assess its benefits; and to present original data on the use of the pulmonary artery catheter in European countries. DATA SOURCES: Selected relevant articles from the literature and data from a recent multicenter European study. DATA EXTRACTION AND SYNTHESIS: It has recently been suggested that pulmonary artery catheter use increases mortality. As a result, some have recommended placing a moratorium on pulmonary catheter use or suggested conducting large multicenter trials to assess the positive and negative effects of pulmonary catheter use. Although there is limited evidence showing an improved outcome with pulmonary artery catheter use, many leaders in intensive care medicine feel that the pulmonary catheter is a useful tool, when used correctly. We believe that misuse of the pulmonary artery catheter is common. The incidence of complications is low and, with improved training of insertion techniques, the frequency of complication would decrease further. The pulmonary artery catheter is a monitoring tool and, as such, is only as good as the interpretation of the data it generates. Clinical trials on such an accepted technique are difficult to conduct and their cost/benefit ratio is debatable. CONCLUSIONS: A moratorium on pulmonary artery catheter use is not necessary and clinical trials in heterogeneous ICU populations are not warranted. Improved training in the insertion, interpretation, and implementation of the pulmonary artery catheter and the data it generates is required. As an alternative to expensive clinical trials on the pulmonary artery catheter, we propose that our limited financial resources for clinical investigation be invested in the development of innovative techniques that may reduce the need for pulmonary artery catheter in the future.

APACHE↗

PubMed1998

Selective iNOS inhibition is superior to norepinephrine in the treatment of rat endotoxic shock.

S-methyl-isothiourea (SMT) is a potent inhibitor of NO synthase (NOS) with relative selectivity towards the inducible isoform (iNOS). We compared SMT and norepinephrine for the treatment of experimental endotoxic shock. Anesthetized rats challenged intravenously with lipopolysaccharide (LPS), 10 mg/kg, were treated after 1 h with a 4-h infusion of norepinephrine (titrated to maintain blood pressure within baseline values), SMT at low dose (0.1 mg x kg-1 x h-1), or at high dose (1 mg x kg-1 x h-1), or an equivalent volume of saline (2 ml x kg-1 x h-1). In saline-treated animals, LPS increased plasma nitrate and produced hypotension, low cardiac output (CO), lactic acidosis, and signs of liver and kidney dysfunction. Norepinephrine maintained blood pressure (BP) and reduced the fall in CO, without affecting lactic acidosis, organ dysfunction, and nitrate accumulation. The latter was dose-dependently blunted by SMT. Treatment with this agent prevented hypotension, through systemic vasoconstriction with the high dose and a maintained CO with the low dose. Low, but not high, dose SMT blunted lactic acidosis. Both doses reduced the signs of renal, but not liver, dysfunction. In additional studies, we obtained evidence that, in contrast with the high dose, SMT at low dose did not interfere with the function of constitutive NOS. These findings suggest a potential advantage of selective iNOS inhibition over standard adrenergic support in the therapy of septic shock.

Animals↗

PubMed1997

Cross-species characterization of the promoter region of the cystic fibrosis transmembrane conductance regulator gene reveals multiple levels of regulation.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is highly conserved within vertebrate species. Its pattern of expression in vivo seems to be tightly regulated both developmentally and in a tissue-specific manner, but shows differences with species. To identify transcriptional regulatory elements in the CFTR promoter region, we have used a combined approach based both on the analysis of the chromatin structure in vivo in rat tissues and on evolutionary clues (i.e. phylogenetic footprinting). In CFTR-expressing tissues, 15 DNase I-hypersensitive sites were identified within a 36 kb region encompassing exon 1. Eleven of them are clustered in a 3.5 kb region that exhibits eleven phylogenetic footprints observed when comparing sequences from eight mammalian species representing four orders (Primates, Artiodactylia, Lagomorpha and Rodentia). Comparison of the two sets of data allows the identification of two types of regulatory elements. Some are conserved between species, such as a non-consensus cAMP response element (CRE) and a PMA-responsive element (TRE) located respectively at positions -0.1 and -1.3 kb relative to ATG. Some are species-specific elements such as a 300 bp purine.pyrimidine (Pu.Py) stretch that is present only in rodents. Analysis of protein/DNA interactions in vitro with rat tissue protein extracts on the conserved elements revealed that the TRE site binds a specific heterodimeric complex composed of Fra-2, Jun D and a protein immunologically related to Jun/CRE-binding protein in the duodenum, whereas the CRE-like site binds ATF-1 ubiquitously. Functional analysis in Caco-2 cells showed that the CRE-like site supports a high basal transcriptional activity but is not able by itself to induce a response to cAMP, whereas the TRE site acts as a weak transactivator stimulated by PMA. Lastly, we found that the rodent-specific Pu.Py stretch confers nuclease S1 hypersensitivity under conditions of acidic pH and supercoiling. This indicates a non-B DNA conformation and thus reinforces the biological significance of non-random Pu.Py strand asymmetry in the regulation of transcription. Thus the tight transcriptional regulation of CFTR expression involves the combination of multiple regulatory elements that act in the chromatin environment in vivo. Some of them are conserved throughout evolution, such as the CRE-like element, which is clearly involved in the basal level of transcription; others are species-specific.

Activating Transcription Factor 1↗

PubMed1997

Nutritional factors and colon carcinoma: a case-control study involving French Canadians in Montréal, Quebec, Canada.

BACKGROUND: In a population-based case-control study of colon carcinoma and nutrition involving the francophone community in Greater Montreal, a total of 402 cases (200 males and 202 females) and 668 controls (239 males and 429 females) were interviewed. METHODS: Cases from 1989-1993 were identified through the admission offices of 5 major francophone teaching hospitals in Montreal and were ages 35-79 years. Controls matched by age, place of residence, and language were selected by a modified random digit dialing method. Information on dietary intake was collected with a quantitative food frequency questionnaire. RESULTS: No associations were evident between colon carcinoma and total energy, protein, or carbohydrate consumption, whereas a suggestive inverse association was found with total fat intake, with an odds ratio (OR) of 0.78 (P = 0.0637), and with saturated fat intake as well (OR = 0.71, P = 0.0893). A strongly significant inverse association was found with dietary fiber (OR = 0.50, P = 0.0018). The strongest inverse association concerning fiber was found with fiber from vegetable sources (OR = 0.57, P = 0.0096), and a suggestive (although nonsignificant) inverse association (OR = 0.74, P = 0.0687) was found with fiber from fruits. Calcium was inversely associated with risk (OR = 0.69, P = 0.0411), as was dietary intake of vitamin A (OR = 0.67, P = 0.0162), retinol, (OR = 0.069, P = 0.0409), vitamin E (OR = 0.53, P = 0.0028), and alphatocopherol (OR = 0.63, P = 0.0256). Although there was no association demonstrated between dietary beta-carotene intake and risk, a suggestive (although nonsignificant) inverse association with intake of other types of carotene was observed (OR = 0.76, P = 0.0740). No association was found between intake of other nutrients investigated in this study and risk of colon carcinoma. CONCLUSIONS: There is strong evidence from epidemiologic studies that high intake of fat and meat are risk factors for colorectal carcinoma in humans, whereas high intake of vegetable and fruit are inversely associated with risk of colon carcinoma. The findings from this study are in agreement with this observation.

Adult↗

PubMed1997

Effects of exogenous and endogenous nitric oxide on the contractile function of cultured chick embryo ventricular myocytes.

Nitric oxide (NO) has been shown to be a ubiquitous intercellular autacoid in the heart and, in cultured rat ventricular myocytes, to decrease the contractile responsiveness to isoproterenol (ISO). The aim of the present study was to investigate whether exogenous (sodium nitroprusside, SNP) or endogenous nitric oxide generated from L-arginine modulated the response to ISO in cultured chick embryo ventricular myocytes. SNP 1 microM or L-arginine 1 mM had no effect on baseline contractile function. Superfusion with ISO 100 nM significantly increased myocyte amplitude of shortening to 1.31 +/- 0.06 (ratio to baseline amplitude). Initial superfusion with SNP 1 microM or L-arginine 1 mM attenuated the response to ISO to 0.89 +/- 0.05 and 1.09 +/- 0.07 respectively (P < 0.05). Potassium ferrocyanide which is not a NO donor and D-arginine the inactive substrate of NO synthase did not attenuate the response to ISO. Myocyte cGMP content was significantly increased by incubation with SNP 1 microM (31.65 +/- 3 fmol/well) but not by L-arginine 1 mM (11.1 +/- 0.3 fmol/well) as compared to myocytes incubated in control medium (11 +/- 0.9 fmol/well). Preincubation with SNP 1 microM or L-arginine 1 mM significantly attenuated the ISO mediated-increase in cAMP content from 4.33 +/- 0.2 pmol/well (ISO 100 nM alone) to 1.48 +/- 0.36 fmol/well and 1.72 +/- 0.21 pmol/well respectively. Potassium ferrocyanide and D-arginine had no effect on myocyte cGMP or cAMP content. Chick embryo myocytes have measurable and LNMMA-inhibited NO synthase activity as measured by the conversion of [3H] L-arginine to [3H] L-citrulline. In conclusion, these results demonstrate that in cultured chick embryo ventricular myocytes both exogenous and endogenous NO elevate cGMP. This may account for the inhibition of beta-adrenergic agonist-stimulated increases in cAMP and amplitude of shortening via an unidentified intracellular negative coupling.

Adrenergic beta-Agonists↗

PubMed1997

Carcinoma of the lung in three brothers and two sisters.

Documentation of familial aggregation of five siblings with lung cancer is presented. Lung cancer was not observed in their parents nor among their children, which is consistent with the hypothesis of recessive inheritance, although strong environmental factors such as tobacco smoking may contribute to the development of lung cancer in such families.

Adult↗

PubMed1997

Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study.

PURPOSE: Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (PaO2/FIO2 < or = 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial. MATERIALS AND METHODS: Respiratory dysfunction was graded daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score (LIS) and the PaO2/FIO2 ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course. RESULTS: NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and PaO2/FIO2 ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution (FiO2 at day 3, P < .01 for NAC and P < .05 for placebo; PaO2/FIO2 at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 +/- 0.62 v 1.76 +/- 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 +/- 0.21 for the NAC v 2.15 +/- 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the PaO2/FIO2 evolution did not differ significantly in both subgroups. CONCLUSIONS: In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support.

Acetylcysteine↗

PubMed1997

Characterization of eleven antigenic groups in Trichinella genus and identification of stage and species markers.

Several monoclonal antibodies (Mabs) were raised against the L1 muscle stage (L1M) of Trichinella spiralis (Ts) and Trichinella pseudospiralis (Tp). Western blot analysis of various antigenic preparations established that Mabs described by different authors recognized 8 antigenic fractions (TSL1-TSL8) in crude extracts of infective larvae. The TSL1 fraction was immunodominant and present on the cuticle of different parasite stages. Mabs against Trichinella T5 (T5) and Ts were selected in order to extend the previous studies to another Trichinella phenotype. Only 35% of the selected Mabs recognized linear epitopes and 71% reacted with soluble or excretory-secretory antigens in a dot blot procedure and ELISA test. The targets of the Mabs were identified by immunoprecipitation with [35S]methionine-labelled L1M worm lysate. Mabs prepared from mice immunized with the whole parasite (T5) recognized a wider panel of antigens in different parasitic organs. Seven antigenic structures were distinguished on the cuticle and several epitopes were identified in the gut, haemolymph and stichocytes. Eleven antigenic groups were established according to their indirect immunofluorescence pattern on cross-sections of the worm. Monoclonal antibodies raised against Ts soluble antigen mainly recognized epitopes in stichocytes and on the cuticle surface. All the selected Mabs recognized T5 and Trichinella britovi (Tb) strengthening the link between these 2 species. Four Mabs were used to differentiate antigenic structures among 6 Trichinella phenotypes and to develop a new tool to follow gene flow within the Trichinella genus.

Animals↗

PubMed1997

Effect of L-lysine on nitric oxide overproduction in endotoxic shock.

1. An enhanced production of nitric oxide (NO) from L-arginine, related to the diffuse expression of an inducible NO synthase (iNOS), contributes to the pathogenesis of endotoxic shock. Since iNOS activity depends on extracellular L-arginine, we hypothesized that limiting cellular L-arginine uptake would reduce NO production in endotoxic shock. We investigated the effects of L-lysine, an inhibitor of L-arginine uptake through system y+, on NO production, multiple organ dysfunction and lactate levels, in normal and endotoxaemic rats. 2. Anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 10 mg kg[-1]) received a 5 h infusion of either L-lysine (500 micromol kg(-1) h(-1), n = 12) or isotonic saline (2 ml kg(-1) h(-1), n = 11). In rats treated with saline, LPS produced a large increase in plasma nitrate and L-citrulline concentrations at 5 h, both markers of enhanced NO production. LPS also caused severe hypotension, low cardiac output and marked hyperlactataemia. All these changes were significantly reduced by L-lysine administration. 3. Endotoxaemia also caused a significant rise in the plasma levels of alanine aminotransferase (ALAT), lipase, urea and creatinine, and hence, liver, pancreatic and renal dysfunction. These changes tended to be less pronounced in rats treated with L-lysine, although the differences did not reach statistical significance. 4. Similar experiments were conducted in 10 rats challenged with LPS vehicle in place of LPS and then treated with L-lysine (500 micromol kg(-1) h(-1), n = 5) or saline (2 ml kg(-1) h(-1), n = 5) for 5 h. In these animals, all the haemodynamic and metabolic variables remained stable and not statistically different between both treatment groups, except for a slight rise in ALAT, which was comparable in L-lysine and saline-treated rats. 5. In conclusion, L-lysine, an inhibitor of cellular L-arginine uptake, reduces NO production and exerts beneficial haemodynamic effects in endotoxaemic rats. L-lysine also reduces hyperlactataemia and tends to blunt the development of organ injury in these animals. Contrastingly, L-lysine has no effects in the absence of endotoxin and thus appears to act as a selective modulator of iNOS activity.

Animals↗

PubMed1997

The reliability of recollections of family history: implications for the medical provider.

BACKGROUND: Identification by medical providers of families at higher risks for breast cancer relies on patients' recollection of family histories. While patients seem to report the occurrences of breast cancer in their first-degree relatives accurately, little is known about the precision of reports of ages at diagnosis of cancers in relatives, one of the most revealing clues with regard to hereditary transmission. Moreover, the methods used in previous studies to elicit the family reports render their applicability to the medical setting questionable. METHODS: Confirmatory pathology records were sought and compared with reports of breast cancer events among 125 first-degree relatives by 68 women with breast cancer and 37 women without the disease. RESULTS: Sixty-seven (90.5%) of the reports of the occurrence of breast cancer in relatives by affected women and 32 (97.0%) of those by unaffected women were accurate. Women reporting several affected relatives often overreported the presence of breast cancer events. Nearly 89% of the reports of age at diagnosis were correct within five years. The average error in the reports was 2.0 years. The precision of reports of age at diagnosis did not differ according to the educational level of the proband, the age at which the relative had been diagnosed, or the type of relative affected. However, the mean error in reporting the age at diagnosis of relatives was significantly larger among probands 70 years old or older compared with younger probands. CONCLUSIONS: These results suggest that relying on reports by patients with and without breast cancer should not critically affect the assessment of breast-cancer risks for family members. Nevertheless, verification by examination of pathology records is justified when decisions about patient management and referral for genetic counseling are made based on reports of several affected relatives.

Adult↗

PubMed1997

Intensive care physicians' insufficient knowledge of right-heart catheterization at the bedside: time to act?

OBJECTIVE: To evaluate French, Swiss, and Belgian intensive care physicians' knowledge about the pulmonary artery catheter. DESIGN: Survey study by questionnaire. SETTING: Eighty-six European university and nonuniversity intensive care units (ICUs). SUBJECTS: One hundred thirty-four ICUs identified from the directories of two European intensive care medicine societies were asked to participate. Five hundred thirty-five critical care physicians working in 86 ICUs participated. INTERVENTIONS: In any particular ICU, all physicians were to complete--simultaneously, anonymously and without prior notice--a multiple choice questionnaire consisting of 31 questions regarding all aspects of bedside pulmonary artery catheterization. This questionnaire was the same one already used and extensively validated in a similar study conducted several years earlier in the United States and Canada. MEASUREMENTS AND MAIN RESULTS: The percentage of correct answers per participant (score) was tabulated. Sixty-eight percent of respondents still in training (n = 232) believed that their knowledge of the pulmonary artery catheter was less than adequate; 36% of those who had completed their postgraduate training (n = 294) also believed their knowledge to be inadequate. The mean score of all respondents was 72.2 +/- 14.4%, significantly lower (p <.0001) in case of uncompleted postgraduate training (67.3 +/- 14.7%, lower quartile 56.7%, median 70.0%, upper quartile 76.7%), as compared with completed postgraduate training (76.1 +/- 13.0%, lower quartile 70.0%, median 80.0%, upper quartile 86.7%). When using multivariate analysis, the location of the ICU in a university hospital, the belief of respondent that his/her knowledge of the pulmonary artery catheter was adequate, and the responsibility for supervising catheter insertion were the only independent predictors of good performance on the questionnaire (p < .001 for all three variables). It was impossible to identify any subcategory of physicians with a uniformly good knowledge of the pulmonary artery catheter. The proportion of incorrect answers to some basic items was disturbingly high. For instance, approximately 50% of the respondents, whether trained or in training, did not correctly identify pulmonary artery occlusion pressure from a clear chart recording. CONCLUSIONS: Knowledge of right-heart pulmonary artery catheterization is not uniformly good among ICU physicians. Accreditation policies and teaching practices concerning this technique need urgent revision.

Attitude of Health Personnel↗

PubMed1997

Control of nuclear transcription of vitamin D-dependent genes by vitamin D.

Vitamin D acts on the genome via its active metabolite, calcitriol, which is bound to its nuclear receptor (vitamin D receptor) and a DNA response element. The characterization of the DNA target of the vitamin D receptor in vitamin D-activated or -repressed genes and structure-function analysis of the vitamin D receptor have led to several advances. These include a better understanding of the mechanisms of transactivation via the vitamin D receptor by the description of direct and indirect interactions of the vitamin D receptor with the basal transcriptional machinery. Physiological evidence for heterodimerization of the vitamin D receptor with the retinoid X receptor, and with other liganded or unliganded nuclear receptors, has indicated how the genetic response to vitamin D can be modulated. This modulation can also be brought about by cooperation between vitamin D receptor and transcription factors, by the action of a dominant negative isoform of vitamin D receptor, and by cross-talk between the signalling pathways for vitamin D and growth factors. These new concepts, plus the development of analogues of calcitriol, all indicate considerable progress towards vitamin D therapy for several disorders, including renal diseases.

Animals↗

PubMed1997

L-canavanine improves organ function and tissue adenosine triphosphate levels in rodent endotoxemia.

Overproduction of NO by an inducible NO synthase (iNOS) plays a major role in the pathophysiology of septic shock, and selective inhibition of iNOS in this setting could be of great therapeutic value. In the present study, we evaluated the effects of L-canavanine, a selective iNOS inhibitor, in an animal model of septic shock, with a particular focus on tissue oxidative metabolism and organ functions. Anesthetized rats challenged intravenously with lipopolysacharide (LPS) were treated after 1 h by a continuous infusion of either L-canavanine (20 mg/kg/h; n = 11) or an equivalent volume of saline (2 ml/kg/h; n = 17) given for 4 h. A third group (sham rats; n = 9) did not receive LPS and was treated with a continuous infusion of saline (2 ml/kg/h). At the end of experiments, biopsies were taken from the liver, the kidney, and the small intestine for the measurement of tissue ATP. LPS induced a progressive fall in blood pressure, accompanied by biologic signs of liver and kidney failure, concomitant with a marked decrease in tissue ATP stores. L-canavanine largely prevented hypotension and significantly increased tissue ATP while reducing the signs of organ dysfunction. These effects were associated with a significant improvement in survival during the 5 h of study. We conclude that L-canavanine not only reduces hypotension in endotoxin shock but also largely prevents the detrimental consequences of LPS on tissue oxidative metabolism and major organ functions, allowing a decrease in endotoxin lethality.

Adenosine Triphosphate↗