Biomedical subjects

Michel Burnier

Publications and source records attributed to Michel Burnier.

At least 55 records · Page 3Linked to original sources

PubMed2005

The safety of rofecoxib.

Like all COX-2 inhibitors, rofecoxib has been developed based on the hypothesis that at comparable therapeutic efficacy, it would have a better safety and tolerability profile than conventional NSAIDs. The Vioxx GI Outcomes Research trial has demonstrated that rofecoxib is indeed safer for the gastrointestinal tract than NSAIDs. However, this study has also raised questions regarding the cardiovascular safety of rofecoxib. Thereafter, several epidemiological and case-control studies have reinforced the association between rofecoxib and a higher risk of cardiovascular events. However, at this time, no prospective controlled study is available to conclude definitively on this issue. Several pathogenic mechanisms are evoked to explain why rofecoxib increases the cardiovascular risk. These include the development of a prothrombotic state, a sodium retention and an increase in systemic blood pressure. Recently, new evidence have become available indicating that rofecoxib indeed increases the number of thrombo-embolic events. These data have resulted in the complete withdrawal of rofecoxib from the market. Was it scientifically reasonable to withdraw rofecoxib rather than to adapt its label? Is the safety profile of rofecoxib really much worse than that of aspirin or other traditional NSAIDs? The main consequence of this withdrawal is a considerable threat on the entire class of selective COX-2 inhibitors without a clear evaluation of the balance between the risks and benefits of these compounds.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

Telmisartan/hydrochlorothiazide: a new fixed dose combination.

Many patients with hypertension require two or more antihypertensive drugs with complementary mechanisms of action to lower their blood pressure and attain the therapeutic goals specified in internationally accepted guidelines. Yet, these latter guidelines offer the choice of fixed dose combinations as possible first-step therapies. The angiotensin II type 1-receptor antagonist telmisartan and the diuretic hydrochlorothiazide are two antihypertensive agents that have a well-recognized clinical efficacy. Their combination was shown in randomized, controlled trials to be more effective than each agent alone in lowering blood pressure, due to a dual and synergistic mechanism. Indeed, combining telmisartan with hydrochlorothiazide enhances the antihypertensive efficacy of telmisartan in almost two-thirds of hypertensive patients with mild-to-moderate hypertension. The pharmacokinetics and -dynamics of the combination are similar to monotherapy, and the addition of hydrochlorothiazide to telmisartan does not modify the excellent tolerability profile of the drug.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Circadian variations in blood pressure : implications for chronotherapeutics.

The management of hypertensive patients usually ignores or gives little credit to the biologic rhythms inherent to the disease process and their potential clinical implications. The development of ambulatory blood pressure monitoring and the rapidly growing popularity of home blood pressure measurements by patients have now generated a series of new clinical questions that are directly linked to the chronobiology of the cardiovascular system, such as the clinical interpretation of a blunted nocturnal fall in blood pressure or the difficulty of achieving adequate blood pressure control in the morning. Today, there is growing evidence that night-time blood pressure, and particularly the absence of a decrease in sleep blood pressure, contributes to the occurrence of target organ damages, and that the early morning rise in blood pressure increases the risk of developing cardiovascular events, including stroke, perhaps independently of 24-hour blood pressure levels. On the basis of these observations, it may be necessary to reconsider the way antihypertensive drugs are prescribed in order to obtain smooth, 24-hour blood pressure control, respecting the circadian pattern of blood pressure. Several approaches exist, including the use of drugs that lower blood pressure around the clock and respect the diurnal rhythm. Preliminary studies performed with such agents have provided interesting results. However, there is a clear need for large clinical trials demonstrating the clinical superiority of this approach. In any case, a better understanding of the importance of the circadian variations of blood pressure could certainly have a major impact on our view of the therapeutic management of hypertensive patients.

Antihypertensive Agents↗

PubMed2005

The future of angiotensin II inhibition in cardiovascular medicine.

Drugs, which interfere with the renin-angiotensin-aldosterone cascade such as angiotensin converting enzyme (ACE) inhibitors, have been available to clinicians for more than 20 years. They are now recognized as a very effective approach to treat patients with hypertension, heart failure, diabetic and non-diabetic chronic renal failure or patients with a high cardiovascular risk. The recent development of angiotensin II (Ang II) receptor antagonist has enabled to improve significantly the tolerability profile of this group of drugs while maintaining a high clinical efficacy. Yet, with the availability of Ang II receptor antagonists, new questions have arisen. Is it still possible to gain in efficacy with newer agents? What is the future of drugs such as neutral endopeptidase (NEP)/ACE inhibitors or renin inhibitors? The first objective of this review is to discuss the clinical implications of several large clinical trials that have been published recently with ACE inhibitors and Ang II receptor antagonists such as ALLHAT, LIFE, OPTIMAAL, Val-Heft, SCOPE, and more recently, CHARM, VALIANT and VALUE. With these trials, we can now define more precisely the role of these blockers of the renin-angiotensin system in the management of patients with cardiovascular complications. The second part of this review is devoted to new drugs interfering with the renin-angiotensin system. We discuss the recent results obtained with NEP/ACE inhibitors also named vasopeptidase inhibitors. Several compounds were or are in development but the experience with omapatrilat has blunted the enthusiasms for these compounds. Yet, vasopeptidase inhibitors remain very effective antihypertensive drugs and there is a great therapeutic potential for these agents provided one can define more accurately the risk/benefit ratio and the clinical indications. Finally, we present the recent data obtained with SPP 100, a new renin inhibitor that is actually under clinical development. SPP 100 has a sufficient bioavailability to induce a sustained blockade of the renin-angiotensin system when given orally to normal subjects. Recent studies have shown that SPP 100 lowers blood pressure in hypertensive patients as effectively as an Ang II receptor antagonist.

Angiotensin II↗

PubMed2005

OASIS-HT: design of a pharmacogenomic dose-finding study.

Experimental evidence and observations in humans strongly support an interactive role of mutated alpha-adducin, sodium (Na(+))/potassium (K(+))-adenosine triphosphatase (ATPase) activity and endogenous ouabain in Na(+) homeostasis and the pathogenesis of hypertension. The Ouabain and Adducin for Specific Intervention on Sodium in HyperTension (OASIS-HT) trial is an early Phase II dose-finding study, which will be conducted across 39 European centers. Following a run-in period of 4 weeks without treatment, eligible patients will be randomized to one of five oral doses of rostafuroxin consisting of 0.05, 0.15, 0.5, 1.5, or 5.0 mg/day. Each dose will be compared to a placebo in a double-blind crossover experiment with balanced randomization. Treatment will be initiated with the active drug and continued with placebo or vice versa. Each double-blind period will last 5 weeks. The primary end point is the reduction in systolic blood pressure defined as the average of three clinic readings with the patient in the sitting position. Secondary end points include the reduction in diastolic blood pressure on clinic measurement, the decrease in the 24-h blood pressure, and the incidence of end points related to safety. Secondary objectives are to investigate the dependence of the blood pressure-lowering activity on the plasma concentration of endogenous ouabain and the genetic variation of the enzymes involved in the metabolism of this hormone, and the adducin cytoskeleton proteins. Eligible patients will have Grade I or II systolic hypertension without associated conditions and no more than two additional risk factors. In conclusion, OASIS-HT is a combination of five concurrent crossover studies, one for each dose of rostafuroxin to be studied. To our knowledge, OASIS-HT is the first Phase II dose-finding study in which a genetic hypothesis is driving primary and secondary end points.

Administration, Oral↗

PubMed2004

Artificial neural networks improve the prediction of Kt/V, follow-up dietary protein intake and hypotension risk in haemodialysis patients.

BACKGROUND: Artificial neural networks (ANN) represent a promising alternative to classical statistical and mathematical methods to solve multidimensional non-linear problems. The aim of the study was to compare the performance of ANN in predicting the dialysis quality (Kt/V), the follow-up dietary protein intake and the risk of intradialytic hypotension in haemodialysis patients with that predicted by experienced nephrologists. METHODS: A combined retrospective and prospective observational study was performed in two Swiss dialysis units (80 chronic haemodialysis patients, 480 monthly clinical observations and biochemical test results). Using mathematical models based on linear and logistic regressions as background, ANN were built and then prospectively compared with the ability of six experienced nephrologists to predict the Kt/V and the follow-up protein catabolic rate (PCR) and to detect a Kt/V < 1.30, a follow-up PCR < 1.00 g/kg/day and the occurrence of hypotension. RESULTS: ANN compared with nephrologists gave a more accurate correlation between estimated and calculated Kt/V and follow-up PCR (P<0.001). The same superiority of ANN was also seen in the ability to detect a Kt/V < 1.30, a follow-up PCR < 1.00 g/kg/day and the occurrence of hypotension expressed as a percentage of correct answers, sensitivity, specificity and predictivity. CONCLUSIONS: The use of ANN significantly improves the ability of experienced nephrologists to estimate the Kt/V and the follow-up PCR and to detect a Kt/V < 1.30, a follow-up PCR < 1.00 g/kg/day and the occurrence of intradialytic hypotension.

Aged↗

PubMed2004

Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under a normal-salt diet.

Primary aldosteronism causes severe hypertension in humans (Conn's syndrome) with cardiac hypertrophy, characterized by a fibrosis more severe than the one observed in patients with essential hypertension. This suggests that aldosterone by itself may have specific and direct effects on cardiac remodeling through the activation of the cardiac mineralocorticoid receptor. Experimental evidence obtained in studying uninephrectomized rats treated with aldosterone or deoxycorticosterone (DOC) together with salt loading has led to similar conclusions. To examine the direct consequences of chronically elevated aldosterone levels on cardiac pathophysiology, we analyzed a mouse model (alpha-epithelial Na channel -/-Tg) that is normotensive under normal-salt diet but exhibits chronic hyperaldosteronism. Sixteen-month-old transgenic rescue mice that were kept under a regular salt diet that contains a small amount of sodium (0.3% Na(+)) displayed a compensated PHA-1 phenotype with normal body weight, normal kidney index, normal blood pressure, but 6.3-fold elevated plasma aldosterone levels compared with the age-matched control group. Peripheral resistance of distal colon to aldosterone was shown by a significant decrease of the amiloride-sensitive rectal potential difference, and its diurnal cyclicity was blunted. Despite chronically high plasma aldosterone levels, these animals do not show any evidence of cardiac hypertrophy, remodeling, or fibrosis, using collagen staining and anti-alpha-skeletal and alpha-smooth actin immunochemical labeling of heart sections. Cardiac fibrosis as seen in DOC- or aldosterone/salt-treated animal models is therefore likely to be due to the synergistic effect of salt, aldosterone, and other confounding factors rather than to the elevated circulating aldosterone levels alone.

Aging↗

PubMed2004

Cost-effectiveness of losartan versus atenolol in treating hypertension--an analysis of the LIFE study from a Swiss perspective.

AIMS: To determine the economic benefit of losartan versus atenolol in patients with essential hypertension from the perspective of the Swiss healthcare system. METHODS AND RESULTS: The cost-effectiveness of losartan versus atenolol in the treatment of hypertension was analyzed by applying the results of the LIFE study to the Swiss healthcare system using a decision analysis framework. The cost-effectiveness shows the losartan cohort to provide an additional life expectancy of 0.05 years per patient compared to the atenolol cohort, over a mean follow-up period of 4.8 years. Losartan therapy in hypertensive patients produced net cost savings of CHF 24 per patient and per 4.8 years compared to atenolol from the perspective of the Swiss health care system. This result was robust after varying costs of medication, stroke, myocardial infarction and life expectancy. CONCLUSION: The use of a losartan-based regimen in hypertensive patients with left ventricular hypertrophy in Switzerland is net cost-saving compared with a atenolol-based regimen.

Aged↗

PubMed2004

Female sex hormones, salt, and blood pressure regulation.

There are gender-associated differences in blood pressure (BP) in humans, with men having higher BP than age-matched pre-menopausal women and being at greater risk for cardiovascular and renal diseases. The mechanisms responsible for the gender differences in BP control and regulation are not clear, although there is some evidence that interactions between sex hormones and the kidneys could play a role. However, the response to salt in pre- and post-menopausal women, and in particular the influence of exogenous and endogenous female sex hormones on renal hemodynamics and tubular segmental sodium handling, have been poorly investigated. Recently we have shown that both endogenous and exogenous female sex hormones markedly influence the systemic and renal hemodynamic response to salt. We have found that BP in young normotensive women, regardless of oral contraceptive use, is rather insensitive to salt. However, the renal hemodynamic and the tubular responses to salt vary significantly during the normal menstrual cycle and with the administration of oral contraceptives. Furthermore, after the menopause, BP tends to become salt sensitive, a pattern that could be due to aging as well as to the modification of the sex hormone profile. These observations provide new insights pertaining to potential mechanisms explaining the lower incidence of cardiovascular disease and progression of renal disease in pre-menopausal women (which tend to disappear with the menopause); these observations also emphasize the importance of considering more carefully the phase of the menstrual cycle whenever conducting physiologic studies in women and enrolling women in clinical studies. Finally, increased salt sensitivity in menopausal women strongly encourages the use of diuretics.

Animals↗

PubMed2004

Patients' sibling history was sensitive for hypertension and specific for diabetes.

OBJECTIVE: We examined the analytic validity of reported family history of hypertension and diabetes among siblings in the Seychelles. STUDY DESIGN AND SETTING: Four hundred four siblings from 73 families with at least two hypertensive persons were identified through a national hypertension register. Two gold standards were used prospectively. Sensitivity was the proportion of respondents who indicated the presence of disease in a sibling, given that the sibling reported to be affected (personal history gold standard) or was clinically affected (clinical status gold standard). Specificity was the proportion of respondents who reported an unaffected sibling, given that the sibling reported to be unaffected or was clinically unaffected. Respondents gave information on the disease status in their siblings in approximately two-thirds of instances. RESULTS: When sibling history could be obtained (n=348 for hypertension, n=404 for diabetes), the sensitivity and the specificity of the sibling history were, respectively, 90 and 55% for hypertension, and 61 and 98% for diabetes, using clinical status and, respectively, 89 and 78% for hypertension, and 53 and 98% for diabetes, using personal history. CONCLUSION: The sibling history, when available, is a useful screening test to detect hypertension, but it is less useful to detect diabetes.

Adult↗

PubMed2004

Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent.

BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in decreasing blood pressure in African patients is controversial. OBJECTIVE: We examined the ambulatory blood pressure (ABP) response to a diuretic and an ACE inhibitor in hypertensive patients of East African descent and evaluated the individual characteristics that determined treatment efficacy. DESIGN: A single-blind randomized AB/BA crossover design. SETTING: Hypertensive families of East African descent from the general population in the Seychelles. PARTICIPANTS: Fifty-two (29 men and 23 women) out of 62 eligible hypertensive patients were included.Main outcome measures ABP response to 20 mg lisinopril (LIS) daily and 25 mg hydrochlorothiazide (HCT) daily given for a 4-week period. Results The daytime systolic/diastolic ABP response to HCT was 4.9 [95% confidence interval (CI) 1.2-8.6]/3.6 (1.0-6.2) mmHg for men and 12.9 (9.2-16.6)/6.3 (3.7-8.8) mmHg for women. With LIS the response was 18.8 (15.0-22.5)/14.6 (12.0-17.1) mmHg for men and 12.4 (8.7-16.2)/7.7 (5.1-10.2) mmHg for women. The night-time systolic/diastolic response to HCT was 5.0 (0.6-9.4)/2.7 [(-0.4)-5.7] mmHg for men and 11.5 (7.1-16.0)/5.7 (2.6-8.8) mmHg for women, and to LIS was 18.7 (14.2-22.1)/15.4 (12.4-18.5) mmHg for men and 3.5 [(-1.0)-7.9]/2.3 [(-0.8)-5.4] mmHg for women. Linear regression analyses showed that gender is an independent predictor of the ABP responses to HCT and to LIS. CONCLUSIONS: Hypertensive patients of African descent responded better to LIS than to HCT. Men responded better to LIS than to HCT and women responded similarly to both drugs.

Adult↗

PubMed2004

Reasons for not intensifying antihypertensive treatment (RIAT): a primary care antihypertensive intervention study.

OBJECTIVE: Hypertension is often poorly controlled, despite its importance and despite the availability of very effective treatments. An under-recognized problem is the failure of consensus guidelines to acknowledge the important difference between efficacy in clinical trials and effectiveness in clinical practice. The present survey was designed to prospectively assess what is the target blood pressure (BP) goal defined by a general practitioner (GP) for an individual patient, and what are the reasons for not modifying an antihypertensive drug regimen, when pre-defined individual BP goals are not achieved. DESIGN: Family practice based, open intervention survey. SUBJECTS: Participating GPs enrolled 2621 hypertensive patients. At the first visit each physician was required to assess the cardiovascular risk profile of each patient and to define individual BP targets. INTERVENTIONS: Treatment was started with irbesartan alone or in fixed combination with hydrochlorothiazide. Follow-up visits were suggested after 1 month, 2 months and 4 months. Physicians were asked to report BP values under the new treatment regimen and to indicate whether in their opinion pre-defined BP targets set at baseline were achieved or not and whether the antihypertensive regimen was modified or maintained in relation to whether target BP was reached or not. MAIN OUTCOME MEASURE: To provide reasons for not changing the treatment even though BP goals were missed. RESULTS: Average target BP values defined by the physicians at baseline were 138 +/- 8 mmHg for systolic and 84 +/- 5 mmHg for diastolic BP. Among GPs, defined target BP values did not depend on individual risk stratification, but rather depended on baseline BP values. At baseline systolic and diastolic BP averaged 165/97 +/- 17/10 mmHg, while at the last visit achieved BP averaged 140/84 +/- 14/8 mmHg. There were three main reasons for not intensifying antihypertensive treatment when BP targets were not achieved. These reasons were: (1). the assumption that the time after starting the new drug was too short to appreciate its full effect (44% at first, 14% at last follow-up), (2). that there was a clear improvement or the target BP was almost reached (24% at first, 34% at last follow-up) or (3). that self-measurements were considered satisfactorily (10% at the last visit). CONCLUSIONS: Failure of physicians to follow guidelines is apparently dependent on the belief that baseline BP dictates the target, that a clear improvement in BP might be sufficient and that the full drug effect may take up to 4 months or more to be attained.

Aged↗

PubMed2004

Discordant prevalence of hypertension using two different automated blood pressure measurement devices: a population-based study in Dar es Salaam (Tanzania).

OBJECTIVE: The estimation of blood pressure is dependent on the accuracy of the measurement devices. We compared blood pressure readings obtained with an automated oscillometric arm-cuff device and with an automated oscillometric wrist-cuff device and then assessed the prevalence of defined blood pressure categories. METHODS: Within a population-based survey in Dar es Salaam (Tanzania), we selected all participants with a blood pressure >/= 160/95 mmHg (n=653) and a random sample of participants with blood pressure <160/95 mmHg (n=662), based on the first blood pressure reading. Blood pressure was reassessed 2 years later for 464 and 410 of the participants, respectively. In these 874 subjects, we compared the prevalence of blood pressure categories as estimated with each device. RESULTS: Overall, the wrist device gave higher blood pressure readings than the arm device (difference in systolic/diastolic blood pressure: 6.3 +/- 17.3/3.7 +/- 11.8 mmHg, P<0.001). However, the arm device tended to give lower readings than the wrist device for high blood pressure values. The prevalence of blood pressure categories differed substantially depending on which device was used, 29% and 14% for blood pressure <120/80 mmHg (arm device versus wrist device, respectively), 30% and 33% for blood pressure 120-139/80-89 mmHg, 17% and 26% for blood pressure 140-159/90-99 mmHg, 12% and 13% for blood pressure 160-179/100-109 mmHg and 13% and 14% for blood pressure >/= 180/110 mmHg. CONCLUSIONS: A large discrepancy in the estimated prevalence of blood pressure categories was observed using two different automatic measurement devices. This emphasizes that prevalence estimates based on automatic devices should be considered with caution.

Adult↗

PubMed2004

Angiotensin II receptor blockade prevents acute renal sodium retention induced by low levels of orthostatic stress.

BACKGROUND: Depending on its magnitude, lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal, renal tubular, and renal hemodynamic responses, thereby mimicking the renal responses observed in clinical conditions characterized by a low effective arterial volume such as congestive heart failure. Our objective was to evaluate the impact of angiotensin II receptor blockade with candesartan on the renal hemodynamic and urinary excretory responses to a progressive orthostatic stress in normal subjects. METHODS: Twenty healthy men were submitted to three levels of LBNP (0, -10, and -20 mbar or 0, -7.5, and -15 mm Hg) for 1 hour according to a crossover design with a minimum of 2 days between each level of LBNP. Ten subjects were randomly allocated to receive a placebo and ten others were treated with candesartan 16 mg orally for 10 days before and during the three levels of LBNP. Systemic and renal hemodynamics, renal sodium excretions, and the hormonal response were measured hourly before, during, and for 2 hours after LBNP. RESULTS: During placebo, LBNP induced no change in systemic and renal hemodynamics, but sodium excretion decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3-hour sodium balance was negative at -2.3 +/- 2.3 mmol (mean +/- SEM). With candesartan, mean blood pressure decreased (76 +/- 1 mm Hg vs. 83 +/- 3 mm Hg, candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 +/- 52 mL/min vs. 639 +/- 36 mL/min, candesartan vs. placebo, P < 0.05). Glomerular filtration rate (GFR) was not significantly higher with candesartan (127 +/- 7 mL/min in placebo vs. 144 +/- 12 mL/min in candesartan). No significant decrease in sodium and water excretion was found during LBNP in candesartan-treated subjects. At -20 mbar, the 3-hour cumulative sodium excretion was + 4.6 +/- 1.4 mmol in the candesartan group (P= 0.02 vs. placebo). CONCLUSION: Selective blockade of angiotensin II type 1 (AT1) receptors with candesartan increases renal blood flow and prevents the antinatriuresis during sustained lower body negative pressure despite a modest decrease in blood pressure. These results thus provide interesting insights into potential benefits of AT1 receptor blockade in sodium-retaining states such as congestive heart failure.

Acute Disease↗

PubMed2004

Usefulness of artificial neural networks to predict follow-up dietary protein intake in hemodialysis patients.

BACKGROUND: Artificial neural networks (ANN) represent a promising alternative to classical statistical and mathematic methods to solve multidimensional nonlinear problems. The aim of the study was to verify, by comparing the performance of ANN with that of experienced nephrologists, whether ANN are useful tools in hemodialysis to predict the follow-up (=1 month after the observation used for the prediction) dietary protein intake (PCR), and whether their performance is influenced by the size of the population and by the data pool used to built the model. METHODS: A combined retrospective and prospective observational study was performed in two Swiss dialysis units (84 chronic hemodialysis patients, 500 monthly clinical observations and biochemical test results). Using mathematical models based on linear regressions to evaluate the variables, ANN were built and then prospectively and interinstitutionally compared with the ability of six experienced nephrologists to predict the follow-up PCR. RESULTS: ANN compared with nephrologists gave a more accurate correlation between estimated and calculated follow-up PCR (P < 0.001). The same superiority of ANN was also seen in the ability to detect a follow-up PCR <1.00 g/kg/day expressed as a percentage of correct predictions, sensitivity, specificity, and predictivity. The interinstitutional performance of the ANN is positively influenced by the size and the variability of the population used to build the mathematical model. CONCLUSION: The use of ANN significantly improves the ability of the experienced nephrologist to estimate and to detect an unsatisfactory (<1.00 g/kg/day) follow-up PCR. The size of the population selected to build the ANN is critical for his performance.

Aged↗

PubMed2004

Effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men.

Glitazones are used in the treatment of type 2 diabetes as efficient insulin sensitizers. They can, however, induce peripheral edema through an unknown mechanism in up to 18% of cases. In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of a 6-wk administration of pioglitazone (45 mg daily) or placebo on the blood pressure, hormonal, and renal hemodynamic and tubular responses to a low (LS) and a high (HS) sodium diet in healthy volunteers. Pioglitazone had no effect on the systemic and renal hemodynamic responses to salt, except for an increase in daytime heart rate. Urinary sodium excretion and lithium clearance were lower with pioglitazone, particularly with the LS diet (P < 0.05), suggesting increased sodium reabsorption at the proximal tubule. Pioglitazone significantly increased plasma renin activity with the LS (P = 0.02) and HS (P = 0.03) diets. Similar trends were observed with aldosterone. Atrial natriuretic levels did not change with pioglitazone. Body weight increased with pioglitazone in most subjects. Pioglitazone stimulates plasma renin activity and favors sodium retention and weight gain in healthy volunteers. These effects could contribute to the development of edema in some subjects treated with glitazones.

Adult↗

PubMed2004

[Massive hyperoxaluria].

Primary hyperoxaluria type I is a rare inborn error of metabolism caused by a deficiency of a liver-specific peroxisomal enzyme. It manifests by increased oxalate production that ultimately results in kidney failure, due to urolithiasis and nephrocalcinosis, and finally induces systemic oxalosis and risk of premature death. Primary hyperoxaluria type 2 is mainly responsible of urolithiasis. Enteric hyperoxaluria is a commonly seen adverse event of Crohn disease or after extensive intestinal resection. These affections represent the main etiologies of massive hyperoxaluria. If not recognized very soon and adequately treated, these conditions can progress rapidly to end stage renal failure.

Child↗

PubMed2003

Determination of cardiac contractility in awake unsedated mice with a fluid-filled catheter.

Today, cardiac contractility in mice is exclusively measured under anesthesia or in sedated animals because the catheters available are too rigid to be used in awake mice. We therefore developed a new catheter (Pebax 03) to measure cardiac contractility in conscious mice. In this study, we evaluated the accuracy and utility of this new catheter for assessment of cardiac contractility in anesthetized and conscious mice. With the use of a balloon-pop test, the Pebax catheter with an inner diameter of 0.3 mm was found to exhibit a high natural frequency, a low damping coefficient, and a flat frequency of up to 50.5 +/- 0.6 Hz. Under anesthesia (0.5% or 1.0% halothane), no difference was found in heart rate (HR), left ventricular (LV) systolic pressure (LVSP), the maximum rates of LV pressure rise and fall (LV dP/dt(max) and LV dP/dt(min), respectively), ejection time (ET), and isovolumic relaxation time constant (tau) when measured with either the 1.4-Fr Millar or Pebax 03 catheter. However, when HR, LVSP, LV dP/dt(max), and LV dP/dt(min) were recorded with the Pebax catheter in awake mice, values were significantly higher, and ET and tau were lower, than under anesthesia, suggesting a major impact of anesthesia on these parameters. The Pebax catheter was also used in a normotensive one-renin gene mouse model of cardiac hypertrophy induced by DOCA and salt. In this model, DOCA-salt induced a severe decrease in cardiac contractility in the absence of changes in blood pressure. These data demonstrate that cardiac contractility can be measured very accurately in conscious mice. This new device can be of great help in the investigation of cardiac function in normal and genetically engineered mice.

Anesthesia, General↗