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Alvine Bissery

Publications and source records attributed to Alvine Bissery.

At least 19 recordsLinked to original sources
PubMed2006

Prostate dynamic contrast-enhanced MRI with simple visual diagnostic criteria: is it reasonable?

UNLABELLED: The purpose of this study was to evaluate the accuracy of prostate cancer localization with simple visual diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). A total of 46 consecutive patients with biopsy-proven prostate cancer underwent prostate 1.5 T MRI with pelvic phased-array coils before prostatectomy. Besides the usual T2-weighted sequences, a 30-s DCE sequence was acquired three times after gadoterate injection. On DCE images, all early enhancing lesions of the peripheral zone were considered malignant. In the central gland, only early enhancing lesions appearing homogeneous or invading the peripheral zone were considered malignant. Three readers specified the presence of cancer in 20 prostate sectors and the location of distinct tumors. Results were compared with histology; p < 0.05 was considered significant. For localization of cancer in the sectors, DCE imaging had a significantly higher sensitivity [logistic regression, odds ratio (OR): 3.9, p < 0.0001] and a slightly but significantly lower specificity (OR: 0.57, p < 0.0001). Of the tumors >0.3 cc, 50-60% and 78-81% were correctly depicted with T2-weighted and DCE imaging, respectively. For both techniques, the depiction rate of tumors >0.3 cc was significantly influenced by the Gleason score (most Gleason </=6 tumors were overlooked), but not by the tumor volume. CONCLUSION: DCE-MRI using pelvic phased-array coils and simple visual diagnostic criteria is more sensitive for tumor localization than T2-weighted imaging.

Aged↗
PubMed2006

Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor AVE7688 in humans.

OBJECTIVE: Our objective was to define the pharmacodynamic profile of the new dual neutral endopeptidase (NEP)/angiotensin-converting enzyme (ACE) inhibitor AVE7688. METHODS: We compared the effects of single oral doses of AVE7688 (5 and 25 mg) with those of 10 mg ramipril (R10), a selective ACE inhibitor, in a placebo-controlled crossover study in sodium-depleted normotensive subjects. We also compared the effects of 25 mg AVE7688 with those of a renin-angiotensin system (RAS) blockade induced by a high dose of an angiotensin II receptor antagonist (300 mg irbesartan) and a dual blockade of the RAS (150 mg irbesartan plus 10 mg ramipril) in sodium-replete normotensive subjects by use of the same study design. The in vivo inhibition of ACE and NEP was monitored by measuring the urinary excretion of N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) and atrial natriuretic peptide (ANP), respectively. The intensity of RAS blockade was assessed by the increase in plasma active renin concentration. RESULTS: The 24-hour urine AcSDKP cumulative excretion increased significantly more after 25 mg AVE7688 (919 nmol [95% confidence interval (CI), 803-1052 nmol], P < .05) than after 5 mg AVE7688 (706 nmol [95% CI, 612-813 nmol]) or 10 mg ramipril (511 nmol [95% CI, 440-593 nmol]). The 25-mg dose of AVE7866 significantly and transiently (4 to 8 hours after drug intake) increased urinary ANP (2.02 +/- 1.05 ng/h, P < .05), whereas 5 mg AVE7688 (1.14 +/- 0.77 ng/h) and 10 mg ramipril (0.93 +/- 0.65 ng/h) had no effect compared with placebo (0.80 +/- 0.37 ng/h). In the low-salt panel the rise in plasma active renin concentration achieved 24 hours after dosing by 25 mg AVE7688 (247 pg/mL [95% CI, 157-389 pg/mL], P < .05) was significantly higher than that achieved by 5 mg AVE7688 (129 pg/mL [95% CI, 75-221 pg/mL]) or 10 mg ramipril (113 pg/mL [95% CI, 67-193 pg/mL]), which did not differ. In the high-salt panel group the effects of 25 mg AVE7688 on renin release did not significantly differ from those after administration of the combination of 150 mg irbesartan plus 10 mg ramipril or 300 mg irbesartan alone. All of these active drugs similarly decreased blood pressure compared with placebo. CONCLUSION: AVE7688 at a dose of 25 mg has a favorable pharmacodynamic profile compared with other RAS blockers. These results support further clinical studies of its long-term effects in essential or resistant hypertension, chronic proteinuric nephropathy, and chronic heart failure.

Adolescent↗
PubMed2006

Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis.

OBJECTIVE: Growth-arrest-specific protein 6 (Gas6), an intracellular protein released by apoptotic cells, has been detected in normal plasma. As the Gas6 system has been implicated in mouse susceptibility to sepsis, and as leukocyte apoptosis is thought to play a major role in the physiopathology of human severe sepsis, we studied Gas6 plasma levels and possibly related variables in patients with severe sepsis. DESIGN: Matched case-control study. SETTING: Adult intensive care unit in a university hospital. PATIENTS: Thirty patients with severe sepsis, 30 patients with organ failure not related to infection, and 30 healthy subjects matched for age and gender. INTERVENTIONS: Blood draw. MEASUREMENTS AND MAIN RESULTS: Gas6 plasma levels were quantified using enzyme-linked immunosorbent assay. Whole-blood gas6 messenger RNA levels were measured by quantitative real-time polymerase chain reaction. Gas6 plasma levels were elevated (110 ng/mL [75, 139]; median values [interquartile range]) in severe sepsis patients compared with organ failure patients (85 ng/mL [56, 101]) and healthy subjects (54 ng/mL [49, 68]). In patients with severe sepsis, this increase correlated with the Acute Physiology and Chronic Health Evaluation II severity score, the organ failure Organ Dysfunction and Infection (ODIN) score, and the existence of a septic shock. Gas6 messenger RNA levels were increased in patients with severe sepsis and correlated specifically with the monocyte count. CONCLUSIONS: In severe sepsis, the recently described anti-apoptotic protein Gas6 was found at high levels in plasma and correlated well with the degree of organ dysfunction.

APACHE↗
PubMed2006

Investigation of aldosterone-synthase inhibition in rats.

BACKGROUND: In-vivo investigation of aldosterone-synthase inhibitors requires experimental models to characterize the biological effects of these compounds. METHODS: Seven successive experiments were performed in groups of 2-month-old male spontaneously hypertensive rats. Urinary free aldosterone was the main end-point measured during two contrasted diets: low sodium-high potassium (LS), inducing high urinary aldosterone (839 pmol/24 h, 95% confidence interval 654-1077), and high sodium-normal potassium (HS), inducing low urinary aldosterone (38.1 pmol/24 h; 95% confidence interval, 32.4-44.9). RESULTS: FAD 286 A (10 and 30 mg/kg) decreased urinary free aldosterone by 53 and 87% on the LS diet, and 50 and 75% on the HS. Plasma renin concentration increased three-fold after a 4-week treatment of 30 mg/kg FAD 286 A on the LS diet and did not change on the HS. The combination of FAD 286 A (30 mg/kg) and spironolactone (30 mg/kg) on the LS diet induced a biological picture of severe hypoaldosteronism and was not tolerated, whereas the HS diet prevented these abnormalities. The combination of FAD 286 A (30 mg/kg) and furosemide (30 mg/kg) on the HS diet corrected the diuretic-induced hypokalemia (4.1 +/- 0.2 versus 3.7 +/- 2.2 mEq/l, P < 0.033). CONCLUSION: This experimental model will be useful to screen future aldosterone-synthase inhibitors and study their biological effects in various experimental conditions.

Aldosterone↗
PubMed2006

Alcohol-attributable injuries in admissions to a swiss emergency room--an analysis of the link between volume of drinking, drinking patterns, and preattendance drinking.

BACKGROUND: An association between alcohol consumption and injury is clearly established from volume of drinking, heavy episodic drinking (HED), and consumption before injury. Little is known, however, about how their interaction raises risk of injury and what combination of factors carries the highest risk. This study explores which of 11 specified groups of drinkers (a) are at high risk and (b) contribute most to alcohol-attributable injuries. METHODS: In all, 8,736 patients, of whom 5,077 were injured, admitted to the surgical ward of the emergency department of Lausanne University Hospital between January 1, 2003, and June 30, 2004, were screened for alcohol use. Eleven groups were constructed on the basis of usual patterns of intake and preattendance drinking. Odds ratios (ORs) comparing injured and noninjured were derived, and alcohol-attributable fractions of injuries were calculated from ORs and prevalence of exposure groups. RESULTS: Risk of injury increased with volume of drinking, HED, and preattendance drinking. For both sexes, the highest risk was associated with low intake, HED, and 4 (women), 5 (men), or more drinks before injury. At the same level of preattendance drinking, high-volume drinkers were at lower risk than low-volume drinkers. In women, the group of low-risk non-HED drinkers taking fewer than 4 drinks suffered 47.5% of the alcohol-attributable injuries in contrast to only 20.4% for men. Low-volume male drinkers with HED had more alcohol-attributable injuries than that of low-volume female drinkers with HED (46.9% vs 23.2%). CONCLUSIONS: Although all groups of drinkers are at increased risk of alcohol-related injury, those who usually drink little but on occasion heavily are at particular risk. The lower risk of chronic heavy drinkers may be due to higher tolerance of alcohol. Prevention should thus target heavy-drinking occasions. Low-volume drinking women without HED and with only little preattendance drinking experienced a high proportion of injuries; such women would be well advised to drink very little or to take other special precautions in risky circumstances.

Adult↗
PubMed2005

Can cold or heat shock improve skeletal myoblast engraftment in infarcted myocardium?

OBJECTIVE: Cell death remains a major limitation of skeletal myoblast (SM) transplantation but the patterns of cell survival and proliferation in heart and their potential modulation by thermic stresses like heat shock (HS) and cryopreservation (Cryo) are still incompletely characterized. METHODS: To track SMs in situ, we developed a dual-marker system based on the semiconservative expression of the foreign soluble protein, beta-Galactosidase (beta-Gal) and the constitutive expression of the Y chromosome in a myocardial infarction model. Control medium or Lewis male rat SMs (fresh or subjected to Cryo or HS) were injected in Lewis female rats. RESULTS: There was a massive cell loss early after transplantation in the fresh group, which was only partially compensated for by a subsequent proliferation. Conversely, both Cryo and HS significantly improved early cell survival but blunted subsequent proliferation so that, at 15 days posttransplantation, the total number of engrafted donor-derived Y-positive cells did not differ significantly between the three groups. Most of them expressed a skeletal muscle phenotype. CONCLUSIONS: These data confirm the high death rate of in-scar transplanted myoblasts, demonstrate the ability of those that survive to proliferate and differentiate along the myogenic pathway but do not support the efficacy of either Cryo or HS for increasing the ultimate magnitude of myoblast engraftment.

Adenoviridae↗
PubMed2005

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium.

AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.

Animals↗
PubMed2005

Enhancement of the functional benefits of skeletal myoblast transplantation by means of coadministration of hypoxia-inducible factor 1alpha.

OBJECTIVE: Early cell death remains a major limitation of skeletal myoblast transplantation. Because the poor vascularization of the target scars contributes to cell loss, we assessed the effects of combining skeletal myoblast transplantation with administration of hypoxia-inducible factor 1alpha, a master gene that controls the expression of a wide array of angiogenic factors. METHODS: A myocardial infarction was created in 56 rats by means of coronary artery ligation. Eight days later, rats were randomly allocated to receive in-scar injections of culture medium (control animals, n = 11), skeletal myoblasts (5 x 10(6) , n = 13), adenovirus-encoded hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL, n = 7), or skeletal myoblasts (5 x 10(6)) in combination with an empty vector (n = 3) or active hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL, n = 13). A fifth group (n = 9) underwent a staged approach in which hypoxia-inducible factor 1alpha (1.0 x 10(10) pfu/mL) was injected at the time of infarction, followed 8 days later by skeletal myoblasts (5 x 10(6)). Left ventricular function was assessed echocardiographically before transplantation and 1 month thereafter. Explanted hearts were then processed for the immunohistochemical detection of myotubes, quantification of angiogenesis, myoblast engraftment, and cell survival. RESULTS: Baseline ejection fractions were not significantly different among groups (35%-40%). One month later, ejection fraction had decreased from baseline in control hearts and in those injected with hypoxia-inducible factor 1alpha. In contrast, it did not deteriorate after injections of skeletal myoblasts alone or combined with either the empty vector or active hypoxia-inducible factor 1alpha administered sequentially. The most striking change occurred in the skeletal myoblast plus hypoxia-inducible factor 1alpha combined group in which ejection fraction increased dramatically (by 27%) above baseline levels and was thus markedly higher than in all other groups ( P = .0001 and P = .001 vs control animals and animals receiving hypoxia-inducible factor 1alpha, respectively). Compared with skeletal myoblasts alone, the coadministration of hypoxia-inducible factor 1alpha resulted in a significantly greater degree of angiogenesis, cell engraftment, and cell survival. CONCLUSION: Induction of angiogenesis is an effective means of potentiating the functional benefits of myoblast transplantation, and hypoxia-inducible factor 1alpha can successfully achieve this goal.

Adenoviridae↗
PubMed2005

Compliance of abdominal aortic aneurysms evaluated by tissue Doppler imaging: correlation with aneurysm size.

OBJECTIVES: Several studies have shown that an increase in abdominal aortic aneurysm (AAA) growth rate occurs when the diameter reaches 40 to 50 mm. AAA expansion is related to remodeling of the parietal extracellular matrix. The parietal mechanisms involved in this critical phase of sudden increase remain unexplained. Analysis of AAA wall movements and determination of AAA compliance may provide information about the constitution of the arterial wall. If a change in parietal wall motion somewhere between 40 and 50 mm could be shown, this would contribute to the understanding of the growth of AAA. Furthermore, it would provide a valuable additional parameter for AAA monitoring. This study had two aims: first, to evaluate the relationship between AAA compliance and maximum diameter using the tissue Doppler imaging system; and second, to test the hypothesis of a change in AAA behavior at around 45 mm in diameter. METHODS: Fifty-six patients with AAA (mean diameter, 39 mm) were prospectively investigated using the tissue Doppler imaging system, which provides information concerning arterial wall motion. Maximum mean segmental dilation (MMSD), segmental compliance, pressure strain elastic modulus (Ep), and stiffness were determined and related to the maximum diameter of AAA. Results After natural log transformation of all variables, there was a significant positive linear relationship between maximum diameter and both MMSD (P < .001) and segmental compliance (P < .001) but not with Ep or stiffness (P = .37 and .22, respectively). MMSD and segmental compliance were significantly higher in AAA > or = 45 mm than in AAA < 45 mm (P < .0002 and <. 004, respectively). Ep and stiffness tended to decrease in larger AAAs, but this was not statistically significant (P < .43 and .24, respectively). Dispersion of Ep and stiffness values seemed to be wider among AAA < 45 mm compared with those > or = 45 mm. CONCLUSION: Compliance parameters can easily be measured during routine AAA ultrasound monitoring using the tissue Doppler imaging system. The study showed an increase in MMSD and segmental compliance as well as a nonsignificant trend toward increased distensibility (decreased Ep and stiffness) with increased AAA diameter. A change in dispersion of AAA distensibility may appear around 45 mm in diameter, but a larger study will be needed to clarify this.

Abdominal Wall↗
PubMed2005

Arterial and renal consequences of partial genetic deficiency in tissue kallikrein activity in humans.

Tissue kallikrein (TK), the major kinin-forming enzyme, is synthesized in several organs, including the kidney and arteries. A loss-of-function polymorphism of the human TK gene (R53H) induces a substantial decrease in enzyme activity. As inactivation of the TK gene in the mouse induces endothelial dysfunction, we investigated the vascular, hormonal, and renal phenotypes of carriers of the 53H allele. In a crossover study, 30 R53R-homozygous and 10 R53H-heterozygous young normotensive white males were randomly assigned to receive both a low sodium-high potassium diet to stimulate TK synthesis and a high sodium-low potassium diet to suppress TK synthesis, each for 1 week. Urinary kallikrein activity was 50-60% lower in R53H subjects than in R53R subjects. Acute flow-dependent vasodilatation and endothelium-independent vasodilatation of the brachial artery were both unaffected in R53H subjects. In contrast, R53H subjects consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared with R53R subjects. Renal and hormonal adaptation to diets was unaffected in R53H subjects. The partial genetic deficiency in TK activity is associated with an inward remodeling of the brachial artery, which is not adapted to a chronic increase in wall shear stress, indicating a new form of arterial dysfunction affecting 5-7% of white people.

Adult↗
PubMed2004

Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy?

BACKGROUND: The benefits of skeletal myoblast (SM) transplantation on infarcted myocardium have been investigated extensively; however, little is known about its effects in nonischemic cardiomyopathy models. To address this issue, we tested SM transplantation in CHF147 Syrian hamsters, a strain characterized by a delta-sarcoglycan deficiency that phenotypically features the human setting of primary dilated cardiomyopathy. METHODS AND RESULTS: Cell culture techniques were used to prepare approximately 5x10(6) muscle cells from autologous tibialis anterior muscle, of which 50% were SMs (desmin staining). The cells were injected in 6 sites across the left ventricular wall (n=14). Control animals (n=12) received equivalent volumes of culture medium. Left ventricular systolic function was assessed in a blinded fashion from 2D echocardiographic left ventricular fractional area change, before transplantation, and 4 weeks later. Explanted hearts were processed for the detection of myotubes and quantification of fibrosis. Baseline functional data did not differ between the 2 groups. Four weeks after transplantation, 6 of the 10 surviving grafted hamsters were improved compared with 0 of the 8 survivors of the control group. This translated into a 6% decrease in fractional area change in controls compared with a 24% increase in cell-transplanted hamsters (P=0.001). Engrafted myotubes were consistently detected in all SM transplanted hearts by immunohistochemistry, whereas fibrosis was not worsened by cell injections. CONCLUSIONS: These data suggest that the functional benefits of SM transplantation might extend to nonischemic cardiomyopathy.

Animals↗
PubMed2004

Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium.

OBJECTIVES: The present study was designed as a face-to-face functional comparison of human skeletal myoblasts (SMs) and CD133(+) bone marrow-derived hematopoietic progenitors in an animal model of semichronic myocardial infarction. BACKGROUND: Compared with SMs, bone marrow-derived cells have the advantage of plasticity and might more effectively regenerate ischemic cardiac tissue. However, few data exist on the comparative efficacy of these two cell types in semichronic infarcts. METHODS: A myocardial infarction was created by coronary ligation in 32 nude rats. Ten days later, rats received in-scar injections of human SMs, CD133(+) progenitors, or culture medium. Left ventricular function was assessed before and one month after transplantation by echocardiography and pressure-volume loops. Immunofluorescence, polymerase chain reaction, and in situ hybridization were used to detect cells grafted in the hearts. RESULTS: One month after transplantation, left ventricular ejection fraction decreased by 8 +/- 4% in controls, whereas it increased by 7 +/- 3% in CD133(+)-grafted hearts (p = 0.0015 vs. controls) and further by 15 +/- 5% in SM-treated hearts (p = 0.008 vs. controls). Systolic indices yielded by pressure-volume loops paralleled these data. Engrafted myotubes were identified in all SM-treated hearts by immunofluorescence, whereas in CD133(+)-grafted hearts, few human cells were only detected by polymerase chain reaction. CONCLUSIONS: In the setting of postinfarction scars, the transplantation of bone marrow-derived CD133(+) progenitors improves cardiac function, but this benefit is not superior to that afforded by myogenic cells.

AC133 Antigen↗
PubMed2004

Integrating drug pharmacokinetics for phenotyping individual renin response to angiotensin II blockade in humans.

Renin release into plasma has been used to investigate the drug dose-dependence of renin-angiotensin system inhibition because it is proportional to the interruption of the permanent negative feedback loop of angiotensin II on renin secretion. We investigated the 24-hour between-subject differences in renin profiles by analyzing the time-dependence of individual renin responses in 16 mildly sodium-depleted normotensive subjects exposed in a 4-period crossover study to single oral doses of 8- and 16-mg (C8 and C16) candesartan cilexetil and 80- and 160-mg (V80 and V160) valsartan. C8 had a similar effect to V160 in terms of the increase in active renin concentration and decrease in blood pressure. C16 had the strongest effect and V80 the weakest effect on renin release. Within- and between-subject variability was more marked for valsartan pharmacokinetics than for candesartan pharmacokinetics and influenced variability in renin response. To eliminate some of the variability caused by the pharmacokinetics of each drug, we corrected the area under time curve of plasma renin levels by that of plasma drug levels to obtain an individual normalized index of renin release or "renin/pharmacokinetic index". In these experimental conditions, this index was found to be a reproducible individual characteristic affecting renin response, in addition to the pharmacokinetics and pharmacological properties of angiotensin II type-1 receptor antagonists. The pharmacokinetic-pharmacodynamic model of renin release described here could be of value for the identification and investigation of renin release abnormalities in patients with hypertension and for the comparison of renin-angiotensin system blockers.

Administration, Oral↗
PubMed2004

Aortic compliance in healthy subjects: evaluation of tissue Doppler imaging.

Increased compliance of abdominal aortic aneurysms at maximum diameter over time might be related to rupture. Compliance could, therefore, be valuable in their management. However, such measurement requires a sophisticated system. An original arterial wall-motion measurement technique, based on tissue Doppler imaging (TDI) and providing segmental exploration, was applied to the study of aorta walls. We report its validation in healthy subjects. Technical feasibility was reliable. The time required for sequence acquisition and transfer was suitable for routine clinical use and the quality of the sequences provided precise identification of the aorta wall/lumen interface and accurate segmentation. The values characterising normal aortic compliance were similar to those previously published, and the initial results concerning reproducibility were appropriate for clinical studies. Further refinements may improve it. This study validates the TDI system for measurement of abdominal aortic compliance in healthy subjects. Study of application to aneurysm compliance is in progress.

Adult↗
PubMed2004

Compliance of abdominal aortic aneurysms: evaluation of tissue Doppler imaging.

Expansion of abdominal aortic aneurysms (AAA) is due to remodeling of the parietal extra-cellular matrix and may lead to rupture. This remodeling is reflected by compliance which may be an indicator of AAA behavior and thus useful for clinicians. Tissue Doppler Imaging (TDI) is an ultrasonographic modality which allows wall motion measurements along an arterial segment. It has previously been evaluated in normal aortas and was then evaluated in thirty-five patients with AAA. Mean values (+/-standard deviation) characterizing maximum diameter AAA compliance were dilation 809 mum (+/-465), strain 2.2% (+/-1), pressure strain elastic modulus 3.94 10(5) Pa [3.25; 4.8] and stiffness 28.8 [24; 34.5], last values being expressed as geometric mean [interquartile range]. They were in accordance with those previously obtained with other systems. Segmental parameter values were maximum mean segmental dilation 534 mum (+/-305) and segmental compliance 14.6 (+/-8.3) 10(-2) mum/Pa. Reproducibility was appropriate for clinical studies. The TDI system is simple and reliable for measurement of AAA compliance, and compliance can easily be recorded during routine ultrasound control.

Abdominal Wall↗
PubMed2004

Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the angiotensin II-renin feedback interruption.

Interrupting the renin-angiotensin system (RAS) with a usual daily dose of a single-site RAS inhibitor does not achieve complete and long-lasting pharmacologic blockade. Hormonal and BP effects were compared for 48 h after administration of single oral doses of 300 mg (high dose) of the renin inhibitor aliskiren (A300) and 160 mg (standard antihypertensive dose) of the AT1 receptor antagonist valsartan (V160) and their combination each at half dose (A150+V80) in 12 mildly sodium-depleted normotensive individuals. In this double-blind, placebo-controlled, randomized, four-period crossover study, A300 decreased plasma renin activity and angiotensin I and II levels for 48 h, stimulated immunoreactive active renin release more strongly than V160, and decreased urinary aldosterone excretion for a longer duration than V160. In contrast to V160, the A150+V80 combination did not increase plasma angiotensins. The renin and aldosterone effects of the A150+V80 combination were similar to those of A300 and greater than those of V160. When plasma drug concentrations were taken into account, the A150 +V80 combination had a synergistic effect on renin release. The A150+V80 combination lowered BP at least as effectively as either higher dose monotherapy. In conclusion, in mildly sodium-depleted normotensive individuals, the long-lasting effects of aliskiren alone or in combination with valsartan on plasma immunoreactive active renin and urinary aldosterone effects demonstrate strong and prolonged blockade of angiotensin II at the kidney and the adrenal level. Moreover, a renin inhibitor and AT1R antagonist combination may provide synergistic effects on RAS hormone levels.

Administration, Oral↗
PubMed2004

Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable?

PURPOSE: To evaluate the intra- and interreader agreement of two-dimensional computed tomographic (CT) measurements of pulmonary nodules less than 2 cm in diameter. MATERIALS AND METHODS: Three readers independently made three serial measurements of each of 54 pulmonary nodules measuring 3-18 mm that had been observed on standard-dose multisection CT images obtained in 24 patients who ranged in age from 36 to 81 years (mean age, 54.6 years). There were 14 women (58%), who ranged in age from 43 to 81 years (mean age, 58.9 years), and 10 men (42%), who ranged in age from 36 to 65 years (mean age, 48.5 years). The largest transverse cross-sectional diameter of each nodule was measured at picture archiving and communication system, or PACS, workstations by using high-spatial-resolution reconstructed CT images and identical window settings. Intra- and interreader agreement were determined by using methods described by Bland and Altman: the coefficient of repeatability for intrareader agreement, and methods derived from the 95% limits of agreement defined by Bland and Altman for interreader agreement. RESULTS: The repeatability coefficients were 1.70, 1.32, and 1.51 mm for readers 1, 2, and 3, respectively. The 95% limits of agreement for the difference among readers were -1.73 and 1.73. CONCLUSION: Two-dimensional CT measurements are not reliable in the evaluation of small noncalcified pulmonary nodules.

Adult↗