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Biomedical subjects

F Schmitt

Publications and source records attributed to F Schmitt.

At least 19 recordsLinked to original sources
PubMed1998

Early glomerular dysfunction in patients with sickle cell anemia.

The purpose of this study was to analyze the determinants of glomerular filtration in nonnephrotic young adult patients with sickle cell anemia (SCA). We prospectively screened 14 patients with homozygous SCA who had normal plasma creatinine concentrations and normal or moderately elevated albuminuria (< 1 g/d). Inulin, paraaminohippuric acid, and dextran clearances were evaluated and compared with values obtained from a control group (age-matched healthy volunteers). SCA patients had a significantly higher glomerular filtration rate and effective renal plasma flow than controls (146 +/- 9 mL/min/1.73 m2 v 120 +/- 3 mL/min/1.73 m2 [P < 0.01] and 1,052 +/- 69 mL/min/1.73 m2 v 709 +/- 38 mL/min/1.73 m2 [P < 0.001], respectively). We found no correlation between glomerular filtration rate or effective renal plasma flow and hematocrit. Fractional clearance of neutral dextran was significantly elevated in SCA patients for all radii between 3.4 and 5.4 nm. Theoretical analysis of dextran transport through a heteroporous membrane model revealed a slight increase in the mean radius (ro) of restrictive pores (5.68 nm v5.50 nm; P < .001) and no significant difference in shunt pathway (omega o) values. Among the other hemodynamic parameters, the most significant change was a dramatic increase in ultrafiltration coefficient (41.3 +/- 3.6 mL/mm Hg/min/1.73 m2 v 25.1 +/- 2.6 mL/mm Hg/min/1.73 m2; P < 0.001). Our results suggest that hyperfiltration in SCA patients is associated not only with enhanced renal perfusion but also with an alteration in glomerular permeability and with an increase in Kf. This change in Kf is fully in agreement with the large increase in glomerular area previously described in SCA patients. Based on our results and those of previous morphologic studies, we propose that enhanced transglomerular trafficking of macromolecules associated with podocyte stretch lesions (defects) induced by glomerular hypertrophy may play a role in the genesis of this particular form of focal segmental glomerulosclerosis, which is associated with SCA.

Adult↗
PubMed1998

Acute renal effects of AT1-receptor blockade after exogenous angiotensin II infusion in healthy subjects.

In 10 healthy normotensive volunteers on a normal sodium diet, we evaluated the renal effects of a single oral dose of 50 mg of irbesartan (SR 47436, BMS 186295), an angiotensin II AT1-receptor antagonist, in baseline conditions and during an exogenous angiotensin II infusion (2.5 ng/kg/min). We used a double-blind, placebo-controlled, crossover design. Hormones, blood pressure, renal hemodynamics, and urinary electrolytes were measured during each phase. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was performed, and sieving curves were applied on a hydrodynamic model of ultrafiltration. Irbesartan administration was followed by an increase in active renin and plasma angiotensin II concentrations and renal plasma flow without change of systemic blood pressure, glomerular filtration rate, or plasma aldosterone concentration. Irbesartan did not affect either sieving curves or glomerular ultrafiltration determinants. Angiotensin II infusion at 2.5 ng/kg/min elicited a slight pressor response accompanied by a decrease in glomerular filtration rate and renal plasma flow and an enhancement of fractional dextran clearance over the radius range explored (3.4-5.4 nm). The transcapillary glomerular pressure gradient deltaP and the ultrafiltration coefficient kf were computed to increase by 9% and to decrease by 23%, respectively, without change in intrinsic membrane properties. Pretreatment with irbesartan prevented all these effects of angiotensin II.

Adult↗
PubMed1997

Antibiotics induce genome-wide hypermethylation in cultured Nicotiana tabacum plants.

Plant genomic DNA methylation was analyzed by an improved SssI methyltransferase assay and by genomic sequencing with sodium bisulfite. Kanamycin, hygromycin, and cefotaxime (also called Claforan) are commonly used as selective agents for the production of transgenic plants. These antibiotics caused DNA hypermethylation in tobacco plants grown in vitro, which was both time- and dose-dependent. An exposure of the plantlets to 500 mg/liter cefotaxime for 1 month caused the de novo methylation of 3 x 10(7) CpG sites/haploid genome of 3.5 x 10(9) base pairs. It occurred in high, moderate, and low repetitive DNA and was not reversible upon the removal of the antibiotics. Reversion was only observed in progeny grown in the absence of drugs. Analysis of the promoter regions of two single-copy genes, an auxin-binding protein gene and the class I chitinase gene, showed the hypermethylation to be heterogeneous but biased toward CpGs. The hypermethylation of the class I chitinase and the auxin-binding protein promoters was not a consequence of a drug-induced gene amplification.

Anti-Bacterial Agents↗
PubMed1997

Low urine flow reduces the capacity to excrete a sodium load in humans.

Recent studies in rats suggest that vasopressin and the resulting urinary concentrating activity reduce the capacity of the kidney to excrete sodium. The present study investigates the influence of the level of hydration on the excretion of a sodium load in humans. Eight healthy male volunteers (18-35 yr) were studied twice, in random order, under either low (LowH) or high (HighH) hydration. They drank throughout the study either 0.25 (LowH) or 2.0 ml water/kg body wt (HighH) every 30 min. After 1 h equilibration, urine was collected for 2 h before (basal) and 10 h after the NaCl load (5 g NaCl in 250 ml, infused intravenously over 30 min). Differences in excretory patterns between LowH and HighH were mostly confined to the first 4 h after the load. The increase in Na excretion after the load was more intense under HighH than under LowH (+ 10.9 +/- 2.6 vs. + 5.8 +/- 2.7 mmol/h in the first 4 postload h; P < 0.001). Under HighH, urine flow rate (V) increased markedly (+ 41%), with little change in urinary Na concentration (UNa), whereas under LowH, V declined slightly and UNa rose significantly (+ 33%). The capacity to raise UNa seemed to reach a maximum at approximately 280 mM. In both conditions, the changes in UNa observed after the load were positively correlated with basal UNa. After the load, urea excretion increased under HighH and decreased under LowH, whereas K excretion was unaffected in either condition. These results show that sodium excretion is facilitated by an abundant water supply. The less efficient sodium excretion occurring at low V is probably due to the influence of vasopressin on water, urea, and sodium movements across the collecting ducts. These observations suggest that, in everyday life, a low water intake could limit the capacity to excrete sodium. Whether this could contribute to salt-sensitive hypertension remains to be evaluated.

Adult↗
PubMed1997

Multicenter evaluation of new instruments for Alzheimer's disease clinical trials: summary of results. The Alzheimer's Disease Cooperative Study.

The Instrument Development Project of the Alzheimer's Disease Cooperative Study (ADCS) evaluated new assessments in five domains: (a) cognitive function; (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms, and (e) cognition in severely impaired patients. These new instruments demonstrate excellent discrimination between normal controls and patient groups and show adequate validity and reliability. Stability of measurement and sensitivity to longitudinal change were also demonstrated in each of these areas. Examination of several domain-specific questions also contributed new information on the measurement of cognitive function with different subtasks across AD severity levels, the stability of clinical ratings of global change, and the applicability of behavioral assessment across severity levels. The success of this project enhances the state of the art in the measurement of efficacy in AD clinical trials and also provides a basis for future research on improving AD outcome measures.

Activities of Daily Living↗
PubMed1996

Expression of sialyl-Tn in breast cancer. Correlation with prognostic parameters.

To investigate the expression of a simple mucin-type carbohydrate antigen (Sialyl-Tn/STn) and its putative relationship with established or potentially useful clinico-pathologic prognostic parameters in breast cancer, we studied forty-six cases of invasive breast carcinoma in formalin-fixed, paraffin-embedded tissue sections. STn antigen was detected by the HB-STn antibody using an avidin-biotin-peroxidase method. The parameters studied were tumour size, histologic grade, nodal status, proliferative index (with MIB-1), ER expression, ploidy, c-erbB-2 and p53 expression. STn expression was observed in 18 cases (39%) of breast cancer. The expression of STn was associated with axillary node metastasis, ER negativity and c-erbB-2 expression. A tendency towards an association between STn immunoreactivity and high histologic grade was also found. No correlation was observed between STn immunoreactivity and age, tumour size, proliferative index, ploidy and p53 expression. We conclude that the detection of STn immunoreactivity may be useful for predicting the likelihood of lymph node metastasis and that the outcome of patients with breast cancer should be further investigated in order to find whether or not the data of the present study are confirmed in larger series.

Adult↗
PubMed1996

Renal effects of angiotensin I-receptor blockade and angiotensin convertase inhibition in man.

1. The objective was to compare two means of inhibition of the renin-angiotensin system [angiotensin-converting enzyme inhibition and selective antagonism of angiotensin II subtype 1 (AT1) receptor] on renal function in 10 healthy normotensive volunteers on a normal sodium diet. Since mechanisms of action may differ between both drugs, a synergistic action was further studied by combining the two drugs. 2. The design was a double-blind randomized acute administration of either placebo or a single oral dose of enalapril, 20 mg, followed in each case by administration of the AT1 selective antagonist losartan potassium, 50 mg orally. 3. The methods included measurements of hormones (plasma renin activity, plasma aldosterone), blood pressure and renal function from 45 to 135 min after administration of placebo or enalapril, and from 45 to 135 min after losartan and placebo or losartan and enalapril. Renal function was studied using clearance of sodium, lithium, uric acid, inulin and para-aminohippuric acid. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was determined and sieving curves were applied on a hydrodynamic model of ultrafiltration. 4. Losartan did not change plasma renin activity, blood pressure or glomerular filtration rate, but increased significantly renal plasma flow and urinary excretion of sodium and uric acid. Enalapril increased plasma renin activity and renal plasma flow, and decreased blood pressure without natriuretic, lithiuretic or uricosuric effects. The renal vasodilatation was potentiated when losartan and enalapril were combined, despite a further rise in plasma renin. In contrast to enalapril, losartan either alone or in combination with enalapril significantly depressed fractional clearances of dextran of small radii (34-42 A). These changes in fractional clearances of dextran were presumably related to the rise in glomerular plasma flow since the other major determinants of filtration, i.e. transcapillary glomerular pressure gradient, ultrafiltration coefficient and membrane property, were computed as unchanged by either losartan, enalapril or a combination of both. 5. In conclusion, these findings suggest that in normal sodium-repleted man the renal, hormonal and blood pressure effects of AT1 antagonism and angiotensin-converting enzyme inhibition are not strictly similar and could be synergistic.

Adult↗
PubMed1996

Chronic effects of endothelin-3 on blood pressure and renal haemodynamics in rats.

BACKGROUND: Renal vasoconstriction and systemic hypertension are well-known effects of bolus or short-term endothelin administration. However, the role of endothelin as a circulating hormone remains largely unknown. METHODS: The present study explores the effects of endothelin-3 (ET-3) on renal haemodynamics and systemic blood pressure during a 3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley (SD) rats were infused with vehicle (group 1) or ET-3 (group 2), 10 ng/kg per min; group 3, 50 ng/kg per min) delivered via osmotic minipumps into the right jugular vein for 3 days. On day 3 after pump implantation, rats were anaesthetized with Inactin and surgically prepared for assessment of mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR), and renal vascular resistance (RVR). The same parameters were assessed during a 3-h ET-3 infusion study in SD rats (group 4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET-3, 50 ng/kg per min). RESULTS: In 3-day infused rats, ET-3 induced a significant decrease in RPF (-22+/-7% and -26+/-8% for group 2 and group 3 respectively, P<0.05 vs group 1) and an increase in RVR (+40+/-11% for groups 2 and 3; P<0.05 vs group 1); 50 ng/kg per min ET-3 significantly decreased GFR (-17%, P<0.05 vs group 1). MABP was not significantly affected by endothelin infusion. In acute infusion studies a decrease of the same magnitude was seen for the renal haemodynamics values. 50 ng/kg per min ET-3 increased MABP; a systemic effect that disappeared after the 3-day infusion. CONCLUSIONS: This study suggests that intravenously administered ET-3 in the rat has only a transient effect on systemic blood pressure, whereas it induces alterations in renal haemodynamics after both acute and chronic perfusions.

Animals↗
PubMed1996

Vasopressin increases glomerular filtration rate in conscious rats through its antidiuretic action.

To evaluate the possible influence of chronic alterations in urine concentrating activity (CA) on renal hemodynamics, adult male Sprague-Dawley rats were submitted for 7 days to one of three different levels of CA. CA was either reduced by increasing water intake (mixing the food with a gel bringing 1.6 mL water per g food) (Low-CA), or increased by chronic intraperitoneal infusion of 1-desamino 8-D-arginine vasopressin (200 ng/day) (High-CA). Low-CA, High-CA, and control rats were housed in metabolic cages, ate the same quantity of dry food (the amount provided being slightly lower than the spontaneous intake), and had free access to drinking water. The only difference between groups thus concerned the water intake-vasopressin axis. Radiolabeled (14C)inulin was infused chronically by osmotic minipumps. Urine was collected during Days 5, 6, and 7, and blood samples were taken for determination of plasma composition (P), absolute and fractional (FE) urinary excretion, and clearance (C) of inulin, creatinine, urea, and main electrolytes. This protocol produced mean 24-h urine osmolality (Uosm) ranging from 500 to 3500 mosmol/kg H2O without inducing any disturbance in body fluids or plasma osmolality (Posm). Results show that GFR (Cinulin) was markedly and positively correlated with Uosm (r = 0.798, P < 0.001) and free water reabsorption (r = 0.819, P < 0.001). For Uosm = 2500 mosm/kg H2O, GFR was 47% higher than for Uosm = 500 mosm/kg H2O. Ccreat underestimated GFR in High-CA and overestimated it in Low-CA. FEurea was inversely related to Uosm, as expected from the increased reabsorption known to occur at low urine flows. It is tentatively proposed that the intrarenal recycling of urea, triggered by vasopressin and essential to the urinary concentrating mechanism, might influence GFR indirectly by modifying the composition of the tubular fluid at the macula densa and thus the intensity of the tubuloglomerular feedback control of GFR. Even if this mechanism remains to be confirmed, this study unequivocally demonstrates, in normal conscious rats, that the level of urinary concentrating activity has a major influence on basal GFR.

Animals↗
PubMed1996

Effects of new vitamin D analogues on parathyroid function in chronically uraemic rats with secondary hyperparathyroidism.

BACKGROUND: Treatment with calcitriol or its analogue, alfacalcidol often leads to hypercalcaemia, hyperphosphataemia or both in patients which chronic renal failure and advanced secondary hyperparathyroidism. We tested three new vitamin D analogues (CB 1093, EB 1213, GS 1725) in an attempt to identify potentially non hypercalcaemic compounds, capable of decreasing plasma parathyroid hormone (PTH) concentration. METHODS: Male Wistar AF rats aged 12-14 weeks were fed a synthetic, phosphate-rich diet and underwent either sham surgery (control) or a standard two-step 5/6th nephrectomy. Four weeks later, renal function was mildly decreased in the latter. Chronic renal failure rats were then divided into six groups, with 8-10 rats in each group. They received daily 1.p. injections, from days 0 to 4, of either placebo, calcitriol, or one of the following three active vitamin D analogues: CB1093, 0.25 micrograms; EB1213, 0.25 or 1.25 micrograms; and GS1725, 0.025 micrograms/kg body weight per day, respectively. Sham-operated rats received no drug. On day 5, arterial blood was sampled and rats were sacrificed. RESULTS: At predefined dosage schedules, all three compounds significantly decreased plasma immunoreactive PTH levels (except EB1213 at low dose). The decrement was somewhat less marked than that obtained with calcitriol, at the dose of 0.25 micrograms/kg b.w. per day. However, calcitriol induced a marked increase in plasma calcium and phosphate concentrations at that dose, whereas vitamin D analogues led to a more modest increase in plasma calcium level, and none to a worsening of hyperphosphataemia. CB1093 treatment was even associated with a significant decrease in plasma phosphate level. CONCLUSION: All three calcitriol analogues tested are promising as non-hypercalcaemic agents in the treatment of uraemic secondary hyperparathyroidism. However, more prolonged administration to uraemic rats of calcitriol analogues with slightly modified dosage schedules and of calcitriol with lower non-hypercalcaemic dose is required for an optimal comparison before considering clinical trials.

Animals↗
PubMed1995

A bisulfite method of 5-methylcytosine mapping that minimizes template degradation.

The bisulfite method is a highly sensitive approach to 5-methylcytosine mapping that utilizes the capability of the polymerase chain reaction to exponentially amplify DNA. We have observed that the bisulfite reaction results in a significant level of template degradation due to DNA depurination. Furthermore, our data suggest that the DNA fragmentation which occurs limits the sensitivity of the method. We describe a simple solution to limit degradation of the DNA template.

5-Methylcytosine↗
PubMed1995

Magnetostimulation in MRI.

In national and international bodies, there is active discussion of appropriate safety regulations of levels of magnetic field strength in MRI. Present limits are usually expressed in terms of the switching rate dB/dt, but the validity of this is open to debate. Application of the fundamental law of electrostimulation is well-established, both on theoretical and experimental grounds. Application of this law, in combination with Maxwell's law, yields a very simple equation that we call the fundamental law of magnetostimulation. This law has the hyperbolic form of a strength-duration curve and allows an estimation of the lowest possible value of the magnetic flux density capable of stimulating nerves and muscles. Calculations prove that the threshold for heart excitation is much higher than those for nerve and muscle stimulations. Experimental results from us and other authors confirm the correctness of the derived laws for magnetostimulation. In light of these findings, proposed safety limits should be reconsidered.

Electric Stimulation↗
PubMed1995

Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats.

In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this down-regulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF + TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF + TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

[Echo-planar imaging (EPI) of the abdomen].

The time resolution of echoplanar imaging (EPI) allows the acquisition of images < or = 100 ms, thus eliminating motion-related artifacts of the abdomen. Physical limitations are restrictions in signal-to-noise ratio and spatial resolution. Breath-held acquisitions are recommended to avoid spatial misregistrations and to ensure a defined slice position. Clinical studies have demonstrated the usefulness of EPI for the detection and characterization of focal liver lesions. The development of clinical strategies of EPI for abdominal imaging requires the administration of gastrointestinal contrast agents as in computed tomography. Current clinically approved CT contrast agents appear to be applicable for abdominal EPI because of their long relaxation times.

Abdominal Neoplasms↗
PubMed1994

Initial feasibility studies using single-shot EPI for the detection of focal liver lesions.

Echo planar MR imaging (EPI) has been developed to completely eliminate motion artifacts and is currently being prepared for implementation into clinical MR systems. Thus, the purpose of this study was to evaluate the clinical utility of EPI in the detection of focal liver lesions and to compare EPI with in the detection of focal liver lesions and to compare EPI with contrast-enhanced CT. EPI studies were performed on an experimental 1.0 Tesla whole body system using fat-suppressed single-shot spin echo (SE) and inversion recovery (IR) pulse sequences. A total of 26 liver tumors in 12 patients scheduled for liver resection were prospectively examined and correlated with intraoperative ultrasound, surgery, and pathology as the gold standard. Quantitative analysis of EPI was performed by means of liver signal-to-noise and tumor-liver contrast-to-noise calculations. Diagnostic performance compared with contrast-enhanced CT was assessed by means of ROC analysis. Lesion-liver contrast was highest with EPI SE at a TE-time of 70 ms and this technique showed best lesion detectability as measured by area under curve (AUC) values. Among EPI techniques, the IR sequence with an inversion time of 300 ms to null the liver signal showed high lesion-liver contrast but all four reviewers reported problems assessing liver anatomy. Improved EPI techniques may prove useful for screening of focal liver lesions.

Adult↗