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Biomedical subjects

S Robert

Publications and source records attributed to S Robert.

16 recordsLinked to original sources

Transcranial Doppler to evaluate the effects of antihypertensive medication on cerebral blood flow velocity.

The effect of oral nifedipine on cerebral blood flow velocity was studied in six elderly hypertensive patients using transcranial Doppler. Serial measurements of blood pressure (BP), middle cerebral artery (MCA) flow velocity and nifedipine serum concentrations were obtained over an 8-hour period. The authors found a significant inverse relationship between MCA velocities and nifedipine concentrations, independent of BP changes. These results are consistent with a direct vasodilatory effect of nifedipine on cerebral vessels and support the use of TCD in pharmacodynamic investigations of the cerebral vasculature.

Aged

Determination of free serum digoxin concentrations in digoxin toxic patients after administration of digoxin fab antibodies.

Digoxin fab antibody therapy is known to interfere with digoxin immunoassays causing spurious serum digoxin concentrations. The reliability and precision of three digoxin immunoassays--Baxter Dade Stratus (BDS), Syva affinity column enzyme-mediated immunoassay (EMIT), and the reference assay Abbott TDx fluorescence polarization immunoassay following ultrafiltration (FPIA-UF)--were compared in eight digoxin toxic patients treated with digoxin fab antibodies. Five to eight blood samples were drawn serially up to 204 h post digoxin fab therapy. The serum digoxin concentration in each sample was determined by each of the three assays. The mean (+/- SD) area under the serum digoxin concentration-time curve was significantly lower for FPIA-UF than for BDS or EMIT (86.1 +/- 58.2 vs 158.1 +/- 88.6 and 176.3 +/- 115.3 h.ng/ml p less than 0.01, respectively). BDS correlated better with FPIA-UF (r2 = 0.71) than did EMIT (r2 = 0.45). Predictive performance of the BDS and EMIT assays demonstrated that the mean prediction error (bias) (0.62 vs 0.78 ng/ml) and the mean squared prediction error (precision) (0.48 vs 0.76) differed significantly from zero (p less than 0.05). However, BDS had significantly less bias and greater precision than did EMIT (p less than 0.05). In the presence of digoxin fab antibodies, BDS is a better predictor of free serum digoxin concentration than is EMIT, but both have considerable bias. Based on these results, FPIA-UF should be the assay of choice for determining free serum digoxin concentrations during fab therapy.

Adult

"Brain attack": an indication for thrombolysis?

OBJECTIVE: The primary objective of this article is to introduce the reader to the use of thrombolytics in the acute treatment of ischemic stroke. Theory and experimental evidence to support this approach are emphasized in addition to potential adverse effects of thrombolysis. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: Studies were selected for detailed review if they involved stroke patients and addressed possible toxicities of therapy. Any abstracts concerning ongoing clinical trials also were reviewed. DATA EXTRACTION: Data from animal investigations using tissue plasminogen activator for the acute treatment of several models of cerebral ischemia were used to support the importance of early treatment (within six hours of symptom onset). Also, studies performed in animal models of stroke revealed that thrombolysis could be accomplished safely in acute ischemic stroke. All human studies published to data are anecdotal case reports, but point to the safety of thrombolysis if administered early. Reviews of ongoing multicenter trials are taken from published abstracts and proceedings. DATA SYNTHESIS: Thrombolysis holds promise as a hyperacute therapy for acute stroke; however, the risk of intracerebral hemorrhage remains. Crucial to the success of this and any other therapy for acute stroke is the ability to treat patients within hours of symptom onset. Also, the importance of concomitant medications such as heparin and aspirin has not yet been addressed. CONCLUSIONS: Pharmacists need to be knowledgeable of new treatments of stroke and the risks associated with them. As patient educators, pharmacists can contribute to public awareness by promoting the early recognition of stroke symptoms. As pharmacotherapists, pharmacists need to understand the risks and the important monitoring parameters related to thrombolysis. The results of ongoing multicenter clinical trials are awaited before making a final judgment on the usefulness of thrombolysis in acute ischemic stroke.

Anistreplase

Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients.

OBJECTIVE: The aim of this preliminary investigation was to evaluate the use of aminoglycoside serum concentrations as a surrogate measure of the glomerular filtration rate (GFR) in comparison with other measured and empiric methods against inulin, the criterion standard measure of GFR. DESIGN: A consecutive sample of all eligible patients. SETTING: An eight-bed medical intensive care unit in a university-affiliated tertiary-care teaching hospital. PATIENTS: Ten critically ill medical patients receiving gentamicin or tobramycin for presumed or documented gram-negative bacillary infection were enrolled in the study. The patients were mechanically ventilated and had underlying organ system dysfunction. All ten patients completed the study. INTERVENTION: Patients underwent renal functional assessment by measured inulin (Cl(in)) and 24-hour urinary creatinine clearance (Clcr). Aminoglycoside serum concentrations were used to estimate GFR and were compared with the two measured methods and a creatinine clearance calculated with the Cockcroft-Gault method (ClCG). All evaluations were performed the same day. RESULTS: Cl(in) averaged 51.6 +/- 35.0 mL/min and serum creatinine ranged from 0.3 to 5.4 mg/dL (26.5 to 477.3 mumol/L). Steady-state peak and trough aminoglycoside concentrations were 6.1 +/- 1.4 and 1.3 +/- 0.9 micrograms/mL, respectively. There were no statistically significant differences between the various methods, although the aminoglycoside-calculated GFR (Cl(amg)) 95 percent confidence intervals were smaller than Clcr and ClCG compared with Cl(in). Mean absolute errors were smaller with Cl(amg) than with Clcr and ClCG. Regression results indicated that only Cl(amg) and ClCG demonstrated agreement with Cl(in) (lines not different from y = x). However, the Cl(amg) showed closer agreement, with a mean square error almost half that of ClCG (9.6 vs. 18.1). CONCLUSIONS: Cl(amg) can be used routinely as an estimate of GFR in critically ill patients, with less error than empiric methods.

Adult

Cerebral blood flow changes with enalapril.

Patients with carotid artery occlusive disease (CAOD) may be at increased risk of iatrogenic cerebral hypoperfusion. Using the 133xenon-inhalation technique, we evaluated the effects of enalapril on regional cerebral blood flow (CBF) in 14 patients with chronic hypertension, 7 with CAOD and 7 without CAOD (no CAOD). Regional CBF and blood pressure were measured before and 60 minutes after a single dose of enalapril. Changes in mean arterial pressure after enalapril were not significantly different between the two groups: CAOD -4.67 +/- 8.7 mm Hg, no CAOD -6.18 +/- 8.2 mm Hg. Changes in mean CBF after enalapril were also not statistically different: CAOD -1.0 +/- 3.9, no CAOD 1.0 +/- 2.8. In the CAOD group only, however, changes in CBF were significantly related to increasing age (r = -0.9253, p less than 0.01), such that in patients 65 years or older CBF tended to decrease, whereas in younger patients it increased. Elderly patients with CAOD may be at increased risk of iatrogenic cerebral hypoperfusion, and it may be appropriate to evaluate prospectively the effects of antihypertensive medications on CBF.

Age Factors

[Specific induction by phorbol ester of the gene transcription and of the activity of ornithine decarboxylase in two control and transformed epithelial cell lines. Modulator effect of anti-inflammatory agents].

The mechanism of ornithine decarboxylase (ODC) induction by phorbol ester (TPA) has been studied in two permanent epithelial cell lines, a control (Ctr) and a Benzo (a) pyrene transformed line (BaP-tr); the degree of ODC gene expression (ODC-mRNA) was evaluated in comparison to the ODC activity. A small dose of TPA (4 x 10(-8) M) highly induced ODC activity in these cells. The induction levels differed however, corresponding respectively to 4:1 (induced: basal ODC) in Ctr cells and to 2:1 in BaP-tr cells. This difference reflected the variation of ODC gene expression; the ODC-mRNA induction was 6:1 in Ctr cells and 3:1 in BaP-tr cells. Repetitive TPA treatment decreased the ODC induction in these cells, as compared to that resulting from a single TPA treatment. Studies of ODC modulation were performed in presence of anti-inflammatory agents. In the two cell lines, Indomethacin (anti-cyclooxygenase) did not change the level of ODC induction by TPA. Nordihydroguaiaretic acid (NDGA, anti-lipoxygenase) inhibited this induced ODC. These results differed from that obtained in vivo in mouse skin. Dexamethasone (DXME, anti-phospholipase A2) showed different action according to treatment time. Used together with TPA (t0), DXME inhibited ODC induction by the carcinogen; with three hours delay after TPA (t3), DXME treatment stimulated ODC in the cells. This divergent action may be reproduced by Actinomycin D, while Cycloheximide only exhibited constant inhibition. Studies now in progress suggested that the inhibition of TPA induced ODC by DXME may reflect ODC gene repression, as for the stimulating effect it could be related to ODC post-transcriptional modulation, owing to the decrease of proteolytic action.

Animals

The electrical and spectroscopic properties of planar asymmetrical membranes incorporating chlorophyll a and plastoquinone-9. Model of incorporation of chlorophyll a and plastoquinone-9.

We have studied the incorporation of chlorophyll a and plastoquinone-9 in Montal-Mueller membranes. In particular, we have been interested by the influence of both the lipid : chlorophyll a ratio and the asymmetry of incorporation of the constituents on the electrical and fluorescence spectroscopic properties of the planar membranes built up from these constituents. The phospholipid matrix was made from phosphatidylethanolamine and phosphatidylserine. The monitoring of the fluorescence spectral properties of chlorophyll a incorporated in various concentrations leads to the conclusion that chlorophyll a is incorporated in the bilayers in monomeric form inside microdomains. It is shown that chlorophyll a is positioned in these microdomains in such a way that the porphyric ring is interacting with the polar head of the lipid molecules where the interface polarity shows a dielectric constant varying between 25 and 35. The phytyl chain is embedded in the bilayer core, serving as an anchor, running parallel to the aliphatic chains of the phospholipids. We have also monitored the position of the plastoquinone-9 molecules within the bilayer. We found that plastoquinone-9 is incorporated in the center plane of the bilayer, increasing the thickness of the bilayer. This result confirms evidence, gathered in the literature from monolayer and differential scanning calorimetry studies, that long chain quinones and especially plastoquinone-9 are embedded deeply within the hydrophobic core of the bilayer. We also show that when chlorophyll a and plastoquinone-9 are present together in the bilayer, the quinolic ring of the plastoquinone-9 molecule positions itself in the free volume created by the bulky porphyric ring of a chlorophyll a molecule.

Chemical Phenomena

Is there a reliable index of glomerular filtration rate in critically ill patients?

Assessment of renal function in critically ill patients is important for appropriate individualization of dosage regimens and nutrition, but is complicated by a high incidence of acute renal failure (ARF). The most common cause of ARF in intensive care unit (ICU) patients is hypoperfusion. Other causes of ARF include intrinsic injury, nephrotoxicity, and postrenal obstruction. ARF is associated with a decreased glomerular filtration rate (GFR), reduced or maintained urine output (nonoliguric renal failure), and alterations in other commonly obtained urinary indices. Twenty-four-hour or shorter urinary creatinine clearance studies may overpredict GFR as creatinine is both filtered and secreted. The use of serum creatinine in empiric predictive equations is impaired in ICU patients because of decreases in creatinine production due to immobilization and malnutrition or increases in creatinine production due to catabolic illnesses. Adjustment of empiric methods by employing lean body weight, ideal body weight, or corrected serum creatinine values has not been evaluated against uncorrected values in this population, but is routinely performed in clinical practice. Inulin and radiolabeled substances are not practical for routine clinical use and may overpredict GFR in ARF due to backleak of large molecular-weight substances through the tubules. Comparative clinical trials have shown essentially equivalent performance of empiric methods relative to 24-hour urinary creatinine clearance in adults. No studies have compared these methods to a reference method for determination of GFR. Until conclusive data become available, clinicians should cautiously compare results from at least two independent methods of assessment to estimate renal functional impairment in ICU patients.

Acute Kidney Injury

Monitoring serum digoxin concentrations during digoxin immune Fab therapy.

Measurement of serum digoxin concentrations (SDCs) is used routinely in the diagnosis of digoxin toxicity. Following administration of the antidote, digoxin immune antigen binding fragments (Fab), SDC monitoring is hampered by assay-related problems because of the presence of Fab in the serum. Recent evidence has suggested several available methods to monitor free SDC during Fab therapy. This report describes the utility of monitoring free SDC following Fab administration. Free SDCs were obtained using an ultrafiltration and fluorescence polarization immunoassay system in three patients over periods of up to 204 hours after Fab administration. In each case, the decline in free SDC was temporally related to the resolution of digoxin toxicity; in one case, digoxin intoxication recurred and was associated with a rebound increase in free SDC. In addition to the therapeutic benefits, prospective monitoring of free SDC in two of the patients also may have resulted in cost savings secondary to reduced hospital stay or less use of Fab.

Adult

Effect of feeding regimen on behavior of growing-finishing pigs supplemented or not supplemented with folic acid.

The effect of restricted feeding on the frequency of abnormal behaviors and gastric ulcers was investigated in 72 market pigs. Half of the pigs were fed restricted (R) amounts of feed twice a day (0800 and 1600) and received 90 to 95% of the intake recorded for the other half, which were allowed ad libitum (A) access to feed with addition of feed once a day at 0800. In each feeding group, 24 pigs were supplemented with folic acid. The animals were housed in pairs and the behavior of each animal was recorded during 24 h at 18 and 20 wk of age. The results showed that the A group ate more frequently during light hours than the R group at 18 wk, but not at 20 wk. However, the frequency of eating behavior was higher in the R group than in the A group at 20 wk during the 2 h after feed distribution. Feeding regimen had an effect on the frequency of redirected behaviors during the 2 h preceding feed distribution. The percentage of time spent nibbling on the penmate was higher in R than in A pigs at 18 wk, whereas that of rooting on the penmate was higher at 20 wk. Moreover, the proportion of pigs performing redirected behaviors was higher in the R than in the A group at both ages. The overall frequency of gastric ulcers was similar in pigs given the two feeding treatments, but severe ulcers were more frequent in the R than in the A group. Some interactions were also found between feeding regimen and folic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Effects of continuous stray voltage on health, growth and welfare of fattening pigs.

The effects of continuous stray voltage were evaluated on growing-finishing pigs between the ages of 8 and 21 weeks. Seventy-two pigs were assigned to six blocks of 12 animals each. The following treatments were randomly distributed in each block according to a 2 x 3 factorial design: feeding level (restricted or ad libitum) and voltage level (0, 2 or 5 volts (V) as a difference of potential between feeder or drinker and the metallic floor). During daytime, stray voltage at 5 V decreased (p less than 0.05) the eating frequency in both feeding groups and the drinking frequency in restricted-fed pigs. The mean duration of drinking bouts and the total time spent at the drinker were also lower (p less than 0.05) in this last group during the hour following meal distribution. Daily feed intake and average daily gain were lower (p less than 0.05 and less than or equal to 0.08, respectively) in the 5 V group than in the 2 V and the control groups from 17 to 21 weeks of age. Finally, gastric lesions, hematological and biochemical variables were not affected (p greater than 0.05) by stray voltage.

Animals

Ticlopidine: a new antiplatelet agent for cerebrovascular disease.

Ticlopidine is a new prototype antiplatelet drug chemically unrelated to currently available agents. It causes an alteration in platelet membrane reactivity to a variety of aggregating stimuli and a marked prolongation of bleeding time, the mechanism of which remains unclear. Two major phase III multicenter trials, the ticlopidine-aspirin stroke study (TASS) and the Canadian-American ticlopidine study (CATS) reported that the agent may reduce the occurrence of stroke, myocardial infarction, or vascular death in patients of both sexes who have had recent cerebral ischemia. Ticlopidine has been well tolerated in preliminary studies, with the most commonly described adverse effects being rash and gastrointestinal complaints. The most important adverse effect is neutropenia, which was reported in both TASS and CATS, approximating a frequency of 0.9% and 0.8%, respectively. Ticlopidine holds considerable promise as adjunctive therapy in selected patients.

Cerebrovascular Disorders

Body composition analysis by bioelectrical impedance: the effects of time of day and body side on estimated gentamicin pharmacokinetics.

To assess if repetitive measures are useful in a clinical setting, the effects of time of day and body side on bioelectrical impedance (BI) measurements were evaluated. Fifteen healthy, male volunteers underwent serial BI measurements at 0, 3, 6, 9, 24, and 48 hours on both sides of the body using a four-electrode plethysmograph. Analysis of variance for repeated measures indicated that the mean resistance (R) value of the right side was statistically lower from that of the left side (447 +/- 27.9 vs 457 +/- 29.1 ohms; p = 0.006). Both R and reactance (Xc) varied significantly over time. For R, the mean response at 0, 6, 9, and 48 hours was different from the overall mean of the remaining time points (p less than 0.007). Only times 6 and 24 hours were significantly different for Xc (p less than 0.006). No relevant time and side effects were noted in calculated gentamicin pharmacokinetic parameters on incorporation of BI measurements into impedance-derived predictive equations for clearance, volume of distribution, and elimination constant. Correlation coefficients of reliability were high within 1 day and across days (R greater than or equal to 0.8407). These data suggest that under normal conditions, BI analysis provides reliable results, and that time and side standardizations in its measurements are not necessary.

Adult

Effects of intramuscular injections of folic acid on serum folates, haematological status and growth performance of growing-finishing pigs.

In a first trial, 48 piglets aged 5 weeks, grouped into 6 blocks of 8 pigs each, were used to determine the effect of intramuscular injections of folic acid on serum folates, haematological status, growth performance and carcass characteristics. Each block consisted of 2 pens of 4 pigs; in one pen, pigs received, by weekly intramuscular injections, an increasing volume of a solution containing 5 mg/ml folic acid, while in the other the animals were non-injected controls. The concentration of serum folates in treated pigs was 19% higher (P = 0.005) than in controls. There was no effect of treatment (P greater than or equal to 0.29) on haemoglobin and haematocrit. During the starting period, (5-11 weeks) average daily gain was not influenced by folic acid injections but feed intake and feed conversion were decreased (P = 0.07 and P = 0.05 respectively). No effect of folic acid (P greater than or equal to 0.23) was noted from 11-23 weeks of age, suggesting that the supplement was suboptimal during the growing-finishing period. In a second trial, 72 piglets aged 9 weeks were assigned to 6 blocks of 12 animals each. The following treatments were randomly distributed in each block according to a 2 x 3 factorial design: level of feeding (restricted vs ad libitum) and weekly intramuscular injections of increasing volume of solutions containing either 0, 15 or 30 mg/ml of folic acid. The variables studied were the same as in Trial 1. Concentrations of serum folates varied quadratically (P = 0.0001) with the dose injected, a plateau being attained with injections of 15 mg/ml. There was no effect of treatment (P = 0.043) on haemoglobin and haematocrit. During the growing period (9-15 weeks), no effect (P greater than or equal to 0.72) of folic acid was noted on growth performance. However, during the finishing period (15-21 weeks), folic acid given at a dose of 30 mg/ml decreased (P = 0.006) feed intake while no effect (P greater than or equal to 0.13) of the vitamin supplementation was noted on average daily gain and feed conversion. In both trials, there was no effect (P greater than or equal to 0.21) of any treatments on carcass characteristics. These results indicate that a supplement of folic acid administered by intramuscular injections was effective in increasing concentration of serum folates of starting or growing-finishing pigs. This supplement may be associated with a decrease in feed intake.

Animal Feed

[Anesthesia for extracorporeal lithotripsy in the treatment of renal lithiasis].

Extracorporeal shock wave lithotripsy has become the main technique for treating renal lithiasis. It has many repercussions on anaesthesia. The fundamental technical concepts of lithotriptors are reviewed. The problems due to the different systems (electrohydraulic or piezoelectric--the most widespread in France) are discussed. Electrohydraulic systems, which are more adapted to the treatment of large stones (diameter greater than 2 cm), require the immersion of the patient. As a result, there are analgesic, cardiovascular, respiratory and temperature repercussions on the anaesthetic management of these patients. General anaesthesia is generally more appropriate for this technique. On the other hand, piezoelectric systems are more adapted to the treatment of medium-sized or small calculi (diameter less than 2 cm), and do not require immersion. Anaesthesia is often not required for the use of this technique, but, if necessary, local, regional or general anaesthesia may be used. For either technique, the anaesthetic protocol must be adapted to the patient's and the surgical indications.

Anesthesia