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Biomedical subjects

J Biollaz

Publications and source records attributed to J Biollaz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Determination of the polyfructosan sinistrin in biological fluids by HPLC with electrochemical detection.

A sensitive HPLC method with electrochemical detection was developed for the determination of the polyfructosan sinistrin in human plasma and urine. Proteins and interfering components such as glucose were removed from plasma and urine samples by solid phase extraction on C18 cartridges. Chromatographic separations were achieved at 85 degrees C on a 300 mm x 7.8 mm i.d. column, using ion moderated partition chromatography with distilled water at a flow rate of 0.6 ml min-1. After post-column addition of NaOH 0.3 M (0.6 ml min-1), the electrochemical detection of the eluate was performed with a sequence of three potentials (0.05 V, -0.8 V, 0.6 V) of specific pulse duration 300, 100 and 100 ms respectively. Xylose was used as internal standard for the quantitative determinations. The calibration curves were linear (r2 > 0.992) over the working range 5-300 micrograms ml-1. This method has been characterized, validated and applied successfully in a study comparing two modes of glomerular filtration rate determination in healthy volunteers (bolus vs. constant rate infusion of sinistrin).

Chromatography, High Pressure Liquid↗
PubMed1996

Determination of trace lithium in biological fluids using graphite furnace atomic absorption spectrophotometry: variability of urine matrices circumvented by cation exchange solid phase extraction.

A graphite furnace atomic absorption spectrometry method has been developed for the quantitative determination of submicromolar endogenous concentration of lithium in human plasma and urine using pyrolitically-coated graphite tubes in combination with ammonium nitrate matrix modification. This latter treatment could not completely abolish the interferences caused by the matrix, notably in urine samples. The variability of the urinary matrices required an additional standardization procedure by solid-phase extraction on strongly acidic cation exchange cartridges. Matrix-matched samples were used for the establishment of calibration curves with the addition-calibration method. Calibration curves were linear up to 0.72 mumol/l (1.0 > r2 > 0.99). The described method enables accurate measurements of trace-lithium in biological samples at concentrations down to 0.03 mumol/l with intra- and inter-day variabilities < 10%. The method was applied to the determination of trace-lithium levels in urine and plasma samples from healthy individuals enabling the calculation of its fractional excretion (FeLi) (median range 17.3%), a value which reflects the functional capacity of the kidney to reabsorb sodium and water at the proximal tubular portion of the nephron. This sensitive method can thus be used as an investigative and diagnostic tool in various renal pathophysiological conditions, in clinical research, and may also be applied to studies on the trace-lithium status of population in connection with psycho-affective disorders.

Cations↗
PubMed1996

Effects of neuropeptide Y on intrarenal hemodynamics, plasma renin activity and urinary sodium excretion in rats.

Neuropeptide Y (NPY) is a vasoconstrictor peptide possibly involved in the regulation of renal sodium handling and renin release. This investigation was undertaken to assess in conscious normotensive rats the acute effects of a non-pressor dose of NPY on renal plasma flow, glomerular filtration rate, sodium excretion and plasma renin activity. Experiments were also performed during concomitant beta-adrenoceptor stimulation with isoproterenol. NPY per se had no effect on the studied parameters. Renal plasma flow was increased by isoproterenol and was significantly higher when the beta-adrenoceptor stimulant was infused alone (13.4 +/- 2.1 ml/min, p < 0.05, mean +/- SEM) that when administered together with NPY (7.2 +/- 2.0 ml/min). This was also true for glomerular filtration rate (3.3 +/- 0.3 vs. 1.8 +/- 0.3 ml/min, p < 0.01) and plasma renin activity (6.3 +/- 1.7 vs. 2.1 +/- 0.4 ng Ang I/ml/h, p < 0.05). Our data however do not allow to deduce whether the inhibitory effect of NPY on isoproterenol-induced renin release is mediated by changes in intrarenal hemodynamics or a direct effect on juxtaglomerular cells.

Adrenergic beta-Agonists↗
PubMed1995

Whole-blood pharmacokinetics and metabolic effects of the topical carbonic anhydrase inhibitor dorzolamide.

Following a single-dose, open-label, pilot pharmacokinetic study in six subjects, the systemic pharmacokinetics and metabolic effects of dorzolamide after topical ocular administration were investigated in a double-blind, randomised, placebo-controlled study in 12 healthy volunteers. The subjects received a controlled diet on the 5 days before treatment initiation and throughout the study. For 14 days, a bilateral q.i.d. regimen of 3% dorzolamide, consisting of approximately 7.7 micrograms per day (21.3 mumol) dorzolamide hydrochloride, or placebo was given. Blood and urine electrolytes and acid-base profiles were measured 1 day prior to treatment and on days 1, 7 and 14 of treatment, and 24-h urine samples were collected daily. Topically applied dorzolamide was slowly taken up in erythrocytes and eliminated with a half life of approximately 120 days. Compared to the pre-study values, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium and citrate excretions. Two other volunteers given acetazolamide (125 mg q.i.d.) and assessed with the identical set of observations demonstrated marked metabolic changes. In spite of the prolonged and marked inhibition of carbonic anhydrase in red blood cells by dorzolamide, clinically significant metabolic and renal effects were not observed. The ocular tolerability profile was acceptable to all subjects.

Administration, Topical↗
PubMed1995

Characterization of the angiotensin II receptor antagonist TCV-116 in healthy volunteers.

The purpose of this study was to assess the inhibitory effect of TCV-116, an orally active angiotensin II (Ang II) antagonist, on the pressor action of exogenous Ang II and to determine the compensatory rise in plasma renin activity and Ang II levels. Twenty-three male volunteers were treated for 8 days in a double-blind fashion with either placebo or TCV-116 (1, 2, or 4 mg PO daily) and challenged on the first, fourth, and eighth days with repeated bolus injections of Ang II. An additional 4 subjects received 8 mg PO daily in a single-blind fashion. The inhibitory effect on the systolic blood pressure response to Ang II was long lasting and clearly dose related. Six hours after 4 mg TCV-116, the systolic blood pressure response to a given dose of Ang II was reduced to 40 +/- 4% and 35 +/- 8% of baseline value on days 1 and 8, respectively. TCV-116 induced a dose-related increase in plasma renin activity and Ang II levels that was more pronounced on the eighth than on the first day of drug administration. Despite this compensatory mechanism, the relation between the time-integrated systolic blood pressure response to Ang II and the time-integrated CV-11974 levels, the active metabolite of TCV-116, was not different between days 1 and 8. In conclusion, TCV-116 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of Ang II in men.

Administration, Oral↗
PubMed1995

Short-term and sustained renal effects of angiotensin II receptor blockade in healthy subjects.

We investigated the short-term and sustained hormonal and renal effects of angiotensin II (Ang II) receptor blockade in normotensive healthy volunteers. Twenty-four subjects maintained on a fixed sodium diet were randomized to receive for 8 days a placebo or 10 or 50 mg doses of the Ang II antagonist irbesartan (SR 47436, BMS 186295) according to a double-blind, parallel group design. Plasma renin activity, plasma immunoreactive Ang II and aldosterone levels, blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 8 hours after the first and eighth administration of each dose of irbesartan or placebo. Ang II receptor blockade with irbesartan induced a dose-dependent compensatory increase in plasma renin activity and plasma angiotensin levels and a significant decrease in plasma aldosterone levels. The compensatory rise in plasma renin activity and Ang II levels was more pronounced on day 8, reflecting a long duration of the blocking effect of irbesartan. Irbesartan induced small changes in blood pressure and did not significantly modify renal blood flow and glomerular filtration rate. However, a significant decrease in filtration fraction was observed during receptor blockade on days 1 and 8. The tubular effects of irbesartan were characterized by a dose-dependent increase in sodium and chloride excretions. Interestingly, the cumulative natriuretic response to Ang II receptor blockade was similar on days 1 and 8, suggesting that in these subjects, renal Ang II receptors are not blocked over 24 hours during repeated administration even though this antagonist has a long duration of action (t1/2 of 15 to 17 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Renal sodium handling in patients with untreated hypertension and white coat hypertension.

Renal tubular sodium handling was investigated prospectively in 48 normotensive subjects, 53 untreated hypertensive patients, and 13 patients with white coat hypertension using endogenous trace lithium as a marker of proximal sodium reabsorption. A 12-hour daytime ambulatory blood pressure recording was performed in all patients to confirm the diagnosis of hypertension. Patients were included in the white coat hypertension group if their office blood pressure was above 160/90 mm Hg but the mean value of their 12-hour ambulatory recording was lower than 140/90 mm Hg. All participants were studied on their normal diet and ate salt freely. Fractional excretions of sodium (FENa), lithium (FELi), and potassium (FEK) were measured simultaneously before blood pressure recording. FENa was significantly higher in hypertensive patients (0.84 +/- 0.05%, P < .05) than in normotensive control subjects (0.60 +/- 0.06%), and FELi was comparable in the two groups (15.4 +/- 0.65% in hypertensive patients and 17.0 +/- 0.9% in control subjects). However, the relation between FENa and FELi was significantly different in normotensive subjects and hypertensive patients (P < .001), so that for a given increase in FENa a smaller increase in FELi was observed in hypertensive patients. In addition, the ratios of urinary lithium to sodium and urinary potassium to sodium were significantly reduced in hypertensive patients, suggesting an increased proximal reabsorption of sodium. Similar alterations in renal tubular sodium handling were observed in patients with white coat hypertension. These results suggest that an increased sodium reabsorption in the proximal tubule may contribute to the maintenance of hypertension and that white coat hypertension might represent a prehypertensive state.

Absorption↗
PubMed1994

Fractional excretion of trace lithium and uric acid in acute renal failure.

The early distinction between prerenal azotemia, characterized by an avid proximal tubular sodium reabsorption, and ATN, in which proximal tubule function is depressed, remains an important but difficult clinical task. Indices of acute renal failure based on urinary sodium excretion may be helpful but have several limitations, among which is the use of diuretics. The effectiveness of the fractional excretion of uric acid (FEUA) and that of endogenous lithium (FELi) in the diagnosis of acute renal failure has been evaluated in an unselected group of 46 patients, 28 with prerenal azotemia and 18 with ATN. In the entire group, FELi concurred with the clinical diagnosis in 78% of the patients, whereas the fractional excretion of sodium (FENa) and FEUA were in agreement in only 63 and 50%, respectively. FELi was more sensitive to identify hemodynamic renal failure, because 93% of prerenal failure patients had a low FELi, contrasting with a low FEUA in only 68% and a low FENa in 75%. The major reason for the discrepancy between FENa and FELi was the administration of diuretics. In both acute renal failure groups, FENa was higher in the subgroups receiving diuretics. In contrast, diuretic therapy had no effect on FELi in either group. These results suggest that FELi is more accurate than either FENa or FEUA for distinguishing prerenal azotemia from ATN. The superiority of FELi appears especially relevant in patients treated with the usual diuretics.

Acute Kidney Injury↗
PubMed1993

[Follow-up drug treatment in the practitioner's office].

The therapeutic drug monitoring begins to extend from specialized laboratories into the practitioners office. A systematic approach to these new problems is, therefore, recommended, following these guidelines: The rationale for measuring a drug level must be established. The precision of technical equipment and employed methods has to be optimal. The practicability and reliability of the methods (accuracy, precision, intra- and inter-series, variability) have to be assessed, and quality-control is mandatory. A result must be interpretable. Next to analytical precision, the result has to be attributed unequivocally to a sample, which in turn had to be collected under optimal circumstances. Finally, drug monitoring has to be an integral part of individual therapy plans. In this context understanding the therapeutic range and the pharmacokinetics is essential. Competences needed to manage an entire drug monitoring program are thus many-fold. Only a multidisciplinary team appears able to provide sufficient expertise. The conditions implied in this development burden a medical office financially by needed material and personal resources.

Drug Monitoring↗
PubMed1993

Early evening nizatidine intake with a meal optimizes the antisecretory effect.

The importance of the temporal relationship between meal and nizatidine intake was studied in a six-armed, double-blind, placebo-controlled trial. Eleven healthy volunteers received early (18.00 hours) or late (21.00 hours) supper, with either placebo, early (18.00 hours) nizatidine, or late (21.00 hours) 300 mg nizatidine. Ambulatory 21-hour gastric pH-metry was performed and plasma nizatidine concentrations were determined by high pressure liquid chromatography. Early-nizatidine/early-supper (median pH 2.50), but not late-nizatidine/late supper (median pH 2.30), produced significantly higher median 21-hour pH values than did early-nizatidine/late-supper (median pH 1.90). Concomitant food delayed the absorption of nizatidine but did not change the drug's bioavailability. Oral nizatidine should be taken with food, preferably early in the evening, to optimize its anti-secretory effect.

Adult↗
PubMed1993

Renal effects of nimesulide in furosemide-treated subjects.

In clinical settings where effective plasma volume is decreased, nonsteroidal anti-inflammatory drugs (NSAIDs) may induce acute renal failure. We have evaluated the effects of single and repeated doses of nimesulide on renal haemodynamics and electrolyte excretion in 8 healthy volunteers during a prolonged course of furosemide (frusemide). Under these study conditions, renal prostaglandin synthesis is expected to be elevated, with renal function being dependent upon increased levels of prostaglandins. Nimesulide induced an acute but transient decrease in indices of renal haemodynamics. Furosemide-induced increases in plasma renin activity and aldosterone levels were blunted, and urinary excretion of prostaglandin E2 was markedly reduced by nimesulide. The magnitude and time course of the natriuretic, kaliuretic and diuretic effects of furosemide were attenuated by nimesulide. Although the transient nature of the observed renal haemodynamic changes suggests that the risk of developing acute renal failure is small, the rise should be taken into account in patients with renal dysfunction. Sodium and potassium retention, and the blunting of the diuretic-induced electrolyte excretion, could be of clinical relevance. Nimesulide appears, therefore, to share the prostaglandin-dependent renal effects of other NSAIDs.

Adult↗
PubMed1992

[Value of simultaneous determination of cyclosporin blood levels using specific and nonspecific methods in liver transplantation].

Cyclosporine's narrow therapeutic window and the large inter- and intra-individual variation of its pharmacokinetics require therapeutic monitoring. Cyclosporine is metabolized in the liver and excreted with its metabolite into the bile. An accumulation of metabolites occurs in liver dysfunction, leading to a high cyclosporine blood concentration when measured by a non-specific method (polyclonal antibodies). Specific methods (HPCL, monoclonal antibody) are therefore recommended by some authors. We evaluated the potential usefulness of simultaneous cyclosporine determination by a non-specific (fluorescent polarisation TDx, polyclonal antibodies) and a specific method (I125-RIA, monoclonal antibody). 10 patients were followed from 51 days to 32 months after hepatic transplantation. 2 patients who showed no graft rejection presented a polyclonal antibodies/monoclonal antibody ratio below or equal to 4 throughout their evolution. Other patients presented a rise of this ratio during periods of liver dysfunction, particularly in acute graft rejection. When bilirubin concentrations are plotted versus this ratio, an hysteresis is present during periods of acute rejection, but not during an episode of histological hepatitis. The same holds true for alkaline phosphatase and gamma-GT. These data suggest that this ratio could be a sensitive test for early detection of rejection. Simultaneous cyclosporine blood determination with specific and nonspecific methods may be useful in the follow-up of liver-transplanted patients.

Adult↗
PubMed1992

The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers.

We have studied the effects of quinidine on ECG intervals and on the pharmacokinetics of flecainide and its two metabolites in 6 healthy men in an open randomized crossover study. Flecainide acetate (150 mg) was given as a constant rate i.v. infusion over 30 min. Quinidine (50 mg orally), given the previous evening, did not change the volume of distribution of flecainide (7.9 vs 7.4 l.kg-1), but significantly increased its half-life (8.8 vs 10.7 h). This was attributable to a reduction in total clearance (10.6 vs 8.1 ml.min-1 x kg-1), most of it being accounted for by a reduction in non-renal clearance (7.2 vs 5.2 ml.min-1 x kg-1). The excretion of the metabolites of flecainide over 48 h was significantly reduced. These findings suggest that quinidine inhibits the first step of flecainide metabolism, although it may also reduce its renal clearance, but to a lesser extent (3.5 vs 2.9 ml.min-1 x kg-1). The effects of flecainide on ECG intervals were not altered by quinidine. Thus, quinidine tends to shift extensive metabolizer status for flecainide towards poor metabolizer status and may also alter its renal excretion.

Adult↗
PubMed1992

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Administration, Oral↗
PubMed1992

[Loss of ganglion cells in the retina secondary to vincristine therapy].

We report the case of a 25-year-old black female from Zaire with AIDS diagnosed 2 years earlier. Nine months before her death, she was treated for a disseminated Kaposi sarcoma with vincristin, adryamycin and bleomycin. At that time, visual acuity was normal and ophthalmologic examination was unremarkable except for the presence of bilateral Drusen and a cotton wool spot OS. Three months after the onset of chemotherapy, the patient complained of progressive visual field constriction, which progressed to blindness within a 4 month period. Five months after the onset of the tri-therapy a bilateral CMV retinitis developed, which was successfully treated by intravitreous injections of ganciclovir. This therapy was stopped as soon as blindness was established, with subsequent massive bilateral recurrence of the CMV retinitis. Histologic examination showed complete atrophy of the retinal ganglion cells and areas of CMV retinitis. The optic nerve was demyelinated and exhibited astrocytic gliosis. Immunohistochemistry confirmed the presence of CMV in infected retina and revealed the absence in the optic nerve of the class III beta-tubulin isotype and of the 200 kd neurofilament subunit. In contrast, oculomotor nerves appeared intact. The presence of HIV in the eye and in the optic nerve was excluded using PCR technique. The retinal ganglion cell loss and optic nerve atrophy appeared to be purely degenerative in nature, since there was no evidence of vascular occlusion, inflammation or retrobulbar compressive process. We therefore conclude that blindness was caused by vincristine therapy. The patient actually received 22 mg of vincristin intravenously in 11 courses over 7 months, although discontinuation was recommended by us after 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Once-a-week azithromycin in AIDS patients: tolerability, kinetics, and effects on zidovudine disposition.

Toxoplasmic encephalitis is one of the leading causes of morbidity in patients with AIDS. Lifelong treatment is needed to prevent relapses, and primary prevention is desirable in high-risk patients, but the available drugs are often poorly tolerated. Azithromycin (AZM) has been considered a drug candidate because of its efficacy in the animal model and its kinetic properties, which would allow intermittent administration. The tolerability and kinetics of AZM and its effect on the disposition of zidovudine (ZVD) were therefore evaluated in a preliminary open study in nine human immunodeficiency virus-infected patients. AZM was administered once weekly for 5 weeks 2 h before the usual morning ZVD dose. The day before and on the first and fifth AZM dosings, blood samples were drawn every 30 min during 5 h for determination of the concentrations of ZVD and its glucuronide metabolite. Blood samples were drawn for AZM measurement over 72 and 360 h on the first and fifth AZM administrations, respectively, as well as before and 3 h after dosing on the second, third, and fourth AZM dosings. After the first and fifth administrations, maximum AZM concentrations in serum were 0.6 +/- 0.1 and 0.8 +/- 0.2 microM (mean +/- standard error of the mean), respectively; times to peak concentration in serum were 3.7 +/- 0.2 and 2.9 +/- 0.4 h, respectively; areas under the plasma concentration-time curves were 9.2 +/- 1.6 and 9.3 +/- 2.0 micrograms.h/ml, respectively; and half-lives were 61.0 +/- 5.4 and 63.8 +/- 6.7 h, respectively. On days -1, 1, and 29, ZVD kinetic parameters were as follows: maximum concentrations in serum, 3.1+/- 0.6, 4.3 +/- 0.6, and 4.2 +/- 0.9 microM, respectively; times to maximum concentrations in serum, 1.1 +/- 0.4, 0.8 +/- 0.2, and 1.2 +/- 0.3 h, respectively: areas under the plasma concentration-time curves, 5.3 +/- 0.9, 5.9 +/- 0.6, and 5.7 +/- 0.8 microgram . h/ml, respectively; and half-lives, 1.3 +/- 0.08, 1.4 +/- 0.04, and 1.3 +/- 0.04 h, respectively. Except for transient mild abdominal cramps that occurred at 2 to 3 h postdose (6 of 45 exposures) and nausea (4 of 45 exposures), neither subjective nor objective side effects were observed. The kinetics of AZM were similar after the first and repeated administrations, and the disposition of ZVD was not altered by this treatment. The efficacy of AZM in preventing cerebral toxoplasmosis can therefore be safely tested in human immunodeficiency virus-infected patients concomitantly treated with zidovudine.

Acquired Immunodeficiency Syndrome↗