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J Vuorinen

Publications and source records attributed to J Vuorinen.

15 recordsLinked to original sources
PubMed1996

A three-step procedure for assessing bioequivalence in the general mixed model framework.

Bioavailability data arising from a standard two-period cross-over study are routinely analysed to establish bioequivalence between test and reference formulations. Current regulatory guidelines only require evidence of equivalence in average bioavailability for the assessment of bioequivalence. Under normality assumptions, this is achieved by demonstrating equivalence between the formulation means (step 1). However, the equivalence of formulation variances should also be assessed to get evidence of population bioequivalence (step 2), since a difference in variability of bioavailability may also pose significant problems in drug safety and efficacy. On the other hand, even population bioequivalence does not ensure that an individual subject could be expected to respond similarly to the two formulations. Therefore, whenever individual bioequivalence is the ultimate goal, the magnitude of intra-subject correlation should always be examined as the final stage (step 3). In this paper, these three successive concepts of bioequivalence are cast into the general mixed model framework and a stepwise testing procedure for the global assessment of bioequivalence is proposed. In addition to this, important issues addressed in the regulatory guidelines, such as verification of the model assumptions and application of the log-transformation, are discussed. Lastly, an example is presented to illustrate the proposed three-step procedure on the original and log-transformed scale of measurement.

Analysis of Variance↗
PubMed1996

The effect of enoxaparin in prevention of deep venous thrombosis in hip and knee surgery--a comparison with the dihydroergotamine-heparin combination.

A randomized study was carried out in order to compare the low-molecular heparin enoxaparin to heparin-dihydroergotamine (HDHE) combination, as prophylactic anti-thrombotic measure in patients undergoing hip replacement or knee replacement surgery or fractures of the femoral neck. A total of 165 patients both female and male were included in the study. The patients were randomized into two treatment groups. One group was treated with heparin-dihydroergotamine 0.5 mg + 5,000 IU twice a day and the other with enoxaparin 40 mg once daily. All patients were examined with Doppler ultrasound on day 3-5 and after the termination of medication which was the end of the study. Positive Doppler ultrasound findings were confirmed either by duplex Doppler or phlebography and clinical signs of pulmonary embolism were confirmed by isotope scintigraphy. The overall incidence of thromboembolic events was low (3%). One deep venous thrombosis (DVT) was seen in the enoxaparin group and two cases of pulmonary embolism in the heparin-dihydroergotamine group. Thus, the two regimens showed comparable efficacy and the overall safety was comparable. However, enoxaparin caused significantly less injection site haematoma. Correspondingly, the size of the injection site haematoma was significantly smaller in the enoxaparin group.

Adult↗
PubMed1994

High dose toremifene in advanced breast cancer resistant to or relapsed during tamoxifen treatment.

Fifty patients with advanced breast cancer refractory to prior tamoxifen therapy were assigned to investigational treatment with high-dose toremifene administered 120 mg orally twice a day. Treatment was generally well tolerated. The majority (80%) of the patients had no side effects, and among the remaining 10 patients reported side effects were mostly mild and/or transient. Two objective tumor responses were observed: one complete response (CR), duration 6.2 months, and one partial response (PR), duration 8 months. The response rate was thus 4% (95% CI: 0.5 to 14%). In addition 3 patients experienced a mixed response, some metastatic sites responding, while at other sites disease progressed; 22 patients had disease stabilization for > 2 months. A subset analysis disclosed that a small subgroup of patients, including 7 patients in this study, who had achieved CR at some of the sites during preceding tamoxifen therapy, experienced a long progression-free time during high dose toremifene treatment. The median time to progression in this subgroup of patients was 9.4 months (95% CI: 3.8 to 9.4) as opposed to 2.1 months (95% CI: 2.0 to 2.8) for all the remaining 43 patients, which is a significant decrease in disease progression (p < 0.03). Such results reveal that although this kind of second-line hormonal treatment with high dose toremifene cannot be recommended for all tamoxifen failures, there might be a subset of patients, i.e. those who achieve CR in some lesion during tamoxifen therapy, who benefit from this type of treatment.

Adult↗
PubMed1994

Does thermal stress decrease uterine blood flow in hypertensive pregnancies?

The aim of the study was to determine the acute effects of thermal stress on maternal and fetal circulatory responses in normal and hypertensive patients. Therefore we studied 14 healthy pregnant women and 12 women with compromised pregnancies during short-term heat stress using color Doppler ultrasound in addition to conventional follow-up methods. The uterine vascular resistance increased significantly during the exposure in the high-risk pregnancy group without change in the control group. The results of the present study give strong support to our earlier studies that short-term heat stress seems to be safe in uncomplicated pregnancies but may be detrimental in high-risk pregnancies.

Adult↗
PubMed1992

Uptake of 2-fluoro-2-deoxy-D-[U-14C]-glucose during chemotherapy in murine Lewis lung tumor.

Mice bearing intramuscular Lewis lung tumor were treated with BCNU and doxorubicin (ADM) to study chemotherapy-induced changes in the uptake of 2-fluoro-2-deoxy-[U-14C]glucose (FDG). A decreased FDG uptake, tumor regression and a diminished proportion of aneuploid versus diploid cells as evaluated by DNA flow cytometry were seen after treatment with BCNU but not with ADM; HPLC indicated that most of the 14C activity in tumors was from FDG6-phosphate. The results suggest that changes in FDG uptake reflect the effectiveness of antitumor therapy. FDG may be valuable in follow-up studies of cancer treatment.

Adenosine Triphosphate↗
PubMed1992

Intramuscularly administered dexmedetomidine attenuates hemodynamic and stress hormone responses to gynecologic laparoscopy.

The hemodynamic and endocrine effects of three different doses of dexmedetomidine (0.6, 1.2, and 2.4 micrograms/kg), oxycodone (0.13 mg/kg), and saline solution, injected intramuscularly 45-60 min before induction of general anesthesia, were compared in a double-blind, randomized study involving 100 women undergoing gynecologic diagnostic laparoscopy. Anesthesia was induced with thiopental (4.5 mg/kg) and maintained with 0.3% end-tidal isoflurane and 70% nitrous oxide in oxygen. Arterial blood pressure and heart rate increased after endotracheal intubation and during laparoscopy in all groups, but the maximal mean arterial pressure after tracheal intubation was lower in the dexmedetomidine 2.4-micrograms/kg group (104 mm Hg [SD 19]) than in the saline solution group (130 mm Hg [SD 12]). Dexmedetomidine (2.4 and 1.2 micrograms/kg) attenuated the maximal heart rate after intubation (84 [SD 11] and 101 beats/min [SD 15], respectively) compared with saline solution (116 beats/min [SD 19]). On the other hand, 40% of the patients in the dexmedetomidine 2.4-micrograms/kg group received atropine in the postanesthesia care unit for bradycardia (heart rate < or = 40 beats/min). Preoperative anxiety and sedation before and after preanesthetic medication were evaluated by the patients with the aid of a profile of mood-state questionnaire; only dexmedetomidine 2.4 micrograms/kg produced significant anxiolysis and sedation. Plasma concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylglycol, cortisol, and beta-endorphin increased less in the dexmedetomidine 2.4-micrograms/kg group in response to tracheal intubation and surgery than in the saline solution group.

Adrenergic alpha-Agonists↗
PubMed1991

A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.

The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (ASA physical status I-II) women undergoing cervical dilatation and uterine curettage. The premedicants were administered i.m. 60 min before induction of anaesthesia with thiopentone. Nitrous oxide 70% in oxygen and thiopentone were used for maintenance. Both premedicants were tolerated well and no serious haemodynamic or other adverse events occurred. Dexmedetomidine caused moderate reductions in arterial pressure (maximally by 20%) and heart rate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia less than 45 beat min-1. Both premedicants decreased the plasma concentrations of noradrenaline by about 50%, but only dexmedetomidine attenuated the catecholamine response to anaesthesia and surgery. The thiopentone requirements were decreased significantly (P = 0.003) by both dexmedetomidine (17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2) min after midazolam, 8.5 (5.2) min after dexmedetomidine and 5.6 (11.4) min after placebo (P = 0.006 between midazolam and placebo groups, other differences ns).

Adrenergic alpha-Agonists↗
PubMed1990

Moclobemide, an inhibitor of MAO-A, does not increase daytime plasma melatonin levels in normal humans.

1. Plasma melatonin concentrations were determined after administration of single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was later continued in an open fashion by giving a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Neither drug had any effects on plasma melatonin levels, in spite of very marked MAO-A inhibition after moclobemide (as evidenced by up to 79% average decreases in the plasma concentrations of 3,4-dihydroxyphenylglycol, a deaminated metabolite of noradrenaline) and over 90% inhibition of MAO-B activity in blood platelets after deprenyl. 3. It is concluded that daytime human plasma melatonin levels do not accurately reflect MAO-A inhibition in acute drug studies.

Adult↗
PubMed1989

Alfentanil obtunds the cardiovascular and sympathoadrenal responses to suxamethonium-facilitated laryngoscopy and intubation.

Alfentanil 75 micrograms kg-1 or saline (control group) was given 1 min before induction of anaesthesia in 20 healthy patients premedicated with diazepam 0.14 mg kg-1 and pethidine 1 mg kg-1. Anaesthesia was induced with a sleep dose of thiopentone preceded by glycopyrrolate. Suxamethonium 1 mg kg-1 was used to facilitate laryngoscopy (which lasted 10 s) and tracheal intubation. Arterial pressure, heart rate and noradrenaline concentration in mixed venous plasma increased significantly after suxamethonium, and increased further after laryngoscopy and intubation in the control group (n = 10). The QT interval of the ECG was prolonged after the administration of suxamethonium, and was prolonged further after laryngoscopy and intubation. All these changes were attenuated in patients pretreated with alfentanil (n = 10), but four patients had chest wall rigidity. Changes in the QT interval correlated directly with the changes in plasma noradrenaline concentration (r = 0.67). Plasma adrenaline concentrations decreased during induction of anaesthesia in both groups.

Adult↗
PubMed1989

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Ca2+-induced lateral phase separation in phosphatidic acid/phosphatidylcholine monolayers as revealed by fluorescence microscopy.

Phase separation in mixed monolayers of phosphatidylcholine (PC) and pyrene-labeled phosphatidic acid (PA) was observed by fluorescence microscopy on an air/water interface as a function of subphase Ca2+ concentration and lateral packing pressure of the film. Below 45 mN m-1 and in the absence of Ca2+ no indications of phase immiscibility were observed. Addition of 1 mM Ca2+ caused extensive phase separation, which was evident immediately after spreading of the film. Further increase in Ca2+ concentration up to 30 mM increased the pyrene excimer intensity of the separated phosphatidic acid enriched domains. In the presence of Ca2+ (1-30 mM) and at surface pressures below 10 mN m-1 phase separation was always evident. However, as surface pressure exceeded 10 mN m-1, mixing of PC and PA occurred. Upon decompression of the film, phase separation reappeared at surface pressures close to 10 mN m-1. The surface textures of the film before and after the compression and subsequent relaxation were different. Inclusion of 30 mol% cholesterol increased the number and decreased the size of the PA domains. In films containing 50 mol% cholesterol no phase separation could be detected at the resolution available.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1984

Duplicate loci for supernatant and mitochondrial malic enzymes in vendace, Coregonus albula (L.).

There is electrophoretic variation in the vendace (Coregonus albula L.) supernatant malic enzyme (MEs). This is the first observed case of variation of this enzyme in salmonids. The phenotypic distribution among 33 populations studied indicates, that both supernatant and mitochondrial (MEm) malic enzymes are encoded by a duplicate pair of loci, Me-(1,2) then represent the mitochondrial and Me-(3,4) the supernatant form of the enzyme. Both pairs seem to contain one fixed and one variable locus. At both variable loci, Me-2 and Me-4, four alleles were found segregating and their products combine as tetramers within, but not between pairs. At Me-4 extensive between population heterogeneity was observed.

Animals↗
PubMedDate not supplied

Fieller's confidence intervals for the ratio of two means in the assessment of average bioequivalence from crossover data.

The two-period crossover design is the most commonly used study design for bioequivalence of one test formulation to be assessed in comparison to one reference formulation. Consequently, in this paper, all derivation is based on this particular design. It is assumed that for the underlying statistical model the usual assumptions of normality and additivity are satisfied on the original scale of measurement and that it is wanted to base the assessment of average bioavailability on the ratio of the unknown population means for the test and reference formulation. The purpose of this paper is to illustrate that it is reasonable to assume a uniform covariance structure for the two-period crossover design, because the demand of equal variability in bioavailabilities, in addition to equal average bioavailabilities, for the reference and test formulation makes the assumption of uniform covariance structure very realistic, and also because the properties of a decision rule based upon a Fieller's confidence interval under a uniform covariance structure are competitive with those of the corresponding rule based on a general covariance structure.

Bayes Theorem↗