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Biomedical subjects

C Palm

Publications and source records attributed to C Palm.

17 recordsLinked to original sources

Etomidate-Lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine.

BACKGROUND: Propofol is associated with a high incidence of injection pain in children, even if given together with lidocaine. A new lipid formulation of etomidate (Etomidate-Lipuro) has been found in adults to cause very little discomfort during i.v. injection. The aim of the present prospective, double-blind, randomized trial was to compare the incidence of injection pain during i.v. induction of anaesthesia between propofol with added lidocaine (previous standard) and this new etomidate formulation in paediatric patients. METHODS: A total of 110 paediatric patients, aged 2-16 years, scheduled for outpatient surgery were planned to be included in the study. The primary end point of the study was the incidence of injection pain during induction of anaesthesia as assessed by a four-point scale as described previously. The occurrence of myoclonic muscular activity was registered as a secondary end point (four-point scale). An interim analysis after 80 patients was requested by the Ethics' Committee. RESULTS: The study was stopped after the inclusion of 80 patients. A significantly lower incidence of injection pain was found in the Etomidate-Lipuro group as compared with the propofol-lidocaine group (5.0% vs 47.5%, P<0.001). The use of etomidate was associated with a significantly higher incidence of myoclonic activity compared with propofol-lidocaine (85.0% vs 15%, P<0.001). CONCLUSIONS: The use of a new lipid formulation of etomidate is associated with significantly less injection pain than propofol with added lidocaine in children. This finding may warrant a change in clinical practice in order to avoid unnecessary pain in children.

Adolescent↗

The role of V2 vasopressin antagonists in hyponatremia.

Hyponatremia is a frequent electrolyte disorder. It is often found in congestive cardiac failure, liver cirrhosis, plasma volume contraction and in SiADH. In these disorders hyponatremia is caused by nonosmotic vasopressin and sustained fluid intake. This provides a rationale for V2 vasopressin receptor antagonists in the treatment of hyponatremia. There is now convincing evidence from different animal models of congestive cardiac failure that peptide and non-peptide V2 vasopressin antagonists effectively increase renal water diuresis and plasma sodium concentration. In addition, several of the experimental studies also showed an improvement of hemodynamic changes of cardiac failure in response to V2 antagonists. Data in patients indicated that oral non-peptide V2-antagonists correct hyponatremia and may improve hemodynamic derangements in cardiac failure. In addition, experimental and clinical studies of V2 antagonists have been undertaken in liver cirrhosis and SiADH. In those studies hyponatremia was improved or corrected, too. Taken together, V2 vasopressin antagonists promise to become therapeutic agents in hyponatremic disorders.

Animals↗

Nucleotide sequence and predicted functions of the entire Sinorhizobium meliloti pSymA megaplasmid.

The symbiotic nitrogen-fixing soil bacterium Sinorhizobium meliloti contains three replicons: pSymA, pSymB, and the chromosome. We report here the complete 1,354,226-nt sequence of pSymA. In addition to a large fraction of the genes known to be specifically involved in symbiosis, pSymA contains genes likely to be involved in nitrogen and carbon metabolism, transport, stress, and resistance responses, and other functions that give S. meliloti an advantage in its specialized niche.

Agrobacterium tumefaciens↗

The composite genome of the legume symbiont Sinorhizobium meliloti.

The scarcity of usable nitrogen frequently limits plant growth. A tight metabolic association with rhizobial bacteria allows legumes to obtain nitrogen compounds by bacterial reduction of dinitrogen (N2) to ammonium (NH4+). We present here the annotated DNA sequence of the alpha-proteobacterium Sinorhizobium meliloti, the symbiont of alfalfa. The tripartite 6.7-megabase (Mb) genome comprises a 3.65-Mb chromosome, and 1.35-Mb pSymA and 1.68-Mb pSymB megaplasmids. Genome sequence analysis indicates that all three elements contribute, in varying degrees, to symbiosis and reveals how this genome may have emerged during evolution. The genome sequence will be useful in understanding the dynamics of interkingdom associations and of life in soil environments.

Bacterial Adhesion↗

Quantification of doxorubicin in plasma--a comparative study of capillary and venous blood sampling.

Doxorubicin, an anthraquinone glycoside, is currently one of the clinically most important antineoplastic drugs. The aim of the present study was to identify potential concentration differences of doxorubicin in plasma from capillary and venous blood samples. Sixteen patients (seven females and nine males; median age: 37 years, range: 1-77 years) were included. The quantitative analysis of doxorubicin was carried out by reversed-phase liquid chromatography with fluorometric detection. The concentration of doxorubicin in capillary and venous samples were closely correlated (r=0.98; p<0.0001). The median plasma concentration ratio capillary/venous was 1.13 (95% confidence interval: 1.06-1.20) and not affected either by plasma drug concentration, age or the body mass index of the patient. The concentration ratio was significantly higher in males (median: 1.18) than in females (median: 1.01). The observed concentration differences of doxorubicin in plasma from capillary and venous samples are of minor importance only. Capillary blood sampling is recommended for use in pharmacokinetic studies of doxorubicin, especially in pediatric patients, in order to avoid sometimes traumatic venous blood sampling.

Adolescent↗

Color line search for illuminant estimation in real-world scenes.

The estimation of illuminant color is mandatory for many applications in the field of color image quantification. However, it is an unresolved problem if no additional heuristics or restrictive assumptions apply. Assuming uniformly colored and roundly shaped objects, Lee has presented a theory and a method for computing the scene-illuminant chromaticity from specular highlights [H. C. Lee, J. Opt. Soc. Am. A 3, 1694 (1986)]. However, Lee's method, called image path search, is less robust to noise and is limited in the handling of microtextured surfaces. We introduce a novel approach to estimate the color of a single illuminant for noisy and microtextured images, which frequently occur in real-world scenes. Using dichromatic regions of different colored surfaces, our approach, named color line search, reverses Lee's strategy of image path search. Reliable color lines are determined directly in the domain of the color diagrams by three steps. First, regions of interest are automatically detected around specular highlights, and local color diagrams are computed. Second, color lines are determined according to the dichromatic reflection model by Hough transform of the color diagrams. Third, a consistency check is applied by a corresponding path search in the image domain. Our method is evaluated on 40 natural images of fruit and vegetables. In comparison with those of Lee's method, accuracy and stability are substantially improved. In addition, the color line search approach can easily be extended to scenes of objects with macrotextured surfaces.

Algorithms↗

[Hyponatremia--with comments on hypernatremia].

Disorders of the serum sodium concentration (hypo- and hypernatremia) are amongst the most frequent electrolyte disorders in clinical medicine. They are attributable to disturbance of to water metabolism. Hyponatremia is almost always a condition of water excess while hypernatremia is due water deficiency. Physiological normonatremia (normal plasma osmolality) is maintained by an integrated system involving regulated water intake via thirst and control of water excretion via antidiuretic hormone secretion. Therefore hypo- and hypernatremia should be analyzed in terms of dysregulated ADH secretion, fluid intake and renal water excretion. Hyponatremia is usually a disorder of vasopressin excess, due to 'non-osmotic' vasopressin release. The latter may occur in two different settings: (I) SIADH, (II) baroreceptor mediated vasopressin secretion (cardiac failure, liver cirrhosis). This entities are easy to distinguish in clinical practice. SIADH is associated with striking lower plasma concentrations of urate, creatinine and urea. In SIADH the blood pressure is normal and there is no edema. In contrast in the hyponatremia of liver cirrhosis and heart failure the plasma measurements indicated are usually slightly elevated, the blood pressure is low and there is edema. The typical patient with hypernatremia is old and has no thirst sensation. Hypo- or hypernatremia may cause major neurologic symptoms. These symptoms are more related to the rate of change in the serum sodium concentration than to the absolute level of a hypo- or hypernatremia reached. The traditional treatment for hyponatremia used to be water restriction. However V2-Vasopressin-Antagonists may provide a better treatment modality in the future. Hypernatremia is treated by slow rehydratation.

Diagnosis, Differential↗

A comparative pharmacokinetic study of doxorubicin and 4'-epi-doxorubicin in children with acute lymphocytic leukemia using a limited sampling procedure.

Antraquinone glycosides are an important class of antineoplastic drugs, frequently used for treatment of a variety of malignancies in children. Doxorubicin (Dox) is the most frequently used drug within this class of antineoplastics. 4'-epi-doxorubicin (Epi), a Dox isomer, was developed with the aim of reducing risks for fatal heart toxicity observed with Dox. The aim of the present study was to investigate the pharmacokinetics of Dox and Epi in children with acute lymphocytic leukemia. In total 31 patients (13 females and 18 males; median age 5.4 years; range 0.73-15.3 years) were studied using a simplified sampling procedure. The pharmacokinetic differences of the two drugs were established by their simultaneous administration. The plasma pharmacokinetics of neither Dox nor Epi correlated with the age of the patients. There were no gender differences in dose-normalized maximum concentrations of neither Dox nor of Epi. The inter-patient variation of the dose-normalized maximum concentrations of Dox and Epi is larger among females than among males. The Cmax ratio Dox/Epi was 1.39+/-0.19 (mean +/- SD). The pharmacokinetic differences of Dox and Epi in children, although less pronounced than in adults, are still of a magnitude that might be of clinical importance.

Adolescent↗

The treatment of hyponatraemia using vasopressin antagonists.

Hyponatraemia is a frequent electrolyte disorder. It is primarily attributable to vasopressin excess plus sustained fluid intake. Hyponatraemia causes CNS symptoms, especially during the first 2-4 days; these symptoms are related to brain swelling. Hyponatraemia occurs in the setting of liver cirrhosis and congestive cardiac failure, in which it is related to stimulation by low arterial blood pressure acting through baroreceptors. Hyponatraemia also occurs in the syndrome of inappropriate antidiuretic hormone secretion, usually from neoplasms releasing vasopressin. The conventional treatment of hyponatraemia used to be fluid restriction and treatment of the underlying disorder. This kind of treatment has been unreliable, cumbersome and difficult to comply with for the patient. In the future, effective vasopressin V2 antagonists will become available for clinical use in the treatment of hyponatraemia, and are expected to improve the management of hyponatraemia. Pharmacological characteristics and observations of biological effects of three antagonists are reported in the present article.

Antidiuretic Hormone Receptor Antagonists↗

Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leukopenia after chemotherapy.

The median bioavailabilities of aciclovir after administration of aciclovir and its prodrug valaciclovir were 21.5 and 70.1%, respectively, in 12 patients with malignant hematological diseases with leukopenia after chemotherapy. The interindividual variations of the bioavailability were 48.5 and 21.0% after administration of aciclovir and valaciclovir, respectively. Neither the bioavailability nor the interindividual variation of area under the concentration-time curve of oral aciclovir or valaciclovir differed from that reported in healthy volunteers.

Acyclovir↗

Pharmacokinetics and effects of intravesical oxybutynin on the paediatric neurogenic bladder.

OBJECTIVE: To evaluate the pharmacokinetics of both oxybutynin and its active metabolite, N-desethyl oxybutynin (NDO), when the drug is instilled directly into the bladder in children with myelodysplasia and neurogenic bladder disturbance, in whom it may improve continence and decrease the risk of upper urinary tract deterioration. PATIENTS AND METHODS: The study comprised 13 children (five girls and eight boys, mean age 9.3 years, range 1-15) with neurogenic bladders who were treated using clean intermittent catheterization and intravesical instillation of a sterile, pharmacy-produced solution of oxybutynin. Steady-state minimum plasma levels of oxybutynin and NDO, together with their effect on urodynamic variables and incontinence, were evaluated. The dose (0.04-0.17 mg/kg, mean 0.1 mg/kg) was instilled twice daily. RESULTS: The effects of the drug on incontinence and urodynamic variables were pronounced, improving both in most cases. Minimum plasma levels were < 0.3-7.2 ng/mL for oxybutynin and 0.8-14 ng/mL for NDO. The ratio of oxybutynin to NDO was 0.29-0.83 (mean 0.47). CONCLUSION: There was no clear relationship between minimum plasma levels of the drug or NDO and their clinical effects; however, the combination of oxybutynin and NDO seemed to be more strongly correlated with the clinical effects.

Administration, Intravesical↗

Plasma levels of clonidine following epidural bolus injection in children.

BACKGROUND: The use of clonidine as an adjunct to epidural administration of local anesthetics in children has been reported to substantially improve the duration and quality of postoperative analgesia. The aims of the present study were to determine the pharmacokinetic profile and to investigate the interaction between postoperative sedation and analgesia after epidurally administered clonidine in children. METHODS: Plasma levels of clonidine (0-10 h postop) and assessment of postoperative analgesia and sedation (0-24 h postop) were performed at predetermined intervals following lumbar epidural administration of bupivacaine 2.0 mg/kg and clonidine 2 mg/kg in 8 children undergoing ureteral re-implantation surgery using general anesthesia (age range: 1-9 yr, weight range: 9-41 kg). Plasma levels of clonidine were analyzed by radioimmunoassay, and sedation and analgesia were assessed by previously described scoring systems. RESULTS: The venous plasma pharmacokinetics of clonidine following epidural administration showed a considerable interindividual variation. Cmax and Tmax values of clonidine were found to be within the 0.45-0.77 ng/mL and 48-193 min range, respectively. The time to absorb 95% of the clonidine dose from the epidural space into plasma varied between 36 min and 7.6 h. In 6 of the 8 patients postoperative analgesia substantially outlasted the duration of sedation (> or = 2 h). Sedation could not be detected in any patients at plasma concentrations below 0.3 ng/mL. CONCLUSIONS: The pharmacokinetic profile associated with epidural clonidine administration in children (1-9 y) was similar to that previously reported in adults. The postoperative analgesia seen after administration of epidural bupivacaine-clonidine during general anesthesia in children cannot only be explained by residual postoperative sedation.

Adrenergic alpha-Agonists↗

Association of blood loss during delivery to B-hemoglobin.

OBJECTIVE: To study the association between blood loss during delivery and B-hemoglobin before and after delivery (3 days and 10 weeks, respectively). MATERIALS AND METHODS: Information on blood loss for 693 women, 93.9% of all parturients during the study period, was extracted from the original medical records. B-hemoglobin was analyzed at the antenatal maternal health care unit at the last visit before delivery, in capillary samples taken on the ward on the 3rd day, or 10 weeks after delivery. Associations were estimated with Pearson's parametric correlation coefficient. RESULTS: Altogether, 31.3% of all parturients had a higher B-hemoglobin value on the 3rd day after delivery than on the last visit to the maternal health care unit before delivery; the mean intrapartum blood loss was 375 ml (range 100-2,200 ml). The correlation coefficient between B-hemoglobin on the 3rd day after delivery and blood loss was r = -0.53. When the last value recorded at the antenatal maternal health care unit was included in the analysis, the correlation coefficient remained virtually unchanged (r = -0.52). Only 14 (blood loss < or = 600 ml), or 11% (blood loss >600 ml) of the variation in the B-hemoglobin was accounted for by the amount of blood loss. No significant correlation coefficient was evident for B-hemoglobin 10 weeks after delivery vis-à-vis blood loss, irrespective of whether iron supplementation was administered (r = 0.01) or not (r = 0.17). CONCLUSION: The weak association between intrapartum blood loss and B-hemoglobin suggests that the value of B-hemoglobin determined after delivery may be less indicative than previously thought. This conclusion is strengthened by the fact that only a minor part (< or = 14%) of the variation in B-hemoglobin on the 3rd day after delivery is explained by the amount of blood lost.

Biomarkers↗

Methotrexate plasma pharmacokinetics: importance of assay method.

Intravenous methotrexate (MTX) therapy is widely used for treatment of various neoplastic diseases in children. The optimization of the MTX dose and/or the subsequent leucovorin rescue is based on pharmacokinetic data calculated from plasma concentrations collected after cessation of the MTX administration. The influence of the MTX assay method on the subsequent pharmacokinetic evaluation was studied in 13 children with acute lymphoblastic leukemia. Plasma samples were collected after administration of MTX (5-8 g/m2) as 24 h infusions. All samples were analyzed by five different analytical procedures, viz. liquid chromatography (LC), enzyme inhibition assay (EIA), two fluorescence polarization immunoassays (FPIA1 and FPIA2) and enzyme multiplied immunoassay (EMIT). Using measurements from the four non-chromatographic procedures, only about 50% of determined pharmacokinetic parameters (area under the plasma concentration time curve, calculated by the trapezoidal rule and from pharmacokinetic modelling, and the terminal half life time) were within the range 75-125% of the values obtained from LC data. We conclude that the clinical outcome of MTX therapy using estimated MTX pharmacokinetics as guidelines for proper dosing of MTX and/or leucovorin rescue might be affected by the lack of accuracy of non-chromatographic procedures for MTX analysis. There is still a need for improving the accuracy of the procedures aimed at therapeutic drug monitoring of MTX.

Adolescent↗