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Biomedical subjects

A Nergårdh

Publications and source records attributed to A Nergårdh.

At least 19 recordsLinked to original sources
PubMed1992

Receptor function studies in specimens from the proximal human urethra obtained by transurethral resection.

During transurethral resection (TUR) for prostatic hyperplasia, specimens were taken from the proximal urethra. Muscle strips thus obtained were mounted in an organ bath and muscle contraction was induced by adding increasing concentrations of noradrenaline (NA), methoxamine (alpha 1-agonist) and clonidine (alpha 2-agonist). NA and methoxamine induced a dose-dependent muscle contraction, but clonidine had no effect. The influence of prazosin (alpha 1-antagonist) and yohimbine (alpha 2-antagonist) on the NA-induced muscle contraction was also evaluated. Both antagonists had an inhibitory effect, which was much more potent with prazosin. The specimens taken during TUR were found to be suitable for in vitro receptor function studies. The alpha-adrenergic receptor function in the proximal human urethra was found to be mainly of the alpha-type.

Adrenergic alpha-Agonists↗
PubMed1992

Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases.

The progressive myoclonus epilepsies (PME) are a heterogeneous group of rare genetic disorders. Unverricht-Lundborg disease and Lafora's disease are two major classic forms of PME. We recently assigned the gene for Unverricht-Lundborg disease (EPM1) to human chromosome 21 band q22.3. We have now refined the localization of EPM1 by linkage analysis between the disease phenotype and nine DNA markers in 13 Finnish families. Loci MX1 and CD18 flank the EPM1 interval, which spans a distance of about 3.5 megabases. In this 20-centimorgan interval, no recombinations were detected between EPM1 and marker loci BCEI, D21S19, D21S42, D21S113, D21S154, and PFKL. Within this interval a maximum multipoint lod score of 11.04 was reached at loci D21S154-PFKL. In two Swedish families with Unverricht-Lundborg disease no recombinations were detected. In three Italian families with Lafora's disease the linkage results suggested that EPM1 is not the locus for Lafora's disease.

Chromosome Mapping↗
PubMed1991

Pharmacokinetics of total and free valproic acid during monotherapy in infants.

The pharmacokinetics of free and total valproic acid (VPA) in plasma and whole blood after oral administration during steady state was investigated in seven infants (mean age 10.7 months) receiving monotherapy. The VPA concentrations in whole blood closely followed those in plasma but at a reduced level. A positive correlation was found between dose and mean plasma concentration (r = 0.71). Mean terminal half-lives were similar in plasma and whole blood (12.5 and 15.5 h, respectively), but were considerably longer than for free VPA (6.4 and 6.5 h, respectively; P less than 0.01). There was a significant decrease in half-lives with increasing age (P less than 0.05). Plasma and whole blood clearance for total VPA was higher than reported in older infants and adults (17.8 and 28.9 ml/kg per hour) and was considerably higher for free VPA (127.6 and 188.8 ml/kg per hour, respectively). The increase in clearance compared with that in older subjects is well in concordance with a lower protein binding of VPA (mean 85.3%). Of special importance is that the percentage of unbound VPA increased with increasing concentrations of total VPA. The fraction of unbound VPA in plasma increased even more in subjects with low albumin concentrations (P less than 0.01).

Blood Proteins↗
PubMed1990

Monitoring of phenytoin in epileptic children: value of the single morning sample.

The intra-individual variation in plasma concentration of phenytoin was studied in ten clinically well controlled children on monotherapy. The drug concentration was determined in routine pre-dose samples taken on three to five different mornings. On two of these occasions, plasma phenytoin was also determined at 0.5, 1, 2, 3, 5 and 7 h after the dose. The difference between the highest and lowest morning concentrations in a patient varied between 7.5 and 40 mumol/l (mean 20.1 mumol/l). Half of all morning concentration values were lower than 40 mumol/l. This often-recommended lower limit for good seizure control should therefore be reconsidered. The two concentration versus time curves in each patient during 7 h after administration differed considerably in shape, and the first curve could not be used for prediction of the second curve. The ratio between unbound and total drug was very stable and amounted to 9.4, SD 0.94% (n = 168). It is concluded that the conventional single morning sample is satisfactory for routine monitoring in well-controlled children on monotherapy with phenytoin. In problem patients, and during combination therapy, however, more extensive investigation will be necessary, including repeated morning samples as well as determination of dose-interval curves and protein binding.

Adolescent↗
PubMed1989

Lidocaine treatment of neonatal convulsions, a therapeutic dilemma.

Three infants with neonatal convulsions were given lidocaine infusions for three days, three weeks and three months, respectively, and the plasma concentrations of lidocaine and its metabolites were analyzed by HPLC. After a prolonged infusion there was considerable accumulation of the metabolites. This may account for the difficulty of stopping the infusion without relapse of the seizures.

Female↗
PubMed1988

Pharmacokinetics of free and total sodium valproate in adolescents and young adults during maintenance therapy.

The pharmacokinetics of total and free valproic acid (VPA) in plasma and whole blood was investigated in seven adolescents and young adults (mean age 17.3 years) during a dosage interval at steady state. The concentration curves of VPA in whole blood after an oral morning dose (mean 8.2 mg/kg body wt.) closely followed those in plasma but at a reduced level. The apparent volume of distribution (Vd) of total VPA was 0.150-0.197 l/kg body wt. and of free VPA 0.911-1.58 l/kg body wt., which indicates considerable distribution of unbound VPA as well as drug binding to extravascular proteins. The terminal half-life of free VPA (6.4-6.7 h) was significantly shorter (P less than 0.05) than the half-life of total VPA (10.4-11.9 h). The binding of VPA in plasma was concentration dependent and fluctuated considerably within the individual dosage intervals. Concentrations of unbound VPA in plasma water of whole blood varied to a corresponding degree, since distribution to blood cells was low (mean 2.2%). It is concluded that there are substantial differences in the pharmacokinetics of free and total VPA. This may contribute to the well-known poor correlation between dose, plasma concentrations and effect of VPA.

Adolescent↗
PubMed1987

Changes in cholinergic innervation and neuropharmacologic properties in idiopathic hypotonic urinary bladders.

Tissue specimens from hypotonic and normotonic human urinary bladders were investigated histochemically, chemically and neuropharmacologically. In hypotonic bladders the density of acetylcholinesterase (AChE)-positive nerves was markedly reduced and the nerve AChE staining intensity was weak. The concentration of acetylcholine was significantly lower than in specimens from normotonic bladders. At field stimulation the contractions were weak. The observations indicated that sparse cholinergic innervation and reduced acetylcholine synthesis are important for the impaired contractility in idiopathic dystonic bladder.

Acetylcholine↗
PubMed1986

Influence of valproic acid on the gonadotropin-releasing hormone test in puberty.

Twelve epileptic adolescents on valproate (VPA) treatment were studied by means of clinical observation and gonadotropin-releasing hormone stimulation (GnRH) tests. Five patients were investigated before and during VPA treatment. Before treatment the basal and peak levels of gonadotropins were appropriate for age; during treatment both levels were depressed and the areas under the curves were significantly decreased. The long-term effect of VPA was studied in an additional seven patients. The basal levels of gonadotropins were as low and their response to GnRH as poor as in the second test of the first five patients--i.e., during VPA treatment. No recovery was noted in two patients after dose reduction or in a further two patients 10 months after the discontinuation of VPA treatment. In all the patients, however, the usual clinical signs of pubertal development and maturity were unaffected by VPA treatment. The significance of the results for sexual development and fertility is therefore uncertain.

Adolescent↗
PubMed1986

The effect of noradrenaline on the contractile response of the urinary bladder. An in vitro study in man and cat.

In this study, bladder muscle strips from the detrusor of man and cat were used to evaluate the modulating effects of adrenergic agonist and antagonists on the field stimulation induced contractile response. Noradrenaline (NA) inhibited and phentolamine enhanced the contraction in a dose-dependent manner. Propranolol did not influence the field stimulation response. When a study of the combined effect of adrenergic drug influence was performed, the NA-induced inhibition was partly reversed by propranolol but a further increase of the contractile response compared to the control was seen, when phentolamine was added. No species differences were found. The conclusion drawn from these results is, that the inhibiting effect of NA on the contractile response is mediated via alpha- and beta-adrenergic receptors. The former could be located on the short parasympathetic intramural neurons while the latter probably are located on muscle cells.

Aged↗
PubMed1983

Neurotransmission in activation of the contractile response in the human urinary bladder.

The endogenous contracting transmitter at the neuromuscular junction in strips from human urinary bladder has been investigated using field stimulation and selective antagonists. Atropine in low concentrations was found to inhibit bladder contractions whereas higher concentrations of the drug sometimes had the opposite effects. Indomethacin inhibited, phentolamine enhanced and methysergide had no dose-dependent effect on the field stimulation response. It is proposed that acetylcholine is one of the transmitter substances responsible for the contraction of the human detrusor. Species differences which could be responsible for the alleged atropine-resistance of the bladder are discussed. It is concluded that anticholinergic drugs should be of therapeutic value for treatment of muscular hyperactivity in the human urinary bladder.

Acetylcholine↗
PubMed1982

Plasma concentrations of valproate during maintenance therapy in epileptic children.

A total of 20 children with various types of epilepsy were treated with valproate, 11 with monotherapy and 9 with valproate in combination with phenobarbitone, phenytoin, or carbamazepine. Valproate was given either every 8 or 12 h. At least two different dose levels were tried in each patient. The pharmacokinetics of valproate during the interval between doses was determined using a gas chromatographic technique. The clinical effect of the treatment was assessed by interviewing the parents. The plasma concentrations showed considerable fluctuation during the intervals between doses. The mean increase from pre-administration to peak level was 82% when the dose interval was 12 h, and 62% when it was 8 h. The mean plasma half-life of valproate, using a one-compartment model, was 10.9 +/- 1.3 h (mean +/- SD). The plasma half-life of valproate was decreased when the drug was combined with the other anti-epileptics. The calculated area under the concentration versus time curve was linearly related to dose, both in a single patient on four dose levels and when different patients were compared. The clinical effect of valproate monotherapy was best in patients with absences, usually good in myoclonus and less favourable in other types of epilepsy. For children with absences, the optimal dose range of valproate was between 20 and 40 mg/kg/24 h. In comparison, the myoclonic types of epilepsy needed a slightly higher dose level, between 30 and 60 mg/kg/24 h. In the latter group a "therapeutic window" seems to exist, since patients below and above the suggested dose levels were not well-controlled. Therapeutic monitoring of valproate does not appear meaningful when the drug is used as monotherapy. However, in combination therapy, determination of the plasma levels of all anti-convulsants used may be helpful. The large fluctuations of valproate during a dose interval must be taken into consideration when the clinical effects are analysed.

Adolescent↗
PubMed1982

Effects of narcotic analgesics, especially pethidine and norpethidine, on renal pelvic smooth muscle in patients with hydronephrosis.

Relaxation of the renal pelvic smooth muscle is usually attempted as a symptomatic treatment in painful colic of the upper urinary tract. The spasmolytic potency of morphine, pethidine, pentazocine, fentanyl, naloxone and papaverine was evaluated using noradrenaline-contracted pelvic strips from hydronephrotic patients. The order of spasmolytic potency was found to be fentanyl greater than pethidine = papaverine greater than pentazocine = naloxone. Morphine produced a dual effect, starting with contraction followed by relaxation. Norpethidine, which is the only metabolite of pethidine occurring in human plasma, had the same relaxing potency as its parent compound, pethidine. Thus, an active metabolite may play a role in the outcome of spasmolytic drug treatment.

Analgesics, Opioid↗
PubMed1982

Observations on the internal sphincter mechanism during the filling phase in children with hyperactive neurogenic bladder.

The internal sphincter mechanism in the urinary bladder was investigated in three groups of children. Two groups had neurogenic bladder, one of them with and one without detrusor hyperactivity. The third group had no myelodysplasia and normal detrusor activity in the filling phase. In this group the sphincter contractions were sustained at high pressure level, with superimposed waves of substantial amplitude. Myelodysplasia of segments below L3 was associated with hyperactivity of the detrusor. The general sphincter pattern in this condition was the same as in the normal group, but the behavior of the sphincter was not synchronized with the pressure fluctuations in the bladder. In the children with low thoracic or high lumbar level of lesion ther was no detrusor hyperactivity. Their sphincter mechanism could be characterized as passive, with low mean pressure and low amplitude of superimposed waves. When detrusor hyperactivity is present, it seems to be the main factor in leakage from neurogenic bladder. In the absence of detrusor hyperactivity in neurogenic bladder, passivity of the internal urethral sphincter due to dissociation from the spinal centers is proposed as the explanation of incontinence.

Adolescent↗
PubMed1981

Diagnosis of detrusor hyperactivity in children with neurogenic bladder.

Detrusor hyperactivity and its reproducibility was investigated in 22 patients with myelodysplasia and neurogenic bladder. The examinations were performed with microtransducers in the bladder, proximal urethra and rectum. Hyperactivity was found in 15 children all belonging to low lumbar and sacral neurological lesion groups. Patients without hyperactivity mostly had their levels of lesion higher in the spinal cord. In 6 children without neurologic disease no hyperactivity was found.

Adolescent↗
PubMed1981

Influence of atropine and isoprenaline on detrusor hyperactivity in children with neurogenic bladder.

Bladder hyperactivity defined as unconscious, involuntary detrusor contractions giving rise to intravesical pressure increase of at least 15 cm H2O and of minimum 15 sec duration, has been examined in 9 children with myelodysplasia and incontinence. The effect of atropine and isoprenaline on the hyperactivity pattern was evaluated. Atropine had a dose-related inhibiting influence on both frequency and amplitude of detrusor contractions whereas isoprenaline was without these favourable effects.

Adolescent↗
PubMed1981

Neuromuscular transmission in the corpus-fundus of the urinary bladder. An in vitro study in the cat.

In muscle strips from the corpus-fundus of the cat bladder the intramural nervous system was activated by field stimulation. The resulting muscle contraction could not be inhibited by atropine, phentolamine or quinidine. These drugs enhanced the response. Tetrodotoxin, methysergide, cyproheptadine and indomethacin blocked the field-stimulation response in a dose dependent manner. The interpretation of these results with references to transmission at the neuromuscular junction of the bladder is discussed.

Animals↗
PubMed1980

A comparison between microcrystalline and conventional phenytoin preparations: relative bioavailability and steady-state plasma concentrations.

Plasma concentrations of two phenytoin products (a conventional phenytoin acid preparation and a microcrystalline form of phenytoin acid) were studied after single dose administration and during steady-state conditions in four healthy male volunteers. Relative bioavailability for the conventional tablet in comparison with the microcrystallin was in the range of 48-80% during single dose administration and in the range 54-95% at steady-rate. The microcrystalline preparation gave, as expected, a higher rate of absorption. During steady-state conditions, however, this higher rate of absorption was associated with considerable fluctuations in plamsa concentration during the dosage interval. The mean maximum plasma concentration was about 50% high than the value at the beginning of the dose interval (2-dose concentration value) when the microcrystalline product was administered. The corresponding figure was only about 25% for the conventional tablet. Since upward fluctuations in plasma concentrations may be associated with side effects, the more even level obtained with the conventional product may be an advantage from the clinical point of view. An incresed rate of bioavailability is not a clinical improvement if it occurs at the expense of greater fluctuations in plasma concentration during the dose interval.

Biological Availability↗