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Biomedical subjects

A Wallin

Publications and source records attributed to A Wallin.

At least 163 records · Page 9Linked to original sources

Distribution of phenobarbital in whole blood during pregnancy and perinatally--an in vitro study.

The distribution of phenobarbital (PB) in whole blood and its fractions in 8 pregnant women, in 10 mothers and infant pairs at delivery and in 7 controls was studied by equilibrium dialysis. The lowest protein binding was in cord plasma. A correlation was found between the maternal and cord plasma PB binding. The adult plasma PB binding ratio was correlated with the molar albumin concentration, but no such relation was found in cord plasma, suggesting inhibition of binding by other factors. As a counterpart to the lower protein binding in maternal and cord plasma, the fraction of PB distributed to erythrocytes in those groups was significantly higher. The apparent concentration of PB in maternal erythrocytes was increased. The distribution of drugs to the various fractions of whole blood is an important consideration perinatally, since the binding characteristics of plasma and blood cells in mother and fetus will be crucial determinants for the placental transfer of drugs.

Bilirubin↗

Phenobarbital prophylaxis for hyperbilirubinemia in preterm infants. A controlled study of bilirubin disappearance and infant behavior.

Phenobarbital (PB) has been used at several pediatric centers for prophylaxis against neonatal hyperbilirubinemia. However, few attempts have been made to evaluate this procedure quantitatively, and a variety of dose schedules has been proposed. Therefore, a randomized, controlled clinical trial was performed in which the effects on bilirubin disposition and on neonatal behavior was quantitated. Forty-three preterm infants were randomized into one of four dose groups and given 0, 4, 8, or 12 mg of PB per kg in a single dose within the first few hours after birth (mean 2.2 h). The total serum bilirubin disappearance rate was found to be significantly increased (p less than 0.01) only in the 12 mg/kg group. This effect was not evident until postnatal day 7. The 4 and 8 mg/kg groups were not significantly different from the control group at any time. Infant behavior was monitored by a non-invasive time-lapse filming technique. The time spent in quiet sleep was found to be proportional to the plasma PB concentration at one day of age (r = 0.61). The infants in the 12 mg group spent a larger proportion of time in quiet sleep than the other groups (p less than 0.05). The plasma half-lives, plasma clearances and volumes of distribution of PB were similar in the three dose groups. No correlation was found between the pharmacokinetics and the gestational age of the infant. It is concluded that in order to enhance the bilirubin disappearance rate, PB has to be administered in doses that will affect behavior.

Bilirubin↗

Time-lapse filming of newborn infants. A new technique in monitoring of behavioral states.

Knowledge of the newborn infant's behavior is of great importance for an understanding of postnatal adaptation and the influence of exogenous stimuli, such as drugs. To date, however, the methods used have been to sophisticated and complex for use on a busy ward. Moreover, procedures for monitoring physiological parameters in this age group should be non-invasive and gentle for the infant, and acceptable to parents and personnel. In this paper, a simplified technique is presented where observation of the infant can be registered with an ordinary super-8 movie camera adapted to time-lapse. Heart rate, EMG and vocalization are recorded simultaneously. The time-lapse filming technique is relatively easy to learn, it is simple and economic and can be used even during routine clinical care. Assessments were made from the films only, from the recordings only and from a combination of films and recordings. All these modes of assessment were found to be satisfactorily reproducible. Filming combined with respiratory recording gives sufficient information to classify neonatal infant behavior.

Adaptation, Physiological↗

Symphysis-fundus measurement in prediction of fetal growth disturbances.

Graphic supervision of pregnancy by symphysisfundus (SF) tape measurement was introduced in an area of north Stockholm in 1972. Subsequently a considerable and persistent drop in perinatal mortality was seen. SF-tape measurements reflect the fetal growth and correlate well with fetal crown-rump length. Over a 2-year period SF-growth data were collected for all infants admitted to the neonatal unit in the area. In all, 812 singletons were studied. Maternal smoking habits in the first trimester were recorded. A group of 283 normal neonates served as controls. A highly significant statistical difference was found on comparing the mean birth weights of infants associated with high, "normal", and low and/or static SF-curves from 34 weeks of gestation and onwards. The sensitivity in detecting LGA infants by high SF-curves was 74%, with a specificity of 84%. The proportion of mothers with uncertain expected dates of confinement (EDC) was high among those having "normal" SF-curves, yet giving birth to SGA infants. After correction for gestational age, the SF-curves adjusted for dates were in most cases low and/or static during the weeks prior to delivery. The sensitivity and specificity would thereby have increased to 95% and 93%, respectively, in detecting SGA infants had their dates been certain. Maternal smoking showed an overall incidence of 37% in the first trimester. No increase in incidence was seen among mothers to preterm infants. There was as could be expected a highly increased ratio of smoking mothers to infants with birth weight less than -1 S.D., regardless of gestational age. SF-tape measurement is recommended as a graphic method of supervising pregnancy for the detection of accelerated and retarded fetal growth. Early and correct determination of gestational age, however, is a prerequisite.

Birth Weight↗

Plasma concentrations of phenobarbital in mother and child after combined prenatal and postnatal administration for prophylaxis of hyperbilirubinemia.

Phenobarbital is known to reduce serum bilirubin concentration in the newborn infant, but optimal dosage is unknown. Ten pregnant women and their infants were given a standard regimen including prenatal maternal administration and postnatal administration to the infant during the first week of life. The plasma levels of phenobarbital in the infants were found to increase during the period of administration, and to remain high for many days beyond the period of hyperbilirubinemia. Optimal dose schedules for phenobarbital should be based both upon pharmacologic effects (including those other than bilirubin disposition) and upon the pharmacokinetic profile of the drug in the newborn infant.

Female↗

Oxygen consumption of the newborn rabbit treated with pulmonary surfactant.

A method is described for measuring oxygen consumption of small animals. It was used for 151 newborn rabbits delivered on the 27th, 28th, 29th, and 30th day of gestation. Half of the neonates were given a pharyngeal deposition of a concentrated surfactant (SA) suspension prior to their first breath. The remaining neonates served as controls. The survival rate among the immature rabbits treated with SA was significantly higher. The treatment did not affect oxygen consumption in any age-group. With increasing maturity, the neonates consumed more oxygen, and the controls delivered on the 30th day of gestation consumed 29.6 +/- SEM 4.2 ml oxygen per kilogram and minute.

Age Factors↗

Calpain and calpastatin in normal and Alzheimer-degenerated human brain tissue.

The Ca2(+)-dependent neutral proteases calpain I and II as well as their specific inhibitor, calpastatin, were isolated from normal and Alzheimer-degenerated frozen human brain tissue. In the Alzheimer group calpain I activity was higher in cortex than in mesencephalon. The calpastatin activity was lower in cortex in both groups. This may implicate a higher Ca2(+)-dependent proteolysis in cortex compared to mesencephalon. In the Alzheimer group the cortical calpain II level decreased with an increasing degree of neuropathological changes. In the control group, the level of calpastatin decreased as the number of plaques and tangles increased. Evidence was obtained for a correlation of net calpain activity and the extent of neuropathological changes in cortex.

Aged↗

Significance of decreased lumbar CSF levels of HVA and 5-HIAA in Alzheimer's disease.

The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 123 patients with Alzheimer's disease (AD) and 57 healthy controls. Despite CSF sampling under strictly standardized conditions, a wide variability in values among both patients and controls was found, as well as fluctuations in repeated samples from individual patients. This suggests that several unknown factors influence the lumbar CSF levels of monoamine metabolites. The AD group showed significantly lower mean levels of HVA (p less than 0.0001) and 5-HIAA (p less than 0.0001) than the control group. A relation between severity of disease and HVA was also found. The widespread neurotransmitter disturbance in AD, together with the nonspecificity of reduced lumbar HVA and 5-HIAA levels, suggests that the changes are nonspecific, secondary to the cerebral degeneration in AD.

Aged↗

Increased proteolytic activity in lymphocytes from patients with early onset Alzheimer's disease.

The levels of calpains (m-calpain and mu-calpain) in peripheral blood lymphocytes from patients with Alzheimer's disease were determined via Western blotting. The Ca-dependent proteolytic activity and the calpastatin activity were estimated using incubation with exogenous substrate. Evidence was obtained for an increased Ca-dependent proteolytic activity in lymphocytes from patients with early onset Alzheimer's disease. There was also an increased level of membrane-bound mu-calpain in this group of patients. The observed changes may be caused by a general dysregulation of Ca homeostasis in peripheral cells of early onset Alzheimer victims.

Age of Onset↗

Lack of differences in blood and tissue concentrations of endogenous ethanol in conventional and germfree rats.

Headspace gas chromatography was used to determine the concentrations of endogenous ethanol in blood and tissue of conventional and germfree rats. In all biological specimens analysed, the four principal volatile endogenous substances were identified as methanol, acetaldehyde, ethanol and acetone. No statistically significant differences in the concentrations of endogenous ethanol were noted between conventional and germfree animals. In whole blood, liver, kidney, and brain of germfree rats the concentrations of endogenous ethanol were 4.2 +/- 0.19 microM, 5.1 +/- 0.55 microM, 8.2 +/- 0.59 microM and 4.4 +/- 0.17 microM (means +/- SE), respectively. The higher concentration in kidney was also observed in conventional rats. Our results suggest that ethanol is a normal metabolic intermediate in rats and does not exclusively arise from microbial fermentation reactions in the gastrointestinal tract.

Acetaldehyde↗

VIP-sensitive adenylate cyclase, guanylate cyclase, muscarinic receptors, choline acetyltransferase and acetylcholinesterase, in brain tissue afflicted by Alzheimer's disease/senile dementia of the Alzheimer type.

Biochemical parameters were determined in autopsy material from several brain regions of thirteen patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) (mean age 75 years) and from brains of ten age-matched controls (mean age 76 years). Choline acetyltransferase specific activity was significantly lower in the nucleus caudatus, putamen, left thalamus, hippocampus and the cortex from gyrus hippocampus and the temporal lobe in AD/SDAT, acetylcholinesterase specific activity was significantly lower in the hippocampus, parietal and left frontal lobe in AD/SDAT samples than in corresponding samples from aged-matched controls. A compensatory increase of muscarinic receptors was found in the nucleus caudatus and left frontal lobe samples in AD/SDAT. Guanylate cyclase activity was not significantly altered in AD/SDAT in the brain regions examined. The basal, non-stimulated activity of adenylate cyclase was significantly (p less than 0.05) elevated in hippocampus samples from AD/SDAT patients and the enzyme activity stimulated by the vasoactive intestinal polypeptide VIP (2 microM) or forskolin (10 microM) was also elevated in AD/SDAT although not significantly.

Acetylcholinesterase↗

Decreased monoamine metabolites in frontotemporal dementia and Alzheimer's disease.

The concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (HMPG) in the cerebrospinal fluid (CSF) of patients with clinical frontotemporal dementia (FTD; n = 30), early onset Alzheimer's disease (EAD; n = 33), late onset Alzheimer's disease (LAD, n = 27) and normal controls (n = 31) were determined using HPLC. ANCOVA showed no significant effect of neuroleptic medication, extrapyramidal signs, myoclonia or gender on the CSF levels of the monoamine metabolites. Homovanillic acid was significantly reduced in all diagnostic groups (FTD, p = 0.0002; EAD, p = 0.016; LAD, p = 0.013). 5-Hydroxyindoleacetic acid was significantly reduced in EAD (p = 0.013) and in LAD (p = 0.0014), and HMPG was reduced in LAD only (p = 0.020). HMPG was significantly higher in FTD compared to EAD (p = 0.0005) and LAD (p = 0.0003). CSF-5-HIAA was significantly reduced in patients with antidepressant medication (p = 0.006). ANCOVA within the FTD group showed no significant effect of neuroleptic or antidepressant medication, extrapyramidal signs, myoclonia, gender or FTD subtype on the CSF levels of the monoamine metabolites. The results suggest that CSF-HMPG might differentiate FTD from EAD and LAD, but not from normals.

Adult↗

Teratogenicity of the class III antiarrhythmic drug almokalant. Role of hypoxia and reactive oxygen species.

The class III antiarrhythmic drug almokalant (ALM) was given to pregnant rats on Gestation Day 11 (125 micromol/kg) or 13 (25 micromol/kg). Other groups were pretreated with alpha-phenyl-N-t-butylnitrone, (PBN; 850 micromol/kg intraperitoneally) 1 h before administration of ALM or given (-)-2-oxo-4-thiazolidine carboxylic acid (OTC; 250 micromol/kg subcutaneously) 4 h before administration of ALM. PBN is a spin-trapping agent that can capture reactive oxygen species (ROS), and OTC is an antioxidant. Controls received tap water only. All groups (eight in total) consisted of 7 to 10 pregnant rats. ALM induced cardiovascular defects, orofacial clefts, and tail defects after administration on Day 11, and reduced the size of digits on Day 13. Pretreatment with PBN prevented induction of all the above-mentioned malformations by ALM. The results also indicated that OTC may have some protective effect against ALM-induced teratogenicity but not to the same extent as PBN. The results support the hypothesis that almokalant induces malformations via induction of episodes of embryonic arrhythmia/cardiac arrest, which result in hypoxia followed by reoxygenation and generation of ROS.

Abnormalities, Drug-Induced↗

Longitudinal EEG findings in dementia related to the parietal brain syndrome and the degree of dementia.

EEG slow-wave activity was correlated with the regional brain syndrome profile in 74 patients with dementia. The EEGs were visually assessed using a semiquantitative rating scale. The intensities of four regional brain syndromes (parietal, frontal, subcortical, global) and the degree of dementia were rated. The patients were examined twice with a 1-year interval. A significant relationship was found between the increase in EEG slow-wave activity and the increase in intensity of the parietal brain syndrome. A somewhat lower significance was found for the relation between increase in slow-wave activity and increase in dementia degree. The results suggest that the EEG deterioration in dementia mainly reflects the gradual decline of parietal brain function.

Aged↗

Occurrence of delirium in different regional brain syndromes.

Old age and organic brain disorder are major risk factors for delirium in the elderly. The localization of the brain damage in dementia may be of importance for this risk. The aim of the present study was to investigate the rate of delirium in patients with different regional brain syndromes. Included in the study were 194 demented patients. The occurrence and intensity of four regional brain syndromes were estimated: parietal lobe syndrome, frontal lobe syndrome, subcortical syndrome and global brain syndrome. The analyses showed that the rate of delirium was significantly higher when a global brain syndrome was predominant than when any one of the other syndromes predominated.

Aged↗