Communication of results of necropsies.
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Biomedical subjects
Publications and source records attributed to A Berlin.
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Neuroendocrine changes associated with performance testing requiring sustained attention were assessed in eight normal male subjects. To verify whether the hormonal pattern was modified by chronic stimulation of opiate receptors, eight heroin addicts also were studied. Reaction times were similar in normal and addict subjects. In normal individuals, consistent and significant increases in plasma ACTH and beta-endorphin and in urinary epinephrine and norepinephrine were observed, whereas serum prolactin (PRL) progressively decreased over the testing period. Despite maintained performance capabilities, heroin addicts showed a blunted response of ACTH and a paradoxical decrease in endorphin levels. As the normal subjects, both epinephrine and norepinephrine in urine showed the same significant increase over baseline values. Serum PRL showed a similar trend towards decreased values over the testing period in both groups.
Forty-four elements (Al, Sb, As, Ba, Be, B, Br, Cd, Ce, Co, Cr, Cs, Cu, Eu, Ga, Au, Hf, In, Ir, Fe, La, Lu, Mn, Hg, Mo, Nd, Ni, Pb, Rb, Sm, Sc, Se, Ag, Sr, Ta, Tb, Tl, Th, Sn, W, U, V, Zn, Zr) have been determined in the dialysate for hemodialysis (HD) and fluids for hemofiltration (HF) and continuous ambulatory peritoneal dialysis (CAPD). Multiple determinations have been performed for each dialysis fluid. Several trace elements (TE) showed remarkably elevated average levels; moreover, different bathes of the same commercial product may present a wide variability in TE concentration. The data point out the pivotal role of dialysis fluids in contributing to TE imbalance in dialysis patients and allow the assessment of the potential element exposure of patients on regular dialytic treatment. Patients on HD treatment would be exposed on a weekly basis to milligrams of Al, B, Ba, Br, Cu, Fe, Ni, Pb, Rb, Sr and Zn; on HF, the highest exposures are due to Al, B, Br, Fe, Pb and Zn; on CAPD to B, Br, Fe and Zn. The weekly exposure for several TE appears to be 50- to 12,000-fold higher than the corresponding values on the amount absorbed via the diet (HD: Au, Ba, Be, Ce, Ga, La, Sc, Ta, Th, V, Zr; HF: Be, Ce, Ta, Th, V, Zr; CAPD: Au, Be, Ce, Ga, V, Zr).(ABSTRACT TRUNCATED AT 250 WORDS)
Performance in a vigilance task and the associated neuroendocrine changes during the performance in the task were examined in healthy subjects and in three groups of male heroin-addicts both before undergoing rehabilitation programmes and at various intervals from withdrawal (5 days, 1 to 2 mon, and 3 to 48 mon, respectively). Plasma levels of ACTH, beta-endorphin (EP) and prolactin (PRL) were measured every 10 min before and during performance. In drug addicts, simple reaction times never showed any significant difference as compared to control values. Despite similar baseline levels, ACTH exhibited a markedly depressed response to psychological testing in drug-addicts as compared to controls. Whereas a three-fold increase in ACTH was observed in 'normal' subjects during the performance (from 17 to 54 ng/l), mean values from drug-addicts remained unchanged. EP levels showed a wide scatter of individual values and inconsistent time courses over performance testing: after short-term abstinence, EP showed a three-fold increase over baseline control values but, contrary to what seen in 'normal' subjects, no changes over time were recorded. After long-term abstinence, basal EP was close to control values, but its increase during the testing period was still blunted. PRL levels decreased over the testing period both in controls and in heroin addicts. Thus, despite the lack of obvious signs of neurotoxicity, drug abusers show neuroendocrine changes consistent with a long-lasting selective impairment of the hypothalamic modulation of pituitary secretion.
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In this work, definition and interpretation of different functional parameters, which were obtained through urodynamic investigations, are given. Normal patterns in child age are presented. They were the results of personal studies in patients with normal urinary tract. The pressure curve must be seen as an entity. The so-called after contraction is no detrusor contraction. But possibly it is the result of a determined lapse of contracting and relaxing occurrences in the different parts of the bladder and its outlet at the end of micturition.
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Seven members of one family had rare, inherited syndrome of follicular atrophoderma, basal cell carcinomas, and localized anhidrosis. Associated findings in some subjectes were generalized hypohidrosis and "eczema" involving the face shortly after birth. This syndrome shows dominant inheritance, possible x-linked. Follicular atrophoderma is an important skin manifestation, as it has been associated in all reported cases with other systemic or cutaneous abnormalities.
Epidural analgesia with bupivacaine was used for elective cesarean section, and repeated maternal and neonatal blood samples were collected over 24 h for calculation of drug concentration. A gas-chromatogrphic micro-method was used for the analysis. The aim of this investigation was to evaluate the placental transfer and the elimination rate of the drug. No signs of systemic toxicity were observed in any mother or child, despite relatively high blood concentrations. The fetal-maternal ratio of concentrations at delivery was higher than in previous studies, most probably due to the protein-binding characteristics of bupivacaine and the dosage used. The biological half-life of the rapid phase of elimination (alpha-phase) in the newborn was shorter than in the mother (P less than 0.002), indicating a more rapid distribution process. The half-life of the slow phase of elimination (beta-phase) in the newborn was of the same magnitude as in the mother, indicating that neonatal elimination processes of bupivacaine may be well developed at birth.
Therapeutic failure of griseofulvin therapy are fairly common, espcially when toe nail infections are treated. The reasons for the failures remain largely unknown. The aim of the present investigation was to study whether pharmacokinetic factors may be responsible. At first, single-dose and steady-state pharmacokinetics of griseofulvin were analysed in volunteers by means of a gas-chromatographic technique. It was found that there was no difference in plasma levels of the three brands of griseofulvin commercially available in Sweden, whereas there was a singificant difference of absorption between individuals. The plasma half-life varied considerably from day to day in the same individual. In the second part of the investigation griseofulvin plasma concentrations were determined in 27 patients treated with griseofulvin for onychomycosis and related to the therapeutic result. All patients but one were initially improved but the therapeutic effect faded in 15 patients after 5-20 months of treatment ("partially healed" patients). In 11 patients the nail infections were clinically healed after 6-24 months. However, no statistically significant difference of the plasma griseofilvin levels could be demonstrated between the healed and partially healed groups. Some possible reasons for the therapeutic failure are discussed.
Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)beta) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, alpha and beta obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
Lumbar epidural analgesia with bupivacaine was administered to 33 women for relief of pain during labor. At delivery blood samples were drawn from the umbilical cord vessels and from a maternal peripheral vein. Blood samples were also collected from the noenate and its mother, 1, 4, and 20 hours after delivery. Analyses of bupivaccaine concentrations were carried out in all samples with a gas-chromatographic technique. The drug concentration in the umbilical vein (UV) was usually higher than the corresponding umbilical artery value (UA), but with increasing time interval between the last bupivaccaine infection and delivery the UA/UV drug concentration ratio rose. After delivery the rate of drug decline in blood was similar in mother and newborn infant. The clinical condition of the infant was unrelated to the drug concentration in the umbilical cord vessels.
A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N,N-bis (phenylcarbamoyl methyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0+/-1.1 mug/ml (mean+/-SE) at the end of infusion to 3.5+/-0.5 mug/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7+/-0.1 mug/ml. In these patients 22+/-2% (mean+/-SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.
Lumbar epiduval analgesia with bupivacaine was given to 37 women for uncomplicated labor. After the blcokade serial determinations of pH and bupivacaine concentration were made in fetal scalp blood and maternal venous blood and there was continuous monitoring of the fetal heart rate. Fetal scalp blood pH was within normal limits and no pathologic FHR tracings were elicited by the blockade, although a temporary decrease of the baseline fetal heart rate irregularity was seen in about one-fifth of the cases. Fetal drug concentrations were low and about one-fourth of corresponding maternal values. After reinjection of bupivacaine the degree of drug accumulation was fairly similar in fetal and maternal blood.
The arteriovenous concentration difference of bupivacaine in plasma after epidural injection in man and after intramuscular injection in dog was studied. In man, arterial concentration was higher than peripheral venous ocncentration during an initial period of about 30 min, after which time period venous and arterial concentrations became fairly similar. Comparable results were obtained in the animal experiments. In addition, the experiments in dog indicated that the concentration of bupivacaine was fairly similar in central venous plasma and arterial plasma, but higher than the peripheral venous plasma concentration. These factors have to be taken into consideration when toxicological studies of local anaesthetic drugs are made.
Plasma levels of diazepam and N-desmethyldiazepam were investigated in 19 children by a gas chromatographic method permitting the use of capillary sample. Intravenous administration was studied in 3 children and the plasma level curves showed a rapid decline during the first hour. Absorption and elimination after rectal administration of a solution in 16 children were similar to those after intramuscular administration. Diazepam given by suppository to 5 children gave much lower plasma levels and delayed time to peak levels. Recurrence of seizures in 2 children indicated that the anticonvulsants plasma level was of the order of 150 to 200 mug/liter. No significant side effects were observed. Thus rectal administration of a solution of diazepam is a practical method to arrest convulsions in children.
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Sixty-six European laboratories participated in an intercomparison program of lead, mercury, and cadmium analysis in blood, urine, and aqueous solutions. The experimental protocol was designed in such a way that the effect of precision, experience, and analytical method could be evaluated. For all the analyses, the scatter of the reported results is important. The major factor influencing the variability of the results is the intralaboratory variation. Analytical methods and degree of experience do not seem to have a significant influence. However, with the exception of mercury determination in urine, a satisfactory intralaboratory precision is not sufficient to make the interlaboratory variation acceptable. It appears that systematic errors are responsible for the high interlaboratory variation observed between "precise" laboratories.