Biomedical subjects
Publications and source records attributed to M Weiss.
Two case reports of sudden cardiac death are detailed here. Holter monitoring plays an important role in documenting arrhythmias leading to sudden cardiac death. In addition, the importance of the Lown grading concept should not be underestimated. Our two case reports and a subsequent review of the literature demonstrate both points.
Based on a stochastic pharmacokinetical model (which mirrors topological properties of the circulatory system) it is shown by reinterpreting results of Wise (1974) that if the transit times of circulating drug molecules have a generalized inverse Gaussian distribution the corresponding residence times are gamma distributed. The condition that the probability of elimination of a drug molecule in a single circulatory passage is sufficiently small appears to be valid for most drugs. Thus theoretical evidence is given for fitting blood concentration-time curves following bolus injection of a single dose by power functions of time.
The bounds of the accumulation profile can be predicted on the basis of the mean disposition residence time (MDRT) of a drug. The time to reach 90% of the plateau level (t0.9) is less than 3.7 MDRT. This prediction can be improved if, in addition, the variance of disposition residence time (VDRT, CV2D = VDRT/MDRT2), or the terminal exponential coefficient (lambda), is known. For CV2D----1 or lambda MDRT----1, the time to reach steady state (t0.9) approaches 2.3 MDRT (limiting case of monoexponential drug disposition curve). Conditions are stated under which lambda can be regarded as the principal determinant of the accumulation rate.
Taking into account drug concentration differences within the circulatory system, a unique definition of each of the basic pharmacokinetic parameters, clearance (CL), steady-state volume of distribution (Vss), and mean disposition residence time (MDRT), is given which is generally valid for linear systems. The conventional relationship MDRT = Vss/CL holds theoretically only in the case of right atrial sampling following bolus intravenous injection. The values based on blood drug concentration from a peripheral venous sampling site are influenced by the pharmacokinetic properties of the lungs and the sampling tissue. Practically, the pulmonary extraction ratio and the mean transit time through the sampling tissue may thereby be of particular importance. Thus the effect of the sampling site on the pharmacokinetic parameters estimated by standard (classical) methods is quantitatively explained.
Steroidogenesis by subcellular fractions of adrenal cortex proper (C.P.) and special zone (S.Z.) of female possum (Trichosurus vulpecula) was studied. Mitochondrial, microsomal and cytosol cell fractions were incubated with appropriate substrates in the presence of an NADPH-generating system. The major products formed from [3H]progesterone and [3H]17 alpha-hydroxyprogesterone by the microsomal fraction of the C.P. were 11-deoxycortisol and 11-deoxycorticosterone and 3 alpha (beta)-hydroxy-5 alpha-androstan-17-one by the S.Z. The mitochondrial fraction converted [3H]11-deoxycortisol to cortisol in yields twenty times higher by the C.P. than by the S.Z. and to 17 alpha, 20 beta,21-trihydroxy-4-pregn-3-one thirty times higher by the S.Z. The conversion of [3H]androstenedione to 11 beta-hydroxyandrostenedione by the C.P. was approximately double that of the S.Z., while 18-hydroxyandrostenedione (tentatively identified) formed the highest yield in both zones. Incubation of the same substrates with cytosol formed two 5 beta-pregnane and two 5 beta-androstane derivatives in total yields less than 5% by C.P. and greater than 60% by S.Z. Aromatase activity, estimated by the release of [3H2O] from [1 beta 3H]testosterone, in the adrenals of 8 possums, was in each experiment negligibly low. Determination of total enzyme activities in the two zones revealed that 11 beta, 18 and 21-hydroxylases were higher in the C.P., while 17 alpha-hydroxylase was higher in the S.Z. Similar results were obtained when the rates of formation of hydroxylated products were estimated in the presence of saturating amounts of substrates. Active 5 alpha- and 5 beta-reductases, C17-20-lyase and 3 alpha (beta) and 20 beta-hydroxysteroid dehydrogenases were found almost exclusively in the S.Z. We conclude that the S.Z. at lower levels of activity than the C.P. could contribute to the basal secretion of corticosteroids. In addition, the S.Z. has a high capacity to form C19 steroids and 5 alpha- and 5 beta-reduced steroids. The possible role of the S.Z. in possum is discussed.
The effect of gonadotrophin and oestradiol administration on adrenocortical special zone (S.Z.) development and steroidogenesis was studied in immature female possums. Adrenals were examined histologically to determine S.Z. formation, and cell-free homogenates were incubated with 3H progesterone in the presence of an NADPH-generating system. Treatment with PMS + hCG, resulted in the development of S.Z.s. varying in volume from 10 to 60% of the total adrenal gland. This response was independent of ovarian status (i.e. immature or multifollicular). Treatment with porcine FSH (NIH-FSH-P2) also induced development of a S.Z. Oestradiol treatment was ineffective. The appearance of the S.Z. was associated with a change in steroidogenesis. The adrenals of controls produced cortisol and corticosterone in yields of approx. 70%, while these products were less than 22% in the animals with S.Z.s. The major conversion products in the treated animals were 5 beta-reduced pregnane derivatives, in yields ranging from 67 to 93%. The yields of products from the oestradiol treated animals closely resembled those of the controls. It was concluded that FSH is capable of inducing the development of an adrenocortical S.Z. in immature female possums and consequently stimulating adrenal steroid reduction. It appeared that oestradiol was not involved in this process.
After inoculation into 2 foals, Berne virus induced neutralizing antibody, but did not cause clinical symptoms. In a horizontal study of seropositive mares and their offspring, a decline of maternal antibodies and a sudden synchronous seroconversion in all foals were observed, again without clinical symptoms. The virus is widespread in the Swiss horse population and has been so during the last decade; rises in antibody titers were noted in 9% of paired sera sampled at random. Positive reactions were also obtained in serum neutralization tests and ELISA using small numbers of horse sera from Germany, France and the U.S.A. The results of neutralization tests and ELISA were correlated in 83% of random samples tested; 13% were neutralization-positive and ELISA-negative and in 4% the inverse was observed. Neutralizing activity was found in the sera of other ungulates (cattle, goat, sheep and pig), laboratory rabbits and 2 species of wild mice (Clethrionomys glareolus and Apodemus sylvaticus). Inconclusive results were obtained with feline and human sera; those from dogs and foxes (Vulpes vulpes) were consistently negative. The probable occurrence of antigenic variants in Berne-type viruses is discussed.
In infected embryonic mule skin cells, Berne virus directs the synthesis of two main polypeptides (22K, 20K); in addition, virus-specific proteins with apparent molecular weights of greater than 200K, 80K to 120K, 32K and 17K were detected after radioimmune precipitation. The replication of Berne virus was reduced more than 1000-fold by actinomycin D, when the drug (0.1 to 1.0 micrograms/ml) was added during the first 8 h after infection; alpha-amanitin (25 micrograms/ml) produced a similar though less pronounced effect. U.v. preirradiation of the cells for greater than or equal to 5 s led to a dramatic decrease in the production of extracellular virus. The results presented support our suggestion that Berne virus is a representative of a new family of animal viruses.
Explore the source record for details and available documents.
An open, multi-centre clinical trial was carried out in 537 hospital patients and 2138 general practice patients to evaluate the efficacy and tolerance of isosorbide 5-mononitrate in the treatment of angina pectoris. Prior to entry into the trial, angina attack frequency and acute glyceryl trinitrate consumption were assessed during previous, in most cases unsatisfactory, anti-anginal therapy. After a treatment-free washout period of 3 days, graded multi-stage exercise testing was performed and then treatment started with 20 mg isosorbide mononitrate 3-times per day. Exercise testing was repeated after 14 days' therapy and, in the case of the hospital patients, also 4 to 5 hours after the first dose of isosorbide mononitrate. At the end of the 14-day treatment period, angina attack frequency and glyceryl trinitrate consumption were again assessed. Similar results were obtained for both hospital and general practice patients. Changing to isosorbide mononitrate resulted in a marked reduction in angina frequency, with complete elimination of angina attacks in approximately half of the patients; nocturnal angina, present in approximately 20% of the patients during previous therapy, virtually disappeared during isosorbide mononitrate therapy. Exercise tolerance and performance improved in the majority of patients, with a marked increase in the number of patients able to exercise to the level at which some symptom other than angina pectoris caused them to stop. ST-depression during exercise and exercise-induced arrhythmias also showed clear reductions during isosorbide mononitrate therapy. Tolerance to isosorbide mononitrate was good, the expected 'nitrate headaches' being the only common side-effect reported. The results were such that continuation of treatment with isosorbide mononitrate after the trial was recommended by the attending physician in 77% of the hospital patients and 87% of the general practice patients.
An open, multi-centre trial was carried out to investigate the efficacy and tolerance of isosorbide mononitrate used as anti-anginal therapy in a large group of patients under normal general practice conditions. A total of 10,229 patients with coronary heart disease of average duration of 4 years entered the trial, of whom 8769 had sufficiently severe symptoms to be included in the analysis of results. Most of the patients (92.3%) had previously been treated with cardiovascular drugs. In the trial, all patients were treated with oral isosorbide mononitrate, 20 mg 3-times daily, for a period of 14 days. Treatment resulted in an improvement of angina (compared with the situation during previous therapy) in 79.9% of the assessed patients, complete abolition of angina attacks being achieved in 52.1% and a reduction in frequency of attacks in a further 28.7%. This reduction in angina was associated with a reduced acute consumption of nitrates used for the treatment of attacks. In the smaller sub-group of patients who had received no previous anti-anginal therapy, isosorbide mononitrate treatment resulted in improvement in 91% of patients, complete abolition being achieved in 77.5%. Nocturnal angina was almost totally eliminated by isosorbide mononitrate treatment and this can probably be explained in terms of the favourable pharmacokinetic profile of the drug. 'Nitrate headache', observed in 20.5% of the patients, was the only common side-effect of treatment. The absence of hypotension or tachycardia in significant numbers of patients indicates that isosorbide mononitrate should be well tolerated, as well as efficacious, in all patients with coronary heart disease.
It has been established that the effect of LH on ovarian steroid formation results initially in a rise of overall steroid production, which 2-4 h later is followed by a decrease in the formation of C19-steroids. To determine the reason for this decrease, the course of 17 alpha-hydroxyprogesterone (17 alpha-OHP) metabolism in immature rat ovaries (10,000 X g supernatant) stimulated to ovulate with pregnant mare serum gonadotropin (PMSG) was investigated. Employing optimal conditions the C17,20-lyase was estimated from the formation of androstenedione from 17 alpha-OHP as substrate. The Michaelis-Menten constant Km was 61 +/- 4 microM and V varied according to the time after PMSG administration. The initial activity at 0 h was 340 pmol min-1 mg-1 protein. It decreased 48 h after PMSG to 160 pmol, followed by a slight rise at 54 h and followed by a 60% fall at 57 h, at the height of the LH-surge. The activity declined to undetectable levels at 60 and 64 h (8 h before ovulation) and remained undetectable after ovulation at 72 and 96 h after PMSG. The enzymes 5 alpha-reductase and 20 alpha-hydroxysteroid dehydrogenase were estimated from the formed 3 alpha, 17 alpha-dihydroxy-5 alpha-pregnan-20-one and 17 alpha, 20 alpha-dihydroxy-4-pregn-en-3-one, respectively. In the unstimulated ovary the 5 alpha-reductase was 405 pmol; it decreased to 110 pmol 48 h after PMSG and continued to decrease. The 20 alpha-hydroxysteroid dehydrogenase activity which was undetectable in untreated rats, rose to 330 pmol 60 h after PMSG, 8 h before ovulation. The changes in enzyme activities when tracer amounts of [3H] 17 alpha-OHP were used agreed with the pattern of kinetic studies. From these incubations eight metabolites were isolated, one of them, 5 alpha-pregnane-3 alpha,17 alpha, 20 alpha-trioi, has not been previously identified. It is concluded that the decrease in C17,20-lyase activity limit the formation of C19-steroids in preovulatory follicles shortly before ovulation.
The effect of elevated plasma epinephrine concentrations (approximately equal to 800 pg/ml) on ketone body kinetics was determined in postabsorptive normal subjects using primed-continuous infusions of 3-14C-acetoacetate. Infusion of epinephrine (60 ng/kg/min) resulted in a transient increase in total ketone body production to a maximum of 2.5-fold the basal rate within 45 min (P less than 0.01 versus controls). Ketone body uptake increased with a delay, compared with production, causing a 2.8-fold increase in total ketone body concentrations (P less than 0.05 versus controls). Plasma free fatty acid (FFA) and blood glycerol concentrations increased transiently during epinephrine; their course was similar to that of ketone body production. Epinephrine administration resulted in hyperglycemia, hyperlactatemia, and a modest increase in plasma insulin and glucagon concentrations. To assess epinephrine's effect on ketone body kinetics during lack of insulin, and to avoid epinephrine-induced alterations in plasma insulin and glucagon concentrations, epinephrine was also infused combined with somatostatin (6.5 micrograms/kg/h). During somatostatin infusion, epinephrine administration resulted in an enhanced and sustained elevation of total ketone body production from 4.4 +/- 0.8 to 15.1 +/- 1.2 mumol/kg/min (P less than 0.01 versus somatostatin alone). Ketone body concentrations increased markedly from 310 +/- 63 to 1763 +/- 137 mumol/L (P less than 0.01 versus somatostatin alone); the ketonemic effect was enhanced due to a 40% decrease of the metabolic clearance rate associated with somatostatin infusion. The increase in plasma FFA and blood glycerol concentrations during somatostatin-induced insulin deficiency was transiently enhanced by epinephrine, such that they increased to 3.2- and 5.6-fold their basal values after 45 min, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
The relationship between blood pressure and behavioural syndromes assessed by means of an "adjective test" was examined in a group of 467 pre-adolescents. Preliminary results suggest that certain specific behaviour characteristics can be identified in individuals with elevated blood pressure already in childhood and adolescence. Cluster analysis showed that subjects with higher blood pressure do not constitute a psychologically homogeneous group but can be classed into one of the following three subgroups: individuals with "High Academic Performance", "Dysthymic Behaviour" or "Behavioural Disturbances". The relationship between blood pressure and behavioural factors is not mediated by covariables such as social status, sexual maturity, body mass, smoking habits, etc.
In 6 patients with no apparent kidney function the elimination of contrast medium was examined using 125I-labelled diatrizoic acid. Also blood level time curves and concentrations of dialysate were measured, showing a biexponential fall. The kinetic data established by computer-aided analysis according to the two-compartment model yielded elimination values not achieved by a healthy kidney; however a maximum elimination rate of 80.7 +/- 4.7% of the dose administered was calculated for a dialysis period of more than 10 hours. As the contrast medium plasma level was reduced the efficacy of haemodialysis fell.
A male blue monkey (Cercopithecus mitis stuhlmani), a subspecies of the Sykes group, was purchased from a commercial trapper as an adult in July 1978 and kept at the Institute of Primate Research, Kenya, for 2 years. The animal developed acute respiratory distress and died. Small nodular foci were found in the lung at necropsy and diagnosed as bronchogenic carcinoma on histopathology.
Cellulose acetate electrophoresis (pH 8,6 ionic strength 0,05) puts in evidence the soluble complexes "albumin-protamine" which are easily distinguished from albumin being more positively charged. The albumin-protamine complexes formed in serum or plasma, after addition of protamine, undergo in vitro a dissociation progressing with time to the complete restitution of albumin. This dissociation is slowed down by the inhibitors of the carboxypeptidase B (SCPB), an enzyme present in plasma and serum, but is not influenced by the inhibitor phenylmethyl-sulfonyl fluoride (PMSF). A protamine which had lost its four C-terminal arginines by the action of a DFP-treated carboxypeptidase B (CPB) still formed complexes with albumin (and, besides, remained able to neutralize heparin). On the contrary protamine degraded first by CPB, and afterwards by the DFP-treated carboxypeptidase A (CPA) lost these two properties. These results suggest that the dissociation of albumin-protamine complex in plasma and serum requires a protaminase action additional to the action of SCPB.