Biomedical subjects
Publications and source records attributed to S Braun.
An extremely rare case of foreign body related actinomycosis of the finger is described. To the best of our knowledge, this condition had not been previously reported. Subtotal excisional biopsy followed by penicillin therapy eventually yielded a well functioning finger.
Advanced resuscitation techniques are dependent on drug therapy to increase survival. Because drugs must reach their site of action instantaneously, the choice of appropriate route of administration may be critical. To study the pharmacokinetics of drug administration by peripheral and central venous routes during resuscitation, nine mongrel dogs were studied. Arterial blood pressure and electrocardiograms were monitored continuously. Cardiac output was evaluated before resuscitation to determine control levels. After thoracotomy and fibrillation of the heart, cardiac massage was started with a frequency of compression maintained at 60/min. Bolus injections of two different radioisotopes were given simultaneously through a peripheral and a central vein. Isotope activity was sampled through a catheter in the right femoral artery at 5 second intervals for 90 seconds and at 30 second intervals for 210 seconds. The major differences between the two routes of administration were that central injection produced a 270% higher peak concentration (p less than 0.001) and significantly shorter lag times to the first appearance of tracer (16 +/- 7 versus 38 +/- 13 seconds, p less than 0.05) and times to peak concentration (13 +/- 5 versus 27 +/- 12 seconds, p less than 0.01). In contrast, there were no significant differences in area under the time-counts curve, mean residence time, total body clearance and steady state volume of distribution. The central compartment volume of distribution was significantly smaller after central than after peripheral injection (26.1 +/- 56 versus 76.3 +/- 16.5 ml, p less than 0.01). The therapeutic implications of these findings must be investigated for individual drugs used during cardiorespiratory resuscitation to determine the most appropriate route and dosage for each agent.
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Cellular adhesion is important during metastasis, as metastatic cells must escape from the primary site into lymph and blood systems, there to adhere specifically to sites in distant organs. We have recently selected monoclonal antibodies which prevent adherence of B16 mouse melanoma cells to tissue culture dishes, and also markedly reduce experimental lung metastasis in mice when injected before or with the tumor cells. Here, we investigated which step in the metastatic process may be affected by the antibodies. The possible inhibitory effect of antibody on tumour cell adherence to vascular endothelial monolayers and to purified components of the underlying extracellular matrix - fibronectin, laminin and collagen type IV - was studied using in vitro assays. We found that the antibodies significantly blocked attachment to laminin, suggesting that specific basement membrane components play an important role in attracting or otherwise modifying the behaviour of metastatic tumour cells.
Several synthetic random polymers of tyrosine containing glutamic acid, alanine, and lysine in various proportion served as substrates for tyrosine-specific protein kinases. The Km values for these substrates were much lower than for small polypeptides such as angiotensin. For the protein kinase coded by Fujinami virus, the best substrates (with the lowest Km) were polymers containing glutamic acid, alanine, and 8 to 10% tyrosine; for the insulin receptor protein kinase, the best substrate was a polymer containing 80% glutamic acid and 20% tyrosine. These polymers serve as inexpensive and tyrosine-specific substrates that can be used even with crude extracts and analyzed by the convenient filter paper assay. Several synthetic polymers with ordered sequences were found to be potent inhibitors of these tyrosine-specific protein kinases.
A modification of a classic Johnson stone basket has been made, such that this basket can pass easily over an angiographic guide wire. With this modification, the Johnson stone basket is an excellent instrument for use in an antegrade or a retrograde fashion for retrieving impacted ureteral calculi. Eleven patients had ureteral calculi manipulated. Of the six ureteral calculi manipulated with standard retractable baskets, only three were successfully extracted from impacted positions. Of the five manipulated with the modified Johnson stone basket, however, four were successfully extracted. The modified Johnson stone basket is an essential instrument in percutaneous manipulation of ureteral calculi.
The time course of thyroglobulin (Tg) was monitored in patients with differentiated thyroid carcinoma after ablative therapy (thyroidectomy + 131I-treatment) with particular respect to endogeneous antibodies (Tg-ABs). In 232 patients (196 without Tg-ABs, 36 with Tg-ABs at the time of treatment) a sensitivity of 88% (accuracy, 93%) was found at the first follow up examination. Twelve months later, 11 of the 36 patients did not present Tg-ABs, therefore, the sensitivity increased to 91% (accuracy, 94%) at that time. It is expected that the determination of Tg can also be employed in patients presenting ABs initially.
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A prospective controlled trial was carried out to determine the influence of etomidate and thiopentone on serum levels of cortisol and plasma levels of adrenocorticotrophic hormone (ACTH). There were two groups of nine healthy male volunteers: one group was given 0.3 mg/kg body wt. etomidate and the other 4 mg/kg body wt. thiopentone intravenously as a bolus. The hormone levels were measured before and every 30 min after injection of the anaesthetic over a period of 5 h. After thiopentone, cortisol levels dropped from a mean value of 13.2 micrograms/dl to a minimum of 9.0 micrograms/dl after 90 min and fluctuated between 9.2 and 10.9 micrograms/dl until the end of the experiment. Etomidate induced a more pronounced decrease in cortisol levels (from the 90th min the differences to the levels after thiopentone were statistically significant) from 13.9 micrograms/dl to a minimum of 5.0 micrograms/dl after 150 min. After 300 min cortisol levels had recovered only to 7.7 micrograms/dl. Plasma levels of ACTH were also different in the two groups. After thiopentone they decreased from 26.1 pg/ml to 18.2 pg/ml after 30 min, then increased to 30 pg/ml after 300 min. After etomidate, ACTH levels were as high at 30 min as before the injection and increased continuously to 67.1 pg/ml by the end of the experiment; from the 150th min on, the differences to the ACTH levels after thiopentone were statistically significant. We conclude from these hormone levels that a single intravenous bolus injection of thiopentone induces a slight but statistically significant and ACTH-independent decrease in adrenal cortisol secretion in healthy volunteers not stressed by an operation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Serum thyroglobulin (hTg) measurements by commercial radioimmunoassay were performed in the follow-up of 118 patients with differentiated thyroid carcinoma undergoing I-131 local and whole-body scans following surgery and I-131 therapy. Patients with positive anti-hTg antibodies (23% of cases) were excluded. In all remaining I-131 accumulating residual, recurrent, or metastatic tumors, hTg levels were elevated (greater than 6.25 ng/ml, minimum detectable value). Twelve patients with neither recurrence nor metastases had elevated hTg levels. Sensitivity and specificity depended on the threshold used for elevate d hTg levels. At an hTg-threshold of 6.25 ng/ml sensitivity has 100%, specificity has 82%. As hTg levels were reported to depend on endogenous TSH stimulation, it is not yet advisable to replace I-131 scans totally by hTg determination. After having determined an hTg "baseline" below detectable values (less than 6.25 ng/ml), we reduced the number of I-131 scans by half. However, elevated hTg levels were an indication for an I-131 scan. Therefore, on the basis of 23% of our patients who had anti-hTg antibodies the need exists to develop a commercial assay which is independent from antibodies.
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Solubilization of purified turkey erythrocyte membranes at increasing cholate to protein ratios and in the presence of salt, extracts up to 20% of the beta-adrenergic receptor together with the GTP stimulatory protein (Ns) of adenylate cyclase. Upon removal of the cholate, by active absorption on Bio-beads, the functional interaction between the beta-receptor and the GTP regulatory protein Ns is quantitatively restored. The receptor (R) in the presence of l-isoproterenol and p[NH]ppG is able to catalyze the activation of Ns to its permanently active state, N's p[NH]ppG, with a rate constant (kon) identical to that of the native membrane. Reconstitution of the R/Ns mixture using poly(ethyleneglycol)-6000 restores the receptor binding properties as effectively as SM-2 Bio-beads. Unlike SM-2 Bio-beads, however, poly(ethyleneglycol) is not as efficient in restoring the R to Ns functional coupling. In this communication we also report on the ability to monitor quantitatively N's . p[NH]ppG, using native turkey erythrocyte membranes in the presence of Lubrol-PX as the source of the catalytic unit (c) of adenylate cyclase. The latter method is as efficient as using S49 AC- lymphoma cell membranes but much less expensive. Using this technique, we also demonstrate that when the Ns to C interaction is nullified, employing treatment with N-ethylmaleimide, the parameters which characterize R to Ns coupling remain unchanged.
Ketoconazole (Nizoral), an oral broad spectrum antifungal agent, inhibits ergosterol synthesis in fungi and cholesterol synthesis in mammalian cells by inhibition of the 14-demethylation of lanosterol. After a blunted cortisol response to ACTH in normal men after ketoconazole has been shown by others we studied the influence of the antifungal agent on the cortisol secretion in a patient with a cortisol producing adrenal adenoma in vivo and in vitro. Repeated oral doses of ketoconazole (200 mg every 5 h over a period of 48 h) induced a reproducible clear-cut fall of serum cortisol levels under 2.5 micrograms/dl. The inhibitory effect of the cortisol secretion could be detected first 5 h after the first dose, 9 h after the last dose cortisol levels recovered. In addition the inhibitory effect of ketoconazole on cortisol secretion could be reproduced in vitro by incubating tissue slices of the excised adrenal tumor together with the antifungal agent in concentrations equivalent to therapeutic serum levels. These findings emphasize that patients with an autonomous cortisol production caused by an adrenal tumor are prone to dangerous hypoadrenalism if treated with ketoconazole.
A new and rapid method of protein kinase assay is presented which is suitable for low-molecular-weight substrates, irrespective of their electrophoretic or chromatographic mobility. It depends on the phosphorylation of the substrates with [gamma-32P]ATP, hydrolysis of the pyrophosphate bonds by boiling in 1 N HCl, extraction of 32P with isobutanol-benzene, and measurement of the radioactivity of 32P-labeled phosphoesters in the water phase. The method is shown to be suitable for both tyrosine- and serine-phosphorylating protein kinases.