Horace F. Martin

Cardiovascular Effects of 1,1,1-Trichloroethane

Acute exposure of anesthetized dogs to 1,1,1-trichlorothane (TCE) results in a dose-dependent, biphasic decline in arterial pressure similar to that observed following exposure to a commercial solvent containing TCE. The initial phase of pressure decline is associated with peripheral vasodilation whose magnitude exceeds concomitant, reflex, positive chronotropic and inotropic effects on myocardial function. The peripheral dilation could be reversed by injection of the α-agonist, phenylephrine hydrochloride. The second phase of pressure decline is primarily associated with a depression of myocardial function; heart rate, stroke output, and myocardial contractility declined. Injection of Ca++ ameliorated the TCE-induced alteration of myocardial contractility and blood pressure was protected. The data suggest that comprehension of the mech- anism(s) by which TCE induces cardiovascular depression may lead to more effective clinical management of the toxic effects of this compound.

Computed normal values for peak acid output based on age, sex and body weight

The value of gastric analysis in the clinical management of patients with duodenal ulcer disease has been limited by lack of information on the expected normal gastric acid production following maximal stimulation. A table of peak acid outputs utilizing the augmented histamine test and based on age, sex and body weight of the individual was devised using the method of least squares.Results of the peak acid output in 64 patients with proven duodenal ulcer and in 38 normal controls, when compared to the computed normal values based on age, sex and body weight, revealed that 90% of patients with duodenal ulcer fell outside the expected normal range, and 92% of the normal subjects fell within the computed normal range. It is felt that these tables are helpful in recognizing individuals with duodenal ulcer or its diathesis.

Histidine decarboxylase inhibition and gastric secretion

SummaryIn a series of rats whose histamine formation was blocked by either pyridoxine deficiency or decarboxylase inhibition with 4-bromo-3-hydroxybenzy-oxyamine dihydrogen phosphate (NSD-1055), we found that basal and gastrin-stimulated gastric secretion was markedly lowered. Histamine stimulation, however, was an effective stimulus in these inhibited rats. Vagal-induced acid secretion through insulin hypoglycemia and direct parasympathomimetic stimulation with bethanechol, the parasympathomimetic drug, were also not blocked in these animals.These results suggest that, at least in the rat: (1) histamine may be an important endogenous chemostimulator of gastric secretion; (2) gastrin stimulates the parietal cell directly through histamine release; and (3) vagal stimulation apparently utilizes, in part at least, a mechanism other than histamine release.

Effect of 1,1,1-trichloroethane on mitochondrial metabolism.

Abstract The effect of 1,1,1-trichloroethane (TCE) on rat liver (and heart) mitochondrial metabolism was assessed by studying the respiratory control characteristics associated with ATP synthesis from added ADP as well as low level Ca 2+ uptake. With pyridine nucleotide-linked substrates, there is a marked decline in State 3 (ADP) respiration (I 50 = 0.65 μmoles TCE/mg of mitochondrial protein). This respiratory inhibition was found to be due to interruption of electron transfer at the rotenone-sensitive site on the electron transport chain. Interestingly, the ADP/0 ratio is largely unaffected. In contrast, succinate-linked State 3 (ADP) respiration is not inhibited by TCE (in this same concentration range), but there appears to be an apparent uncoupling due to enhanced State 4 (ADP) respiration. This latter effect is due to the release of an ATPase activity dependent on exogenous Mg 2+ . In the absence of exogenous Mg 2+ ATP synthesis and ATPase activity are largely unaffected by TCE. From studies on low level Ca 2+ uptake, the data indicate that the halocarbon alters the passive permeability characteristics of the mitochondrion to Ca 2+ and H + , but the Ca 2+ binding and sequestration mechanisms are unaffected. In conclusion, the data provide a mechanistic basis for the previously described, TCE-induced depression of myocardial respiration and the alteration in myocardial contractility observed during acute exposure to this drug.

Liquid chromatographic profile classification of acute and chronic leukemias

Reversed-phase high performance liquid chromatography and multivariate discriminant analysis are used for the classification of acute and chronic leukemias. Plasma or serum profiles, mainly of nucleosides, bases, and aromatic amino acids, are segmented into specific retention time intervals. Peak areas in each retention time interval are summed such that the chromatographic profile can be represented as a pattern vector formed from the linear combination of peak areas. The preprocessing techniques of autoscaling and variance weighting minimized inadvertent weighting and reduced the contribution of nondescriptive data components in the development of the discriminant function. The acute lymphocytic leukemia plasma samples and controls were classified with 100% sensitivity and specificity. Chronic leukemia serum samples and controls were categorized with sensitivity and specificity values of 93.7 and 87.6%, respectively.

Economic Aspects of Instrument Evalution and Acquistion Part 1 Economic Aspects of Instrument Evalution

As the title implies, this two-part series will be devoted entirely to the economic aspects of instrument evaluation (Part 1) and acquisition (Part 2). The essential elements dealing with the economics of instrument testing are outlined in Table 1. A knowledge of comparative testing costs between the present technology utilized in the laboratory and that introduced via new instrumentation is as vital to management in its decision-making process as the instruments accuracy, precision, and observed effects on diagnostic testing. In situations where the technical data derived from instrument evalutions are essentially equivalent, the fine balance between making an acquisition or not wil undoubtedly be influenced strictly by economics, especially if savings in operational can be realized.

Insulin regulation of RNA synthesis

During periods of nitrogen exportation from the cell, mitochondrial carbamoyl phosphate is synthesized, thus initiating the urea cycle. During times of nitrogen conservation by the liver cell, carbamoyl phosphate is synthesized in the cytosol of the cell, whereupon the de novo pyrimidine synthesis pathway is initiated. The de novo pathway provides pyrimidines for increased ribonucleic acid synthesis. Formerly, it was believed that these two pathways functioned irrespective of one another. However, recent experimental evidence indicates that, when excess ammonia is present, mitochondrial carbamoyl phosphate passes from the mitochondria into the cell cytosol, where it is metabolized by the de novo pyrimidine synthesis pathway. When ornithine and excess ammonia are both present, mitochondrial carbamoyl phosphate no longer passes from the mitochondria into the cytosol to be metabolized by the de nova pathway. Thus the metabolic fate of mitochondrial carbamoyl phosphate, and that of excess nitrogen, is determined by the presence or absence of ornithine. In turn, this key molecule is the substrate for the cytoplasmic enzyme ornithine decarboxylase. When ornithine decarboxylase is stimulated by insulin, ornithine is metabolized to putrescine. The activated ornithine decarboxylase combines with ribonucleic acid polymerase, activating the later enzyme. When ornithine is acted upon by ornithine decarboxylase, it is no longer available for the perpetuation of the urea cycle and mitochondrial carbamoyl phosphate levels rise until the carbamoyl phosphate passes into the cytosol to be metabolized by the de novo pathway. Increased amounts of pyrimidines are available for the activated ribonucleic acid polymerase. Therefore insulin, through its stimulation of ornithine decarboxylase, achieves cellular nitrogen retention by regulating nitrogen incorporation into newly synthesized ribonucleic acid.

Approach to the establishment of a routine analysis of serum copper by atomic absorption

Summary 1. A method is described for the establishment of a routine laboratory assay of metals in serum with an attempt to study all significant possibility of interference with the method. 2. Appropriate steps are taken in establishment of the method to eliminate significant interferences and to insure that all the metal is being measured and that only that metal is contributing to the assay. 3. A previously reported assay for serum copper is evaluated by the established protocol.

Instrument Optimization and Reliability

ABSTRACT As a continuation of past articles on instrument evaluation (1-4), two topics will be discussed: (i) optimization and (ii) reliability of instrumentation (or methodology). Although both have a great bearing and influence on much of the subject matter relating to the obtainment of valid technical data, they are of paramount importance today, specifically in areas of laboratory operations concerned with “cost-containment.”

Instrument Justification, Selection, and Technical Evaluation in Clinical Chemistry Part 2 Technical Aspects of Instrument Evaluation

The primary concern or objective of Part 2 is instrument evaluation based on a technical approach that is applicable to laboratory equipment of varying degrees of complexity [see item 1, Table 2, Part 1 (1)].