Assessment of clinical laboratory techniques in the measurement of oxygen saturation in whole blood. The accuracy and advantages of determining percentage of hemoglobin oxygen saturation of whole blood by advanced instruments of oximetry, gas chromatography, and the computation of oxygen saturation from pO2 and pH data are compared with the Van Slyke-Neill manometric method. It was found that oximetry is extremely fast, less expensive, and more accurate than in the past, the apparatus requires little training to operate and has diminutive service maintenance. The gas chromatograph proved to be highly accurate and could serve as a standard calibration check method in place of the more time-consuming Van Slyke-Neill apparatus for oximetry and pO2 and pH electrode instrumentation. Computation of O2 saturation from pO2 and pH data also proved to be accurate, confirming that this method is more useful during cardiac surgery because it can provide additional acid-base information. In the low oxygen saturation range (less than 60%), all three methods proved to be of similar sensitivity.


Purification and properties of beta-lactamase from Bacteroides fragilis. Beta-Lactamase activity was detected either biologically or using the chromogenic cephalosporin 87/312 in 20 clinical isolates of Bacteroides fragilis with penicillin G minimal inhibitory concentrations of 10 to 100 micrograms/ml. Strain AM78 (minimal inhibitory concentration, greater than 1,000 micrograms/ml) was used to optimize the conditions for production, assay, and storage of the enzyme. The enzymes are cell associated, with less than 1% of activity being found in culture fluids during growth, and can be released from the cell surface by modified osmotic shock procedure. This procedure causes concomitant release of cyclic phosphodiesterase activity. Substrate profiles and the effects of inhibitors were determined for enzymes partially purified by osmotic shock release and gel filtration. The enzymes are cephalosporinases with some penicillinase activity and are inhibited by p-chloromercuribenzoate, cloxacillin, and carbenicillin. The molecular weight, as determined by gel filtration, is 29,000 to 31,000. A method for the purification of the beta-lactamase from strain AM78 is described: the specific activity of the purified enzyme was 3,424 U/mg, about 3,000-fold that of the crude, cell-associated enzyme.


Approach to systemic vasculitis.

Approach to systemic vasculitis. Systemic vasculitis is a confusing subject which has been difficult to classify and understand. Improvements in therapy increase the importance of early diagnosis. This paper reviews the clinical and pathological differences of the systemic vasculitides, and a working approach to the differential diagnosis of vasculitis is formulated based on the size of the vessel involved. Vessel size and histopathology determine to what group of diseases a particular syndrome belongs, thereby allowing subclassification and a more rational approach to management.


Intravenous abuse of propylhexedrine.

Intravenous abuse of propylhexedrine. Propylhexedrine, a local vasoconstrictor, is the active ingredient in the Benzedrex nasal inhaler. In a six-month period, the Office of the Medical Examiner of Dallas County has encountered three deaths resulting from intravenous injection of propylhexedrine. Two of these individuals showed vascular changes in the lungs, apparently from chronic intravenous injections of this drug. Body distribution of the drug was determined in all of the cases by gas chromatographic analysis. An experiment was conducted to determine "therapeutic blood concentrations" in which a normal subject inhaled propylhexedrine from the Benzedrex inhaler. The maximum blood concentration was only 1/30 of the minimum concentration encountered in the reported cases.


Human penetrating keratoplasty using modified M-K medium. Preservation of donor tissue for human keratoplasty has been evaluated using modified M-K medium. The medium has been modified by changing the antibiotic and buffer and adding a pH indicator. These changes offered theoretical and practical advantages. There were no primary donor failures in 50 consecutive penetrating keratoplasties with an overall success rate of 92 percent. Clinical specular microscopy revealed good endothelial cell survival.


Enzyme histochemical patterns in the normal human amnion: amniotic histochemical patterns. The histochemical distribution of 14 enzymes in the human amnion at term are described. Adenosine triphosphatase, 5'-nucleotidase, acid phosphatase and nonspecific esterase show continuous gradations of enzyme activity. Cells with intense activity are prominent in acid phosphatase and nonspecific esterase preparations. A distinct subpopulation of amniotic cells can be defined by their alkaline phosphatase activity. The possible correlations with morphological studies are discussed.


Control of the uteroplacental circulation in health and disease. The various neurohumoral and intrinsic factors that control the uteroplacental hemodynamics in health and disease and in responses to physiologic and pharmacologic stimuli have been reviewed. The following conclusions may be derived: We still need improvement in our methodology of monitoring uterine blood flow. The present methods, which have some reliability, are not easily applicable to human subjects and even in animals their use presents problems of accuracy and sensitivity with which the investigator must become familiar. The marked and progressive increase in uterine blood flow that occurs during pregnancy is caused by complex factors, some of which are hormonal and hemodynamic in nature. The increased vascularity of the pregnant uterus and the opening of the arterioles during the process of formation of the intervillous space are important factors that facilitate the increase in uterine blood flow. The increment seems to be totally derived from the increment in the cardiac output that occurs during pregnancy. There seems to be no redistribution among the regional blood flows of the body. In the anesthetized condition the blood flow to the uterus depends largely on the perfusing pressure; the critical closing pressure seems to be around the 40 mm Hg level. This linear flow-pressure relationship does not, however, apply to the unanesthetized condition. A rise or fall in the perfusing pressure in the conscious state may be accompanied by an increase or decrease in the uterine blood flow, depending on the underlying mechanisms. Factors that lead to alpha-adrenergic stimulation produce an increase in uterine vascular resistance and a decrease in flow, irrespective of the status of the perfusing pressure. beta-adrenergic stimulation may increase uterine blood flow either through their vasodilating action or through their myometrial relaxing effects. Hypertensive diseases are most often accompanied by a decrease in uterine blood flow, whereas hypoxic states may decrease the flow even though the arterial pressure may not change significantly. It is extremely risky to extrapolate from information obtained in the anesthetized animal to the unanesthetized, conscious animal. Likewise, data obtained from normotensive conditions may not hold true for the hypertensive or hypotensive states. This is of particular relevance when one is dealing with the effects of pharmacologic agents that act on the cardiovascular system. Uterine contractions, whether induced through spontaneous or oxytocin-induced labor, produce a decrease in uterine blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)


Fetal response to periodic sleep apnea: a new syndrome in obstetrics. Periodic sleep apnea, a chronic sleep deprivation state, in which marked changes in the arterial PO2 and PCO2 tensions have been recorded, is a relatively new syndrome not previously reported in pregnancy. It is characterized by episodes of apnea, prevalently obstructive, during sleep. The majority of patients with this syndrome have snored heavily for years, suggesting a causal relationship between snoring and periodic sleep apnea. The effects of prolonged snoring on alveolar ventilation and systemic pressure(s) suggest that this snoring has physiopathological implications on maternal cardio-respiratory reserve and indirectly upon the fetus, especially as there are recordable changes in fetal heart rate and also a change in the acid-base status of the fetus. The possibility that this syndrome may have an adverse effect upon the fetus is stressed.


Plasma hypoxanthine in neonatal hypoxia: a comparison of two methods. Hypoxanthine levels were determined in both venous and arterial cord blood of 42 neonates. Two methods were compared, a PO2 electrode determination and an HPLC (high-pressure liquid chromatography) method. A good correlation was found between the two methods. However, the HPLC method was more sensitive, more reproducible and easier to perform. Hypoxanthine levels in the umbilical artery were found to be higher than in the vein. A significant negative correlation between pH and hypoxanthine level was established. The studies showed that plasma hypoxanthine levels by themselves did not provide an absolute diagnosis of intrauterine hypoxia.


Interoceptive conditioning through repeated suppression of morphine-abstinence. II. Relapse-testing. The reinforcing properties of etonitazene, both conditioned and unconditioned, were measured in rats that had received saline only by continuous intravenous infusion ("saline" group) and in two groups of rats that had been physically dependent on morphine to equal degrees (and presumably had developed equal degrees of tolerance to morphine): one by once daily passive intravenous injection of morphine ("injection" group) and the other by passive continuous intravenous morphine infusion at the same daily doses for approximately the same number of days ("infusion" group). Prior to passive saline and morphine administration, all rats were trained to press right- and left-sided levers for water reinforcement from 1600 to 0800 hrs to a not more than 60-40 split, and these and other measures ("baselines") were repeated after recovery from the early (acute) morphine-abstinence syndromes. Then etonitazene, 5 micrograms/ml, was substituted for water on the nonpreferred side and all measures were repeated from 1600 to 0800 hrs once every two weeks for 20 weeks (10 "relapse" tests). It was postulated that the daily cycles of morphine-abstinence and suppression of abstinence in the injection group only would generate latent interoceptively conditioned reinforcing properties of morphine because of conditioning of suppression of abstinence to the concomitant internal sensorial effects of morphine, which would persist after morphine withdrawal and be transferred to the internal effects of another opioid, etonitazene. It was found that across the first nine relapse tests, the injection group consumed significantly more etonitazene than the infusion group, while there were no significant differences in water consumption.(ABSTRACT TRUNCATED AT 250 WORDS)


Neonatal respiratory distress syndrome (RDS) in cases of premature labor treated by betamimetic drugs. In 87 premature labors, 31 were treated with betamimetic drugs. The incidence of RDS in the treated group has been lower than in the non-treated group, especially when gestational age was shorter than 35 wk and when newborn's weight was lower than 2000 g.


Role of a radiologic technologist trained as a physician assistant in diagnostic radiology. This article describes a program for physican assistants in diagnostic radiology at the University of Kentucky, currently the only one in the country. Available only to graduates of AMA-approved radiologic technology programs who have two years of field experience, it consists of two additional years of intensive education in many aspects of radiological medicine.


A perspective: the external degree as a viable educational model in nursing. The external degree is not new in higher education. However it has not as yet been fully developed. Its usefulness has been demonstrated at the undergraduate level where students are able to move up the career ladder to licensure or degree. It appears to be a viable alternative for nurses seeking educations at the masters level also. By definition it is a nontraditional method of delivery. Nursing as a profession abounds with nontraditional potential students. The author has made no attempt to sell the "external degree" to nursing educators. The focus has been on heightening the awareness of readers to this rapidly developing change in higher education. In a time when concepts such as recurrent education, part-time students, credit for life and work experience, meaningful education and the adult student are much discussed in higher education, nursing educators should not be left behind. The external degree, modified or unmodified may well be the mechanism needed for providing quality education for nurses with varying backgrounds.


pH profiles: Part I--One pH, or many?

pH profiles: Part I--One pH, or many? Examples of particular characteristics of tear pH are given for a contact lens patient, both previous to fitting and following.


pH profiles: Part II--Descriptive analyses. Two approaches, together with their advantages and limitations, are given for the analysis and classification of tear pH changes observed for patients.


Temperature sensitivity of DNA synthesis in mouse testicular germ cells in vitro. The effect of temperature on testicular DNA synthesis in mice was studied in vitro. By using cultures of cryptorchid testis, DNA synthesis of differentiated germ cells, such as intermediate and type B spermatogonia and resting primary spermatocytes, was shown to be temperature-sensitive, while that of undifferentiated type A spermatogonia was not. DNA synthesis of non-germ cells was not temperature-sensitive. This temperature sensitivity of germ cells in DNA synthesis may be one cause of the thermal inhibition of germ cell differentiation.


Head-to-head association in bovine spermatozoa induced by catecholamines. Noradrenaline, adrenaline, and isoproterenol induce head-to-head association in bovine spermatozoa in a Tris-HCl-buffered medium. Noradrenaline was the most and isoproterenol the least efficient. This effect was stimulated by Ca2+, Mg2+ and Mn2+, Ca2+ being more efficient than the other two ions. At 2 X 10(-6) M Ca2+, oxidation products of adrenaline dissociated spermatozoa associated by washing; at 2 X 10(-5) M Ca2+, the dissociating effect was transformed into association. The induction of association by adrenaline was blocked by both alpha- and beta-adrenergic blockers at low concentrations (2 X 10(-7) M). Both cAMP and dibutyryl substituted cAMP (db-cAMP) induced association in the Tris-buffered medium at 2 X 10(-6) M Ca2+. Further increase in association was brought about by increasing the Ca2+ concentration to 2 X 10(-5) M. Prolongation of the treatment with cAMP increased association. When combined with cAMP under the same conditions as used in the combination with adrenaline, L-propranolol did not inhibit association induced by cAMP. In an identical experiment, performed in Tyrode solution, L-propranolol inhibited association induced by cAMP. At 2 X 10(-5) M, theophylline, caffeine, and papaverine induced association in the presence of 2 X 10(-5) M Ca2+. The results are compatible with the hypothesis that catecholamines act via receptors and formation of cAMP.


A sensitive radiometric assay for cysteic acid decarboxylase activity in crude enzyme preparations of rat liver and brain. 1. A method is described for the synthesis of L-[U-14C]cysteic acid from L-[U-14C] cysteine hydrochloride and for its subsequent utilisation as a substrate for cysteic acid decarboxylase activity in liver and brain. 2. The enzyme determination relies on the entrapment of radio-labelled carbon dioxide in Hyamine hydroxide. 3. The assay is sensitive, reliable and convenient and is particularly suitable for measuring the activity of the decarboxylase in crude enzyme preparations.


Hexokinase of the adult dog heartworm, Dirofilaria immitis. 1. Dirofilaria immitis hexokinase was relatively heat stable and had a pH optimum range between 7.8 and 8.2. 2. Mean Vmax was 0.40 +/- 0.10 (S.D.) mumole/min/100 mg of worm. 3. Mean Km values were 0.32 mM for glucose, 0.86 mM for fructose and 0.39 mM for ATP. 4. Glucose-6-phosphate was not a strong product inhibitor. 5. Starch gel electrophoresis demonstrated at least three isozymes.


Emergence of antibiotic resistance in hospitals, 1935-1975. A limited review of the changes in susceptibility of common bacterial pathogens to available antibacterial agents is presented. Significant developments in recent years include the following: (1) the emergence of Streptococcus pneumoniae with decreased resistance to penicillin and of some strains resistant to several antibiotics; (2) a decline in prevalence of multi-drug-resistant Staphylococcus aureus after 1960 following their increasing prevalence in the preceding years (these changes were methicillin-resistant (and multi-drug-resistant) S. aureus and the marked differences in their prevalence in different areas (these changes also were related to appearance of new phages in those organisms); (4) an increasing resistance to multiple drugs among enterococci but not among viridans streptococci or among nonenterococcal group D streptococci; (5) the emergence of beta-lactamase-producing Neisseria gonorrhoeae; (6) the emergence and spread of sulfonamide-resistant Neisseria meningitidis; (7) the occurrence of beta-lactamase-producing strains of Haemophilus influenzae and occasional strains resistant to chloramphenicol; (8) the focal occurrence of chloramphenicol-resistant Salmonella typhi in Vietnam and in epidemic form in Mexico; (9) the demonstration of marked differences in prevalence of resistance to multiple drugs in common pathogens to the most widely used antibiotics in different geographic areas. The dominant factor in the emergence and spread of antibiotic-resistant bacterial pathogens, whether in hospital wards or in the community, is clearly the intensive use of the antibiotic agents to which resistance emerges and then spreads.


Effect of nutritional factors and cortisol on tyrosine aminotransferase activity in liver of brook trout, Salvelinus fontinalis Mitchill. 1. Starvation for over 50 days increased the activity of Tyrosine aminotransferase (TAT) from brook trout liver and decreased liver glycogen. 2. Cortisol (6-40 mg/100 g body wt) increased TAT activity, optimally 72 hr post-injection; liver glycogen response to cortisol was variable while tissue water either increased or remained constant. 3. Fish fed high-protein/low-carbohydrate had greater TAT activity than fish fed low-protein/high carbohydrate. There was food-induced peak of activity indicating a "diurnal rhythm" analogous to that of rat TAT. 4. TAT activity in brook trout appears to be correlated with protein catabolism.


Phosphonoglycoprotein from Metridium senile--heterogeneity of glycoproteins containing aminoethylphosphonic acid. 1. After separation by SDS gel-chromatography, analysis of AEP-containing glycoproteins from M. senile, indicated 66% amino acids with 220 AEP res./1000 res. and 30% carbohydrate for high mol. wt (greater than 10(7) forms and 80% amino acids with 25-50 AEP res./1000 res. and 10% carbohydrate for low mol. wt (2-4 x 10(4) forms. 2. Uronic acids, sulfate, lipid, and sialic acids were absent. 3. Mild base digestion released AEP-hexosamine containing oligosaccharides and destroyed ser-thr residues in the high mol. wt components. 4. Phosphonoglycoproteins appear to be acidic connective tissue components with AEP linked to hexosamine containing oligosaccharide side chains.


Genetic determinants of microbial resistance to antibiotics. Emergence of antibiotic resistance is related to the ease of mutation, to the extent of exchange of genetic information in bacteria by conjugation, transformation, and transduction, and to the large-scale use of antimicrobial agents in the biosphere. In addition to the development of resistance through chromosomal mutation and exchange of chromosomal genes among organisms, there is a more profound enlargement of the gene pool by the dissemination and amplification of plasmids. Two examples of the exchange of antibiotic resistance are analyzed: the transfer of plasmids from Bacteroides fragilis to Escherichia coli and the emergence of antibiotic-resistant strains of STreptococcus pneumoniae. Plasmids encoding antibiotic resistance in B. fragilis were transferred to E. coli by DNA-mediated transformation and conjugation. The beta-lactamase in the transformants and transconjugants displayed the same substrate specificity and electrophoretic mobility as the donor strain. The plasmid apparently was integrated rapidly into the chromosome of the recipient strain. Multiple antibiotic-resistant strains of S. pneumoniae were analyzed for plasmids, and none were detected. Furthermore, no evidence of linkage between the traits of multiple antibiotic resistance was observed. beta-Lactamase was not detected in the penicillin-resistant strains; therefore, it is likely that the resistance in these strains was chromosomal rather than plasmid-mediated. The range of genetic exchange and the use of Koch's postulates in determining the genetic mechanism of antibiotic resistance are illustrated and discussed.


Carp (Cyprinus carpio) muscle fructose 1,6-bisphosphatase: purification and some properties. 1. Fructose 1,6-bisphosphatase from the white muscle tissue of the carp, Cyprinus carpio L. was purified. 2. The mol. wt of the enzyme was 145,000. Its subunit mol. wt was ca. 35,000. 3. The enzyme exhibited neutral pH optimum, activation by monovalent cations, and temperature-dependent allosteric AMP inhibition. 4. Carp muscle fructose 1,6-bisphosphatase was 10- to 30-fold more sensitive to AMP inhibition than the carp liver enzyme. 5. The carp muscle enzyme was less sensitive to AMP inhibition than the muscle enzyme from a homeothermic mammal. These results are interpreted as an example of temperature-adaptation of an enzyme regulatory property.


High activity of NADP-dependent malic enzyme in mitochondria from abdomen muscle of the crayfish Orconectes limosus. 1. Mitochondria isolated from abdomen muscle of crayfish Orconectes limosus exhibit malic enzyme activity in the presence of L-malate, NADP and Mn2+ ions after addition of Triton X-100. Under optimal conditions about 230 nmole of reduced NADP and an equivalent amount of pyruvate are produced per min per mg of mitochondrial protein. 2. The pH optimum for decarboxylation of L-malate is about 7.5. 3. The apparent Km for L-malate, NADP and Mn2+ ions was found to be 0.66, 0.012, and 0.0025 mM, respectively. 4. The requirement for Mn2+ can be replaced by Mg2+, Co2+ and Ni2+ ions; however, higher concentrations of these ions than Mn2+ are required for a full stimulation of malic enzyme activity. 5. Oxaloacetate and pyruvate inhibited the enzyme activity in a competitive manner with apparent Ki values of 0.05 mM and 5.4 mM, respectively.


Purification and properties of the adenosine deaminase from the midgut gland of a marine bivalved mollusc, Atrina spp. 1. The adenosine deaminase has an approximate molecular weight of 130,000-140,000 and the composition of two polypeptide units (mol. wt about 68,000) is suggested, by means of SDS disc electrophoresis. 2. Both the alpha (Vm/Km) and beta (Vm) parameters were varied with pH and temperature. RSS (relative substrate specificity) adenosine and deoxyadenosine values for alpha and beta were 1.2 and 1.1, respectively. 3. Adenine, 2'-, 3', 5'-AMP, 5'-deoxyAMP, ADP and ATP were not deaminated by the enzyme. 4. Inhibition by Mg2+ was found in reaction with adenosine at pH 8 but not with deoxyadenosine at the same pH. Mn2+, which did not affect the reaction rate at pH 4 and 5, showed competitive inhibitory effects at pH 6, 7 and 8.


Lipogenic activity of catfish liver. Lack of response to dietary changes and insulin administration. 1. Some of the physical, chemical and kinetic properties of catfish liver lipogenic enzymes (acetyl-CoA carboxylase and fatty acid synthetase) were investigated. 2. The liver lipogenic enzymes of catfish exhibited maximal activity at 37 degrees C, even though these fish usually live at temperatures not above 24 degrees C. 3. The activity of the lipogenic enzymes of catfish liver was always low, regardless of the proportions of lipids or carbohydrates in the diet and could not be raised by insulin administration. 4. Under the conditions of the experiments, catfish liver fatty acid synthetase produced more stearate than palmitate and no myristate.


Creatine phosphokinase isoenzymes and Trypanosoma cruzi infections. 1. Substantial increases in total creatine phosphokinase (CPK) and in isoenzymes from heart (CPK-MB) and skeletal muscle (CPK-MM) were observed during acute infections with the House 510 and House 11 strains of Trypanosoma cruzi. 2. In infections with the reticulotropic Tulahuen strain total CPK levels were lower and the isoenzyme pattern was essentially normal. 3. Gamma-glutamyl transpeptidase was considerably increased in the Tulahuen but not in the House 510 and House 11 infections. 4. These findings are useful in assessing tissue damage during T. cruzi infections and they also demonstrate differences between myotropic and reticulotropic strains which may aid in their taxonomic classification.


NAD-linked glutamate dehydrogenase in Trypanosoma cruzi. 1. Epimastigotes of Trypanosoma cruzi, Tulahuén strain, contained a NAD-linked glutamate dehydrogenase (EC 1.4.1.3), in addition to the already known NADP-linked enzyme enzyme (EC 1.4.1.4). 2. The partially purified NAD-linked enzyme had a higher molecular weight and was much more labile than the NADP-linked enzyme, and was inhibited by purine nucleotides. 3. These results further emphasize the difference in glutamate metabolism between the parasite and its mammalian host.


Effects of 2,4-dinitrophenol on trichomonads and Entamoeba invadens. 1. 2,4-Dinitrophenol (2,4-DNP) in substrate level concentrations (200 microM-1 mM) temporarily inhibits H2 production by Tritrichomonas foetus and Trichomonas vaginalis as well as the accumulation of metronidazole, dependent on its reduction by the two trichomonad species and by Entamoeba invadens. 2. 2,4-DNP competes for the reducing equivalents which are necessary for H2 production or for the reduction of metronidazole, thereby inhibiting these processes. 2,4-DNP is reduced to 2-amino, 4-nitrophenol. 3. 2,4-DNP in concentrations up to 800 microM has no effect on the uptake of O2 by these organisms. 4. 2,4-DNP has some toxicity for T. foetus.


Comparative studies of galactokinase activity on mammal's red blood cells. 1. ATP: D-galactose-1-phosphotransferase activity was measured in human, pig, cow, rabbit, mouse and rat red blood cells. Mean values of galactokinase activity was markedly lower in the human and pig erythrocyte as compared to those of the other species. 2. The permeability to galactose of the red cells studied was always higher than galactose phosphorylation. 3. The affinity constants of galactokinase for galactose ranged from 119 to 291 microM and from 178 to 406 microM for ATPMg2-. 4. The thermostability values of the galactokinase of the species studied were similar. The pH-optimum is pH 7.5 for the human, mouse and rabbit enzyme and pH 8.0 for cow, pig and rat galactokinase.


Peroxidases produced by the marine sponge Iotrochota birotulata. 1. Two peroxidases, differing in ionic character and substrate specificity, have been isolated from the tropical marine sponge Iotrochota birotulata. 2. Both peroxidases catalyze the oxidation of a number of substrates, and one peroxidase possesses a specificity similar to the terrestrial fungal enzyme chloroperoxidase. 3. Based on inhibition studies utilizing sodium azide, potassium cyanide and 8-hydroxyquinoline, it appears that the peroxidases from I. birotulata are haemoprotein complexes. 4. One peroxidase appears to possess subunit structure, and requires bound divalent metal cations for activity.


A schizophreniform behavioral psychosis mediated by dopamine. The authors conducted a study in which schizophrenic-like behavioral disturbances were induced in members of a macaque social colony by the chronic administration of d-amphetamine. Animals given the drug showed hypervigilance, hyperactivity, fragmented and repetitive behaviors, and progressive social withdrawal as well as the development of solitary stereotypies. The syndrome was dissected pharmacologically with alpha-methyl-para-tyrosine, chlorpromazine, pimozide, and haloperidol. Based on the behavioral findings and the known mechanisms of action of these drugs, the authors conclude that the major elements of the psychotic-like behavior induced by d-amphetamine were mediated by dopamine systems.


Renal tubular function in patients on long-term lithium therapy. The authors conducted a study in which 10 patients with recurrent affective disorders who responded completely to long-term lithium therapy but who were otherwise unselected were tested for renal tubular concentrating and acidification ability. Despite frequent symptoms of thirst, polyuria, and nocturia, all patients were able to concentrate urine normally and all showed normal renal tubular acidification ability. A significant correlation was found between erythrocyte lithium concentration and maximum urinary osmolality.


Comparative study on the activity, pH optimum and thermal stability of some glycosidases and acid phosphatase from pig and mule leukocytes. 1. alpha-D-mannosidase, beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetylgalactosaminidase, alpha-D-glucosidase and acid phosphatase activities were studied in circulating blood leukocytes from Sus scropha var. domestica L. (pig) and Equus asinus x caballus (mule) by spectrophotometric procedures using p-nitrophenyl derivatives as substrates and three different buffer solutions. 2. The highest specific activity corresponds to acid phosphatase. The specific activities of the glycosidases, all relatively close together in all cases, were low in comparison with that of phosphatase. 3. Generally, each of the above-mentioned enzymes shows one common peak for the pH optimum between 3.5 and 6.0, except alpha-D-glucosidase, which shows two peaks. 4. The pH optima values are generally similar in three buffer solutions employed. 5. Specific activities of the studied enzymes show a parallelism in leukocytes from both pig and mule. Also, this parallelism is observed in their pH optima values. 6. Thermal stability of alpha-D-mannosidase is high whereas that of acid phosphatase is low, in both materials. For other enzymes, differences in the thermal stability was observed according to their source.


Glutamine synthetase in kidneys of monkey and man. 1. The synthesis of gamma-glutamylhydroxamate from glutamate and hydroxylamine has been utilized as an approximation of glutamine synthetase activity in kidneys of rabbit, rat, dog, monkey and man. 2. Kidneys of rabbit contain glutamine synthetase in high activity; those of rat, in intermediate activity; and those of dog, monkey and man, in negligible activity. 3. No more enzyme is present in kidneys of the latter two species than in those of the dog, in which the enzyme is generally considered to be absent.


NADP-specific glutamate dehydrogenase in Metridium senile (L.). 1. An NADP-specific glutamate dehydrogenase (E.C. 1.4.1.4) of mitochondrial origin has been detected in M. senile, a sea anemone. 2. Substrate specificity and starch gel electrophoresis experiments indicated an absence of the NAD(P) glutamate dehydrogenase (E.C. 1.4.1.3). 3. This NADP specific GDH activity appears to be the sole GDH activity in species of the animal phylum Coelenterata.


Preliminary characterization of the delta-9 desaturase of Tetrahymena pyriformis W. 1. In vitro assay conditions have been defined for measurement of delta 9 desaturase activity in Tetrahymena pyriformis W. 2. The reaction depends on the presence of oxygen and a reduced pyridine nucleotide cofactor. FAD supports a low level of enzymatic activity. 3. Both stearyl-CoA and palmityl-CoA are acceptable substrates. Oleate formation is maximal at 30 degrees C. 4. Delta-9 desaturase activity appears to be localized in the microsomal fraction. Delta-6 and/or delta 12 desaturase activities have also been observed. 5. When the specificity of the delta 9 desaturase towards stearyl-CoA and palmityl-CoA was observed at 30 and 16 degrees C it was found that lowering the assay temperature did not affect specificity. Stearyl-CoA was more readily desaturated at both temperatures. 6. Exogenous oleyl-CoA and diisopropylfluorophosphate had little effect on delta 9 desaturase activity. However, cyanide strongly inhibited desaturation and a sensitivity to sulfhydryl-binding reagents has also been demonstrated.


Glutamine-dependent carbamoyl-phosphate synthetase and control of pyrimidine biosynthesis in the parasitic helminth Schistosoma mansoni. 1. Carbomoyl-phosphate synthetase in Schistosoma mansoni utilizes L-glutamine as well as ammonia as nitrogen donor but does not require N-acetyl-L-glutamate for the activity. 2. The enzyme activity was inhibited by UDP, UTP, ADP and AMP, among which UDP was the most effective. 3. Aspartate carbamoyltransferase and dihydroorotase were also found and copurified with the synthetase. 4. Relative activities among these three enzymes were 1:30-60:3-8 throughout the purification. 5. These results suggest that the synthetase plays a key role in the control of pyrimidine biosynthesis de novo.


[Effect of antianginal drugs on the exertion electrocardiogram]. In order to evaluate the clinical efficacy on penbutolol (Hoe 893 d), a new adrenergic blocking agent, two groups of 10 patients (A & B) with ischemic heart disease were chosen. These were submitted to exercise testing for 3 minutes, and placebos, nitroglycerin, and propranolol were used as reference preparations. As an index of indirect consumption of oxygen we determined the maximum cardiac frequency (MCF), maximum systolic arterial pressure (MAP) and the maximum double product (MDP). An electrocardiographic control of the patients was also included to observe ST segment changes. The patients from group A received 0.8 mg. of nitroglycerin sublingual as the first treatment and 40 mg. of propranolol as the second. The patients from group B received initially a placebo P.O. and then 25 mg. of penbutolol P.O. In both groups the exercise testing was repeated 10 minutes after the administration of the first substance and 10 minutes after the second. The results showed that 25 mg. of penbutolol and 40 mg. of propranolol have similar therapeutic effects over the degree, intensity, and duration of the differences in elevation of the ST segment, MCF, MAP, and MDP when you compare the results of their own controls with those obtained with the active principle. There is no significant difference observed in the results obtained in each parameter studied between penbutolol and propranolol. During the period of this clinical study there were no undesirable collateral effects caused by the oral administration of the investigated drugs.


Automatic measurement of the oxygen affinity of Cancer magister hemocyanin. 1. The P50 of Cancer Magister hemocyanin in hemolymph was 40.0 mm at 25 degrees C, nmax = 3.9; at 14 degrees C, 15.0 mm and 3.4; and at 10 degrees C. 10.2 mm and 3.3. 2. In the absence of Ca2+ and Mg2+, the P50 at 25 degrees C was in the range of 150 to 250 mm, depending upon pH. 3. Our results show that temperature variation and pH variation may be important factors in the physiological regulation of oxygen delivery in this species. 4. The automatic recording device of Imai et al. (1970) previously used for the study of hemoglobins, was found to be eminently suitable for the study of O2 affinities of hemocyanins.


Microheterogeneity of mammalian haptoglobins in isoelectric focusing. 1. Human haptoglobin type 1-1, porcine haptoglobin, and equine haptoglobin were isolated and purified. 2. These haptoglobins were similar in polyacrylamide gel electrophoresis and in subunit structure but showed microheterogeneity in isoelectric focusing. 3. Isoelectric points of human haptoglobin as determined with photopolymerized gels were found to be 4.03-4.24, of porcine haptoglobin 4.0-4.30, and of horse haptoglobin 3.80-4.15, respectively. 4. Results obtained with chemically polymerized gels were 0.08-0.3 pH units higher. 5. Examined haptoglobins differed also in the ability of complex formation with hemoglobin, in sialic acid content and in antigenic specificity.


A comparative characterization of cytosolic superoxide dismutase/(SOD) from hog liver and erythrocytes. 1. Conditions of preparation and purification of superoxide dismutase from hog liver and erythrocytes were established. 2. The enzymes from both tissues were compared in respect to electrophoretic mobility, pI value, amino acid composition and spectrophotometric profiles and some differences were observed. 3. Conditions of enzyme dissociation were elaborated and molecular weights of subunits obtained from both kinds of SOD were found to be approx. 16,000. 4. Effect of heat and pH on the enzyme activity were tested. Both enzymes exhibited a relative thermostability.


Significance of the variation in isozymes of liver lactate dehydrogenase with thermal acclimation in goldfish--II. Effect of pH. 1. Effect of pH on liver lactate dehydrogenase (LDH) and its isozymes was examined in the goldfish acclimated to different temperatures and some purification of the LDH was attempted. 2. The optimal pH and the Km value at 30 degrees C of the enzyme were independent of acclimation temperature. 3. the optimal pH of isozyme was more basic in the order of LDH-1, LDH-2, LDH-3, LDH-4 and LDH-5. Km values of isozymes at 30 degrees C were higher in the order of LDH-1, LDH-3 and LDH-5. 4. There was no change in the enzyme activity during thermal acclimation.


Characteristics of delta 1-pyrroline-5-carboxylate reductase from Drosophila melanogaster. 1. Biochemical properties of delta 1-pyrroline-5-carboxylate reductase from d. melanogaster have been investigated. 2. The enzyme is stable below 4 degrees C. 3. the pH optimum of the enzyme is 5.7. It is rapidly inactivated below pH 5.4. 4. The Km values for NADPH and delta 1-pyrroline-5-carboxylate are 1.6 x 10-5 and 2.5 x 10-6 M, respectively. 5. the estimated molecular weight of the enzyme is 225,000. 6. the enzyme is weakly inhibited by L-proline (Ki = 0.12 M).


Alanine aminopeptidase activity and autolysis in the tails of Rana catesbeiana larvae during metamorphosis. 1. Alanine aminopeptidase activity and autolysis increase concomitantly in tail tissue of Rana catesbeiana tadpoles during metamorphosis. 2. significant increases first appear at Taylor and Kollros state XX and coincide with the beginning of tail regression as determined by the tail wt body wt ration. 3. The results suggest a role of alanine aminopeptidase in the mechanism of tail resorption.


Composition of glycoproteins secreted by tracheal explants from various animal species. 1. The acidic and neutral glycoproteins secreted by cultured tracheal explants from pigs, sheep, rats, mice, monkeys, guinea pigs, dogs and chickens were purified and fractionated by column chromatography on DEAE-cellulose and by electrophoresis on cellulose acetate. 2. The ratios of acidic to neutral mucus glycoproteins were compared for the above animals with that of mucus glycoproteins secreted by cultured human bronchi. 3. The observed ratios of acidic to neutral glycoproteins ranged from 4.0 (mouse) to 7.2 (chicken and pig) from cultured tracheae; secreted human bronchial mucus had a ratio of 2.7. 4. The ratio of acidic to neutral glycoproteins secreted by tracheal explants varied with duration of incubation of the trachea in culture.


Regulation of avian erythrocyte AMP-deaminase. 1. Kinetic data for avian erythrocyte AMP-deaminase in lysate supernatants and 2000-fold purified enzyme were consistent with an allosteric model having four binding sites for substrate. 2. Relative to the purified enzyme, AMP-deaminase in lysate supernatants exhibited a greater S0.5 and enhanced sensitivity toward phytic acid, but was far less sensitive toward potassium ion. 3. In the absence of potassium chloride, the enzymatic activity in lysates exhibited hysteresis at subsaturating 5'-AMP. This response was modified reversibly by allosteric ligands. 4. It is concluded that the characteristics of avian RBC AMP-deaminase, as expressed in lysates, may reflect important intermolecular interactions and better represent the regulatory properties of this enzyme in erythrocytes.


Comparative studies on muscle AMP-deaminase--I. Purification, molecular weight, subunit structure and metal content of the enzymes from rat, rabbit, hen, frog and pikeperch. 1. AMP-deaminase (EC 3.5.4.6) from skeletal muscle of frog and pikeperch was purified to homogeneity and compared with the homogeneous enzymes purified from rat, rabbit and hen skeletal muscle. 2. Their molecular weight was close to 280,000, every enzyme consisted of four identical subunits of molecular weight about 70,000. 3. All enzymes were found to contain about two atoms of zinc per molecule. 4. Minor differences of u.v.-absorption spectra between amphibian and fish muscle enzyme as compared with mammalian and bird muscle enzyme were found.


Comparative studies on muscle AMP-deaminase--II. Regulation by monovalent cations, ATP and orthophosphate of the enzyme from hen, frog and pikeperch muscle. 1. Michaelis constants, maximum velocity and pH-dependence of the reaction catalysed by homogeneous AMP-deaminase preparations from hen, frog and pikeperch skeletal muscle were compared, as well as the influence of monovalent cations, ATP and inorganic phosphate. 2. ATP was found to activate the enzymes in the absence of K+ and at optimum (150 mM) KCl concentration. 3. Absolute dependence on potassium ions and considerable dependence of Km and Vmax on the kind of monovalent cation present in the medium were found for pikeperch enzyme.


Biochemical studies of supernatant malate dehydrogenase allozymes in Drosophila melanogaster. 1. A biochemical comparison was made among cytoplasmic malate dehydrogenase allozymic variants from Drosophila melanogaster. Experiments were carried out on enzyme extracted from six different genotypes: three homozygotes and their respective heterozygotes. 2. The allozyme forms (MDH A, MDH B, MDH C) were indistinguishable in terms of NAD and L-malate optima, while they are distinguishable in terms of NADH and OAA saturation conditions. Activities were inhibited at concentrations greater than 0.36 and 0.40 mM NADH for BB and AA, CC, respectively, while in relation to OAA inhibition was observed at concentrations higher than 3 or 6 mM for the AA, CC and BB, respectively. 3. differences among genotypes were also observed in thermal stability: Km values for OAA, L-malate, NADH and NAD: and pG optima. 4. A simple method is presented for the separation of the cytoplasmic from the mitochondrial malate dehydrogenase.


Metabolic changes in Crithidia fasciculata accompanying physiological adaptation to growth in the presence of carbonyl cyanide m-chlorophenylhydrazone. 1. Crithidia fasciculata adapted to growth in the presence of 10(-5) M carbonyl cyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, maintained adenosine phosphate pools and an adenylate energy charge comparable to those of control cells. 2. CCCP-adapted cells in the presence of the uncoupler respire endogenous substrate at a greater rate than control cells and this effect of CCCP appears readily reversible. 3. CCCP-treated, adapted cells, supporting high endogenous respiration rates, were not responsive to added substrates which significantly stimulated the oxygen utilization of normal C. fasciculata. 4. CCCP-adapted cells, provided with [U-14C]-labeled proline, utilize this substrate at 67% the rate of control cells, but divide the isotopic label between CO2 and protein in a ratio identical to that of normal cells. 5. The transport of alanine and proline by adapted C. fasciculata was severely impaired, while the transport of tyrosine and leucine was unaffected.


Methotrexate nephrotoxicity.

Methotrexate nephrotoxicity. The use of high dose methotrexate therapy in the treatment of malignant disease has been complicated by nephrotoxicity. Analysis of the basic physico-chemical properties of methotrexate has allowed the development of improved techniques of administering methotrexate, at high dose, which greatly reduces the incidence of nephrotoxicity.


Perspectives in the treatment of mental disorders in developing countries: Africa. 1. Although many parts of Africa are "catching up" with the technological advances of the developed world in many spheres, including medical practice, traditional forms of treatment conspicuously exist side by side with orthodox treatment. 2. None of the few reports of clinical trials from different parts of Africa have taken into account the variations in the clinical presentation of mental disorders, the nutritional status and general physical health of African patient populations in their discussions of the effectiveness of psychotropic agents. 3. Research into traditional forms of treatment and the effectiveness of psychotropic agents in populations in different states of general health and nutrition is seen as a priority.


The effects of drugs on the processes regulating the functional activity of brain monoamines. 1. By study of the synthesis and turnover of brain monoamines and with the use of behavioral models which indicate the functional activity of brain 5HT and dopamine, it is possible to unravel the mechanisms by which some drugs produce behavioral effects. 2. Using these techniques the acute and chronic effects of certain neuroleptics, propranolol and other beta-adrenergic blocking agents, repeated electroconvulsive shock, and lithium upon the functional activity of brain 5HT and dopamine are examined. 3. The clinical relevance of these studies is discussed.


Adverse effects in maintenance treatment: practical and theoretical considerations. 1. Subsequent to the introduction of therapeutically effective psychotropic drugs, there has been a decrease in the resident population in mental hospitals. 2. Since maintenance therapy with neuroleptics and lithium may alleviate and/or prevent relapse in a considerable percentage of schizophrenic and manic depressive patients, there is a gradual increase of these patients in the community. 3. In this paper some of the adverse effects of long-term pharmacotherapy with psychotropic drugs will be presented, and possible negative effects of the increase in fertile marriages among community-based patients will be discussed.


Short and long-term effects of neuroleptics in relation to their cellular mechanism of action. 1. Some mechanisms of action of neuroleptics at cellular level are reviewed, mainly the effects on synaptic transmission and the effects on chromatin. 2. As regard to the effects at synaptic level, a brief review is presented on the available evidence in support of the currently prevailing dopamine hypothesis. 3. Studies carried out on the mechanisms and sites of action of neuroleptics on chromatin show that: a. Behavioral changes caused by psychotropic drugs in experimental animals are associated with chromatin alterations and induced macromolecular syntheses. b. Parkinsonian and possibly drug-induced extrapyramidal symptoms are associated with aberrations in protein synthesis. c. Destabilization under "stress" of the heterochromatin in schizophrenics seems to be due to histone modifications and is partly prevented by neuroleptic treatment.


Perspectives in chemotherapy of schizophrenic psychoses. 1. The treatment of schizophrenic symptoms has not the same efficacy in acute and chronic phases of the disease and on the various target symptoms of schizophrenia. 2. The ideal antipsychotic drug might have different properties, sometimes contradictory, to be effective both on paranoid and hebephrenic symptoms which seem to be a mirror image of the same disorder. 3. Basic perspectives in the chemotherapy of schizophrenic psychoses must be founded on better methodological considerations in clinical trials, on a better use of antipsychotic drugs with the help of pharmacokinetic data and computerized EEG and also on new neurochemical findings. 4. Recent data on the mode of action of neuroleptics open up new therapeutic classes of drugs. Such are GABA-like drugs and, more recently, beta-blockers.


Treatment of schizophrenia.

Treatment of schizophrenia. 1. Progress in 25 years' history of the neuroleptics is briefly reviewed. 2. Development of certain butyrophenones more directly effective in "minus" symptoms of schizophrenia and introduction of depot neuroleptics is discussed. 3. Extrapyramidal motor side effects (EPMS) are still a serious problem in the treatment. 4. Clozapine does not have EPMS. This drug could therefore become the starting point of a series of less hazardous antipsychotic drugs. 5. The neuroleptics can be used as tools for exploration of the etiopathogenesis of schizophrenia. Some important pharmacological mechanisms, i.e. their antidopaminergic activity, are briefly outlined.


Psychopharmacological perspectives in childhood psychoses. 1. Neuroleptic drugs are still widely employed in childhood psychoses, but new experiences on a large number of cases in this field, have shown the usefullness of antidepressive drugs, either alone or associated with neuroleptics, also when depressive symptoms are not clearly evident. 2. This peculiar aspect, still noticed in pathological situations of less gravity, calls again attention to childhood depression and to the difficulty of identifying it. 3. The problem is developed and discussed as follows: a. The psychopathological features regarded from the psychodynamic point of view; b. The neurofunctional background in various ages; c. The pharmacodynamic characteristics of the drugs; d. The good results with lithium treatment in several cases allow the authors to outline some clinical pictures as well as biochemical markers as to recognize endogenous depression in childhood.


Perspectives in the treatment of the psychoneurological disorders: affective disorders. 1. Current research strategies in the pharmacotherapy of the affective disorders are reviewed in an attempt to highlight major trends and areas of particular promise. 2. There has been some progress toward the identification of biologically defined subgroups by assessing amine metabolites in urine or cerebrospinal fluid which may lead to a more rational choice of therapies for depressed patients. 3. The use of drugs with receptor agonist properties may help define biological substrates altered in affective illness and lead to new approaches to treatment, such as utilization of low doses of receptor agonists which may preferentially stimulate presynaptic receptors. 4. Study of time-dependent and adaptive changes in receptor sensitivity may also add an important perspective in conceptualizing the cyclic process in manic-depressive illness and its treatment.


Azidomorphines: a new family of potent analgesics with low dependence capacity. 1. Structure-activity relationship studies with new semi-synthetic isomorphine derivatives revealed that substitution of an azido group in position 6 (azidomorphines) greatly increases the analgesic potency whereas tolerance and dependence liability tend to decrease. 2. Azidomorphine (6-deoxy-6-azidodihydroisomorphine) and 14-hydroxyazidomorphine (6-deoxy-6-azidodihydro-14-hydroxyisomorphine) being in animal tests 40-300 times more potent than morphine, are the most effective analgesics among the semi-synthetic morphine alkaloids. 3. As demonstrated on mice, rats and rhesus monkeys, a remarkable dissociation between the analgesic potency and physical dependence capacity was the result of the introduction of the 6-azido group into dihydroisomorphine. 4. A dichotomy between analgesic effect and tolerance and addiction liability was demonstrated with azidomorphine also in man and the new substance proved to exert significantly less untoward effects than either morphine or pentazocine. 5. Rymazolium (Probon) a new non-narcotic analgesic which strongly potentiates the analgesic and antagonizes the respiratory depressant effect of morphine alkaloids in animals proved to hinder the development of tolerance to morphine in animals and man. 6. The azidomorphine-rymazolium association was found to be less respiratory depressant than azidomorphine administered alone. In patients with chronic intractable pain, an association of azidomorphine (0.5 mg) and rymazolium (150 mg) achieved total pain relief without noticeable euphoria and none of the twelve patients showed, according to the Himmelsbach scoring system, acute abstinence syndromes after nalorphine administration.


Is a dopaminergic system involved in thyrotropin releasing hormone induced hyperthermia and in its potentiation by amphetamine? 1. A dose-related hyperthermia is obtained in mice with TRH administered intraperitoneally. 2. This hyperthermia is reinforced by amphetamine given at doses which usually cause hypothermia. 3. p-Chloroamphetamine and L-Dopa also reinforce TRH hyperthermia. Apomorphine is not significantly active. 4. TRH hyperthermia is lowered significantly by alpha-methyl-tyrosine and haloperidol but not significantly by pimozide and chlorpromazine. TRH + Amph hyperthermia is not lowered by any of the DA antagonists tested even at doses reversing Amph hyperthermia. Direct participation of DA receptors is then doubtful. 5. All these variations of temperature have their acme a 15 min except for reserpine which, given 22 hours before, potentiates TRH + Amph hyperthermia after 30 min.


Enkephalin-dopamine interactions in behavioral arousal. 1. Central injection of a long lasting enkephalin analog (D-Ala2-leu-enkephalin-amide) produced a syndrome of stereotyped motor activity. 2. This activation syndrome was significantly reduced by two dopamine (DA) blockers (pimozide, fluspririlene) and by an agonist of inhibition-mediating DA receptors [(3,4-dihydroxyphenylamino)-2-imidazoline]. 3. Intact DA functioning is necessary for the occurrence of this enkephalin-mediated behavioral syndrome.


AHR-6646: a new, long-acting neuroleptic. 1. AHR-6646 blocked d-amphetamine lethality in mice under aggregated conditions when the pretreatment interval was between one hour and seven days. 2. Conditioned avoidance responding in mice and cats was suppressed by AHR-6646 in doses that did not impair escape behavior. The duration of this effect was markedly prolonged. 3. AHR-6646 produced catalepsy in rats. The onset of this effect was delayed and the duration was prolonged when compared with that of chlorpromazine. 4. Apomorphine-induced pivoting in mice with unilateral lesions of the caudate nucleus was suppressed by AHR-6646. 5. AHR-6646 was a potent antiemetic agent in dogs, with a delayed onset and prolonged duration of action.


An intrarenal effect of somatostatin on water excretion. Intrarenal infusion of somatostatin in anesthetized dogs produced a prompt increase in urine flow in association with a decrease in urinary osmolality and an increase in free water clearance. These changes occurred in the absence of changes in arterial pressure, renal plasma flow, osmolar clearance, electrolyte excretion or cyclic AMP excretion. The diuretic effect occurred primarily in the infused kidney indicating a direct intrarenal action rather than suppression of vasopressin secretion. This diuretic action of somatostatin may result from inhibition of the action of vasopressin on the renal medulla but other possible mechanisms cannot be excluded.


Serum and pituitary concentrations of prolactin and growth hormone in mice during a twenty-four hour period. The objective of this study was to investigate changes in the secretion of prolactin (PRL) and growth hormone (GH) occurring during a 24 h period in the mouse. Adult female mice of the C57BL/St strain and male mice of the C3H/St strain, maintained on a 14 h light and 10 h dark schedule, were used. Serum and pituitary concentrations of PRL and GH were measured by radioimmunoassay in samples collected by decapitation at hourly intervals through 24 h. Serum PRL concentrations in female mice averaged higher during the daylight hours and lower at night. However, the pattern was just the opposite in males: the values were lower during the day time and higher and variable during the night. Pituitary PRL levels dropped significantly after the onset of the dark phase in mice of both sexes. Serum GH concentrations of female mice did not fluctuate significantly with the time of the day, but those of male mice displayed a distinct flux: the levels were low from 0800 h until 1500 h, began to rise in the afternoon, and remained relatively high throughout the night. Pituitary levels of GH did not change with time in mice of either sex. The data suggest the existence of daily rhythms in the secretion of PRL and GH in mice, with marked differences related to sex. In general, the changes were most pronounced for serum PRL in females and for serum GH in males.


Serum cholesterol and bowel flora in the newborn. Bottle-fed infants have a total serum cholesterol of 147 mg/100 ml on the fifth day of life and their stools contain more Escherichia coli than Lactobacilli organisms. The ratio of these bacteria can be reversed by adding bicarbonate or Lactobacilli to feeds. This change is associated with a decrease in total cholesterol to a mean 119 mg/100 ml over the next 3 days. Lactobacilli organisms predominate in the stools when serum cholesterol is low and may play a role in the metabolism of cholesterol.


Serial pH changes in the duodenal bulb during smoking. The effect of smoking on the pH of the duodenal bulb was studied in 10 normosecretors and 10 hypersecretors using a Beckman pH electrode. The pH was monitored during three study periods, basal, smoking, and postsmoking, of 1 hr each. The pH remained below 3.5 significantly longer during the smoking period compared to the basal period for both groups. The bulbar pH remained under 3.5 during the smoking period longer in the hypersecretor group compared to the normosecretor group (60 versus 20%). Hypersecretors who were smokers exhibited acidic bulbar pH values longer and more consistently than hypersecretor-nonsmokers during smoking. In 5 hypersecretors with data for both bulbar pH and bicarbonate output, inhibition of bicarbonate output during smoking was generally associated with acidic pH values in the bulb. These observations suggest that the association between cigarette smoking and peptic ulcer disease may be attributable to, in part, the persistently acidic pH values in the duodenal bulb during smoking. This study further suggests that the degree and the duration of acidification of the duodenal bulb during smoking are influenced by the secretory and the smoking status of the subject.


Somatostatin in mucosa of stomach and duodenum in gastroduodenal disease. In order to study the distribution of somatostatin in the upper digestive tract in man, biopsies were taken through endoscopy or at surgery from the fundus, antrum, and duodenal bulb in 15 subjects with no gastroduodenal lesion, 12 patients with severe antral and/or fundic atrophy in the sampling area, 28 patients with an active duodenal ulcer, and 14 patients with a nonmalignant gastric ulcer. The specimens were extracted in 2 N acetic acid and tested for somatostatin content with a specific radioimmunoassay. In the control subjects, the somatostatin concentration (nanograms per milligram of wet weight) was 0.60 +/- 0.12 in the fundus, 1.68 +/- 0.33 in the antrum, and 1.35 +/- 0.30 in the duodenal bulb. Atrophy of the gastric mucosa was associated with a reduction of the somatostatin concentration in the fundus and the antrum. No significant variation was observed in the present series of patients with gastric ulcer. Duodenal ulcer was associated with a reduction of the somatostatin concentration in the antrum (P less than 0.02). These results indicate that somatostatin is widely distributed from fundus to duodenal bulb in adult human subjects, and that lower antral concentrations are observed in patients with duodenal ulcer.


Hypersensitivity reaction to sulfasalazine with severe hepatotoxicity. Sulfasalazine hepatotoxicity has been poorly documented in the literature. We report a case of a young female with inflammatory bowel disease who developed severe hepatotoxicity as part of a systemic hypersensitivity reaction to sulfasalazine. The clinical, biochemical, and histopathological features resemble those of sulfonamide-induced hepatic injury. Although rare, our case as well as previous reports indicate the serious nature of the illness.


An analgesic comparison of floctafenine (Idarac) and dihydrocodeine in post-operative pain. A double-blind crossover study comparing floctafenine 200 mg, a new analgesic drug, and dihydrocodeine 60 mg, was performed on 72 patients suffering from post-operative pain. Degree of pain relief by floctafenine was similar to that of dihydrocodeine but the relief afforded by the former was of longer duration. Side-effects associated with dihydrocodeine were statistically higher than those associated with floctafenine. Floctafenine was demonstrated to be an effective analgesic with an insignificant incidence of untoward side-effects.


Teichoic acids of group D streptococci with special reference to strains from pig meningitis (Streptococcus suis). Immunoelectrophoresis revealed in phenol extracts from S. faecalis and S. faecium a mixture of free and lipid-bound teichoic acids, both reactive with Group D antisera. In phenol extracts from S. suis only lipid-bound teichoic acid, also reactive with Group D antiserum, was seen. This difference probably accounts for the low yield of Group D antigen from S. suis as compared with S. faecalis and S. faecium when heating at pH 2 is used for extraction. When phenol is used good yields are obtained from S. suis as well as from S. faecalis and S. faecium. Lipoteichoic acids from S. faecalis and S. faecium have a backbone structure the same as or similar to that of Group A streptococcal teichoic acid. Lipoteichoic acid from S. suis has a structure differing from that of S. faecalis and S. faecium, e.g., possibly in the attachment of its glucosyl substituents. Precipitation reactions between S. suis lipoteichoic acid and Group D antisera were specifically inhibited by glucose. Reactions between S. bovis phenol extracts and some Group D antisera were also specifically inhibited by glucose, but extracts from S. faecalis and S. faecium were not. This may indicate a monosaccharide glucosyl substituent in teichoic acid from S. suis and S. bovis instead of the di- or trisaccharide previously postulated as the glucosyl substituent in the teichoic acid of S. faecalis.


Selective viral immunosuppression of the graft-versus-host reaction. Graft-vs.-host (GVH) reactivity of parental lymph node (LN) cells was assayed by measurements of 3H-thymidine incorporation in vivo in spleens of irradiated F1 recipients. Preincubation of parental LN cells with vesicular stomatitis virus (VSV) for 2 h at 37 degrees C followed by washing resulted in an 85-90% reduction in splenic radioactivity, as did injection of VSV on days 0-2 after recipients received untreated parental LN cells. In contrast, 3H-thymidine incorporation in the spleens or irradiated F1 hosts was not affected by VSV when F1 bone marrow cells were incubated with the virus. In addition, preincubation of F1 B cells with VSV still allowed these syngeneic B cells to be recruited into proliferation by mitomycin-treated parental LN cells. The inhibitory effect of VSV, thus, seems to be specific for T-cell proliferation. These observations suggest that viral immunosuppression might be capable of being developed into a useful strategy for selective deletion of lymphocytes capable of reacting against histocompatibility antigens and initiating GVH reactions.


Pilus-specific, lipid-containing bacteriophages PR4 and PR772: comparison of physical characteristics of genomes. The genomes of pilus-specific, lipid-containing phages PR4 and PR772 were studied electron microscopically. An identical mol. wt. of 10.9 x 10(6) was obtained. The genomes are unique (non-permuted) and have cohesive ends. From the similarities in size and denaturation maps of the genomes and failue to demonstrate non-homology in heteroduplexes, reported morphological ambiguities were clarified. The known serological difference between the phages could not be related to non-homology of their genomes. It is concluded that phages PR4 and PR772 are the same phage.


The homogeneity of the faecal coliform flora of normal school-girls, characterized by serological and biochemical properties. The homogeneity of fecal coliform flora in 52 schoolgirls was studied by serotyping and biotyping 10 randomly selected colonies in one fecal culture from each child. Ninety-eight clones were identified and of these 52 were dominant and 46 were minor strains. The probability of including at least one isolate of the dominant clone in a small random sample of colonies was calculated to be 86% for one colony, 94% for 2, 97% for 3, 99% for 4, and 99.3% for 5 randomly selected colonies.


Abortive growth of human lymphocytes carrying a dormant Epstein-Barr viral genome. When P3HR-1 lymphoblastoid cells expressing Epstein-Barr virus (EBV)-related antigens at very low frequency were cocultivated with human umbilical cord blood lymphocytes and the cell-free mixed culture fluid was applied to fresh cord lymphocytes, cells morphologically distinct from normal lymphocytes became evident after one to two weeks' exposure. The abnormal cells became abundant after one month and were easily identified by B-cell markers and a variety of morphologic abnormalities. Such abnormal B-lymphocytes appeared to be negative for EBV-determined nuclear antigen (EBNA), but when the immunofluorescence-negative cells were exposed to pokeweed mitogen and 5-iododeoxyuridine, a striking EBNA induction occurred. The growth of these abnormal cells was limited and they could be maintained for no more than three months. The implications of these findings are discussed in relation to the biological activity of EBV.


The susceptibility of Vero cell cultures for human adenoviruses. Human adenoviruses 1 to 28 were shown to produce a cytopathic effect in Vero cell cultures. Viruses of subgroups III and IV (Ad 1, 2, 5, 6, 12, and 18) were readily passaged in Vero cell cultures and were produced in high amounts. This was also found for Ad 11, 16, and 21, while Ad 3, 4, and 7 showed a lower degree of multiplication and Ad 14 could not be passed serially. For Ad 8, 26, 27, 20, 25, and 28, a multiplication in Vero cells could not be proved, while the remaining serotypes of subgroup II showed a moderate degree of multiplication. The sensitivity of Vero cells to small amounts of virus was lower than that of HeLa cells. No adaption of adenoviruses to Vero cells after 5 Vero passages was observed. Attempts to enhance virus multiplication by coinfection with SV40 failed.


A/New Jersey/76 influenza vaccine trial in seronegative schoolchildren: comparison of a subunit vaccine with a whole-virus vaccine. In the present vaccination trial, 202 seronegative schoolchildren comprising both sexes and aged 11 to 12 years were vaccinated i.m. in the upper arm with either the subunit vaccine at a dosage of 600 CCA or 200 CCA or with a whole-virus vaccine at a dosage of 200 CCA, using the double-blind procedure. Both vaccines were prepared from the strain A/New Jersey/76 (x 53a-recombinant). The vaccination was followed four weeks later by a booster injection. In tests of local and systemic reactogenicity, it was found that at both dosages the subunit vaccine caused a low frequency of minor adverse reactions. The whole-virus vaccine was marked by a significantly higher rate of adverse reactions, whether of the local or systemic variety. The whole-virus vaccine had, however, a higher immunogenicity than the subunit vaccine, and due to the relatively high rate of adverse reactions it causes, it is not recommended for the vaccination of seronegative children. Because of its low reactogenicity, the subunit vaccine can be given at higher dosage, and it is a matter for consideration whether a better antibody response might not result from two booster injections.


A comparison of staphylococcal nasal carrier rates in Germany and Poland. Frequencies of different staphylococcal nasal carrier classes were studied in groups of students of nursing and of laboratory personnel in Cologne, West Germany, and in Krakow, Poland, by six consecutive samplings of their nasal vestibules. The general number of persistent carriers of S. aureus appeared to be lower than in previous studies, paralleling the diminished numbers of staphylococcal infections in populations. Differences in numbers of persistent carriers between the Cologne and Krakow groups were probably related to the incidence and types of S. aureus in the environment.


Course of coxsackie B antibodies during juvenile diabetes. Sera of 83 patients with insulin-dependent diabetes of early onset were tested for latex agglutination-inhibiting antibodies to coxsackie virus types B1-B5. We could not find any evidence of a causal association between Coxsackie B virus infection and diabetes.


The use of IgM antibody responses in the diagnosis of primary infections to measles, rubella, mumps, and M. Parainfluenzae viruses. One-hundred and twenty-seven sera were tested to determine whether a primary infection could be identified by a determination of the class of antibody (IgM) detected in serum collected in the period after a viral infection. Serum was collected from patients with a history of measles (18 cases), rubella (24 cases), mumps (12 cases), and M. parainfluenzae type 3 infections (9 cases). The results of the serological assays are compared with clinical observations and the limitations of the methods under consideration are discussed.


The genetic fine structure of the complex locus aro3 involved in early aromatic amino acid biosynthesis in Schizosaccharomyces pombe. The complex locus aro3 of Schizosaccharomyces pombe was subjected to genetical fine structure analysis. By comparing the complementation map and the meiotic recombination map, the aro3 locus could be subdivided into the five adjacent subregions A, B, C, D and E. Out of 115 aro3 alleles, 26 nonsense alleles and 30 missense alleles could be identified by the criteria of nonsense suppressor sensitivity and leakiness, respectively. Most alleles with a pleiotropic complementation pattern are of the nonsense type. We conclude from the polarity of the complementation patterns characterising the nonsense alleles that the translation direction proceeds from subregion. A to subregion E. Antipolar effects in complementation are more frequent than in the analogous system of the arom gene cluster of Neurospora crassa.


Lambda encodes an outer membrane protein: the lom gene. lambda infected minicells synthesize a polypeptide (M(r) = 20,500) which is incorporated almost exclusively into the outer membrane of the minicell envelope. The gene (lom = lambda outer membrane) encoding this polypeptide has been mapped in the non-essential region of the lambda genome between coordinates 39.4% and 40.7% of lambda.


Decreased UV mutagenesis in cdc8, a DNA replication mutant of Saccharomyces cerevisiae. A DNA replication mutant of yeast, cdc8, was found to decrease UV-induced reversion of lys2-1, arg4-17, tyr1 and ura1. This effect was observed with all three alleles of cdc8 tested. Survival curves obtained following UV irradiation in cdc8 rad double mutants show that cdc8 is epistatic to rad6, as well as to rad1; cdc8 rad51 double mutants seem to be more sensitive than the single mutants. Since UV-induced reversion in cdc8 rad1 and cdc8 rad51 double mutants is like that of the cdc8 single mutants, we conclude that CDC8 plays a direct role in error-prone repair. To test whether CDC8 codes for a DNA polymerase, we have purified both DNA polymerase I and DNA polymerase II from cdc8 and CDC+ cells. The purified DNA polymerases from cdc8 were no more heat labile than those from CDC+, suggesting that CDC8 is not a structural gene for either enzyme.


Studies on the induction of petite mutants in yeast by analogues of berenil. Characterization of three mutants resistant to the compound Hoe 15,030. Compound Hoe 15,030 is an analogue of berenil which is as effective as berenil in inducing petite mutants in Saccharomyces cerevisiae. Hoe 15,030 has greater stability than berenil in aqueous solution, and is less toxic to yeast at high drug concentrations. Mutants of S. cerevisiae strain J69-1B have been isolated which are resistant to the petite inducing effects of Hoe 15,030. Three mutant strains (HR7, HR8 and HR10) were characterized and each was shown to carry a recessive nuclear mutation determining resistance to Hoe 15,030. The degree of resistance to Hoe 15,030 is different for each mutant, and each was found to be co-ordinately cross-resistant both to berenil and to another analogue of berenil, Hoe 13,548. However, the three mutants show no cross-resistance to other unrelated petite inducing drugs, including ethidium bromide, euflavine and 1-methyl phenyl neutral red. Further studies on the mutants revealed that each strain exhibits characteristic new properties indicative of changes in mitochondrial membrane functions concerned with the replication (and probably also repair) of mitochondrial DNA. Thus, mutant HR7 is hypersensitive to petite induction by the detergent sodium dodecyl sulphate under conditions where the parent J69-1B is unaffected by this agent. Mutant HR8 is even more sensitive to sodium dodecyl sulphate than is HR7, and additionally shows a markedly elevated spontaneous petite frequency. Isolated mitochondria from strains HR8 and HR10 (but not HR7) show resistance to the inhibitory effects of Hoe 15,030 on the replication of mitochondrial DNA in vitro.


Bacteriophage SPP1 polypeptides synthesized in infected minicells and in vitro. Minicells produced by B. subtilis CU403divIVB1 and infected by SPP1 synthesize at least 46 polypeptides which can be separated by polyacrylamide gel electrophoresis. These polypeptides represent the expression of 86% of the SPP1 genome's coding capacity. Infection of minicells by sus mutants and deletion mutants of SPP1 has permitted a correlation of genetic location with gene product and has shown that SPP1 normally synthesizes at least 8 non-essential polypeptides. Restriction fragments of SPP1 produced by EcoRI digestion of SPP1 DNA have been purified and used as template DNA in a coupled transcription/translation system derived from E. coli to determine the polypeptides encoded by the individual fragments. SPP1 expression in minicells differs from SPP1 expression in nucleated cells (Esche, 1975) in that late syntheses are not dependent on phage DNA replication in infected minicells.


Genetic control of maltase synthesis in yeast. IV. Function of the MAL4 gene: extragenic suppression of a maltase negative mutant. A new series of maltase negative mutants have been isolated from yeast strains carrying the MAL4 gene. These mutants are allelic to the MAL4 gene and fail to ferment maltose, sucrose, and alpha-methylglucoside. Most revertants isolated from these mutants restore the ability to ferment above sugars, and also produce the same levels of maltase as the parental strains. One of the revertants (NA-520-R1), however, ferments maltose slowly, and produces 24 fold less enzyme than the parental strain. Genetic studies revealed that revertant (NA-520-R1), is not a true back mutation but is carrying an extra-genic suppressor, which suppresses the mal4 allele in mutant (NA-520). Since several lines of published evidence indicate that the MAL4 gene is a regulatory gene, it is suggested that the MAL4 gene codes for a regulatory protein, which acts as a positive regulatory element in maltase synthesis.


Proton conductor vs. cold in induction of Ca(2+)-dependent competence in Escherichia coli. In order to elucidate the molecular mechanisms of Ca(2+)-dependent competence in gram-negative bacteria an attempt was made to induce the competence at room temperature in presence of a proton conductor, carbonylcyanide-m-chlorophenylhydrazone (CCCP). Escherichia coli K12 cells treated with Ca2+ at 25 degrees or 37 degrees C in presence of CCCP became permeable for transforming plasmid and transfecting DNAs and DNA-binding antibiotic actinomycin C (AmC) and rubomycin (Rm) at room temperature. The efficiencies of transformation and transfection, however, were by 1-3 orders of magnitude lower compared to cells, treated with Ca2+ at 0 degree C, though both recipients did not differ significantly in their susceptibility to AmC and Rm. Possible mechanisms of Ca2+ action in both recipient systems are discussed in terms of molecular interactions.


Molecular characterization of the genomes of actinophages SH3, SH10, SH11, and SH12 infecting Streptomyces hygroscopicus. Some physico-chemical properties of the DNAs released from the actinophages SH3, SH10, SH11, and SH12 are described. The four phage DNAs have a linear double-stranded secondary structure and are unique with respect to their high G.C contents which, from melting studies and buoyant density experiments, were found to be in the range of 68-73 mol-%. The DNA molecular weights were determined by sedimentation velocity experiments and by electron microscopic length measurements, the mean values of the two corresponding data sets being 34.0 x 10(6) (SH3), 26.7 x 10(6) (SH10), 26.1 x 10(6) (SH11), and 28.7 x 10(6) (SH12) with a mean relative error of +/- 5%. From different observations it was concluded that SH10 DNA, and possibly also SH11 and SH12 DNA, have cohesive ends and can undergo intramolecular or intermolecular association to form ring-like monomers or linear and ring-like multimers. Cleavage of the DNAs of SH3, SH10, SH11, and SH12 by EcoRI restriction endonuclease delivered two, one, zero, and two cleavage sites, respectively, and by BamHI restriction endonuclease eight, zero, zero, and zero cleavage sites, respectively.


Aberrant immunity behaviour of hybrid lambda imm21 phages containing the DNA of ColE1-type plasmids. Hybrid lambda and lambda imm21 bacteriophages carrying various ColE1-type plasmids have been constructed in vitro. The lambda imm21/plasmid recombinants display aberrant immunity behaviour, giving clear plaques under conditions where the parental phages give turbid ones and being able to grow on homoimmune lysogens. lambda imm lambda/plasmid recombinants show no such unusual behaviour. Studies with hybrids of a lambda imm21 cITS phage carrying pMB9 DNA showed the operation of the plasmid's replication system to be the basic cause of the aberrant immunity behaviour. The plasmid replication system could act as a complete alternative to the phage system during vegetative phage growth. The probable reason that lambda imm21 phages show such altered phenotypes when carrying a functional plasmid replication origin, whereas lambda imm lambda and lambda imm434 (Mukai et al., 1978) phages do not, is the relative ease of titration of the phage 21 repressor to allow transcription from pR21. Various uses are considered for the altered phenotypic behaviour of lambda imm21/ColE1-type plasmid hybrids.


[Thin layer chromatographic extraction of the histologic section--a combination of microanalytic and histochemical methods]. Thin layer chromatography as extraction method for histological sections. A combined microanalytical and histochemical procedure. A combined histochemical and chromatographical procedure is described to identify tissue components such as lipids, free amino acids, carbohydrates and steroids in cryosections. Fixed or unfixed sections are extracted by solvents of decreasing or increasing polarity. The extracts are then analysed by chromatographical techniques known from analysis of tissue homogenates. The extracted sections can be controlled by histochemical staining. Our technique is demonstrated in detail by analysis of lipids in bovine seminal vesicle epithelium, by analysis of free-amino acids in rat brain and pituitary and by analysis of steroids in male rat adrenal gland.


[The specificity and sensitivity of the gelatin base protease substrate film test ]. Highly sensitive gelatin substrate films prepared according to a recent variant of the procedure are studied for their susceptibility to the action of various endopeptidases and exopeptidases. Trypsin, papain, elastase, and chymotrypsin are found to hydrolyze the gelatin films most easily, while higher enzyme concentrations are required in case of pepsin, plasmin and collagenase. The exopeptidases, i.e. leucine aminopeptidase, amino acid arylamidase and carboxypeptidases A and B do not cause lysis of gelatin substrate films. The example of a rabbit blastocyst protease involved in implantation is given to demonstrate the application of gelatin substrate film tests for studies of enzymes which have no or little activity against known synthetic substrates (like BANA or GPNA) but hydrolyze gelatin films. Studies of interactions of this blastocyst protease with various inhibitors of known specificity, however, show that the active center of this enzyme nevertheless has striking similarities to trypsin (and also to chymotrypsin). The enzyme is possibly related to elastase. It is emphasized that, besides this, there are a number of different protease type enzymes in rabbit blastocyst and uterine tissues, some of which can be demonstrated only with chromogenic substrates and some only by gelatin methods. Aspects of applicability of the two types of protease tests are briefly discussed.


[Histologic-histochemical findings in the salivary glands of guinea pigs after sectioning the chorda tympani]. We investigated Gl. submandibularis and Gl. sublingualis of the guinea-pig 1, 2, 5, 7, 14 und 28 days after section of the Chorda tympani with histological-histochemical methods. The innervation pattern of both glands (Gl. submandibularis: aminergic-cholinergic double innervated; Gl. sublingualis: cholinergic innervated) remains unchanged. In the gland cells the following effects were observed: a) Gl. sublingualis. In the first 3 days apocrine and holocrine secretion phenomena are often seen, suggesting a maximal stimulation of the gland parenchyma. They are accompanied with cellular reactions of the interstitial space. In a second phase a new gland cell population appears that uniformly exhibits intracellular accumulation of secretion products. Involution begins from the 14th day on. Secretory cells are dedifferentiated to intercalated duct cells; autophagic processes help to degradate the accumulated secretion granules. b) Gl. submandibularis. Here the effects are less dramatic. The accumulation of the secretory granules starts as soon as 24 h after section of the Chorda and is maximal between the 5th and 8th p. o. day. Involution of the gland begins from the 14th day on. The accumulated secretory granules show high activities of two histochemically demonstrable enzymes, the cholinesterase and the peroxidase.


Histochemical and biochemical investigations of adenosine triphosphatase in vertebrate mixed muscles. Mammalian and avian muscles were examined histochemically and biochemically to determine the relative contribution of membrane bound (mitochondrial and sarcotubular) ATPases under the same conditions employed for myofibrillar ATPase. For histochemically investigated Ca+(+)-ATPase activity following incubation at pH 9.4 according to the calcium-citro-phosphate technique, avian muscle displayed distinct mitochondrial localization in both dark and light staining fibres. However, mitochondrial localization did not occur in mammalian muscle fibres. Pretreatment of unfixed frozen sections with ouabain, cyanide and acetone did not prevent the reticular distribution in avian muscle fibres. The present study demonstrates that "myofibrillar" localization is achieved by the Ca+(+)-precipitation technique: provided frozen sections are pretreated with cold acetone, fixed in a fixative containing oligomycin or azide and then incubated in a medium containing glycine-NaO H as buffer. Mitochondria prepared by successive mechanical homogenization or by Nagarse treatment plus 2 min homogenization develop different ATPase activities at pH 9.4 7.4 6.0 and 4.35 as well as stimulation by 70 mM Ca++ at these pHs compared to those ATPase activities in the homogenate of mixed hamster hind leg muscles. Glycerol-3-phosphate dehydrogenase and creatine kinase (both located at the outer surface of the inner mitochondrial membrane) and succinate dehydrogenase and glutamate dehydrogenase (localized at the inner mitochondrial membrane and in the matrix resp.) also show different activities in both mitochondria preparations indicating different membrane properties of both mitochondria. Evidence is obtained that using the calcium-citro-phosphate technique at pH 9.4 oligomycin-sensitive and -insensitive ATPases are activated by Ca++ in both mitochondria preparations. Since in muscle homogenate less than 10% of Ca+(+)-stimulated ATPase activity is oligomycin-sensitive, mitochondrial ATPase exhibit only a small portion of total ATPase from mixed hamster hind leg muscles.


[Cytochemical studies of ultrathin frozen sections of blood platelets]. Results obtained by conventional techniques and freeze-ultramicrotomie have been compared. Ultrathin frozen sections of platelets, which are fixed by glutaraldehyde, freeze-protected by polyvinyl-pyrrolidone and encapsulated in gelatin show a well preserved fine structure after staining with buffered OsO4, phosphotungstic, phosphomolybdic or ammoniummolybdic acid. The preservation of polysaccharides or mucopolysaccharides depends on a suitable fixation, that of glycogen in certain cases depends on a double fixation (glutaraldehyde and OsO4). Cytoplasmic nucleoproteins like ribosomes are visible only after drying of sections and staining with uranyl-acetate. Lipids, both membrane lipoproteins as well as lipids in the matrices of cell organelles, are well preserved. For example the zinc-iodide osmiumtetroxide reaction yields positive results in frozen sections contrary to such obtained by conventional methods. Furthermore, the extraction of altered lipids after staining with dyes like acridine orange does not take place with this method. For this reasons the freeze-ultramicrotomy seems to be an useful alternative method.


Acute decompression sickness: 50 cases.

Acute decompression sickness: 50 cases. In a review of the most recent 50 consecutive cases of acute decompression sickness in US Navy divers undergoing training at the Naval School, Diving and Salvage, in no instance was recompression following the initial treatment necessary, nor was there any permanent morbidity post-treatment. Factors common to this series are 1) strict physical screening and conditioning; 2) physician and diver awareness of the signs and symptoms of decompression sickness; 3) short surface interval between symptom onset and recompression; 4) aggressive diagnostic and therapeutic use of hyperbaric oxygenation, and 5) judicious use of adjunctive measures such as intravenous fluid and dexamethasone (Decadron). In the ideal management, the physician sees the patient shortly after symptom appears. As soon as central nervous system involvement appears, 100% oxygen by mask is administered and the patient is recompressed supine to 60 feet of sea water.


Evaluation of cardiac arrests managed by paramedics. The effectiveness of cardiac resuscitations by Cincinnati paramedics was monitored for one year. The outcome of every arrest was assigned to one of four categories: dead on arrival, died in the emergency department, died in the hospital or discharged alive, and each patient was followed until death or discharge from a hospital. Of the 147 people in the study group, 22 left the hospital alive, a long-term success rate of 15%, and another 26 died during hospitalization, 18% of the study population. This data is comparable to success rates reported by other prehospital care systems. Furthermore, this data indicates approximately 15% of people who have cardiac arrests outside of a hospital can survive through prompt intervention by trained personnel.


Extension of emergency medical care: continuing emergency care clinic. An alternative follow-up system, a Continuing Emergency Care clinic (CEC) was developed at The Medical College of Pennsylvania in an attempt to increase emergency department patient compliance for follow-up. One year after the CEC was in operation, in an attempt to determine variables influencing the effectiveness of the clinic, a total of 375 emergency department patients given follow-up appointments to the CEC were studied. Results showed that a change in the structure of the clinic appointment and a shift in the line of responsibility for follow-up care directly to the emergency physician are two major variables positively affecting patient compliance.


Resuscitation algorithm for management of acute emergencies. Assuming that unrecognized or inadequately corrected hypovolemia results in higher mortality and morbidity rates, we developed a systematic approach to resuscitation that would: 1) identify criteria to aid in the recognition of hypovolemia and ensure the expeditious correction of this defect without interfering with diagnostic workup and management; 2) define criteria to prevent fluid overload which may jeopardize the patient's course, and 3) express these criteria in an explicit, systematic, patient care algorithm, ie, protocol, useful to both the resident and the practicing physician. We are now conducting prospective clinical trials with one service using the algorithm and the others acting as the control group. Preliminary results comparing patient outcomes suggest that the algorithm improves patient care by shortening resuscitation time and results in fewer hospital days, intensive care unit days, febrile days, and days on mechanical ventilation as well as reduced mortality. The algorithm provides a systematic plan to organize patient care so that the most urgently needed procedures are not delayed or overlooked.


Preventing complications of subclavian vein catheterization. The proximity of the subclavian vein to several important structures of the arm, neck and chest make serious complications in subclavian catheterization occur in 0.4% to 9.9% of cases. Complications can be in immediate, chronic and late categories. An understanding of the anatomy, venography and a step-by-step technique of catheterization will help prevent complications and assist the physician in recognizing them when they occur.


Evaluation of physician skills in cardiopulmonary resuscitation. Thirty-five physicians at various levels of postgraduate training in internal medicine were evaluated for performance skills in cardiopulmonary resuscitation (CPR) according to standards of the American Heart Association. They were given instruction in only the cognitive knowledge related to CPR through lectures and a demonstration of the technique, without supervised manikin practice. Only 22% (8) of the physicians tested were able to adequately compress and ventilate the manikin in a simulated cardiac arrest. Although physicians are proficient in the use of drugs during resuscitative efforts, it is also imperative that they be able to perform basic CPR.


Assessing the validity of EMS data.

Assessing the validity of EMS data. Variation in the assessment of basic clinical data gathered by emergency medical technicians and emergency department nurses was studied. Prior to testing, precise definitions, categories and procedures were developed and tolerance limits for the quantitative variables were created. Each participant evaluated four consecutive patients simultaneously with another evaluator setting the standard. The results indicate that the error rate is low to moderate for the different variables. For the quantitative variables, the error rate is over 20% and, when an error does occur, it is often very large. This indicates a need for ongoing emphasis on accurate measurement and, in cases where highly accurate data is essential, the use of multiple observers.


Airless paint gun injuries: an update.

Airless paint gun injuries: an update. The airless paint gun delivers paint at pressures approximating 3,000 psi. Paint accidently injected into the skin under this pressure causes a devastating injury which is a result of the paint material, the level of bacterial contamination, and the pressure at which the paint is delivered. The time interval between injury and treatment seems a critical determinant of outcome. Decompression of the closed vascular compartments of the hand must be begun immediately to release the underlying tissue distended by the injected paint. Judicious wound debridement must be performed. Immediate antibiotic treatment is indicated in all patients. Studies seem to indicate that steroids limit the severity of inflammatory response. A regimen of hydrocortisone sodium succinate, 100 mg IV, administered immediately before surgery should be followed by a seven-day tapering course of oral prednisone starting with 40 mg on the first postoperative day. Recent safety measures and consumer warnings through the Consumer Product Safety Commission may reduce the number of airless paint gun injuries.


Airway management in patients with central nervous system depression. In central nervous system (CNS) depressed patients, a sequential approach is necessary to prevent airway obstruction and aspiration of vomitus. Endotracheal intubation is indicated if the lash reflex is absent, response to stimulation is not purposeful, or airway obstruction develops when the patient's neck is flexed. Aspiration may result from CNS depression, abnormal glottic function, or extreme debilitation. It may occur in cannulated patients with improper cuff management or after decannulation while glottic reflexes are ineffective.


Gasoline contact burns.

Gasoline contact burns. In the past four years, four cases of gasoline contact burns have been treated at the Detroit General Hospital Emergency Department. Signs are erythema and blister formation within 24 hours. Treatment is removal of contaminated clothing and washing the surface with soap and water plus open exposure of the wounds. Renal failure is not caused by skin absorption but may develop following inhalation.


Methemoglobinemia: nitrobenzene ingestion. In an unusually severe case of multiple toxin ingestion, a 48-year-old man ingested approximately 300 cc of Hoppe's Gunpower Solvent #9, which contains kerosene, denatured ethyl alcohol, oil and nitrobenzene. The major manifestation was nitrobenzene-induced methemoglobinemia of rapid onset. Treatment involves the judicious use of 1% methylene blue plus, in severe cases, hemodynamic and ventilatory support. The patient recovered after 48 hours and was transferred to the psychiatric service with continued follow-up for a mild poison-induced hemolytic anemia.


A new technique for subclavian puncture. A new technique for performing and teaching subclavian punctures based on the finding of a new landmark--a small tubercle on the medial aspect of the deltopectoral groove, is presented. This tubercle has been found to be easily palpable on 92% of individuals examined. With this new landmark and the technique described the novice can quickly master this procedure with very little difficulty. The author found that both clinicians inexperienced in subclavian puncture and nursing personnel performed the procedure successfully after the first or second trial.


Prioritizing clinical and nonclinical issues for emergency department quality assessment studies. There is a need at both the emergency department and national level for a systematic method to prioritize clinical and nonclinical areas for research and quality assessment. A method has been developed and applied that allows frequently presenting diagnoses and management issues to be rated in terms of morbidity generated, efficacy of (optimal) clinical intervention, discrepancy between optimal and current treatment, and the impact of an evaluative intervention study on improving care. Also, a summary research priority score was derived. When this method was used by physicians, nurses and administrators at the Johns Hopkins Hospital Adult Emergency Department, a reasonable level of agreement between the three responding groups emerged.


Respiratory function following application of MAST trousers. To determine whether counterpressure suits such as the medical anti-shock trousers (MAST) reduce functional ventilation, 25 consecutive patients who received MAST support were reviewed retrospectively. The indications for use of MAST were systolic pressure below 80 mm Hg or clinical signs and pressure below 100 mm Hg. In the five patients with head injuries severe acidosis developed, with a mean pH of 7.19. The other groups had only mild acidosis. Although counterpressure suits have been shown to affect mechanical pulmonary function, alveolar ventilation is not significantly impaired.


Falls from heights.

Falls from heights. Falls from heights are most commonly due to accidents in children and suicide, accident, and crime-related incidents in adults. Two types of injury result from falls from heights: injury resulting from direct impact and deceleration-type injury. The injuries resulting from direct impact are mostly fractures. The body position at impact is crucial. The deceleration forces immediately post-impact result primarily in visceral and internal injury, including cranial injury. There is a lack of correlation between os calcis fractures and vertebral fractures. Spinal cord injury is infrequent. Survival figures are higher than usually assumed.