PH metric method for the determination of nicotinic acid in plasma. The acidimetric method for the determination of nicotinic acid (NA) using Lactobacillus plantarum ATCC 8014 (Lactobacillus arabinosus 17-5) has been simplified and thus made less time consuming, and the sensitivity has been increased fivefold by replacement of the titration by a pH determination. As the regression of the decrease in pH on the amount of NA was found linear within a range of 1 to 4 ng of NA per ml, the calculations were performed according to the slope-ratio principle. The NA concentration of plasma was determined with a coefficient of variation of 5 to 7%, which rose to about 10% at low NA concentrations. Assays of fasting plasma samples from 13 hyperlipidemic male patients showed a group mean NA concentration of 80 +/- 55 ng/ml (mean +/- 2 standard deviation), before treatment, and 705 +/- 544 ng/ml (mean +/- 2 standard deviation) during therapy with sustained release NA preparations, of which a single dose, ingested during steady-state conditions, doubled or tripled the plasma concentration within 1 to 3 h.


Detection of pneumococci in respiratory secretions: clinical evaluation of gentamicin blood agar. The use of sheep blood agar containing 5 microng of gentamicin per ml has been suggested as a means of selectively isolating Streptococcus pneumoniae from respiratory secretions. We have tested this method, in parallel with standard methods, on 844 respiratory specimens in a clinical laboratory and have confirmed that the yield of pneumococci can be increased approximately 40% by using agar containing gentamicin. However, since the antibiotic suppresses the growth of staphylococci, group A streptococci, and gram-negative bacilli, gentamicin agar cannot be used as a replacement for the standard method. The requirement for duplicate plating raises the cost per additional pneumococcal isolate to prohibitive amounts. Although the method is useful in studies designed to isolate only pneumococci, it cannot be recommended for the routine clinical laboratory. An unanticipated observation from our study is that the yield of pneumococci in respiratory secretions can be increased 10-fold simply by screening sputum for the presence of leukocytes using the Gram stain. This is in agreement with results reported from other laboratories.


Reactivation of Newcastle Disease Virus Neutralized by Antibody. In an effort to improve current technology for detection of Newcastle disease virus in convalescent birds, a procedure has been developed for efficient reactivation of virus that has been neutralized by antibody. The reactivation capabilities of fluorocarbon treatment, ultrasonic treatment, pH extremes, and proteolytic digestion were evaluated using the LaSota strain of virus. Reactivation was maximum after proteolytic digestion with either trypsin or papain, and reactivation effciency was up to 100%, depending on the enzyme used for digestion and the amount of antibody in the neutralization mixture. Reactivation at pH extremes was considerably less efficient than reactiviation by proteolytic digestion, and neither fluorocarbon nor ultrasonic treatments effectively recovered antibody-neutralized Newcastle disease virus.


Rapid method for determining nitrate utilization by yeasts. A test for the nitrate-reductase activity in yeasts has been developed, in which the reaction may be read after only 10 min of incubation. The rapidity of the test is due to the optimization of pH, substrate concentration, and temperature for the reaction.


Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy. Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role.


Hydrolysis of the elastase substrate succinyltrialanine nitroanilide by a metal-dependent enzyme in rheumatoid synovial fluid. A new type of enzyme hydrolyzing the elastase substrate succinyl-L-alanyl-L-alanine-4-nitroanilide has been found in cell-free rheuma todi synovial fluid. Normal plasma and osteoarthritic synovial fluid contained relatively little enzyme. The pH optimum was 8.0. Unexpectedly, the enzyme activity was not due to leukocyte elastase or any proteinase bound to alpha2-macroglobulin. The enzyme activity was metal-dependent being inhibited by chelating agents but not by di-isopropylfluorophos phate or thiol-blocking reagents. Gel chromatography showed the enzyme activity was associated with material of high molecular weight. On Sepharose 4B chromatography two-thirds of the activity eluted in the void volume and one-third in a position of about 106 mol wt. Utracentrifugation showed that both components were associated with lipid. The buoyant density of the higher molecular weight material was 1.15-1.22 g/ml., and that of lower molecular weight material was 1.2-1.33 g/ml. No latency of the enzyme was revealed by freezing and thawing or treatment with detergents. The nature of the enzyme is discussed. It is likely to be a proteinase possibly bound to some kind of membrane fragment.


Metabolic studies in patients with nadolol: oral and intravenous administration. Nadolol-14C, 2,3-cis-5-(3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,3,4-tetrahydro-2,3-naphthalenediol, a nonselective beta-adrenergic blocking agent, was administered orally and intravenously at 2-mg doses to patients with mild cases of essential hypertension. Terminal plasma half-times after oral and intravenous doses were an average of 12.2 and 9.8 hours, respectively. After oral doses, an average of 24.6 and 76.9 per cent of the dose was excreted in urine and feces, respectively, whereas, after intravenous doses, an average of 72.9 and 23.3 per cent of the dose was excreted by the same routes. Calculations of absorption, based on urinary excretion and on areas under the plasma concentration-versus-time curves, indicated that oral doses of nadolol-14C were absorbed to the extent of 33.6+/-2.4 per cent (+/- S.E.). The average overall volume of distribution after intravenous administration was 2.09+/-0.51 1./kg (+/- S.E.), and the average volume of the central compartment was 0.30+/-0.04 1./kg. Only unchanged nadolol-14C was excreted in the urine and feces of patients after either oral or intravenous administration of the drug.


Electroencephalographic responses to photic stimulation in habitual smokers and nonsmokers. Two studies are reported in which electroencephalograms (EEGs) of habitual cigarette smokers and of nonsmokers were taken before and after they were required to smoke a cigarette. The EEGs were scored for incidence of EEG "driving" responses to photic stimulation, an index that appears to reflect the balance between central adrenergic and cholinergic nervous systems. The findings suggest that smokers tend to have a central autonomic balance less in favor of adrenergic functioning than do nonsmokers. Cigarette smoking may alleviate a possible central adrenergic insufficiency of smokers. These findings suggest a solution to "Nesbitt's paradox," which has reference to the fact that while nicotine is a central adrenergic stimulant, smokers describe the effect of smoking in sedational terms (i.e., as relaxing or calming).


A method for evaluating anxiolytic sedatives. Although anxiolytic sedatives are widely used in clinical practice, the methodology for assessing treatment effect of these compounds has not been well developed. The present double-blind study was designed to refine methodology for evaluating anxiolytics. Choice of rating scale, patient selection, maintenance of the double-blind status, the subjects' environment during the study, and the subjects' understanding of the study are discussed as considerations in reducing sources of variability and bias in the study of anxiolytics. After placebo prescreening, 14 subjects with diagnoses of anxiety recieved 3 to 6 mg lorazepam daily for four weeks, while 14 control subjects received placebo. The Hamilton Anxiety Rating Scale (HARS) and the Wang Anxiety Rating Scale (WARS), with its Anxiolytic Adjunct Scale (AAS), were used to assess changes in anxiety. The Wang and Hamilton ratings correlated well at both comparison periods. Lorazepam demonstrated significant superiority to placebo and produced no serious adverse effects. Anxiolytic efficacy did not differ significantly among the four weekly ratings.


Comparison of triazolam, flurazepam, and placebo as hypnotics in geriatric patients with insomnia. The safety and efficacy of 0.25 mg triazolam were compared to those of 15 mg flurazepam and placebo in 41 geriatric outpatients suffering from insomnia. The patients were randomly assigned to one of the three treatment groups. The medication was taken at bedtime for 28 days. Tolerance development was also studied. Triazolam was found to be significantly better than placebo in how much the medication helped the patients sleep, in sleep onset, in duration of sleep, number of nighttime awakenings, in quality (depth) of sleep, and in feeling of restfulness in the morning. Triazolam was significantly better than flurazepam in duration of sleep and was rated higher than flurazepam in all other variables. Flurazepam was significantly better than placebo in only two variables--onset of sleep and quality (depth) of sleep. Side effects were reported in each treatment group, and one patient on placebo discontinued because of side effects. There was no decrease in hypnotic effect over this four-week period, therefore, no evidence of tolerance development on either of the active compounds. Both active compounds provided the same amount of relief from insomnia after four weeks as they had after one week. Laboratory analyses and poststudy physical examinations showed no deleterious effects over the four-week period.


The use of drugs for behavior modification as it relates to the practice of optometry--Part II. Drugs used in behavior modification are considered with respect to type, specific agents, conditions for which they are used, and associated ocular and visual side effects. Relevant types include narcotic analgesics, sedatives and hypnotics, antipsychotics, antianxiety drugs, antidepressants, psychomotor stimulating agents, caffeine, the antihistamines, estrogen and progestins, vitamins, disulfiram, and illicit drugs and chemicals.


Burns of the foot.

Burns of the foot. The most severe trauma a patient can sustain is a major burn. When a person is seriously burned, initial care begins with maintaining an adequate airway and adequate blood volume and urinary output by intravenous fluids. After the patient has been stabilized, the wound is of primary importance, and postage stamp split thickness grafts are used for skin coverage. When these are secure and a maximal range of motion has been obtained, reconstructive procedures should be started.


Soft tissue trauma of the foot.

Soft tissue trauma of the foot. Before and since podiatric physicians began treating patients with foot ailments, soft tissue trauma has been a major challenge. Soft tissues, the outermost tissues, are traumatized with more ease and frequency than are skeletal tissues within. Management of soft tissue trauma must be deliberate and directed toward not only immediate, but also long-term results. Timing and expertise in management are essential for the successful treatment of soft tissue trauma of the foot.


[Pendulum testes: a degraded from of cryptorchism]. In 22 cases of sterility we have been able to single out under the name of "pendulum testes" a syndrome showing the following features: --clinically, testes that are often small and soft and normally found in the lower part of the scrotum, but with a tendency to ride up toward the inguinal canal and stay there so that an attempt to bring them down manually into the scrotum in unsuccessful; --cytologically, often accompanied by very poor sperm formation, and; --histologically, showing tubule pathology. We approach this picture as that of crytorchidism for in our opinion pendulum testis is a degraded form of latter. This leads us to discuss for both conditions problems of classification and indications for treatment.


An evaluation of elution techniques in the study of immune complex glomerulonephritis. Antigen and antibody from glomerular immune complex deposits in rabbits with experimental bovine serum albumin-(BSA) induced chronic serum sickness (CSS) were quantitated in elutes from kidneys in which a portion of the antigen and antibody had been radiolabeled. The largest quantities of 125I BSA eluted with 1 M roprionic acid at pH 2.7 (86%) and 0.1 M borate buffer at pH 11.25 (80%). However, these buffers yielded less functional anti-BSA antibody than 0.02 M citrate buffer at pH 3.2 (344 mug/g kidney). Citrate buffer-eluted anti-BSA antibody was reactive in immunodiffusion, immunofluorescence, and radiolabeled BSA binding test systems, but complement fixation was impaired relative to chaotropic ion-eluted antibody. It was found that up to 75% of the eluted antibody was lost to further study by recombination with eluted BSA. This could be prevented by fractionation of the dissociated eluate before neutralization. IgG fractionated eluates were successfully fluorescein conjugated or radiolabeled for use as reagents. Elution of cryostat sections of CSS kidney was also studied; BSA, IgG, and complement (C3) eluted in parallel, and sub-microgram quantities of anti-BSA antibody were recovered.


Studies on cellular inhibition and serum-blocking factors in 28 human patients given marrow grafts from HLA identical siblings. Fifteen patients with aplastic anemia and 13 with acute leukemia were studied 36 to 1547 days after treatment with high-dose cyclophosphamide and/or total-body irradiation and marrow transplantation from HLA identical siblings. Peripheral blood lymphocytes from patients and normals (marrow donors and healthy unrelated individuals) were tested for cell inhibition (CI) of cultured skin fibroblasts from both patients and donors by using the microcytotoxicity assay. In addition, blocking of CI by factors in patient serum was studied. Three groups of patients were studied. Patients in group I were stable long-term survivors without evidence of graft-vs-host diseases (GVHD) between 250 to 1547 days postgrafting. Patients in group II were short-term survivors with or without acute GVHD between 36 and 144 days postgrafting. Patients in group III had chronic GVHD either at the time of testing or developed chronic GVHD subsequent to CI testing between days 61 and 960 postgrafting. Eleven of 14 patients in group I showed absence of both CI and serum blocking and three showed CI and blocking. Patients in group II without acute GVHD showed absence of CI and serum blocking on three occasions, presence of CI and blocking on four occasions, and CI without blocking on three occasions. Patients in group II with acute GVHD showed absence of CI on one occasion and presence of CI and blocking on three occasions. Patients in group III showed absence of CI and blocking on seven occasions and CI without blocking on two occasions. These results suggest that the maintenance of stable graft-host tolerance in long-term survivors after marrow grafting from HLA identical donors does not depend on the presence of serum-blocking factors. Short-term survivors with and without GVHD showed a spectrum of in vitro reactivity with 50% of the patients showing serum-blocking factors, and these results did not appear to be correlated with presence or absence of acute GVHD. Finally, results of the microcytotoxicity assays failed to provide insight into the mechanism of chronic GVHD.


Characteristics of tyrosinase in B16 melanoma. Tyrosine hydroxylase, dopa oxidase, and peroxidase activities were studied in soluble fractions of B16 melanoma tumor homogenates by polyacrylamide gel disc electrophoresis. Stained gels were scanned photometrically and gel slices were assayed radiometrically. In these preparations, the two bands of tyrosine hydroxylating activity were completely separated from the peroxidase activity but coincided with two major bands of dopa oxidase activity. The third dopa oxidase band coincided with the single band of peroxidase activity. The soluble fraction of cultured cell homogenates had no peroxidase activity, but the two tyrosine hydroxylase bands coincided exactly with the two dopa oxidase bands. Therefore, in the soluble fraction of the murine melanoma bifunctional tyrosinase does exist as two electrophoretically separable forms which are independent of peroxidase.


Epidermal nucleases. II. The multiplicity of ribonucleases in guinea-pig epidermis. Ribonuclease activity has been extracted from adult guinea-pig epidermis by sequential homogenization in dilute sodium acetate and sulfuric acid. The extracts were subjected to ammonium sulfate fractionation and to affinity and ion exchange chromatography. Three ribonucleases (I, II, III) were separated from the sodium acetate extract and 6(A, B1, B2, B3, C, D) were isolated from the sulfuric acid extract. The degree of purification varies from 65-fold to 8,700-fold and the apparent molecular weights of the active forms of 8 of the 9 ribonucleases range from 10,000 to 36,500. No phosphodiesterase activity is present in any of the 9 fractions, but there is alkaline phosphatase activity in one (I) and deoxyribonuclease activity in a second (B3). Two of the ribonucleases have acid pH optima (a1, B3), while the others are most active between PHs 6.8 and 7.8. The activity of 4 of the fractions is sensitive to added EDTA (III, A, B2, B3,), but no stimulatory metal ions were found. Low concentrations of the polyamine spermidine enhanced the activity of 3-fractions (III, C, D). Yeast ribonucleic acid is degraded exonucleolytically by 2 fractions (I, A) and endonucleolytically by the remaining 7. In experiments with homopolyribonucleotide substrates, poly U was generally the preferred substrate. Substantial hydrolysis of poly A occurred with 2 fractions (A, B3) and slight hydrolysis of poly G with 2 other fractions (B2, C).


Temperature-sensitive mutants of Streptococcus pneumoniae. I. Preparation and characterization in vitro of temperature-sensitive mutants of type I S. pneumoniae. After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide.


Purification and immunochemical characterization of the outer membrane complex of Bacteroides melaninogenicus subspecies asaccharolyticus. Morphologic study of Bacteroides melaninogenicus subspecies asaccharolyticus by electron microscopy disclosed the presence of a capsule and a cell wall structure otherwise typical of a gram-negative organism. An outer membrane complex was isolated with use of gentle methods. Relative purity of the preparation was confirmed by electron microscopy and by the formation of a single band in a sucrose density gradient. Gel chromatography was used for separation of the major components of the membrane. Antigenicity of the first component, a protein-polysaccharide complex, which cross-reacted with antiserum to another strain of the same subspecies. This component probably represents the capsular antigen and may prove to be the basis for serogrouping. The second membrane fraction differed chemically from the first fraction and represents the lipopolysaccharide component of the outer membrane. Notably, this component lacks 2-keto-3-deoxyoctonate, one of the backbone sugars of aerobic, gram-negative lipopolysaccharides.


A simple method for the separate measurement of transcobalamins I, II, and III: normal ranges in serum and plasma in men and women. A simple method for the separate measurement of the unsaturated binding capacity of the three main circulating vitamin B12 binders, transcobalamins (TCs) I, II, and III,  is described. The method involves batch separation of TC I and III from TC II by means of Quso G32, followed by batch separation of TC I from TC II with the use of diethylaminoethyl. The present study provides the first complete comparison of unsaturated TC I, II, and III in serum versus fluoridinated plasma of a single group of normal men versus women. There are consistently higher values in serum, largely due to an in vitro increment of TC III, prevented by NaF. The results are compared with values for some of these parameters obtained by others with the use of different methods, providing a standard for evaluating significance of results by various methods.


Mechanism by which neutral phosphate infusion elevates urine PCO2. Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics.


Kinetics of the cyanate-hemoglobin reaction in whole blood. The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia.


Use of a competitive protein-binding assay for adenosine 3':5'-phosphate for the study of bovine corpus luteum adenylate cyclase. The use of a competitive protein-binding assay for cyclic AMP, utilizing the binding protein purified from bovine adrenal cortex, for the study of adenylate cyclase activity of the washed 600 g sediment of bovine corpus luteum is validated. A specific assay for cyclic AMP could only be achieved by removal of the degradation products of ATP on a precipitate of nascent BaSO4. Simple dilution of the sample before assay was not sufficient to eliminate interference from degradation products of ATP. An observed variability in optimal ATP substrate and tissue concentrations is though to reflect variability in the enzymic profile of the cyclic corpus luteum. Optima with respect to F-, Mg2+ and pH are more clearly defined and are similar to those reported for adenylate cyclase systems for other tissues.


Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder. Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV.


The Ly phenotype of suppressor T cells arising in mice subjected to a graft-versus-host reaction. T cells with helper and suppressor functions arising during graft-versus-host reaction (B6 vs. BDF1) have been characterized with respect to their Ly surface antigens. Helper cells were found to express the phenotype Ly 1+2- and suppressor cells the phenotype Ly 1+2+. Ly 1-2+ T cells had no suppressive effect in this system. T cells of the host did not contribute to either activity.


The pH-dependent rate of action of local anesthetics on the node of Ranvier. Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility.


Lack of a regulatory function for glutamine synthetase protein in the synthesis of glutamate dehydrogenase and nitrite reductase in Escherichia coli K12. Synthesis of glutamine synthetase (GS) in anaerobic batch cultures of Escherichia coli was repressed when excess NH4+ was available, but derepressed during growth with a poor nitrogen source. In wild-type bacteria there was only a weak inverse correlation between the activities of GS and glutamate dehydrogenase (GDH) during growth in various media. No positive correlations were found between the activities of GS and nitrite reductase, or between GS and cytochrome c552: both of these proteins were synthesized normally by mutants that contained no active GS. Although activities of GS and GDH were low in two mutants that are unable to synthesize cytochrome c552 or reduce nitrite because of defects in the nirA gene, the nirA defect was separated from the GS and GDH defects by transduction with bacteriophage P1. Attempts to show that catabolite repression of proline oxidase synthesis could be relieved during NH4+ starvation also failed. It is, therefore, unlikely that nitrite reduction or proline oxidation by E. coli are under positive control by GS protein. The regulation of the synthesis of enzymes for the utilization of secondary nitrogen sources in E. coli, therefore, different from that in Klebsiella aerogenes, but is similar to that in Salmonella typhimurium.


Evaluation of the role of methional, 2-keto-4-methylthiobutyric acid and peroxidase in ethylene formation by Escherichia coli. During growth of Escherichia coli strain SPA O in the presence of methionine, an intermediate accumulates in the medium. This intermediate reacts with 2,4-dinitrophenylhydrazine, and can be degraded to ethylene either enzymically or photochemically, the latter being stimulated by the addition of a flavin. The pH optimum for the photochemical degradation of this intermediate and 2-keto-4-methylthiobutyric acid (KMBA) is pH 3 whereas the optimum for methional is pH 6. The enzyme which converts the intermediate to ethylene also converts KMBA to ethylene and has many of the properties of a peroxidase including inhibition by catalase, cyanide, azide and anaerobiosis. The enzyme which synthesizes the intermediate is not known but requires oxygen and pyridoxal phosphate. A pathway for ethylene biosynthesis is proposed in which methionine is converted to KMBA which can be degraded either by peroxidase or in a flavin-mediated photochemical reaction. Its relevance to the properties of other ethylene-producing bacteria and to the proposed pathway of ethylene release by higher plants is discussed.


Effect of chaotropic salts and protein denaturants on the thermal stability of mouse fibroblast interferon. Altering the aqueous environment, especially with agents that affect hydrogen bonds, markedly affects the stability of mouse L cell interferon. Low pH stabilizes interferon whereas high pH labilizes it; heavy water further enhances interferon thermostability at pH 2 but not at pH 9. Exposure to the protein denaturants, 4 M-guanidine hydrochloride and 6 M-urea, significantly decreases the activity of interferon at pH 2 and pH9; however, the residual interferon activity is relatively thermostable. Certain chaotropic salts protect interferon against thermal destruction, and in terms of effectiveness, their sequence is in the order SCN- greater than 1- larger than or equal to Cl- = CiO4- - Br- greater than NO3-. Interferon becomes more stable to heat as the NaSCN concentration is increased from 0-25 M to 2-0 M. Molecular sieve chromatography of interferon in the presence of 1-5 M-NaSCN at pH 7 shows a shift in its apparent mol. wt. from 25000 to 42000. Unlike most proteins, the unfolded conformation of interferon appears to be more stable to heat than the molecule with a smaller Stokes' radius.


Changes in primary process expression in hospitalized schizophrenics treated with phenothiazines: two projective tasks compared. It was hypothesized that primary process expression on Gottschalk's Five Minute Verbalization Task (FMV) would be more representative of clinical status in schizophrenia than primary process expression on the Rorschach. Ss were 21 males and 15 females, ages 19-41 years, newly admitted to the hospital and treated with phenothiazines. The FMV was administered at predrug, five weeks, and 13 weeks, and the Rorschach at predrug and five weeks. Primary process scoring was according to the Holt system. Clinical improvement was measured by the Lorr IMPS and the Burdock Ward Behavior Scale. Over time, Ss produced less primary process on the FMV (p less than .001), while on the Rorschach scores did not change significantly. The scores on the FMV but not on the Rorschach paralleled some measures of clinical improvement (p less than .05). In a factor analysis, scores on the FMV and Rorschach were related to specific but different symptoms. It was concluded that the FMV was more effective in determining clinical improvement, while the Rorschach was perhaps more valuable in assessing the nature of the primary process thinking.


Effect of curare on responses to different putative neurotransmitters in Aplysia neurons. We have studied the effects of curare on responses resulting from iontophoretic application of several putative neurotransmitters onto Aplysia neurons. These neurons have specific receptors for acetylcholine (ACh), dopamine, octopamine, phenylethanolamine, histamine, gamma-aminobutyric acid (GABA), aspartic acid, and glutamic acid. Each of these substances may on different specific neurons elicit at least three types of response, caused by a fast depolarizing Na+, a fast hyperpolarizing Cl-, or a slow hyperpolarizing K+ conductance increase. All responses resulting from either Na+ or Cl- conductance increases, irrespective of which putative transmitter activated the response, were sensitive to curare. Most were totally blocked by less than or equal to 10-4 M curare. GABA responses were less sensitive and were often only depressed by 10-3 M curare. K+ conductance responses, irrespective of the transmitter, were not curare sensitive. These results are consistent with a model of receptor organization in which one neurotransmitter receptor may be associated with any of at least three ionophores, mediating conductance increase responses to Na+, Cl-, and K+, respectively. In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses.


Role of the posterior hypothalamus in the development of acute brain swelling. Destructive stereotaxic lesions were made in the posterior hypothalamus, unilaterally or bilaterally, in 26 dogs. In 21 dogs the intracranial pressure (ICP) was maintained in normal range, and in five dogs the ICP was artificially elevated to 300 to 400 mm h2o, preceding the procedures to the hypothlamus. Arterial oxygen and carbon dioxide pressure ((PaO2 and PaCO2) were maintained in the normal range. Before and after each procedure, systemic arterial pressure (SAP) was elevated by intravenous injection of norepinephrine (5 X 10(-3) mg/kg) to determined whether the ICP increases coincidentally with elevation of the systemic arterial pressure. The intracranial pressure/mean arterial pressure ratio of elevation by injection of norepinephrine was not significant regardless of the level of the ICP, or of uni-or bilateral lesions of the hypothalamus. The authors conclude that dysfunction of posterior hypothalamus does not play a specific role in the development of vasomotor paralysis leading to acute brain swelling, under conditons of normal or moderately raised ICP with normal PaCO2 and Pato2 levels.


Studies on the labeling of streptokinase with 99mTc for use as a radiopharmaceutical in the detection of deep-vein thrombosis: concise communication. Streptokinase was labeled with 99mTc using both stannous chloride and stannous pyrophosphate as reducing agents. Sixty to seventy-five percent of the 99m Tc was incorporated into streptokinase using stannous chloride as a reducing agent at pH 1-2, wheras 50-60% was incorporated using stannous pyrophosphate at neutral pH. Increasing the pH from 2 to 7 in the presence of stannous chloride caused the release of 15-20% of the protein-bound 99mTc. Incorporation of 99mTc into protein was relatively slow: labeling required 2-3 hr at room temperature. The concentration of stannous pyrophosphate required for optimum labeling varied between 10(-5) and 10(-2) M. Polyacrylamide-gel electrophoresis showed that the filler substance in commercial streptokinase was also labeled with 99mTc. However pure streptokinase gave a homogenous protein band after polyacrylamide-gel electrophoresis. This protein band coincided with the peak of streptokinase-bound 99mTc. The results obtained may partially explain why 99mTc-labeled streptokinase lacks the necessary specificity for the satisfactory location of blood clots in vivo.


Integration of clinical and academic nursing at the hospital clinical unit level. In a successful attempt to solve problems in Pediatric Nursing at the Medical University of South Carolina, a Department Chairman was named Director-Chairman of Pediatric Nursing and given operational authority over both clinical and academic nursing in Pediatrics. The results were more efficient administration, a higher quality of patient care and an enriched environment for student learning.


Effect of dietary DL-ethionine and/or DL-methionine on egg laying and activities of some cytoplasmic NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica. The effect of dietary DL-ethionine and/or DL-methionine on egg laying, and activities of some NAD linked-dehydrogenases and NADPH-producing enzymes in liver of Japanese quail, Coturnix coturnix japonica was investigated. A 0.30% DL-ethionine plus 0.30% DL-methionine supplemented diet reversed partially the egg laying inhibited by the diet with 0.30% DL-ethionine alone. No inhibitory effect on egg laying was observed for the diet supplemented with 0.30% DL-methionine alone. In marked contrast to the decreased activity of L-glycerol 3-phosphate dehydrogenase and malate dehydrogenase, significantly increased activity of lactate dehydrogenase was obtained for quail fed the DL-ethionine, and the DL-ethionine plus the DL-methionine supplemented diet, respectively. No marked changes in activities of these three dehydrogenases were obtained for quail fed the diet supplemented with DL-methionine alone. Although decreased activity was observed for all of the four NADPH-producing enzymes in quail fed the diet supplemented with DL-ethionine alone, the DL-ethionine plus DL-methionine, the smallest decrease was obtained for NADP-isocitrate dehydrogenase. The diet supplemented with DL-methionine alone induced markedly the respective activity of malic enzyme and  glucose 6-phosphate dehydrogenase. These results indicate a relatively important  function of NADP-isocitrate dehydrogenase for NADPH-production even under DL-ethionine toxicity and suggest complicated relationships between egg production and activities of enzymes associated with carbohydrate and lipid metabolism in quail liver.


Stimulation of neutral amino acid transport by fructose in epithelial cells isolated from rat intestine. Interest in the nutritional and physiological implications of the high dietary intakes of fructose from sucrose and isomerized corn sweeteners has directed attention to the specific metabolic properties of this monosaccharide. Epithelial cells isolated from the small  intestine of Wistar rats fed a stock diet showed 24% to 57% higher transport of 1 mM leucine, isoleucine, valine, alanine, phenylalanine tryptophan and histidine in the presence of 10 mM fructose than in its absence. In contrast, 10mM glucose generally inhibited the transport of these amino acids and 10mM sorbose had no effect on leucine transport. Fructose failed to consistently stimulate the transport of basic amino acids and generally inhibited the transport of glucose and galactose, indicating that the stimulation was relatively specific for neutral amino acids. Cells preloaded with fructose optimally stimulated leucine transport in the absence of extracellular fructose. Ouabain and dinitrophenol inhibited the stimulation of leucine transport by intracellular fructose after 2 minutes. A stimulation mediated by an exchange transport mechanism was rejected on  the basis of the failure of 1 mM neutral amino acids either  to inhibit the transport of 10 mM fructose or to accelerate the movement of fructose out of fructose-loaded cells. Although the mechanism remains unknown, these results demonstrate a specific effect of fructose at the intestinal level that produces a stimulation of neutral amino acid transport.


Influence of dietary lipid on lipogenic enzyme activities in coho salmon, Oncorhynchus kisutch (Walbaum). Coho salmon (Oncorhynchus kisutch), 8 to 18 months of age, were maintained in culture tanks and were fed three semipurified diets. The diets contained 40% of energy from protein and 11.5%, 23%, or 46% of energy from lipid. The body weight gain and food conversion factors were similar among groups of fish fed the diets in each of the three experiments. Wet weight of mesenteric adipose tissue increased with increased amount of lipid in the diet; however, epaxial muscle lipid content was not influenced by the lipid content of the diet. Several hepatic and adipose tissue lipogenic enzymes (fatty acid synthetase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-isocitrate dehydrogenase) were assayed. These lipogenic enzymes exhibited high activities in liver and relatively low concentration in adipose tissue of the fish. The activities of all the hepatic lipogenic enzymes assayed, except for NADP-isocitrate dehydrogenase, were depressed as the level of lipid in the diet was increased; however, the activities of these enzymes in mesenteric adipose tissue were not influenced by the diets fed. The results of this study indicate that dietary lipid depresses hepatic lipogenic enzyme activities and that the liver may be a more important site for fatty acid synthesis than is adipose tissue in coho salmon.


The immediate nucleotide precursor, guanosine triphosphate, in the riboflavin biosynthetic pathway. In the present paper, the nucleotide precursor of riboflavin was investigated by experiments with labeled purines using non-growing cells of Eremothecium ashybii. The added purines, at 10(-4) M, were effectively incorporated into riboflavin at an early stage of riboflavin biosynthesis under the experimental conditions. In particular, both labeled xanthine and labeled guanine were specifically transported to guanosine nucleotides, GMP, GDP, GDP-Mannose and GTP, in the course of the riboflavin biosynthesis. A comparison of specific activities of labeled guanosine nucleotides and labeled riboflavin indicated that the nucleotide precursor of riboflavin is guanosine triphosphate. From the results obtained, a biosynthetic pathway of riboflavin is proposed under "DISCUSSION."


Reconstitution of T-cell function in severe combined immunodeficiency disease following transplantation of early embryonic liver cells. In a 51/2-month-old male infant with adenosine deaminase-positive severe combined immunodeficiency disease, who had no suitable bone marrow donor, immunologic reconstitution was attempted with lymphoid cells obtained from the liver of a 4- to 5-week-old-male human embryo. A mild graft-versus-host reaction began three weeks later. T-cells, which were absent prior to infusion of hepatic lymphoid cells, rose to a maximum of 554/mm3 at 16 weeks post transplantation. A normal lymphocyte response to pokeweek mitogen was not present until 25 to 30 weeks and to allogeneic cells until 39 weeks. Postive in vitro lymphocyte responses to Candida albicans were found repeatedly after 52 weeks. Twenty months following transplantation the patient is free of clinical infection, although he requires regular injections of gamma globulin.


Peritoneal dialysis for severe methyprylon intoxication. The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication.


Development of Haemonchus contortus in vitro and the stimulus from the host. Infective larvae of Haemonchus contortus which have been exposed for about 9 hr to relatively high partial pressures of carbon dioxide at near-neutral pH, as they might be in the rumen, develop slowly to the fourth stage or not at all. But following this treatment, exposure to lower partial pressures of carbon dioxide and higher concentrations of hydrogen ions, such as might be encountered in the abomasal mucosa, brings about development at a rate comparable with that in the sheep.


In vitro adsortpion of acetaminophen onto activated charcoal. In vitro experiments supported in vivo evidence that activated charcoal is effective in adsorbing acetaminophen. In the physiologic pH range, adsorption was rapid and pH independent. Adsorption, however, was dependent upon the quantity of activated charcoal employed, becoming more complete as the quantity of activated charcoal was increased.


Conformational studies of antiradiation agents by NMR: cysteamine and its derivatives. The conformations of cysteamine, thiazolidine, and thiazolidine-4-carboxylic acid were determined in aqueous solutions using NMR spectroscopy. At physiological pH, the population ratio of gauche- and trans-conformers was 3:1. The gauche-rotamer is probably responsible for the antiradiation activity and acts through metal chelation involving sulfur and nitrogen atoms. The puckering of the thiazolidine ring was calculated using NMR coupling constants. The observed results were compared with those obtained in the solid state using X-ray diffraction.


Solubility studies of silver sulfadiazine. The solubility of silver sulfadiazine as a function of pH was determined in nitric acid-potassium nitrate buffer for pH 2-3 and in 2-(N-morpholino)ethanesulfonic acid buffer for pH 6-7. As the salt of a weak organic acid, silver sulfadiazine exhibits the anticipated increase in solubility with an increasing hydrogen-ion concentration. Measurement of the silver-ion concentration was carried out using a silver-ion selective electrode. The methods of known subtraction and known addition were utilized to measure the total concentration of the silver ion in solution. Evidence was obtained to indicate that the salt is completely ionized in aqueous solution.


Metal-ion interaction with penicillins: kinetics of complexation of nickel(II). The kinetics of complexation of nickel(II) with some penicillins and related compounds show that the zwitterionic form of the ligand has very low reactivity compared to the anionic form. The resolved rate constants are interpreted in terms of binding to the ring nitrogen and carboxyl group and not to the side chain.


Kinetics and mechanisms of hydrolysis of 1,4-benzodiazepines II: oxazepam and diazepam. The hydrolysis kinetics of oxazepam and diazepam leading to a benzophenone product and a glycine derivative were quantified from pH 1 to 11. For oxazepam, two intermediates were isolated and identified, indicating a parallel consecutive reaction mechanism. The hydrolysis occurred uncatalyzed and demonstrated acid-base catalysis for both reaction steps. One intermediate was observed by TLC for diazepam hydrolysis. This intermediate, resulting from breakage of the azomethine linkage, was different than the major intermediate isolated for oxazepam hydrolytic degradation (amide hydrolysis preferred). Stability parameters involving rate constant-temperature dependence are reported.


Mechanism of histamine binding II: effect of alkali metal and alkaline earth cations on histamine binding to peptide H. The association constants of histamine with Mg2+, Ca2+, Sr2+, and Ba2+ were determined in buffer solutions at constant pH using an ion selective electrode. These cations enabled histamine to bind to peptide H. A minimum cation binding concentration was required for histamine binding. A linear relationship existed between the minimum cation binding concentration and the log of the equilibrium constant for the histamine-cation complexes, indicating that the specificity of the alkaline earth cations in promoting histamine binding was due to the difference in their ability to complex with histamine. The monovalent cations, Nat, Kt, and Cst inhibited histamine binding to peptide H, with the extent of inhibition dependent on cation concentration. An ion-exchange mechanism or a conformation change in the peptide may account for the inhibition.


Motor innervation of the smooth muscle of the rat seminal vesicle. Frequency-related isovolumetric contractions of the rat seminal vesicle elicited with transmural electrical stimulation were blocked by tetrodotoxin but unaffected by hexamethonium. The postganglionic motor innervation of the rat seminal vesicle is purely excitatory and contains both an adrenergic and a cholinergic component which are excited simultaneously during transmural stimulation. Contractions elicited by adrenergic nerve stimulation were mediated by norepinephrine acting via alpha adrenoceptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous norepinephrine were antagonized by phentolamine and potentiated by cocaine, 2) pretreatment of animals with reserpine or 6-hydroxydopamine produced a marked depletion of tissue norepinephrine concentration and reduced the responses to transmural stimulation to a level which resembled that of untreated organs in the presence of phentolamine, 3) the residual responses of vesicles from pretreated rats were not modified by phentolamine or cocaine, and 4) responses to tyramine in untreated organs were antagonized by phentolamine but not by cocaine and were observed in organs from reserpine-pretreated rats only after repletion with exogenous norepinephrine. Responses elicited by cholinergic nerve stimulation were mediated by acetylcholine through muscarinic receptors, i.e., 1) responses of untreated vesicles to transmural stimulation and to exogenous acetylcholine were antagonized by atropine, 2) the residual responses to transmural stimulation of vesicles from animals pretreated with reserpine of 6-hydroxydopamine were nearly abolished by atropine and 3) physostigmine potentiated and prolonged the responses of organs from untreated and reserpine-pretreatd animals to transmural stimulation; these effects of physostigmine were abolished by atropine.


Organ culture of rat superior cervical ganglia. The maintenance of adrenergic function has been investigated in organ cultures of adult rat superior cervical ganglia. Tyrosine hydroxylase and monoamine oxidase activities decreased gradually through 72 hours of culture. Dopamine beta-hydroxylase activity gradually increased in the cultured ganglia to 150% of that seen in fresh ganglia after 14 hours in culture. The level of norepinephrine increased in the cultured ganglia to a maximum of 225% of that seen in control ganglia. The increases in both dopamine beta-hydroxylase activity and in norepinephrine levels required protein synthesis but they were not dependent on the presence of nerve growth factor. The accumulation of norepinephrine in the cultured ganglia could not be explained by an increased rate of amine synthesis. Turnover measurements suggest that the accumulation can be explained by a decreased rate of amine metabolism in the cultured ganglia. A comparison of the distribution of amine storage vesicles showed that the number of heavy vesicles was greater in cultured than in fresh ganglia. The results suggest that sympathetic ganglia develop an increased capacity for amine storage in culture and that this leads to an increase in intracellular levels of norepinephrine.


Effects of ethosuximide on transmission of repetitive impulses and apparent rates of transmitter turnover in the spinal monosynaptic pathway. The effects of ethosuximide on spinal monosynaptic transmission were studied in cats. The drug in doses of 200 or 400 mg/kg deepened the decline of monosynaptic response amplitude evoked by trains of 10 stimuli to a motor nerve at 2, 5 or 10 Hz, without affecting the transmission of single isolated impulses. The patterns of decline were analyzed under the assumption that they reflect a partial depletion of the apparent transmitter stores in the presynaptic terminals, each incoming volley releasing a constant fraction of the store while a constant fraction of the instant size of the depleted part is being replenished per second. Ethosuximide increased the fractional release without a consistent effect on the fractional rate of replenishment. It is suggested that the resulting more rapid and more profound depletion of the apparent transmitter store could account for the observed preferential depression of repetitive transmission in the spinal monosynaptic pathway by this drug.


The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord. Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo.


Serotonin and dopamine as neurotransmitters in mytilus: block of serotonin receptors by an organic mercurial. The effects of mersalyl, bromo-LSD (BOL) and methysergide (UML) on the relaxation of catch by certain indole and catechol derivatives were studied in the anterior byssus retractor muscle of Mytilus. Mersalyl antagonized relaxation in response to serotonin whereas BOL and UML were less effective. Two other indole derivatives, ergotamine and gramine, were also blocked by mersalyl; BOL and UML antagonized relaxation in response to dopamine more effectively than did mersalyl. Two other catechols, epinephrine and norepinephrine, were also blocked more effectively by BOL and UML than by mersaly. Relaxation in response to neural stimulation was blocked more effectively by mersalyl than by BOL. The blocking action of mersalyl on neural relaxation reversed very poorly after washing the drug, but complete reversal was induced by brief exposure to dithiothreitol. It is concluded that the evidence supports an hypothesis that the transmitter released by relaxing nerves is serotonin. It is suggested that mersalyl blocks serotonin by combining with a sulfhydryl group at or near the site on the receptor to which the indole nitrogen attaches.


Specific enhancement of norepinephrine-induced contraction in rat veins after beta adrenergic antagonists. Propranolol markedly increased the norepinephrine-induced maximal force in circular smooth muscle of the rat portal, mesenteric, renal and, to a lesser extent, femoral veins without affecting aortic or mesenteric artery responses to norepinephrine. Furthermore, two other beta receptor antagonists, practolol and N-isopropylmethoxamine, specifically enhanced maximal venous responses to norepinephrine. Contractions to norepinephrine, but not to serotonin, were increased by propranolol only in veins, even after the vasodilator, papaverine. The ability of propranolol to enhance norepinephrine-induced contraction in these rat veins paralleled the effectiveness of isoproterenol to relax such tissues. In addition, beta receptor antagonists enhanced the response of veins to the field stimulated release of norepinephrine from sympathetic nerves. These data support the conclusion that beta adrenergic stimulation modulates norepinephrine-induced constriction in certain rat veins but not in the aorta or mesenteric artery.


Urinary carbon dioxide tension in lithium carbonate-treated patients. Renal acidification was studied in 12 lithium carbonate-treated psychiatric patients. The urinary Pco2 response to oral sodium bicarbonate loading, a qualitative index of distal hydrogen ion secretion, was evaluated in all patients and the results were compared with those obtained in 10 control subjects. The average maximal urine to arterial blood Pco2 difference (U-A Pco2) in the psychiatric patients [26 +/- 3 (S.E.) mm Hg] was significantly lower (P less than .001) than that of control subjects (51 +/- 3 mm Hg) and only three patients had values greater than 31 mm Hg (2 S.D. below the mean control value). Eight of these patients were also evaluated with NH4CL acid loading. Seven of eight patients had a minimal urine pH less than 5.30 after NH4CL administration; only one of the seven had a normal U-APco2 after bicarbonate loading. Three patients were evaluated prior to treatment and after 2 weeks of lithium administration. Pretreatment U-APco2 values were normal. After therapy the values were lower in all three patients becoming definitely abnormal in two. The present investigation, in concert with previous animal studies, demonstrates that chronic lithium carbonate therapy in man may result in decreased U-A Pco2.


The development of some metabolic responses to hypoxia in the foetal sheep. 1. Foetal and maternal plasma metabolite and catecholamine concentrations have been measured in chronically catheterized sheep, 95-145 days pregnant. 2. With increasing gestational age there was rise in foetal plasma lactate, free fatty acid and ketone body concentration and in maternal plasma in free fatty acid and ketone body concentration. With the exception of alpha-amino nitrogen none of the plasma metabolites showed any correlation with foetal blood gas or pH values; alpha-amino N was inversely related to foetal blood pH. 3. Hypoxia in the foetuses was induced by causing the ewe to breathe 9% O2 with 3% CO2 in N2. This had a small effect on plasma metabolites in the ewe, mainly producing an increase in free fatty acid and ketone body concentration. 4. In the foetus hypoxia was associated with a large rise in plasma lactate and a small rise in alpha-amino N, the magnitudes of which did not change over the gestational range studied. Consistent and large increases in foetal plasma glucose, free fatty acid and ketone body concentration in response to hypoxia were seen only between 130 and 145 days. 5. In foetuses of 130-145 days the magnitude of the hypoxia-induced rise in plasma glucose and free fatty acid concentration was proportional to the plasma catecholamine concentration. 6. The concentration of acetate in foetal plasma was lower than and proportional to that in the maternal plasma. Neither concentration changed significantly during hypoxia. 7. The results are discussed in relation to the ability of the foetal sheep independently to control the concentration of its plasma metabolites and to mobilize its carbon stores at times of need. They indicate that in the sheep plasma catecholamines are important regulators of plasma glucose and free fatty acid concentrations late in foetal life.


Possible explanations for the differences in secretory characteristics between conjugated and free bile acids. 1. The hepatic extraction fraction and maximum excretory rate of conjugated cholate are greater than those of free cholate (studied after acute taurine depletion); the possibility that this difference might be due to greater bile-to-blood back-diffusion of un-ionized cholic acid (pKa 5-5) compared to that of taurocholic acid (pKa 2) has been investigated by varying the pH of bile by secretin or acetazolamide administration in the anaesthetized dog. 2. The mean biliary pH during free cholate excretion in the control state in twenty-three experiments was 7-5 (at which approximately 1% of cholate is un-ionized). Three to fourfold changes in the hydrogen ion activity of bile (which resulted in changes of the same magnitude in the percentage of un-ionized cholic acid) had no significant effect on the total (mainly free) cholate maximum excretory rate. It is concluded that back-diffusion of un-ionized cholic acid in the bile ducts is not an important determinant of the secretory performance of free cholate. 3. The bile flow rate associated with mainly free cholate excretion is much higher than that associated with taurocholate excretion at the same rate; the extra bile flow appears to arise largely by means that are independent of the osmotic effect of cholate excretion, as the osmotic coefficient (osmolality/total solute concentration) of bile containing mainly free free cholate (calculated directly) was only slightly greater than that of bile containing mainly taurocholate (obtained by extrapolation) at the same total cholate concentration. 4. The peak hepatic excretory rate of taurocholate following the instillation of the entire contents of the gall-bladder of a fasted dog into the distal ileum was only about one fifth of the maximum rate attainable; at the peak rate taurocholate is almost completely removed in the first passage of blood through the liver.


The effect of calcium injection on the intracellular sodium and pH of snail neurones. 1. Ion-sensitive glass micro-electrodes were used to measure the intracellular pH (pHi) and the intracellular sodium ion concentration, [Na+]i, in identified Helix aspersa neurones. 2. The injection of small volumes of 0-1 McaCl2, which increased the membrane potential by 10-15 mV for 1-2 min, had little or no effect on [Na+]i. Increases of up to 1 mM in [Na+]i could be reversibly induced by larger injections. 3. Calcium injection caused an immediate decrease in pHi, which appeared to be directly proportional to the amount of calcium injected. Injections causing hyperpolarizations of 10-20 mV which recovered in 2-5 min caused pHi decreases of 0-04-0-15 units. After each of these injections both pHi and the membrane potential recovered exponentially but with different time constants. 4. The injection of calcium at a low rate could decrease pHi without affecting the membrane potential. 5. Neither membrane potential nor pHi were affected by the injection of small volumes of 0-1 M-MgCl2, Injection of CoCl2 produced a large transient decrease in pHi but no significant change in membrane potential. 6. Exposure of the cell to saline equilibrated with 2-5% CO2 greatly reduced the pHi decrease caused by calcium injection but had only small effects on the membrane potential response. 7. It is concluded that most of the injected calcium is exchanged for protons inside the cell.


Facilitation of transmitter secretion from toad motor nerve terminals during brief trains of action potentials. 1. End-plate potentials produced by brief trains of action potentials (5-7 at 50-100 Hz) were recorded at toad sciatic-sartorius neuromuscular junctions. When transmitter secretion was depressed in solutions containing magnesium, the increase in amplitude (growth pattern) of successive end-plate-potentials was greater than could be accounted for by arithmetic summation of facilitation (arithmetic model) as proposed by Mallart & Martin (1967). 3. With e.p.p.s of normal quantral content or in solutions in which the calcium concentration was lowered, growth patterns were occasionally reasonably close to those predicted by the arithmetic model but there was always some degree of disparity. 4. A simple, two-step, kinetic model is described which is more consistent with the varied growth patterns of end-plate potentials that have been recorded. The model can predict growth patterns of e.p.p.s with high or low quantal content.


Extracellular potassium and trasmitter release at the giant synapse of squid. 1. The effects of changes in extracellular K concentration, [K]0, on synaptic transmission were studied at the squid giant synapse with intracellular recording from the presynaptic terminal and post-synaptic axon. 2. The amplitudes of both the presynaptic spike and the e.p.s.p. varied inversely with [K]0. On the average, a 10 mV change in spike height was accompanied by a 3-1 mV change in e.p.s.p. amplitude. 3. The amplitude of the presynaptic spike after-hyperpolarization (AH) varied inversely with [K]0. On the average, increasing [K]0 resulted in a 20% change in e.p.s.p. amplitude per mV change in presynaptic spike AH. 4. Repetitive antidromic stimulation of the post-synaptic giant axon resulted in an exponential decline in the post-synaptic spike AH, a depolarization of the presynaptic membrane potential and a reduction in the AHs of presynaptic spikes. This suggests that the K which accumulates in the extracellular spaces around the post-synaptic axon also affects the presynaptic terminal. 5. Repetitive antidromic stimulation of the post-synaptic axon resulted in a reduction in the amplitude of e.p.s.p.s. elicted by stimulation of the presynaptic axon. The reduction in e.p.s.p. amplitude relative to the change in presynaptic spike AH was quantitatively close to the change produced by increasing [K]0, suggesting that the reduction in e.p.s.p. amplitude is due to the accumulation of extracellular K at the presynaptic terminal. 6. Repetitive stimulation of the presynaptic axon reduced the amplitudes of the e.p.s.p. and the presynaptic spike AH. On the average, a 1 mV change in presynaptic spike AH was accompanied by a 204% change in e.p.s.p. amplitude, suggesting that K accumulation may only contribute to a small extent, under these conditions, to the depression of transmitter release.


[Arteriographic appearances seen in the course of development of the lesions of polyarteritis nodosa (author's transl)]. Three cases of polyarteritis nodosa (P.A.N.) studied by abdominal arteriography with a follow-up examination between the 6th and 9th month are reported. In the first case, the initial arteriogram showed only the appearances of endarteritis. The second arteriogram, 9 months later, following a worsening of general condition, revealed diffuse aneurysms in the abdomen. In the second patient, who had multiple aneurysms at the time of the initial examination, arteriography agter 6 months following a new episode of the disease with an acute abdominal syndrome and collapse revealed, alongside the multiplication of the aneurysms with rupture of one of them, the disappearance of some ectasias with the obliteration of certain arteries. In the third patient, the follow-up arteriogram after treatment showed disappearance of the renal arteriograms which the first study had revealed 7 months before. These three cases give an idea of the different radiological appearances of P.A.N. The appearance of endarteritis with no specific characteristics indicates and inflammatory localisation of the disease. This is an initial stage leading to ectasia. Aneurysms may progress to rupture or may multiply. Endarteritis and ectasia may also progress towards scarring and disappear. A method of early diagnosis, arteriography makes it possible to institute treatment before the lesions reach a stage at which they must inevitably develop either into aneurysms or lead to obstruction with distal ischaemia.


The role of the urologist in barren marriages. This paper is addressed to the gynecologist, who is generally the first to be consulted by the patient because of her failure to conceive. Early in the study there arises the problem of assigning individual factors. Is the patient involved solely, or is there also a male factor? Excluding the female's role to bear and nurture the fertilized cell until maturity, the frequency of subfertility in the male is just as great as it is in the female. Evaluation of the male should be done early in the study of the childless couple because it is less complex and less time consuming. Assignment of the relative fertility of husband and wife depends on the correlation of the findings in each. For that reason, also, treatment of the subfertile husband should not be undertaken until it is definitely determined that his wife is either reproductively normal or has remediable abnormalities. On the other hand, improvement of the fertility of one partner may be sufficient to induce pregnancy. Frequent communication between gynecologist and urologist is of utmost importance. An attempt is made to clarify for the gynecologist the abnormalities that may be encountered, the treatment to be employed and the prognosis. The mere fact that hormone administration is generally not effective in the male should not lead to the conclusion that treatment of the male is useless and that nothing can be done to improve his semen quality.


Synthesis and biological activity of some vinyl-substituted 2-nitroimidazoles. In previous studies 1-methyl-2-nitro-1H-imidazole-5-carboxaldehyde and 1-methyl-2-nitro-5-vinyl-1H-imidazole were found to posses interesting antimicrobial activities. We have now prepared some 2-nitro-1H-imidazoles in which the 5-vinyl chain bears selected functional groups (CHO, COCH3, NO2) as well as nitrogen-condensation derivatives of the carbonyl functions. Furthermore, 5-methyl-2-nitro-1-vinyl-1H-imidazole has been synthesized. All the compounds, and some intermediates, have been assayed for antimicrobial activity. Several of them exhibited significant antibacterial and antitrichomonal activity in mice.


N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor. The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine.


5-allyl-9-oxobenzomorphans. 3. Potent narcotic antagonists and analgesics-antagonists in the series of substituted 2',9beta-dihydroxy-6,7-benzomorphans. 5-Allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan methiodide (1) has been converted in a selective two-step process to the corresponding 9beta-hydroxy intermediates 4 and 6, which in turn were transformed via modified von Braun demethylation-acylation to the amides 11 and 21, respectively. These were reduced and demethylated to give a series of 5-allyl-2',9beta-dihydroxy-2-substituted 6,7-benzomorphans 13 and 23, some of which have been found to be highly potent narcotic antagonists and/or analgesics. The resolution of the most interesting compounds (23a and 23b) and pharmacological properties of the optical isomers are also described. Reduction of the double bond in 13 and 23 to give 14 and 24, with one exception, did not appreciably alter pharmacological profiles, while cyclization to the tetrahydrofuranobenzomorphans 25 substantially reduced the level of activities.


Synthesis and narcotic agonist-antagonist evaluation of some 2,6-methano-3-benzazocine-11 propanols. Analogues of the ring C bridged oripavine-7-mehtanols. A general synthesis of variously substituted 2,6-methano-3-benzazocine-11-propanols is described. Nine N-CH3 derivatives and their corresponding N-cyclopropylmethyl counterparts were prepared and studied in the mouse acetylcholine induced writhing and rat phenazocine antagonism tests. The results are compared with literature information on the bridged oripavine methanols. It is concluded that the synthetic analogues have a different structure-activity profile, in general being weak agonists but potent antagonists.


Adrenergic agents. 4. Substituted phenoxypropanolamine derivatives as potential beta-adrenergic agonists. A series of 1-(substituted phenoxy)-3-(tert-butylamino)-2-propanols in which the ring substituents were 3,4-dihydroxy (6f), 3- and 4-hydroxy (6g and 6h, respectively), 3-hydroxy-4-methylsulfonamido (6i), its 3,4-transposed isomer (6j), and 4-methylsulfonylmethyl (6k) was prepared and examined for beta-adrenergic agonist and/or antagonist properties. Two of these compounds, 6f and 6j, were potent beta-adrenoreceptor agonists in in vitro tests that measure a compound's ability to relax guinea pig tracheal smooth muscle and to increase the rate of contraction of guinea pig right atria. Several compounds had a dose-dependent effect. Although they produced potent beta-adrenergic agonist activity at low concentrations, 6g, 6h, and 6j antagonized the effects of a standard beta-adrenoreceptor agonist at higher concentrations. The methylsulfonylmethyl derivative 6k produced beta-adrenergic blocking effects as demonstrated by attenuation of isoproterenol-induced increases in the rate of contraction of an isolated rabbit heart preparation. On the basis of these pharmacological results, coupled with NMR spectral data, it appears that the previous suggestion that aryloxypropanolamines interact with beta-adrenocreceptors as a consequence of their ability to assume an orientation in which the benzene ring the ethanolamine moieties can be superimposed on those of corresponding adrenergic phenylethanolamines is invalid. An alternative "bicyclic" rigid conformation involving two intramolecular hydrogen bonds in the protonated form of the aryloxypropanolamines is suggested to account for the similar beta-adrenoreceptor activity of these compounds and related phenylethanolamines.


Plasmalemma transport of OH- in Chara corallina: dynamics of activation and deactivation. The light-mediated, time-dependent rise in the pH value at the center of an alkaline band was analyzed using the methods of numerical analysis. From this analysis an expression of the time-dependent build-up of OH- efflux was obtained for these bands. This information can now be employed to determine whether the light-activated transport of OH- and HCO3- influences the electrical properties of the plasmalemma. The dark-induced deactivation of OH- transport was also characterized, revealing a transition from efflux to a transient influx phase during deactivation. Numerical analysis of the steady-state OH- diffusion pattern, established along the surface of an alkaline band, revealed that the OH- efflux width was wider than previously envisaged. It was also found the OH- sink regions exist on either side of the efflux zone. These, and other characteristics revealed by the numerical analysis, enabled us to extend the OH- transport model proposed by Lucas (J. Exp. Bot. 1975, 26:347).


Growth of a heterologous tumor cell line in neonatal rats with graft-versus-host disease. The ability of a hamster tumor cell line (T20) to grow and exhibit type H virus particles was significantly enhanced in neonatal DA rats with graft-versus-host disease (GVHD). Tumor growth peaked on days 4 and 7 in control littermates receiving adult syngeneic cells or no cells at birth, respectively, and then subsequently disappeared. However, tumor nodules in animals with GVHD became significantly larger than those in controls by day 7 and continued to grow until death. In addition, a marked plasma cell infiltration was noticed in such rapidly growing tumors from animals with GVHD only. In the light of previous studies, evidence is discussed for an environment within animals with GVHD conducive for tumor cell growth because of a depletion of T-cell areas within their tissues.


Carcinoma in situ of the ectopic testis. A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis.


Childhood gonadoblastoma and seminoma in a dysgenetic cryptorchid gonad. A case of gonadoblastoma and seminoma occurring in a genotypic male child with ambiguous genitalia is presented. A review of the literature establishes that children with intersex disorders who possess a Y chromosome and undescended gonads stand a particularly high risk of having this type of gonadal neoplasm and should be explored.


Acute bacteremia in asplenic renal transplant patients. Four cases of overwhelming bacteremia were observed in asplenic renal transplant patients 12 to 20 months after transplantation. The bacteriologic findings and presentation of these infections are characteristic of post-splenectomy sepsis reported in nontransplant patients. It is suggested that the absence of the spleen, more than immunosuppression with azathioprine and prednisone, predisposes to these late, uncommon infections after transplantation.


Prune-belly syndrome in a 54-year-old man. A 54-year-old man was diagnosed as having prune-belly syndrome, a deficiency of abdominal musculature, cryptorchidism, abnormalities of the urinary tract, and chronic renal failure. The patient was asymptomatic until the diagnosis was made at the age of 54 years; he is one of the oldest living patients to be reported in detail. Recognition of the syndrome in adults with chronic renal failure is important.


Antibiotic susceptibility of Streptococcus pneumoniae isolated from clinical materials (author's transl). We tested the drug-susceptibility of 112 strains of Streptococcus pneumoniae isolated from various clinical materials since January 1975 to May 1976, and observed the changes of susceptibility of this pathogen. All strains tested remained very sensitive to benzylpenicillin and cephaloridine, but 59.8% of strains were resistant to tetracycline and 44.7% to chloramphenicol, and about 90% of chloramphenicol-resistant strains were also resistant to tetracycline. The percentage of resistant strains to tetracycline or chloramphenicol is increasing. Cross-resistance between tetracycline and doxycycline or chloramphenicol and thiamphenicol was observed. On this time we found three strains resistant to macrolides. Two of these strains were resistant to erythromycin, josamycin, oleandomycin, spiarmycin, mydecamycin, lincomycin, clindamycin and tetracycline, but one was resistant to josamycin, spiramycin, mydecamycin and chloramphenicol.


T cell function detected in murine bone marrow cells. Mouse bone marrow cells were fractionated by BSA discontinuous density gradient centrifugation, and a small lymphocyte rich fraction was obtained at the high density. Cells of this fraction were shown to respond in vitro to T cell mitogens and alloantigens. Furthermore, they were able to mount a graft-versus-host reaction when assessed by spleen weight assay and by the method of inhibiting erythroid cell growth by allogeneic lymphoid cells. The results indicate that these lymphocytes possess T cell functions. On the other hand they were found to carry only little theta antigen assessed by the cytotoxic test and by the absorption test. It is presumed, therefore, that the amount of theta antigen on a cell might not correlate with T cell functions, and these lymphocytes might be mature ones in the course of postthymic maturation. Hemopoietic stem cells were determined by spleen colony formation and the peak of colony-forming efficiency was seen at the low density. These observations imply that immunocompetent cells causing GVHR can be separated from hemopoietic stem cells. This procedure may be applied for prevention and reduction of GVHR in allogeneic bone marrow transplantation in human.


Physicochemical properties of a liquid ion exchanger microelectrode and its application to biological fluids. Double-barreled potassium or chloride ion-selective microelectrodes were constructed using a liquid ion exchanger. Technical details of the fabrication of double-barreled microelectrodes, having a PD sensor as one barrel and an ionic sensor as the other, are described. The sensitivity of K+ or CI- ion-selective microelectrodes exhibited an approximately Nernstian response over a temperature range of 7 degrees-37 degrees C, and the electromotive force (EMF) was stable within +/- mV for a few hours. The rise time was less than 1 sec. The effect of pH on the electrode response was negligible over a physiological range of pH 5.6 to 7.8. The selectivity constants of the K+ microelectrode to other cations were 0.011 for Na+, 0.200 for NH+4, and less than 0.002 and 0.001 for Ca++ and Mg++, respectively, while that of the CI- microelectrode was 0.067 for HCO-3. Glucose or urea has no effect on the EMF. Protein has a significant effect on ion exchanger membrane only when the concentration of the tested ion is low and protein is high. On the basis of this background the determination of K+ and CI- activity was carried out both in vivo and in vitro on several biological samples, such as serum, tissue and cellular fluids, and other protein-containing fluids. The values obtained with the microelectrode were consistent with those obtained with the other conventional methods or with the current theory on electrolyte solutions. These results were taken to assure the practical application of these electrodes to biological studies in many fields.


Effects of intracellular pH on plateau formation following the action potential of squid giant axons. When squid giant axons were intracellularly perfused for about 10 min with 100 mM K+ solutions containing Pronase or Protease Type VII at a concentration of 0.1-0.5 mg/ml, the action potential developed a long-lasting plateau. The plateau persisted after switching to an enzyme-free solution at standard pH (7.3 +/- 0.1) as the intracellular perfusate. The plateau was promptly and completely suppressed when the intracellular pH was lowered below 6.5. Upon increase of pH again to the standard level, the plateau promptly reappeared. With alkaline intracellular pH plateau formation was enhanced. Lowering the pH of the extracellular medium to 5 did not influence the plateau. The duration of the action potential under bi-ionic conditions (inside Cs+, outside Ca++) decreased with low intracellular pH and increased with high intracellular pH. The plateau duration of the action potential from axons intracellularly perfused with solutions containing 10 mM tetraethylammonium also decreased with low intracellular pH and increased with high intracellular pH. The underlying mechanisms for the pH effects remain to be explored.


Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. To study whether sodium bicarbonate given in cardiopulmonary resuscitation may produce life-threatening hyperosmolality or hypernatremia, arterial blood was analysed for blood gas, alcohol, blood urea nitrogen, electrolyte and osmolality. The blood was drawn after resuscitation in successful cases, and while effective massage and ventilation were being applied in unsuccessful resuscitations. Seven of the 17 resuscitations were successful. Serum sodium concentrations ranged from 135 to 154 with one exception and did not correlate with the amount of sodium bicarbonate administered. Arterial pH ranged from 6.38 to 7.71; only one patient had metabolic alkalosis. Serum osmolality ranged from 301 to 407. The data suggests a net increase in osmolality of 6 mOsm/50 mEq of sodium bicarbonate.


Cryptorchidism and abdominal pain.

Cryptorchidism and abdominal pain. In this case report, abdominal symptoms simulating acute appendicitis were due to recurrent torsion of an intra-abdominal testicle. Cryptorchidism frequently goes unnoted. Most undescended testicles are in the groin and easily palpable. If not, they can be absent, retroperitoneal or intra-abdominal. An intra-abdominal testicle is more likely to occur on the right than the left.


Acid-base relationships in the different body compartments: the basis for a simplified diagnostic approach. Special characteristics of cellular buffering must be taken into account in order to describe accurately acid-base relationships in the whole body. In particular, tissues other than blood are able to neutralize mineral acid independent of changes in Pco(2) and hence independent of large changes in extra- and intracellular pH. Although mechanistic details remain to be clarified, relationships that describe this tissue buffering in quantitative terms are well established. In this report, emphasis is placed on quantitative relationships that stress the need for diagnostic interpretation derived from acid-base changes within the whole body rather than simply within the blood compartment. Theoreticalproblems with respect ot buffering mechanisms in various body compartments are reviewed and analyzed.


[Use of coronaroactive agents with beta-stimulating effect in ischemic heart disease]. In feline experiments and 65 clinical cases of ischaemic heart disease the efficacy of a new beta-stimulating agetn -- Ildamen -- was studied, the obtained effect was compared to that of Euphillin. Ildamen was found to be highly effective in patients with a moderately decreased coronary reserve and without atherosclerotic lesions in the coronary vessels.


Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities. The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence of imposed bicarbonate ion gradients, comparable to those occurring in vivo. With mucosal (M) pH lowered to the point of zero net hydrogen ion secretion, the transepithelial flow of bicarbonate ions (JHCO3) from serosa (S) to M was 0.91 +/- .06 y mole/hr in response to a 20 mM HCO3- gradient. After AMB addition to M, back diffusion of hydrogen ions from M to S (-JH) increased from zero to 0.36+/-0.05 micronmole/hr, whereas bicarbonate ion transport from S to M (JHCO3) failed to increase (0.91+/-0.06 before and 0.82+/-0.09 micronmole/hr after AMB). In contrast to M addition, S addition of AMB had no effect on either -JH or JHCO3. The defect in urinary acidification induced by AMB is characterized by a large increase in the permeability for hydrogen ions rather than that for bicarbonate ions and depends on direct exposure of the luminal cell membrane to AMB. The permeability increase is cation selective, not only for hydrogen ions but also, as shown previously, for potassium ions, and to a lesser extent, for sodium ions. The results are consistent with the formation by AMB of aqueous half pores in the luminal membrane. Although the passive permeabilities for bicarbonate and chloride ions are not affected primarily, they may increase after prolonged exposure, probably as a results of paracellular leaks that are not specific for AMB.


[The role of proximal osteomy of the tibia in the treatment of arthrosis of the knee joint]. The results of heigh tibia osteotomy performed between 1970 and 1975 in 20 cases in the material of the Orthopaedic Department of the "Semmelweis" University Medical School, Budapest, are reported. In 13 cases good--in 6 cases satisfactory results have been obtained. In 1 case the surgical intervention was of no effect. With regard to the explicit pain-relieving effect the operation is recommended by the authors in the treatment of knee arthrosis.


[Restoration problems in frontoglabellar skull defects]. Replacement problems of frontoglabellar skull defects and their recent operative methods come under review. A new method for the prevention of infection of paranasal sinus origin is reported in the article. Possibilities for producing good contour frontal area prothesis are considered here. The new method developed by the authors for orbital roof replacement is justified not only by cosmetics but physiology as well.


[Post-traumatic protrusion of the hip joint]. 23 patients with post-traumatic protrusion of the hip joint--due to fracture of the base of the acetabulum--have been re-examined by the authors. On the basis of the radiomorphological alterations developed in consequence of the fracture and according to the severity of the articular deformation the cases have been classified into four categories. The relationship between the morphological alteration, the functional ability of the joint and the subsequent arthrosis--as well as the problems of the social rehabilitation are discussed.


[Malignant degeneration of chronic suppurative bone diseases]. Out of 1189 patients with osteomyelitis of the Hungarian Institute of Medical Rehabilitation malignant degeneration in the region of purulent bone process has been observed in 6 cases by the authors. Out of them 5 cases were carcinoma planocellulare and 1 case was sarcoma gigantocellulare. During the detailed analyses of the cases it is pointed out by the authors that on the basis of the standpoint established regarding the rehabilitation in locomotor diseases the indication of the amputation in patients with osteomyelitis is not absolutely limited to the cases undoubtedly malignized. Rehabilitation and resocialization of the patients is better promoted with the performed amputation and the up-to-date manufactured prosthesis than by a series of unsuccessful and hazardous therapeutical experiments.


[Ultrastructural changes in the skeletal muscles following nerve and tendon injuries in man. II. Nerve injuries]. The alterations occuring in the fine structure of the man's hand muscles after traumatic nerve injuries have been examined by the authors. In the muscle portions taken in the 6th--16th weeks after the injury considerable atrophy of the contractile components, the desorganisation of the myofilaments, and the atropy of the mitochondrium and the sarcoplasmatic reticulum have been observed. The motor end-organs are athropic or their place is indicated but by a single great vacuolum. In the motor nerve fibres the typical picture of Waller's degeneration was seen.


[Structure and configuration of human tendons. II. Development of tendon structure during ontogenesis]. In infants born in the 24th--30th weeks of the gravidity the praenatal development and the process of the organization of the tendinous structure have been examined by the authors. By means of photo- and polarization microscopic examinations it was found that the tendon of the flexor hand muscles (M. flexor carpi radialis, M. flexor digitorum comm.) shows mature tendinous structure earlier, than the tendons of the flexor muscles of the lower extremity (M. semitendinosus femoris, M. triceps surae). The tendons of the extensor muscles of the lower extremity (M. quadriceps femoris, M. tibialis ant.) are underdeveloped and inordinate in the foetal life--their structure develops only during the postnatal life.


[Synovial chondrochromatosis of the metacarpophalangeal joint]. A rare case of synovial chondromatosis sited on the IVth metacarpophalangeal articulation of the left hand of a women is reported. The pathogenesis, the histology and the method of treatment are discussed. 2 years after the operation the patient is symptom-free and without complaints.


[Oto-palato-digital (Taybi) syndrome].

[Oto-palato-digital (Taybi) syndrome]. A case of dysmorphogenetic syndrome, described by Taybi, is reported. The syndrome is characterized by hardness of hearing of conduction type, submucous cleft palate and anomalies involving the bony frame, especially the digits.


[Luxation fracture of the hip joint. I. Posterior fractures with dislocation]. 41 cases of posterior sprain fracture are analysed by the authors. 4--10 years after the injury 31 patients appeared at the check-inspection. On the basis of the late results it is stated by the authors that the immediate diagnosis and the reposition of the luxation are of the greatest importance. Conservative treatment yields generally satisfactory results. In the authors' opinion, osteosynthesis is indicated but in fractures concomitant with the fracture and dislocation of great piece of the acetabulum and in juvenile patients.


[Local soft tissue ossification of traumatic origin]. Under the effect of trauma, in 4 patients the development of metaplastic bone-tissue in the soft-parts of mesenchymal origin has been observed by the author. In 3 patients the development of supernumerary articulations proved the appearance of cartilaginous tissue; in consequence, the presence of cartilaginous tissue may play an important role in the metaplastic soft-parts ossification.


A systems analysis of the impact of physician extenders on medical cost and manpower requirements. This paper presents a descriptive narrative of a mathematical manpower model and the results of an analysis of the effect physician extenders have on medical costs and manpower requirements. The model is extensively developed, through the use of a new medical classification system in the area of delegation of specific task areas and patient visits to physician extenders. Additionally the models incorporate a complete cost structure for a group practice. Field trials in seven HMOs indicate that the models accurately represent the actual system and can be used effectively as planning aids. Results are presented that analyze the use of physician extenders from the following viewpoints: minimum cost solution for adult medicine, pediatrics and obstetrics/gynecology (OB/GYN); maximum physician extender use; effect of physician extender salary on minimum cost utilization; level of independence exercised; size of clinic and regional manpower planning; and a case study of HMO planning. The type of results presented include cost analysis, manpower analysis, and the types of patient visits best delegated to physician extenders (PE).


Physician receptivity to nurse practitioners: a study of the correlates of the delegation of clinical responsibility. A survey to measure physician receptivity to nurse practitioners was conducted in North Carolina in 1973. All North Carolina physicians were asked to rate a list of 35 clinical tasks of varying levels of difficulty and responsibility according to their willingness to delegate these tasks to nurse practitioners. Using eight items from this list that were good discriminants of physician attitudes towards delegating responsibility, task delegation scores were correlated with physician characteristics and their responses to questions about recruitment, training, reimbursement, and willingness to hire nurse practitioners. Thirty-four per cent of the respondents would hire a nurse practitioner, whereas 52% approved of the concept but would not hire one. Physicians who had previously worked with a nurse practitioner were more willing to hire one and had a higher task delegation score. Sixty-eight per cent of respondents would share their load with nurse practitioners in their offices, while 6% would have them work in satellite clinics away from the physicians' offices. Most physicians wanted their own nurse trained as a nurse practitioner in a program that combined a didactic course at a medical center with on-the-job training. The authors conclude that there is a potential demand for nurse practitioners in North Carolina and that the training program must prepare the nurse practitioners for the tasks physicians are willing to delegate to them.