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Presents a study which assessed the efficacy of hemodialysis in removing flucytosine and amphotericin B from the blood and correlated the hemodialyzability of the drugs with protein-binding characteristics. Effectiveness of flucytosine and amphothericin B in the treatment of systemic mycoses in man; Information on the patients and methods used in the study; Results and discussion.

The susceptibilities of herpes viruses to three nucleoside analogues were studied with a standardized cell-culture assay. Cytosine arabinoside (ara-C) was the most active drug; MICs were: 0.25–0.75 µg/ml for herpes simplex type 1,0.37–2.0 µg/ml for herpes simplex type 2, and 0.37–4.0 µg/ml for varicella-zoster. Adenine arabinoside (ara-A) was 20-fold less active against herpes simplex and varicella-zoster. Ara-A demonstrated an additive effect with ara-C and with 5-iodo-2′-deoxyuridine (IUDR) against herpes simplex type 1; ara-C and IUDR were antagonistic. The MIC of ara-C for 80% plaque-reduction of cytomegalovirus was 2.0–4.0 µg/ml; none of the drugs inhibited cytomegalovirus by 100%. The MICs of all three nucleoside analogues against herpes simplex virus were considerably higher when assayed at pH 8.0 rather than at pH 7.0. Herpes simplex type 2 was significantly more resistant to IUDR than herpes simplex type 1 only when tested in a strongly buffered alkaline medium. The usefulness of these in vitro antiviral assays, however, has to be demonstrated by further laboratory and clinical studies. [ABSTRACT FROM PUBLISHER]

Hydrocortisone produced choleresis in anesthetized dogs receiving taurocholate and ampicillin. There was an increase in mean concentration of ampicillin in serum after infusion of hydrocortisone with no change in mean rate of biliary excretion of ampicillin. In dogs receiving creatinine in addition to taurocholate and ampicillin, hydrocortisone also produced an increase in mean levels of ampicillin in serum. The mean rate of biliary excretion and the rate of renal clearance of ampicillin were constant in these dogs. In dogs receiving creatinine, taurocholate, and ampicillin without infusion of hydrocortisone, mean concentration of ampicillin in serum, minute biliary weight, and renal clearance rate of ampicillin remained constant throughout the 150 min of study, while mean biliary concentration of ampicillin and rate of excretion decreased during the last 40 min. The increased concentrations of ampicillin in serum of dogs during and after infusion. of hydrocortisone seems due to decreased diffusion of ampicillin from plasma into the hepatocyte. Preliminary chromatographic studies of rat liver supernate on Sephadex G-75 indicate that bioactivity of ampicillin appears at a position in the elution pattern where Y protein should be eluted. Y protein binds anoinic metabolites of cortisol. Competitive or noncompetitive inhibition by hydrocortisone of binding of ampicillin to Y protein could explain the increased concentrations in serum during and after infusion of hydrocortisone. [ABSTRACT FROM PUBLISHER]

, , 38-50. Coronary perfusion and hypothermia both have disadvantages, and excellent clinical results are obtained without them, though short operations, spontaneous cooling of unperfused hearts, hyperglycaemia, heparinization, and young and cyanotic subjects may allow more tolerance of ischaemia. Functional, macroscopic, histological, ultrastructural, chemical, and metabolic evidence of the inadvisability of ischaemia, especially of hypertrophied hearts, abounds, though statistical support and histochemical proof are lacking. Isovolumic function tests permit accurate assessment of compliance. Succinic dehydrogenase distribution is the most relevant enzyme assay of myocardial transport; freed phospholipids indicate cellular membrane disorganization. Adenosinetriphosphate response of myosin (myocardial ATP ase) is shown quantitatively by change of birefringence. Ventricular oedema may be detected by changes in weight. These tests were used to compare continuous normothermic, intermittent hypothermic, and intermittent normothermic perfusion over two hours in isolated, cross-perfused canine hearts. Isolated hearts are very sensitive to imperfections of maintenance, but cross-perfusion minimizes perfusion-induced deterioration. Normothermic continuously perfused hearts performed significantly better than intermittently perfused hearts, among which cooled hearts functioned better than normothermic hearts after two hours. Succinic dehydrogenase and acid haematein tests showed significant benefit from cooling during intermittent perfusion. The experimental preparation and techniques of assessment proved sensitive enough to demonstrate these differences, though cooling preserved cellular enzymes better than it did function. This work gives histochemical and statistical support to existing evidence that intermittent ischaemia for two hours can be ameliorated by moderate hypothermia but is not as effective for myocardial maintenance as constant perfusion with normal blood. [ABSTRACT FROM PUBLISHER]

We have determined unidirectional influxes by measuring rate of uptake between 0.5 and 1.0 min of incubation in 5 mm galactose.H-inulin was used to correct for galactose in residual mucosal solution. Influx was greatly depressed by removing Na from or adding 10 m phlorizin to the incubation medium. Influx was also greatly depressed by making the mucosal solution anaerobic during a 10-min preincubation period. The same severe inhibition of galactose influx by mucosal anaerobiosis also occurrend under conditions in which the epithelial cells did not gain Na. After taking into account the effect of the mucosal unstirred water layer, influxes could be normalized to a concentration of 1.0 mm at the membrane surface. It was estimated that at 1.0 mm the phlorizin-sensitive component of galactose influx was reduced 93% by 10 min of mucosal anaerobiosis. Unidirectional effluxes were estimated by subtracting steady-state downhill mucosal-to-serosal flux from influx. The ease of efflux was apparently augmented 2.8-fold by mucosal anaerobiosis. After 10 min of mucosal anaerobiosis, there was no longer any directional preference for movement of galactose across the brush border and there was no uphill transport, in spite of the persistence of a large Na gradient. These results provide strong evidence against the theory that ion gradients provide the major source of energy for directional preference and uphill transport. [ABSTRACT FROM AUTHOR]

The rate of valinomycin-induced KCl efflux from human red cells and ghosts was measured in the presence and absence of phlorizin. Extracellular phlorizin accelerated the KCl efflux. The effect depended on the phlorizin concentration and showed half saturation at about 0.4 mM phlorizin. Hunter's procedure was used to calculate Cl permeabilities ( P) by means of the Goldman equation from rate constants of K loss in valinomycin-treated ghosts. For saturating phlorizin concentrations a 20-fold increase, approximately, of P was calculated. The observed increase in P is in contrast to the almost total inhibition of Cl equilibrium exchange. Similar to the effects on anion exchange permeability the effect on P is only observed when phlorizin is present at the outer surface of the erythrocyte membrane while internal phlorizin is without effect. A similar asymmetry was observed in the stimulation of valinomycin-induced K exchange at identical K concentrations on both sides of the membrane. The effects of phlorizin were only observed if net KCl flow was out of the cells but not if it was in the opposite direction. The effect of phlorizin on net KCl movements and sugar transfer were unaltered when the phlorizin was subjected to several consecutive purifications. This indicates that the observed effects are due to the glycoside and not to contaminations with its aglycone. [ABSTRACT FROM AUTHOR]

Studies with xanthine oxidase from cow's milk, mouse liver, and human liver show allopurinol to be a competitive inhibitor of xanthine oxidation. The Ki values vary with the source of enzyme and pH and are 15 to 200 times lower than the Km for xanthine under the same conditions. The kinetics of the inhibition by allo-xanthine are quite different, since the inhibition becomes progressively stronger with time in the presence of substrate. Allopurinol is converted in vivo in all animals to allo-xanthine. In lower animals, allopurinol and allo-xanthine are cleared rapidly; in man, allopurinol is cleared rapidly but allo-xanthine appears to be reabsorbed by the kidney tubule and is excreted slowly. The slow clearance of allo-xanthine suggests that part of the therapeutic activity of allopurinol is due to the maintenance of adequate levels of its metabolite. This must be considered when uricosuric agents are used in combination with allopurinol since such agents increase the excretion of allo-xanthine. The metabolic experiments with radioactive allopurinol in man were done in collaboration with Drs. R. W. Rundles and E. Metz of Duke University School of Medicine. We are indebted to T. J. Taylor, A. Kovensky, F. Benezra, and I. Canellas for their technical assistance. The helpful advice and encouragement of Dr. George H. Hitchings are gratefully acknowledged. [ABSTRACT FROM AUTHOR]

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Deals with a study which described marrow culture studies of patients with idiopathic ineffective erythropoiesis. Case reports and selection of patients; Results and discussion.

Presents a study that observed five patients dying with amyloidosis to examine the possibilities of the cause of the disease. Manifestations of cardiac amyloidosis; Speculation on the cause of functional disturbances in cardiac rhythm and conduction; Result of infiltration of ganglia within the heart.

Provides information on a study which determined the effect of chronic renal failure and factors associated with this condition on blood ammonia levels. Cause of the formation of ammonia in the gut; Result of the rate of generation of ammonia; Status of the ammonia content of the blood according to a study.

Deals with the association of arterial thrombi to blood platelets. Role of platelets in explaining the mechanisms involved in arterial thrombogenesis; Activity of adenosine diphosphate; Factors that cause platelet aggregation and degranulation.

Provides information on a study which examined the serologic and cellular functional alterations in the immune response of patients with sarcoidosis. Serum complement activity; Reactivity of cultured lymphocytes; Pathogenesis of sarcoidosis.

Presents a study which examined kidney biopsies on patients with varied renal diseases by the immunofluorescent technique for the presence of gamma globulin, complement and its components. Materials and methods used in the study; Specificity of staining; Differential diagnosis between pure nephrosis and the nephrotic stage of chronic glomerulonephritis.

Presents a study which described the response of patients to treatment with cephalothin, a derivative of cephalosporanic acid. Advantages of cephalothin; Materials and methods used in the study; Effectiveness of cephalothin for bacterial infections.

Describes the case of a patient with histologically proven thyroiditis. Patient's history and physical characteristics; Degree of hypothyroidism; Detection of antithyroid antibodies in the sera of the patient.

Studies tubular alterations produced by osmotic diuresis with mannitol, a polyhydric alcohol of the sugar mannose. Complex structure and function of the tubules; Rate of tubular transport maximum for para-amino-hippuric acid.

Describes patients having reversible retinal detachment associated with renal insufficiency. Case histories; Relation between renal disease and lens anomalies; Formation of the retina or disunion between the posterior portion of vitreous body and the retina.

Disruption of mast cells was measured by incubating the peritoneal washings of a rat with the substances under test. The incubate was filtered and the histamine in the undisrupted mast cells on the filter was assayed using guinea-pig ileum. Measurements were also made on disruption of rat peritoneal mast cells . Disodium cromoglycate (DCG) reduces the disruption of peritoneal mast cells produced by Compound 48/80, human plasma, dextran, and trypsin inhibitors. Compound 48/80 produced its greatest mast cell disruption at a calcium concentration of 0·2-2 mM CaCl. DCG was effective in reducing the mast cell disruption at all calcium concentrations. Mast cell disruption by surface active agents was also reduced by DCG. experiments showed that DCG reduced the disruptive effect of Compound 48/80 on rat mesenteric mast cells. Calculations based on bronchial morphology show that the concentrations of DCG used in these experiments may be attained therapeutically in the bronchial mucosa of man. [ABSTRACT FROM PUBLISHER]

Serial liver function tests were performed in 29 adult patients following cardiopulmonary bypass for various open-heart procedures. In 22 patients there was a rise in serum bilirubin above 1·5 mg./100 ml., with clinical jaundice in 19 and bilirubinuria in 15 patients. The incidence of jaundice was related to age, the severity of pre-operative cardiac failure, and the duration of perfusion. Possible mechanisms for jaundice are discussed, and evidence is presented that liver damage may follow extracorporeal circulation. [ABSTRACT FROM PUBLISHER]

After cultivation in a modified Trowell-system (organ ciilture) oocytes of 12- to 40-day-old rats were studied under the light and electron microscope. The cultivation period was 72 hrs. Egg cells from primary and early secondary follicles which are characterized by the lack of a zona pellucida and by one or at most two very large Golgi's complexes located near the nucleus do not show any alterations. The other egg cells are characterized by membrane packages which can otherwise only be observed in mature egg cells right before or after the ovulation. Meiotic processes or the formation of polar bodies are only seldom to be seen. These egg cells are surrounded by a thick zona pellucida. From these findings the following conclusions can be drawn: [ABSTRACT FROM AUTHOR]

The concept that interaction between sodium-dependent transport systems represents competition for energy inherent in the transmembrane sodium gradient was examined with the use of isolated intestinal epithelial cells. The isolated cells exhibit transport interactions which are more significant in magnitude than those which have been described for intact tissue preparations. Accumulation of 1 mm valine is inhibited 60% by 10 mm 3-OMG. Conversely, uptake of 1 mm 3-OMG is inhibited only 20% by 10 mm valine. These data suggest that 3-OMG must discharge the cellular Na gradient more effectively than valine, if Na gradient dissipation can be taken as a basis for the inhibitory interaction. However, entry of 10 mm 3-OMG is significantly slower than the entry of 10 mm valine. Even if appropriate corrections are made for passive substrate entry and for differences in Na/substrate entry stoichiometry, it appears that valine should be somewhat more effective than 3-OMG in discharging the Na gradient. In light of these facts, it seems unlikely that the mechanistic basis for interaction between sugar and amino acid transport systems can be related to concomitant co-entry of Na. It is suggested that the interaction results instead from competition for energized intermediates generated at limited rates by basic energy transduction events associated with the cell membrane which serve in support of a variety of active transport systems. [ABSTRACT FROM AUTHOR]

The role played by transmembrane K gradients in providing an energy input for Na-dependent monosaccharide transport systems was evaluated with the use of isolated intestinal epithelial cells. Experimentally imposing a K gradient in a sense reversed from normal did not lead to extrusion of sugar from cells which had been pre-equilibrated withC-3-OMG, even in situations where a reversed Na gradient was also imposed. Furthermore, cells preloaded with K have no better ability to accumulate 3-OMG than do cells depleted of K, when the two populations are compared under identical incubation conditions. Fluxes of K associated with the sugar carrier could not be detected in terms of suspected sensitivity to agents which immobilize the sugar carrier. In addition, fluxes of sugar in response to imposed K gradients were not demonstrable in cells de-energized by preincubation with DNP, no matter in which direction the K gradient was imposed. Finally, the severe inhibitory effects of K on Na-dependent sugar transport by the cells disappears in de-energized cells, despite the fact that Na-dependent carrier-mediated sugar entry still occurs. All of these facts are difficult to reconcile with a significant role for cellular K gradients in supporting active sugar transport as envisioned by the ion gradient hypothesis. We have suggested instead a fundamental Na-dependent energy transductive event which depends on ATP, and which can generate a membrane-bound energized intermediate which serves to support a variety of active transport events. An analogy is drawn between this concept for animal cell plasma membranes and the better documented phosphotransferase system for sugar transport described for certain microorganisms. [ABSTRACT FROM AUTHOR]

A study of muscles of the dystrophic mouse has failed to substantiate earlier claims that these muscles were especially resistant to fatigue in vitro or that fast muscles are preferentially damaged. It has been found that the fast muscle selected for previous studies is very often unable to withstand isolation in an organ bath if it is working, and both the difficulty in removing the normal gastrocnemius muscle intact and the need to trim it surgically contribute independently toward its deterioration in vitro. The smaller dystrophic gastrocnemius muscle is less liable to excision damage, is able to satisfy its resting metabolic needs in nutrient solution, and requires no damaging dissection, but is nevertheless unable to recover normally from fatigue. Using EDL and soleus muscles which are small enough to withstand isolation in vitro, no differences are found between fatigue patterns of normal and dystrophic specimens. Responses to rest, KCl, and 2 mM caffeine are also quite similar, and the only distinguishing biomechanical characteristic we have found in dystrophic mouse muscle is a weaker contraction and a longer total twitch time. [ABSTRACT FROM AUTHOR]

The article analyzes cultures taken from 203 patients to compare the effects of topical antibiotics in vitro and in vivo. The results indicate that more than half of the cultures grew single organisms, and streptococci were present in nearly a third of the cultures. Based on the results the author suggests that in trials of topical antibiotic and antibacterial substances only purely infective or severely infected conditions be included.

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)