Histomorphology and proteolytic activity in the gastric apparatus of frugivorous, carnivorous and omnivorous species of birds. The histomorphology of the gastric apparatus, the pepsin level and the optimum pH for pepsin were investigated in Psittacula krameri (frugivore), Lanius schach (carnivore) and Acridotheres tristis (omnivore) species of birds. The proventricular glands were found to be made up of oxynticopeptic cells. The lobules of the oxynticopeptic cells are polyhedral; they are the largest in P. krameri, and the smallest in A. tristis. However, their greater number in A. tristis enables a higher secretion of hydrochloric acid and pepsin. The villi are more developed in A. tristis than in L. schach and P. krameri. The gizzard is larger in A. tristis than in P. krameri and A. tritis than in the carnivore L. schach. Koilin lining is beset with horny cones, which were well developed in A. tristis, moderately developed in P. krameri and absent in L. schach. The pepsin activity is higher in the proventriculus of the carnivorous L. schach and the omnivorous A. tristis than in the frugivorous P. krameri. Slight pepsin activity was also observed in gizzard tissue extracts in all the three species. The optimum pH for pepsin was found to be 1.5 for P. krameri and 1.8 for both L. schach and A. tristis.


Phospholipase C from Bacillus cereus. Action on some artificial lecithins. The hydrolysis by phospholipase C from B. cereus of several lecithins of different fatty acyl chain length was examined. The enzyme showed significant activity towards mono-molecularly dispersed short chain lecithins and the reaction obeyed normal Michaelis-Menten kinetics. Rate vs. substrate concentration curves obtained with dihexanoyl-, diheptanoyl- and dioctanoyllecithins showed marked discontinuities in the region of the known critical micelle concentrations for these substrates and distinctly higher rates were obtained just above these levels. Using these three lecithins at levels below their respective critical micelle concentrations, rate increases were noted if the reactions were allowed to proceed to a sufficiently great extent. The presence of deoxycholate in the reaction system had little or no effect on the rate of enzyme-catalysed hydrolysis of lecithins of fatty acyl chain length less than or equal to Cbeta, but for fatty acyl chain lengths greater than C10, significant rate increases occurred. The pH profile for the enzyme activity was also examined.


Inactivation of somatostatin by peptidases in different areas of the rat brain. With the availability of a sensitive and specific radioimmunoassay for growth hormone-release-inhibiting hormone (somatostatin or GH-RIH), it has been possible to investigate the presence of peptidase enzymes capable of inactivating this hypothalamic hormone in the hypothalamus and other brain areas of the rat. It was found that both supernatant and particulate fractions from male rat hypothalami rapidly inactivated somatostatin and that the enzymes involved have an optimum pH of 7.3. Peptidase activity was significantly higher in the supernatant than in the particulate fraction from the hypothalamus, thalamus, cortex and cerebellum. Besides confirming the presence of peptidases inactivating the release-inhibiting hormone in the hypothalamus (the site of somatostatin synthesis and release), the results may indicate that somatostatin has a functional significance outside the hypothalamus-anterior pituitary axis but within the central nervous system.


Corticotrophic and melanotrophic functions in congenital adrenal hyperplasia. In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and beta-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor). The results indicate a significant increase in plasma ACTH and beta-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and beta-MSH levels, in some only the plasma ACTH values were high and beta-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provcative tests. Lastly, it must be emphasized that no modifications of plasma beta-MSH after synthetic MIF infusion were found in subject with normal or high plasma beta-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man.


Complex of D-glyceraldehyde-3-phosphate dehydrogenase with Cu2+ ion. The properties of ternary Cu-enzyme-coenzyme complex. The formation of ternary Cu-enzyme-coenzyme complex from cupric ion and D-glyceraldehyde-3-phosphate dehydrogenase holoenzyme results in similar spectral changes as the formation of binary Cu-apoenzyme complex, which indicates that the complex bonds between cupric ion and the holoenzyme, and cupric ion and the apoenzyme are similar. Spectrophotometric titration, chemical modification experiments and inhibition studies with cupric ion gave evidence that cupric ion is selectively bound on Cys-149 residue also in the Cu-GAPD-NAD complex. The charge transfer interaction between the coenzyme and Cu-GAPD, i.e. the difference spectrum of the combination of NAD with Cu-GAPD complex, is different from that of the enzyme-coenzyme complex in the absence of cupric ion. The shape of this "modified enzyme-coenzyme charge transfer spectrum" is influenced by various anions. The difference absorption does not depend on the pH in the range of 5.5 to 9. This indicates that the bound cupric ion abolishes the effect of deprotonation of a functional group in the protein on the charge transfer interaction. It is suggested that this functional group is a histidine imidazole, which activates the Cys-149 thiol group in the native enzyme and binds the metal ion in the cupric complex in a Cys-Cu-His chelate structure.


The testing of the antibiotic sensitivity of bacteria on an agar medium: The problem of a double zone of inhibition. When the sensitivity of Micrococcus luteus ATTC9341 to streptomycin, erythromycin, oleandomycin and spiramycin was tested by an agar diffusion method using antibiotic impregnated filter paper disks on unbuffered Penassay Seed Agar two zones of inhibition were observed around the disks after an incubation period of 24 hours at 30 degrees C. The pH of the M. luteus seeded Penassay Seed Agar was measured before and after 24 hours incubation at 30 degrees C and found to be 6.6 and 8.7, respectively. When the Penassay Seed Agar was buffered to pH 6.1 and the sensitivity of the microbe to the antibiotics was tested as before no double zones of inhibition could be observed. The phenomenon of the double zones of inhibition may possibly be due to the pH increase of the medium from a relatively low level to the optimum range of activities of the antibiotics during the incubation period.


Effect of propranolol and related drugs on transmembraneous pH differences in liposomes. Propranolol (1-isopropylamino-3-(1-naphtoloxy)-propan-2-ol) a beta-adrenergic receptor blocking agent was found to cause changes of transmembraneous pH in liposomes prepared from Soy-lecithin and cardiolipin. When the external pH was neutral and the internum of the liposomes acidic, the drug decreased the pH gradient. When the externum was acidic and the internum neutral, the gradient was increased by the drug. The effect of butacaine was similar to that of propranolol, while procaine, timolol and practolol were ineffective. It is suggested that the charged form of propranolol is bound to the membrane and dislocates protons from binding sites in the membrane and that the uncharged form of propranolol penetrates the membrane. After penetration it could associate with protons in the intraliposomal compartment and hence increase the pH of the interior. Depending on the direction of the pre-existing proton gradient propranolol would thus be able to increase or decrease the pH difference across the liposomal membrane.


On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long-term administration. The liver microsomal p-hydroxylation of amphetamine to parahydroxyamphetamine (pOHA) was dependent on NADP and inhibited by carbon monoxide indicating the involvement of cytochrome P-450, SKF 525-A, fenfluramine and desmethylimipramine were the most effective inhibitors of this pathway of amphetamine metabolism. Repeated administraion of phenobarbital resulted in reduced p-hydroxylation of amphetamine in vitro. Chronic administration of amphetamine reduced the microsomal p-hydroxylation of amphetamine without apparent changes in the cytochrome P-450 levels or in the activity of NADPH-cytochrome c reductase. The aromatic hydroxylation of aniline and the demethylation of ethylmorphine was not affected by this treatment. However, the 455 nm complex formed during the microsomal metabolism of N-hydroxy-amphetamine was increased by the long-term administration of amphetamine. These results indicate some pecularities of the in vitro hydroxylation of amphetamine by rat liver microsomes. Amphetamine disappeared from the perfusate of the perfused liver at the same rate in rats given a single dose of amphetamine and in rats given amphetamine orally for four weeks. The excretion of pOHA and its conjugate increased at 60 and 90 min. and 30, 60 and 90 min. respectively in the perfusate of the same experiment as compared to the controls. The total excretion of radioactive amphetamine metabolites at the end of the perfusion was increased in the perfusate and reduced in the bile compared to the control experiment.


[Measurement of transport in mucous membrane in the human nose with Cr-51-labeled resin beads]. The mucociliary transport of the human nasal mucosa was studied by using very small resin beads tagged with 51Cr. Several modifications of previous methods were introduced, e.g. kind of nuclide, particle size, pH, mode of application, measuring technique and reduction of local irradiation. Finally arrangements implying exact measurements of transport not only horizontally but also vertically or obliquely were obtained. No mucociliary transport was demonstrated in five of nine subjects with a common cold 10 days before or one week after the investigation. Xylometazolin as a nasal spray diminished the mucociliary transport significantly. In addition, the effects on mucociliary transport caused by homolateral or contralateral experimental nasal obstruction as well as by tobacco smoking were studied in healthy subjects. Finally, patients with various diseases: pollen allergy in free intervals, chronic rhinitis, septal deviation or perforation, and condition after laryngectomy were also investigated.


Distribution of coronary blood flow in the left ventricular wall of dogs evaluated by the uptake of Xe-133. The distribution of coronary blood flow was estimated in anesthetized dogs by counting the activity in tissue blocks of the left ventricular free wall immediately after bolus injection of Xe-133 into the aortic root. No differences in the uptake of isotope were observed between the apex and the base of the heart; between areas supplied by the anterior descending and circumflex branches of the left coronary artery; or between the endo- and epicardial halves of the wall. In most experiments a bolus injection of the isotope into the left coronary artery was followed by a difference in activity between areas supplied by the left anterior descending and left circumflex branches. This indicated inadequate mixing of blood and isotope in the main stem of the artery. The uneven distribution did not result in differences between the epi- and endocardial activity concentrations. The results from one normal, anesthetized dog in which tissue activities were measured after constant rate infusion of Xe-133 into the left coronary artery for 8 min were in accordance with the general assumption of equal epi- and endocardial volumes of distribution (values of lambda).


The ability of ATP-free granule material from bovine adrenal medulla to bind inorganic cations and biogenic amines. Bovine adrenal medullary granules isolated by millipore filtration were depleted of CA and ATP by dialysis. The resulting material showed an ability to bind inorganic cations and biogenic amines in a concentration-dependent manner. The similarity of the uptake curves, the identical uptake maxima and the narrow pH range (between 4-7) over which the uptake of the inorganic and organic cations took place indicated a binding of these ions to common sites. In addition, the fact that all the uptake curves fitted the Rothmund-Kornfeld equation for cation exchangers corroborated the cation exchanger properties of the dialyzed granule material. The CA binding capacity corresponded to 20-30% of the normal CA content of bovine medullary granules.


Effect of hypercapnia and hypocapnia on tryptophan and tyrosine hydroxylation in rat brain. The effects of induced hypo- and hypercapnia upon the rate of hydroxylation of tryptophan and tyrosine in the rat brain were studied by measuring the accumulation of 5-HTP and DOPA following administration of the aromatic L-aminoacid decarboxylase inhibitor 3-hydroxybenzylhydrazine HCl (NSD 1015). The results suggest that the hydroxylation of tryptophan varies directly with the tissue Po2. On the other hand, the hydroxylation of tyrosine did not show a simple relationship to Po2 but appeared to be influenced by pH changes.


Angiography of the testicular artery. II. Cryptorchism and testicular agenesis. A selective angiography of the testicular artery was performed in 7 boys and 7 men without a palpable testicle in order to localize cryptorchid testes or to establish testicular agenesis. The examination could be carried out in all cases, and the angiographic diagnosis was confirmed at operation and at a subsequent microscopy in the 12 cases hitherto operated upon. The width of the artery and its branches are also presented.


Factors affecting urate reabsorption in the rat kidney. 1. Urate transport in the rat appears to be saturable. However, affinity of the transport system for urate is very low and transport far from saturated at physiological plasma concentrations. 2. Since increase of the nonionized fraction of uric acid by a factor of five failed to increase urate reabsorption, transport cannot be due to nonionic diffusion but rather involves ionized urate. 3. Increases in luminal flow rate markedly depress urate reabsorption in the loop of Henle, which results in wash out of medullary urate.


Uric acid transport characteristics in human erythrocytes. Taken all together the results show that the RBC transport of U.A. seems to be partly of passive nature, closely similar to others mineral or organic anions, and partly of active nature related to compound of the membrane playing a role in cellular metabolism. It remains to be precised the role of the membrane itself and to characterize the membrane site which could be responsible of a part of the transport of U.A. through erythrocyte membrane.


The pressor activity of burimamide: a relationship between chemical constitution and pressor activity of burimamide and related histamine H2-receptor antagonists. Burimamide, a histamine H2-receptor antagonist, has been shown to cause pressor responses in pithed rats. The response can be prevented by prior removal of the adrenal glands or by pretreatment with the alpha-adrenoceptor antagonist, phentolamine, 5 mg/kg, suggesting that the pressor response to burimamide is due to release of catecholamines from the adrenal glands. The pressor activity of burimamide has been compared with that of metiamide and two close chemical analogues, methylburimamide and thiaburimamide, in order to identify which chemical features of the compounds are necessary for this activity. Methylburimamide was the most potent pressor agent, followed by burimamide, metiamide and thiaburimamide. The pressor effects (and presumably catecholamine-releasing activities) appear to be related to the basicities of the compounds. We conclude that the release of catecholamines by these histamine H2-receptor antagonists is probably due to their cationic (imidazolium) forms.


A new semi-defined medium for Trypanosoma brucei sspp. A new, easy to prepare semi-defined medium for the cultivation of trypanosomes of the T. brucei complex is introduced. Containing the two commercially available media MEM (Minimum Essential Medium) and Medium 199 TC45 as well as 10% inactivated foetal calf serum (fcs), the medium supports optimum growth and direct adaptation of bloodstream forms. Growth characteristics, glucose uptake, amino acid utilization and the ultrastructure of trypanosomes grown in this medium are described briefly.


Anaemia in trypanosomiasis: mechanisms of erythrocyte destruction in mice infected with Trypanosoma congolense or T. brucei. Studies in mice infected with T. brucei or T. congolense showed that increased red cell destruction in the spleen occurred as from the third day of patent parasitaemia and this resulted in a marked reduction of the half-life of transfused syngeneic 51Cr labelled cells. There was a progressive increase in the osmotic fragility of the red cells, especially in T. congolense infected mice which also showed a more severe anaemia. The antiglobulin test was only rarely positive in the late stages of T. brucei infection. Incubation of normal red cells with plasma from infected mice in vitro did not result in haemolysis, but in the case of plasma from T. brucei infected mice, it caused an appreciable reduction in the half-life of the cells when transfused into normal mice. It is suggested that mechanisms of red cell destruction in trypanosome infections are complex and may vary with the species of trypanosomes, the host and the stage of infection.


Susceptibility of a rodent-adapted strain of Trypanosoma vivax to Berenil, Samorin and Novidium. The susceptibility of a rodent-adapted strain of Trypanosoma vivax (Leeflant strain Y58) to Berenil, Samorin and Novidium was tested in mice. When infected mice were treated on the second day of detectable parasitaemia, there was complete cure with Berenil at 10 mg/kg, Novidium at 4 mg/kg and Samorin at 0.2 mg/kg body weight respectively. Berenil and Novodium at lower doses rendered the mice aparasitaemic for a few days followed by heavy parasitaemia (relapse) and death. Lower doses of Samorin, on the other hand, were curative for none or only some of the mice but without relapses. These observations are related to the accepted modes of action of these drugs and their use in the field.


Observations on the feeding and defecation patterns of three triatomine species (Hemiptera: Reduviidae). A comparative laboratory study of feeding and defecation behavior of three species of tritomines (Rhodnius prolixus, Triatoma infestans and T. dimidiata) indicated evident differences among the species and among the different stages of same species. Time required for a full blood meal was related to the size of the specimen. Insects required an average of 11-28 min for engorgement although some finished within 10 min. T. dimidata frequently interrupted the act of feeding, a probable explanation of the higher number of defecations before finishing a blood meal observed in the species. R. prolixus was superior to the other two species in number of defecating insects and in rapidity and frequency of defecations within a given time. T. dimidiata was inferior in all three parameters and T. infestans was intermediate. Males of all species tended to be less effective. A "defecation index" is proposed for comparing this different behavior in triatomine specimens under standard conditions. Effectivity of the insects according to the measured parameters is discussed in relation to the prevalence of Chagas' disease in those areas where they are principal vectors.


Comparison of infectivity of Trypanosoma cruzi blood stream trypomastigotes and metacyclic trypomastigotes from Rhodnius prolixus. Four strains of Trypanosoma cruzi (Y, BG, M and Peru) retain their ability to infect Rhodnius prolixus and to produce virulent infections in mice for from 12 to 39 years. About 60 or more metacyclic trypomastigotes were consistently lethal to mice. The mean number of metacyclics per bug ranged from 1.2 to 17.3 x 10(3). Comparative studies of virulence of metacyclics and blood trypomastigotes showed the blood forms to be slightly more virulent. The route of injection was shown to be more significant in varying the host response to infection, subcutaneous inoculation being the preferred route.


Immunization against Trypanosoma cruzi using killed antigens and with saponin as adjuvant. The immunization of mice with killed epimastigotes or trypomastigotes with saponin SPL as adjuvant was challenged by inoculation of blood or metacyclic trypomastigotes of T. cruzi. Immunogenic preparations were obtained by freeze-thawing of formalin treatment. The protection was effective against homologous and heterologous challenge, and lasted up to 12 weeks after the last immunization. The immunization was also effective against metacyclic trypomastigote challenge. The immunogenicity of the killed T. cruzi suspension was retained after freeze-drying.


Worms: transmission from animals to man. It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog.


Sudden infant death syndrome (crib death). Sudden infant death syndrome (SIDS) is diagnosed by the absence of lethal autopsy findings, or in a resuscitatable, "near miss" form with cyanosis, apnea, and bradycardia. The event is unexpected, although a minor respiratory infection is common, and occurs during sleep, between 1 and 6 months of age. There is growing evidence that the victims have had previous hypoxic episodes. Although suffocation is no longer considered a tenable explanation, other forms of airway obstruction are still postulated by many; the evidence, however, favors hypoxia as the common feature. A lethal arrhythmia had been proposed by several groups, based on inappropriate reflex activity, "pathology" of the conduction system, and the long QT syndrome, but the evidence is against arrhythmia as the primary event in most cases of SIDS. Based on the reversible "near miss," apnea is likely as the primary event in SIDS. Several reflexes have the ability to produce apnea, in addition to the relatively common sleep apnea; the crucial aspect, rather, appears to be thefailure of the immature infant to resume respiration. The possibility exists that the infant, who did not have to breather for 9 months of fetal life, literally is not alarmed and aroused by the persistance of apnea. In human and animal studies, respiratory infections and sleep deprivation have been proved to increase the likelihood and duration of sleep apnea. If primary apnea continues for long (45 seconds or more), a dangerous positive feedback develops into hypoxic apnea. Hhis will persist until circulatory failure occurs, or until gasping occurs. The gasp is a highly effective mechanism at birth, but will occur too late for autoresuscitation after the anerobic capacity of fetal life dimineshes; we believe this capacity lasts for approximately 1 month, accounting for the hiatus of crib death, sparing the first month. The "near-miss" infant, after resuscitation, should be monitored at home, if practical, until 6 months of age. A simple cardiac monitor for bradycardia has definite advantage over an apnea monitor alone.


Coronary arterial narrowing in Takayasu's aortitis. A patient with Takayasu's aortitis and angina pectoris due to severe narrowing of the right and left coronary arterial ostia is described. Takayasu's arteritis produces a panaortitis, with thickening of the adventitia predominating, and an inflammatory cell infiltrate involving the adventitia, outer media and vasa vasorum. Narrowing of the coronary arteries in this disease is due to extension into these arteries of the processes of proliferation of the intima and contraction of the fibrotic media and adventitia that occur in the aorta. The distal coronary arteries usually do not manifest arteritis and are normal in caliber. Angina pectoris may be the first symptom of the disease if the coronary arteries are the initial site of severe arterial narrowing. The coronary arterial bypass graft operation is effective therapy for treating coronary arterial narrowing due to Takayasu's arteritis.


Derangements of myocardial metabolism preceding onset of ventricular fibrilliation after coronary occlusion. To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.


Effect of gallstone-dissolution therapy on human liver structure. To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.


Studies on the pathogenesis of diet-induced dog gallstones. Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.


Absorption of short-chain fatty acids from the human ileum. Acetate, propionate, and n-butyrate are the major short-chain fatty acid (SCFA) anions in the gastrointestinal tract of animal and man, accounting for 90% of total SCFA in stool water. Their absorption from the human ileum was investigated in 8 volunteer subjects by the triple-lumen perfusion technique. Each test solution contained one of the SCFAs at a concentration of 0-100 mM; sodium, potassium, and bicarbonate concentrations were kept constant, as were pH and osmolality. Absorption of each SCFA was found to be rate-limited with an apparent K'm between 22 and 27 mM and a calculated Vmax between 0.54 and 0.82 mmol/hr cm. Water, sodium, and chloride transport were not affected by substantial rates of SCFA absorption. Rather, significant stimulation of calculated bicarbonate secretion and a rise in intraluminal pH were consistently observed. The results are compatible with either of two mechanisms for SCFA absorption: an anion exchange between bicarbonate (or hydroxyl) and SCFA ions, or protonation of the SCFA anion at the mucosal surface followed by simple diffusion of nonionized SCFA into the absorbing cell.


Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences. Intraluminal pH in the lower esophagus has been recorded during a 3-hr period following a ligh meal and a consecutive 12-hr nocturnal period in 20 patients with typical symptoms and radiological evidence of gastroesophageal reflux and in 10 patients without such signs of reflux. Evidence of acid reflux was obtained in 3 of the patients without reflux during the postcibal period but in only one during the 12-hr nocturnal period. In contrast all except one of the 20 patients who had evidence of reflux showed spells of high acidity both in the postcibal and nocturnal periods. There was no clear correlation between the frequency of paf high acidity in the nocturnal period. Those patients with endoscopic evidence of severe esophagitis showed a significantly longer duration of high esophageal acidity in the nocturnal period. We conclude that nocturnal exposure of the esophageal mucosa to acid is a major factor in the causation of reflux esophagitis.


Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients. The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients.


Antimicrobial and other properties of a new stabilized alkaline glutaraldehyde disinfectant/sterilizer. The properties of stabilized alkaline 2% glutaraldehyde solution (SGS) are discussed. SGS is discussed with regard to its chemistry, antimicrobial properties, organic soil resistance, toxicity, corrosivity and chemical stability. SGS retains the maximum antimicrobial activity of alkaline glutaraldehyde solutions and the chemical stability heretofore observed only with acidic glutaraldehyde solutions. These improvements, along with the inherent resistance of glutaraldehyde to neutralization by organic soil, allow SGS to be continuously used for 14 days in situations of high dilution, or 28 days in situations of low dilution.


Propoxyphene: a review.

Propoxyphene: a review. A critical analysis of information on propoxyphene that has been published since the drug's introduction is presented. Propoxyphene is discussed with regard to its chemistry, metabolism and pharmacokinetics, analgesic efficacy, analgesic efficacy of combination products, nonanalgesic uses, adverse effects, overdosage, and dependence and abuse. Both the hydrochloride and napsylate salts are covered. It is doubtful that propoxyphene hydrochloride 65 mg provides an analgesic effect equal to that of aspirin 650 mg. There is no conclusive evidence that combinations of propoxyphene with other analgesics are more effective than propoxyphene or other analgesics alone.


Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay. A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa.


Bilateral atrial myxomas with multiple arterial aneurysms--a syndrome mimicking polyarteritis nodosa. This patient, previously described as having polyarteritis nodosa with multiple aneurysms shown by angiography, was recently found to have bilateral atrial myxomas. The angiographic demonstration of multiple cerebral aneurysms has been described in a few cases of left atrial myxoma. This uncommon tumor is also accompanied by "constitutional" manifestations. Thus, a syndrome mimicking polyarteritis nodosa may be produced. Cardiac myxoma should be borne in mind in conditions with multifocal organic involvement, and they should be included in the list of conditions causing multiple arterial aneurysms.


Gonadotropin receptors in human corpora lutea of the menstrual cycle and pregnancy. Binding of 125I-human choriogonadotropin (hCG) to homogenates of corpora lutea of the menstrual cycle and pregnancy was examined. While corpora lutea of the menstrual cycle bound 125I-hCG, most of the corpora lutea of pregnancy from six to 34 weeks' gestation bound little or none of the added 125 I-hCG. Further exploration into various possibilities for the above findings led to the conclusion that these corpora lutea either contain very few gonadotropin receptors or lack them altogether. The selected properties of gonadotropin receptors in corpora lutea of the cycle were studied. The apparent dissociation constant for binding was about the same (2.6 to 3.8 x 10-10M) in all but one corpus luteum. In this one sample the constant was three- to five-fold higher (1.3 x 10-9M). The binding was quite rapid and reversible, and it exhibited dependence on the amount of 125I-hCG, homogenate protein, pH of the incubation media, and duration of incubation. hCG and human lutropin (hLH') competed for 125I-hCG binding, but hCG subunits (alpha and beta), human follitropin, and ovine prolactin did not. Although hCG and hLH were parallel in inhibiting 125I-hCG binding, hLH was found to be relatively less effective. The studies with various enzymes revealed that gonadotropin receptors are protein in nature.


Effect of fenoterol (Th1165a) infusion on uterine and umbilical blood flow in pregnant sheep. The effect of fenoterol (Th1165a) upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term, nonlaboring chronic sheep preparations. During intravenous fenoterol infusions to the ewe in either incremental doses from 0.025 to 0.200 microng per kilogram per minute or constant infusions of 0.025 microng per kilogram per minute for 120 minutes. UtBF and UmBF did not change significantly. Dose-related maternal tachycardia, hyperglycemia, and relative acidemia occurred, but there were no significant changes in mean maternal and fetal arterial pressures or fetal heart rate. The simultaneous infusion of propranolol (2 microng per kilogram per minute) with fenoterol (0.200 microng per kilogram per minute) blocked the maternal tachycardia but resulted in a significant decrease in UmBF and a significant increase in UtBF. In all of the maternal infusions. UtBF significantly rose and plateaued up to 14 per cent above the control level during the 120  minute recovery period after infusion. A non-beta-adrenergic effect of fenoterol is suggested  as the cause of this UtBF increase.


The effect of umbilical vein occlusion on fetal oxygenation, cardiovascular parameters, and fetal electroencephalogram. In 11 fetal sheep experiments, the blood pressure in the fetal aorta (FA) and in the umbilical vein (UV) was measured following umbilical vein occlusion (UVO), as was the fetal heart rate (FHR), pH, Pco2, and oxygen saturation (So2) in both fetal vessels, and umbilical blood flow (Qumb) of the common UV. The fetal electroencephalogram was recorded continuously throughout the experiment. The results (No. = 17) were grouped according to the response of FA So2 into moderate (So2greater than40 per cent, mean 49.8, S.D. 6.3, and severe So2less than40 per cent, mean 20.4, S.D. 9.2). After 8 to 10 seconds, the fetal blood pressure in FA increased. Umbilical vein blood pressure increased to 25 mm. Hg (S.D. 8) and 35 mm. Hg (S.D. 9) in the moderate and severe groups, respectively. As a result of the decreased perfusion pressure (FA-UV blood pressure) across the fetal side of the placenta, the Qumb fell from 147 ml. per kilogram per minute (S.D. 57) and 30 ml. per kilogram per minute (S.D. 55) to 84 ml. per kilogram per minute (S.D. 48) and 120 ml. per kilogram per minute (S.D.22), respectively. The fall in FA So2 was related to the decrease in Qumb: FA So2=37.6 x log Qumb - 22.8 (2alphaless than 0.001). There was a mild decrease in So2 from 70 to 55 per cent when Qumb fell from 250 to 120 ml. per kilogram per minute. Below 80 to 120ml. per kilogram per minute, the fall in FA So2 was almost linear. The So2 in the UV remained constant so that arteriovenous difference for oxygen (AV Do2) increased. Oxygen consumption decreased almost linearly when Qumb fell below 80 to 120 ml. per kilogram per minute. The fetal electroencephalogram showed no significant change in voltage and the faster activities. From these observations, it is concluded that a decrease in Qumb following UVO jeopardizes the fetus only if a critical Qumb of 80 to 120 ml. per kilogram per minute and fetal artery So2 of 50 to 60 per cent is achieved.


Cardiovascular effects of fever in the ewe and fetal lamb. Ewes carrying fetuses with permanently implanted cannulas developed fevers following intravenous injections of bacterial pyrogen (1 microng). During the rising phase of the fever, maternal heart rate increased, but no consistent changes in mean arterial blood pressure (MABP), arterial pH, PO2, or PCO2 were observed during the course of the fever. Fetal temperature, which was initially 0.3 to 0.8 degrees C. higher than maternal temperature rose in parallel with the ewe's temperature. During the maternal fever, fetal MABP, pH, PO2, and PCO2 remained unchanged, but on several occasions the fetal heart rate developed irregularities that persisted after the fever had subsided. These observations suggest that maternal fever does not appear to have adverse effects on fetal oxygenation but has a variable effect on cardiovascular function.


Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli. Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle.


Vitamin A1 intestinal absorption in vivo: influence of luminal factors on transport. Intestinal absorption of [3H]retinol was studied in the unanesthetized rat. Luminal perfusate was recirculated through isolated intestinal segments with intact vascular and lymphatic circulation. Apparent saturation kinetics were found in physiological concentrations of retinol, whereas a linear relationship between the concentration and absorption rate was found at pharmacological concentrations of retinol in the perfusate. In physiological concentrations, retinol uptake in vitro by everted gut sacs was unaffected by anoxia or metabolic inhibitors and uncouplers. In vivo retinol absorption rate was decreased when sodium taurocholate concentration was raised above 5 mM, or when 2.5 mM linoleic or linolenic acids were added to the perfusate. Absorption increased markedly as the thickness of the unstirred water layer was diminished. Variations in perfusate pH from 4.5 to 8.6 did not change the retinol absorption rate. In vivo absorption of retinol in physiological concentrations is mediated by a saturable, carrier-mediated passive absorption mechanism modified by the presence of fatty acids of varying chain length.


Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog. Studies were performed to evaluate the effects of the chronic administration of furosemide on hydrogen and electrolyte excretion in dogs on a normal electrolyte diet and in the absence of electrolyte or volume depletion. Control daily excretion in five dogs averaged 64 meq for Na, 51 meq for K, 66 meq for Cl, and 17 meq for net H. Furosemide, 40 mg, in the drinking water 3 times daily was given for 4 days. On day 1 Na excretion averaged 128 meq, but thereafter was not significantly different from control levels. Over 4 days cumulative net H excretion increased 63.6 meq and plasma HCO3 rose 6.6 meq/liter. The same dogs were restudied by the same protocol except that, to obviate electrolyte depletion, NaCl and KCl were administered daily in quantities sufficient to replace urinary losses. All dogs remained in positive Na, K, and Cl balance. Body weight, hematocrit, plasma albumin, creatinine, and plasma renin activity were unchanged, indicating the absence of electrolyte or volume depletion. Nonetheless, cumulative net H excretion increased 61.2 meq and plasma HCO3 increased 4.3 meq/liter. Two adrenalectomized dogs receiving steroid replacement showed similar changes in net H excretion and plasma HCO3. These experiments suggest that chronic furosemide administration may enhance H excretion and generate alkalosis even in the absence of volume or electrolyte depletion and without increased aldosterone secretion.


Effect of parathyroid hormone on urinary acidification. The effect of parathyroid hormone (PTH) administration on urinary acidification was studied in intact and thyroparathyroidectomized dogs. PTH administration resulted in a significant increase in urine pH and HCO3 excretion. In dogs with maximally acid urine caused by Na2SO4 infusion PTH administration also led to a significant increase in urine pH and to a decrease in ammonium excretion. To examine the effect of PTH on H+ secretion in the distal nephron we measured the urine-blood (U-B) PCO2 gradient in dogs with maximally alkaline urine (urine pH greater than 7.8) before and after PTH administration. After infusion of the hormone, HCO3 excretion increased significantly but the U-B PCO2 gradient remained unchanged. The effects of PTH infusion on urinary acidification in animals with distal renal tubular acidosis caused by LiCl administration were also studied. PTH administration to these dogs increased HCO3 excretion to the same level seen in normal dogs. These data suggest that PTH does not inhibit distal H+ secretion but increases HCO3 excretion by depressing proximal HCO3 reabsorption.


Distribution of adenine nucleotides in the perfused rat heart. A computer technique for determination of the distribution of adenine nucleotides among compartmented, protonated, and metal-chelated species has been developed for the perfused rat heart. This procedure requires knowledge of tissue levels of creatine, creatine phosphate, ATP, ADP, and AMP and the glycolytic and respiration rates. The method is applicable to any physiological state of the organ and has been applied to transient behavior in aerobic, anoxic, and ischemic hearts. The results suggest that ADP uptake and ATP export by mitochondria are normally linked and equal in rate during aerobic metabolism or short-term anoxia but become separate and unequal during ischemia, so that mitochondrial adenine nucleotides, primarily AMP, accumulate.


Computer simulation of energy metabolism in anoxic perfused rat heart. We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed.


Computer simulation of rat heart metabolism after adding glucose to the perfusate. An experiment where perfused rat hearts receiving no substrate are suddenly given glucose with insulin in the perfusate is simulated with a computer model of cardiac energy metabolism. Mitochondrial metabolism is quantitatively reorganized under cytoplasmic control, with fatty acid oxidation undergoing a two-step decrease. There is an unspanning of the Krebs cycle (different reactions going at different rates) due primarily to slowing of alpha-ketoglutarate dehydrogenase; this ends when cytoplasmic glucose reaches a new steady state. Mitochondria in vitro are known to have higher pH than their surroundings; it is found here that this also holds in situ. Under these conditions, glycolysis is coherently substrate controlled, as is phosphofructokinase, usually considered the typical example of an allosteric enzyme. Limitations on simple methods of analyzing metabolic data of this type, e.g., use of lactate/pyruvate ratios to calculate NADH/NAD ratios, are discussed. Here a large volume of enzyme and other biochemical information has been integrated into a physiologically meaningful system.


Relationship between gastric mucosal pH and site of peptic ulceration. Measurements of mucosal pH of resected stomachs were carried out in gastric and duodenal ulcer patients. Low mucosal pH along the lesser curvature and relatively higher gastric pepsin levels were found. It is suggested that this lower pH affects gastric ulcer occurrence in the limited "lesser curvature area" where 63 per cent of the ulcers were situated. It is also suggested that increased pepsin activity present in gastric ulcer patients may be another factor affecting gastric ulcer formation by virtue of pepsins activated at higher pH. In duodenal ulcer patients, these factors are "overshadowed" by high acid-pepsin secretory activity of gastric juice.


The role of analgesics in respiratory depression: a rabbit model. The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl.


Formaldehyde formation as a metabolite of methoxyflurane. The production of formaldehyde as a metabolite of enzymatic biotransformation of methoxyflurane was observed in vitro in hepatic microsomal preparations derived from Japanese monkeys, rabbits and Wistar strain rats. Production rates of formaldehyde were 0.80-2.50 n moles/mg protein/min in the induced group which was pretreated with phenobarbitone, and 0.15-0.68 n moles/mg protein/min in the non-induced group. This reaction needed the presence of NADPH and oxygen. Formaldehyde production was almost completely inhibited by addition of 25% CO. Further degradation of formaldehyde did not occur in microsomal suspension. No detectable species difference was observed among the animals used in this study. These results indicate that the biotransformation of methoxyflurane is preceded by interaction with cytochrome p-450 in hepatic microsomes in the presence of NADPH and oxygen.


[Anaesthesia with flunitrazepam (rohypnol) and fentanyl for geriatric patients (author's transl)]. Favorable clinic experiences with an anaesthetic involving rohypnol (flunitrazepam) and fentanyl led to an investigation of the haemodynamic effect of this procedure in a group of 9 geriatric patients, aged from 86 to 95 years. Anaesthesia was induced with 0.5 mg rohypnol and 0.1 to 0.2 mg fentanyl depending on the narcotic effect of rohypnol, intubation was performed under relaxation with suxamethonium and long term relaxation was achieved with pancuronium. The patients were normoventilated with nitrous oxide/oxygen. The individual values of the changes in cardiac output and total peripheral resistance showed a great variation. There was a significant correlation between the relative changes in mean arterial pressure and total peripheral resistance (r = 0.69, p less than 0.05) but no correlation between mean arterial pressure and cardiac output (r = 0.09). This indicates that the pronounced drop in arterial pressure which occurred in 4 patients can be explained by a decrease in total peripheral resistance. Careful dosage of the drugs, in particular of fentanyl, and knowledge of adequate measures to treat a decrease in blood pressure if it occurs, appears to be a prerequisite for the use of this type of anaesthesia in poor risk patients.


[Paresis of the tympanic nerve--a rare complication of spinal anesthesia (author's transl)]. Acut impairment of hearing following spinal anaesthesia is described. The cause, treatment of and incidence rate of neurological complications of spinal anaesthesia are discussed.


Alpha-adrenergic blocking action of fentanyl on the isolated aorta of the rabbit. The contractile response of helically-cut strips of rabbit ascending aorta to transmural electrical stimulation was attenuated in a dose-dependent manner by treatment for 20 min with fentanyl, 10(-6) to 10(-5) M. Fentanyl also shifted the dose-response curve of the contractile response of aorta to norepinephrine to the right. The  response to transmural stimulation was more resistant to fentanyl than was the response to an equipotent dose of norepinephrine. The inhibitory effect of fentanyl was neither prevented nor reversed by naloxone, but was partially reversed by repeated washing of the preparations. The contractile responses to histamine and serotonin were not significantly altered by fentanyl. Treatment with fentanyl as well as phentolamine protected alpha-adrenergic receptors from persistent blockade by phenoxybenzamine. Morphine to 10(-3) M failed to influence the dose-response curve of norepinephrine significantly. It may be concluded that fentanyl reversibly blocks alpha-adrenergic receptors in a competitive manner in vascular smooth muscle, and the potency of fentanyl is approximately 1/30 that of phentolamine.


The splitting of sperm heads from tails in eight mammalian species and the measurement of their sizes. Ejaculated spermatozoa from man, the Euopean wild boar and the bull, and spermatozoa from the cauda epididymes of the rabbit, rat, mouse, hamster and Guinea pig were treated with a sonic bath, a sonic probe, trypsin with and without prior treatment with a sulphhydryl reagent, pronase and alkalis. The fragments produced were counted and sized in an accurately calibrated Coulter Counter, Model ZB Industrial, before and after Zaponin treatment to lyse accompanying debris and the peripheral cytoplasm. Head and tail fractions were separated on sucrose gradients. Each species required different conditions for cleavage or fragmentation. Rabbit and bull spermatozoa were cleaved by the ultrasonic bath exactly into heads and tails, producing twice the number of particles with two peaks in the size distribution curves butith some 60% loss of total sperm volume which became the soluble fraction. The ultrasonic probe, and for the bull, pronase, produced the same cleavage but these more drastic treatments dissolved a considerable portion of the tail fraction. Rodent spermatozoa, especially the rat, were cleaved perfectly into heads and tails by mild trypsin treatment. All the nonrodent spermatozoa were resistent to trypsin cleavage, although prior treatment with a sulphhydryl reagent caused swelling and subsequent trypsin action caused digestion into miscellaneous pieces. Spermatozoa from the boar and from man could not be cleaved by any of the procedures. The sonic probe produced fragmentation with progressive dissolution of the tail fragments and a single peak in the size distribution curve corresponding to small stripped heads. The soluble fraction always constituted a large proportion of the original whole spermatozoa.


[Membrane oxygenators in cardiac surgery: progress]. This study tries to define if the membrane oxygenators are available during cardiac surgery under E.C.C., and if their performance are superior to those of conventional oxygenators. Two series of research are done. In the first one, we compare performance of two membrane oxygenators: the Rhône-Poulenc heart-lung machine (10 cases) and the Travenol TMO Teflo machine (100 cases). The general impression is good: the two proposed systems seem to be perfectly well adapted to surgical utilization conditions, avoiding excessive ventilations and eventually allowing to keep on E.C.C. in postoperative. In the second part of this work, two series of patients are studied, one oeprated under membrane oxygenator (Teflo), the second under bubble oxygenator (Bentley Q 100). Comparative study shows small differences between the two groups. Only the post-operative enzymatic profile is clearly for the membrane oxygenator which also insure a waking and a postoperative recovery of highest quality. These first observations justify to keep on using of membrane oxygenators in cardiac surgery.


[Methods of sampling and preservation of blood used during extracorporeal circulation]. The blood supply of Cardiac Surgery Centers set quantitative and qualitative problems to the Centers of blood dispatch. In this work, from a Lyonese experience on 4,000 E.C.C., authors try to define the best preservative solution, especially for the respiratory function of the red blood cell. The C.P.D. solution (citrate, phosphate, dextrose) answers to requirements in this field when the blood used is less than 48 hours old. In the meantime, it is not impossible that studies based on definite criteriums of evaluation and on severe comparisons allows to adapt new process from which some are described and criticized in this work.


[Value of using cell concentrates, preserved by freezing, during extracorporeal circulation]. The effectiveness of transfusions of frozen red cells has presently been clearly demonstrated. The authors present their technique of preparation of these cells and their experience of this material in 51 cases of ECC. The results observed plead in favour of the notion that frozen-defrosted blood, combines the advantages of washed blood, freed from all plasma and cellular contaminants of fresh blood with preservation of the oxyphoric power. Going beyond the realm of ECC, the authors think that cryopreservation of blood should be applied to the majority of indications for transfusions.


[Technics, value and limitations of hemodilution in extracorporeal circulation]. Hemodilution during E.C.C. is into use for more than 15 years. Its interest is obvious (blood economy, beneficient action on viscosity, prevention of "sludging"), but opinions are different concerning the best level of hemodiultion. The authors defend the notion of a moderate dilution (hematocrit larger than or equal to 25 p. 100) required to maintain a high perfusion pressure. For atherosclerotic patients, they describe the hemodilution technics tried on more than 4,000 cases since 1964. The advantages of hemodilution concern on one hand the diminution or the disparition of drawbacks and complications due to the obtainment and to the administration of homologous blood and on the other hand the beneficient intrinsical effects of the blood dilution on the tissular perfusion. In convenients are those due to changes in the concentration of sodium, chlore and specially potassium which may be responsible of serious cardiac arrythmias. Because of increasing difficulties concerning the use of homologous blood (obtaining difficulties and complications relative to its use), the authors consider the utilization of autologous blood taken off before the operation on the patient and freezed.


[Biological aspects of extracorporeal circulation]. Two problems are looked at in this work. That of glucose which is administered in considerable quantities during ECC and that of the iso-enzymes. The administration of glucose has two aims: one being the mechanical nature i.e. as an agent which decreases the risks of platelet aggregation, the other bio-energetic. But, owing to the CRABTREEE effect, an excess of glucose blocks the biosynthesis of ATP and a non-metabolisable structural analogue which has mechanical properties identical with glucose, such as fucose or rhamnose could be supplied instead. As far as the iso-enzymes are concerned, the author after having looked at the general value from the standpoint of signs and symptoms, suggests the study of two of them, cardiac lactic-dehydrogenase and the MB fraction of creatine phosphokinase could enable the follow-up of the course and of the consequences of extra-corporeal circulation.


[Sodium supply in operations under extracorporeal circulation in children]. In order to explain the edematous appearance found in infants after ECC associated with hyponatremia, the authors studied the supply of sodium per and post-operatively in 42 children aged from 11 days to 13 years undergoing correction of the cardiopathy under ECC. This study enables one to find that there is an inflation of sodium after intervention under ECC, which is even more important, the longer the duration of the ECC. It is not related to a failure in urinary excretion of Na+ and predominates in infants. It is related with the supply of sodium during transfusion and seems to be the cause of certain respiratory complications met with following ECC.


[Hemodynamic parameters which should be watched during and immediately after extracorporeal circulation]. The author studies only the usual investigations required for watching E.C.C. during the operatory period and directly afterwards. During E.C.C., one must essentially oversee the flow (2,4l/m2 or 70 ml/kg), the arterial pressure (70 torrs) essential factor for myocardiac injection, the C.V.P., where excess is factor of cerebral oedema, the peripheric vascular resistances (P.V.R.) which inform on the level of vasomotoricity. Control of pulmonary capillary pressure (P.C.P.), which is under E.C.C. the reflection of the left ventricular pressure (L.V.P.) is also a capital element of this watching (any elevation of L.V.P. is factor of sub-endocardiac ischemia and of acute pulmonary edema). In post E.C.C., the same parameters will be watched. A cardiac output equal or inferior to 2 l/m2 involve an immediate treatment. The C.V.P. allows adaptation of blood quantity. Calcul of V.P.R. sets treatment of low cardiac output. C.P.C. control allows evaluation of left ventricular efficacity. These datas must be completed by calcul of subendocardiac viability by studying the arterial pressure curves which inform on oxygen supply and demand, and by the contractility index measure (aortic output speed and measure of systolic interval).


[Protection of the myocardium by hypothermia during extracorporeal circulation. Experimental and clinical study]. Hypothermic protection of myocardia during E.C.C. has been estimated on a 35 dogs experimental series and on a clinical series of 700 acquired cardiopathies of adult, including 400 valvular replacements and 300 aorto-coronary by-pass. Experimental results have been estimated by biochemic and morphologic controls done on myocardic samples took up by drillbiopsy. The biochemical study includes among others a dosing of the high-energy phosphorus compounds (P.C. and A.T.P.). Morphological study was done by optic and electronic microscopy. Results made clear the superiority of the hypothermic ischemia at 10 degrees C on the continued perfusion at 32 degrees C with fibrillative heart. An hypothermic protection method with successively cold perfusion of the coronary system and a heart immersion in a salted solution at 4 degrees C has been utilized during valvular and coronary surgery on human in 700 cases. The total mortality was of 5,8 p. 100. The rate of post-operative infarcts was 2,4 p. 100. Incidence of intra-ventricular conduction troubles has been 1,1 p. 100. There was no relation between mortality and morbidity of myocardic origin and the lasting of the ischemic clamp, which were of 21 mn up to 165 mn. The low incidence of complications of myocardic origin is due to the hypothermic protection of the myocardia.


[Myocardial protection by coronary perfusion and specific problems of myocardial protection in combined valvular and coronary surgery]. The quality of the myocardial protection by bilateral coronary perfusion was studied in a consecutive series of 80 patients treated by isolated aortic replacements (47 cases) or multiple replacements (mitro-aortic, or mitro-aortic and tricuspid) 33 cases. Four low outputs (5 p. 100) were observed with only one death. Five post-operative necroses (6.25) were noted. The overall surgical mortality was 6.25 p. 100 (5 cases out of 80). There were two deaths in the series of the 47 single replacements and three deaths (9) in the series of multiple replacements. At the same time, the myocardial protection was studied in a consecutive series of 12 cases of valvular replacements combined with coronary shunts. In all of the cases, the shunt or shunts were carried out first, the myocardial protection was subsequently ensured by a coronary perfusion carried out by means of the shunts and directly through the coronary orifices. There were 2 deaths (16), 2 necroses (16) both responsible for deaths and no low output in the 10 survivors. Coronary perfusion very certainly ensures an excellent quality of myocardial protection if certain criteria are respected: hypothermia, moderate (28 degrees) bilateral perfusion with a mean perfusion pressure above 100 also ensuring a good flow through the sub-endocardial layer, which remains particularly sensitive to ischiemia. In cases of associated shunts, they must be carried out, first of all, in cases of tight senoses, over 60.


[Computer analysis of a method of myocardial protection used in a series of 547 operations under extracorporeal circulation in adults]. During 4 years (1970-1974), the numerous pre, per and post-operative datas collected for each adult operated under E.C.C. by the same surgeon, have been analysed on computer (547 cases). The myocardic protection method was unvariable: steady hypothermia of 30 degrees C, induced ventricular fibrillation, myocardic anoxia time less than 15 mn, strict out-bubbles of the left cavities. A direct perfusion of the coronary arteries has been used in case of aortotomy. Analysis of the early post-operative mortality causes and of the various post-operative myocardic complications did not reveal any baneful influence of this myocardic protection method. The average post-operative left auricular pressure, the most reliable test of the left ventricular dynamics, or its post-operative variations are independent of the ventricular fibrillation time, the perfusion time or the coronal output used.


[Changes in myocardial tolerance to ischemia as a function of circulatory arrest mechanisms]. This study tries to specify the tolerance limit of heart to ischemia and has three parts. In the first one, the author considers the heart resistance in normothermy related to the circulatory arrest type, the anesthetic technique, existence or not or a ventricular fibrillation. Everybody is tody in agreement to admit that 35 to 45 minutes are the security limit of the cardiogenous circulatory stop. In the second part, conditions of cardiac tolerance to ischemia in hypothermy are foreseen. The security margin is here large, provided a nonagressive realization of the cooling. Lastly, the author reports the looseness of the biochimic, histochemic or histologic criteriums which permit an appreciation of the heart functional capacity, appreciation which still persist to be essentially clinical.


[Neuroplegia and extracorporeal circulation. Comparison between combinations of droperidol-phenoperidine and chlorprothixene-dextromoramide in cardiac surgery]. After a quick review of the physiopathology of extra-corporeal circulation, the value of the use of neuroplegic drugs in cardiac surgery is recalled by means of pharmacological arguments. The experimental differences existing between the combinations droperidol - phenoperidine and chlorportixene - dextromoramide, on the rate of flow and on the pressure of the perfusion, and on the esophago-rectal thermic gradients during E.C.C. is then demonstrated. Statistic calculation confirmed the superiority of chlorprotixene in the realm of tissue perfusion during E.C.C. under hypothermia.


[Drug protection of the myocardium during cardiac surgery]. During aortic clamping, drug protection of the myocardium, far from supplanting hypothermia, complements it, particularly in the case of left ventricular hypertrophy. Ultramicroscopy and new techniques of histobiological exploration of the myocite have enabled one to distinguish the lessions provoked by anoxia from those induced by reperfusion. At present, drug protection, extended to energetic solutions and electrolytes, aim at preserving energy metabolism by stocking of the substrate and at avoiding interferences which precipitate exhaustion of the adenosine triphosphate and phosphocreatinine reserves. In order to do this, hemodilution in particular is limited in subjects with decompensated cardiopathy; choice of anesthetics is orientated towards neuroleptanalgesia or fluothane, and it is attempted to neutralize the adrenergic reaction by the use of beta-blocking substances. Furthermore, it is preferred to interrupt electrogenesis at the stage of polarization: depolarizing cardioplegic solutions rich in potassium and sodium are rejected and in preference membrane stabilizers are used (procaine, magnesium, tetrodoxine...) The ultramicroscopic analysis of the structural modifications leads to sparing of the integrity of the lysosomial membrane by corticoids and alkalines. The use of calcium is deferred, anti-calcium techniques are even proposed (washing poor in calcium, verapamil). Cellular edema is prevented and treated by solution (mannitol - sorbitol) whose osmolarity must be less than 300 M osm/l. A conditioning of the biochemical and physicial structures and of cardiac work is being more and more thought of which leads to the classification of beta stimulating substances as negative, and their indications must be seriously thought of and used with reserve.


[Shivering during recovery after cardiac surgery under extracorporeal circulation. Inconveniences and methods of prevention]. Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering.


[Preventive treatment of acute renal failure in cardiac surgery]. The prevention of acute renal failure after cardiac surgery under extracorporeal circulation is possible during the pre-, per- and post-operative phases. During "ECC" the maintenance of "correct" renal perfusion is imperative, the same is also true of the post-operative period; the re-establishment of good hemodynamics is the best guarantee of maintenance of renal function. The prevention of infection is the second imperative.


[Deep hypothermia on the infant: physiopathology and technics of ECC]. In 81 operations for correction of infants's cardiopathies, authors used, associated with E.C.C., a deep hypothermia allowing a circulatory arrest of an average duration of 52 minutes, according to the technics described by BARRAT-BOYES in 1971. From this experience, authors study the modifications brought to the organism by this hypothermia, and discuss the technical aspects in pre, per and post-operative periods. Mortality of this series is of 13,5 p. 100. It is in relation with the cardiopathy or it's correction, without anu possibility or directly charge the technique of hypothermia in its determinism. The early mortality includes a bilateral phrenic paralysis, an air embolism, three septic complications and two neurologic complications probably related to a poor thermic repartition. Advantages of this technique concern the possibility to operate in a bloodless field and a diminution of E.C.C. time.


[Cerebral arterial embolism during extracorporeal circulation]. From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G.  and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen.


[Brachial diplegia--a post ECC neurological complication of a specific type]. Five cases of neurological disorders occurring after extra-corporeal circulation are presented owing to the singular nature of the clinical picture made up by the essential element of a progressive brachial diplegia, free from any sensory disorder. The topography of the lesion--single medullary lesion or bilateral encephalic--is discussed. An anatomic document enables the elimination of any médullary involvement in one of the cases, thus pointing to a bilateral central lesion. The physiopathological problems are looked at.


[Early neurological complications after cardiac surgery under ECC]. A non-trifling frequency (3,3 p. 100) of neurologic complications is observed after surgery under E.C.C. The part of some factors has been analysed and discussed, especially those played by the type of the system used, quality of the E.C.C., and the patients' conditions. Many problems are still unresolved. The actual gravity of observed troubles must bring a better harshness in preventive treatment, and to a more adjusted treatment when these troubles are noted.


[Pulmonary complications after extracorporeal circulation. ECC lung syndrome]. Pulmonary complications after cardiac surgery under extracorporeal circulation remain frequent and sometimes grave, in spite of the great progress which has been made over the past 20 years in the methods of cardiorespiratory assistance. The authors analyse the clinical and radiological repercussions of perfusion on the lung, in 40 patients operated under ECC for coronary revascularisation. The simutaneous study of the arterial, and mixed venous blood gasses and of the alveolar gases, in 20 of these patients showed the constant occurrence of a shunt syndrome, without alveolar hypoventilation or disorders in peripheral circulatory flow. Ventilatory alcalosis, hypocapnia, hypoxemia and the rise in the alveolar arterial oxygen gradient is increased during the second post-operative day. Among the variables studied (duration of ECC, degree of hypothermia, duration of the intervention, duration of anesthesia, pleurotomy) only the latter intervened in a statistically significant manner in this study, in the increase in hypoxemia. 46 pulmonary biopsies carried out before and after ECC in 23 coronary patients were examined with the electron microscope. The initial alveolar involvement affects the septal microcirculation with signs of an increase in capillary permeability leading to an interstitial and epithelial destruction. The use of a membrane oxygenator prevents some of the alveolar lesions, as has been proved by the study of five pulmonary biopsies carried out in dogs submitted to ECC of long duration. Catherterization of the pulmonary artery carried out in 35 patients by means of a SWAN-GANZ catheter, before the intervention enabled supervision of the degree of importance and speed of the hemodynamic variations in the pulmonary circulation during the different phases of ECC (during the phase of ventricular fibrillation). The rise in the flow of left output can lead to the occurrence of negative pulmonary intravascular pressures which can be prejudicial for capillary trophicity. The syndrome of "ECC lung", a veritable "induced post-agressive lung" must be placed in the group of refractory hypoxemia of which it represents one of the most typical pictures.


[Technics of anesthesia and hypothermia for the infant. Choice of replacement fluid for the circuit]. Sixty-five infants were submitted to complete repairment of a congenital cardiopathy under profound hypothermia and ECC. Description of the preparation of the young surgical patient, of the anesthesia, of the technique of ECC. The overall mortality was 35.5 p. 100. The hypothermia induced by ECC, does not introduce any supplementary risks as long as strict technical rules are respected.


[Use of a membrane oxygenator in extracorporeal circulation in the child. Preliminary conclusions]. The comparison of two types of oxygenators, the bubble and membrane oxygenator, in cardiac surgery under ECC, in infants. The results were not subjected to a statistical study. However, it seems that the membrane oxygenator enables one to obtain a satisfactory hematosis in a simpler fashion (the addition of CO2 being avoided) than with the bubble oxygenator and leads to less hemolysis than the latter. In the cases of closed circuit ECC with recirculation, the use of the membrane oxygenator also gives greater security of manipulation of the blood mass.


[Fluid mass distribution during extracorporeal circulation]. The author first recalls close relations existing in physiologic conditions between central venous pressure and blood mass. During E.C.C., this relation is out of truth through the action of venous correlations and of outout. Then studying distribution of blood mass in the different compartments, he notes that during E.C.C., the total organic fluid mass changes a little, but that the extracellular volume increases when the blood mass grows less. To these modifications shares in a seclusion of blood in the visceral compartment.


[Proteins and blood volume after cardiac surgery under ECC and hemodilution]. The variations in protein, bodyweight and circulating blood volume during operation are studied in 18 patients operated under ECC. The frequency of hypovolemia with hypoproteinemia and over hydration of the interstitial medium is confirmed. The prolongation of ECC beyond 120 minutes is accompanied by a considerable reduction in the plasma sector. The frequency of hypovolemia must render the use of diuretics prudent. The existence of hypoproteinemia and interstitial overload suggests the value of albumin perfusions.


[Direct action of extracorporeal circulation on platelets and coagulation factors]. Concerning a study carried out in 250 patients, the authors confirm the classical notions concerning the fall in platelets, fibrinogenesis, factor II, XII AT3 and plasminogen during ECC. A more precise study of platelet levels shows important variations depending on the patients, whereas the length of time of ECC, the degree of importance of aspiration the first minutes of ECC, appear to be aggravating factors. There is no correlation between the type and the length of the circuit. Furthermore, from the morphological standpoint, thrombocytic changes are also noted. The same can be said of platelet function. In the last part of the work, the authors studied the causes of platelet consumption and their prevention. On the whole, and in practice, consumption of coagulation factors during ECC remains a little disturbing. It is, however, worth continuing to study their prevention.


[Coagulation deficits and hemorrhagic consequences after cardiac surgery under ECC]. I--A statistical study of the results of tests of hemostasis was carried out in patients who had undergone major cardiac surgery with extra-corporeal circulation. There were two series of patients (1.504 and 547 operated) suffering mainly from congenital cardiopathies, valvulopathies or coronaritis. Bearing in mind the hematocrit and the total protein level, the following was studied before and after ECC and 24 hours after the intervation: the blood platelet level, fibrinogen, prothrombin and its cofactors, antithemophilic factors A and B, FDP amd fibrinolytic activity. The fall in platelet stickiness is specifically pointed out, and also the fall in the level of fibrin stablizing factor (factor XIII) which is met with after ECC, and which can explain the persistence of certain hemorrhagies. Furthermore, the fall in antithrombin III level then its rise can contribute to the "heparine rebound" occurring in certain cases after neutralization of heparinemia with protamine. II--The deficits in the quantitatively and qualitatively variable hemostatic factors do not necessarily lead to hemorrhage. Hemorrhage, due to biological causes, are met with in 5 to 6 p. 100 of the cases. Most of the time they are provoked by a residual hemorrhage or a "heparine rebound", deficits in coagulation factors, a DIVC syndrome, difficult to diagnose and to treat, or fibrinolysis, much more rarely nowadays, owing to the almost routine use of antiproteases. Sometimes, the check up of coagulation can be barely disturbed and local abnormalities in biological hemostasis which are still not well understood, are invoked in order to explain the hemorrhage.


[Variations in hemostasis in the infant under deep hypothermia]. Effects on hemostasis of deep hypothermia on infant has been studied on 29 infants operated upon for a cardiopathy under deep hypothermia. Results of this study show a diminution of the coagulation factors rate, an augmentation of the fibrinolytic activity and an unforeseable variability of the residual heparin leading in all cases to a complement of the heparin neutralization by Protamine.


[Physiopathology of low cardiac outputs after ECC and their treatment]. Etiologic circumtances of low cardiac outputs are studied according as they concern a diminution of the precharge (hypovolemy of different reasons), an augmentation of the postcharge (by augmentation of aortic impedance or resistance to blood flow) or a cardiac deficiency. The latter can be of non-ischemic origin (effects of beta-blocking drugs, cardiac arrhytmias tamponade, deficience of myocardiac fiber, metabolic disease) or ischemic:--during E.C.C.: diminution of available oxygen (hypothermial), arterial pressure and output too low, clamping time or ventricular fibrillation too long;--after E.C.C.: insufficient surgical correction, coronary embolism lack of balance between apport and expense of oxygen. Therapeutics ways are discussed regarding the different etiologies. The central rule is that it is better to relieve an ischemic myocardia than lash it. But treatment of low cardiac outputs is most often an average solution which must be choose in regard to a well understood physiopathology.


[Hemodynamic aspect of post ECC cardiac failures. Study of 193 cases]. The aim of this study is to define the hemodynamic characteristics of this "clinical model" of acute cardiac failure observed after cardiac surgery carried out under extra-corporeal circulation, which constitutes the essential cause of "post-operative low cardiac output syndrome". The 193 patients in this study make up a representative sample of patients operated, treated and studied according to a homogeneous methodology for a period of 1 year. The clinical analysis of the post-operative circulatory condition, after exclusion of non cardiogenic syndromes, led to grouping the cases into 5 classes of circulatory change of increasing severity, each corresponding to a specific "therapeutic necessity". The hemodynamic results (intra-vascular pressures, oxymetry, cardiac output by "Cardio-Green" dilution method) are given for each of the five classes, thus defining the "hemodynamic profile" and the statistical reliability of the main objective parameters. This gives proof of the therapeutic indications for the main therapeutic procedures actually known, for which we prevent the hemodynamic effects noted for each of them. Thus, three "degrees of cardiac failure" are found: less severe (classes I and II) call for simple metabolic equilibration and possibly diuretics: the systolic work is above 160 gm/m2. Decompensated circulatory failure (classes III and IV) corresponds to a more important reduction in systolic work (9) 15 gm/m2, i.e. between 20 et 40 p. 100 of the basal value), and call for sympatho-mimetic cardiotonic agents: isoprenaline and/or dopamine. Below this value, in spite of medical treatment, the hemodynamic situation can still be sometimes reversible under circulatory assistance (diastolic counter pressure by means of an aortic balloon). Confronted with the clinical picture, the hemodynamic study enables the quantification of the circulatory change, and specification of the cardiogenic part and thus especially helps the carrying out of the treatment.


[Acute renal failure after cardiac surgery under extracorporeal circulation]. Acute renal failure (ARF) following cardiac surgery under extra-corporeal circulation is a grave but infrequent complication. Numerous physiopathological factors accounting for its origin are analyzed, those related to ECC and those of the immediate post-operative period. The course of these cares of ARF and the elements of the treatment are looked at.


[Kidney failure after ectracorporeal circulation in cardiac surgery]. The renal function of 113 patients undergoing cardiac surgery under ECC was studied. In 32 p. 100 of the cases renal involvement was noted which was moderate in 18 p. 100 of the cases, severe in 10 p. 100 of the cases and anuric in 4 p. 100 of the cases. Valvular surgery was complicated once in every three cases by renal involvement, the repair of congenital malformations once out of every two cases, and coronary surgery in 17 p. 100 of the cases. The fall in renal perfusion represents the essential factor in this renal involvement, which should be avoided by the maintenace during ECC of a high output level and a satisfactory perfusion pressure and by the recovery of correct hemodynamics after the intervention.


L(+) lactate dehydrogenase activity from the electric organ of Electrophorus electricus (L.). Properties of L(+) lactate dehydrogenase (LDH) of Electrophorus electricus (L.) electric organ were studied, comparing the substrates pyruvate and lactate. Electric organ LDH is a soluble enzyme with a pH optimum of 7.4 for pyruvate and 9.0 for lactate. The apparent Km was lower for pyruvate (Km = 2.5 X 10(-4) M) than for lactate (Km = 1.5 X 10(-2) M). With lactate as a substrate at pH 7.4, malonate, oxalate and pyruvate inhibited competitively. For pyruvate as substrate at pH 9.0 malonate inhibited non-competitively and oxalate shiwed uncompetitive inhibition. The different effects of the carboxylic acids on LDH activity suggest different stereospecificities of the two enzyme-coenzyme complexes in the forward and reserve reactions. The reactions of electric organ LDH with substrates and inhibitors are consistent with electrophoretic analysis suggesting that the enzyme is of the M-type.


Influence of reagent quality and reaction conditions on the determination of serum albumin by the bromcresol green dye-binding method. In an age of reference methodologies and sophisticated quality control techniques it is surprising that so little attention is paid to the quality of the reagents that are used. This paper reports on an investigation of the bromcresol green dye-binding procedure for the estimation of serum albumin in which particular attention has been paid to changes in the reagent components that contribute to the performance of the method. It has been shown that detailed attention to the quality control of the reagents can improve the precision and interlaboratory comparison in the estimation of serum albumin.


[Endocrine polyadenomatosis associated with prolactin pituitary adenoma and an intrathyroidal parathyroid adenoma]. A pituitary adenoma was removed transsphenoidally from a 20-yr-old woman with secondary amenorrhea, galactorrhea, and hyperprolactinemia. Light and electronic microscopy, immunocytology characterized a prolactin cell tumor. The patient also underwent three surgical explorations for hyperparathyroidism. Only after selective catheterization of thyroid veins with radioimmunoassay for parathormone, an intrathyroidal parathyroid adenoma was found. No other case of proven prolactin adenoma in Wermer's syndrome has been reported.


Renal function during and following obstruction. The effects of urinary-tract obstruction on renal function have been clarified using modern physiologic techniques in animal models. These effects are obviously dependent on the severity and duration of obstruction, together with the presence or absence of extrarenal factors, particularly uremia, as exemplified by the differences in renal function between bilateral and unilateral obstruction. The beneficial effects on the unilateral postobstructive kidney of volume expansion (5) and the importance of azotemia in determining POD (20, 21) have possible clinical applications. Further experimental work is required to understand the mechanism responsible for the altered renal hemodynamics and decreased GFR, as well as the abnormalities in medullary function resulting from obstruction. Improvement in the management of this common clinical problem may then be forthcoming.


Effect of anesthetic drugs on myocardial performance in man. All potent CNS depressant drugs can depress cardiac function in man in a dose-dependent manner. The dose-effect curve is considerably flatter with several drugs (diethyl ether, cyclopropane, fluroxene, isoflurane, and ketamine), presumably from sympathetic nervous-system activation. Potent analgesics and tranquilizers appear to produce less depression, but have been incompletely studied. Neuromuscular blocking drugs and regional anesthesia produce minimal effects on the heart in healthy people. However, not as much is known about diseased man. For instance, nitrous oxide produces more depression in "muscle" function in IHD patients (43), while diazepam (28) and morphine (44) do not adversely affect pump function in this class of patients. Fluroxene (45) is more depressant in VHD patients, but nitrous oxide (46), morphine (30), fetanyl (46), and droperidol-fentanyl (46) seem to have equivalent effects to those seen in health patients. In any given patient, therefore, accurate prediction of the effect of any anesthetic drug on cardiac performance is not possible. Adequate monitoring and careful titration of drug dose offer the safest method of assuring a satisfactory response.


[Synthetic medium for the biosynthesis of gentamicin]. A synthetic medium for biosynthesis of gentamicin was developed. It includes maltose, gelatine, potassium phosphate, ammonium sulphate, cobalt chloride, sodium chloride, magnesium sulphate and zinc sulphate. The dynamics of the biochemical changes in the above medium was studied.


[Penicillin amidase from E. coli. Some physicochemical properties of the soluble enzyme]. Homogeneity of the enzyme was shown with the methods of gel filtration and disc electrophoresis. The molecular mass of penicillinamidase (PA) was determined. Sorption of PA by a carboxylic ion exchanger within a wide range of pH was studied. The values of pH in the ion exchanger phase under the conditions of the enzyme sorption were estimated. The ion exchange technique for determination of the isoelectric points of the proteins is described and the isoelectric point of PA is determined. It is proposed to use the method for estimation of close ionization constants of amphoteric an weak electrolites for interpretation of the bell-like pH dependence of kinetic and equilibrium parameters of the enzymatic reaction. The ionization constants of Michaelis complex of PA were evaluated. The activation energy of benzylpenicillin hydrolysis catalized by PA was determined.


[Penicillin amidase from E. coli. Some physicochemical properties of the enzyme incorporated into polyacrylamide gel]. The physico-chemical properties of penicillinamidase (PA) immobilized in polyacrylamide gel (IPA) were investigated. It was shown that simple incorporation of PA into polyacrylamide gel was not effective because of gradual washing out of the enzyme. The use of a complex method for the immobilization (immobilization in the presence of a linking agent) resulted in higher stability of IPA, the choice of the optimal ratio of the reagents being of paramount importance. The mechanical strength of IPA was studied in model experiments.


Penicillin resistance and penicillinase production in clinical isolates of Bacteroides melaninogenicus. The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of Bacteroides melaninogenicus. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration >/=0.8 mug/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 mug of clindamycin per ml. All isolates with penicillin MIC values >/=0.8 mug/ml produced beta-lactamase using a slide method. A micro-iodometric assay was used to quantitate beta-lactamase production in six isolates. The beta-lactamase activity of B. melaninogenicus was comparable to that of a Staphylococcus aureus isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the beta-lactamase-producing strains of B. melaninogenicus were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy.


Clinical and histological study of coal tar phototoxicity in humans. Coal tars of different origin were compared with regard to their capacity to cause a phototoxic reaction in human skin. The photosensitizing potencies were found to differ. Tars that were partially refined had less activity than crude coal tar. An extract of tar, liquor carbonis detergens, was the least photosensitizing. The phototoxic reaction to coal tar was found to be a two-stage process, an immediate wheal associated with sharp burning, followed by a raised, red, infiltrated lesion peaking at 24 to 48 hours. The phototoxic reaction was completely prevented when arterial blood flow was cut off. The histological findings were prominently epidermal, with strong intracellular edema sometimes leading to microvesicles. It seems a possibility that assaying phototoxic potentiality may provide a convenient measure of therapeutic efficacy of materials derived from coal tar.


Comparison of the effects of alclofenac, flurbiprofen, and prednisolone on acute inflammatory response in the rat. The fluid and cellular phases of the inflammatory response were measured using a technique employing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Fluribiprofen and prednisolone were equipotent and were capable of almost completely suppressing fluid and cellular responses, while alclofenac was less potent at nontoxic dose levels. Study of the patterns of cellular exudation by image analysing computer showed that alcofenac appears unique in that it produces a well-defined cell-free zone between the edge of the implanted cubes and a band of neutrophil polymorphs within the cubes.


Alpha-Isopropylmalate synthase from Alcaligenes eutrophus H 16 I. Purification and general properties. alpha-Isopropylmalate (IPM) synthase, the first enzyme in the biosynthesis of L-leucine, was purified to a specific activity of 12 micronmole/min x mg protein from the valine-isoleucine double auxotrophic mutant A-81 of the hydrogen bacterium Alcaligenes eutrophus H16. The activity in crude extracts of derepressed cells was 0.106 micronmoles of isopropylmalate formed per min and per mg protein. Gel electrophoresis and regel electrophoresis of the isolated main band resulted in several distinct bands, which were not altered by the additions of substrate alpha-ketoisovalerate, feedback inhibitor leucine or other effectors. The isoelectric points of the enzyme protein was between 3.9 and 4.0. The molecular weight was 114 500 daltons and 100 000 respectively in the absence and presence of the feedback inhibitor leucine. The enzyme activity depended strongly on the pH, the optimum is at pH 8.2. The enzyme was could labile and exhibits temperature anomalies.