[Blood picture of calves from primiparae kept under large-scale production conditions in the early postnatal period]. Twelve calves of the Red Spotted breed and its crossbreds born by first-calvers, kept in a large-capacity stable of a dairy farm, were subject to the study of the ontogenetic development of the values of the blood picture from birth up to the 10th day of age. The erythrocyte and leucocyte count, the packed cell volume and the relative and absolute number of neutrophils reached the significantly highest levels in calves before drinking the colostrum. The amount of haemoglobin, MCV and MCHC reached the highest values on the first day after birth. The values of the red blood picture decreased in the first week of life and reached the minimum on the tenth day. The leucocyte count decreased during the first to second day after birth, the decrease being due to a drop of the absolute number of neutrophils, and on the tenth day the leucocyte count returned to its initial value. Neutrophils prevailed in the peripheral blood of new-born calves whereas lymphocytes prevailed in the peripheral blood from the fourth day of life on. The amount of cosinophiles in the peripheral blood of the calves was about 0.5% up to the fourth day; on the seventh day it exceeded 1%. The relative number of monocytes was at its minimum level just after birth and showed a significant increase during the second to fourth day.


An epizootic among knots (Calidris canutus) in Florida. II. Ultrastructure of the causative agent, a Besnoitia-like organism. Multinucleated cysts near the luminal surface of the thoracic aortas of diseased knots (Calidris canutus) were similar to besnoitia cysts. Ultrastructurally, the cyst had four distinct layers. The central area included a vacuole that contained a sporozoan with a conoid, polar ring, micronemes, rhoptries, nucleus, mitochondria, dense bodies, a lipid-like vacuole and endoplasmic reticulum. External to the vacuole was a layer with organelles typical of vertebrate cells. The wall of the cyst was irregular in thickness and was bound by a strongly osmiophilic membrane. There was a loose, acellular area of intertwined strands between the cysts wall and layer of organelles.


Paecilomycosis in a nonhuman primate (Macaca mulatta). Focal granulomas caused by fungi in the genus Paecilomyces occurred at subcutaneous and laryngeal sites in a Rhesus monkey. Slight wheezing was noted 8 months before the monkey died. Death was unexpected and was caused by asphyxiation after occlusion of the larynx by a fungal granuloma.


Paracoccidioidomycosis (South American blastomycosis) in a squirrel monkey (Saimiri sciureus). A female squirrel monkey (Saimiri sciureus) had granulomatous lesions in the liver and colon. There were many fungal organisms in sections of liver and many of these organisms had multiple buds on their surface. Although we did not prepare fungal cultures, the appearance of the organisms was sufficient to identify them as Paracoccidiodes brasiliensis, the cause of paracoccidioidomycosis (South American blastomycosis).


A morphometric study of the inhibition of autophagic degradation during restorative growth of liver cells in rats re-fed after starvation. In the parenchymal cells of the liver of adult male rats re-fed on the evening of the fifth day after a period of absolute starvation, a nearly complete absence of autophagic vacuoles (AV) has been found by the morphometric determination of the fractional cytoplasmic volume of AV. The mean value for that parameter increased only gradually during periods of re-feeding. The value was found to be in the range of the control values only on, or after, the fifth day of re-feeding. As in previous experiments, in the control animals the number of AV was again found to be dependent on a circadian rhythm with maxima during the light, and minima during the dark, periods. This rhythm reappeared in the period of re-feeding without a shift in phase. In the controls as well as in the re-fed animals the "segregated fraction" was highest for microbodies, intermediate for mitochondria and glycogen, but rather low for the remaining components of the cytoplasm. It is suggested that the long term inhibition of cellular autophagy, found in the present study, plays an important role in the restorative cellular growth of the liver during the recovery from the atrophy induced by starvation.


Gentamicin nephrotoxicity. II. Physiological, biochemical and morphological effects of prolonged administration to rats. The purpose of this investigation was to determine the morphological, physiological and biochemical effects of gentamicin upon the rat kidney following prolonged administration of the antibiotic. Sprague-Dawley and Fischer 344 strain rats were given 3, 10, 20 or 40 mg gentamicin per kg body weight per day for 28 days. Morphologic alterations were evaluated by light and electron microscopy. Functional parameters included glomerular filtration rate, PAH secretion, renal plasma flow, sodium reabsorption, potassium excretion, urine volume and protein, and serum urea nitrogen. Oxidative metabolism of mitochondrial fractions from renal cortical homogenates was evaluated by oxygen uptake and P:O ratios. The results indicate focal proximal tubular injury, decreased tubular maximum secretion of PAH, and altered oxidative metabolism at the higher dose levels of gentamicin. Neither elevations of serum urea nitrogen nor alterations in glomerular filtration rate, renal plasma flow, or sodium or potassium excretion were observed. Thus, it appears that high dose levels (40 mg per kg per day) alter the structure and function of some proximal tubular segments when administered over prolonged periods. The alterations appear reversible. Although nephro-toxicity is identified under these conditions in rats, extrapolation to human patients usually receiving much lower doses must be guarded.


The influence of adrenoceptor activity on cell proliferation in colonic crypt ipithelium and in colonic adenocarcinomata. The effects of chemical sympathectomy and of the injection of amines or amine-receptor blocking drugs on cell proliferation in colonic crypts and in dimethylhydrazine-induced colonic carcinomata is examined in rats using a stathmokinetic technique. In animals which had been chemically sympathectomized by injection of 6-hydroxydopamine cell proliferation essentially ceased in the colonic crypts but continued at a normal rate in the tumours. Stimulation of alpha-adrenoceptors by metaraminol, a drug with properties similar to noradrenaline, caused acceleration of cell proliferation in colonic crypts but not in tumours. Conversely, blockade of alpha-adrenoceptors by phentolamine inhibited cell proliferation in crypts but not in tumours. Injection of adrenaline, predominantly a beta-adrenergic agonist, inhibited cell proliferation in the tumours but not in colonic crypts whereas blockade of beta-adrenoceptors by propranolol accelerated cell proliferation in tumours but not in colonic crypts. It is postulated that cell proliferation in the crypts of Lieberkühn in rat colon resembles that in rat jejunum in being controlled by the autonomic nervous system. However, tumour cell proliferation does not appear to be subject to such regulation.


Observations on the association of annulate lamellae with vinblastine-induced paracrystals in tumour cells in vitro. Tumour cells in vitro responded to prolonged treatment with colchicine with the formation of annulate lamellae. Following the colchicine treatment, paracrystals were induced with vinblastine. A close association of annulate lamellae with vinblastine-induced crystals was observed. The hypothesis that annulate lamellae and the related unclear membrane with the pore complexes may play a role in the control of the cytoplasmic microtubule complex is discussed.


Immunofluorescent studies of epidermal protein during UV induced carcinogenesis. Previous studies with agar diffusion technique demonstrated that antibodies produced in rabbits by injection of urea extractable proteins of rat cornfied cells cross react with proteins extracted from normal epidermis of hairless mice using the same technique. In the present study we investigated by indirect immunofluorescence microscopy the immunoreactivity of epidermal proteins in normal and ultraviolet light (UVB) induced hyperplasia and malignant transformation. Reactivity to the antibody was seen over the entire epidermis of nontreated skin and hypertrophied epidermis which occurred at 6-8 weeks after initiation of UVB irradiation. However, the reactivity diminished when malignant changes took place in the epidermal cells. Almost complete disappearance of the immunoresponse was observed in squamous cell carcinoma produced by further UVB radiation. These results suggest that the reactivity of this urea extractable protein serves as an additional immunologic marker for normal epidermal cells. Alterations in the immunoreactivity parallels UVB induced carcinogenesis.


Motility of L 5222 rat leukemia cells in the flattened state. Evidence against emperipolesis. Emperipolesis is the term for the assumed penetration of living cells into other living cells. As reported earlier, L 5222 rat leukemia cells, migrating in vitro, change from a spherical to a spread configuration when they meet flat cells, and continue to move in this shape within the contours of the target cells. Whether or not this close cellular association corresponded to emperipolesis could not be determined with phase and interference contrast cinemicrography alone. In combination with transmission electron microscopy, it could be demonstrated that the compartment, in which the spread leukemia cells move, is not the cytoplasm of the target cells, but the narrow space created by the target cells and the underlying glass surface. Thus, emperipolesis could be ruled out for L 5222 leukemia cells. On this basis the reported observations on emperipolesis are reviewed, and a critical attitude regarding the occurrence of emperiopolesis in general is advocated.


Different proliferative responsiveness of fibroblasts and mesothelial cells in the rat mesentery following administration of compound 48/80 at various hours of the day. The proliferative responsiveness of fibrolasts and mesothelial cells in the mesenterial membrane of normal rats was studied quantitatively after a single i.p. injection of the mast-cell activating and histamine-releasing drug Compound 48/80. To make some allowance for a possible chronobiologic effect of the circadian type on the induced proliferation, the drug was given at 1 a.m., 9 a.m., or 5 p.m., and the animals were examined 16, 24, and 32 h later. The proliferation was estimated by cytophotometric Feulgen DNA measurements in individual fibroblast and mesothelial cell nuclei, and by mitotic frequency counting. The main result was that a larger fraction of fibroblasts than of mesothelial cells was stimulated to proliferation, regardless of the hour of treatment with Compound 48/80. It was further demonstrated that in control animals the fraction of cells of either fibroblastic or mesothelial type present in the S cum G2 cell-cycle phases varied markedly at different hours of the day. Quantitative differences appeared in the induced proliferation with regard to the hour of treatment. The most vigorous proliferative response appeared after administration of the drug at 9 a.m. The fraction of cells in the S cum G2 cell-cycle phases was then increased at 16 h and the fraction of dividing cells at 24 h after treatment, illustrating the promptness of the induced proliferative reaction.


[Acceleration of the metabolism of carcinogens in the maternal body and embryos]. Outbred mice on the 19th-21st day of pregnancy were injected intravenously 3,4-benzpyrene (BP) in the dosage of 15 mg/kg or 9,10-dimethyl-1,2-benzanthracene (DMBA) in the dosage of 40 mg/Kg in control groups, and moreover preliminary injected BP (24 hours before) in experimental groups. The BP concentration of embryos and the maternal liver 15 minutes following the injection of the basic dose of the carcinogen in increased dosage of preliminary exposure first would decrease, reach the minimum, in preliminary dosage equal to 0.75 mg/Kg, and then would increase up to values observed in control experiments with the dosage of 30 mg/Kr 7.5-15 mg/Kg, and then it would fall again in the dosage of 30 mg/Kg. The preliminary injection of BP in the dosage of 0.75 mg/Kg produced a sharp fall in the carcinogen concentration in embryos and the maternal organism during the first moment of observation (after 5 minutes), but it failed to influence the rate of subsequent decrease of the substance level. An explanation of the two effects observed is suggested based on the assumption that there exist two enzymatic systems metabolizing BP: one-premanently present in the liver and the other-induced by the carcinogen. The preliminary BP injection did not influence the concentration of DMBA.


[Simple method of determining total deoxyribonucleosides in human urine]. A method for quantitative estimation of total deoxyribonucleosides in human urine is based on the preliminary purification of urine usina ion exchange resin Dowex 1X 8 in OH- form, subsequent treatment of urine with acetone-ethynol mixture and the quantitative estimation of deoxyribonucleosides content by a microbiologic method. Urine of healthy persons contained 95.4+/-12.7 microng of deoxyribonucleosides.


[Modifying effect of DDT and of its various metabolites on the toxic effect of 7,12-dimethylbenz(alpha)anthracene]. In rats a preliminary three times injection of DDT in doses of 10 and 100 mg/Kg eliminated completely DMBA (30 mg/per 100 g of weight) lethal effect and prevented or decreased the development of adrenal necrosis. Among the metabolites under study (DDT, DDON, DDMU, DDE, DDA, DVR) DDE was found to render the strongest protective action in its single administration in a dose of 10 mg/Kg a day before the exposure to DMBA.


[Characteristics of the proteins of tooth enamel]. Three groups of proteins, distinguished by solubility in acidic and neutral media, were found in enamel. Molecular weight of the major part of proteins, insoluble at neutral pH, was about 20000; these proteins readily interacted with Ca2+, developing tri- and tetrameric molecules. High molecular enamel protein reversibly disaggregated after removing of Ca2+ by various methods. The insoluble protein had a highly regular structure. Mineralization of the protein appears to occur due to development of bonds between Ca2 and some amino acid residues.


[Mechanism of increasing the effect of antineoplastic agents by hydrazine sulfate]. The results of the in vivo and in vitro experiments indicated that hydrazine sulphate is a new potent inhibitor of the biotransformation of physiologically active compounds, including those with an antitumor effect. It is suggested that hydrazine sulphate renders an inhibitory effect by retarding the access of xenobiotics to microsomal enzymes active centers metabolizing them. The retardation of antitumor compounds biotransformation effected by hydrazine sulphate in vitro enabled the explanation of the enhanced effect of cytostatics, used in combination with hydrazine sulphate in vivo. This fact seems to speak in favour of the perspective clinical application of hydrazine sulphate for potentiation of the antitumor effect of cytostatics.


Further observations on the preparation of antiglobulin reagents reacting with c3d and c4d on red cells. A simplified method was developed for preparing rabbit red cells coated only with human C3d by the alternative pathway; these cells were injected into the donor rabbit to prepare an anti-C3d serum. Monkey red cells were sucessfully coated with human C4d, using a low-ionic-strength method, and these cells were injected into the donor monkey to prepare anti-human C4d. The reactions of these reagents were compared with those of antisera raised to complement-coated red cells by previously described methods and with those of antisera obtained by immunizing rabbits with purified soluble human C3d.


[Effect of a parenterally administered casein hydrolysate on the secretory activity of the stomach with different degrees of gastric gland denervation]. Experiments carried out on dogs helped ascertain the casein hydrolysate capable of provoking gastric secretion both with retained gastric innervation and without preservation of the vagal and sympathetic innervation. As this been shown earlier the effect of nitrous substances on the gastric secretion is realized mainly through the agency of the nervous mechanism. The observed secretion in dogs with denervated isolated pouches, however, occuring in response to administration of casein hydrolysate may be explained by mobilization of gastrin under the effect of nervous impulses and its action on the gastric glands. This assumption has been confirmed by tests carried out with the inhibitorglycomacropeptide which inhibits mainly the action of gastrin on the gastric glands.


Automated readout of sample identification and test results in a BG-8 blood grouping machine. A fully automated readout unit for the BG-8 blood-grouping machine, printing Idee identification numbers with matching ABO grouping and rhesus (D) typing results is described. In 6,737 samples, no incorrect blood group was recorded. Two rhesus (D) positive samples were overlooked, however, and 16.4% of the samples had to be retested because of irregular reaction patterns. Better results are to be expected with properly selected test cells and anti-D serum. The readout unit is easily operated and is not disturbed by clots. The additional equipment needed replaces the modules which were necessary for recording on filter paper.


[Protein-calorie deficiency and the immune processes]. The paper deals with issues that concern the influence of alimentary factors, of protein-caloric deficiency in particular, on the function of the immune system. Subject to a consecutive study was the pathogenesis of disorders in endocytosis of antigens, in humoral and cellular immunity and in reactions of hypersensitivity with proteinic deficiency. An inference is drawn to the effect that immunogenesis and a number of immune reactions are extrmely sensitive to alimentary effects and, above all, to the proteinic deficiency. Mention is also made of the fact that under certain conditions alimentary factors can direct favourably the course of a given immune process.


[Role of the thyroid gland in the effects of parenteral feeding]. In 82 albino rats with experimental thyrotoxicosis the assimilation of parenterally administered amino acid mixture of mori-amine S-2 was investigation. In thyrotoxicosis the assimilation of the amino acid mixture was found to be down. It is only a combination of mori-amine S-2 with vitamins, hormones and 6-methyluracil that facilitates the utilization of free amino acids by the  tissues (this being borne out by a falling level of aminic nitrogen in the blood, skeletal muscles, heart and liver), persistently upholds the positive nitrous balance, prevents losses of the body weight and foces down oxygen consumption.


Circadian variations in microsomal drug-metabolizing enzyme activities in rat and rabbit tissues. 1. The circadian variations in drug-metabolizing enzyme activities have been measured in microsomal fractions from the livers, lungs, and intestines of rabbits and in the livers and intestines of rats. 2. Circadian rhythms in enzyme activities in the rat intestine show 2 peaks in activity (around 0500 and 1900 h) with two intermediate troughs around 1200 and 2400 h. This twin-peaked (biphasic) profile contrasts with the single maximum and minimum in activity observed in rat liver. 3. Rabbit hepatic, pulmonary, and intestinal microsomal drug-metabolizing enzyme activities also show a biphasic profile during a 24 h period. This profile is less distinct in liver than in intestine, and less distinct in intestine than in lung. Consequently, rat and rabbit hepatic drug metabolizing enzyme activities show a considerable species difference with respect to their circadian profiles in activity.


Species differences in metabolism of tiaramide hydrochloride, a new anti-inflammatory agent. 1. Urinary excretion of the radioactivity in 24 h after oral administration of [14C]tiaramide hydrochloride was 67% of the dose in mice, 59% in rats, 41% in dogs and 74% in monkeys. 2. The serum half-lives of tiaramide after intravenous administration were approximately 0-2 h in mice, 0-8 h in rats and 0-5 h in dogs. 3. Marked species variations were noted in the composition of metabolites in the serum and urinary radioactivity. The major metabolites found were 1-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-piperazine (DETR) and 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazineacetic acid (TRAA) in mice, TRAA and 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazineethanol 1-oxide (TRNO) in rats, TRNO and tiaramide-O-glucuronide (TR-O-Glu) in dogs, and TRAA and TR-O-Glu in monkeys. 4. The binding of tiaramide to plasma protein of the various species of animals and human was about 24-34% and the extent of the binding of tiaramide to human plasma protein was independent of drug concentration within the range of 1-100 micron.


Suppression of cell-mediated immunity in experimental Chagas' disease. The effect of acute infection with the Tulahuén strain of Trypanosoma cruzi on the cellular immune response in Swiss mice was studied. Mice were immunized with either Freund's complete adjuvant or oxazolone, a skin sensitizing agent, and subsequently skin-tested with either BCG protoplasm or oxazolone to detect delayed hypersensitivity. Depression of the response to these antigens was observed in infected mice during the stage of marked parasitemia. Mice which were responsive to oxazolone before infection lost their ability to respond as the infection progressed. When immunized with live attenuated T. cruzi before infection with virulent organisms, mice developed a greater than normal sensitivity to oxazolone and survived infection. These experiments do not conclude whether immunosuppression due to infection with T. cruzi is directed toward induction or expression of the cell-mediated immune response to the antigens employed.


Polymorphism of the third component (C3) of complement and of Transferrin (Tf) in Belgium. The phenotypes of C3 and of Tf were determined in 818 and 576, respectively, unrelated individuals living in Liege. The gene frequencies observed are: (formula: see text) The application to disputed paternity cases and to the study of twins is discussed.


[State control of human (immunoglobulin anti-D (Rho)]. Principles governing the state control of Anti-D(RHo) Immunoglobulin, the requirements for the quality and the results obtained by testing 105 batches are outlined and discussed.


[Detection of Bacillus cereus-toxins (author's transl)]. During the logarithmic state of growth, B. cereus produced extracellular toxins, which could be precipitated by ammoniumsulphate. The toxins were not dialysable. 9 strains of B. cereus were tested and showed lethal, hemolytic, and phospholipase-C-reactions. The lethal toxin injected i.v., killed mice within 20 minutes. An intradermal injection of the 9 toxin-precipitates in rabbits produced skin reactions, which could be neutralized by a specific antiserum against the B. cereus strain B-4ac. Relatively high doses (50 mg/ml) of the toxin caused fluid accumulation after injection in ligated loops of rabbit gut (Tab). The hemolysin of the tested B. cereus strains was found to be thermolabile. The phospholipase-C activity withstood the temperature of 55 degrees C for a period of 10 minutes. The prepared specific antiserum, which inhibited the phsopholipase-C activity totally, had no effect on the hemolysis. Intradermal and enteropathogenic activities point to the presence of an enterotoxin. For detection of the enterotoxin, the skin-test in guinea pigs or rabbits seems to be most appropriate.


Serodiagnostic value of extracellular antigens of an actively proteolysing culture of Candida albicans (immunodiffusion-test). Cell-free, dialysed and concentrated culture filtrate of a Candida albicans strain, after proteolysis in serum-protein medium (bovine albumine), and after growth in Sabouraud glucose broth (for comparison) were used as antigens for the detection of precipitating antibodies in 558 samples of serum originating from defined groups of patients and healthy persons serving as controls. The differing distribution of antibodies against these two antigens as observed in the various groups of our patients calls for further studies of such antigens on the basis of proteolysis within the serodiagnostics of Candida albicans-mycoses.


[The phototoxic activity of carcinogenic polycyclic hydrocarbons and their degradation products in the biological test (author's transl)]. The phototoxic activity of carcinogenic polycyclic hydrocarbons was evaluated using ciliates of the species Tetrahymena pyriformis maintained in sterile, semisynthetic media. This ciliate-light-test was developed into and standardized for a rapid microbiological assay of carcinogenic activity of polycyclic aromatic hydrocarbons. --In this fashion, six polycyclic aromatic compounds with differing carcinogenic activities were tested:benzo(a)-pyrene, benzo(b)fluoranthene, indeno(1,2,3-c,d)pyrene, benzo(a)anthracene, fluoranthene, and cyclopenteno (c,d)pyrene. An essential parallelism between phototoxic and carcinogenic activities, resp., was clearly obvious. --The combined effects of benzo(a)pyrene and fluoride ions was also investigated using the ciliate-light-test. Fluoride ions in the concentration of 1 ppm did not affect the phototoxicity of benzo(a)pyrene, suggesting that fluorides possess no cocarcinogenic activities. --Degradation products of benzo(a)pyrene obtained by UV-irradiation (mixtures of quinones) were also tested for phototoxic activity. It could be shown that such degradation products entirely free from benzo(a)pyrene still possessed 50% of the activity of the original, non-irradiated solution. This is taken to indicate that the degradation products products resulting of UV-irradiation may still retain a measure of carcinogenic activity, --a finding of considerable importance from the viewpoint of environmental hygiene.


[Preliminary tests of the influence of wastewaters from sugar-factories upon the numbers of intestinal bacteria in water (author's transl)]. This work presents the results of experiments dealing with the influence of wastewaters from 2 sugar factories in the Czechoslovakia upon some representatives of intestinal bacteria: E. coli, C. feundii, E. aerogenes, S. anatum, S. schottmuelleri, S. typhi-murium, Sh. sonnei and Str. faecalis. The experiments were carried out at 30, 20 and 10 degrees C. The experiments have shown that the presterilized waste-water from sugar factory (in Bohemia and in Slovakia) caused rapid multiplication of the test-organisms: E. coli, C. freundii, E. aerogenes, S. anatum, S. schottmuelleri, S. typhi-murium, less by Sh. sonnei and Str. faecalis, at 30, 20 and 10 degrees C. The intensity of multiplication was direct proportional to the concentration of waste water and was effective to dilution 1:1000 (diluted with presterilized surface waters Vltava, Danube).


Blood poisonings at slaughter and their consequences. Contamination of pig blood by Str. faecium and P. fluorescens realized either through the bleeding knife or through intravenous injection. Bacterial counts made in the organs and muscles showed a large contamination of the organs and a smaller contamination of the muscles. In the case where Str. faecium and P. fluorescens were injected into the blood circulation, only Str. faecium could be re-isolated in muscles and organs. Study of the bactericidal activity of total blood and plasma showed a marked antimicrobial activity against P. fluorescens and a slightly activity against Str. faecium.


Homologous radioimmunoassay for canine prolactin. A homologous double antibody radioimmunoassay has been developed for canine prolactin. Purified canine prolactin was iodinated by lactoperoxidase/H2O2 to an average of 101 "+/- 10.1 muCi/microgram. Antiserum was used at a final dilution of 1:80 000 and at this concentration bound approximately 20% of the added tracer in the absence of competing unlabelled prolactin. Partial cross-reaction was observed with ovine and bovine prolactin but there was no cross-reaction with a highly purified canine growth hormone preparation. Dilutions of pregnant and lactating bitch sera were parallel to the purified canine prolactin standard curve. Mean prolactin levels in normal male and anoestrous females were 8.8 +/- 0.8 and 12.6 +/- 2.6 ng/ml, respectively. Thyrotrophin-releasing hormone (TRH) induced a consistent elevation in prolactin levels 15--30 min after intravenous injection.


Effect of prolonged oral administration of TRH on plasma levels of thyrotrophin and prolactin in normal individuals and in patients with primary hypothyroidism. Forty mg TRH/day was given orally for 3 weeks to 10 euthyroid women and 10 women with primary hypothyroidism on low replacement doses of thyroxine. Once weekly oral TRH was replaced by an iv TRH-test (0.4 mg) with measurement of serum concentration of TSH, prolactin (PRL), thyroxine (T4), triiodothyronine (T3) and cholesterol. In the normal group, mean serum T4 concentration increased after one week and remained elevated. Serum TSH concentration showed a slight tendency to decline. Maximal rise in TSH concentration after iv TRH (deltaTSH) fell from a mean of 4.0 ng/ml to 1.4 ng/ml within one week and stayed low. T3, cholesterol, PRL and deltaprl were normal and unchanged throughout. In the hypothyroid group T4, T3, cholesterol, PRL and deltaPRL were not influenced by the TRH administration. In 2 patients (with the highest serum T4 concentrations) serum TSH concentration was normal and resistant to iv TRH. Of the 8 patients with elevated TSH, basal level and deltaTSH did not change in 2 (with subnormal T4 levels and the highest TSH levels). In the other 6 (with intermediate T4 levels) basal TSH fell from a mean of 10.1 ng/ml to 4.2 ng/ml, and deltaTSH from 10.0 ng/ml to 3.3 ng/ml after three weeks. It is concluded that in addition to feed-back effect of thyroid hormones, the pituitary response to long-term administration of TRH is determined by other factors. Among these may be reduced pituitary TRH receptor capacity and the activity of the TSH producing cells.


Lymphocyte reactivity in healthy subjects and cancer patients. Lymphocytes of 40 cancer patients with solid tumors as well as of 40 normal subjects were stimulated by phytohemagglutinin (PHA), purified protein derivative (PPD), streptokinase-streptodornase (SK-SD) and candidin (Cand) and the extent of their stimulation was expressed by the index of reactivity. The cumulative frequency distribution of reactivity indices was significantly higher in normal individuals than in cancer patients. The highest extent of information relevant to the discrimination between patients and normal subjects is obtained following stimulation of lymphocytes with Cand and in decreasing order with PPD, SK-SD and PHA. The percentage of normal subjects and patients having reactive lymphocytes was found to be the highest following stimulation with PHA, lower with PPD and the lowest to Cand and SK-SD. The importance of using increasing numbers of stimulants to achieve maximal detection of lymphocyte reactivity is documented and discussed.


Acquired pyruvate kinase deficiency with hemolysis in preleukemia. Acquired erythrocyte pyruvate kinase deficiency may appear as a symptom secondary to various hematologic disorders, e.g. acute leukemia, sideroblastic anemia, polycythemia vera. The case of a 68-year-old patient with PK deficiency (1.75 U/g Hb) and severe hemolytic anemia is presented, who 1 year later showed acute myeloid leukemia. It is considered that a dialysable inhibiting factor may play a pathogenetic role in this enzyme change since enzyme activity was raised by dialysis. A survey of the literature is presented.


Anti-gamma-globulin activity, DNA and antibodies to DNA in nonlupoind cryoglobulinemias. Anti-gamma-globulin activity, free DNA, and DNA binding were studied in 19 cryoglobulinemias: 8 patients with Waldenström's disease (WD), 9 patients with essential cryoglobulinemia (EC), and 2 with chronic aggressive hepatitis (CAH). Antihuman gamma-globulin activity was detected in all sera and dissolved cryoprecipitates but two from EC and one from the CAH group. By diphenylamine assay we found DNA in two sera from WD and in one serum and cryoprecipitate from EC. An antibody to denaturated DNA was shown only in sera from the two patients with CAH and from one patient with EC. Nonspecific binding was more frequent.


Combined G-6PD and 6-PGD deficiency in a Hindu boy. A case of drug-induced haemolytic anaemia due to G-6PD deficiency is documented because of the associated asymptomatic 6-PGD deficiency--a combination probably reported only once before. Our studies of the patient's family suggest that 6-PGD deficiency is inherited through a simple autosomal dominant gene.


Pyridoxal-5-phosphate-resistant sideroblastic anaemia with trisomy 8 mosaicism in the bone marrow. A patient with sideroblastic anaemia manifested a trisomic condition for chromosome number 8 in 75% of his bone marrow cells. Cytogenetic studies of peripheral lymphocytes demonstrated a normal male karyotype. The anaemia was resistant to treatment with pyridoxal-5-phosphate; this is in contradiction with the response achieved in some patients with the primary acquired form of sideroblastic anaemia.


A case of lambda type tetramer Bence-Jones proteinemia. A 50-year-old woman was found to have an extramedullary plasmacytoma of the thoracic vertebrae and a bone marrow plasmacytosis of 72%. In the serum of this myeloma patient, M-bow percipitin line was seen only with anti-lambda chain serum, but not with antisera against mu, alpha, gamma, delta, ipsilon and kappa chains. Gel filtration of the serum on the Sephadex G-200 column demonstrated the monoclonal lambda chain in the A-fraction along with transferrin and suggests a molecular weight of 88,000 and a tetrameric light chain. Bence-Jones protein has never been detected in the patient's urine.


Biochemical studies of isolated rat hepatocytes from normal and phenobarbital-treated liver as obtained by rate zonal centrifugation. Cell suspensions from normal and phenobarbital treated livers were analysed by rate zonal centrifugation in ficoll gradients. No difference in the microsomal cytochrome P-450 and NADPH-cytochrome C reductase content and in the incorporation rate of radioactive leucine was noted between light and heavy hepatocytes. After centrifugation of a mixture of radioactive phenobarbital-treated cells and normal liver cells, the specific radioactivity was constant, indicating that the hepatocytes from drug-treated liver had the same density as the normal cells.


A comparative study of the urinary bladder and the intramural portion of the ureter. The bladder belonging to eleven mammalian species were investigated, and as a result the following observations were made: (1) a submucous ureter was found in the case of most of the species examined; (2) histological investigation revealed three types of intramural ureters, and (3) downward extension of ureteric musculature, separate from bladder musculature, to the seminal colliculus in the male, or to the lower end of the urethra in the female, was found. A suggestion is presented to explain the manner by which the ureteric openings change their relations to those of the mesonephric ducts development. It seems that 'after absorption of the common segment of the Wolffian duct, breaking down of the ventral wall of ureter' is the most likely process.


Measurements on the kidneys and vasa recta of various mammals in relation to urine concentrating capacity. Maximum urine-concentrating capacity (UCC) differs widely among mammals of different species, being very high in some desert species (e.g. kangaroo rats) and very low in freshwater acquatic species (e.g. beaver). In this study, kidneys of 21 species of mammals from widely different habitats were studied in histological sections to determine whether differences in UCC can be attributed to differences in kidney structure. Parameters studied included the ratio of medullary to cortical thickness, the proportional subdivision of the medulla into inner and outer zones, and the dimensions of the vasa recta expressed in terms of the total area and the number of lumens within the vascular bundles. Determinations were made at a level where the size of individual vasa recta bundles has reached a constant maximum size, i.e. in the distal half of the outer zone. A positive correlation was found between the UCC and the ratio of medullary length to cortical thickness. No clear correlation existed between the proportion of the medullary length comprised of outer or inner zones and the UCC, although a trend to higher UCC in animals with relatively longer inner zones was apparent. Thus, it appears that the relative length of the entire medullary region is a major factor determining UCC, but the length of individual medullary zones is of lesser importance. A correlation was also found between the density of vasa recta per cubic millimeter of medullary tissue (the number of lumens regardless of identify in bundles, based on the number counted at the level sampled) and the UCC of the species. Data reported here support the view that UCC can be correlated with two parameters of kidney structure - the length of medulla relative to that of cortex and the density of vasa recta within the outer zone. It is proposed that the anatomical characteristics of the vascular supply to the medulla - that is, the vasa recta - are equally as important for the concentration of urine as is the primary mechanism determined by the characteristics of the loop of Henle and collecting ducts.


Inhibition of the synthesis of phospholipase C in Bacillus cereus by a component of the growth medium. A low molecular weight compound, probably of peptide nature, present in the Beef Heart Extract component of the growth medium, inhibits post-transcriptionally the biosynthesis of phospholipase C by a strain of Bacillus cereus. The compound also prevents the increase of proteolytic activity in the growth medium, thus suggesting that the synthesis of another enzyme, an extracellular protease, is also inhibited, and that the inhibitory compound may therefore have a more general effect on exoenzyme synthesis in this strain of Bacillus cereus.


Methodological aspects of an agar plate technique for determination of biologically active 5-fluorouracil in blood, urine and bile. A microbiological agar plate technique for estimation of 5-fluorouracil concentrations in blood, urine and bile from man, dog and pig was evaluated. Different bacterial test strains, media modifications and techniques for inoculation were studied. The strain Streptococcus faecalis ATCC 8043, recommended previously by Clarkson et al., was found to be the most suitable. The influence of prediffusion, dilution, antibiotics and chemotherapeutic agents and their antagonists, as well as the effect of storage of samples containing 5-fluorouracil were examined. A detailed methodological description is presented. The method seems to be sufficiently sensitive and practical for routine determination of cytotoxic compounds from 5-fluorouracil in serum, plasma and urine.


Glycogen synthetase and phosphorylase activity in slow and fast twitch skeletal muscle fibres in man. Glycogen synthetase (I + D) and  phosphorylase (à + b) activity was determined in human skeletal muscle biopsies with different muscle fibre composition and in dissected an pooled batches of the two main muscle fibre types: slow twitch (ST) and fast twitch (FT), respectively. Glycogen synthetase (I + D) activity remained unchanged as the per cent of FT fibres increased, but phosphoyrlase (à + b) activity was found to increase. A similar activity pattern was found in dissected and FT fibres as compared to ST fibres, i.e. the same glycogen synthetase activity but heightened phosphoyrlase activity.


Interaction of nutrition and infection in the hospital setting. A substantial portion of hospitalized patients suffer from protein-calorie malnutrition acquired as a result of their illness, their semistarvation dietary regimens, or the combination of both insults together. When energy needs are not met by the diet, the deficient calories must come from body stores, muscle, or visceral protein and fat. The status of these stores can be assessed clinically by easily performed measurements. In adult kwashiorkor-like syndromes, the insulin response to the combined stimulus of catabolic stress and carbohydrate feedings reduces the mobilization of fat and protein stores. In adult marasmus there is hypoaminoacidemia and loss of skeletal muscle. Both forms of malnutrition have a profound impact on immune function. Nutritional support should be given preeminent consideration as an additional necessary form of these patients.


Magnitude of the host nutritional responses to infection. This review describes the scope, complexity, and magnitude of host nutritional responses throughout the course of an infectious process. These responses include prominent changes in nitrogen and protein metabolism, altered rates of carbohydrate and lipid production and utilization, and changes in mineral, electrolyte, trace element, and vitamin metabolism. It is postulated that these responses develop in a relatively predictable sequence which is influenced by the adequacy of host antimicrobial defense mechanisms, the severity and duration of illness, and specific localization of an infectious process within the body. In addition to hormonal regulatory effects, the metabolic and nutritional responses of the host are also influenced by biologically active substances released when host cells participate in phagocytic activity and local inflammatory responses.


The relationship between dietary intake, weight change, nitrogen balance, and protein turnover in man. We have examined the relationships between protein turnover, protein synthesis, and protein breakdown and dietary intake, weight change, and nitrogen balance in children who were recovering and had recovered from severe protein-energy-malnutrition. Protein metabolism was measured by giving [15N]glycine and measuring the enrichment of urinary urea. The level of dietary protein did not affect protein metabolism. There were highly significant correlations between both protein flux and protein synthesis and the ad libitum dietary intake, nitrogen balance, and weight change. Over the range of dietary intake, 60 to 270 cal/kg per day, the protein synthesis rate increased 5-fold. Large changes in dietary intake resulted in small changes in protein breakdown, with breakdown being least on an inadequate intake. Changes in the rate of protein breakdown did not contribute to changes in nitrogen balance or body weight.


Use of specific fluorescent antibodies for the identification of hemoglobin C in erythrocytes. Antibodies against hemoglobulin C (alpha2beta2 6Glu leads to Lys) were produced by immunizing horses and were purified by affinity chromatography. As expected from the bivalency of both the antibody and the antigen, the purified antibodies failed to produce immunoprecipitates upon reaction with the corresponding antigens. Identification of hemoglobin C in individual erythrocytes was achieved by reacting the fluorescein isothiocyanate-conjugated antibodies with the hemoglobin antigen in fixed smears of peripheral blood. Red cells from persons having a hemoglobin C gene were labeled strongly upon reaction with anti-Hb C-FITC; there was no labeling of red cells containing normal hemoglobins or Hb S, suggesting that the anti-Hb C antibodies recognize only the amino-terminal segment of the beta chains that contain lysine in position beta6.


Drug therapy reviews: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics--part 4: aminoglycosides. The aminoglycoside antibiotics are reviewed with regard to mechanism of action, bacterial resistance, antimicrobial spectrum, combinations with other agents, pharmacology, dosages in patients with normal and impaired renal function, adverse reactions, therapeutic use, prophylatic use and selection. Streptomycin is suggested in the therapy of tuberculosis, brucellosis, tularemia and yersinia infections; several of these require the coadministration of another agent. The choice between streptomycin and gentamicin for combination therapy of enterococcal endocarditis may be simplified by knowledge of the prevalence of high-level streptomycin-resistant strains in the hospital or by use of an in vitro screening test. Neomycin is the agent used orally in the treatment of hepatic encephalopathy. Paromomycin is indicated only for the treatment of amebic infections. The major difference among gentamicin, tobramycin and amikacin lies in the low but increasing prevalence of gram-negative bacilli which are resistant to gentamicin and tobramycin and susceptible to amikacin. In those institutions in which gentamicin-resistant strains are of concern, amikacin is the aminoglycoside of choice in high-risk patients until the infecting bacterium has been determined.


Pathogenesis of acute pelvic inflammatory disease: role of contraception and other risk factors. In a case-control study of matched pairs, the risk of acute pelvic inflammatory disease (PID) was 4.4 times higher in intrauterine contraceptive device (IUD) users than in nonusers (p less than 0.001). Of approximately 500,000 cases of acute PID occurring annually in the United States, an estimated 110,000 are attributable to IUD's, costing over forty-four million dollars per year. PID was attributable to the IUD in 77 per cent of IUD users. No particular type of IUD was implicated. The relative risk of acute PID in IUD users over nonusers was higher in nulligravid women than in previously pregnant women and was directly related to socioeconomic status (SES), but the total annual risk of PID in IUD users appear inversely related to SES. IUD use significantly increased the risk of nongonococcal PID. Fever occurred in 13 (21 per cent) of 61 IUD users and 59 (41 per cent) of 143 nonusers (p less than 0.025). Among women with nongonococcal PID, and adnexal mass greater than or equal to 6 cm. was noted in 14 (40 per cent) of 35 IUD users and in only 12 (15 per cent) of 78 nonusers (p less than 0.01). An increased risk of gonococcal PID was found among non-Caucasians and women not using contraception, while the risk of nongonococcal PID was increased among women with a past history of gonorrhea. Oral contraceptive use may protect women with gonorrhea from developing PID. Menstruation precipitates the onset of symptoms of gonococcal PID.


Late decelerations and brain tolerance of the fetal monkey to intrapartum asphyxia. Eight monkey fetuses near term were subjected to regulated asphyxia during labor by mechanically constricting the maternal abdominal aorta and diminishing blood flow to the uterus. A magnitude of asphyxia was produced and maintained for an initial three hours that was close to but not sufficient to elicit late decelerations. The asphyxia was then augmented during a fourth hour to cause late decelerations of magnitudes of 5 to 15 per cent of the initial heart rate. After termination of the fourth hour of asphyxia, the fetuses were delivered by hysterotomy and provided intensive care. During the three to nine months of survival after birth, all animals were neurologically intact; on necropsy the brains were free of pathologic changes both grossly and microscopically. These results support the thesis that fetal heart rate monitoring during labor exhibits a sensitivity sufficient to diagnose asphyxia of the fetus of clinical significance before it reaches a magnitude that may cause permanent neurological injury. The results are particularly pertinent to those clinical circumstances where the decreases in intervillous space blood flow brought about by uterine contractions are accentuated due to low maternal blood pressure.


Fluorescein pattern of the choriocapillaris in the neonatal rhesus monkey. Seven neonatal rhesus monkeys were studied by serial fundus photography and fluorescein angiography at weekly intervals during the first 12 weeks of life. The neonatal rhesus showed little pigmentation of the fundus during the first six weeks of life. The fluorescein angiograms showed a definite sequential as well as segmental filling pattern at the level of the choriocapillaris. This filling pattern was based on individual units called lobules. In addition there was a segmental flow in the macula; that is, the nasal macula filled before the temporal macula.


Light microscopic quantitation of the endothelial vacuoles in Schlemm's canal. Twelve rhesus monkeys were used for an experiment in which intraocular pressure was maintained at various levels between 0 and 50 mm Hg for one hour. A quantitative light microscopic analysis was made of the changes in the vacuolation of the endothelium lining Schlemm's canal. At 0 mm Hg, giant vacuoles were not found; at 8 mm Hg the counts of vacuoles were significantly lower than the corresponding 15 mm Hg controls; at 22 and 30 mm Hg the counts were significantly higher than the 15 mm Hg counts; and at 50 mm Hg 71 counts of vacuoles were less than at 22 and 30 mm Hg. Within the range of 8 to 30 mm Hg, change in pressure was shown to produce alterations in both vacuole numbers and their dimensions. The number of vacuoles increased linearly with increase in pressure, whereas mean vacuolar volume increased in a nonlinear manner.


Cutaneous vascular fibrinolytic activity in the local Shwartzman reaction. A fibrin slide test was utilized to study cutaneous vascular plasminogen activator activity in normal rabbit, rat, monkey, and human skin and in rabbit skin following development of the local Shwartzman reaction and after substituting epsilon-aminocaproic acid for the preparatory injection of endotoxin in the local Shwartzman reaction. Cutaneous vascular plasminogen activator activity was also studied in rats after attempted induction of the local Shwartzman reaction following inhibition of fibrinolysis with epsilon-aminocaproic acid and/or pregnancy. Plasminogen activator activity was detected in vessels of normal rat, monkey, and human skin but was absent in skin from normal rabbits and rabbits with the local Shwartzman reaction. Intradermal injection of epsilon-aminocaproic acid failed to prepare for the local Shwartzman reaction. In the rat, which has greater cutaneous vascular plasminogen activator activity than the rabbit, inhibition of vascular activator with epsilon-aminocaproic acid and/or pregnancy failed to prepare for the local Shwartzman reaction. These studies indicate that although the markedly diminished level of cutaneous vascular plasminogen activator in the rabbit may be important in the pathogenesis of the local Shwatzman reaction, factors other than inhibition of fibrinolysis are also necessary for preparation of the reaction.


Clinical conditions associated with defective polymorphonuclear leukocyte chemotaxis. Impressive numbers of clinical conditions are associated with defective leukocyte chemotaxis. In many, this cellular dysfunction is associated with other abnormalities of the immune response, but in others abnormal chemotactic responsiveness of leukocytes is the only abnormality of function identified in the laboratory. Patients are usually selected for study because of unusually severe, recurrent infections or poor response to antimicrobial agents, and therefore a frequent association between abnormality of chemotaxis and infection would be expected. Many patients demonstrate abnormal chemotaxis during remissions as well as during infections, and there seems little doubt that abnormality of chemotaxis is related to susceptibility to infections. Partial classification of disorders of chemotaxis was attempted. Major abnormalities are found when there is a primary cellular disorder or cell-directed inhibitors of chemotaxis are found. Less marked abnormalities are found when chemotactic factors are deficient.


What is quality care? A clinician's view. The prospect of national health insurance means the establishment of government criteria for reimbursable psychiatric treatment. These cost-control standards are certain to be justified on the basis of quality maintenance as well. Such preestablished criteria would not only fail to insure quality, they would likely undermine it. Steps toward an urgently needed definition of "quality treatment" are considered.


Split-line patterns of the mandible following masseterectomy in adult and growing monkeys. Architectural changes of the mandibular ramus following masseterectomy were analyzed by means of the split-line technique in both adult and growing monkeys. The right masseter muscle was resected in ten tufted capuchin monkeys (Cebus apella) and they were sacrificed following a 12-month period. Along with modifications in the shape of the mandible, the masseterectomy induced structural changes as revealed by alterations in the split-line patterns. These changes were much more evident in the adult animals. In growing monkeys, intrinsic forces determine an architecture of mandibular growth, represented by the direction of the splits. This is not influenced by the lack of mechanical factors like muscle action. Conversely, the final fibrous architecture of the bone in the adult monkey may be modified by extrinsic mechanical factors.


Condylar translation and the function of the superficial masseter muscle in the rhesus monkey (M. mulatta). The relationship between translation of the mandibular condyle during symmetrical mandibular rotation, i.e., symmetrical jaw depression and elevation, and the function of the superficial masseter muscle was examined in light of relative torque and the length-tension relationship for muscle. Lateral cephalograms of live adult rhesus monkeys (Macaca mulatta) were analyzed using two models: (1) Model A, normal symmetrical jaw rotation accompanied by condylar translation; and (2) Model B, mandibular rotation about an axis fixed at the position of the condyles during centric occlusion. The decrease in relative torque and the excursion of the superficial masseter at mouth-open positions are significantly greater in Model B than in Model A. Symmetrical rotation of the jaw about a fixed axis would result in a 35% greater loss of maximum producible tension at maximum gape than rotation associated with condylar translation. These results suggest that condylar translation during mandibular depression and elevation functions to minimize reduction in relative torque and excursion of superficial masseter muscle, thereby maintaining optimal potential for exerting maximum tension during jaw closure.


Serum total and free thyroxine and triiodothyronine during dynamic muscular exercise in man. The effect of strenuous dynamic muscular exercise on serum-free thyroxine (FT4) and free triiodothyronine (FT3) concentrations has been studied in 10 healthy subjects. In the course of 7.8-19 min of treadmill exercise (protocol of R. A. Bruce), the group showed a mean increase in serum albumin concentration of 11.4% (P less than 0.01). Five subjects demonstrated an increase in FT4 concentrations (x = +54%) and five showed decreased FT4 (x = -36%). The difference in FT4 concentrations was accounted for primarily by acute alterations in dialyzable fraction T4 (DFT4) rather than total serum T4. Mean changes in DFT4 were statistically significant (P less than 0.02) when increased FT4 and decreased FT4 groups were compared. Acute exercise was accompanied by a 9% decrease in dialyzable fraction T3 (DFT3) (P less than 0.02) in the 10 subjects, but the concomitant decrease in FT3 concentration was not significant. Changes in DFT4 and DFT3 and FT4 and FT3 concentrations were not correlated. Trends in double product (heart rate times blood pressure) with maximal exercise and in double-product recovery after exercise suggested that increased FT4 concentrations developed in subjects who were physically better trained.


Cerebral circulation: effect of stimulation and blockade of dopamine receptors. The effects of stimulation and blockade of dopaminergic receptors on cerebral blood flow and metabolism were investigated in 15 anesthetized baboons. The intravenous administration of apomorphine resulted in immediate, dose-dependent increases in cerebral blood flow (increased by 58% following 0.1 mg/kg apomorphine) which were always accompanied by increases in cerebral oxygen consumption (increased by 36% with 0.1 mg/kg) and glucose uptake (increased by 72% with 0.1 mg/kg). It is suggested that the primary action of apomorphine is on cerebral metabolism and secondarily on cerebral blood flow rather than directly on cerebral vascular smooth muscle. Pimozide, at doses that totally blocked apomorphine-induced increases, was without effect on cerebral blood flow and metabolism. The dilatatory response of the cerebral circulation to hypercapnia was preserved during dopamine-receptor blockade. The basal level of overall cerebral metabolism and hemispheric cerebral blood flow does not appear to be dependent to any large extent on the activity of the dopaminergic pathways in the central nervous system.


Utilization of former military medical corpsmen in the provision of jail health services. In an effort to improve the quality of health services within a large urban jail, former military medical corpsmen have been employed as an integral component of a jail health service. Medical corpsmen are responsible for the performance of intake medical evaluations, delivery of prescription medications, triage for physician sick call, and provision of elementary health services on the jail tiers. Utilization of medical corpsmen has been associated with improved rates of medication delivery as well as beneficial effects in relation to tuberculosis and venereal disease control, and a more appropriate utilization of physician services. Effective utilization of medical corpsmen requires cooperation from the correctional staff as well as consistent supervision and support by qualified physicians.


Differences in the virulence of Plasmodium knowlesi for Macaca irus (fascicularis) of Philippine and Malayan origins. This report summarizes the results of a comparative study of the virulence of the "S-M," H, and C strains of P. knowlesi for Indian rhesus monkeys (Macaca mulatta) and cynomolgus monkeys [M. irus (fascicularis)] of Malayan (West Malaysia) and Philippine origins. Each of the above strains produced fulminating, uniformly fatal infections in the rhesus monkey and mild, chronic infections, characterized by relatively low level parasitemias in cynomolgus monkeys of Philippine origin. In striking contrast, the H and C strains produced infections in cynomolgus monkeys of Malayan origin which were indistinguishable in severity from infections produced in M. mulatta. The circumstances of the study precluded evaluation of the virulence of the "S-M" strain for M. irus of Malayan origin. Even so, the available data make it necessary to qualify the long-held belief that infections with P. knowlesi in M. irus invariably follow a benign course.


Search for Trypanosoma rangeli in endemic areas of Trypanosoma cruzi in Argentina and Brazil. Because the presence of Trypanosoma rangeli in Argentina and Brazil has not been confirmed, a serach was carried out in man and triatomine insects. Fifty-nine of 207 persons (28.5%) were infected when studied with one or more xenodiagnosis (40 Triatoma infestans/xenodiagnosis); 0.1% to 13% of 7,821 bugs' feces and 4% of 875 dissected midguts showed T. cruzi in Giemsa stained smears. One of 6,980 hemolymph samples and 1/875 salivary glands showed few flagellates which may have originated in the gut. They were not found in stained smears. Thirteen percent of 188 wild-caught domiciliary T. infestans showed only T. cruzi in the gut and feces. Although the presence of T. rangeli could not be demonstrated, the study indicates that examination of pooled hemolymph and random samples of salivary glands and midguts can be carried out together iwth the usual examination of extracted feces in any species of triatomine, including those with salivary glands lacking the pink color present in the genus Rhodnius. Unless this procedure is widely used it will not be possible to differentiate T. rangeli and other possible trypanosome infections from those of T. cruzi nor to determine, therefore, the true prevalence of Chagas' disease in a given human population.


Anaesthetic considerations on von Recklinghausen's disease (multiple neurofibromatosis). Abnormal response to muscle relaxants. Two cases of abnormal response to muscle relaxants in patients with von Recklinghausen's disease are reported and the literature is reviewed. A 31 year-old female showed high sensitivity to both suxamethonium and tubocurarine, and 57 year-old male showed also high sensitivity to tubocurarine. Anaesthetic problems which might be encountered in patients with von Recklinghausen's disease are concomitant phaeochromocytoma, renal hypertension, kyphoscoliosis, deformity of the spine, and intralaryngeal neurofibroma.


Oral cromolyn therapy in patients with food allergy: a preliminary report. In a preliminary double-blind, placebo controlled, crossover study, 10 out of 16 patients (62.5%) had remissions in acute symptoms of food allergy with oral cromolyn therapy. The effective dosage for each patient had to be sought individually. No serious side effects were encountered.


Cromolyn sodium, five to six years later. Ninety-five children with difficult to treat asthma were given cromolyn in double-blind, crossover studies. Of these, 70 were studied for the next five to six years by open trial cromolyn prophylaxis to determine decreasing dependency on bronchodilators or corticosteroids. Evaluated at two-month intervals, 28 children required prednisone and bronchodilators, 37 required round-the-clock bronchodilators only and five required neither. Peak expiratory flow rates were below 80% of predicted normal in eight patients, the remaining 62 showed reversibility of airways obstruction. Exercise-induced asthma was reported by 44 during the first two years but persistent improvement in exercise tolerance occurred in 24 patients. IgE specific RAST indicated a continuing extrinsic element in the etiology of 38 of 45 patients tested. Cromolyn was an effective prophylaxis for children with chronic asthma; however, it was difficult to evaluate in 17 steroid-dependent subjects. Attempts to reduce the need for and especially to discontinue steroids were not as successful as other reports indicate.


Demonstration of organ-characteristic glycoproteins in human semen. Tridacnin M, a galactosyl-specific reagent prepared from the bivalve clam Tridacna maxima (Röding) was used for the demonstration of 2 different glycosubstances with terminal galactosido units in human semen. The results obtained by immunodiffusion tests indicate that the seminal plasma contains a water-soluble glycoprotein with two carbohydrate chains, one of them having a terminal beta-galatosyl group whereas the other one seems to have a terminal N-acetyl-neuraminic acid group and a subterminal beta-galactosyl group. This glycoprotein is a secretion product of the seminal vesicles and, therefore, of diagnostic significance: it is absent in cases of bilateral occlusion of the ampullae. Another glycosubstance with terminal galactosido-residues could be demonstrated on the surface of sperm cells by agglutination reactions. This glycosubstance is an integral part of the spermatozoan membrane because it cannot be removed by repeated washings.


Insecticidal activity of propoxur- and carbaryl-impregnated flea collars against Ctenocephalides felis. Ten dogs were fitted with 10% propoxur-(0-isopropoxyphenyl methylcarbamate) and 10 dogs were fitted with 16% carbaryl-(1-naphthyl-N-methylcarbamate) impregnated flea collars. Ten cats were fitted with carbaryl-impregnated flea collars. There were 5 control animal for each trial. Insecticidal activity against experimental infestations with the cat flea (Ctenocephalides felis) was evaluated. The propoxur collars on dogs reduced the flea populations by 90% within 2 days of infestation for at least 13 weeks. By the 16th week, the flea population was reduced 65% in 2 days and 87% in 7 days. In subsequent infestations, efficiency was less than 80% after 7 days. Carbaryl collars on dogs reduced the flea population by as much as 80% in 2 days for a period of 16 weeks. An efficiency of at least 80% at 7 days was maintaned for 17 weeks. Carbaryl collars on cats reduced the flea population within 2 days by 80% or more for a period of at least 19 weeks--the last experimental infestation.


Effect of aerosol immunization with RE 595 Salmonella minnesota on lung bactericidal activity against Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa. Intrapulmonary bactericidal activity was measured after mice were given 3 weekly aerosol exposures to acid-hydrolyzed Re 595 Salmonella minnesota. Ten days after their last immunization, mice were challenged with aerolized Serratia marcescens, Enterobacter cloacae, or Pseudomonas aeruginosa. Quantitative bacterial counts in ground lung were obtained immediately after exposure and again 4 hours later. Enhanced bactericidal activity against Serratia marcescens and Enterobacter cloacae was seen in immunized animals, whereas no difference with Pseudomonas aeruginosa was noted. In separate studies, immunization with Serratia marcescens yielded a similar enhancement of lung bactericidal activity. Mucociliary transport, as measured by disappearance of aerosolized Serratia marcescens labeled with phosphorus-32, was identical for both immunized and control animals. Using a standardized in vitro mouse alveolar macrophage phagocytic system, lung washes from animals immunized with Re 595 Salmonella minnesota had significant opsonic activity for Serratia marcescens but not for Pseudomonas aeruginosa.


Galactorrhea-amenorrhea syndrome: diagnosis and therapy. Tests of prolactin regulation in the galactorrhea-amenorrhea syndrome were compared in 18 patients with normal pituitary fossae, seven patients with prolactin-secreting adenomas, and eight normal women. Mean basal prolactin was highest in patients with adenomas and was elevated in those with normal fossae when compared with normal subjects (278 versus 73 versus 10.2 ng/ml). Levodopa, water loading, or luteinizing hormone-releasing hormone testing were of no predictive value in the diagnosis of adenoma. Some patients with adenomas show a greater prolactin response after administration of thyrotrophin hormone-releasing hormone (TRH) than of chlorpromazine, whereas these responses are usually similar in patients with normal fossae. A mean basal prolactin level above 150 ng/ml or an increase of more than 100 ng/ml after TRH administration in a patient with hyperprolactinemia unresponsive to chlorpromazine stimulation strongly suggests a prolactin-secreting tumor. However, because some patients with tumor have prolactin levels below 150 ng/ml, or do not respond to TRH stimulation, or both, functional studies alone cannot permit the diagnosis of all adenomas before the appearance of radiographic changes.


Renal failure associated with demeclocycline in cirrhosis. Three patients with cirrhosis, ascites, and dilutional hyponatremia were treated with demeclocycline in an attempt to correct the abnormal water retention. Demeclocycline administration (600 to 900 mg/day for 8 to 9 days) resulted in [a] increased blood urea nitrogen and plasma creatinine concentrations; [b] reduction of the inulin clearance by between 63% to 78% and of paraaminophippurate clearance by 36% to 77%; and [c] an impairment of the renal concentrating ability. Urine osmolality decreased to hypotonic levels, but polyuria did not appear, probably because it was prevented by the reduction of the glomerular filtration rate. Renal failure was reversible on withdrawal of demeclocycline. No other causes than demeclocycline administration could be found to explain the reduction of the glomerular filtration rate and the estimated renal plasma flow.


[Reticulate erythema with mucinosis (R. E. M. Steigleder syndrome) (author's transl)]. We described a case similar to the four cases reported by Steigleder, Gartman and Linker in 1974 and entitled: "R.E.M. syndrome reticular erythematous mucinosis, a new entity?". In our case, clinical and histological findings were strictly identical to those previously reported. Furthermore, we detected no antibodies in the cutaneous lesions.


Complications after megavoltage therapy of Hodgkin's disease. 56 patients with Hodgkin's disease treated with large field megavolt irradiation are presented. Complications in the parenchymal organs were few, although patients developed an appreciable grade of pulmonary radiofibrosis, two patients had a myocardial infarction and one patient thrombosis of the portal veins. Depression of the bone marrow frequently interfered with the radiation treatment. In five cases radiotherapy had to be discontinued. In three cases bone marrow depression persisted to the time of death. The total mode treatment was often to be discontinued and the treatment with cytostatics was started. The extended and total node treatment for Hodgkin's disease must be planned to spare as much of the bone marrow as possible.


Malignant external otitis: further considerations. Malignant external otitis is an infection which begins in the external auditory canal. It is uniformly caused by the Gram negative Pseudomonas aeruginosa organism and mainly affects elderly diabetics. It spreads to the soft tissues beneath the temporal bone and, if not properly treated leads to facial nerve palsy, mastoiditis, sepsis, osteomyelitis of the base of the skull, sigmoid sinus thrombosis, multiple cranial nerve palsies and death. Experience with 72 patients in varying stages of the disease is summarized. Stressed are the diagnostic criteria of nonresponsiveness to the usual methods of treatment, continued suppuration, and the continuing reformation of granulation tissue in the floor of the external auditory canal. Medical treatment is recommended with hospitalization and intravenous carbenicillin and gentamicin. Minor surgical debridement is helpful. All patients should be treated medically for as long as improvement continues, reserving surgical intervention only in the event a plateau is reached or symptoms and signs become worse under treatment. With or without a major surgical procedure, it is imperative to continue treatment for at least seven days after apparent cure in order to avoid recurrent disease possibly at a site distant from the canal.


Tympanometric patterns found in middle ear effusions. In 120 ears of 67 children with a history of recurrent acute otitis media or otoscopic evidence of persistent middle ear effusion, or both, tympanograms were obtained using an otoadmittance meter and an electro-acoustic impedance bridge. Myringotomy was performed immediately following the tympanometric evaluation confirming the presence or absence of middle ear effusion. The comparison of myringotomy findings with a tympanometric pattern classification revealed 85.8% overall correct association with the presence or absence of a middle ear effusion for both instruments. In 83.3% of the cases, there was agreement in the classification of the tympanogram between the otoadmittance meter and the electro-acoustic bridge.


[Lysis of bacterial protoplasts and spheroplasts and suppression of their dehydrogenase activity by neotehomycin]. Neotelomycin induced lysis of the protoplasts of Bac. megaterium and inhibited their succinate dehydrogenase activity. Direct correlation between the lytic activity of the antibiotic and its effect on succinate dehydrogenase was found. Neotelomycin had no effect on the dehydrogenase activity of the protoplast lysates. Possibly, suppression of the protoplast succinate dehydrogenase of Bac. megaterium under the effect of neotelomycin was due to significant structural changes caused by the antibiotic in the protoplast membranes and leading to their lysis and not to the direct effect on the enzyme. Neotelomycin had practically no effect on the spheroplast dehydrogenase activity of E. coli resistant to the antibiotic and did not induce their lysis. Resistance of E. coli to neotelomycin must be associated not with the presence of the antibiotic non-permeable cell wall but the peculiar properties of the membrane cytoplasm.


[Anthracycline antibiotic, beromycin. The formation of complexes with DNA and the suppresion of nucleic acid biosynthesis]. Beromycin, an antitumor anthracycline antibiotic formed in vitro complexes with native and denaturated DNA and ribosomal RNA. Beromycin had a comparatively low constant of DNA binding and to a less extent increased the melting temperature and viscosity of DNA than the other anthracycline antibiotics. A peculiar property of beromycin was very slow binding with DNA, the complex formation was completed in 60 minutes. Beromycin had a selective inhibitory effect on synthesis of nucleic acids in bacterial and tumor cells. Beromycin inhibited synthesis of RNA in the DNA-dependent RNA-polymerase reaction when both the native and denaturated DNA were used as the template. A lower biological activity of beromycin as compared to the other anthracycline antibiotics, such as rubomycin or carminomycin may be explained by lower affinity of this antibiotic to DNA.


[Study of the effect of microconcentrations of glucose on the biosynthesis of penicillin]. A method of "acute" experiments with significant dilution of the fermentation broth is proposed for studying the effect of easily assimilable substrates on growth of the culture and production of the antibiotic by it. The effect of microconcentrations of glucose on the parameters of the process kinetics was studied with respect to penicillin. The specific effect of microconcentrations of glucose on the specific rate of the culture growth and productivity was noted.


In vitro activity of p-hydroxybenzyl penicillin (penicillin X) and five other penicillins against Neisseria gonorrhoeae: comparisons of strains from patients with uncomplicated infections and from women with pelvic inflammatory disease. Minimum inhibitory concentrations (MICs) of six penicillins against 95 strains of Neisseria gonorrhoeae from patients with uncomplicated anogenital infections and 22 strains from women with pelvic inflammatory disease were determined by an agar plate dilution method, using an inocula replicator. Against all 117 strains, the order of activity observed was: BL-P1654 > penicillin X > penicillin G > ampicillin > amoxicillin = carbenicillin. MICs against strains isolated from women with gonococcal pelvic inflammatory disease were significantly higher than those against isolates from uncomplicated infections: BL-P1654, P < 0.001; penicillin X, P < 0.001; penicillin G, P < 0.001; ampicillin, P < 0.001; and amoxicillin, P < 0.05. MICs of penicillin G were >/=0.125 mug/ml against 33 (36%) of the 92 strains from patients with uncomplicated infections, as contrasted with 15 (68%) of the 22 isolates from women with pelvic inflammatory disease (P < 0.01). The means of the MICs of penicillin G were 0.06 mug/ml for the former and 0.14 mug/ml for the latter.


Comparison of the curative antimalarial activities and toxicities of primaquine and its d and l isomers. This investigation was undertaken to determine whether either d-primaquine or l-primaquine has sufficient advantage over primaquine to warrant evaluation for curative activity in human volunteers infected with Plasmodium vivax. It was found: (i) that the capacities of the isomers and the racemate to cure infections with Plasmodium cynomolgi in rhesus monkeys were essentially identical; (ii) that the subacute toxicities of the isomers and racemate for this monkey were qualitatively the same, but that l-primaquine was three to five times as toxic as d-primaquine and at least twice as toxic as primaquine; and (iii) that the acute single-dose toxicities of the isomers for mice were not only qualitatively different, but that the d isomer was at least four times as toxic as l-primaquine. Since previous appraisals of curative activity and tolerability of 8-aminoquinolines in rhesus monkeys have correlated well with appraisals in human volunteers, attention was focused on results acquired with these test subjects. The relevant evaluations showed that d-primaquine had a therapeutic index at least twice that of primaquine. If this advantage carries over to man, problems that now complicate routine use of primaquine might be obviated. Therefore, a critical comparison of d-primaquine and primaquine in human volunteers seems indicated.


Localization of arylsulfatase in Pseudomonas C12B. Arylsulfatase was released almost completely from intact cells of Pseudomonas C12B after osmotic shock or after treatment with lysozyme. These results suggest that the enzyme is cell wall associated in this soil isolate.


Growth kinetics of Colpoda steinii on Escherichia coli. Colpoda steinii was grown in two-stage continuous cultures with Escherichia coli as prey species. The concentration of prey and the ciliate mean cell volume, dry weight, and number per milliliter were determined at known growth rates. Steady states were reached in the second-stage continuous cultures at all growth rates. Although changes occurred in mean cell size of the ciliates and in the number per milliliter at various growth rates, the yield of protozoan biomass per unit of prey consumed was constant at all growth rates. The data were compared with several equations proposed to describe the kinetics of protozoan growth as a function of prey density.


Epoxidation of aldrin to exo-dieldrin by soil bacteria. Twenty-two strains of soil bacteria, including representatives of the genera Bacillus, Micromonospora, Mycobacterium, Nocardia, Streptomyces, Thermoactinomyces, and Pseudomonas and 10 unidentified gram-negative, motile, rod-shaped bacteria, were shown to degrade aldrin to its epoxide dieldrin. In every case, the exo-stereoisomer of dieldrin was produced exclusively.


The effect of 2,4-dichlorophenoxyacetic acid on growth and nitrogen-fixation of blue-green alga Anabaenopsis raciborskii. Sodium salt of 2,4-dichlorophenoxyacetic acid (80% active ingredient), commonly applied for the control of aquatic weeds, was used to observe its effect on the growth and nitrogen fixation of a heterocystous bloom forming blue-green alga Anabaenopsis raciborskii. A concentration of 10 microgram per ml of 2,4-D showed stimulation of growth and nitrogen fixation and these were almost unaffected in presence of its 100 microgram per ml in the medium. The alga could tolerate up to 800 microgram per ml in liquid culture media with and without nitrate nitrogen and up to 90 microgram per ml on to agar plates. Nitrogen fixation was inhibited in presence of its higher concentrations.


Pathologic analysis of mink mortality in New England mink. The underlying cause of death of a group of New England mink, which died in 1969 to 1970 was explored. PCB and chlorinated hydrocarbon pesticide levels were measured. Aroclor 1254 levels in these mink were elevated 73 fold over levels in healthy mink in 1974. DDT levels were elevated 5 times and DDE 3 times over those control animals. Gross pathology revealed desions of the lungs, liver and kidneys. There lesions were confirmed microscopically. The lungs of the New England mink showed inflammation and congestion. Areas of inflammation were also present in the liver. Massive areas of necrosis were seen in the kidneys, both in the medullary and cortical areas. Kidney involvement was greater than any other organ. P.A.S. positive material was seen in each of these organs with the kidneys showing largest amounts of this material. Since the New England mink did not show lesions of the G.I. tract, did not exhibit fatty degeneration of the liver, which PCB toxicity is known to induce in mink and because they showed areas of congestion, inflammation and positive P.A.S. material, PCB's were not considered the toxic agent. However, fungus or bacterial infection might be the causative agent.


Residues of PCB's and DDT in the western Lake Superior ecosystem. Fish from western Lake Superior (1972-73) contained DDT and PCB residues at concentrations greater than o.1 ppm. The most predominant PCB's were those containing 3 to 6 chlorine atoms per molecule, and GLC data indicated that the mixtures were most like the commercial product Aroclor 1254(2). Other chlorinated contiminants identified by GC/MS analyses and occurring at concentrations less than 0.1 ppm were hexachlorobenzene (C6Cl6), chlordane, nonaclor, and dieldrin. Lindane, which has been previously reported in Lake Superior, was below the detection limit of approximately 0.01 ppm. The relationship between the size of lake trout and the concentration of total DDT in the fish was compared to measurements reported in previous studies. The comparison suggests that DDT residues have declined since 1968. The concentration of PCBs was estimated to be 0.8 ng/L in Lake Superior water and 0.1 ppm in large zooplankton. The apparent bioconcentration factor for PCBs in Lake Superior fish ranged from 10(5) to 10(6). The concentration of total DDT and PCBs in the larger Lake Superior fish exceeded the 5 ppm tolerance level established by the U.S. Food and Drug Administration for these chemicals in fish tbe used for human consumption.


Postoperative nutritional support using needle catheter feeding jejunostomy. Needle catheter jejunostomy was used as an adjunctive surgical procedure in 110 patients. In 19 patients (or 17%) the jejunostomy was of value for the administration of post-operative nutritional support using an elemental diet and it may serve as an alternative route for the administration of supplementing fluids and electrolytes if intestinal function is intact. The clinical experience with the catheter jejunostomy establishes it as a satisfactory technique for postoperative nutritional support in patients requiring esophageal and proximal gastric resection and repair, and gastric surgery in the elderly and debilitated. It is also useful in patients undergoing complicated biliary, pancreatic, and duodenal surgery in whom anastomotic difficulties are anticipated.


Renal decapsulation in the prevention of post-ischemic oliguria. The delayed onset of anuria/oliguria in acute tubular necrosis has been theorized to represent a complicating compartment syndrome, i.e., parenchymal swelling within an unyielding capsule. To test this proposition, 12 monkeys had suprarenal aortic cross-clamping, followed by unilateral renal decapsulation to create an experimental as well as a control kidney unit in the same animal. Histologic examination uniformly confirmed tubular necrosis at death or sacrifice. Subsequent split renal function studies (creatinine, urea, and free water clearances) indicated significantly greater maintenance of renal function by the decapsulated kidney than by its paired control. Clinical evaluation in 21 hemorrhagic shock patients, with the capsule of one kidney stripped, revealed on follow-up that 15 developed a renal failure consistent with acute tubular necrosis. Although three patients with polyuric failure died before split studies could be run and two others have been too recent for computer analysis to have been completed, nine of the remaining ten had significantly greater renal plasma flows (194 versus 121 ml/min M(2), p < .01) and significantly greater urine flows (.99 versus .18 ml/min M(2), p < .01) on the decapsulated side than on the control, as determined by differential renal scans. No significant difference in these same lateralized renal functions was noted in the tenth patient with renal failure and in the six survivors without renal failure. Renal decapsulation as prophylaxis reduced the anticipated incidence of oliguria/anuria from an expected 75% to 7% (p < .01) in these 21 shock patients. Such data suggest that delayed renal ischemia, possibly based on a compartment syndrome, may be the cause for a progression of acute tubular necrosis from polyuria to oliguria and then to anuria.


[Correlation between the orientation of the data wave and the topography of pre-excitation in the Wolff-Parkinson-White syndrome]. A comparison between the epicardial siting of the zone of pre-excitation of the ventricle in Wolff-Parkinson-White syndrome and the ECG has allowed us to distinguish 6 topographical types, according to the orientation of the delta wave in the horizontal plane, and especially in the frontal plane which is often ignored: right anterior, left lateral, right of left anterior paraseptal, and right or left posterior paraseptal. The association of a heart defect with ventricular hypertrophy, or the coexistence of several associated accessory pathways prevents such correlation and makes it imperative to carry out intracavitary investigation and epicardial mapping to localise the accessory pathway if surgery is contemplated.


[Risk factors in mitral valve replacements]. The authors report 137 isolated mitral valve replacements carried out between 1966 and 1975, with an operative mortality of 13.1%. Certain risk factors are demonstrable:--from the clinical point of view: previous cardiac surgery, 3 or more attacks of cardiac failure, a prolonged preoperatives course, atrial fibrillation, and cardiomegaly on the X ray. The combination of these risk factors is very serious as when three or more risk factors are operative at the same time, the mortality is 40%. Reduced ventricular function preoperatively was an essential factor governing operative mortality; improved results follow earlier indications for surgery.


[Outcome of corrected and uncorrected tricuspid insufficiency after repair with prostheses in mitral and mitro-aortic valve diseases. Apropos of 159 cases]. This is a study of 159 patients with tricuspid incompetence (TI) associated with a mitral or mitro-aortic valve defect. The mean age of the patients at operation was 25.5 years. The TI was left untreated in 84, corrected by semi-circular annuloplasty in 39, and corrected by a prothesis in 28, by a Carpentier ring in 6, and by Kay's plasty in 2. The 33 early deaths (21%) are regrettable. The long-term outlook was studied with a mean follow-up period of 26 months. The overall mortality rises, if these are included, to 42 (26%). By comparing the preoperative findings in those with good and poor results, we have been able to identify a certain number of risk factors: a preoperative course of greater than or equal to 6 years, a number of attacks of cardiac failure greater than or equal to 3, a cardiothoracic ratio greater than or equal to 0.70, a mean right atrial pressure greater than 12, a mean pulmonary arterial pressure of greater than or equal to 50. Severe TI is also a poor prognostic factor. If the three groups of patients are compared, bearing in mind the fact that their preoperative state was very similar, and that the TI was either left untreated or repaired by annuloplasty or prosthesis, it appears that such a correction improves neither the surgical mortality nor the long-term prognosis. It therefore seems to us that a functional TI can be treated expectantly since its resolution depends more on the unified treatment of the whole underlying disorder and on the state of the myocardium than on any localised correction of the TI.


[Long-term outcome of valve prostheses. Apropos of 299 operated patients]. The authors report a series of 299 operated cases betwen 1966 and August 1975. The operative mortality was 16%, usually a result of low output states and arrhytmias. Long-term survival was 74% at 3 years and 64% at 6 years, being better in those with only one valve replacement. The late results were very good taken as a whole. The few poor results were associated especially with a degenerating myocardium. The mitral group were favoured with a better 5 year survival rate and by clinically, and above all haemodynamically severe tricuspid incompetence. Thromboembolic complications, which are a major hazard, were favoured by irregular and inadequate anticoagulant therapy. In patients under 20 it would seem possible to stop after 6 months' effective treatment. Children have had generally better results than adults, probably because of the better state of their myocardium.


[Aortic valve replacement at the cardiac insufficiency stage]. 80 adult patients with isolated aortic valvulopathy and cardiac insufficiency have been investigated. Among 10 non operated patients, there has been 9 deaths during a three years follow-up. Among 70 operated patients early mortality is not higher than among patients without cardiac failure, but late mortality is significantly higher (27, 1 p. 100), bacterial endocarditis and sudden deaths being particularly frequent. Subjective improvement is constant among survivors but cardiomegaly and left ventricular hypertrophy do not change much. The authors think aortic valve replacement is beneficial even in patients with cardiac failure.


[Re-operations on patients with ball valve prostheses]. Out of 989 cases with a ball-valve prosthesis, 66 have been reoperated (6.7%). 2.9% of the cases reviewed annually have thus been reoperated. The main indications for reoperation were displacement (75.5%), malfunction (10.5%) which was related to a failure of the material of the prosthesis or to the deposition of fibrinous plaques, and associated lesions (14%) which were valvular, coronary or myocardial. There were multiple complications in 36 patients. The operative mortality was 31.8% (21.7% over the last two years). On statistical analysis, the significant risk factors were a previous history of bacterial endocarditis, grouping in Class IV of the NYHA classification, enlargement of the QRS complex (0.12 s), urgency of reoperation, and prolonged extracorporeal circulation (2 hours). The rapid fall in survival time was due in part to late deaths (16 patients). By way of contrast, the clinical result was satisfactory in 71% of the survivors. Analysis of the causes of failures has lead to a search for ways of preventing the necessity for reoperation.


[Aorto-coronary bypass. 1. Immediate results evaluated in a sample of 357 operated patients]. Over a period of 36 months, 357 patients have had one or several aorto-coronary bypass graft operations, either alone (305 patients) or in combination with another surgical procedure. 230 (66.4%) of these patients had acute coronary insufficiency: unstable angina or "menance syndrome" in 177, Printzmetal's angina in 34, threatened extension of an infarction in 14, and post-cannulation stenosis in 5. 75 patients had chronic coronary insufficiency, and in the 52 others the coronary lesions were associated with valvular or myocardial lesions. A total of 489 grafts were carried out, 261 of which (53.4%) were on the anterior descending artery. Of the 305 patients with grafting and no other surgical procedure, 190 (62,3%) had one single graft, 104 (34.1%) had 2 grafts, and 11 (3.6%) had 3 grafts. For theses 305 patients, the mortality during the first month (6.9%, or 4.5% for the last six months of the series) was influenced by age (a mean of 52.1 in the survivors and 57.1 in the deceased, p less than 0.001), a preoperative infarction less than 8 days old (p less than 0.001), significant changes in left ventricular function (a mean ejection fraction of 44.9% +/- 0.20 in the deceased, and 61.5% +/- 0.19 in the survivors, p less than 0.001), a mean end-diastolic volume of 252 ml +/- 98 in the former and of 136 ml +/- 51 in the latter, p less than 0.001). The advent of a postoperative infarct thus increases the mortality. An infarct complicated the progress of 11.1% of patients. The probability of such a complication occuring depends upon the state of the vascular bed distal to the bypassed artery and on the duration of the extracorporeal circulation.


[Aortocoronary bypass. 2. Long-term results evaluated in 318 survivors]. Of the 318 patients surviving the first postoperative month 14 died secondarily, 5 were lost to follow-up, and 299 were therefore reviewed with a mean follow-up of 16.6 months (extremes of 2 and 42 months). The percentage of late infarcts was 5.9%. Complete disappearance of the angina occurred in 80.3% of patients. Persistant angina was commoner in females (p less than 0.05) and in patients with a lesion affecting all three trunks (p less than 0.05). On the other hand age, the clinical indications for bypass, the presence of an infarct preoperatively, and the development of an infarct immediately postoperatively did not affect the functional result. The cardio-thoracic ratio decreased significantly, from0.51 +/- 0.07 to 0.47 +/- 0.05 (p less than 0.001). 45 coronary arteriograms in a total of 63 grafts were analysed. 73% were patent after a follow-up period of 10.5 months. The patency rate was 88.6% when coronary arteriography was carried out systematically, and 63% (p less than 0.002) when it was indicated by persistant or recurrent angina. The actuarial survival curve in patients with 2 or 3 trunk involvement demonstrates clearly the superiority of surgical over medical treatment.


[Coronary arteriography in recent myocardial infarct]. Sixty patients with a recent transmural acute myocardial infarction had seletive coronary arteriography carried out between the 7th and the 29th day (mean 17 +/- 2 days) after the onset of the condition. The anterior infarction (n = 25 cases) had a total obliteration in 36% of cases, and most often (64%) a stenosis of the anterior descending artery with an excellent distal bed (80%). The collateral circulation is often zero (76% of cases); 80% have adjacent lesions on the right coronary or circumflex artery, but 7 patients out of 25 would have been able to have a preventive bypass operation. The posterior infae lesions are often sited electively at the level of the artery of the S/A node or in the middle of the second vertical segment in the region of the right ventricular branch. Thus the infarct is the result of a complex lesion of the right coronary and circumflex arteries, because the latter is affected in three cases out of four. 63% of patients with a postero-inferior infarction have diffuse lesions, and 13 out of 35 could have had a preventive bypass procedure. This study shows: 1. That this investigation is well-tolerated after a recent infarction; 2. The high incidence (43%) of stenoses at the edge of the area of necrosed myocardium; 3. The importance of this investigation in finding the nearby lesions which are very frequently associated: in 33% of cases, preventive bypass would have possible.


[Long-term anticoagulant therapy in subjects over 75 years of age. 100 cases]. 100 patients (median age 79 years) were given anticoagulant therapy (ACT) for a period of time averaging 5 years 3 months (522 follow-up years).--Out of 3 522 Quick tests, converted into prothrombin times and all carried out in the same laboratory, the prothrombin time was at or less than 32% in 60.5%, and 34% in 69.6% of the tests.--The mean therapeutic doses were less than 27% of those for adults, and were decreased by 3 mg of phenindione per year over the age of 75, only the actively treated cases being retained.--The risks are the same as those for the middle-aged adult. They depend more on the quality of the investigations than upon age. In the group which has been studied, slight or frank haemorrhagic complications (0.05/year/patient) were the result of a demonstrable overdosage in only one case in four. They were not responsable for any deaths in this series.--because of the referral patterns, the patients studied consisted of 79 with ischaemic heart disease, 27 with peripheral vascular disease, 9 cerebrovascular accidents, and 6 with thrombo-emoblic problems, not counting the 23 complications during the course of the study. In those patients with ischaemic heart disease, well-regulated anticoagulant treatment was associated with a favourable clinical course, and the correlation was significant.--there is not argument against the administering of a full and prolonged course of ACT to a patient of more than 75 years of age.


[Incidence and evaluation of the risk of coronary disease. Prospective study in Paris]. The Paris prospective study in an epidemiological study of 7,453 middle-aged men born in France, and initially free from ischaemic heart disease. The current mean follow-up time is 4 years. The mean annual incidence is 5.1 per 1000, which is about one half that found in similar american studies. This incidence is related to the cholesterol level, to the blood pressure, to cigarette consumption when the smoke is inhaled, to diabetes mellitus, and to major abnormalities on the electrocardiogram. These five factors are mutually independant in their prediction of the risk of future illness. A formula has been derived by statistical analysis, and takes these five factors into account: the incidence of illness rises exponentially as a function of this formula. New cases of ischaemic heart disease are distributed, but with a very patchy incidence, in this population, of which only a very small number remain disease-free. A table has been drawn up to show the probability of a middle aged male contracting ischeamic heart disease within 4 years, and takes the 5 factors into account: this probability varies between 0.5 per cent and 34 per cent.


[Spontaneous and post-surgical outcome of incomplete forms of atrio-ventricular canal]. 125 patients with an incomplete type of atrioventricular canal defect (AVC) were followed up over a very long period. A study of the changes in parameters which are not open to great variability has allowed a more precise approach to the spontaneous and postoperative course of this congenital cardiac defect. The fact that the condition is usually well during the first three decades is not a justification for witholding operation; complications occur after the thirtieth year, and the operative risk becomes greater. Although only 41 patients in this series underwent surgery, we have been able to assess the surgical results and, as has been reported in the literature, these appear to be good. It is therefore necessary to extend the indications for surgery to include all the incomplete forms of AVC defect, and especially to operate during childhood or adolescence in order to minimise the risks of surgery.