[A computer program for the implicit regression of the Hill equation]. A computer program for implicit regression of the Hill equation. The fundamentals for the regression of implicit functions following the Gauss method are dealt with. Basing on these fundamentals a program for the regression of the Hill equation is described. The binding constant, the Hill coefficient and end extinction can be estimated. The mean errors of parameters were calculated in the linear model. The program was written in ALGOL 60 for the computer Robotron 300. The program is available on request.


[Studies on the magneto-optical rotation of porphyrins, hemins and methemoglobin compounds]. Using the method of magneto-optical rotation (MOR) various porphyrin derivatives, hemin and heme compounds, and a number of methemoglobin complexes were investigated. The spectra were recorded from 450-600 nm; with methemoglobin also in the Soret region. 1. The metalfree porphyrin derivatives (deutero-, meso-, hemato- and protoporphyrins) were measured in strongly acidic aqueous solution. The derivatives thus present as di-cations yield highly resolved MORspectra, where the Q-bands (Oo leads to; Oo leads to 1) originated from the pi-pi transitions of the porphyrin display the curve shape characteristic of an A-term, this proving the presence of the D4h symmetry. An exception is the protoporphyrin, in which the pi-electron system of the porphyrin is perturbed by the influence of pi-electrons of the vinyl group, causing poor resolution, line broadening, and shift of the Q-bands into the lower-energy spectral region. 2. With iron porphyrins (hemin, heme and their complexes) the charge of the iron and the nature of axial ligands determine the position and intensity of the O-bands in the MOR spectrum. Low-spin complexes have a higher symmetry than the high-spin complexes. Whereas with hemin (S = 5/2), the iron located outside the heme plane strongly disturbs the porphyrin pi-system, the high symmetry of porphyrin is greatly retained in the case of heme. This can be explained by the enhanced binding distance between the bivalent iron and the porphyrin to great for a strong coupling between the microsymmetry of the iron and the macrosymmetry of the porphyrin pi-system.


[NMR spectroscopic characterization of deuterohemin complexes in aqueous media]. 1H-NMR measurement and NMR susceptibility measurements were carried out with deuterohemin complexes in aqueous solution. The hydroxyaquo complex of deuterohemin, which is dimeric in weakly alkaline medium, turns into a low-spin dicyano complex on addition of cyanide. This reaction proceeds in two steps: whereas in the first, slow step a dimeric low-spin hydroxycyano complex is formed, in the second step the latter is converted quickly into the dimeric dicyano complex. The pK values for the overall reaction, the first and the second step were measured to be 23.25; 0.39 and 22.86, respectively. The values of free energy variation obtained therefrom suggest that conformational changes are decisive in the liganding of methemoglobin.


[Molecular and complex-chemical studies on methemoglobin from Chironomus thummi thummi and various isolated fractions]. 1. Six different hemoglobin (Hb) fractions were isolated and characterized from the larvae of Chironomus thummi thummi using column chromatographic procedures. 2. Chromatographic and sedimentation-analytic studies (sedimentation coefficients of 2.0 +/- 0.2 (S)) have shown three Hb fractions to exist basically in a monomeric form. The molecular weight of component M-2 was determined by sedimentation equilibrium technique to be 15,470 +/- 400. The dimeric Hb was found to have sedimentation coefficients of 3.0 +/- 0.1 (S) in the weakly acidic pH region. In alkaline milieu, the reversible dissociation proceeds into the monomeric molecules (S20, W = 1.9 +/- 0.1 (S)). Molecular weights vary between pH 5.7 and 9.8 not only with hydrogen ion concentration, but also with protein concentration in correspondence with a dissociation-association equilibrium consisting of monomers and dimers. 3. For the Hb fraction M-2, a friction ratio of f/fo = 1.03 was calculated, suggesting an almost spherical shape of this protein. In contrast, the dimeric component appears to have a much more asymmetric structure (f/fo = 1.19). 4. The indivdual MetHb fractions bind the ligands: fluoride, imidazole and azide with different affinities.


[The supramolecular organization of oxyhemoglobin in erythrocytes. A small-angle x-ray scattering study]. From X-ray scattering diagrams of concentrated solutions of hemoglobin the pair-correlation function of the molecules is calculated. At a concentration of 324 g/l the distance between neighbouring molecules amounts to 65 A. The number of direct neighbours of one molecule is 9. The pair-correlation function cannot be described by the assumption of a lattice-cell-model; therefore, a lattice-vacancy-model with fluid order is proposed.


[Brain transections for the localization of tremorigenic brain regions in the rat]. In rats transections of the brain have been carried out to localize tremorigenic centres. Ablation of cortical and diencephalic brain areas caused moderate reduction of oxotremorine induced tremor. A makred decrease of tremor intensity has been observed after transections eliminating the tegmental parts of the formation reticularis. We found in caudal sites of transections a shift of the tremor frequency to lower values including changes of distribution as well as the appearance of spontaneous tremor. Both the intensity of oxotremorine induced tremor and the appearance of spontaneous tremor was found to depend on body temperature. Harmine-induced tremor was influenced in opposite direction by ablation of the rostral brain areas.


[A statistical study of the interspike-interval distribution of cortical neurons]. Spontaneous activity was recorded extracellularly by glass microelectrodes from 54 neurons of the Gyrus sigmoideus posterior of unnarcotized and gallamine-immobilazed cats, and the sequential and nonsequential interspike-interval histograms were determined using the multi-channel analyzer CAT 400 C. The interval distributions were characterized by graphic criteria, and it was attempted to describe these distributions mathematically by four biparametric distributions, the Weibull, lognormal, gamma and normal distributions. 80% of the frequency distributions of type I (exponential), II (left skew, gamma-similar) and IV (almost symmetrical) could be assigned to these distributions, namely 43% of the lognormal distribution, 32% of the Weibull distribution, and 5% of the gamma distribution. The interval histograms of the type III (left skew, steep) and V (bimodal) could not be described by any of the distributions selected.


[A method for the objective determination of tremors in the rat]. Two methods for determining tremors in the rat, acceleration pick-up and electromyogram, including electronic evaluation by impluse rate and frequency are described technically, and the results obtained with either method are compared. Both methods allow quantitative analysis of the drug induced (arecoline) tremor. Electromyographically, the tremor effect can be recorded already after lower doses compared with the electro-mechanical method. Besides, the EMG can be employed on immobilized animals.


[Tremor following intracerebral carbachol injection. 1.Carbachol sensitivity of various brain structures]. Tremor produced by intracerebral injection of carbachol. I. Susceptibility of different brain areas to carbachol Microinjections of carbachol into the lateral ventricle of rats caused tremor depending on dose. Intensity and duration of motor effects after injection of carbachol (30 mug/3 mul bilateral) into different brain areas were found to depend on localization: strongest tremor was elicited by injections into the nucleus caudatoputamen and cortex cerebri, moderate tremor by administration into the substantia nigra reticularis, globus pallidus and thalamic brain regions. Target areas of mean sensitivity were demonstrated in more rostral and caudal parts of the formatio reticularis. The injection of carbachol into the nucleus ruber, nucleus linearis and substantia nigra compacta brought about lowest tremor values. Ablation of the site of injection from the remaining brain abolished tremor induced by carbachol contrary to the tremor induced by oxotremorine.


[Studies on the mechanism of action of peptide attacking smooth muscle. II. Differentiation of biologic activity of tachykinins in affinity and intrinsic efficacy]. Under the condition of receptor blockade produced by continuous presence of an agonist in the organ bath, it was attempted to determine the dissociation constants for C-terminal partial sequences of the substance P at an isolated guinea pig ileum, by analogy with the method involving irreversible antagonists, and to compare them with the biological activity at the guinea pig ileum and the rat colon (ED50 values). Differentiation of the biological activity at the guinea pig ileum into affinity and "intrinsic efficacy" allows one to explain quantitative differences in determining the biological value on both isolated organs, and to reveal the contribution of the individual amino acids to affinity and "intrinsic efficacy".


[Studies on the mechanism of action of peptides attacking smooth muscles. III. The effect of N-azylation on the activity of C-terminal partial sequences of eledoisin, physalaemin and substance P on the guinea pig ileum]. C-terminal pentapeptides of eledoisin, physalaemin, and the substance P, when N-substituted with acetyl, halogenacetyl and other acyl residues, are increased in their action more than  100fold, reaching the activity of acylated hexa- and heptapeptides. The effect found with a number of compounds is interpreted as the influence of predominantly hydrophobic substituents upon the peptide sequence essential for the action. Polar groups in the acylic residue seem to cause additional increase in action.


[Interactions between prostaglandins E2 and F2alpha and isoprenalin in the dog heart in situ]. The effects of PGE2 and PGF2alpha on the isoprenaline induced elevation of myocardial contractility were studied on hearts of anesthetized dogs. The steady state effects were determined after single or simultaneous infusion of the substances. Two indices of contractility were used for the quantification of inotropic effects. PGE2 but not PGF2alpha showed positivinotropic effects. PGE2 significantly inhibited the inotropic responses induced by isoprenaline (p less than 0,01); whereas PGF2alpha was without any effect in this direction. The results are discussed with respect of a postjunctional action of PGE2.


Unusual increase in mitochondrial glycerolphosphate dehydrogenase activity in primary cultures of rat liver cells. Primary cultures of neonatal rat liver cells show an increase in the activity of mitochondrial glycerolphosphate dehydrogenase between the second and tenth day of cultivation. At the end of cultivation the activity level exceeded that of liver tissue in vivo. Replacement of normal serum by hypothyroid serum or addition of triiodothyronine to the medium did not influence significantly the enzyme activity in vitro, in contrast to the very marked effects of thyroid hormones observed in vivo.


[Stimulation of the renal excretion of p-aminohippuric acid by repeated application of phenobarbital]. The rate of renal excretion of p-aminohippuric acid can be accelerated by repeated administration of phenobarbital in adult rats. This stimulation could not be observed in newborn and young rats.


[Serological identification of spectrin in the 2 dimensional immunoelectrophoresis]. Using polyvalent antisera directed against solubilized human erythrocyte ghosts in the immunoelectrophoresis we obtained some precipitation arcs. Antisera against the purified spectrin allowed the identification of spectrin in the crossed immunoelectrophoresis.


The use of antigen-coated protein beads as immunoadsorbent for the purification of antibodies. A procedure is described using antigen-coated beads of calf serum as immunadsorbent for the purification of antibodies against ferritin and against leukemia-sarcoma virus-induced antigens.


Fluorescence and chemical reactivity as empirical indices of matrix-induced alterations in immobilized enzymes. The fluorescence emission and chemical reactivity of soluble and Sepharose-bound leucine aminopeptidase and carboxypeptidase A were investigated and the results compared. Both natural fluorescence and the fluorescence of fluorescein-labeled enzymes were utilized. The front-surface viewing technique enables us to measure the apparent fluorescence quantum yields and the rotational relaxation times of fluorescent groups within native unbound and carrier-fixed enzymes. The chemical reactivity was probed with Ellman's reagent and iodoacetic acid. Both types of methods were found to be useful in detection and quantitation of matrix-induced alterations in immobilized enzymes.


[The effect of diffusion, electric transport and convection on heterogeneous enzyme catalysis]. The consideration of electric and volume transport additionally to diffusion leads to the dependence of concentration profiles in heterogeneous enzyme catalysis on additional parameters (e. g. electrical field strength, convection velocity) which are valuable for influencing and optimizing these systems. For autocatalysis the local periodic concentration profiles are influenced essentially by these phenomena (change of onset and wavelength). When diffusion is negligible equations are given to determine the kinetic parameters vmax and KM from transport measurements.


[Tying with thread of the rat coronary arteries, a method for the production of experimental coronary stenosis]. A method is described for producing a localized coronary artery stenosis by tieing two threads around the Ramus descendens of the left coronary artery, which produces progressive cell proliferation of the vascular wall. Studies on 102 male Wistar rats (70 experimental and 32 sham-operated control animals) have shown coronary artery stenosis narrowing the lumen by more than 50% (up to and exceeding 90%) to develop after 7 days in 30% of the animals, after 14 days in 75%, and after 21 days (postoperatively) in 100%. In about one-third of the cases subtotal infarction in the supply area of the left coronary artery occured as a result of post-operative damage to the coronary artery with obturating thrombosis. The induction of effective coronary stenosis limiting the coronary reserve offers possibilities for further experimental studies on the role of relative coronary insufficiency in the pathogenesis of myocardial infarction.


[Coronary flow measurements on the isolated rat heart following experimental coronary artery stenosis]. A stenosing proliferation of the vascular wall was produced by exposing the Ramus descendens of the rat's left coronary artery to continued mechanical stimulation. Two weeks after the operation the hearts were perfused according to a modified Langendorff method, and the flow rate was measured under aerobic conditions and following short-time anoxia. Under either experimental conditions, the flow rate proved to be significantly decreased.


[Determination of local brain blood flow by means of switched heating]. It is demonstrated by model experiments that the determination of stationary and instationary data (amplitude and shape of the heating signal) allows the two components of local brain perfusion (flow rate and volume flux) to be measured separately. Since perfusion and temperature are measured at the same site, the convection data are free of variations of the local brain temperature. The dependence of the amplitude of the heating signal on the flow rate is described by the equation Ao = a - e-bv + c, with the parameters a, b, c being represented as a function of the convection-free space around the sensing probe. It is shown by animal-experimental data that the magnitude of the convection-free space around the sensing probe is variable. A tentative algorithm is proposed for practical application of the method.


Transfer of maternal plasma free fatty acids into the rat fetus. The amount of maternal plasma free fatty acids passing to the fetus has been determined to be 0.09 mumoles fatty acids per min per each litter. Taking account of the increase of the total fetal fatty acid pool due to the fetal growth (0.2 mumoles fatty acids per min for each litter) we conclude that the maternal circulation is the source of about half of fetal fatty acids on day 21 of pregnancy.


Studies on the metabolism of free fatty acids of the plasma in non-pregnant female and pregnant rats. In non-pregnant female and pregnant rats the concentration (0.41 mumoles/ml and 0.49 mumoles/ml), the turnover time (0.6 min and 0.8 min), and the irreversible disposal rate (8 mumoles/min and 7 mumoles/min) of plasma free fatty acids (FFA) were determined. The results indicate that there are no major differences in the metabolism of the plasma FFA between non-pregnant female and pregnant rats.


[Blood pressure behavior and pathomorphology in the rat following application of high doses of depot angiotensin]. In 55 rats, not accustomed to the process of blood pressure measurement and given daily doses from 1.25 - 10.0 mg angiotensin in depot form for up to 3 days, as much as 70% of the animals died of circulatory failure. Blood pressure increase was either absent or was very low after low doses. Histologically, the myocardium revealed focal destruction of muscle fibres with mesenchymal cell proliferation in many places; the epithelium of numerous renal tubuli was changed hydropically; the liver showed focal necroses of the parenchyma; the adrenal cortex showed stress reactions, and the arterioles of the splanchnic area -- changes of the plasmatic vasculose from the 3rd day of experiment. By contrast, in 51 rats accustomed to the measuring process prior to the experiment and given high doses of angiotensin, only moderate blood pressure rise and scattered cases of death (4%) occurred, low doses caused a strong blood pressure elevation. With otherwise equal histologic organ diagnoses, liver necroses were absent, except for two cases. This differential response of the two animal groups to varying angiotensin doses and the pathogenesis of the changes observed are discussed.


[Biphasic effect of angiotensin II on conditioned reflectory reaction patterns in albino rats]. 40 male albino rats were used to investigate the influence of one single i. v. dose of 10 ng/kg Angiotensin II upon established and stabilized conditional-reflectory response pattern (two-dimensional conditional-reflectory decision process and periodicities of conditional-reflectory processes). At normotonous blood-pressure values, Angiotensin II exerted a biphasic action on the conditional-reflectory response pattern. In the first phase of action (up to 30 min after injection) there prevailed centralnervous inhibition processes, while the second phase of action (30-70 min after injection) was marked by a general centralnervous excitation, which is reflected by extremely short times of response, and a pronounced sensitivity to optic, acoustic and tactile stimuli. The decision capacity of the animals was considerably reduced in both phases. The periodicities of conditional-reflectory processes (duration of periods in the minute range) are strongly disturbed in the first phase of action, and tend to normal in the second phase. Furthermore, Angiotensin II was found to have a selective, hierarchically ordered influence with regard to the duration and intensity of action. Thus, the information processing activity of the CNS underwent most pronounced changes. The centralnervous regulatory functions were less affected; the blood pressure regulation showed little and transient influence by Angiotensin II. In the discussion, the neurotropic and algogenic action of Angiotensin II, and the relation of the octapeptide effect with pathogenetic mechanisms of experimental neurotically induced hypertonia are dealt with.


[Cholinergic effect on the dopamine turnover in the rat corpus striatum]. The peripheral administration of oxotremorine caused a significant increase in dihydroxyphenylacetic acid (DOPAC) in the striatum of rats, dopamine (DA) level was unaffected. Injection of oxotremorine into the substantia nigra failed to change the content of dopamine and its acid metabolites homovanillic acid (HVA) and DOPAC in striatum. Injection of oxotremorine or carbachol into the substantia nigra or into the caudate nucleus did not significantly influence the DA-turnover. The partly inconsistent results are discussed in connection with literature data in regard to the existence of excitatory as well as inhibitory cholinergic systems, which are located differently and are involved in the regulation of DA-turnover.


[Animal experimental studies on the pharmacokinetics of streptokinase]. By the use of native and radioactively labelled streptokinase its distribution and elimination were determined in rabbits and compared to the course of the fibrinolytic action. Particularities of the pharmacokinetics of the activator of fibrinolysis were studied and related to the therapeutic effect.


[The mechanism of action of peptides acting on smooth muscle. II. Relationships between angiotensin II and adrenergic systems with reference to blood pressure regulation]. To explore the molecular and subcellular effects of Angiotensin II during the early phase of an experimental hypertension, biochemical and morphological changes induced by continued administration of subpressoric Angiotensin II doses were traced in rats. After the treatment, the endogenous noradrenalin and dopamine content was changed in various brain regions, the turnover rate of noradrenalin was lowered, and the neuronal 3H noradrenalin uptake was delayed and reduced. Electron microscopy revealed an increase in number and granulation of adrenergic vesicles in the hypothalamus, and characteristic changes at pre- and postsynaptic membrane complexes. The interaction between central effects of angiotensin II and the adrenergic system presumably involves disturbance at the level of neuronal membranes.


[Electron microscopic studies on the peritoneal exudate of the mouse to determine the effect of colloidal carbon on the primary immune response to heterologous erythrocytes]. Antibody production to sheep erythrocytes was markedly depressed in mice injected intraperitoneally with colloidal carbon. Peritoneal exudate cells were investigated electron microscopically with regard to mechanisms responsible for lower antibody production. Peritoneal macrophages were not disturbed in antigen phagocytosis and antigen digestion. Only in connection with immunosuppression was there an increase in antigen containing macrophages in the peritoneal cavity. The changing relation of antigen-stimulated macrophages and lymphocytes in favour of the macrophages and its consequence to decreased immune response is discussed.


Tobacco Chemistry.29. (7S)-10-Oxo-4xi-methyl-7-isopropyl-5E-undecen-4-olide, a New Thunbergan-type Nor-isoprenoid isolated from Greek Nicotiana tabacum L. The structure of a new C15-lactone, (7S)-10-oxo-4xi-methyl-7-isopropyl-5E-undecen-4-olide, isolated from Greek tobacco, has been determined mainly be 1H NMR, 13C NMR and high resolution MS, and its absolute configuration established by degradation to (2S)-5-oxo-2-isopropylhexanal. The carbon skeleton of the new compound indicated that it is derived from a thunbergane precursor and constitutes the first C15 nor-thunberganoid in tobacco.


Intestinal glycoproteins of germfree rats. IV. Oligosaccharides obtained by chemical degradation of a water-soluble glycoprotein fraction. Removal of sialic acid from the glycoprotein and subsequent degradation with sodium hydroxide-sodium borohydride resulted in the formation of a number of low-molecular weight carbohydrate compounds of which three were isolated and characterized: 2-deoxy-2-acetamido-D-galactitol; O-alpha-6-fucopyranosyl (1 leads to 2)-O-Beta-D-galactopyranosyl-(1 leads to 3)-2-deoxy-2-acetamido-D-galactitol (oligosaccharide I); O-Beta-D galactopyranosyl-(1 leads to 3)-2-deoxy-2-acetamido-D-galactitol (oligosaccharide II). From an acetolysate of the desialized glycoprotein a fourth component was obtained and characterized to be O-Beta-D-galactopyranosyl-(1 leads to 4)-2-deoxy-2-acetamido-D-glucose (oligosaccharide III).


Intermediates in the penicillic acid biosynthesis in Penicillium cyclopium. Feeding experiments using 14C-labelled precurosrs demonstrate the following sequence of the biological formation of penicillic acid in Penicillium cyclopium: orsellinic acid leads to 2-O-methylorsellinic acid leads to 1,4-dihydroxy-6-methoxy-2-methylbenzene leads 6-methoxy-2-methyl-benzoquinone(1,4)leads to penicillic acid.


Chemical composition of angelica root oil. The volatile constituents of angelica root separated by extraction with etherpentane and by extraction with alcohol-water were investigated by means of glass capillary and preparative gas chromatography, IR, UV, NMR and mass spectrometry. 16 monoterpene hydrocarbons, 13 sesquiterpene hydrocarbons, 12 monoterpene alcohols, 4 oxygenated sesquiterpenes, 11 esters, 3 lactones, 7 aliphatic carbonyl compounds and 4 aromatics were identified. Twenty additional compounds identified were present only in the alcoholic sample. These consisted of ethyl ethers of monoterpene alcohols, ethyl esters of long-chain fatty acids, and acetals. The relative proportion of many compounds was found to depend on the method used to isolate the essential oil.


Effect of total cavo-portal shunt on pulmonary fibrin deposition after intra-aortal infusion of thrombin in the dog. The effect of total cavo-portal shunt on the deposition of fibrin in the lungs and liver in dogs was studied after intra-aortal infusion of thrombin. 125I-labelled fibrinogen was used for calculation of the amount of fibrin. The pronounced pulmonary trapping of fibrin seen in non-operated control dogs did not occur in dogs submitted to the shunt operation; in these dogs a considerable trapping was seen in the liver. These results indicate that in generalized thrombinaemia the microclots are mainly formed in the venous circulation and transported to the nearest capillary network, where passive mechanical filtration occurs.


Replacement of blood loss with physiological saline in major surgery. This clinical investigation confirms the results of previous reports on the possibility of safely replacing blood lost during operations with physiological saline. The percentage saving of blood transfusions has been 50.1%. We are convinced that even greater saving will be made when surgeons become accustomed to the method.


Utilization of intravenous glucose and fructose in the postoperative period. A comparison is made between the utilization of glucose and fructose given intravenously at the rates of 1 g kg-1 h-1 and 0.5 kg-1 h-1 to 6 and 10 patients, respectively, who had undergone stomach surgery. Each patient served as his own control. The maximum rise in the total blood sugar concentration during both the rapid and the slow glucose infusions (227 mg% and 171 mg%) was significantly larger than during the fructose infusions (86 mg% and 52 mg%). The maximum rise in blood glucose of an average 23 and 18 mg% during the administration of fructose seems to indicate that only a small percentage of fructose is converted directly to glucose. Hypoglycemia after the infusions was most pronounced after the use of glucose. During the rapid infusions the patients lost a significantly larger amount of the infused sugar in the urine when glucose was administered (12.9% vs 4.7%), and the greater loss of sugar was accompanied by a greater loss of water. During the slow infusions there was no difference in sugar excretion between the two carbohydrates. At the infusion rate of 0.5 g kg-1 h-1 6 times as much lactate was excreted during the fructose infusions as during the glucose infusions (1.8 mg as compared with 0.3 mg lactate kg-1 infusion h-1). The study seems to indicate that there is a renal threshold for lactate at blood concentrations of 10-15 mg%.


Glycogen storage in rat liver and skeletal muscle in thermal trauma. III. Effect of adrenal demedullation. Glycogen synthesis is reduced following trauma, especially in skeletal muscle. The author has shown previously that after an experimentally inflicted burn in the rat the glycogen storage in skeletal muscle is about 40% of the normal. In the present study an attempt was made to assess the importance of the endogenous adrenalin production in the adrenal medulla for this reduction in glycogen storage. With this aim the glycogen storage in the liver and skeletal muscle during a standardized glucose infusion was studied 20 hours after infliction of a burn both in rats with intact adrenal glands and in rats subjected to adrenal demedullation. In the muscle the glycogen storage was reduced in both groups, and to the same extent. In the liver no change in glycogen storage was recorded for either group. The results indicate that the catecholamines produced in the adrenal medulla, i.e. mainly adrenalin, are not the only cause of the reduced glycogen storage in skeletal muscle after trauma.


Acute paraplegia caused by a spontaneous extradural heamatoma of the conus medullaris area. Four patients with a typical clinical picture of spinal extradural heamatoma of the conus area are presented. Initial symptoms were acute low back pains. The development of symmetrical paraparesis took place in a matter of hours, and spread to total paraplegia. The sensory level was as high as the groins and bladder and rectum paralysis developed early. All patients were over 63, mean age 67 years. Two patients had coagulation defects, one was on anticoagulants, and the other had a severe thrombocytosis. Two patients had used salicylates for rheumatic pains; in one of those patients there was a hemangioma on PAD . In 2 patients, the neuroradiological diagnosis was confirmed with rhizography (Figs. 1 and 2); in the third patient the rhizography was misleading but in her and in a fourth patient the oxygen-myelography was diagnostic, showing an extradural compression in the conus area. Haematomas were removed in all patients through an extensive decompressive laminectomy within 24 hours from the onset of the symptoms. Recovery was good in 2 cases, and fair in one patient who had a poor recovery of the bladder function. In on patient, both paraplegia and bladder paralysis were permanent after 3 years. The differential diagnosis by myelography between the cauda equina syndrome caused by typical disc compression from the one side and from vascular medullary syndromes and myelitis from the other side should be clear. For good functional recovery, early myelography and operative decompression are imperative.


Detection of thyroid cysts by ultrasonic examination. Ultrasonic examination of 80 thyroid nodules was carried out in order to detect fluid-filled lesions of the gland. The results of preoperative ultrasonic examinations were compared with the findings at surgery. For the ultrasonic diagnosis "cyst", a predictive value of 88% was calculated. It is concluded that ultrasonic examination represents a reliable tool for the detection of thyroid cysts.


Papillary thyroid carcinoma in Denmark 1943-68. I. Incidence and clinical features. On the basis of nation-wide Danish data on 1691 cases of thyroid carcinoma during the years 1943-1968, the author reports on 416 cases of papillary thyroid carcinoma reported to the Danish Cancer Registry. Diagnosis was made prior to surgery in about 40% of the cases, in accordance with previous experience. Papillary thyroid carcinoma tends to be less frequent in Denmark than elsewhere, contrary to the assumption of an increased occurrence in areas where goitre is not endemic. For thyroid carcinoma age-adjusted male incidence rates are lowest in Denmark and Great Britain, while female rates for Denmark are second lowest, being lower only in Great Britain. On the other hand, age-adjusted mortality rates are higher in Denmark than in any other country. These findings are discussed. In the past decade the annual number of reported cases has been constant, indicating that the incidence is stationary, although interest in a knowledge of C.T. is on the increase.


The peripheral blood pressure in legs with venous ulcers. Venous ulcers require effective compression treatment which is, however, contra-indicated in cases of arterial insufficiency. In elderly patients with typical venous ulcers the question arises whether they may have concomitant arterial insufficiency. In early studies is was proved that arterial insufficiency in the lower limbs may be diagnosed as a low systolic blood pressure in the great toe as compared with the systolic arm blood pressure. In the present investigation the systolic blood pressure in the great toe was measured in 48 patients with verified venous ulcers. The toe blood pressure and the pressure difference from arm to toe were studied and compared with the corresponding values in normal subjects. 35 patients had no evidence of arterial insufficiency, but in 13 cases signs of concomitant arterial insufficiency was found. The method of measuring the systolic blood pressure in the toes seems to be a simple and reliable method for estimating the degree of arterial insufficiency even in patients with chronic venous disease.


Reactive hyperaemia of the human lower limb. A comparison between the effect of tourniquet occlusion, selective arterial occlusion and intra-arterial papaverine injection. Reactive hyperaemia of the lower limbs in 30 non-atherosclerotic subjects and in 24 patients operated for arterial occlusive disease was investigated preoperatively by electromagnetic flowmetry of the femoral artery. In normal limbs maximal flow values after 5 minutes of tourniquet occlusion averaged 482% of basal flow. Maximal flow increased little when occlusion time was extended beyond 2 minutes. This indicated that occlusion times shorter than the conventional 5 minutes were sufficient in clinical reactive hyperaemia tests. Selective occlusion of the normal femoral artery induced a maximal flow, which was about 50% of that obtained by tourniquet occlusion. The flow increase observed after papaverine injection in this group was 88% of the response induced by 5 minutes of tourniquet occlusion. After arterial reconstruction 5 minutes of selective occlusion of the reconstructed artery induced a maximal flow, which was only 150% of basal flow, whereas papaverine injection increased blood flow to 261.0% of basal level in this group. It is concluded that the hyperaemia induced by intraarterial papaverine injection is considered a useful index of the possibility of flow increase after arterial reconstructions.


Postoperative leg vein thrombosis and pulmonary embolisn after upper abdominal operations. A prospective study with 125I fibrinogentest and pulmonary scintigraphy. The incidence of postoperative deep venous thrombosis in the lower limbs and of pulmonary embolism has been studied in 49 patients operated upon for gallbladder and gastric diseases. 125I fibrinogen test was performed preoperatively and usually five times postoperatively. Pulmonary scintigraphy was also performed preoperatively and usually twice after the operation. An attempt was made to evaluate the prophylactic effect of Dextran 40. Only one patient developed a deep vein thrombosis without clinical signs. Postoperative pulmonary embolism was found in 13 patients, all but one clinically silent. The second postoperative pulmonary scintigraphy showed that the emboli had disappeared or diminished in 6 patients. Because of the low number of patients with deep venous thrombosis the prophylactic effect of Dextran 40 could not be assessed. The present investigation showed that the incidence of deep venous thrombosis in the legs was low after operations in the upper part of the abdomen while the incidence of pulmonary embolism was high. No connection between leg vein thrombosis and pulmonary embolism could be demonstrated.


Evaluation of peroperative cholangiography during cholecystectomy. In a retrospective investigation comprising 219 choledochotomies, of which 57 were explorative (26%), and 162 were choledocholithotomies (74%), an attempt has been made to evaluate the indications for exploration of the common duct and the diagnostic reliability of post-explorative cholangiography. Retrospectively, we find that explorative choledochotomy was justified in 40 out of 57 cases, unless the risk of overlooking stones in the bile ducts was to be increased. In the remainder of the cases (17/57) it was a question of either misinterpretation or of non-evaluable cholangiograms. A diagnostic reliability of 93.6% was obtained at post-explorative cholangiography, making incidence of residual stones at postoperative cholangiography 6.4%. The errors were due to either technically poor cholangiograms (4/14) or misinterpretations (10/14). The conclusion is that peroperative cholangiography is a most important aid in diagnosing stones in the bile ducts before as well after choledochotomy, but that the results presumably to some extent can be improved by using radiological expertise.


The Mallory-Weiss syndrome.

The Mallory-Weiss syndrome. During a 41/2-year period, 1970-74, 174 patients with upper gastro-intestinal bleeding were admitted to the Department of Surgical Gastroenterology, Rigshospitale, Copenhagen, Denmark. In 11, a Mallory-Weiss syndrome was diagnosed. In 10, the diagnosis was made by means of gastroscopy, and in 1 patient at operation. It was not possible to make the diagnosis by means of X-ray examination of the oesophagus or the stomach. In one patient, a hiatal hernia was found. The etiology was violent and repeated vomiting. In 9 of the cases the syndrome was cuased by chronic alcoholic debauch and migraine. In 1 patient, the disease was caused by an abrupt external trauma of the abdomen after a traffic accident. In the last patient, the cause of the disease was uncertain. The treatment was entirely conservative, i.e. blood replacement, in 10 of the patients. The bleeding stopped after this treatment, and it was not necessary to use a Sengstaken-Blakemore tube, nor was a later surgical exploration needed, except in one patient in whom an emergency operation was required because of extensive and persistent bleeding. At operation, 3 mucosal tears were sutured. At the time of discharge, all 11 patients were feeling well. Based on the present material, and cases reported in the literature, we have concluded that emergency gastroscopy is the most reliable diagnostic measure in patients with the Mallory-Weiss syndrome. The treatment ought to be as conservative as possible with replacement of the blood, and surgical intervention should be performed only in the few patients with incontrollable bleeding.


Studies on small intestinal obstruction. III. Circulatory effects of artificial small bowel distension. Feline small-bowel circulation was studied during in vitro homologous perfusion of denervated intestine, following artificial and successive elevation of the intraluminal pressure. The specimens were inflated with nitrogen in 20 mmHg increments to the 100 mmHg level. Each pressure level was maintained for a 10-minute period. After deflation the specimens were studied for a further 60 minutes. Blood flow, vascular resistance, capillary filtration, and oxygen consumption were significantly affected by the distension. In the post-distension period flow rate and vascular resistance remained on levels differing significantly from the control values, whereas capillary filtration and oxygen consumption reverted immediately to levels not differing from the control values. It is concluded that, in isolated and denervated small intestine of the cat, an elevated intra-intestinal pressure affects the consecutive vascular sections in a similar manner, probably by simple mechanical compression. Flow rate is reduced less than capillary filtration, suggesting an opening of short-circuiting shunts in the bowel wall. In the post-distension phase vascular resistance remains elevated, while the exchange circulation is rapidly and completely restored, suggesting an extensive closure of the short-circuiting shunts.


Studies on small intestinal obstruction. IV. Circulatiory effects of artificial small bowel distension after obstruction. Feline small-bowel circulation was studied during in vitro homologous perfusion of denervated intestine shortly after release of an in vivo small-bowel obstruction. Blood flow, vascular resistance, capillary filtration, and oxygen consumption were determined. A previous study demonstrated that any microcirculatory impairment accompanying obstruction was rapidly ameliorated after decompression of the bowel. In the present study the specimens were distended in 20 mmHg increments to the 100 mmHg level. Each pressure level was maintained for a 10 minute period. After deflation the specimens were studied for a further 60 minutes. The results indicate that the microcirculation of the previously obstructed intestine reacts to a considerable distension in essentially the same way as does that of non-obstructed intestine. Certain findings suggest, however, that, by way of enhanced distensibility, an obstruction may render the capillary bed more susceptible to a moderate in crease in intra-intestinal pressure, an increase that in itself does not reduce the capillary filtration rate in non-obstucted intestine.


Volvulus of the colon.

Volvulus of the colon. The results of treatment for volvulus of the colon during 13 years in a community hospital are analysed, It is concluded that sigmoid volvulus should be treated with proctoscopic examination and insertion of a rectal tube, unless signs of gangreana or peritonitis are present. In patients without accompanying sever diseases, elective resection should be performed later. Repeated tube decompressions should be attempted in patients with recurrence and high operative risk. Unsuccessful tube decompressions or signs of a non-viable colon should be followed by emergence laparotomy and, probably, resection of the sigmoid colon whether gangraena is present or not. Volvulus of the cecum should be treated with operative reduction and pexia or cecostomy, unless gangreana necessitating a hemicolectomy is present.


Five cases and five unusual indications for autogenic renal transplantation. Five cases of renal autotransplantation representing five different indications for the procedure are presented and discussed.


[Obstetric prognosis in cases of conjugal sterility evaluation and management of 224 couples]. A retrospective study was carried out in 224 sterile couples examined at the Obstetric and Gynecological Clinic of Genoa University for diagnosis and treatment. The study was performed between November 1, 1970 and May 31, 1973. Secondary sterility was not included. Altogether 84 pregnancies were obtained which amounts to a success rate of 37.5%. Of these 84 pregnancies, 15 started after hysterosalpingography and 17 occurred in couples who had not been given any treatment. Gonadotropin therapy yielded good results in cases treated for anovulation (30% pregnancies) and for slight oligoasthenospermia (32.65% pregnancies). Clomiphene treatment, too, gave good results, with 50% pregnancies. In sterility probably due to inflammatory conditions, the success rate obtained by medical treatment with 12%, while surgical management of tubal occlusions, performed in six cases, yielded only one pregnancy; a single pregnancy was equally obtained in three cases of uterine malformation submitted to Strassmann's operation. Also, only one pregnancy followed surgical treatment of the male partner (ligature of the left internal spermatic vein) in three cases of oligoasthenospermia. Among the couples where deficiencies could be ascertained in both partners, 33.33% of the women became pregnant. As for the evolution of the pregnancies obtained, only 9.52% aborted and 2.39% were ectopic.


Chemical sterilization: effects of a single high dose of 3-chloro-1,2-propanediol on the testes and epididymides of dog. A single high dose (70 mg/kg) of 3-chloro-1,2-propanediol (alpha-chlorohydrin) caused pathological degeneration in the testes of dog when examined after 33 days. The seminiferous tubules were depleted of spermatogenic elements. Epididymal epithelium was regressed, the lumen was empty and the passage through the duct was unimpaired. Alpha-chlorohydrin inhibited the synthesis of RNA and sialic acid of the testes and epididymides. A single high dose of alpha-chlorohydrin increased the total cholesterol/g of wet testis tissue which could be correlated with the testicular atrophy. Antiandrogenic nature of the compound has been discussed.


Glucose and insulin tolerance throughout the menstrual cycle. On the basis of the behaviour during menstrual cycle of the pituitary hormones plasma levels, the Authors have studied during the different periods of the cycle (follicular, ovulatory and luteal) the effects of OGTT and ITT's on the plasma levels of Glucose, insulin, HGH and Cortisol. Significantly lower levels of IRI, HGH and Cortisol were found in follicular phase compared to ovulatory period and luteal phase except for Cortisol in luteal phase. A slightly higher glucose tolerance was found in follicular phase as well as a reduced hypoglicemia under insulin load. Reduced HGH response to ITT was found in follicular phase as well as a reduced Cortisol response compared to the results observed in ovulatory and luteal phase. These data sustain the concept that hormonal variations occurring in an ovulatory cycle are also capable of modifying the woman's body response to various stimuli such as OGTT and ITT.


[Basal values and circadian variations of testosterone, 17beta-oestradiol, FSH and LH in the plasma of normal adult males]. The Authors have determined the concentrations of Testosterone, 17beta-oestradiol, FSH and LH by of radioimmunologic assay in blood of seventy normal adult men blood drawn between eight and eleven a.m.) and in blood of thirteen normal adult men blood drawn at eight and twelve a.m., four and eight p.m.). Average values under basal conditions, and circadian variations have been discussed and confronted with those obtained by other authors.


Changes in sialic acid levels in the dog epididymides under normal and altered physiologic conditions. Sialic acid is secreted by the caput, corpus and cauda epididymides of an adult mature dog. 2- alpha-Chlorohydrin administration results in a considerable reduction in the sialic acid content of the epididymides. 3- Single subcutaneous injection of CdCl2 depletes the content of caput epididymides. Whereas in the corpus and cauda region, the sialic acid contents did not change. 4- The epididymides of caput and cauda ligated side showed a marked decrease in contents of sialic acid as compared with that of non-ligated control epididymides of the same animal. Bilateral vasectomy and 72 hour vascular occlusion resulted in the reduction in the sialic acid content of the epididymides. 5- It is interesting to note that the decrease in sialic acid in the epididymides coincided with the absence of sperms and reduced secretory activity of the luminal epithelium. 6- The significance of these changes is discussed.


A new method for the diagnosis of pelvic pathology by gammagraphy. Part I - description of the method and normal results. This is an original method for the diagnosis of pelvic congestion, consisting in the utilization of a radio-isotope suitable for vascular examinations. We have chosen the 13mIn, injected into the patients under operating conditions identical in dosage per kg weight, position, length of exposure, day of cycle etc. The radioactivity emitted is received by an external detector, in this case the Gamma camera. The correlation between a higher degree of radioactivity and the presence of pelvic varicosities is analysed. The criteria employed were: 1 degrees the gammagraphic immages; 2 degrees the profiles taken at the level of the infundibulus and 3 degrees the "information units" measured and accumulated by the gammacamera at each point of the profile. A description of a normal pelvic gammagraphy was made, with the characteristics which define it and differenciate it from the pathologies. Finally the physiological gammagraphic variations present in multiparous patients were considered.


A new method for the diagnosis of pelvic pathologies Part II - interpretation of abnormal images. The results presented are those presented are those obtained on the diagnosis of pelvic congestion by means of the use of radioactive isotopes, following an original method proposed by us and previously described. It has been carried out on 100 patients, of whom 6 were normal and 94 presented some gynecological pathology in the internal genitals. Laparatomy was carried out, proving the lesions visually in 51 cases. The diagnosis was correct in 98% of the cases. Finally the advantages which it presents over phlebography were analysed, and the possibilities of the method in gynecological practice suggested, since it can be used in a great number of genital diseases to carry out a diagnosis of vascular pathology.


Obstetrical analgesia assessed by free fatty acid mobilisation. Two groups of six parturients each have been compared. One group received centrally acting analgesics, sedatives and intermittent nitrous oxide and the other group was given epidural anaesthesia. The serum free fatty acid (FFA) concentrations of the parturients in the former group increased steadily during labour, attaining peak values between 1050 and 1750 mumol/l at delivery. In parturients belonging to the epidural group, the serum FFA concentrations remained level or even fell towards the time of delivery. It is suggested that the increase in serum FFA reflects a stress induced adrenergic lipolysis which may be used to assiss the various methods for obstetrical analgesia. It is concluded that epidural anaesthesia is superior to the conventional methods of pain relief. Analyses of blood sampled from the unbilical veins show that the concentrations of FFA in the blood of the newborns do not reflect the corresponding maternal values. Thus, epidural anaesthesia does not seem to deprive the fetus of FFA during labour since the factor limiting its transfer appears to be independent of the concentration gradient over the placental membrane.


A rational approach to dosage and preparation of parenteral glucocorticoid substitution therapy during surgical procedures. A short review. A rational physiological schedule for parenteral glucocorticoid substitution therapy during surgical procedures is proposed based on the principle of imitating the normal hypothalamic-pituitary-adrenocortical response to surgery. The schedule includes the injection of 25 mg cortisol intravenously in all patients together with induction of anaesthesia. Following major surgery, 100 mg cortisol dissolved in saline or glucose is continuously infused intravenously every 24 hours until gastrointestinal function permits oral intake of usual glucocorticoid substitution therapy. In case continuous cortisol infusion is undesirable, 25 mg cortisol is injected intravenously every four hours. Following minor surgery, usual oral glucocorticoid therapy is started immediately after the operation. It is recommended to use water-soluble cortisol preparations and not cortisone acetate, which results in limited plasma cortisol levels.


Blood circulation in the kidney of the cat under methoxyflurane (penthrane) anaesthesia. In order to establish whether methoxyflurane causes any change in renal vascular resistance, the renal venous flow was measured by means of a drop recording technique in six cats under methoxyflurane anaesthesia. Arterial pressure was recorded simultaneously, and the renal vascular resistance was calculated. Methoxyflurane caused a significant reduction of the renal vascular resistance to about 85% of control value at an anaesthetic depth characterised by loss of the corneal reflex. At a deeper anaesthetic stage characterised by steady state circulation and absence of any reflexes, no further significant fall in renal vascular resistance occurred. Autoregulation and depression of the sympathetic activity are assumed to explain the reduction of the renal vascular resistance.


The interaction of tilidine and pethidine in postoperative pain. The mode of interaction between the new, non-narcotic analgesic tilidine and pethidine was studied in the treatment of postoperative pain. The potency ratio 3:1 (pethidine:tilidine) found previously was used in the comparison. Thus 0.25 mg/kg of pethidine with 0.75 mg/kg of tilidine and 0.5 mg/kg of pethidine with 1.5 mg/kg of tilidine were compared with 0.5 mg/kg and with 1.0 mg/kg of pethidine. These drug combinations proved to be equipotent with the pethidine dosages used. Consequently the mode of interaction seemed to be additive synergism. The onset of action was slightly faster with pethidine, but the duration of action was longer with pethidine-tilidine combinations. Respiratory depression and sedation were less evident after pethidine-tilidine combinations than after equianalgesic doses of pethidine. Circulatory effects were similar in all groups. No statistical difference in other side effects could be demonstrated between the groups.


Brain damage following collapse of a polyvinyl tube: elasticity and permeability of the cuff. A 13-year-old boy undergoing tympanoplasty lasting 3 1/2 hours developed serious airway obstruction at the end of surgery leading to permanent brain damage. It appeared that the no. 7 Portex "blue line" endotracheal tube had collapsed under the cuff. This was concluded because deflation of the cuff had promptly relieved the obstruction of the airway. Further support for this conclusion was the finding that shortly after extubation the inflation of 8 ml air caused the tube to collapse. Collapse of these tubes cannot normally be produced unless they have been made to collapse shortly before. Investigation of such tubes in vitro at 37 degrees C showed that overinflation of the cuff caused a symmetrical collapse of the tube wall along the x-ray opaque blue line. The collapse occurred with cuff pressures varying from 310 mmHg up to 460 mmHg for tubes from different batches. During anaesthesia with 66% nitrous oxide, this gas together with carbon dioxide were found to diffuse into the cuff at steady rates of 3.69 vol % and 0.36 vol % per hour, respectively. Corresponding increases in intracuff volumes were found. It is advised that disposable tubes should be carefully inspected before use and that endotracheal cuffs should be deflated periodically during anaesthesia to avoid excessive rise in cuff pressure.


Whole-brain blood flow and oxygen metabolism in the rat after halothane anesthesia. A recent modification of the Kety-Schmidt wash-out technique for 133xenon was used to measure whole-brain blood flow (CBF) and oxygen consumption (CMRO2) 1 to 4 hours after termination of halothane anesthesia in 15 Wistar rats. In this 3-hour experimental period, mean CBF and CMRO2 were reduced to 29 and 43% of control values, respectively. CBF and CMRO2 determined at the beginning and end of the experimental period were not significantly different from each other. Cerebral venous O2 tension was significantly higher than in the control group, supporting recent suggestions of a primary, intrinsic effect of halothane on the homeostatic control of this variable. It is concluded that halothane is not useful for cerebral metabolic studies in the rat.


Suppression and regeneration of rat bone marrow under the influence of methotrexate. An EM study. Adult male rats were given daily injections of methotrexate for 12 days, during which time specimens of femoral bone marrow were taken for correlative light- and electron-microscopic study. After 12 days methotrexate was discontinued and specimens were taken the marrow recovered from the effect of methotrexate. Normal rat bone marrow was used as a basis of comparison. As methotrexate was administered, cell division ceased and the immature erythroblasts and myelocytes proceeded in the maturational process and a rapid hypocellularity of the marrow developed. Eosinophilic leukocytes, lymphocytes, large fat cells, erythrocytes, and phagocytic reticuloendothelial cells were the only formed elements remaining after 12 days of methotrexate treatment. Two days after methotrexate was discontinued, myeloblasts, myelocytes and proerythroblasts were plentiful, and on the third day the marrow exhibited an erythroid hyperplasia. By the eighth day all cell types were present though the marrow still was hypocellular. 14 days post methotrexate the marrow returned to normal.


Nature and fate of the ureteric membrane closing the primitive ureterovesical opening. 83 albino rat embryos were used to investigate and ascertain the presence of the ureteric membrane closing the mouth of the primitive ureterovesical opening. The membrane is found to be derived from the stratified etithelium lining the urogenital sinus and later the developing urinary bladder. It progressively thins out and bulges in the bladder cavity as a result of the increasing functional differentiation and activity of the developing kidney, where the excreted urine dilates the lower end of the ureter till it forms a small cyst-like dilatation before the membrane finally ruptures. The destruction of the ureteric membrane occurs caudal to its center and is immediately followed by dilatation of the bladder cavity and differentiation of mits musculature and lining epitherlium.


Lack of development, factor of congenital ureterohydronephrosis. Female Swiss mice (25-30 g) received a single subcutaneous injection of 200 mug nucleotoxic substance (chloraminophen) on day 11 of pregnancy. The fetuses taken from the treated mother on day 18 show a significant lack of development and urinary anomalies, such as ureterohydronephrosis (26%) and renal agenesis (few cases). Ureterohydronephrosis seems to be caused by lacking development of the ureterovesical junction region.


Succinic dehydrogenase activity of the respiratory muscles of a fresh-water teleost, Bagarius bagarius (Ham.) (Sisoridae, Pisces). Functional morphology including the origin, insertion, and innervation of the respiratory muscles in relation to buccal pressure pump and opercular suction pumps in a fresh-water bottom dwelling siluroid fish, Bagarius bagarius have been studied. Histochemical studies were made on the succinic dehydrogenase activity of adductor mandibulae, retractor tentaculi, levator operculi, dilatator operculi, adductor operculi, intermandibularis, interhyoideus, hyohyoideus superior and constrictor branchialis. The intensity of reaction reveals the presence of three types of muscle fibres in some of the respiratory muscles. The muscle containing red muscle fibres are mostly innervated by the branches of the VIIth cranial nerve. The retractor tentaculi consists of superficial white muscle fibres and the interior part is dominated by red muscle fibres. The muscles (adductor operculi, levator operculi, dilatator operculi, interhyoideus, hyohyoideus superior) concerned with the opercular suction pumps are of mixed type and consist of white and red muscle fibres, whereas adductor mandibulae and intermandibularis are made up entirely of white muscle fibres. The adductor muscle bundles of the constrictor branchialis, which are responsible for movement of gill filaments, are dominated by the red muscle fibres. The abductor part, however, is made up entirely of white muscle fibres.


Cartilage canals in the human spheno-occipital synchondrosis during fetal life. Spheno-occipital synchondroses were studied histologically in eight human fetuses ranging from 100 mm CRL to term. Cartilage canals were present in all seven specimens over 110 mm CRL. With age the canals grew longer and wider and the larger ones developed some branching. The histologic structure, external morphology and spatial arrangement of these cartilage canals were described. Some attributes of cartilage canals were reviewed from available data in the literature and their significance for the present findings discussed. It was suggested that the canals, containing blood vessels and connective tissue elements, actively invade the cartilage of the synchondrosis. It was suggested further that they probably serve as a source of nutrition or as an extension of the perichondrium (and a source of prospective chondroblasts) or both.


Semimicroscopical observations on the crista stapedis. Adult and fetal human stapes were removed by means of the stereoscopic microscope in order to compare the size of the lamina or crista that joins the crura of the stapes and rests in the lateral aspect of the basis. 65 out of 110 specimens showed cristae of different sizes, whereas the remaining 35% did not possess this structure. The cristae were classified into large, medium-sized and rudimentary. Several incomplete or irregular structures were also found. The cristae or laminae divide the lateral aspect of the base into two fossae: a small upper one and a large lower one, although several variations were found. An edge of the pillar groove was usually continuous with the cristae; however, compact pillars were found at the point where they reach the base, where the cristae orginates. Asymmetrical cristae and changes in the general shape of the stapes were found in several specimens. Two ossicles showed crista with orifices due to resorption or to the passage of vessels.


Antagonistic response of chlorpromazine and formalin in effecting quantitative changes in the neurosecretory material in the teleost Clarias batrachus (L.). The hypothalamoneurohypophysial complex of Clarias batrachus maintains an appreciable quantity of neurosecretory material (NSM) under normal conditions. Stress caused by the injection of formalin depletes 70-90% of the stainable NSM from all the component parts of the neurosecretory system, namely the nucleus preopticus (NPO) the neurosecretory tract, and the neurohypophysis. Formalin apparently releases the NSM and stimulates the neurons of the NPO. Chlorpromazine (CPZ) treatment seems to cause quantitative increase of NSM throughout the neurosecretory complex. Simultaneous injection of CPZ and formalin showed that the formalin-induced depletion of NSM could be inhibited by CPZ.


Electrostimulation and morphologic study of the nerves to the bone marrow of the albino rat. The innervation of the bone marrow of the albino rat was investigated by electrostimulation and morphological methods. Stimulation of the lumbar sympathetic trunks resulted in the release of reticulocytes and neutrophils into the circulating blood. The effects of stimulation on other cell types in the bone marrow could not be definitely established. It was concluded that the nerve fibers to the bone marrow were distributed to the arteries. It is postulated that the transmitter substance released at the autonomic nerve endings may have an effect upon the permeability of the venous sinusiods and the mobility of the blood cells in the marrow parenchyma resulting in their release into the circulating blood.


[A histochemical and biometric comparison of the long peroneal muscle and its innervation in Gallus gallus and Coturnix c. japonica]. Following a previous comparison of the peroneus longus muscle of the quail and the starling, the present paper deals with a comparative study of this muscle in two birds of the order Gallinaceae, the quail and the bantam, bearing in mind certain data found in the starling. The study deals with the types of muscle fibres, their frequency in various parts of the muscle, their lipid content and their innervation. In the quail, two types of fibres are found, with a low and high lipid content respectively, while the bantam and starling have also a third, intermediate type. These intermediate fibres have a characteristically intermediate lipid content, peripherally situated nuclei and areas with a myofibrillar structure. The proportion of the two of three types of fibres varies with the species and in the distal and proximal parts of the muscle. The innervation of the peroneus longus muscle is different in the three species. In the quail, the two types of fibres have only one arboriform motor end-plate per fibre. In the bantam, the two types of homologous fibres also have only one motor end-plate, but with fewer arborifications. The intermediate fibre type, on the other hand, is innervated by several small nerve endings for each muscle fibre. This type of multiple innervation is also found in the starling. The peroneus longus muscle is thus functionally different in the two birds of the order Gallinaceae, whereas the rapid and slow system of innervation is found in the bantam and the starling. In the quail and the bantam, there is a strong positive correlation between the diameter of the muscle fibre and the longitudinal extent of the motor end-plate. This correlation is not marked in the starling. The characteristics of the innervation revealed by the cholinesterase activity concentrated in the synaptic grooves were confirmed by a direct study of the nerve fibres, using the Bielschowsky-Gros method. In the quail only 'en plaque' endings are found, while in the bantam and the starling both 'en plaque' and 'en grappe' endings are present. A parallel is drawn between the differences in function of the peroneus longus muscle and the characteristic features of its histology and innervation in the three species.


Trigeminothalamic fibre connections in the donkey (Equus asinus) studied by means of the retrograde cell degeneration method. In this study the left thalamus of seven very young donkeys was transected and the trigeminothalamic fibre connections were investigated by means of the retrograde cell degeneration method. The animals were allowed to survive for a period of 15-45 days and the paraffin sections of the brain stem were stained according to the Klüver-Barrera and the thionine methods. It was found that the principal sensory trigeminal nucleus exhibited retrograde cell changes and cell losses, in its dorsal part, only at the side ipsilateral to the thalamic transection. As far as the nucleus of the spinal tract is concerned, slight changes were found, mainly contralaterally, in its oral subnucleus only. These findings suggest that in the donkey the main trigeminothalamic projection follows an ipsilateral course to the thalamus.


Human embryo (12 mm) with mesohydronephrosis and ureterohydronephrosis. This report describes a human embryo with a length of 12 mm (horizon XVII Streeterm 35 +/- 1 day old), in which the following malformations appear: Dilation on both sides of the Wolffian ducts, and the more caudal mesonephritic glomerules (mesohydronephrosis). Dilatation of both ureters and renal pelvis (uretero-hydronephrosis). These malformations are the result of the accumulation of liquid secreted by the mesonephros in a cloaca which is dilated, unwalled and blocked by an epithelial plug which is continuous with the cloacal membrane.


Response of the pituitary of the catfish, Heteropneustes fossilis (Bloch), to bilateral ovariectomy. Hypophyseal response to bilateral ovariectomy was studied in the catfish, Heteropneustes fossilis, during the prespawning (May) and the spawning (July) periods. During the prespawning period, a significant increase in the number of granulated PAS-positive basophils in the proximal pars distalis of the castrates was recorded on day 45 post-ovariectomy; thereafter a gradual degranulation of basophils was observed. However, in the spawning period a dramatic increase in the number of granulated basophils of the castrates was seen on day 8 post-ovariectomy and the number decreased thereafter. This differential response of the hypophysis to ovariectomy is discussed.


Electron-microscopic study of monotreme neuroglia. Glia cells were examined in the brains of a mature platypus and an immature echidna. In the echidna a few dark, organelle-rich glia cells were encountered. The lighter glia cells had resemblances with the single type of glia cell encountered in the brain of the platypus. These cells were characterised by highly homogeneous areas of nuclear chromatin and light cytoplasm containing dark, finely granular condensations which frequently surrounded Golgi membranes. Microtubules were present within the cytoplasm but neither filaments nor glycogen-like particles were encountered. It was concluded that the cells described conformed to the types of neither astrocytes nor oligodendrocytes as encountered in metatherian and eutherian mammals. Among their functional capacities such cells presumably include, either in the immature or mature forms, the roles of both astrocytes and oligodendrocytes.


Abdominal vagal paraganglia: distribution and comparison with carotid body, in the rat. A study was made of the distribution of abdominal vagal paraganglia in the gastro-oesophageal region of 12 rats. In all rats 4-40 paraganglia were found embedded in, or closely associated with, the vagus nerves and their branches. The paraganglia consisted of groups of rounded, weakly chromaffin-positive cells surrounded by flattened cells and supplied by small nerves and blood vessels. The paraganglia were morphologically identical to simultaneously fixed carotid body tissue and showed similar fluorescence characteristics.


Transplantation of the future coronal suture on the dura mater of 3- to 4-month-old rats. From fetal rat skulls, tissue containing the presumptive coronal suture was excised and transplanted onto the exposed dura mater of adult rats. Donor animals were sacrificed at specific ages determined by developmental stages of the suture as occurs in the rat. Thus, sacrifices were made at (a) the 19th day of fetal life when a blastema formation in the suture is not yet observable; (b)  the 20th day when blastema formation becomes apparent, and (c) the 21st day when the blastema is clearly visible. From the results of these experiments, the following conclusions could be drawn: (1) transplants from 19- and 20-day-old fetuses are not capable of autonomous development in host tissue; continuation and regulation of this process occur in situ only; (2) within the connective tissue of the 19- and 20-day transplants the process of suture formation is arrested; instead chondrogenetic activity occurs, resulting in the production of ectopic cartilage, and (3) when formation of the blastema has been completed prior to transplantation, i.e. at the 21st day, its capability of producing a suture in the host tissue remains unimpaired. Sutures originating from these transplants do not ossify, not even when left in situ for 2 or 3 weeks. These findings suggest the existence of an osteogenesis-inhibiting mechanism located in embryonic sutural tissue, being transmitted to the developing dura.


[Acetylcholinesterase activity in spiral ganglion cells in rats]. Acetylcholinesterase has been demonstrated in the spiral ganglion cells by the method of Karnovsky and Roots. After incubation for 24 h the content of AchE was measured with the help of a three-stage scale. 22% of the cells showed strong, 50% medium and 28% weak AchE activity. Within the spiral ganglion perikarya, the enzyme was equally distributed.


Hepatocytic ultrastructure in splenectomized rats treated with pregnenolone-16alpha-carbonitrile, a microsomal enzyme inducer. Pregnenolone-16alpha-carbonitrile (PCN), given orally at the dose of 6.8 mg/100 g body wt, twice daily for 3 or 6 days, increased liver weight in intact rats, and reduced zoxazolamine paralysis in both unoperated and splenectomized animals. The steroid induced smooth endoplasmic reticulum proliferation in the hepatocytes of intact and splenectomized rats, while splenectomy alone caused rough endoplasmic reticulum fragmentation and vesiculation. It appears that the spleen does not influence the hepatic action of PCN.


Meal timing dominates the lighting regimen as a synchronizer of the eosinophil rhythm in mice. Mouse eosinophils undergo circadian fluctuation, and the phasing of the rhythm normally is synchronized to the environmental light-dark cycle if food always is available. This study was undertaken to determine whether or not the same rhythm could be synchronized to restricted feeding schedules. It was found that if food is available ad libitum for only short spans (in this case, 4 h during each 24 h period), the rhythm becomes synchronized to the feeding schedule. In addition, restricting food to certain 4 h spans causes the amplitude of the eosinophil rhythm to increase significantly over that of normal, light-dark synchronized animals. Not all rhythmic variables synchronize to restricted feeding schedules. Some remain synchronized to the light-dark cycle; the phasing of others seems to be the result of an interaction between both the light-dark cycle and the feeding schedule. These studies help dispel the popular misconception that all body functions react in the same manner to different synchronizers and emphasize that one must not generalize about the synchronizing effect of feeding or lighting.


Quantitative investigation of stem cell candidates in the bone marrow of growing guinea pigs. Possible candidates for hemic stem cells were studied in a quantitative investigation of the bone marrow of growing guinea pigs. The stem cell candidates were classified as lymphoid cells of types I-IV, roughly corresponding to small lymphocytes, large lymphocytes, micromyeloblasts and myeloblasts of other authors. The cellular content of the bone marrow of guinea pigs of three different ages was determined. All types of nucleated cells per femur were found to increase with age. When the cellular content was related to the body weight, a peak number of lymphoid cells was found in the intermediate age group with the exception of the lymphoid cells of type III, which reached its peak in the oldest animals. This cell type has been suggested by Dicke et al. as the probable stem cell responsible for colony formation.


The harp seal, Pagophilus groenlandicus (Erxleben, 1777). XVII. Structure and metabolic adaption of the caval sphincter muscle with some observations on the diaphragm. Three types of fibre, dark (type 1), light (type 2) and intermediate, were distinguished in the caval sphincter muscle of the diaphragm in the harp seal (Pagophilus groenlandicus) using histochemical and electron-microscopic techniques. The dark fibre contained large peripheral aggregations of mitochondria, numerous lipid droplets and dense aggregates of glycogen granules. The same features were observed in the dark fibre of the diaphragm muscle too. In the light of the low oxidative enzyme activity and high lipase activity observed in the diaphragm and other skeletal muscles of the harp seal in previous studies, it is postulated that these mitochondrial aggregations and lipid droplets represent an adaptation for the generation of heat through non-shivering thermogenesis comparable to that in the brown adipose tissue. Such ability to generate and maintain heat by uncoupling the oxidative phosphorylation process should enable the caval sphincter muscle to function efficiently in regulating the cardiac return of blood from the inferior vena cava during a dive when the body temperature as a whole drops. The lack of the regional differences in the fibre composition of the harp seal diaphragm, as were reported in the rat diaphragm, is attributed to the seal's large body size, lower metabolic rate and diving habit.


Causes of death in transposition of the great arteris. A clinical and autopsy study of 140 cases. The causes of death were assessed in 140 infants and children with transposition of the great arteries studied clinically and post mortem. Half of the children were under one month old. Death occurred during the first year of life in 118 cases. Balloon atrial septostomy and/or cardiac surgery were performed in 37 cases, and 7 patients died following operations for extracardiac malformations. Congestive heart failure was the most common single cause of death, occurring in 109 cases. All but 7 patients were cyanotic. Extracardiac malformations were encountered in 39 patients and were considered a main cause of death in 22 of these. Various infections, mostly pneumonia, occurred in half of the cases. Forty-one patients had vascular accidents in various organs. These complications were more common in operated than in nonoperated cases. Miscellaneous causes of death, including hyaline membrane disease and/or pulmonary atelectases, occurred in 30 patients. The study illustrated the complex symptomatology and therapeutic problems presented by critically ill infants with transposition of the great arteries.


Health screening of four-year-olds in a Swedish county. I. Organization, methods and participation. Since January 1969, a systematic health screening has been offered to 4-year-olds resident in the county of Uppsala, Sweden, at the ordinary Child Health Centres by the regular staff. This report describes some organizational and methodological aspects and presents participation rates and reasons for non-participation. From the overall experience it is concluded that the program is feasible with respect to systematic examinations and data collection, acceptance by the public and the staff, and with respect to the strain on existing resources. The reasons for and the importance of program changes are discussed, and the main advantages and drawbacks of the decentralized approach are mentioned. Finally, a theoretical framework for a quantitative evaluation of effectiveness is presented.


Health screening of four-year-olds in a Swedish county. II. Effectiveness in detecting health problems. Quantitative results obtained during the first 3 years of operation of a routine health screening program for 4-year-olds are presented. From these figures it is conccluded that the effectiveness in detecting previously unknown health problems needing treatment is high enough to justify the continuation of this systematic health screening by the ordinary child health staff. However, the total prevalence of newly detected anomalies was lower in our population than in similar studies where the screening was performed by a few teams of specially trained professionals. The consequences of this observation are briefly discussed.


LDH-isoenzymes in children. A comparison of values from capillary and venous blood. A comparison has been made of serum values of LDH-isoenzymes obtained by simultaneous sampling of capillary and venous blood in 40 normal children. No satisfactory correlation between the paired values could be found. Evaluation of the pattern of serum LDH-isoenzymes in children therefore requires a reference, i.e. normal values of isoenzymes obtained by the same technique of blood sampling.


Systolic time intervals in newborn infants. Systolic time intervals, calculated from the carotid artery pulse curve have been used for some time to assess left ventricular performance. Normal values have been established for adults and older children, but few investigations have been made on newborn infants, generally with partly contradictory results. Therefore a study has been undertaken in 29 normal newborn infants 1/2-119 hours old, and 9 infants 2-3 months old to establish normal values for different intervals. They were found to differ from those reported for adults and older children, most clearly seen in the relatively long preejection period (PEP). Statistically significant differences were found between the PEP of 20 infants below 47 hours of age and 9 infnats 2-3 months old: PEP 82 ms and 68 ms respectively. (p less than 0.01); the same is true of the quotient PEP/LVET (left ventricular ejection time), which was found to be 0.41 and 0.35 resp. (p less than 0.01). By adult standards this would mean impairment of left ventricular function. A possible explanation of this could be a difficulty for the left ventricle to cope with the systemic circulation during the first days of life even in normal newborns, a difficulty not fully compensated for even at 3 months of age.


Menarcheal age in Northumberland.

Menarcheal age in Northumberland. A second survey of age at menarche in north-east England, how it is affected by family environment and how it affects physique, was carried out in 1960-70 on a large sample of schoolgirls in the suburbs of Newcastle. Age at menarche shows no independent effect of social class or of position in sibship, but is strongly influenced by the size of family in which a girl grows up. Menarche is associated with pronounced increments in height and weight, in the presence of which no consistent effects of variables of the family environment on physique can be clearly identified. The results are very similar to those from the first study in South Shields, County Durham.


Glucosephosphate isomerase deficiency in a Dutch family. A mentally retarded girl with severe hemolytic anemia due to glucosephosphate isomerase deficiency is described. The deficiency was detected in erythrocytes, leukocytes, thrombocytes, liver and muscle tissues. Besides the glucosephosphate isomerase deficiency, a glutathione instability of unknown origin was found in the erythrocytes of the propositus.


Acute liver failure and encephalopathy (Reye's syndrome?) during salicylate therapy. A case of hepatotoxicity and encephalopathy (Reye's syndrome?) associated with salicylate therapy is presented and the aetiology of this syndrome is discussed. Hepatotoxicity developed with salicylate serum concentrations not exceeding therapeutic serum levels. The importance of controlling serum salicylate concentration and transaminase activity particularly during the first fourteen days of therapy is emphasized.


Generalized myopathy and cerebral malformations possibly related to an enteroviral infection. A study was made on a case of generalized muscular hypotonus manifested at birth. Serological findings and epidemiological data suggested an association to a recently described enterovirus infection (enterovirus candidate 71) known to cause neurological disease in man. Autopsy revealed cerebral malformations and generalized myopathy compatible with a viral etiology of the disease.


The role of the parathyroids for the adaptation to a low calcium intake. 3. The long-term effect of parathyroidectomy on the adaptation to a low calcium intake in adult rats with special reference to plasma calcium, bone tissue and adrenal glands. One-year-old selectively parathyroidectomized rats responded with a plasma calcium reduction to below 4.1 mEq./1 in 86 per cent at a normal and in 100 per cent at a low dietary calcium intake. Among the former, 17 per cent normalized their plasma calcium level within 8 weeks and another 40 per cent between the 8th ana 27th week of observation. Among the latter, only 10 per cent showed a normalization and first after the long-term period of observation. On the normal level of dietary calcium the parathyroidectomized animals with persistently reduced plasma calcium showed a significantly increased bone mass which was paradoxical in view of their inability of adaptation. On the low level of dietary calcium a normal bone resorptive activity was maintained despite parathyroidectomy possibly through the action of increased levels of 1,25-dihydroxycholecalciferol provoked by the profoundly reduced plasma calcium. This was, however, insufficient for adaptation and no osteoporosis developed. For the adaptation to a reduced calcium intake skeletal calcium reserves had to become mobilized through the action of the parathyroids with resulting osteoporosis. This was brought about by increased mobilization of skeletal calcium with resulting osteoporosis, a phenomenon which could be seen also among the parathyroidectomized animals on a low dietary calcium and with a normalized plasma calcium level. This osteoporosis was similar to that found in the calcium deficient intact animals. The described bone changes were progressing in character and there was no major influence by any eventual effect on bone growth. At histological and morphometric analyses of the adrenal cortex no apparent changes were found after parathyroidectomy.


The role of the parathyroids for the adaptation to a low calcium intake. 4. The long-term effect of parathyroidectomy on the adaptation to a low calcium intake in adult rats with special reference to calcium metabolism. One-year-old selectively parathyroidectomized rats showed, on a normal dietary intake of calcium, phosphorus and vitamin D, a reduction in plasma calcium to below 4.1 mEq./1 in 86 per cent and on restricted calcium intake in 100 per cent. On the normal level of dietary calcium, normalization of plasma calcium occurred 17 per cent within 8 weeks and in another 40 per cent between the 8th and 27th week of observation while on the low level only 10 per cent of the animals normalized their plasma calcium and first after the long-term period of observation. This was most probably accomplished by successively restored parathyroid activity from aberrant parathyroid tissue as deducted from data regarding the metabolism of calcium, magnesium and inorganic phosphate. Adaptation, viz. normalization of plasma calcium, was brought about by mobilization of skeletal calcium with resulting osteoporosis, as reported in our previous study on the same animals. Intestinal net absorption of calcium showed no significant difference between normocalcemic normophosphatemic intact and hypocalcemic hyperphosphatemic parathyroidectomized animals at the respective level of dietary calcium. Thus, parathyroidectomized animals with persistently reduced plasma calcium showed a normal adaptory increase in intestinal calcium absorption upon chronically restricted calcium intake. In the discussion of the regulation of this adaptory system the possible effects of the plasma concentrations of both calcium and inorganic phosphate upon the intracellular Ca22+concentration in the kidney tubules must be considered. Plasma magnesium did not appear to have a primary influence. Intestinal absorption of inorganic phosphate was not dependent upon the presence of the parathyroids but followed that of calcium suggesting a regulation by the action of 1,25-dihydroxycholecalciferol.


Effects of supply and withdrawal of fluoride. Experimental studies on growing and adult rabbits. 8. Phosphatase activity in fluorotic bone. Growing rabbits were given 200 ppm of fluoride in the drinking water during 14 weeks. During this period excessive fluorotic changes developed in the diaphyses of the femur and tibia. The alkaline phosphatase and pyrophosphatase activities increased simultaneously in the fluorotic bone whereas the ratio between the activities remained constant. Acid phosphatase activity also increased. The increase in enzyme activities was regarded as due to the increased bone turnover and not as a primary consequence of fluoride ingestion.


Chronic rheumatic valvular heart disease. An autopsy study. The incidence of chronic rheumatic valvular heart disease in Iceland was investigated via autopsies performed from November 1965 through December 1974. During this period, approximately 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these are included in the study. At autopsy, males were found to outnumber females by 2:1. Rheumatic valvular heart disease was found in 38 subjects, i.e. in 1.08 per cent of the cases, the sex distribution being 0.67 per cent males and 1.83 per cent females. As regards the hearts with chronically deformed valves, the deformity was of rheumatic origin only in 20 per cent of the cases; the majority, or 69 per cent, presented calcified aortic stenosis. Hospital records applying to most of the subjects were available and according to these, only 18 per cent disclosed a history of rheumatic fever. The diagnosis of rheumatic valvular disease was first established at autopsy in 71 per cent of the cases. An evaluation of the functional derangements of the diseased valves was not attempted, but there is reason to believe that many of the lesions were too mild to provoke significant symptoms and signs. Previous doubts about the existence of rheumatic heart disease in Iceland have been settled in this study.


Malignant hyperthermia in a family. The ultrastructure of muscle biopsies of healthy members. Twelve healthy relatives of two children who died of malignant hyperthermia--volunteered to give biopsies of striated muscle. Electron microscopy of their muscles revealed nonspecific myofibrillary degeneration and profound alterations of parts of muscle fibres. Furthermore, constructional faults were found in the architecture of the muscle. Previous investigations correlated with these abnormalities support the assumption, that inborn errors of metabolism may involve membranes of other tissues as well as striated muscle.


Skeletal fluorosis in immobilized extremities. The effect of immobilization on skeletal fluorosis was studied in growing rabbits. One hind leg was immobilized by an external fixation device extending below the wrist joint and above the knee joint, the extremity being in a straight position after severance of the sciatic nerve. The animals, aged 7 weeks at the beginning of the experiment, were given 10 mg of fluoride per kg body weight and day during 12 weeks. In the tibiae, development of the skeletal fluorosis was more irregular than that observed in previous studies of normally active animals, being most excessive in the mobile bone. The immobilization effect was most profound in the femora as the cortical thickness and the femur score were significantly higher than those in the mobile femora. It was suggested that an altered muscular activity was the reason for the observed changes.


Deoxyribonucleic acid content in the laryngeal mucosa with special reference to polyploid cell nuclei. The DNA content was measured by microphotometry in morphologically normal squamous epithelium of the larynx, in hyperplastic epithelium of the vocal cords and in invasive squamous-cell carcinoma. The average nuclear DNA content in the squamous-cell carcinoma was elevated in comparison with that of normal epithelium, and the values showed a much wider dispersion. During premitotic DNA synthesis, the nuclear content of DNA is doubled. Polyploid cell nuclei with a nuclear DNA content of more than twice the model value (the stem cell of the tumour) are therefore a distinct sign of an abnormally elevated content of DNA. In morphologically normal epithelium no polyploid cell nuclei were revealed, while such nuclei were present in all cases of invasive squamous-cell carcinoma. Polyploid cell nuclei were found in six out of 20 patients with hyperplasia of the epithelium of the vocal cords. Among these six patients, manifest invasive carcinoma developed inthree, carcinoma in situ in one, while the condition remained benign in two, probably because the pathological tissue was completely removed. The presence of polyploid cell nuclei should thus arouse a strong suspicion of malignancy and calls for close supervision of the patient.


Growth patterns and chromosome constitutions of human malignant tumours after long-term serial transplantation in nude mice. Five human malignant tumours, heterotransplanted to athymic nude mice, have been re-investigated after long-term serial transplantation, and their growth patterns and chromosomal constitutions compared with their early appearance. After 27-56 passages over 3 1/2--5 1/2 years, all of the tumours--two adenocarcinomas of the colon, two malignant melanomas, and one Burkitt's lymphoma--retained the cytological and histological appearance of the inoculated human material. All the mitoses observed in the chromosome studies were of human karyotype. The fact that no total chromosomal species shift, no interspecies hybridization, and no changes in biological properties appeared--as observed in some other heterotransplantation systems--would indicate that human tumours grafted to nude mice are more suitable models in, e.g., studies concerning cancer chemotherapeutics.


The effect on the rat liver of long-term administration of different alcoholic beverages together with inadequate diets. Rats were given 36 per cent of calories as ethanol, gin, brandy, whisky or red wine together with hypocaloric (25 per cent of normal), hypocaloric--low-protein--highfat, or hypocaloric--low vitamin diets for several months and compared with rats given isocaloric amounts of glucose instead of alcohol. In spite of high mortality rate no severe liver lesions occurred, especially no cirrhosis. Congeners present in different alcoholic beverages therefore seem to lack important hepatotoxic effects at least in the rat.


Collagen development in granulation tissue as compared with collagen of skin and aorta from injured and non-injured rats. Granulation tissue in rats was produced by subcutaneous implantation of viscose cellulose sponges. Granulomas, aortae, and skin samples were taken 4, 8, 14, 22, 33, and 42 days after the sponge implantation and compared with age-matched non-operated rats. 14C-proline was given 4 hours before death to animals killed on day 0, 14, and 42. The 14C-OH-proline activity in salt insoluble collagen was higher in granulation tissue and aorta than in skin. This indicates a faster formation, or an increased stability of the intermolecular cross-links in granulation tissue and aorta, than in skin. The percentage of free OH-proline was than in skin, reflecting a relatively increased collagen degradation in granulation tissue. An increased collagen degradation may also, in part, explain a registered higher alpha/beta ratio in collagen from granulation tissue than from skin, as well as the increase in alpha/beta ratio in the older granulomas. The sponge implantation did not affect the collagen of aorta and skin, but caused a decrease in the dry weight of aorta and skin, and an increase in the number of granulocytes in the blood.


Variation in distribution of antral gastrin cells. Using immunoperoxidase technique a considerable variation in the number of antral gastrin cells was demonstrated in patients with atrophic gastritis. This variation must be taken in consideration when the number of gastrin cells is to be estimated on the basis of gastric biopsies.


Spontaneous toxic nephropathy in poultry associated with ochratoxin A. At a poultry slaughterhouse 14 birds with macroscopic renal changes were collected, and the kidneys were examined histologically and the muscular tissue was analysed for ochratoxin A residues. Out of 14 birds 5 birds had ochratoxin A residues ranging from 4.3 to 29.2 mug/kg. In 4 of these birds a toxic nephropathy was found characterised by atrophy and degeneration of proximal and distal tubules and interstitial fibrosis. The possibility of birds with ochratoxin A residues being presented for human consumption is discussed.


The postnatal development of some twitch and fatigue properties of the ankle flexor and extensor muscles of the cat. The isometric responses of the medial gastrocnemium (MG), soleus (SOL) and anterior tibial (TA) muscles to single shocks and different modes of repetitive stimulation were studied in kittens of varying postnatal ages and in adult cats. The postnatal decrease in time-to-peak and half-relaxation time of the twitch contractions were similar for the MG and TA muscles and adult values were attained at around 6-7 weeks of age. The SOL muslce displayed a transient decrease in contraction time during the first postnatal weeks, followed later by a slowing towards adult values. The susceptibility to fatigue during iterative stimulation was smallest in the SOL at all ages studied, and usually largest in TA. It changed only little for the MG and SOL postnatally while increasing markedly for the TA up until 6-7 weeks of age. Tetanic contraction resulted in similar depressions in contractile tension of all three muscles in the youngest kittens, but the SOL displayed a greater ability to recover from this depression than the MG and, in particular, the TA muscles. Tetanus resistance increased postnatally and adult responses were attained at 6-7 weeks of age.


The influence of rheological and collapse factors on pre- and post-capillary flow resistances in the skeletal muscle vascular bed of the cat. The importance of passive-elastic changes of vascular dimensions and shifts in regional effective viscosity for the pre-/postcapillary resistance ratio (RA/RV), and hence mean capillary pressure (PC), was analyzed in cat calf muscles. Reductions of mean venous distending pressure below 6-8 mm Hg induced marked RV increases due to escalating venous collapse. This mechanism tends to delimit the PC reductions and rate of transcapillary fluid absorption during intense precapillary vasoconstriction. Comparisons of RA/RV for erythrocyte suspensions (Hct 40-50) and cellfree perfusates at identical vascular dimensions showed that RA/RV was considerably higher, and PC correspondingly lower, for the erythrocyte suspension except at very low flows. This RA/RV difference increased with increasing flow and at very high flows PC was about 10 mm Hg lower during perfusion with the erythrocyte suspension. These findings apparently diverge from the known influence of the tube radius and linear flow velocity on effective in vitro viscosity of blood. Since distal precapillary and proximal capillary sections, both having smaller diameters than the erythrocytes, are located upstream to the point of filtration-absorption equilibrium, they contribute in this respect to RA. It is therefore suggested that the increasing RA/RV with erythrocyte perfusion, particularly at higher flows, is not due to genuine viscosity factors but to friction losses when cells in "bolus flow" are squeezed through the narrowest precapillary sections.