[Haematological diseases with primary otorhinolaryngological manifestation (author's transl)]. There are reports of 10 haematological diseases with primary oto-rhino-laryngological manifestation. The clinical diagnoses were confirmed by laboratory results. The actual diseases were primarily hidden by a tonsillitis, bleeding of the nose after an eye-operation, by an extreme dyspnoe, or by a tumor-like change in the larynx. The authors stress the general necessity of immediate laboratory examinations in dept. of oto-rhinolaryngology.


[Ichthyosis hystrix gravior typus Rheydt: an otologic-dermatologic syndrome (author's transl)]. A case of congenital ichthyosis hystrix gravior combined with non-progressive inner ear hearing loss bordering on deafness is reported. None of the syndromes of keratinization disturbances combined with hearing loss of the inner ear known up to now is comparable. The patient was examined by the dermatologic and otorhino-laryngologic clinics. The findings were presented at the "Südwestdeutschen Dermatologen-Kongress in Heidelberg 1976". Particular otologic findings were a non-progressive inner ear hearing loss bordering on deafness, a fungus-covered cell detritus in the cartilaginous part of the external ear canal, and hyperkeratosis of the auricula. Specific dermatologic findings were skin hyperkeratoses most prominent on face and extremities. In it's ultrastructure, this type is basically different from all other types of inherited ichthyoses that have been studied by electron microscopy. Combined with a lack of normal tonofilaments, an unusual synthesis of large amounts of mucous granules is present under the large spines that is not normally found in healthy skin. No other members of the family are affected.


[Occupational dermatoses reported in the Lódź district in the years 1972-1976]. 108 cases were evaluated. It was stated that they were mostly caused by an exposure to allergic effects of industrial allergens: metal compounds, epoxides, paragroup compounds, turpentine, formalin and rubber components. Location and clinical picture of dermatoses constitute mainly dermatitis and contact eczema on the skin of hands. The cases referred mainly to the men employed in building, chemical, textile and metal industries. Opening a center performing allergic tests with industrial allergents, which at the same time could determine their occurrence in work environment, provides the basic condition for a proper diagnosis and prophylaxis of occupational dermatoses.


[Effect of surface roughness of polymers on thrombus formation]. Thromboresistant properties of fluoroplast-4, lavsan, polymethylmetacrylate, carbon glass, employed in various devices contacting the blood and presenting different degrees of the surface roughness, were studied. The thromboresistant properties of polymers were judged on the ground of modified methods for determining the blood coagulating time, thromboelastograms, with reference to the prothrombin complex factors concentration, the amount of fibrinogen, heparin blood tolerance, the thrombocytes adhesion index, their splitting and flattening. A higher class of the polymer surface roughness was found to raise the thromboresistant properties of the surface. In case of polymers with high mechanical and strength properties the surface roughness is of greater importance in the genesis of thrombosis than in polymers possessing elastic properties.


X-ray structures of two oxidation states of a flavin-nicotinamide biscoenzyme and models for flavin--nicotinamide interactions. The flavin nicotinamide biscoenzymes Flox(-)--C3--Nic+ and H2Flred--C3--Nic+ assume extended conformations in the solid state. In both derivatives the nicotinamide and flavin groups associate through hydrogen bonding. The bending angle of the reduced flavin moiety is less than half that in any previously reported 1,5-dihydroflavin structure. This effect is apparently due to ring stacking interactions.


Juvenile Huntington chorea: clinical, ultrastructural, and biochemical studies. A brain biopsy from a 20-year-old patient whose clinical course was marked by progressive dementia and chorea since age 10 years showed increased amounts of lipofuscin, abnormal mitochondria, and other organelles in cortical neurons, neurites, and astrocytes. Juvenile Huntington chorea was confirmed at autopsy. High levels of three histone-like proteins (molecular weight 10,000 to 16,000) in the microsomal fraction of purified neurons were found by SDS-polyacrylamide gel electrophoresis. Fatty acids were abnormal in white matter sphingomyelin. These ultrastructural and biochemical findings conformed to those established in adult Huntington chorea, thus strengthening the concept of a uniform pathologic process in adult and juvenile Huntington diseases in spite of some clinical and histologic differences.


Histochemistry and acetylcholine receptor distribution in normal and denervated monkey extraocular muscles. In monkey extraocular muscles (EOM), a battery of histochemical reactions delineates three muscle fiber types, coarse, fine, and granular. Normal EOM are compared with EOM denervated by intracranial oculomotor nerve section. The experimentally denervated EOM fibers did not show the constellation of histologic responses typical of denervated limb muscle, making a diagnosis of a denervation process in EOM muscle very difficult. Although the denervated fine and granular fibers (but not the coarse fibers) develop diffuse extrajunctional acetylcholine receptors (AChR) following experimental denervation, this is not a reliable criterion of denervation because not all of those fibers developed it and they did not show it beyond a 12-week period following nerve section; moreover, myopathic mechanisms have previously been shown capable of provoking diffuse extrajunctional AChR in limb-muscle fibers.


The visually evoked potential in Huntington disease. The visually evoked potential was abnormal in 17 of 18 patients with Huntington disease. Both early and late wave components were affected, and the averaged amplitude for the patients was reduced in comparison with 50 normal control subjects. Despite striking attenuation and disorganization of the complex, latency of initial wave components was normal. The abnormality was not present in patients with a variety of other nonfocal cerebral disorders nor in 13 children of patients with Huntington disease.


Neurophysiological and behavioural changes during mental work in children with Down's syndrome. Telemetered EEG and ECG were recorded from 18 Down's syndrome children (5;6--11 years) during rest, a visuomotor and a cognitive test, exploration and play. Simultaneously the behaviour was observed and recorded. In comparison with normal children (3;9--5;5 y. resp. 5;6--7;6 y.) the Down's syndrome children showed a low degree of motor activity, reduced attention and exploration and little variation of heart rate in relation to test difficulty. The main findings in the EEG (parieto-occipital recording) were a low amount and a small variability of alpha waves and a high amount of beta waves. This EEG phenomenon which is obviously not due to high activation is discussed with regard to possible connections with defective neurophysiological mechanisms of attention.


[Specific and aspecific myocardial changes in progressive muscular dystrophy and their importance in rehabilitative treatment]. Clinical and instrumental parameters studied in over 200 progressive muscular dystrophy patients during a period of about 10 yr revealed four different types of cardiopathy in this disease. The most interesting finding was that 38% of patients with Duchènne's dystrophy presented a clinical and ECG picture reminiscent of that of obstructive hypertrophic cardiomyopathy. Some suggestions are made for the pharmacological and rehabilitative management of subjects with myocardiopathy in the course of myodystrophy.


Comparative evaluation of laparoscopy and hysterosalpingography in infertile patients. A comparative study of hysterosalpingography (HSG) and laparoscopy in the investigation of infertility is presented. From 1973-1977, 352 cases were investigated with both HSG and laparoscopy. In 57.67% of the cases there was complete agreement between HSG and laparoscopy. The study included 168 cases of unexplained infertility and 184 cases with abnormal hysterosalpingographic findings. Pelvic adhesions were demonstrated in 151 cases by laparoscopy as compared to 76 cases in which its presence was only suspected by HSG. Laparoscopy revealed a 57.14% of associated pelvic pathology in cases of unexplained fertility. The present study concludes that laparoscopy as compared to HSG is not only more informative, but also more accurate and conclusive.


The regulation system of granulopoiesis. Extracts containing the granulocytic chalone (GCh) have been prepared from bone marrow conditioned medium by ultrafiltration and column chromatography. This preparation selectively inhibits myeloid cells and does not affect other, e.g., lymphoid cells. The action on myelopoiesis seems to include all mitotically competent immature granulocytes as indicated also by an inhibitory effect on bone marrow colony formation in agar. Results obtained by this technique and by applying mild trypsinization of bone marrow cells prior to testing chalone responsiveness indicate that GCh acts via membrane receptors. Finally the apparent antagonistic role of colony stimulating factor and GCh as regulators of granulopoiesis is discussed and a model of the regulation system is described.


[Formation of membranes of the basic substance by hemocytes of Alveonasus lahorensis (Argasidae) ticks]. Observations have shown that in vitro haemocytes of A. lahorensis are capable of forming different structures, even membrane ones. These structures include mucopolysaccharides. Haemocytes are supposed to take part in the formation and deposition of the basic (intercellular) substance and in the building of tunica propria which can be considered as components of the inner medium.


[Distribution characteristics of Leishmania tropica major strains of differing virulence in natural and territorial complexes of the Murgab eco-area (southeastern Turkmenistan)]. In September--October of 1973 and 1974 263 specimens of Rhombomys opimus were shot in the territory of the Murghab stationar. The seeding of the material (a piece of tissue) from all animals into NNN medium was done. 9 strains of L. tropica major were isolated from this material the virulence of which was studied on 2.5--3 months--old golden hamsters, Cricetus auratus. Differences in the virulence of the isolated strains according to their natural-territorial complexes are shown. These differences depend apparently on the specific composition of the vectors. It is shown that the specific composition of sand flies as well as other epizootical characters are determined by the landscape of the territory where  nidi of zoonosis cutaneous leishmaniasis are situated.


[Phenology of sandflies of the subspecies Paraphlebotomus inhabiting the burrow of the great gerbil in the Karshi Steppe]. Oberservations were conducted (1960 to 1973) on the sand flies of the subgenus Paraphlebotomus inhabiting the burrows of Rhombomys opimus in the Karshinskaya steppe (Uzbekistan). Ph. mongolensis is most abundant in oasis, Ph. caucasicus--in loess low-mountain areas. Throughout the territory investigated Ph. mongolensis has two generations per season. The emergence of imago of this species in oasis begins early in May with the first peak of abundance at the end of May--beginning of June and with the second peak in the first decade of August. The flight of Ph. mongolensis ceases in general to the middle of September. In the northern part of the territory investigated Ph. caucasicus has two mass generations with peaks in the second decade of June--first-second decade of August. In the southern part of the territory three peaks of abundance of ph. caucasicus were noted: in the middle of May, end of June--beginning of July and the end of August--beginning of September. Therefore, the presence of three generations per season can be suggested here.


[Microsporidians (Protozoa, Microsporidia) of lower crustaceans from the reservoirs of Leningrad Province]. 18 species of microsporidians were found in crustaceans of the Leningrad region. Of them 6 are referred to known species, 7 are described as new ones and 5 are identified to the genus. Some preliminary data are given on the influence of microsporidians on the host population, their specificity and variability.


[Mechanism of attachment of Dactylogyrus extensus and D. achmerowi (Monogenoidea) to host gills]. The mechanism of adhesion was studied in two species of the genus Dactylogyrus. The muscular system of the disc of both species is described. Data are given on the presence of rudiment of the 8th pair of hooks and on the possible function of this formation as well as the data on the adhesion of the postlarva of D. extensus.


The ultrastructural development of the schistosome egg granuloma in mice. Hepatic granulomas from mice infected with Schistosoma mansoni for periods of 8 weeks to 1 year studied by electron microscopy. The different cell types present in the granulomas suggested that whilst a delayed hypersensitivity response predominated during early stages of infection an Arthus-type reaction associated with delayed hypersensitivity occurred at later stages of infection.


Muscle fiber types in women athletes and non-athletes. Muscle biopsies were obtained from the vastus lateralis muscle of 5 female collegiate field hockey players and 5 untrained female students. The fibers were classified histochemically as fast-twitch-oxidative-glycolytic (FOG), fast-twitch-glycolytic (FG) and slow-twitch-oxidative (SO). The fibers were found to be similar to those of males in distribution and histochemical properties, but were smaller. In the women athletes all 3 fiber types were larger than the respective fibers in the controls. Also, the athletes had a much higher percentage of oxidative fibers (SO + FOG), 83% vs. 46%. A direct relationship between fiber size and oxidative activity was observed in fast-twitch fibers, whereas the reverse was found in slow-twitch fibers.


A system for intravascular, radially orientation-independent electromagnetic flow- and diameter-sensing. The difficulty of optimally orienting an intravascular loop probe of an extracorporeal field electromagnetic flow meter is circumvented by uniting 2 mutually perpendicular loop sensors into a single flow-diameter probe. When one of the loops is unfavorably oriented in the magnetic field, the orientations of the other loop is more favorable. The most unfavorable case is a 45 degrees angle between the magnetic field and the planes of the loops, when the signal drops to 70.7% of the optimal value. By taking the square root of the sum of the squares of the 2 loop transducer signals, one obtains an output for flow and diameter measurements which is independent of the probe orientation. This operation can be accomplished electronically.


Induction of Na-K-ATPase in plasma membranes to rat cecum mucosa by diet: time course and kinetics. Dietary polyethylene glycol (PEG) induces an increase in the specific activity of Na+-K+-activated adenosine triphosphatase (Na-K-ATPase) in the cecum mucosa of rats. Using cecum mucosa homogenates and cellular subfractions obtained by differential centrifugation, the induction process was studied with respect to time course, subcellular distribution and properties of the enzyme. In comparison with controls, Na-K-ATPase specific activity was stimulated in PEG treated rats in the total homogenate and the microsomal (105000 X g) but not in the mitochondrial (9000 X g) or nuclear (1000 X g) sediment. The specific activity of Mg-ATPase did not change in any of the fractions. Na-K-ATPase induction was statistically significant after 2 days and complete after 1-2 weeks, in parallel with the previously described stimulation in net sodium absorption. Kinetic analysis showed Vmax for ATP to be doubled while Km for ATP, Na and K as well as the optimal Mg/ATP ratio and Ki for ouabain remained unchanged. It is proposed that Na-K-ATPase and active sodium transport are closely associated in rat cecum and that dietary Na-K-ATPase stimulation is due to the induction of more enzyme molecules per unit basolateral cell membrane.


The effect of serotonin receptor blocking agents--cyproheptadine and danitracen--on serotonin turnover in the rat brain. Cyproheptadine (CPH), 0.5 mg/kg ip, did not affect the cerebral serotonin (5-HT) level, but elevated the level of 5-hydroxyindoleacetic acid (5-HIAA). Danitracen (DN), 1 mg/kg ip, depressed the cerebral 5-HT level and elevated the 5-HIAA level, but at a dose 10 mg/kg did not affect the levels of either the amine, or its metabolite. Both CPH and DN, 1 mg/kg, significantly potentiated the disappearance of 5-HT after administration of p-chlorophenylalanine. DN, in a low dose, accelerated the disappearance of 5-HT after inhibition of 5-HT synthesis by alpha-propyldopacetamide. The rate of accumulation of 5-HIAA after probenecid, was increased only by CPH. CPH did not affect the 5-HT accumulation after pargyline, while DN depressed its accumulation. The results of experiments on the levels of 5-HT and 5-HIAA, and on the rate of disappearance of 5-HT after inhibition of tryptophan decarboxylase suggest that CPH and DN increase the 5-HT turnover. The results of studies on the turnover rate of 5-HT after administration of probenecid and parygline do not corroborate fully this assumption. Possibly, this discrepancy may depend on differences in the action of 5-HT in various brain areas and interaction of serotoninolytics tested with effects of the MAO inhibitor.


Nomifensine and central monoamine neurons: histofluorescence studies. The effect of nomifensine (NF) on the content of serotonin (5-HT) and catecholamines (CA) in discrete regions of rat brain was studied with the histofluorescence technique of Falck, NF, 20 and 40 mg/kg ip, produced, after 30 min, a depression of 5-HT content in the neurocytes of dorsal and median raphe nuclei (NDR and NMR). The blockade of dopamine receptors by spiperone did not abolish the action of NF in NDR, and inhibited the effect in NMR only in some animals. NF did not affect significantly the CA content in the striatum (caudate nucleus--putamen), hypothalamic paraventricular nucleus, and paraventricular rotundocellular nucleus. The results indicate, a direct action of NF on 5-HT neurons in the rat mesencephalon. In addition, the drug may also act indirectly on 5-HT neurons in NMR, via dopaminergic system.


Reliability of the tonic vibratory reflex. Reliability of the tonic vibratory reflex was examined in 30 able-bodied subjects over different time periods (5-minute, 24-hour, and 2-week intervals) and with different coupling pressures (20 mm Hg and 45 mm Hg). A high average correlation ( r = 0.85) was found for intraday test-retest situations. The average 24-hour and 2-week interval interday correlatins were r = 0.64 and r = 0.54, respectively. Various pressures of vibrator head attachments did not produce significantly different tonic vibratory reflex responses. All subjects showed a significant decrease in tonic vibratory reflex responses over the 2-week period (F = 9.71, DF 8,224). The conclusions were that a) intraday but not interday tonic vibratory reflex responses were adequate for diagnostic purposes, and b) that the reasons for the significant decrease of the tonic vibratory reflex response over time need further investigation.


The application of solid dispersion technique in the preparation of therapeutic tablets. Part 1: Paracetamol, amylobarbitone, and caffeine tablets. A trial was made to study the possibility of preparing high-quality therapeutic tablets by direct compression of the solidified drugcarrier melt via solid dispersion technique. Paracetamol-mannitol, amylobarbitone-urea and caffeine-nicotinamide systems were investigated. Phase diagrams of the first two systems were found to be of the simple eutectic type, while that of the third system was a peritectic type. Solubility studies were also carried out. Dissolution rate studies showed that the fused mannitol/paracetamol (80:20), urea/amylobarbitone (80:20) and nicotinamide/caffeine (50:50 and 70:30) solid dispersions exhibited better rates of dissolution than those of the pure drugs. Comparative studies were carried on with tablets prepared by direct compression of the drug-carrier solidified melt exhibiting the highest dissolution rate and by slugging the pure drug and the drug-carrier physical mixture of corresponding composition. The physical properties and dissolution rate data showed the superiority of the tablets prepared by the solid dispersion technique. The drug release from these tablets was 4.5, 7.6 and 3.7 times greater than that from tablets prepared from pure paracetamol, amylobarbitone and caffeine respectively.


The results of non-operative management of stiff joints in the hand. We selected 500 patients randomly from a total of 1300 patients seen in our Hand Rehabilitation Center between 1971 and 1975; 212 of the 500 presented with a chief complaint of stiff hand joints. Of the 212 patients treated non-operatively, 173 responded sufficiently to this treatment alone. Of the 789 stiff joints, 686 responded sufficiently to this treatment alone. The results of this regime of non-operative treatment of stiff joints provide excellent functional improvement in most patients, with a large saving of money through the reduction in disability payments required.


[Favorable, unfavorable and indifferent side effects of pharmacotherapy of psychoses]. Not all side-effects are undesirable side-effects of a treatment. Under certain conditions allergic side-effects during the therapy of phasic psychotics affect a turn in the course of the basic illness and bring a premature end to depression. As a result of the observation of a sudden cure of a deep vital depression in a 73 year old patient in direct chronological connection with the appearance of an allergic urticaria, studies were carried out, in the 8 years following, of a total of 18 cases of similar circumstances; during the treatment of an endogenous depression the development of intercurrent allergic skin reactions showed: in 6 cases the psychosis completely disappeared with the development of the urticaria; in 8 cases the symptoms were considerably relieved so that only the remains of vegetative disorders persisted; in 4 cases no effect could be determined. In 2 cases the same allergic reaction was consciously provoked by a reapplication of the medicaments concerned during a following depressive phase; again with favourable results since under these conditions coincidences are not very probable, the conclusion can be made, and experimentally supported, that allergic drug reactions may be employed in the course of depressions, with careful avoidance of complications.


Na+ and K+ dependent ATP-ase and structural modifications in hypokinetic rats. In rats the hypokinetic state obtained by restraint in special cages, produces after 30 days, a marked decrease in Na+ and K+ dependent ATP-ase in the skeletal muscle. After 15 days hypokinesia the enzymatic content of the investigated tissues did not change. In the left cardiac ventricular muscle Na+ and K+ dependent ATP-ase decreased after 15 days and particularly after 30 days hypokinesia. These changes were brought about by the hypofunctional state of both muscles, which also produced structural alterations. In the skeletal and cardiac muscles electron microscopy revealed fibrillar atrophy and mitochondrial alterations typical of an affected function. In the cardiac muscle, in which these changes were more accentuated, the dissociation of the intercalar disc was also noted, aspects partially described by others.


[The effectiveness of the serotonin antagonist Divascan in migraine therapy]. It appeared from the evaluation of a clinical test of the serotonin antagonist in 22 patients that DIVASCAN proved itself particularly effective in cases of ophthalmic migraine, in the second place in cases of migraena simplex with vegetative accentuation and likewise in cases of migraena cerebellaris. Besides this there is a favourable effect on the tendency to the edema and facial pain.


[Surgical reoperations for complicated pyeloplasties]. Comments are made in connection with a statistics concerning 41 pyeloplasties and 14 re-interventions for complications of pyeloplasties. The author reviews cases in which the reconstruction failed and stresses the problems related to the performance of the intervention and the post-operative care. Early post-operative urography is recommended, on extenation of the patient, in view of checking if the kidney is functional or not. Also the quality of pyelo-uretheral anastomosis is checked by this method.


[Anatomo-surgical aspects of the liver in situs inversus]. The hepatic veins and the intra-parenchymal branches of the portal vein and of the hepatic artery were dissected in two isolated livers form subjects with situs inversus. As a general observation, the intra-hepatic distribution of the portal vein in these cases represented a "looking-glass image" of the normal liver. The intra-hepatic branches differ from the normal by the presence of a large interarterial anastomotic canal in one of the cases. In the other case branches were found, of the left hepatic artery, for the upper sub-segments of the right lobe, that were irrigated from the venous standpoint, by the right branch of the portal vein.


[Thyroid radiography and thyroid lymphography]. A detailed representation is made of the technique used in the performance of thyroidography and an analysis is carried out of the authors' personal experience Thyroidography and thyroido-limphography have been applied in 40 patients with various diseases of the thyroid gland. The authors evaluate the method as being simple to perform, accessible, well tolerated and capable to provide significant morphological data (size of the lobes, the presence of retrosternal thyroid tissue, structure of the gland), also allowing for visualization of the cervical limph-nodes.


[Congenital tracheoesophageal fistula: operation and cure]. On the basis of their personal experience, covering approximately 100 cases of oeso-thoracal fistulae of various origins and with different anatomo-pathological forms, the authors present a case of oeso-tracheal fistula of congenital origin, in a child aged 4 years, that recovered after surgery. The practical aspects of surgery are stressed, as well as the sequence of surgical stages, evaluating the fact that gastrostomy should be carried out simultaneously, at the end of the thoracal intervention.


[Dissecting popliteal cyst in rheumatoid polyarthritis: clinical and therapeutic aspects]. The authors present a dynamic observation of a patient with advanced rheumatic polyarthritis that developed considerable hydrathrosis of the left knee and popliteal deep cyst of the Backer type. The general treatment was completed with radioisotopic synoviorthesis with Au198 that administered directly in the articulation and in the cavity of the cyst, resulting in the rupture of its wall. The symptomatology of the dissecting popliteal cyst was similar to that of thrombophlebitis. Posterior incision and drainage of the cyst collection have resulted in the disappearance of the local phenomena.


[Laboratory studies of the effect of Pavulon on the blood pressure in induced autonomic dystonias]. In experimental studies performed in dogs Pavulon enhances the hypertensive effects of para- and orthosympathicomymetics (nicotinelike and liberation of cathecholamine respectively), parasympaticolytics lowering essentially the rise of the blood pressure induced by Pavulon, which sympathicolytics--depending on the dose administered--can decrease until zero. These facts have a significant role in the anesthesia and intensive care practice.


Binding of divalent cations by canine cardiac myosin: differences in normal right and left ventricles dependent upon number of light chains. The moles of calcium bound by the left ventricle were 1.5 +/- 0.1, while those of the right ventricle were 2.9 +/- 0.2. The calcium binding constants were the same between myosins of the two cardiac ventricles. The Ca2+ binding constants were approximately 1.1 X 10(5) M-1 for both left and right ventricular myosins. Left ventricular myosin bound 1.3 +/- 0.1 mol of Mn2+, whereas right ventricular myosin bound 2.8 +/- 0.1 mol of Mn2+. The divalent cation Mn2+ only partially competed out Ca2+ (50%). Because of the partial competition, it seemed that Ca2+ and Mn2+ had some sights in common. These studies demonstrate a twofold difference in divalent cation binding (Ca2+, Mn2+) between left and right ventricular myosins. This variation in cation binding between the two ventricles is reflected in similar differences in myosin ATPase activity between the two ventricles.


Regulatory mechanism in arterial smooth muscle contraction. The regulatory mechanism in the aortic actomyosin system was studied. Superprecipitation of desensitized aortic myosin B was not exhibited even in the presence of Ca2+, but was observable only in the presence of native tropomyosin and Ca2+. Reconstituted actomyosin composed of pure aortic myosin and pure skeletal actin did not show superprecipitation. Addition of aortic native tropomyosin and Ca2+ caused a marked superprecipitation. The ATPase of reconstituted actomyosin was enhanced three- or fourfold by aortic native tropomyosin and Ca2+. The extent of superprecipitation of aortic myosin B did not show a biphasic type of response to Mg-ATP concentration. Thus, aortic native tropomyosin induces a real activation of the myosin, actin, and ATP system in the presence of Ca2+, in contrast with the case of skeletal native tropomyosin, which induces the depression of skeletal myosin-actin-ATP interaction in the absence of Ca2+.


Phosphorylation of cardiac myofibrillar proteins. The P light chain of cardiac myosin is phosphorylated and dephosphorylated by highly specific enzymes. These reactions take place in the beating rabbit heart and there is evidence that dephosphorylation of the light chain occurs during the inotropic response produced by adrenaline. The extent of phosphorylation of cardiac troponin I is determined by the functional state of the beating heart. During perfusion of the rabbit heart the basal phosphate content of troponin I increased from the basal level of about 1.5 moles P per mole to about 2.7 moles P per mole at the height of the inotropic response to adrenaline. The three sites of phosphorylation on troponin I are probably located in the N terminal cyanogen bromide peptide of 48 residues.


Binding of [3H]atropine by cardiac plasma membrane-enriched fractions. The binding of [3H]atropine by the primary subcellular fractions and plasma membrane-enriched fractions from atria and ventricles of various species was measured by the Millipore filtration technique. Although all of the primary particulate fractions exhibited binding activities, the bulk of the total homogenate binding activity was associated with the washed particles sedimenting at the lower gravitational forces; this was observed with either atria or ventricles of dog, guinea pig, rabbit, hamster, and rat. Plasma membrane-enriched fractions isolated from the right atrium of guinea pig exhibited atropine binding activities with characteristics similar to dog atrial membranes; binding activity was moderately enriched in these membranes with respect to the starting material.


Effect of acetaldehyde on functioning of cardiac muscle at the ultrastructural level. The effect of acetaldehyde, the hepatic metabolite of alcohol, on the functioning of cardiac muscle was investigated at the subcellular level. Concentrations of acetaldehyde that occur in plasma failed to alter either the microsomal Ca2+-accumulating and ATPase activity or the Ca2+-accumulating activity of the mitochondria. These same concentrations of acetaldehyde inhibited the Ca2+-dependent myofibrillar ATPase.


Effect of ouabain on sodium movement in cardiac cells. A computer simulation indicates that intracellular sodium concentration within a space near the inner surface of sarcolemma fluctuates during a cycle of myocardial function. The sodium transient (a transient increase in sodium ion concentration associated with membrane excitation) is enhanced by the inhibition of (Na+, K+)-ATPase by ouabain, but an accumulation of myocardial sodium does not occur until the inhibition exceeds a critical point. The critical magnitude of sodium pump inhibition that causes a progressive sodium accumulation is dependent on the heart rate.


Histopathological study of hypertrophied myocardium of known etiologies with special reference to correlation of ECG changes. Sixty-two autopsied hearts, with left ventricular hypertrophy (LVH) caused by mitral regurgitation (MR), aortic failure (AR), combined valvular disease (CVD), hypertension (HHD), or ischemia (IHD), and 23 control hearts with normal left ventricles were studied morphologically for analysis of modes of hypertrophy and for ECG-pathology correlation. Basic disorders modify the mode of hypertrophy; that is, elongated AR-type LV makes muscle fiber orientation in the outer layer more vertical, and globular MR-type LV makes it more horizontal than normal. High-voltage QRS correlates with hypertrophy of the outer layer which is often associated with that of the inner layer. ST depression and T changes correspond to relative deterioration of the inner and median layers, respectively.


Ultrastructural aspects of contractile proteins in cardiac hypertrophy and failure. A review is presented in this chapter of morphological changes in contractile elements of cardiac muscle cells in hypertrophy and failure, with emphasis on alterations occurring in human hearts in the late stages of hypertrophy. The formation of new sarcomeres involves the synthesis of a variety of different proteins, their aggregation into filaments, and the organization of filaments into specific tridimensional arrays. Z-line material appears to play an organizer role in the formation of new sarcomeres. The ultrastructural appearance of contractile elements in hypertrophied muscle cells varies according to the cause and the stage of the hypertrophy. Myofibrillar lysis, with preferential loss of thick myofilaments, occurs in the late stages of hypertrophy in association with degenerative changes, including dissociation of intercellular junctions, proliferation of sarcoplasmic reticulum, cellular atrophy, and interstitial fibrosis.


Characterization of myosin from patients with asymmetric septal hypertrophy. Human cardiac myosin isolated from operatively obtained samples of ventricular septum and left ventricular free wall of patients with asymmetric septal hypertrophy (ASH) was compared, with respect to structural and enzymatic properties, to myosin isolated from hearts of patients without heart disease. The following parameters were studied: 1) activation of myosin ATPase activity by K+-EDTA and Ca2+,2) molecular weight of the heavy and light chains of myosin as determined by electrophoretic migration in SDS-polyacrylamide gels, and 3) ability to form bipolar aggregates at low ionic strength, as examined by electron microscopy. No difference was present in any of these parameters between human cardiac myosin from patients with ASH and from patients without heart disease. Thus, the genetic defect present in patients with ASH is not expressed in the particular structural and functional characteristics of myosin evaluated in this study.


Right ventricular hypertrophy in tetralogy of Fallot. Histopathological studies were carried out on right ventricular myocardium in 104 patients with tetralogy of Fallot (T/F). Detailed analysis of the correlation between morphological and clinical data was performed. Right ventricular hypertrophy in T/F was found to initiate immediately after birth, and the diameter of right ventricular muscle fiber (D) increased with age (r = 0.74). There was a correlation between D and the hemoglobin level. There was, however, no correlation between D arterial oxygen saturation (SaO2), and pulmonary trunk/aorta diameter (PA/Ao) ratio. Histopathological alterations were related directly to D and to the age of the patient, and were unrelated to hemoglobin, SaO2, and PA/Ao ratio. Irreversible histopathological alterations were first observed when the D exceeded 15 micron, when most patients were four years old or more. From these findings, it is considered that the optimal age for corrective surgery to prevent irreversible alteration of the right ventricular muscle fibers in patients with T/F is less than three years.


Increased protein synthesis during right ventricular hypertrophy following pulmonary stenosis in the dog. The synthesis rates of mixed protein in the left and right ventricles were the same in normal dogs, averaging 7.8% per day. After five days, pulmonary stenosis protein synthesis rate in the right ventricle increased rapidly to 13.6% per day and subsequently decreased to near normal by 12 days, during which time the right ventricle protein mass increased by 48% after five days and by 73% after 12 days. Similarly the synthesis rate of the myofibrillar and sarcoplasmic proteins was almost doubled after five days of stenosis. The protein synthesis rate in the left ventricle did not change significantly during the 24 days of pulmonary stenosis.


Electron microscopic studies on ATPase activities in myocardial infarction. Comparative studies of the fine structural changes and histochemical examination of adenosine triphosphatase (ATPase) activity were performed in canine ischemic heart muscle cells following left coronary artery ligation. In the intact myocardial cells, the ATPase activities were observed most intensely in the sarcoplasmic reticulum (SR), particularly in the terminal cisternae (TC), and moderately around gap junctions of the intercalated discs and on myofilaments. Ischemic cellular changes occurred three to 24 hours after coronary ligation and became severe after three to seven days. ATPase activities decreased at around 48 hours and also became weak at three to seven days. Two to three weeks after ligation, improvement of the fine structure and increase in ATPase activities were observed in the ischemic cells, suggesting recovery. ATPase activities in the ischemic cardiac cells appeared to be decreased in parallel with the process of the fine structural changes.


The pathways of protein synthesis and degradation in normal heart and during development and regression of cardiac hypertrophy. The half-life of cardiac myosin heavy chains (HC) was determined, with leucyl-tRNA as precursor, to be 5.4 days. Myosin HC are labeled more rapidly than actin; myosin light chains (LC1 and LC2) are labeled more slowly than HC. The observed differences are attributable to heterogeneity in the half-lives, e.g., actin, and to the effect of dilution by the existing macromolecular precursor pool (LC1 and LC2). Cardiac and skeletal muscle contain a population of filaments that can be released from myofibrils by ATP-relaxing solution. The easily released filaments (ERF) are devoid of alpha-actinin and M-protein. Labeling of ERF is more rapid than that of residual myofibrils. Cardiac and skeletal muscle contains calcium-activated neutral protease, which selectively removes alpha-actinin when incubated with isolated myofibrils. During development of pressure-induced cardiac hypertrophy, the labeling of LC2 is increased. In regressing cardiac hypertrophy the activities of free and total cathepsin D and of acidic RNase are unaltered.


The early phase of insulin release in man--a new method for quantitative analysis. A method is presented for the quantitative analysis of early insulin release in man. There were measured arterial insulin levels after glibornuride administered intravenously. The mathematical procedure has been modified: Modification I is based on the assumption that early insulin release represents a wave like insulin delivery, modification II is based on the assumption that this insulin bolus is immediately followed by a slower insulin release which must be distinguished from the second phase of insulin release. For the calculations there was used a "primary insulin space" derived from experiments with exogenous insulin. The results of calculations were varying up to 1.5 units of early insulin release in healthy volunteers receiving glibornuride with dosages varying up to 50 mg. The value of the presented method for examinations of insulin release for theoretical and clinical purposes is discussed.


Alteration in calcium metabolism in cardiac hypertrophy and failure caused by bacterial infection. Left ventricular hypertrophy was seen in catheterized, uninfected rabbits, whereas contractile failure superimposed upon hypertrophy was observed in catheterized animals after injection with Streptococcus viridans within six days. The infected animals showed marked changes in the ultrastructure of the left heart in comparison to the uninfected rabbits. The levels of calcium and potassium were decreased, whereas sodium was increased in both infected and uninfected hearts; however, magnesium levels did not change in uninfected hearts but were decreased at three days and increased at six days of infection. The microsomal calcium uptake was decreased in six-day uninfected as well as three-and six-day infected hearts. On the other hand, the mitochondrial calcium uptake was increased in six-day uninfected and three-day infected hearts but decreased in six-day infected hearts. The sarcolemmal calcium binding and (Na+,K+)ATPase activities were decreased in six-day uninfected as well as three- and six-day infected hearts. These results dramatic changes in intracellular calcium metabolism in myocardial hypertrophy and failure caused by bacterial infection.


Tolerance to ischemia in the human heart. The tolerance to ischemic cardiac arrest during open-heart surgery depends on the degree of hypertrophy and on the functional impairment of the heart. The angiographically determined muscle mass is a good indicator of the susceptibility of the myocardium to ischemic injury and of its ability to quickly restore myocardial structure upon reperfusion. Tissue from extremely hypertrophied hearts exhibited numerous degenerative alterations.


Cancer of the breast--induction by radiation and role of mammography. Conflict in the management of cancer of the breast exists. Diagnosis by x-ray mammography provides early effective treatment, but x-ray exposure to the breast is cancerogenic. Prudence requires the use of low dose x-rays in mammography, and limits the use of x-ray mammography in the young. Guide lines for the indications for mammography are changing, and large scale population exposure to radiation should await results of demonstration projects in the United States.


Intra-operative ascending aortic flowmetry. Intra-operative flowmetry was carried out before and after cardiopulmonary bypass in 34 patients who underwent aortic root surgery. Most of the patients had either aortic or combined aortic and mitral valve replacement. Flowmetry performed before and after the procedure proved to be a very useful diagnostic tool, particularly in evaluating the immediate postoperative haemodynamic performance of the replaced aortic valve and the completeness of the correction.


[Use of aerosols in obstructive respiratory tract diseases. Clinical-pharmacological studies using fenoterol, salbutamol, ipratropium bromide and terbutaline]. The acute bronchodilator effect of aerosolized fenoterol, salbutamol, ipratropium bromide, and terbutaline was tested in single-blind cross-over trials by whole body plethysmography. In 4 different series, patients with chronic obstructive airway disease were investigated using combined alternating medication. Only commercially available metered dose inhalers were included in this study. Special attention was paid to comparison of the efficacy of administration by the investigator and by the patients themselves. The doses recommended by the manufacturers sometimes resulted in widely different bronchodilation when the metered dose inhalers were administered by the patients. Some possible reasons for these results and some implications with regard to different types of inhalers, single doses, instruction of the patients and evaluation of clinical trials are discussed.


Ingestion of crude oil: sublethal effects in herring gull chicks. A single small oral dose of Kuwait or South Louisiana crude oil caused cessation of growth, osmoregulatory impairment, and hypertrophy of hepatic, adrenal, and nasal gland tissue in herring gull chicks living in a simulated marine environment. These findings suggest that ingesting crude oil causes multiple sublethal effects that might impair a bird's ability to survive at sea.


Atherosclerosis and the hypoplastic aortoiliac system. Between January, 1965, and December, 1975, 204 patients (138 men and 66 women) underwent aortoiliac reconstruction for atherosclerotic occlusive disease. Eighteen patients (9%) had a hypoplastic aortoiliac segment and an analysis of these 18 patients constitutes the basis of this report. There were 17 women and one man, and their ages ranged from 28 to 60 years, with an average of 43 years. Hyperlipidema was present in nine of 13 patients tested. All patients were heavy cigarrete smokers and had lower extremity claudication with weak or absent pulses. Carotid or subclavian artery disease was found in 50%. Angiography demonstrated hypoplasia of the aorta distal to the renal arteries with either occlusion, diffuse narrowing, or, most often, an "hourglass" stenosis. The iliac and femoral arteries also were narrowed. Reconstruction was achieved primarily by aortobilateral-iliac or femoral bypass. There were no operative deaths and all patients were improved initially. It appears that normally occurring atherosclerosis in this portion of the aorta, along with congenital narrowing, accounts for symptoms at an early age. The predominence in women is a puzzle. The prognosis does not appear to be too grim. This may be due to absence of diabetes mellitus and the infrequency of coronary artery disease. All patients are still alive; there has been one major amputation following graft infection 1 1/2 years after operation. When progression of atherosclerosis occurs, it seems to involve the superficial femoral, carotid, and subclavian arteries.


Effect of 6-aminonicotinamide in teratogenic doses on the DNA- and RNA-concentration in rabbit embryos. Pregnant rabbits were injected ip with 5 mg/kg 6-ANA at day 10, 11, 12 or 12.5 respectively of gestation. Embryos removed at day 13 of gestation had reduced DNA and RNA concentrations. The differences (DNA: 14 percent; RNA: 22.4 percent) were significant in the group treated on the twelfth day. Some possible mechanisms are discussed.


6-Aminonicotinamide-induced cleft palate in the mouse: the nature of the difference between the A/J and C57Bl/6J strains in frequency of response and its genetic basis. Cleft palate induction by 6-aminonicotinamide (6-AN) was examined in the A/J and C57BL/6J strains of mice to determine the nature of the strain difference in frequency of cleft-palate response. Probit analysis of the cleft-palate response to dose of different genotypes revealed a family of linear and parallel dose-response curves. The genotypes differ only in dosage tolerance (log ED50) to 6-AN that is required for the cleft-palate response. No evidence for a maternal cytoplasmic effect on 6-AN-induced cleft palate was found under the conditions of the present study. When the difference is dosage tolerance to 6-AN between A/J and C57BL/6J was examined with a single dose and measured by differences in frequency of induced cleft palate on a probit scale, there was some departure from genetic additivity. There was an indication off dominance deviation of the F1 embryos in the direction of C57BL/6J.A3-locus, epistatic model is proposed to account for the difference in embryonic tolerance ot 6-AN-induced cleft palate. There was a suggestion of association with the brown (b) locus.


Spontaneous atrial thrombosis in aged Syrian hamsters. I. Incidence and pathology. Many of the aging Syrian hamsters maintained in our Division spontaneously develop atrial thrombosis accompanied by a consumption coagulopathy. The 50% mortality level is reached earlier by females (16 months) than by males (24 months). The incidence of thrombosis increases with age, beginning at 13.5 months in females and at 21.5 months in males, and the overall incidence (73%) is nearly the same for both sexes. Bilateral ventricular hypertrophy was found in thrombosed hearts. The hearts of most aged hamsters, whether thrombosed or not, had myxoid valvular thickenings and myocardial degeneration. Myodystrophic changes included hypertrophied nuclei, cytoplasmic vacuolation, fiber atrophy, and finally replacement fibrosis. Thrombosis probably resulted from local blood stasis secondary to cardiac failure. These hamsters may be an especially useful model for comparative study of the effects of aging and myocardial degeneration on spontaneous thrombosis.


Fibrin and fibrinogen proteolysis products: comparison between gel filtration and SDS polyacrylamide electrophoresis analysis. The proteolysis of purified human fibrinogen, stabilized and non-stabilized fibrin by plasmin were investigated by gel filtration analysis and SDS polyacrylamide electrophoresis of the reaction products. Plasmin proteolysis of fibrinogen followed the sequential steps previously reported and the two analytical methods yielded concordant results. Large molecular weight proteolysis products, of substantially greater molecular weight than native fibrinogen, were identified by gel filtration analysis following dissolution of stabilized and non-stabilized fibrin clots; with further incubation with plasmin, these proteolysis products gradually diminished in size. On the other hand, SDS polyacrylamide electrophoresis of these fibrin digests demonstrated that while non-stabilized fibrin yielded breakdown products similar in size to those obtained after proteolysis of fibrinogen, stabilized fibrin digests showed moieties of greater molecular size estimated to be of molecular weight 400,000 to 800,000. The final breakdown products of stabilized fibrin differed from those of fibrinogen and nonstabilized fibrin in that fragment D was present in the "double D" cross-linked form.


Increased absorption of iodochlorhydroxyquin by rat intestine in the presence of solubilizing agents. The intestinal absorption of iodochlorhydroxyquin (clioquinol) by the rat was studied by determining the radioactivity in the bile, blood and several organs 90 min after direct application of 125I-labeled clioquinol into the duodenum. The addition of solubilizing agents such as carboxymethyl-cellulose and lauryl sulfate to clioquinol preparation markedly enhanced the intestinal absorption of the drug in either the presence of absence of bile secretion which, by itself, increased the drug absorption. Possible significance of the enhanced absorption of clioquinol by solubilizing agents in the etiology of subacute myelo-optic neuropathy (SMON) in Japan is discussed.


A radioimmunoassay for 7 alpha-hydroxy dehydroepiandrosterone in human plasma. A radioimmunoassay for plasma 3 beta, 7 alpha-dihydroxy-5-androsten-17-one (7 alpha-hydroxy DHA) has been developed using anti-sera raised against 3 beta, 7 alpha-dihydroxy-5-androstene-17 beta-carboxyl-bovine serum albumin conjugate and [1, 2 (n) - 3H] 7 alpha-hydroxy DHA as the radioligand. Significant cross reactivity was found with 3 beta, 7 alpha-dihydroxy-5-pregnen-20-one (44%), 3 beta, 7 beta-dihydroxy-5-androsten-17-one (6%), 3 beta, 6 beta-dihydroxy-4-androsten-17-one (2.5%), 3 beta-hydroxy-5-androsten-17-one (DHA, 2%), 3 beta, 7 beta-dihydroxy-5-pregnen-20-one (2%) and 7 alpha-hydroxy-4-androstene-3, 20-dione (1%). 7 alpha-Hydroxy DHA was extracted from plasma and separated from cross-reacting factors using alumina micro-columns. The separation of bound and free steroid was achieved using dextran-coated charcoal. The concentration of 7 alpha-hydroxy DHA in the plasma of breast cancer patients was significantly lower than the concentrations in the plasma of normal women, hospitalized women suffering from non-endocrine diseases and patients with benign breast disease. The decrease in the concentration of 7 alpha-hydroxy DHA in the plasma of pregnant women was not significant.


Pretransplant monitoring of donor-recipient compatibility. In these studies, pretransplant testing of donor-recipient compatibility was performed in 10 related donor and 26 cadaveric renal transplants using a variety of cell-mediated immunity tests. Mixed lymphocyte culture results did not correlate with acute rejection (AR), acute irreversible rejection, or chronic rejection (CR). Lymphocyte-mediated cytolysis also did not correlate with AR, acute irreversible rejection, or CR. Cell-mediated lympholysis correlated with AR but not with acute irreversible rejection or CR. Antibody-dependent cell-mediated cytolysis (ADCMC) was positive pretransplant in 13 (36%) of the recipients. Of the positive patients, 4 had early severe AR and 9 developed typical CR. Of these 13 patients, 9 or 69% lost graft function to rejection whereas only 3 of 20 (15%) of ADCMC-negative patients lost graft function because of rejection (P less than 0.05). In summary, cell-mediated lympholysis testing demonstrated a capability to predict AR episodes. The most useful pretransplant monitoring assay in this patient series was the ADCMC assay. A positive ADCMC against donor cells pretransplant indicates a relatively poor prognosis for long-term graft survival.


Effects of allogeneic stimulations on the proliferation and differentiation of the hemopoietic stem cell. The effects of allogeneic stimulatins on the hemopoietic system were investigated. Spleen cells of mice activated in vivo with alloantigens were able to produce highly active colony-stimulating factor in the culture medium without any stimulation. But spleen cells of these mice could not release colony-stimulating factor after treatment in vitro with anti-theta serum and complement. The number of granulopoietic progenitor cells (colony-forming unit-culture) in both bone marrow and spleen cells of mice treated with such procedures was significantly greater than that of the control, and the number of pluripotent stem cells (colony-forming unit-spleen) of these mice was markedly increased compared with that of the control, especially in spleen cells. These experiments suggest that T lymphocytes activated in vivo with alloantigens may release active substances in the differentiation and proliferation of hemopoietic stem cells.


Selection of compatible platelet donors: a prospective evaluation of three cross-matching techniques. A prospective study was undertaken to assess the values of platelet aggregometry, lymphocytotoxicity, and mixed lymphocyte cultures in selecting compatible donors for patients refractory to random platelet transfusions. Donors were selected at random without regard to HLA types. Concurrent with each platelet transfusion, platelet aggregometry and lymphocytotoxicity were performed using patient serum and donor cells. The results were compared with HLA types, MLC, and increments in platelet counts. Forty-one transfusions were given to 21 patients; 27 were from related and 14 from unrelated donors. Platelet aggregometry was used successfully in selecting compatible donors in 37 cases (90%) with three false negative and one false positive results. Lymphocytotoxicity was useful in 73 per cent of cases with eight false negative and three false positive results. The response to platelet transfusions correlated poorly with HLA matches or MLC reactions. These data suggest platelet aggregometry and lymphocytotoxicity are useful cross matching techniques in selection of compatible platelet donors.


Histochemical similarity of senile plaque amyloid to apudamyloid. Senile plaque amyloid of both isolated and perivascular (dyshoric) types was compared histochemically to other major types of amyloid. In contrast to most amyloids tested, senile plaque amyloid contained less tryptophan and tyrosine reactivity and more alcianophilia. These histochemical features indicate that senile plaque amyloid is similar to apudamyloid, and suggest that local factors are more important than systemic circulating factors in its genesis. The implications of these histochemical observations are discussed.


Experimental bone marrow fat necrosis.

Experimental bone marrow fat necrosis. We have studied serially by light and electronmicroscopy the development of lesions of the adipose tissue of the bone marrow of the rabbit following intravenous injections of saponin. Two types of steatonecrotic lesions were seen: in the femur giant-cell granulomas surrounding necrotic fat cells and in the sternum, small foci of fat necrosis containing calcified deposits. In both cases the lesions were of ischemic origin and secondary to the destruction of the microcirculation of the bone marrow by saponin. These studies suggest that necrosis of the bone marrow fat cells can contribute to the pathogenesis of myelofibrosis. They also suggest that adipose tissue responds differently to ischemia depending on topography. In hematopoietic marrow necrosis of fat cells is followed by calcium deposits, whereas in fatty marrow necrosis leads to resorptive giant cell reaction.


Fetal development in experimental uremia. Uremic women on hemodialysis with metabolic bone disease (hyperparathyroidism, osteomalacia resulting from defective vitamin D metabolism) and anemia (erythropoietin deficiency) are known to give birth to infants without bone disease or anemia. Therefore, skeletal development (enchondral and desmal bone formation) and hepatic erythropoiesis were evaluated in fetuses of uremic rats. These fetuses failed to show defective mineralisation or evidence of bone disease. Bolus injection of high doses of exogenous PTH into the maternal or fetal organism did not affect fetal bone histology. In addition, no apparent defect of bone mineralisation or bone formation was found in fetuses of ricketic rats. Normal mineralisation in the offspring of uremic rats may be explained by fetal hyperphosphatemia and/or insensitivity of fetal (woven) bone mineralisation to vitamin D. Absence of fetal anemia (normal hematocrits, normal density of hematopoietic cells in the liver) in the presence of maternal anemia is presumably due to the insensitivity of fetal erythropoiesis to erythropoietin.


Acetylcholinesterase-activity in rectal mucosa of children with obstipation. The results are presented of a clinical-enzyme histochemical evaluation of the activity of acetylcholinesterase in the rectal mucosa of 46 children with obstipation. In four cases abundant and coarse acetylcholinesterase positive nerve fibres were present in the lamina propria of the mucosa. Only in these 4 cases was the diagnosis of Hirschsprung's disease supported by the clinical course. Local accumulations of fine acetylcholinesterase positive nerve fibres or accumulations of acetylcholinesterase positive foamy or structureless material were not correlated with Hirschsprung's disease.


Malignant histiocytosis with chronic course. Ultrastructural and ultrastructural cytochemical studies. Four cases of malignant histiocytosis with leukemic manifestations and chronic course were reported. Light microscopic, ultrastructural and ultrastructural cytochemical details of these atypical cells were demonstrated. Ultrastructurally these cells resembled hairy cells most closely among the known varieties of leukemic cells. However, ribosome-lamella complexes were not found and some atypical cells had a few short cytoplasmic projections. In addition, tartrate-resistant acid phosphatase was absent from these cells. We speculate that this leukemic reticuloendotheliosis with a chronic course seen in Japan seems to be analogous to malignant histiocytosis with massive splenomegaly reported by Vardiman et al.


Benign pleural lesion and malignant mesothelioma. In a series of eighteen diffuse malignant mesotheliomas, five cases were encountered in which thoracic surgery with benign nontumorous diagnosis preceded the development of a malignant mesothelioma by several years. The morphological findings in three of these five cases are compared with the morphology of the tumor specimens and an attempt is made to recognize the earliest possible malignant features. Crowding of mesothelial cells, their variability in size and nuclear hyperchromatism are pointed out as warning signs. In relation to these findings, the histogenetic significance of predominantly fibroproliferative versus epithelial-like pleural lesions is discussed. A histogenetic classification, based on the studies of eighteen diffuse malignant mesotheliomas, two benign fibrous mesotheliomas, one pleural fibrosarcoma, and numerous pleural plaques as well as reactive mesothelial lesions, is offered. The therapeutic aspects are mentioned.


Hereditary nephronophthisis with a life span of three decades. Light and electron microscopical, immunohistochemical, clinical and family studies. Familial nephronophthisis was diagnosed in a son and two daughters of a mother who herself died in uraemia at the age of 29 years. The son died at 33 years, two daughters are alive at 30 and 33 years. Our cases suggest a dominant autosomal type of inheritance because the mother married twice; the affected son was from the first marriage and the affected daughters from the second marriage. There was no known consanguinity between the parents. The pathogenesis of the disease can be explained by a slowly progressive process that leads to complete or partial obstruction of the tubules in the corticomedullary area, and also, therefore, to cystic dilatations. Histological evidence for this is provided by the proliferation of fibroblasts around the collecting ducts and other tubules, prominent thickening of the tubular basement membrane, and fibroblasts and collagen fibrils in or inside the thickened basement membranes. An ultrastructural description of affected kidneys is given.


Lymphatic malformation in human fetuses. A study of fetuses with Turner's syndrome or status Bonnevie-Ullrich. In 7 spontaneously aborted fetuses characterized by a large cystic hygroma in the nuchal region and a prominent and generalized edema, the structure and extension of the lymphatic system was studied. In all fetuses marked malformations of this system were found. Although the morphologic appearance seemed to vary greatly it is suggested that the disorder is essentially a generalized hypoplasia and partial agenesis of the lymphatic system, which ceases to extend peripherally at an early embryonic stage. A suggestion as to the mechanism of this growth inhibition is made.


Necrotizing lymphadenitis: possible acute toxoplasmic infection. A rapid rise in serum hemagglutination antibody (HA) titers for toxoplasma was detected about 2 months after the onset of cervical lymphadenopathy in two patients with necrotizing lymphadenitis. These lymph nodes proliferation of histiocytes with nuclear debris, phagocytized macrophages and necrotic areas, and the association suggested that necrotizing lymphadenitis might be caused by acute toxoplasmic infection.


Pituitary adenoma producing thyrotropin and prolactin. An immunocytochemical and electron microscopic study. A pituitary adenoma with suprasellar extension that had caused hyperthyroidism due to secretion of excess thyrotropin (TSH), as well as mild hyperprolactinemia, was studied with differential staining, immunocytochemistry and electron microscopy. Most cells of the tumor strained lightly with aldehyde thionin, which demonstrates the granules of normal thyrotrops, and immunocytochemically with antiserum to the hormone-specific beta chain of TSH. A minority of the cells was immunoreactive for prolactin. Electron microscopy revealed light cells interspersed with highly pleomorphic dark cells. Both were sometimes multinucleated, and contained variable numbers of small secretion granules, multiple Golgi complexes, and abundant endoplasmic reticulum.


Giant cell tumor of bone: fine structural localization of acid phosphatase. The fine structural localization of acid phosphatase in the different cells in a benign giant cell tumor of bone has been studied. Stromal cells type 1 and 2 (fibroblast-like and macrophage-like, respectively) showed the presence of lead phosphate precipitate following incubation in a Gomori-type lead salt medium only in conventional lysosomes. In the multinucleated giant cells, the final product was deposited over lysosome-like organelles, and also over Golgi cisternae, vesicles, and vacuoles. Furthermore, evidence for presence of acid phosphatase was obtained in smooth-surfaced tubular, sausage-, horse-shoe-, and ring-shaped structures and over digestive vacuoles of autophagic or heterophagic origin. Finally, in these cells, many of the tubular and vacuolar elements located subjacent to areas of the plasma membrane with microvillous specializations (abortive brush borders?) were shown to carry acid phosphatase.


Immunohistochemical patterns of hepatitis B surface antigen (HBsAg) in patients with hepatitis, renal homografts recipients and normal carriers. A series of 180, Bouin-fixed and paraffin embedded liver biopsies obtained from 147 patients was investigated for the presence of hepatitis B surface antigen (HBs) by histochemical and indirect immunofluorescence techniques. A comparison between orcein staining and Masson's trichrome preparations for ground glass hepatocytes, showed that immunofluorescence was both the more reliable and the more specific method for detection of HBsAg in liver tissue. The ability to perform this technique on paraffin sections facilitates systematic studies and allows retrospective work-up. IF-HBs positive hepatocytes were found in approximately two thirds of all HBs-positive patients in their serum, but never seen in HBs-negative patients. HBs-positive cells were observed in healthy chronic carriers and in all forms of chronic hepatitis, but never in acute HBs-positive hepatitis. In patients treated with chronic hemodialysis and in renal homograft recipients, the incidence of positive cells was higher than in the chronic hepatitis groups; this could be correlated with the duration of antigenemia at the time of biopsy.


Sympathetic innervation of the human leg arteries. Sympathetic innervation of the human main leg arteries was morphologically investigated by the Formaldehyde-induced fluorescence method of Falck and the silver-impregnation method of Bodian. The following points were established: 1. There is a compact fine-meshed nerve-net directly on the surface of the media. 2. In the dorsal pedal, the anterior tibial, the peroneal, the posterior tibial, and the femoral artery, fine unmyelinated nerve fibers which run on the surface of the media penetrate constantly into the extreme outer layer of the media together with elastic and collagenous elements of the adventitia. 3. There is no difference in the innervation mode of the media of various leg arteries. 4. It seems that there is no correlation between the innervation of the arterial wall and the morbidity difference in the chronic arterial occlusive diseases of leg arteries.


Studies on the vesicular component of the Auerbach's plexus and the substance P content of the mouse colon in the acute phase of the experimental Trypanosoma cruzi infection. A dramatic reduction in the total number of dense vesicles in Auerbach's plexus of the mouse colon was observed during the acute phase of experimental American Trypanosomiasis (Chagas' disease). A significant decrease in substance P activity of the colon of inoculated animals was also measured. It is suggested that this decrease in substance P activity could be related to the reduction in the number of dense vesicles in Auerbach's plexus.


A lymphocyte chalone assay using lymphocyte colony growth in agar capillaries. Using a recently developed method of culturing T-lymphocyte colonies in agar-containing capillary tubes, the capacity of three different lymphoid extracts with lymphocyte chalone (LC) activity to inhibit colony growth was demonstrated. Sephadex fractions from a calf spleen extract were tested on the colony growth of granulocytic cells and PHA-stimulated T-lymphocytes as well as on the in vitro uptake of 3H-thymidine by bone marrow and ConA- and LPS-stimulated mouse spleen cells. The data strongly suggest that it is only the combination of several different assay systems applied to the same fractions that permits a clear-cut determination of a specific lymphocyte proliferation inhibitor like LC.


[Causes of death in thyroid cancer patients]. To determine the necessary extent of surgery in thyroid cancer 128 autopsy reports of patients with thyroid cancer were studied. It was found that in a group of those died from cancer the specific weight of death issues due to papillary cancer, most frequently observed, was small (8.5%), consequently these patients would show a recovery postoperatively. Patients with one lobe involved die following its resection but, as a rule, not because of the process spreading to the second lobe. The prognosis for patients with thyroid cancer largely depends on the histological type of tumor rather than the extent of surgery. All this supports the idea that in appropriate cases it is feasible to continue oneself to the resection of the lateral thyroid lobe for this kind of tumor.


[HL-A system antigen distribution in malignant neoplasm patients]. The distribution of transplantation HL-A antigens in 124 patients (cancer of the stomach, mammary glands, the large intestine, the lung, skeletal sarcoma) was studied in microlymphocyte toxic reaction. A comparison with the results of the analogous examination of healthy persons dwelling in Leningrad indicated certain differences in the frequency of encountering some antigens, and the absence of HLA-B18 antigen among patients. Most frequently (in 62%) an "incomplete set" of antigens was found in a group of patients, antigens typical for the whole locus (more frequently "B") being absent in 7.3%. In 6.4% "extra" (live or more) HL-A antigens were noted. The use of adaptive immunotherapy would significantly change antigenic spectrum of lymphocytes in patients.


[Fractional composition and activity of ATPase proteins in the aorta of rats with vitamin E deficiency]. Proteins, extracted from aorta by 0.15 M NaCl solution, were separated into 10-12 fractions by polyacrylamide gel disc electrophoresis; 5 main protein zones were noted among these fractions. Decrease in content of the 2nd protein fraction, which is similar to blood serum albumins in its electrophoretic mobility, was observed in the E-avitaminous animals. The Ca2+, Mg2+-dependent ATPase activity of proteins, extracted from aorta of E-avitaminous animals, was decreased to 15.9 +/- 1.04 un as compared with control (26.5 +/- 4.7 un).


[Enzyme cytochemical investigations on pleural effusions (author's transl)]. A total of 130 smears from 77 patients with various diseises (42 patients with tumors, 35 patients with specific and non-specific lung diseases) were investigated with enzyme cytochemical methods with regard to the practical application of enzyme cytochemistry in pleural effusions. It is possible to demonstrate all investigated enzymes on normal air-dried  or aceton-fixed smears without any technical problems. Between tumor and mesothelial cells a different reaction on some enzymes (alkaline phosphatase, non-specific esterase, aminopeptidase, beta-glucuronidase) could be found valuable for diagnostic purpose. For application in praxi alkaline phosphatase seems to be most important. 70% of all pleural effusions of tumorous origin contain alkaline phosphatase positive tumor cells.


Inhibition of diethylnitrosamine-induced strand breaks in liver DNA by disulfiram. Disulfiram (DSF) delayed the appearance of diethylnitrosamine (DEN)-induced strand breaks in liver DNA of rats. The fragmentation of liver DNA produced by DEN was studied 4 and 24 h after administration of the carcinogen on alkaline sucrose gradients. A single dose of 500 mg/kg DSF given 1 h prior to carcinogen treatment delayed for at least 4 h the DEN--induced strand breaks in liver DNA. A single DSF pretreatment, however, did not protect against carcinogen-induced strand breaks when observed 24 h after DEN injection. It is possible that continuous administration of DSF might inhibit the DEN-produced damage of the genetic material.


[Mononuclear phagocytes in tumors: differentiation by a rosette technique (author's transl)]. Mononuclear phagocytes in tumors cannot be reliably identified and quantified using morphological criteria alone. For this reason an alternative method, which depends on functional properties is described: Macrophages and monocytes derived from tumors from rosettes with antibody-coated sheep red blood cells and can thereby easily be detected and differentiated from tumor cells.


Per-operative intravascular tumor cell shedding. An experimental methodological study. A previously reported experimental technique for estimation of the per-operative intravascular tumor cell shedding was further studied. A significant increased tumor cell shedding was found in rats after tumor biopsy compared with animals operatively prepared for such a biopsy. An attempt was made to estimate the number of intravascularly shedded vital tumor cells under biopsy.


[Carcinomas in papillary cystadenolymphomas of the parotid gland--definition and differential diagnosis (author's transl)]. Within a collective of 1431 salivavry gland tumors of the salivary gland register (1965--1976) an observation has been done, which has been classified as a "carcinoma in a papillary cystadenolymphoma". Corresponding to the "carcinoma in a pleomorphous adenoma" of the WHO-classification of salivary gland tumors the terminus "carcinoma in a cystadenolymphoma" is further defined. 6 additional cases from the literature are reviewed. The possible role of epithelial metaplasia and of a proceding radiation in the development of carcinomas in cystadenolymphomas are discussed. The following other tumors have to be differentiated from a carcinoma in a cystadenolymphoma: Metastases of other tumors beyond a cystadenolymphoma; malignant lymphoepithelial lesions (predominantly malignant lymphomas in a preexisting immune-sialadenitis of the myoepithelial sialadenitis type; rare carcinomas), and lymphoepitheliomas.


Detection of strand breaks in phiX 174 RFI and PM2 DNA reacted with ultimate and proximate carcinogens. Supercoiled DNA duplexes of phages phiX 174 and PM2 were treated in aqueous solution at neutral pH with ultimate and proximate carcinogens. Subsequently, the carcinogen-treated phage DNAs were subjected to velocity sedimentation in neutral and alkaline sucrose to quantitative introduction of single strand breaks. Reaction of phage DNA with the ultimate carcinogens N-methyl-N-nitrosourea (MeNOUr), N-ethyl-N-nitrosourea (EtNOUr), 7-bromomethyl-benza[a]-anthracene, N-acetoxy-2-acetylaminofluorene [(Ac)2ONFln] and K-region oxides for short periods followed by sedimentation in neutral sucrose gradients led to very few breaks. Incubation with the proximate carcinogens N-hydroxy-2-acetylaminofluorene, 2-acetylaminofluorene, 7-methyl-, and 7,12-dimethyl-benza[a]anthracene did not result in breaks. However, when the phage DNAs were reacted with the ultimate carcinogens under the same conditions but subsequently alkali-denatured and sedimented in alkaline sucrose gradients, single strand breaks were readily introduced. Incubation with the proximate carcinogens followed by alkali denaturation and sedimentation in alkaline sucrose showed that only 7,12-dimethyl-benz[a]anthracene and, to a minor extent, 7-methyl-benz[]anthracene caused alkali-inducible breaks. The ability of N-methyl-N'-nitro-N-nitrosoguanidine to effect breakdown of superhelical phage DNA in alkali was found enhanced in the presence of N-acetyl-cysteine.


Transplacental effects of nitrosamines in Syrian hamsters. II. Nitrosopiperidine. Nitrosopiperidine (NP) was found in Syrian hamsters quantitatively in the maternal blood for more than 8 h after subcutaneous injection, whereas it disappeared from placenta, fetus and amniotic fluid within the same time period. For N6MI, only traces were seen after 2 h in the same tissues. The long-term transplacental effect of a single dose of NP was weak, as demonstrated by a low respiratory tract tumor incidence (P-generation: 54%, F1- generation: 4%). Some tumors occurring in the digestive tract of exposed young were not found in their mothers and not commonly observed in controls. These tumors were considered a borderline transplacental effect. Tumors of other sites (i.e., the urogenital and genital tracts, reticuloendothelial system, endocrine organs and other tissues) corresponded in incidences to the overall fluctuations observed in this hamster colony.


Transplacental effects of nitrosamines in Syrian hamsters. III. Dimethyl- and dipropylnitrosamine. The aliphatic nitrosamines dimethylnitrosamine (DMN), diethylnitrosamine (DEN), dipropylnitrosamine (DPN), and dibutylnitrosamine (DBN) reached fetal tissue in quantitatively measurable amounts after subcutaneous administration to pregnant Syrian hamsters. The compounds were present for at least 2 h in maternal blood, placenta, fetus, and amniotic fluid; DBN was still measurable after 6 h. Only a weak or borderline transplacental effect was seen when incidences and latencies of neoplasms in the respiratory and digestive tracts of the F1-generation were compared with those of the P-generation after exposure to a single dose of DMN or DPN. However, some tumor types occurred at relatively high rates in the young, but were seen only occcasionally in their mothers or in this hamster colony in general.


Immunhistochemical demonstration of different collagen types in the normal epiphyseal plate and in benign and malignant tumors of bone and cartilage. Several benign and malignant tumors of bone and cartilage were examined by means of type-specific collagen antibodies in connection with indirect immunofluorescence technique in order to determine wether there is a positive correlation between cell morphology and gene expression as refered to the synthesis of tissue- or cell-specific collagen. In general benign bone and cartilage tumors show the collagen type corresponding to the original maternal tissue. In malignant osteogenic tumors a strong positive correlation was found between morphologic differentiation of osteosarcoma cells and tissue specific collagen synthesarcomas. Unrelated to the grade of differentiation and the type of malignant tumor, collagen type III could be demonstrated in all tumors investigated, occurring rather from vascular stroma than from the tumor cell itself.


Transplacental effect of nitrosamines in Syrian hamsters. IV. Metabolites of dipropyl- and dibutylnitrosamine. The present investigations showed that assumed and established metabolites of dipropylnitrosamine and dibutylnitrosamine reach the Syrian hamster fetus after subcutaneous (s.c.) treatment of their mothers (at day 14 of gestation). The compounds [2-hydroxypropylpropylnitrosamine, HPPN; 2-oxopropylpropylnitrosamine, OPPN; methylpropylnitrosamine, MPN; N-nitrosobis(2-hydroxypropyl)amine, BHP; and 4-hydroxybutylbutylnitrosamine, HBBN] were still present in the examined tissue (maternal blood, placenta, fetus, amniotic fluid) 4--6 h after s.c. injection. The overall incidence of transplacentally induced tumors was lower in the F1- than in the P-generation and comparatively longer latencies were also observed in the F1- generation. However, in some groups low incidences were found of tumors which did not occur in the mothers (i.e., nasal cavities: BHP, HBBN; trachea: HBBN; lungs: HPPN, BHP, HBBN; liver: OPN, MPN, BHP, HBBN). Compared to exposure at early gestation, the transplacental carcinogenic effect increased at day 14 of gestation. Neoplasms originating in other organs were not associated with a transplacental effect of the examined nitrosamines.


Local and systemic effects of 1-acetoxypropylpropylnitrosamine in Syrian golden hamsters. 1-Acetoxypropylpropylnitrosamine (1-APPN) was synthesized and its biological effect examined in Syrian hamsters after subcutaneous (s.c.) administration. 1-APPN induced mesenchymal and epithelial neoplasms at the injection sites, as well as epithelial tumors in remote organs. Local neoplasms were a.c. sarcomas, mammary adenocarcinomas and Schwannomas, whereas tumors of the respiratory tract (papillary polyps, papillomas, adenomas, epidermoid carcinomas, and adenocarcinomas) were attributed to a systemic effect as were pancreas duct tumors. Neoplasms which originated in the upper digestive and genital tracts of females (papillomas, epidermoid carcinomas) may be related to a systemic and local effect of 1-APPN.


Comparison of the effect of beta-oxidized dipropylnitrosamine metabolites administered at equimolar doses to Syrian hamsters. After subcutaneous administration of dipropylnitrosamine (DPN) to Syrian hamsters, gas-liquid chromatographic analysis of the 16-h urine revealed the DPN metabolites, 2-hydroxypropyl-, 2-oxopropyl-, and methylpropylnitrosamines. In a related series of experiments, hamsters received equimolar doses of the above compounds and of N-nitrosobis(2-hydroxypropyl)-amine (BHP) and 2,2'-dimethyldipropylnitrosamine (DMDPN). The metabolites as well as BHP and DMDPN had a weaker effect than did DPN on the rate and/or latency of respiratory tumors. In the respiratory tract, the segmental tumor distribution and histological types varied according to the compounds. The metabolites of DPN induced additional tumors in the digestive tract. These experiments do not support the concept that the beta-oxidized metabolites of DPN are the proximate carcinogens of the parent compound.


Carcinogenicity of N-nitrosopyrrolidine: dose-response study in rats. Results from a dose-response study in rats are reported, in which daily oral doses of 10, 3, 1, and 0.3 mg/kg bodyweight/day respectively were administered. The three highest dose levels resulted in incidences of liver cancer of 46, 84, and 32% respectively. In the lowest dose group (0.3 mg/kg/day) no statistically significant increase in tumor rate compared to untreated controls was found.


Interrelationship between annulate lamellae and the cytoplasmic microtubule complex in tumor cells in vivo and in vitro. Annulate lamellae were observed in untreated in vivo ascites tumor cells with a diminished cytoplasmic microtubule complex. The ascites tumor cells in vitro responded to prolonged colchicine treatment with the formation of annulate lamellae. Simultaneous treatment with dibutyryl cycle adenosine monophosphate and colchicine seemed to enhance the formation of annulate lamellae. Single pore complexes were found in the granular endoplasmic reticulum in untreated tumor cell in vitro, and a close association of microtubules with the nuclear envelope was observed. Our results suggest the existence of an interrelationship between the cytoplasmic microtubule complex and certain other cell structures, i.e. the nuclear envelope, annulate lamellae, and single pore complexes.


[The carrier potential of liposomes for methotrexate. Changing of the tissue levels of methotrexate in the organs of mice (author's transl)]. Drugs entrapped in liposomes (artificial lipid vesicles) exhibit different pharmacokinetics after intravenous application than drugs injected in a free form. The folidacidantagonist methotrexate can be entrapped in liposomes in a therapeutically useful concentration (0.5 mg MTX/ml) and can be stored with high stability of entrappment. After intravenous injection into the tail vein of mice liposomes entrapped methotrexate is found more enriched in cell systems with high rate of endocytosis and not eliminated by the kidneys within 3 h like free methotrexate. It can be shown, that for the organs liver, spleen, kidney, gut, lung, and blood over a 6 h period liposomes entrapped methotrexate is enriched in the tissues and that for example after 6 h the methotrexate level in the liver is 20 fold higher in comparison to free injected methotrexate.


Induction of the deficient acid DNAse activity in mouse interfollicular epidermis by croton oil as a possible tumor promoting mechanism. Histochemical activity of acid DNAse, intensity of nucleic acid staining and histological alterations in mouse interfollicular epidermis (I.F.E.) were investigated after a single dose or after chronic topical administration of two hyperplastic agents, of which one (croton oil) was a potent tumor promotor, and the other one (podophyllin) did not promote skin carcinogenesis. Podophyllin induced intense uniform I.F.E. hyperplasia without any proliferation of poorly differentiated basal cells, without increased nucleic acid staining and without any appreciably decreased acid DNAse activity. On the other hand, croton oil (as well as TPA) produced almost immediate, distinct hyperplasia of poorly differentiated basal cells with increased intensity in the staining of both nucleic acids and nearly complete deficiency in acid DNAse activity. Similar histochemical and histological patterns were observed at the sites of wounding hyperplasia in untreated control mice. Such wounding hyperplasia was thought also to be a tumor promoting factor. It was suggested that the decrease in acid DNAse activity which occurred almost immediately after administration of potent tumor promoters and which could not be induced by a hyperplastic agent without tumor promoting action may have a particular importance in the mechanisms of tumor promotion.


The methylation of DNA in regenerating rat liver. There was more persistent methylation of liver DNA from rats given [14C]DMN if it was given during liver regeneration, either after partial hepatectomy or a dose of CCl4 compared to otherwise untreated rats. During liver regeneration, DMN metabolism was slowed making the active metabolites available for longer.


[Left ventricular ejection and ejection reserve during isoproterenol infusion in hypertrophic obstructive cardiomyopathy (author's transl)]. In 10 patients with hypertrophic obstructive cardiomyopathy (HOCM) and in 10 patients without heart disease (normals) left ventricular function and myocardial reserve under isoproterenol (Iso) infusion (0.3 microgram/kg B.W./min) were measured. From the monoplane cineangiography of the left ventricle diastolic wall thickness as well as ejection phase contractile indices, ejection fraction (EF) mean velocity of fiber shortening (VCF) and mean normalized systolic ejection rate (MNSER), were calculated. Maximum total load (TL) served as measure for afterload. Wall thickness in HOCM was higher by 73% as compared to normals (p less than 0.001). Hemodynamic values for normals at rest were as follows: EF 68.9 +/- 8.0%, VCF 1.22 +/- 0.19 circ/sec, MNSER 2.25 +/- 0.25 vol/sec and TL 228.6 +/- 37.4 dynes . 10(5). Values for HOCM at rest were as follows: EF 77.4 +/- 7.71% (p less than 0.05), VCF 1.53 +/- 0.3 circ/sec (p less than 0.05); MNSER 2.66 +/- 0.35 vol/sec (p less than 0.01) and TL 288.5 +/- 55.5 dynes . 10(5) (p less than 0.01) as compared to normals. The values under Iso in normals resulted in a significant fall of the TL (p less than 0.05), the enddiastolic volume (EDV, p less than 0.05) and of the enddiastolic pressure (EDP, p less than 0.05), VCF rose by 89% (p less than 0.001), MNSER by 66% (p less than 0.001) and EF by 23% (p less than 0.001). In HOCM under Iso TL rose by 45% (p less than 0.05), EDV and EDP did not change (p less than 0.05), VCF and MNSER rose by 23% (p less than 0.05 respectively p less than 0.01). VCF and MNSER in HOCM with Iso were reduced by 17% respectively by 13% (p less than 0.01) as compared to normals, the EDP was increased by factor 4, while EDV showed no significant difference (p less than 0.05). Our results indicate that the left ventricle in HOCM in spite of its marked hypertrophy is unable to adequately compensate for an acute gain of afterload as induced by the effect of catecholamines. Therefore, we assume stress-related congestive symptoms in HOCM to be caused--aside from other mechanisms--by diminished ejection reserve.


[Cyclic changes in the excitability of the cerebral cortex in alert rats under conditions of direct interference with serotonin and noradrenaline metabolism]. Excitability recovery cycles in the visual cortex before and after administration of 5-OTP, d, 1-DOPA, PCPA and L-methyl-DOPA were studied on 23 alert rats with electrodes chronically implanted in the brain. The appearance of cyclicity under the influence of the drugs was established in the trace processes elicited by a photic stimulus. Differences between the periods of cyclic changes were revealed in conditions of activity predominance of the serotoninergic system (300-400 ms) and the noradrenergic system (200 ms). Their function in the short-term memory mechanisms is discussed.


[Analysis of apomorphine aggessiveness and stereotypy: role of serotonin- and cholinergic systems of the brain]. In male albino rats the electrolytic lesions of the dorsal and median raphe nuclei of the mesencephalon diminished apomorphine-induced aggressiveness (number of attacks, aggressive posture latencies) but didn't influence significantly the intensity of the stereotypy. Both the blockator of tryptophane hydroxylase parachlorophenylamine (PCPA) and 1-tryptophane did not exert any influence on behavioral effects of apomorphine. The raphe-lesion as well as PCPA decreased the level of serotonin and 5-hydroxyindoleacetic acid in the rat forebrain. PCPA decreased in raphe-lesioned rats the dopamine level too. M-cholinoblocking agent atrophine enhanced apomorphine-induced aggressiveness and stereotypy. The blockator of cholinesterase physostigmine had opposite effects. The results suggest that apomorphine induced aggressiveness depends on serotoninergic and cholinergic activity in the brain and there exists a functional link between these neuromediator systems in the CNS.


Major congenital malformations in neonates at U.T.H. Lusaka Zambia. The incidence of major congenital malformations in U.T.H., Lusaka during 1976 is reported. The incidence of some common major malformations are compared with the other series. Central nervous system and Alimentry system malformations were most frequent. The relative low incidence of anencephaly and cleft lip and palate in African newborns is confirmed.


[Gamma rigidity in parkinsonism].

[Gamma rigidity in parkinsonism]. The paper presents the results of the study on a muscle tension in patients with parkinsonism. The great role in the maintenance of the motor tonic activity in parkinsonism is played by an increased excitability (of a static type) of the receptors of the muscle length. The assumption is made that an increased sensitivity in these receptors is the result of the increased fusiomotor activity. The author discusses a possibility of changes in the structure of intrafusal fibres in spindles of the muscle due to which these receptors can preserve an excited state for a long time.


Some histochemical reactions on the neurosecretory cells of Rivulogammarus syriacus chevreux (Crustacea, Amphipoda). The histochemistry of neurosecretory material in neurosecretory cells of Rivulo-gammarus syriacus has been investigated. Histochemically, these cells contain different neurosecretory substances. The material in A and C cells consists of mucopolysaccharides and lipids, that in B, B' and D cells there are a protein containing cystine S-S group, mucopolysaccharides and lipids, and that in E cell contains a weak protein with cystine S-S group, a substance showing beta metachromasia and lipids. The lipids are found in all the cells.


An extended model of the glycolysis in erythrocytes. An extension of a previous model [2] is proposed of the glycolysis of erythrocytes which includes realistic rat laws for the hexokinase-phosphofructokinase system and for the 2,3-P2G phosphatase. Whereas most conclusions previously drawn are reinforced, the mechanism of ATP regulation is different in the present model. The ATP concentration is mainly regulated by the inhibitory action of ATP and the activating effect of AMP on the phosphofructokinase. The role of the 2,3-P2G bypass as a buffer of changes in the ATP demand is of lesser significance than previously thought. Besides the feedback action of the adenine nucleotides on the hexokinase-phosphofructokinase system in the quasisteady state the role of 2,3-P2G as an energy source is important since it can yield ATP for a certain period of time. The present version of the model describes qualitatively the experimental data on the modulation of Na+-K+-ATPase.


[Control of glycolysis in magnesium deficiency: studies on intact red cells and hemolysates]. The behaviour of glycolytic flux and glycolytic metabolic concentrations was studied under conditions of magnesium deficiency. The Mg-deficiency was produced in whole animals (rats) by feeding a diet almost completely free of Mg and in hemolysates of men by the addition of a chelating agent. The results show that the decrease of the free Mg-level is diminished by partial destruction of ATP and 2,3-DPG. The analysis of the control strength of the overall flux leads to the conclusion that the decrease of the glycolytic rate is caused by an inhibition of the hexokinase-phosphofructokinase-control system. The decrease of the MgATP-Complex and free Mg++-level explains the diminished phosphorylation of glucose by the hexokinase. The ATP-inhibition of the phosphofructokinase is amplified by a small increase of free ATP-concentration and a simultaneous decrease of the Fru-6P-level. The increase of the PEP-level is caused by the diminished free Mg++ and MgATP-complex and does not demonstrate a larger control strength of the pyruvate kinase.


Nigerian 'heart muscle disease': the late stages of untreated hypertensive heart failure? Evidence for the hypertensive origin of Nigerian 'heart muscle disease' is presented. Epidemiologically, clinically and pathologically it is similar to hypertensive failure and it is associated with hypertension. It is more severe than hypertensive failure as judged by its prognosis and the myocardial damage at necropsy. The radiographic aortic width and renal histology, but not the retinal arteries have evidence of chronic hypertension in some. Using renal histology and scores on a discriminant analysis it was estimated that 34/62 cases in the necropsy series had been hypertensive . Up to 28 cases had not suffered from chronic hypertension but this figure (3%) of cardiac necropsies does not justify the identification of a highly prevalent myocardial disease in Nigeria. The arguments could apply to South African cryptogenic 'heart disease' and 'Jamaican cardiomyopathy'. The study presents data on the natural history of hypertensive failure.


Mucopolysaccharide histochemistry of the avian tongue. Histochemical features of the lingual glands in Larus ridibundus (L). From the histochemical analysis carried out on the tongue of Larus ridibundus (L.), it has been possible to establish that it is covered by thick stratum corneum on the dorsal surface and shows both in the anterior and posterior portions lingual glands, which histologically consist of aggregates of branched tubules. These glands exhibit identical histochemical reactions which show the presence of neutral mucopolysaccharides, sulfated and unsulfated acid mucosubstances and hyaluronidase-resistant sulfomucins. The acid mucosubstances have no connection with sialic or hyaluronic acid. The seeming absence of sialomucins which may probably not be due to the feeding habits of the animal, could be referred to the phylogenetic aspects of some markedly heterogeneous glycoproteins.


The management of abdominal wall stomata: skin protection, peristomal wound healing and support for the collecting bag. A multi-center study. The specific properties of Stomahesive tested in 116 stomal and 20 fistulous patients render it really useful in stomatherapy where it increases the comfort of the patients: 1. it offers an excellent peristomal skin protection whatever the nature of the stoma or origin of the fistula; 2. it promotes rapid healing of skin lesions, even in ileostomy, transverse colostomy, ureterostomy and fistula patients; 3. it ensures an effective degree of impermeability; 4. it provides a large base for adhesion of the collecting bag; 5. it can be kept on for about 6 days in most cases; 6. The local tolerance is excellent (Acta chir. belg., 1977, 76, 533-537).


Ultrahistochemistry of matrix vesicles in elastic cartilage. Matrix vesicles in the elastic cartilage of epiglottis were negative for acid phosphatase, alkaline phosphatase, and ATPase. This is in agreement with the very rare occurrence of mineralization of elastic cartilage. Only the lysosomes of the chondrocytes showed a positive reaction for acid phosphatase, and a positive reaction for alkaline phosphatase and ATPase was found in relation to the cells of the perichondrium.


[Can we define "histological tolerance" of the abdominal wall after the implantation of various prosthetic materials?]. This experimental work is a comparative trial in the rat of 6 inert prostheses (3 permeable and 3 non-permeable) that are regularly used in man for the repair of large abdominal wall defects. This is performed in both aseptic and septic conditions. Serial macroscopic and bacteriological observations were done. Quantitative histological criteria were defined to characterize the resistance and biological tolerance to the material. This shows that: 1. the width of the cellular reaction, the number of giant, inflammatory, fibroblastic cells confirms the superiority of meshes whatever the implantation conditions; 2. the proportion of fibroblasts to inflammatory cells is a histological expression of the solidity of the repair and of the biological tolerance to the material (Acta chir. belg., 1977, 76, 575-582).