Ultrastructural studies on the endogenous development of Eimeria brunetti. II. Microgametogony and the microgamete. The ultrastructural changes of Eimeria brunetti which occur during microgametogony in the small intestine of the domestic fowl are described. The development of the trophozoite into the microgametocyte  was accompanied by cytoplasmic growth and nuclear division. The developing microgametocytes could be differentiated from developing schizonts because of ultrastructural differences in both cytoplasm and nuclei. The surface area of the microgametocyte was increased by deep invaginations of the limiting membrane. At this developmental stage, the nuclei were situated adjacent to this membrane and protrusions which developed, initiated microgamete formation. Two centrioles were positioned between each nucleus and the limiting membrane and were transformed into the basal bodies of the flagella. The flagella grew out from the basal bodies which then entered the protrusions. A mitochondrion and the dense chromatin-containing portion of the nucleus also entered each protrusion. The microgametes matured while they were attached to the residual cytoplasm of the microgametocyte; they were finally budded off into the parasitophorous vacuole. The microgamete consists of an elongated nucleus which overlaps a mitochondrion towards the arterior of the cell. At this end, a dense plaque (perforatorium) is found together with the 2 basal bodies and their attached flagella. 5 microtubules were apparent and ran longitudinally from the basal body region. In cross section they were arranged in a row of 4 with 1 diagonally opposite; only 2 of these microtubules extended to the posterior tip of the microgamete.


Ultrastructural studies on the endogenous development of eimeria brunetti. III. Macrogametogony and the macrogamete. The ultrastructural changes occurring during macrogametogony in Eimeria brunetti were studied in tissue from the small intestine of infected young domestic fowls. As the macrogametocyte developed, an increase in the volume of the cytoplasm and the nucleus occurred. At this early stage of development the organism was limited by a single unit membrane which possessed a number of micropores. The organism was situated in a parasitophorous vacuole which contained intra-vacuolar folds and intra-vacuolar tubules. The wall forming bodies of type II (WFB II) started to appear before the wall forming bodies of Type I (WFB I). The WFB I developed in the cytoplasmic matric whereas the WFB II were formed within the cisternae of the rough endoplasmic reticulum apparently in association with Golgi bodies. The mature WFB I were homogeneous, limited by a unit membrane, and larger than WFB II which had no limiting membrane but remained surrounded by a membrane of the rough endoplasmic reticulum. Polysaccharide granules were formed in the cytoplasm between strands of the rough endoplasmic reticulum. During maturation the WFB I & II and the polysaccharide granules increased in size and number, and as this occurred a number of electron translucent vacuoles were ejected from the surface of the macrogametocyte. The mature macrogamete possessed a large nucleus with a nucleolus, a number of multi-membranous vacuoles, mitochondria, and canaliculi. The WFB I & II were located at the cell periphery and the polysaccharide granules further towards the interior of the organism. The organism was limited by a unit membrane but during macrogametogony a homogeneous layer had developed which extensively coated the macrog...


Experimental toxoplasmosis in mice and rabbits. Virulence and cyst formation of Toxoplasma gondii. Avirulent Toxoplasma gondii were made virulent by passages in mice, and then attenuated by storage. In contrast to the avirulent parasites, attenuated organisms did not appear to form cysts in mice and rabbits, although parasites could be isolated from such animals as long as three months after their inoculation. Rabbits infected with parasites of attenuated virulence had high antibody levels, and survived challenge with virulent Toxoplasma gondii. Cysts were not detected in the brains of such rabbits following this second infection. By following the generation of Toxoplasma gondii in mouse peritoneal cavities, it was found that attenuated parasites resembled avirulent more than virulent organisms. Although the effect of attenuation was mainly on the parental generation of parasites, some genetic effect seemed to be involved as well.


Granulocyte function in bacterial infections in man. The reduction of nitroblue tetrazolium (NBT) dye and the phagocytic and bactericidal activities of neutrophil granulocytes from 141 patients with bacterial infections and 141 controls have been examined and related to granulocyte morphology. In 115 patients (82 per cent), the NBT reduction capacity was higher than in any control. Vacuolization of the cytoplasm and/or toxic granulation of the neutrophils were demonstrated more often in patients with high than low NBT reduction capacity. In 49 patients (35 per cent), the bactericidal activity of the neutrophils was lower than in any control. Thirty-eight patients (78 per cent) with impaired bactericidal activity had 25 per cent or more peripheral juvenile neutrophils as compared with only 12 (13 per cent) out of 92 patients with normal activity. Vacuolization of the cytoplasm and/or toxic granulation of the neutrophils were demonstrated in 28 patients (57 per cent) in whom the granulocyte function was reduced and in 26 patients (28 per cent) in whom function was normal. Within wide limits, the NBT reduction capacity increased with diminishing bactericidal activity of the neutrophils. Eighteen patients died of infection; 12 had reduced bactericidal activity. Defects in neutrophil granulocyte function caused by bacterial infection may contribute to a fatal outcome of the disease.


In vitro effects of rubella virus, strain RA 27/3, on human lymphocytes. I. Viral inhibition of mitogen stimulation in relation to Rubella Haemagglutination inhibition antibodies. The inhibiting effect of rubella virus on lymphocyte stimulation in vitro was studied, using purified virus of the attenuated strain RA 27/3. Addition of the virus to human lymphocytes from twenty healthy blood donors before stimulation with leuco-agglutinin (LA), a component of phytohaemagglutinin, caused a considerable inhibition of the LA response in some experiments, whereas in other experiments the inhibition was slight or non-existent. If further analysed, the results showed a correlation between the degree of inhibition and the immunity of the lymphocyte donor against rubella, as measured by haemagglutination inhibition (HI). Thus the LA-response was significantly more depressed in a group of lymphocyte donors with HI-titres ranging from 20 to 160 than in another group with HI-titre less than 5. Possible explanations of the virus-induced inhibition of the LA response and possible connection between this phenomenon and the immune response against rubella are discussed.


Isotope-labelled alpha-amino-isobutyric acid as an indicator in cytotoxicity tests. The effect of rabbit antisera on the uptake and release of alpha-amino-isobutyric acid (AIBA) in LS- and P-388 cells was investigated. In the presence of homologous antiserum and complement, the uptake of AIBA was inhibited. In the absence of complement, no effect of antiserum was seen. Using prelabelled cells, the efflux of AIBA was greatly accelerated in the presence of antiserum and complement. The AIBA-uptake method was compared with the trypan blue exclusion test and the 51Cr release technique. The AIBA-uptake method was more sensitive in quantitative cytotoxic studies.


Choline acetyltransferase activity in parotid glands of rats after prolonged treatment with pilocarpine. The enzyme activity, expressed as total activity and concentration, was found to be decreased in the cholinergic neurones of the glands after treatment with pilocarpine for 10 days. The secretion of saliva evoked by the parasympathomimetic drug is thought to have reduced the reflex stimulation of the glands via the cholinergic secretory nerves and thereby lowered the enzyme activity in the nerves.


Influence of acetate on the metabolism of beta-hydroxybutyrate in the perfused hind-quarter of the rat. The effect of acetate, at concentrations normally found during ethanol combustion in intact animals and man in vivo, on the uptake and oxidation of beta-hydroxybutyrate by the perfused rat hind-quarter was studied. The addition of acetate did not significantly affect the total uptake of beta-hydroxybutyrate, but caused a 40% decrease in the oxidation of beta-hydroxybutyrate to CO2. The oxidation of 14C-beta-hydroxybutyrate to 14CO2 accounted for about 10% of the total oxygen consumption by the perfused muscle in the absence of acetate. In the presence of acetate this figure was reduced to about 5%. The addition of beta-hydroxybutyrate did not significantly affect the metabolic fate of 14C-acetate. It is concluded that acetate is preferred as oxidative substrate to beta-hydroxybutyrate. The inhibited oxidation of beta-hydroxybutyrate by acetate did not affect the concentration ratio between beta-hydroxybutyrate and acetoacetate in the medium at the end of the perfusion, indicating that the ability of the muscle tissue to restore an increased redoxlevel, "exported" from the liver during ethanol combustion to extrahepatic tissues, was not impaired by acetate.


Local reflex in microcirculation in human skeletal muscle. The effect of venous stasis of 40 mmHg upon blood flow in human skeletal muscle was studied in four normal subjects and in two chronically sympathectomized patients. Blood flow in skeletal muscle was measured by the local 133Xenon washout technique. Blood flow decreased about 30 per cent during venous stasis of 40 mmHg. In a "passive vascular bed" induced by means of histamine, blood flow decreased only by 16 per cent, indicating that the decrease in blood flow is due to a vasoconstrictor response to increase in vascular transmural pressure. The vasoconstrictor response was unaffected by a spinal sympathetic blockade, but was blocked in areas infiltrated with lidocaine or with phentolamine. The vasoconstrictor response was present in the nonoperated limbs used as a control, but abolished in the denervated arms in the two chronically sympathectomized patients. The findings strongly suggest that the vasoconstrictor response in skeletal muscle is due to a local nervous mechanism involving adrenergic fibres. Thus a local reflex mechanism, most likely a sympathetic axon reflex, seems to be present in human skeletal muscle as in cutaneous and subcutaneous tissue. This indicates that about 45 per cent of the change in total vascular conductance, when a person changes from supine to upright position, is due to this local reflex mechanism operating independently of the central nervous system.


Efflux of 5-hydroxytryptamine from synaptosomes of rat cerebral cortex. The efflux of 3H-5-HT from a crude synaptosome preparation of the cerebral cortex of reserpinized rats was examined. The synaptosomes were loaded with 3H-5-HT by pre-incubation of the homogenate in presence of pargyline and desipramine in order to inhibit deamination of 5-HT and uptake into noradrenergic neurons. The synaptosomes were collected by centrifugation, washed and resuspended in 0.25 M sucrose. No spontaneous efflux of 5-HT was detectable at 0 degrees C but marked efflux was observed at 27 degrees C and 37 degrees C. 4-Chloroamphetamine, low external Na+ concentration, ouabain and the depolarizing agent veratridine markedly accelerated the initial (5 min) efflux. Inhibitors of the neuronal 5-HT uptake, e.g. chlorimipramine, H 102/09 and A 23189, antagonized the 5-HT efflux evoked by these means, whereas desipramine, which is a poor inhibitor of the 5-HT uptake, had only slight effect on the 5-HT efflux. It is suggested that 5-HT can be actively transported out from the synaptosomes by the reversed 5-HT uptake mechanism.


Preferential uptake of 14c-alpha-aminoisobuturic acid into mouse uterine tissue during early pregnancy. The uptake of 14C-AIB into uterine tissue and some other organs was studied during early implantation. Mice in experimentally delayed implantation were given estrogen and 14C-AIB at different time intervals. Mice in delayed implantation given only 14C-AIB displayed a low transport rate into the uterine tissue, comparable with that for the diaphragm muscle. However, if the estrogen injection preceeded that of the 14C-AIB by 4 to 8 h the transport capacity increased by a factor of at least 4 times while the uptake for the diaphargm muscle remained low. Under such conditions 14C-AIB-accumulation into uterine tissue was favoured for at least 4 h of in vivo incubation with the labeled amino acid.


Intra- and extracellular activity of ciliated cells. A method permitting simultaneous recording in vitro of the intracellular and extracellular ( = mucociliary) activity of respiratory ciliated mucous membrane is presented. Using this method the influence of different temperature levels (20 degrees, 30 degrees, 40 degrees C) upon the tracheal mucous membrane of 15 rabbits has been investigated. It is shown 1) that the extracellular ( = mucociliary) activity increases with rising temperatures whereas the intracellular activity is unaffected and remains constant, indicating a temperature influence upon the respiratory tract mucus rather than a change of the intracellular "pace-maker" mechanism; 2) that the restraining effect of the mucus decreases with rising temperatures but is still 10% of the intracellular frequency at body temperature; 3) that the presented method should be useful for future investigations concerning the effect of air-pollution and pharmacological substances upon respiratory mucous membranes.


The effect of teeth amputations on the choline acetyltransferase activity of rat submaxillary glands. The choline acetyltransferase activity in parasympathetically decentralized glands was unaffected by repeated teeth amputations over a period of 2 weeks, while after the same period of time the treatment caused the enzyme activity to increase in innervated glands. It appears that the enzyme in the postganglionic nerve is for its activity dependent on an intact connection with the central nervous system. The increase in enzyme activity is attributed to an enhanced reflex stimulation of the glands from pulpal receptors.


Regulation of the heart of a teleost, Gadus morhua, by autonomic nerves and circulating catecholamines. The cod heart regulation has been investigated by anatomical studies, fluorescent histochemistry, nerve stimulation and drug effects on the perfused heart and electrically paced strips. The effect on the heart of catecholamine release from the head kidney has been studied in a perfused head kidney and heart preparation. Branches of the vagi and the fused 1st and 2nd spinal nerves innervate the heart. Specifically fluorescent fibres were found in these nerve branches, in the ducts of Cuvier, all parts of the heart, bulbus arteriosus and the ventral aorta. Weakly autofluorescent ganglion cells surrounded by specifically fluorescent varicose fibres were present in the walls of the sinus venosus. Vagal stimulation caused bradycardia altered after atropine to tachycardia. Spinal nerve and sympathetic chain stimulation also induced tachycardia, as did provoked catecholamine release from the head kidney. The tachycardia could be blocked by propranolol. Atropine increased and propranolol decreased basic heart rate and contraction force. Adrenergic drugs accelerated and acetylcholine retarded the perfused heart. A positive inotropic effect was obtained with adrenergic drugs on isolated heart strips, while acetylcholine produced a negative inotropic effect on atrial but not ventricular strips. It is concluded from this study that the cod heart has an inhibitory cholinergic nerve supply via the vagi and an excitatory adrenergic supply via both the vagi and the first spinal nerves. Sympathetically controlled release of catecholamines from the chromaffin tissue in the head kidney may also play an important role in the heart regulation.


Regulation of respiration: "The Black Box". A close relation between the state of wakefulness, the electroencephalogram, and the respiration has been demonstrated (Bülow 1963). In the present paper it was assumed that as opening and closing of the eyes influence the EEG and thus probably the state of wakefulness, the responsiveness of the respiratory center may likewise be influenced by the single act of closing the eyes. Seven subjects were studied in the steady state of rest breathing ambient air, 4-5% CO2 in air, or 11% O2 in nitrogen. In experimental periods of 4-5 minutes their pulmonary ventilation and alveolar PCO2 were measured while they randomly were either reading a book, or were blindfolded. It was found that in all three conditions closing of the eyes resulted in a mean decrease of VE of 8 to 14% with a concomitant increase of PACO2 of about 1 mmHg. It is tentatively suggested that other and stronger central or peripheral stimuli impinging on the reticular formation of the brain may explain the changed sensitivity of the respiratory center towards the chemical stimuli in conditions like exercise, chronic hypoxia etc.


The effect of plasma proteins on the capillary permeability in the rete mirabile of the eel (Anguilla vulgaris L.). Measurements of transcapillary exchange of high-molecular dextrans, K+ and THO in the rete mirabile of the eel (Anguilla vulgaris L.) have been made under steady-state conditions while varying the amounts of plasma proteins in the perfusates. When the perfusates contained 20% or less horse serum the permeabilities of D-75 000, K% and THO increased significantly. The effect on the K+ permeability was irreversible while that on D-75 000 and THO was not. The permeability was unaffected when the perfusate contained 30% serum or more. Adding 1.3 g/100 ml bovine albumin to the perfusate maintained the D-75 000 and THO permeabilities unchanged while that of K+ appeared to increase. At an albumin content of 0.33 g/100 ml the effect was similar to that produced by low serum perfusates. Our main conclusion is that lack of the albumin fraction of the plasma proteins reversibly increases the intercellular pore area and irreversibly changes the K+ permeability of the cell membrane.


Coacervate-like membrane structures and olfactory transduction. Current theories concerning the olfactory transduction process are discussed. A hypothesis is formulated, according to which the olfactory receptor membrane contains regions where it has the structure of a lipid-protein coacervate. Such structures may well occur in living cells. Such a membrane would have the ability to change its permeability in response to adorants and a sensitivity comparable to that of the sense of smell. The model also explains the fact that different receptor cells have different sensitivity patterns towards odorants. The model is consistent with the results of experiments that seek to establish the locus of odorant action.


Twenty-four hour variation in flow and composition of leg lymph in normal men. The twenty-four hour variation in concentration and output of total protein, lactate dehydrogenase and alkaline phosphatase has been studied in the peripheral lymph from the legs of 5 healthy volunteers over a period of five days. The highest concentration of these proteins was found in lymph collected during the first two hours after a night's rest. During the day a continuous decrease in concentration occurred without any direct correlation to lymph flow. The variation in lymph protein concentration between early morning and late day was about 40%, lactate dehydrogenase and alkaline phosphate about 90% and 45% respectively.


Flow and composition of leg lymph in normal men during venous stasis, muscular activity and local hyperthermia. Changes in normal human leg lymph protein concentration, output, and lymph flow/lymph protein concentration relationship, as well as lactate dehydrogenase and alkaline phosphatase activity were followed during procedures known to increase capillary filtration as venous stasis, muscular exercise and warming of tissues. Lymph flow increased by 83% during two hour ergometer cycling, and by 117% during two hour warm water foot bath. During a two hour period of venous stasis lymph flow dropped by 50%. There was an increase in lymph flow during the rest period following all three types of experiment, most pronounced after foot warming. An inverse relationship between the lymph flow rate and lymph protein concentration was found. Lymph enzymes followed the same pattern of changes as total protein.


Influence of acetate on the metabolism of palmitate in the perfused hind-quarter of the rat. The metabolism of 1-14C-palmitate and its metabolic interaction with U-14C-acetate were studied in the perfused hind-quarter of the rat. 9% of 1-14C-palmitate taken up was oxidized to 14CO2 accounting for 7% of total oxygen consumption by the perfused tissue. Most label from 1-14C-palmitate was found in the lipid fraction of the muscle tissue. In spite of a 40% inhibition of palmitate oxidation, acetate only caused minor changes in the overall metabolism of palmitate. U-14C-acetate was mainly oxidized to 14CO2 and the oxygen consumption due to oxidation of acetate accounted for 20-30% of the total oxygen uptake. Minor amounts of 14C-acetate were found in muscle lipids. The addition of palmitate did not alter the metabolism of acetate. It is concluded that the presence of palmitate did not affect 14C-acetate metabolism, while the presence of acetate inhibited 14C-palmitate oxidation. The possible sites of interaction are discussed. The found interaction will probably not contribute to any major extent to the disturbed lipid metabolism found in animals and man during ethanol intake. No major changes in the tissue content of high-energy phosphate compounds were found in the presence of palmitate or acetate or both.


Contractile responses to noradrenaline: varying dependence on external calcium of consecutive vascular segments of perfused rat hindquarters. To study the dependency of vascular smooth muscle contractions, produced by noradrenaline, on the concentration of extracellular calcium, experiments were performed on adult male Wistar rats. The hemodynamic characteristics of the isolated, perfused hindquarters were investigated from maximal dilatation up to maximal, noradrenaline-induced constriction under constant flow conditions. Pressor responses to noradrenaline in the consecutive segments of the vascular bed ("proximal" and "distal" precapillary resistance vessels and postcapillary resistance vessels) were determined at low (0.2mM) and at normal (1.5-2.0 mM) Ca++ concentrations in the perfusate. Dependence on external calcium is much greater peripherally. The smallest pre- and postcapillary resistance vessels are the most dependent while the larger, "proximal" resistance vessels are the least dependent on the availability of external calcium. The results illustrate the considerable differentiation of smooth muscle, depending on its location along the vascular circuit. They further indicate that it is likely that the hemodynamically so important microvessels are highly dependent on extrinsic Ca++ sources not only concerning their involvement of remote adrenergic control, but also in their maintenance of normally pronounced "myogenic" tone.


Time course and extent of carotid sinus baroreceptor threshold resetting in rats with renovascular hypertension. To study the extent and time course of arterial baroreceptor threshold resetting to increases in blood pressure, renal hypertension was induced in young normotensive male Wistar rats by unilateral renal artery constriction. At different intervals after operation the extent of baroreceptor threshold resetting in the carotid sinus was examined. Experiments were performed 7, 14 and 25 days after renal artery clipping to enable baroreceptor resetting to be correlated with the rate and extent of cardiovascular changes in rats which had renovascular hypertension of indentical durations (Lundgren et al. 1974). Baroreceptor thresholds in the carotid sinuses were established by progressive clamping of both carotid arteries after partial vascular isolation of the sinuses. The results show that after one week of hypertension baroreceptor resetting is only just apparent but by two weeks resetting is gross and seems to be largely completed. This parallels the adaptive changes in the hindquarters of renal hypertensive rats and it is concluded that baroreceptor resetting is a secondary phenomenon related to the structural changes induced in the vessels by the elevated blood pressure.


Rate-dependent myogenic response of vascular smooth muscle during imposed changes in length and force. A recent study of electrical and mechanical responses to stretch in isolated vascular smooth muscle revealed a clear-cut and graded influence of the rate of change in length, dL/dt (Johnansson and Mellander, 1975). This myogenic "dynamic" response at high rates of stretch was much more pronounced than the "static" response to constant, increased (+40%) length. In this previous study the mechanical responses were recorded as active force. In view of the fact that myogenic reactions in vivo must be associated with changes in vessel caliber, it was considered of interest to investigate the responses to stretch also in smooth muscle undergoing active shortening. In the present study, as in the one referred to above, electrical and mechanical activity in the isolated rat portal vein was studied by the sucrose gap method. However, in the present experiments the mechanical responses were recorded not only as active force but also as active shortening, making possible a comparison of the myogenic responses under these two types of smooth muscle contraction. Dynamic passive stretch was found to be associated with marked increase in spike discharge and mechanical activity under both these experimental conditions and the quantitative relation between spike discharge and rate of passive stretch (or shortening) was similar. Thus, active shortening of the smooth muscle did not interfere with the ability of the vessel to respond myogenically to passive stretch. A further analysis of the results suggested that, for the preparations as a whole, the dynamic excitatory response was more closely related to the rate of change of passive force, dP/dt, than to dL/dt.


Localization of adrenergic receptors in guinea pig ileum and rabbit jejunum to cholinergic neurons and to smooth muscle cells. The localization of adrenergic receptors mediating a relaxing action was investigated in innervated and denervated longitudinal muscle strips from guinea pig ileum and rabbit jejunum. Denervated preparations were contracted by drugs that had a direct effect on smooth muscle cells, such as acetylcholine and histamine, but not by stimuli acting on cholinergic neurons, such as electrical field stimulation or nicotine. After blockade of beta-adrenoceptors, norepinephrine relaxed the innervated guinea pig ileum contracted by electrical field stimulation, by stimulating alpha-adrenoceptors. Norepinephrine in low concentrations did not relax denervated preparations contracted by agents acting directly on smooth muscle. In high concentrations, it relaxed denervated preparations by a nonadrenergic mechanism, resistant to alpha- and/or beta-receptor blockade, but which was also activated by 1-(3,4-dihydroxyphenyl) ethanol. Phenylephrine only had a weak agonistic effect on the electrically stimulated innervated preparation and did not relax the denervated one. The denervated rabbit intestine contracted by acetylcholine was relaxed by norepinephrine and phenylephrine by stimulation of alpha-adrenoceptors. In the innervated preparations both drugs were more effective in inhibiting contractions induced by electrical field stimulation or eserine than those induced by exogenous acetylcholine. Both the denervated guinea pig and rabbit intestine were relaxed by stimulation of beta-adrenoceptors. It is suggested that in the guinea pig ileum alpha-adrenoceptors mediating relaxation are located only in cholinergic neurons, whereas in rabbit jejunum they are located both in these neurons and in the smooth muscle cells. Beta-adrenoceptors are located in the smooth muscle cells of both organs.


Lactate in fast and slow twitch skeletal muscle fibres of man during isometric contraction. Concentration of lactate in fast and slow twitch fibres, respectively, were determined in m. quadriceps femoris after sustained contractions at 25%, 50%, and 75% of maximal voluntary isometric contraction (MVC) until exhaustion as well as after interrupted exercises at 25% and 50% MVC. Maximal lactate concentrations were only found at 50% of MVC performed to exhaustion. Lactate concentration was higher in slow twitch (ST) fibres at 50% MVC compared to in ST fibres at 25% MVC, and higher in fast twitch (FT) fibres at 50% MVC compared to in FT fibres at 75% MVC. After short time isometric exercise (i.e. 75% to exhaustion and 50% and 25% performed for the same period of time as 75% MVC) lactate concentration, expressed as lactate ratio (lactate concentration in FT fibres/lactate concentration in ST fibres) was found to be positively correlated to percent FT fibres (r=0.89). Lactate ratio ranged 0.5-2.0, i.e. at onset of isometric exercise, lactate concentration increase was faster in ST fibres in the muscle rich in ST fibres and faster in FT fibres when the muscle wasrich in FT fibres.


Effect of changes in blood volume distribution on circulatory variables and plasma renin activity in man. In 8 healthy subjects the pressure around the lower body was changed to 40 mmHg above (LBPP) and below (LBNP) atmospheric, thereby altering the amount of blood pooled in the lower body. Heart rate, intraarterial blood pressure, central venous pressure, cardiac output (dye dilution technique) and forearm blood flow (venous occlusion plethysmography) were measured. Plasma renin activity was determined with a radioimmunological method. 6 subjects maintained a relative circulatory steady state during LBNP. LBNP caused significant decrease in central venous pressure (CVP), stroke volume and cardiac output (Q) with an unchanged mean arterial pressure (MAP). Heart rate (HR) increased significantly. Calculated total peripheral vascular resistance (TPVR) and regional vascular resistance (RVR) in the forearm were significantly increased when measured 5-9 min after the onset of LBNP, whereas plasma renin activity (PRA) showed a definite increase only after 19 min of LBNP stimulation. No correlation was found between the changes in PRA and TPVR or RVR. Increasing the pressure around the lower body (LBPP) resulted in a slight but significant increase in MAP as well as a significant but transient increase in CVP. No significant changes were found in HR, Q or TPVR. In the forearm a decrease in RVR was demonstrated. PRA was not significantly changed. The results demonstrate that peripheral vascular resistance and PRA are both influenced by changes in blood volume distribution, possibly elicited via intrathoracic receptors sensitive to changes in central blood volume and/or CVP. The results also suggest that PRA does not play any significant part in the vasoconstriction during LBNP stimulation.


Mental health delivery-systems and post-treatment performance in Nigeria. A retrospective study was made, investigating the post-treatment outcomes of patients in two apparently dissimilar psychiatric therapeutic centres in Nigeria: the Aro Mental Hospital, a custodial facility, and the Aro Community Village Program, a pilot experiment in community psychiatry. A matches sample of 208 treated patients and their next of kin was focussed upon. An organizational study of the milieux was also undertaken. No significant differences exist in the range of therapies which was administered to schizophrenic patients or in the rate of re-admission in the two therapeutic milieux. A significantly greater percent of patients were treated over 3 months on first admission in the community centre than in the hospital centre (P less than 0.05).


"Lithium non-responders" in a lithium clinic. The present study is concerned with the outcome of long-term lithium maintenance therapy administered to 107 manic-depressive patients after more than 12 months. Nine patients failed to respond despite having met the criteria for maintenance within the therapeutic range of lithium. This group, termed "lithium non-responders", had all shown bipolar illness with gross morbidity with frequent cycles, greater than 4 per year, seven had a family history of affective illness (six bipolar). The study did not demonstarte any other clear factors common to the "non-responders" group.


Levodopa treatment of presenile dementia. In Parkinson's disease as well as presenile dementia there is a dopamine deficit in the basal ganglia. Extrapyramidal symptoms are common in presenile dementia, and dementia is a common trait in Parkinsonism. It is reasonable to suggest a partial common etiology and pathophysiology, and the logical consequence is an investigation of levodopa substitution is presenile dementia. Until now very few reports of such studies have been published. The investigations have been uncontrolled or carried out on small or inhomogeneous materials. This investigation is triple-blind, clinically controlled, and the material is very homogenous. After 6 months' levodopa treatment no significant effect is shown either on a broad spectrum of psychiatric items or in cognitive functioning. This negative result is discussed. The probability of a specific Parkinson dementia is mentioned and the significance of the modifying effect of an imbalance in other transmitter systems is emphasized.


Permissible syndromes. The influence of redundancy on patterns of information. A model of clinical decision according to Bayes's formula is described and the problem of redundant informations is evaluated. It is postulated that a definitory and a syndromatic redundancy are unavoidable, which is why it is necessary to develop a correction factor. A series of indicants is investigated in two populations, and it is shown that correction for redundancy results in far-reaching changes in the patterns of information. The permissible syndrome is defined: a subset of informations containing the necessary and sufficient predictive capacity. The methods described may be used for an evaluation of common syndromes and may enable comparisons of information patterns, related to identical or different criteria.


Homicidal aggression in schizophrenic men. In a sample of 205 hospitalized schizophrenics, 59 men were found who made verbal threats to kill or physical attacks some time during their illness. All homicidal aggression occurred during active phases of psychosis, typically in a setting of acute excitement and in recurrent illnesses. Paranoid diagnoses were overrepresented. Closely related females were the prime targets, suggesting a resentment of dependence on a woman. An impersonal, compulsive urge appears to be the motivating force leading to physical attacks.


Clozapine treatment of schizophrenic patients. Plasma concentration and coagulation factors. Eleven male, chronic schizophrenic, hospitalized patients, treated with a constant dose of clozapine (range 200-600 mg daily) as their only neuroleptic medication were studied for a long period of time (minimum 12 weeks). Wide variations in the plasma concentration of clozapine were found in different patients who received the same oral dose, as well as great changes from week to week in the individual patient given a constant dose. The plasma levels of clozapine appeared to have no correlation with either the clinical effect or the side effects. No differences with regard to coagulation factors were found between the patients and the controls.


LSD treatment in a severe case of compulsive neurosis. A detailed account is given of the course and outcome of the treatment with LSD of an incapacitating compulsive-neurotic condition in a 30-year-old male. The treatment took place over 1 1/2 years from the autumn of 1962, and the patient, who has been followed since then, is completely cured symptomatically. In addition, a fortunate change in his general personality has taken place. The events during the LSD sessions revealed the basic elements of a development of his personality since early childhood, particularly the toilet-training period, which resulted in a typical compulsive character neurosis. In turn, this character neurosis became the matrix for the outbreak of his manifest neurotic compulsions which began 4 years before the onset of treatment. The material which emerged was in complete accordance with Freudian theory. No interpretations were given. While under the action of the drug the patient was left alone except for brief visits by the doctor or the nurse. He was free to call them if his anxiety became too strong for him to cope with alone. Besides, he had the support of reporting his experiences to the doctor after the LSD-effect had worn off and discussing them during interviews between the LSD days, still without interpretations being given to him. Practical details of procedure are reported. The necessary caution in employing LSD for treatment purposes, especially the selection of patients, is emphasized: theoretical implications of the psychological material and the course of the curative process are discussed.


Reflex elicitation thresholds in senile dementia. Forty-eight female patients with the diagnosis of senile dementia and 20 elderly healthy women were studied concerning thresholds for orienting responses to intermittent light, the eyelid reflex, and hand withdrawal on electrical pain stimulation. A U-shaped relationship between degree of mental deterioration and reflex thresholds was predicted from two assumptions: (1) that reflex thresholds are progressively increased following the general blunting of cognitive processes, and (2) that active inhibition of certain overt behaviour takes place in patients with little deterioration (as well as in healthy people). The U-shaped relationship was only obtained for the eyelid reflex, and support was only obtained in connection with the orienting response for the assumption that some active inhibition of overt behaviour normally takes place. A further hypothesis was that thresholds for protective-defensive reflexes would not be substantially increased in the most deteriorated cases. This expectation was confirmed only for the hand withdrawal reflex. It is concluded that for the orienting response and for the eyelid reflex there is some relation, although the form is unclear and a rationale is lacking, between the thresholds and degree of mental deterioration. It is further concluded that the threshold for the hand withdrawal reflex is unrelated to the degree of mental deterioration. The inertia of the senile demented patients is stressed as well as their undifferentiated reactions. It is suggested that cognitive defects may partly explain these deficiencies.


Lithium in adult anorexia nervosa. A pilot report on two patients. Two patients suffering from anorexia nervosa for many years who wished to gain weight were treated successfully with lithium carbonate. One patient gained 12 kg and the other 9 kg within 6 weeks. The weight-gain was maintained for a year of follow-up with lithium maintenance therapy.


Digitalisation and digitalis detoxication in the elderly. Twenty-three elderly patients with normal renal function were studied during digitalisation for cardiac failure or atrial fibrillation. Mean serum digoxin concentrations were in the therapeutic range from the fourth day in seven patients given digoxin 0.25 mg daily, from the second day in seven patients given 0.5 mg followed by 0.25 mg daily, and from the first day in nine patients given 0.75 mg followed by 0.25 mg daily. Toxic effects were not encountered in any patient. Serial measurement of serum digoxin concentrations in six patients recovering from digitalis intoxication, all of whom had severe renal impairment, allowed calculation of serum half-times (62 to 189 hours), and elimination constants (9 to 27% per day). The apparent volumes of distribution of digoxin were around 300 litres, and the apparent body contents of the drugs around 20-25 mug/kg body weight. Differences between these figures and those determined by others for younger patients seem mainly to reflect the consequences of renal impairment. If reasonable assumptions are made for fractional absorption, volume of distribution, and elimination constant, serum digoxin levels during digitalisation can be predicted, and are found to agree well with those observed.


Myocardial infarction coincident with cerebrovascular accidents in the elderly. In a three-year prospective study of acute cerebrovascular accident patients admitted to a geriatric unit within 72 hours of the onset, 12.7% had what was considered to be an associated acute myocardial infarction. In the majority of cases, 71%, there was no clinical indication of an acute myocardial infarction and, had it not been for electrocardiographic and enzyme studies, the concurrence of these two conditions might not have come to light. The possible explanations for the concurrence of these two conditions are explored. Patients were followed-up for five years. The mortality rate for the combined acute myocardial and cerebral infarction cases admitted to hospital was 53% in six weeks, and 64% in one year, compared with 26% and 42%, respectively, in those strokes uncomplicated by a cardiac infarction. Only one patient has survived for five years. The recognition of such cases is important in terms of management and prognosis and this may be achieved by ECG recordings followed by enzyme studies in all cases of acute stroke admitted to hospital.


The effect of potassium supplements on total-body-potassium levels in the elderly. Weight, skinfold thickness, grip strength and the total-body-potassium content were measured in 13 healthy elderly subjects before and after a three-month course of potassium supplements given in a dose of 36 mmol per day. There were no significant changes in the total-body-potassium content or in the ratio of total body potassium to lean-body mass. An increase in the right-hand grip strength may well have been a placebo effect.


Chilaiditi syndrome.

Chilaiditi syndrome. The features of the Chilaiditi Syndrome are described, together with the historial background, and a brief review of the literature on the condition is given. The prevalence in our geriatric population was found to be 1% and the 13 cases seen over 22 months are reported briefly. The prevalence increases with age and may be related to the consumption of drugs by the elderly; although in the majority it is asymptomatic, it may, particularly when associated with gastrointestinal symptoms, lead to unnecessary laparotomy. In the geriatric patient, interposition of the bowel should be considered in the differential diagnosis of air under the right hemidiaphragm.


Improving cognitive performance in psychogeriatric patients: the influence of physical exercise. Performance measurement in psychogeriatric patients does not provide full insight into their potential abilities (competence). By systematically varing environmental conditions, performance levels can be seen to vary with them. The experiment discussed here demonstrates the influence of movement therapy on the results of some psychological tests. The subjects were old people (average age 82 years) who at an advanced age were confronted with mental and physical handicaps of such a nature that they had to be admitted to a psychogeriatric nursing home. Forty patients were divided into two groups. Both groups were tested twice with an interval of one month. A control group was tested twice under identical circumstances. In the first test, both groups were examined under the same conditions. The second test of the exercise group took place shortly after the subjects had taken part in physical exercise. The psychological tests consisted of a free-recall task, a test for visuomotor coordination and a recognition task. The results showed that in the free-recall test the exercise group had improved more than the control group. A qualitative analysis of the free-recall and recognition performance seemed to suggest that the exercise group showed greater retrieval activity than the control group. Visuo motor abilities did not significantly vary under experimental conditions, though the observed changes were compatible with improved cognitive performance in the exercise group.


Sublingual varicosities and vitamin C in elderly vegetarians. Twenty-two elderly people, who were vegetarians for many years, had high ascorbic-acid values in plasma (10.2 +/- 0.4 mg/l) and leucocytes (35.9 +/- 1.99 mug/10(8)WBC). Visual and photographic examination of their tongues showed a much lower incidence of sublingual petechiae and varicosities than is general in elderly people. It is proposed that previous, perhaps recurrent, vitamin deficiencies may lead to irreversible changes in the elderly that cannot subsequently be changed by vitamin-therapy. An epidemiological comparison between populations who have long maintained a high vitamin-status and those whose vitamin-status has been variable may be more informative than therapeutic trials of the effect of vitamins on these lesions.


Surgical treatment of obesity: current status. Although the treatment of massive obesity by intestinal bypass can clearly effect substantial weight loss, data are not yet available to compare the morbidity and mortality of the operation with those of marked obesity per se. Surgical mortality rates range from 2 to 10 percent. The majority of patients obtain beneficial, satisfactory results. Close observation is required for management of problems, which may include liver failure, urinary calculi, enteritis, arthralgias, malnutrition and electrolyte depletion.


Exercise rehabilitation after myocardial infarction. Exercise is beneficial to most patients with coronary heart disease. Ideally, training should be monitored but, when this is not possible, training pulse rates should be kept below 70 to 85 percent of the maximum heart rate and the patient should understand the concepts and complications of exercise training.


Dysfunctional uterine bleeding.

Dysfunctional uterine bleeding. Most dysfunctional uterine bleeding is caused by anovulatory cycles. The first step in management is exclusion of local pathology of the reproductive tract, complications of pregnancy or systemic disorders. In the postmenarchal age group, dysfunction of the cyclic center in the hypothalamus is usually present. In the perimenopausal age group, progressive loss of ovarian function leads to anovulation. The age of the patient and the amount of bleeding must be considered when selecting the mode of therapy.


Postexposure antirabies therapy.

Postexposure antirabies therapy. The physician must determine the need for systemic postexposure antirabies therapy by a series of specific questions: Was there really a bite? If domesticated, was the animal adequately vaccinated? Was the animal behaving normally or was the bite unprovoked? Almost all wild animal bites should be considered probably or definitely due to rabies. If systemic antirabies therapy is needed, only the combination of human rabies immune globulin and duck-embryo rabies vaccine should be used, not vaccine alone.


Adolescent psychiatric emergencies.

Adolescent psychiatric emergencies. The adolescent in a psychiatric crisis is best seen alone first, to preclude observer bias. Emotionally charged areas of discussion must not be avoided. Suicidal and homicidal threats or attempts are challenging emergencies. Working with parents is essential for effective management. Is the fire-setter retarded or psychotic? Family therapy is often the treatment of choice in sexual "emergencies." Bizarre behavior should suggest drugs, severe anxiety or psychosis. School phobia is a particularly complex problem.


Complications of vasectomies.

Complications of vasectomies. Impotence is a rare psychologic complication. While scrotal ecchymoses and swelling are common, pain is not. Wound infections are not uncommon but abscesses are. Vasitis, epididymitis or orchitis is unusual. Sperm granuloma can initiate recanalization. The implications of sperm agglutinating antibody formation are not yet clear. Pregnancy is a "complication." The patient should be considered relatively fertile for at least four months postoperatively.


Self-concept and the control of diabetes. Patients who have difficulty in the control of diabetes often have negative self-concepts, feel hopeless and, therefore, become lax about following their regimen. Diabetes, like any chronic disease, does not affect the patient alone. By treating diabetes as a disease involving the whole family, the family physician can help the patient shape a positive self-concept and build a base for good clinical control.


The hemodynamic response to intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction. Sixteen patients with cardiogenic shock complicating acute myocardial infarction underwent serial hemodynamic studies during intra-aortic balloon counterpulsation (IABC) at an assist frequency of 1:1. Significant increase was noted during the first 12 hours of IABC in the systemic artery peak diastolic pressure (assisted), cardiac index, stroke index, and stroke work index. During the second 12 hours further significant improvement was noted in the latter three parameters and, in addition, the systemic artery systolic pressure increased significantly. The pulmonary wedge pressure fell as did the total systemic resistance (TSR) during the first 24 hours of IABC. Patients found to be balloon independent after reduction in balloon assist frequency demonstrated significantly greater increase in systemic artery peak diastolic pressure during the first 12 hours of IABC than did those patients found to be balloon dependent. Likewise, the improvement noted in CI, SI, and SWI during the second 12 hours of IABC was of greater magnitude in balloon-independent than in balloon-dependent patients. The data suggest late hemodynamic deterioration after 48 hours of IABC. It is concluded that IABC is effective in improving the deranged hemodynamics of cardiogenic shock. Maximum response is noted between 24 and 48 hours. It is suggested that patients who are balloon independent may be distinguished from those who are balloon dependent by the hemodynamic response within the first 24 hours of IABC.


The fourth heart sound in patients without demonstrable heart disease. One hundred patients, 17 to 67 years of age, had normal hearts diagnosed on the basis of complete right and left heart catheterization and coronary cineangiography. Phonocardiograms were obtained from each patient, providing an average of 17 recordings per subject for analysis; 75/100 (75%) subjects had a recordable fourth sound; 60/75 (80%) of the latter group had an audible fourth heart sound. It is concluded that recordable and audible fourth heart sounds are common findings in subjects without catheterization evidence of cardiovascular disease.


Early changes in contractility and coronary blood flow in the normal areas of the ischemic porcine heart. The regional responses of normal myocardium distant from an ischemic area were studied during acute anterior descending occlusion in the open-chest chloralose-anesthetized pig. Three markers of regional response in both normal and ischemic areas were used: surface ECG electrode, a force gauge in series with left ventricular outer wall fibers, and coronary blood inflow to each region as determined by electromagnetic cuff-probes. Following brief anterior descending artery occlusion (120 sec)., a characteristic rapid decline in contractile force and evolution of TQ-ST segment changes was observed in the ischemic area. In contrast, in the distant area increases in contractil force (p less than 0.001) and coronary blood flow (p less than 0.002) occurred. These distant responses were essentially obliterated following transection and cannulation of the artery supplying this region (p less than 0.05). The findings are consistent with a reflex neurovascular mechanism operating within the intact heart. This reflex is rapidly activated in order to maintain adequate levels of cardiac performance despite sudden loss of functional myocardial mass.


The effect of coronary artery reperfusion on the extent of myocardial infarction. The effect of the reperfusion on myocardial infarction has been studied in the rat in order to assess the possible reversibility of myocardial damage. The present study deals with reperfusion of experimental myocardial infarction in the rat. Two groups of animals were compared: one was subjected to permanent ischemia and the other was subjected to ischemia of variable duration 1) hour to 24 hours). The differences between infarction caused by permanent ischemia and the evolution of infarction following reperfusion were studied by means of histologic (121 specimens) histoenzymatic (56 specimens), ECG (100 specimens), techniques and study of the mcirocirculation (70 specimens). The size of the infarctions caused by temporary ischemia was found to be significantly smaller in 60% of the cases as compared to the infarctions caused by permanent ischemia. Histoenzymatic study (phosphorylase activity and succinodehydrogenase activity) confirmed the existance of a marginal zone extending over one third of the surface of the ischemic myocardium: reperfusion permitted the salvage of this zone and thereby diminished the extent of necrosis. The latter findings were further confirmed by the ECG study showing earlier regression of ischemic ST changes following early reperfusion. Microcirculatory changes secondary to anoxia may account for the fact that, in a certain percentage of the cases, early reperfusion does not prevent extension of infarction.


Coxsackie virus heart disease and cardiomyopathy. Twenty-two cases of Coxsackie virus heart disease diagnosed from November, 1969, to December, 1971, were re-examined after a period of 42 to 68 months from the acute illness. The patients with hypertension, diabetes, chronic alcohol intake, or aged over 35 were eliminated from the trial. With the purpose of assessing myocardial function, the systolic time intervals were recorded by a noninvasive standard technique. The differences in systolic time intervals between the group of patients with previous viral myocarditis and a group of normal control subjects were not statistically significant. However, the pre-ejection period was clearly prolonged in three patients out of 10, a modification consistent with a depressed myocardial function, as in patients with cardiomyopathy.


Propranolol for patients with mitral valve prolapse. This study evaluates propranolol's effect on symptoms, arrhythmias, and exercise tolerance in 16 patients with mitral valve prolapse. Three patients (19 per cent) experienced symptomatic deterioration with propranolol therapy, seven (44 per cent) were unchanged, and six (37 per cent) noted an over-all symptomatic improvement, primarily due to a reduction in palpitation. Symptomatic improvement continues in these six patients an average of 12.5 months after beginning propranolol therapy. Treatment with propranolol alleviated chest pain in only two of eight patients and it did not improve the ability to perform treadmill exercise. Fatigue did not improve, and in three patients appeared for the first time during propranolol therapy. Premature ventricular contractions were reduced by at least 75 per cent in five of nin patients (56 per cent), and paroxysmal ventricular tachycardia was eliminated in three of four patients. We conclude that propranolol is not uniformly effective in patients with mitral vale prolapse. A trial of propranolol may be instituted fro patients with mitral valve prolapse who have severe symptoms and/or arrhythmias, but the drug should only be continued in those who demonstrate clinical and/or antiarrhythmic response.


Echocardiographic manifestation of annuloaortic ectasia: its "paradoxical" motion of the aorta and premature systolic closure of the aortic vale. The echocardiographic features of annuloaortic ectasia were studied in 12 patients. Eleven of them exhibited skeletal and/or ophthalmic findings of Marfan's syndrome and one was considered as having forme fruste. Echocardiograms revealed not only marked dilatation of the aortic root but also unique motion of the aortic wall and aortic valve. Posterior motion of the posterior aortic wall during early to middle ejection period, i.e., "paradoxical" motion, was noted in eight cases, and premature systolic partial closure of the aortic valve was seen in all cases.


Studies on digitalis. XIII. A prospective study of 649 patients on maintenance treatment with digitoxin. In a prospective study of digitalis intoxication in 649 patients on maintenance treatment with digitoxin a low incidence of digitalis toxicity was found, namely, 5.8 per cent. This is mainly due to a more careful use to digitalis glycosides. It is especially important to reduce the dose of digitoxin in the liver and partly excreted metabolized in the liver and partly excreted through the kidneys as metabolities. Serum half-time of digitoxin is shortened in patients with impaired renal function. Patients with reduced renal function may be treated with digitoxin in the same doses as individuals with normal renal function. This is in contrast to patients treated with digoxin. Digitoxin should therefore be the cardiac glycoside of choice in treatment of patients with renal failure. Digitoxin is further rapidly eliminated in patients with reduced liver function in spite of its extensive hepatic metabolism. In this study extracardia symptoms were found equally often as cardiac signs of toxicity. Patients intoxicated usually had several symptoms and signs of toxicity at the same time. The specificity of commonly used symptoms and signs a digitalis intoxication is very low. In this study atrial tachycardia with block, which has been considered to be an important cardiotoxic arrhythmia, very seldom was found in digitalis intoxication. There is an overlap in digitalis serum concentration between toxic and nontoxic patients. The diagnosis of toxicity was made on clinical grounds. Most of the intoxicated patients had high serum concentrations, but some had concentrations in the normal or low range. Apart from being a guide to the diagnosis of digitalis intoxication, serum digitalis levels may further be a guide to underdigitalization of cardiac patients, especially patients in sinus rhythm.


The use of the systolic time interval for predicting left ventricular ejection fraction ischemic heart disease. A large series of 306 patients with ischemic heart disease was studied with automated systolic time intervals and left ventricular ejection fraction as determined by the angiocardiographic method. It was found the pre-ejection period, left ventricular ejection time, delta values, and PEP/LVET ratio all were related to the ejection fraction. However, in all instances the correlation was too low and the scatter of the data was too large to warrant the use of the systolic time intervals for predicting left ventricular function as indicated by the ejection fraction.


Effectiveness of direct current defibrillation: role of paddle electrode size. Myocardial necrosis from repeated direct current defibrillation discharges is less when the same stored energy is delivered by paddle electrodes that are larger than those presently available on the majority of commercial defibrillators. The present study was undertaken to determine if the larger 12.8 cm. diameter paddle electrodes are as effective as the standard 8.0 cm. diameter paddle electrodes in defibrillation. Ventricular fibrillation (VF) was induced in 45 dogs and each was allowed to remain in ventricular fibrillation for progressively longer time intervals before defibrillation was attempted. With the 12.8 cm. diameter paddle electrodes, the longest duration of VF sucessfully terminated was 1.22+/-1.05 minutes when the 8.0 cm. paddle electrodes were used (p less than  0.02). Ventricular fibrillation was terminated during the first minute with the 12.8 cm. diameter electrode in 88 per cent of trials as compared with a 71 per cent success rate with 8.0 cm. diameter paddle electrodes (p less than 0.04). When the success rates during the first minute of VF for both sizes of paddle electrodes were ploted against the measure transthoracic impedance, a high correlation cofficient (r=-0.94) was found. This study suggest that 12.8 cm. diameter paddle electrodes are more effective for defibrillation of subjects in the 13.5 kilogram (29 to 69 pound) weight range than are paddle electrodes that are only 8.0 cm. in diameter.


The relationship between coronary artery lesions and myocardial infarcts: ulceration of atherosclerotic plaques precipitating coronary thrombosis. A review of 494 myocardial lesions at least 3 cm. in one dimension reveal 418 (85 per cent) related to atherosclerotic coronary lesions, 55 (11 per cent) related to coronary emboli of various types, 18(3.5 per cent) without specific coronary lesions but related to clinical events associated with coronary hypoperfusion, and 3 (0.5 per cent) associated with miscellaneous coronary lesions. In 399 of 418 (96 per cent) atherosclerotic coronary lesions of all ages complete occlusion (remote of fresh) or histological evidence of lumenal recanalization was present. These coronary lesions were situated within extramural coronary artery segments one to several centimeters proximal to the myocardial lesions which were confined to the distribution of the respective partially or totally occluded coronary segments. In the atherosclerotic cornary lesions less than 2 weeks of age partially or totally occlusive thrombus was found in 67 of 69 (97 per cent) cases and a underlying plaque ulceration, erosion, or rupture was present in 64 of 69 (93 per cent) instances. These endothelial and intimal injuries were generally focal in nature, often extending over a length of only 100 to 200 mu. In no instance could it be stated with certainty that the oldest portion of the atherosclerotic ulceration-thrombus complex was younger in age than its associated myocardial lesion. On the contrary, in 10 of 69 (14 per cent) of the cases portion of the coronary thrombus, usually at the site of plaque ulceration, were histologically older than the myocardial lesion. In addition, the presence of thrombus and plaque debris admixtures further suggested the antecedent nature of the coronary lesion in relation to the myocardial lesion. Atherosclerotic coronary lesions associated with myocardial lesions of 2 to 8 weeks of age had identifiable thromboses in all instances and underlying plaque ulceration, erosions, or ruptures in 17 of 21 (80 per cent). Endothelial injuries were more difficult to assess due to the obscuring features of organizing lumenal thrombus. Interface i.e., plaque ulceration, erosions, or ruptures, were reliably detectable up to approximately on month of age. Coronary arter thromboemboli accounted for a significant percentage of myocardial lesions, were usually associated with normal or minimal coronary artery disease, and frequently involved smaller intramural coronary vessels of the heart. Organization and recanalization of thromboemboemboli tended to be rapid and complete so that in the late stages the residual intimal plaque was sometimes difficult to identify. Myocardial lesions related to clinical events associated with coronary artery hypoperfusion centric, and not confined to the distribution of a single coronary artery. They were unassociated with acute coronary lesions and histologically displayed contraction band necrosis more frequently than the embolic and atherosclerotic related lesions. An explanation was found for the overwhelming majority of myocardial lesions...


The effect of ouabain on nutritional circulation and regional myocardial blood flow. The effect of ouabain on myocardial nutritional circulation (rubidium-86 extraction) and regional myocardial blood flow (radioactive microspheres) was studied in the isolated supported canine heart preparation perfused at a constant coronary blood flow. Ouanbain (25 mug per kilogram, intravenously) produced a significant increase in mycocardial contractile force, peak left ventricular systolic pressure, and myocardial oxygen consumption. Ouabain also decreased rubidium-86 extraction (E86RB), rubidium-86 clearance (C86Rb), and the capillary transport coefficient (PS). Intracoronary infusion of ouabain (10 mug per minute) produced significant increases in contractile force (25,50, and 100 per cent above control), left ventricular systolic pressure, myocardial oxgen consumption, and the epicardial-endocardial blood flow ratio (epi/endo) of the left ventricle. When left ventricular systolic pressure was held constant (100 mm. Hg), ouabain infusion (10 mug per minute, intracoronary) increased myocardial contractile force (25,50, and 100 per cent above control) and myocardial oxygen consumption but did not change the epi/endo of the left ventricle. These results suggest that ouabain reduces E86Rb, C86Rb, and PS by producing a shunting of blood flow from endocardium to epicardium in the left ventricle. The increase in left ventricular systolic pressure appears to be responsible for these changes.


The arrhythmogenic effect of static electricity on the dog heart. Seven dogs, three with surgically-induced acute myocardial infarction, were subjected to the effects of static electricity discharged from our fingertips onto the external end of a transvenous right ventricular pacemaker. Initiation of ventricular beats occurred regularly when shocks were perceptible to the generating person and, not infrequently, when energy levels were below perception. In one dog with myocardial infarction, ventricular fibrillation was clearly related to the static discharge. The data obtained in this study support the recommendations of the Electrical Safety Hazard committee that critical care areas not be carpeted in order to minimize static discharges. In addition to low static floor covering in these areas, one can reduce static charge by the use of foot coverings such as those worn in the operating room. We found that no static charge could be developed when wearing the expandable operating room "booties." Since static charges were transmitted through our fingertips, probably the best means of protecting the electrically sensitive patient against the hazard of static electricity is to instruct personnel to wear rubber gloves whenever direct contact with the external ends of a pacing catheter becomes necessary. Routinely, such exteriorized pacemaker ends should also be covered with a nonconductive substance.


Horses lung: Report of two cases.

Horses lung: Report of two cases. Two cases of horseshoe lung are described; one was suspected and the other was diagnosed preoperatively. Both underwent successful surgical treatment. The embryology of this anomaly is briefly reviewed with reference to the closely related scimitar syndrome (anomalous venous return of right lung to inferior atriocaval junction). Diagnostic studies are discussed with stress on the need for a thorough functional evaluation of both the heart and lungs before the surgical indication is made.


Myocardial imaging with intravenously injected thallium-201 in patients with suspected coronary artery disease: analysis of technique and correlation with electrocardiographic, coronary anatomic and ventriculographic findings. Myocardial imaging was performed after intravenous injection of thallium-201 at rest in 50 patients with suspected coronary artery disease and the results were compared with electrocardiographic, ventriculographic and coronary arteriographic findings. The thallium-201 myocardial images were of good quality and compared favorably with images previously obtained with intracoronary particle injection. Myocardial to background ratios averaged 2:1, a considerable improvement over ratios reported with potassium-43. There was complete intra- and interobserver agreement in the interpretation of images in 90 and 82 percent of cases, respectively. Major disagreement occurred in less than 5 percent of cases. Overall, 15 (30 percent) had an abnormal, 10 patients (20 percent) a borderline abnormal and 25 patients (50 percent) a normal myocardial image. Of patients with electrocardiographic Q waves, 91 percent had an image defect. Of 39 patients without Q waves, 13 percent had an image defect. All 30 patients with a normal or borderline abnormal thallium-201 image had a normal ventricular contraction pattern. All patients with a segmental ventriculographic abnormality had an image defect. In all cases, the area of electrocardiographic or ventriculographic abnormality corresponded to the area of the thallium-201 image defect. The systolic ejection fraction was depressed (0.49 +/- 0.18 [mean +/- standard deviation]) in patients with an image defect compared with that in patients with a normal image (0.64 +/- 0.06, P less than 0.005). Coronary arterial lesions were present and usually of high grade in all patients with an abnormal image; however, the presence of high grade coronary stenosis or occlusion as such correlated with image defects only to the extent that prior myocardial infraction was associated. Thus, satisfactory myocardial images at rest appear to be obtained with intravenously administered thallium-201 and electrocardiographic, ventriculographic and coronary arteriographic data suggest that image defects denote regions of prior myocardial infarction.


Regional myocardial perfusion abnormalities on xenon-133 imaging in patients with angina pectoris and normal coronary arteries. With use of semiselective xenon-133 injections and gamma camera recording, myocardial scintigrams were obtained in a series of 20 patients with angina pectoris, abnormal exercise electrocardiograms and normal coronary arteries. Ten patients (Group I) exhibited localized perfusion defects and the other 10 (Group II) a hjemogenous uptake of the tracer. Group I was characterized by more past myocardial infarctions and, most significantly, by male preponderance (P less than 0.001). Computer analysis of regional xenon-133 washout curves revealed that every patient in Group I had a reduced flow rate in the area of the perfusion defect (P less than 0.001). A comparison of this group with 26 patients with similarly abnormal scintigrams but coronary arterial obstruction revealed that myocardial perfusion was 16 to 18 percent greater in the group with normal coronary arteries. In three patients of this group, myocardial perfusion rates were not augmented by atrial pacing in contrast to the response in patients with coronary arterial obstruction. The data demonstrated localized perfusion abnormalities in half of the patients with angina pectoris and normal coronary arteries and constitute evidence that a metabolic disorder is not the sole mechanism for ischemia in this syndrome.


Technetium-99m stannous pyrophosphate scintigrams in normal subjects, patients with exercise-induced ischemia and patients with a calcified valve. Although technetium-99m stannous (99mTc[Sn]) pyrophosphate has been shown to be a specific and sensitive index of myocardial infarction, abnormal images have been reported in patients with unstable angina or ventricular aneurysm. Sixty-one subjects--33 patients subjected to maximal treadmill stress testing, 23 normal subjects and 5 patients with a calcified aortic or mitral valve--underwent imaging with 99mTc(Sn) pyrophosphate to determine whether abnormal images are associated with (1) exercise-induced ischemia, (2) delayed clearance of tracer from the blood pool, or (3) calcified intracardiac structures. Myocardial injury was excluded on the basis of normal MB creatine kinase (CK) values in all patients with stress testing. All eight patients with an abnormal exercise stress test had normal images. Four of 25 patients with a normal exercise stress test had diffusely abnormal images. In some normal subjects diffusely abnormal images were present 60 minutes after injection of the tracer, but became normal 90 to 120 minutes after injection. Variations in clearance of tracer from the blood pool were noted in this group. Patients with a calcified aortic or mitral valve had normal images. We conclude that (1) exercise-induced ischemia is not associated with abnormal 99mTC(SN) pyrophosphate images; (2) images are not necessarily abnormal in patients with a calcified valve; and (3) delayed removal of tracer from the cardiac blood pool may result in diffusely abnormal images even in normal subjects; in these cases, repeat images should be obtained at least 2 hours after injection of the tracer to avoid false abnormal images.


Myocardial stress perfusion scintigraphy with rubidium-81 versus stress electrocardiography. Fifty-six patients who subsequently underwent selective coronary angiography were studied noninvasively with relative myocardial perfusion scintigraphy with rubidium-81 and graded stress electrocardiography in an attempt to evaluate the ability of these tests to identify the presence of significant ischemia and, indirectly, coronary stenosis. Both the sensitivity (0.91) and specificity (0.91) of perfusion scintigraphy were impressive and better than the sensitivity (0.79) and specificity (0.64) of stress electrocardiography, the specificity of scintigraphy significantly so (P less than 0.05). Additionally, perfusion scintigraphy yielded excellent localizing information and was reliable even in the presence of drug effect, conduction abnormalities and nonspecific electrocardiographic abnormalities. Rare cases of triple vessel disease, prior myocardial infarction or single vessel disease with widespread collateral vessels were causes of scintigraphic misdiagnosis. Although ribidium-81 perfusion scintigraphy with the scintillation camera requires special collimation and significant quality control, it provides well resolved images and may prove particularly useful in facilitating quick successive multiple scintigraphic cardiac studies.


Noninvasive detection of subcritical coronary arterial narrowings with a coronary vasodilator and myocardial perfusion imaging. Myocardial perfusion imaging after administration of the potent coronary vasodilator ethyl adenosine-5'-carboxylate, which increases flow to normal areas in excess of that to areas supplied by subcritically stenosed vessels, was investigated as a nonischemia-producing stimulus for detecting subcritical coronary stenosis. Preliminary studies in 10 dogs with reactive hyperemia were performed with thallium-201 and potassium-43 to determine which tracer was a better indicator of increased flow. Neither agent was a linear indicator of increased flow caused by reactive hyperemia but thallium-201, because of its imaging characteristics, was selected as a flow indicator after administration of ethyl adenosine. Five dogs were studied after placement of a subcritical stenosis on the left circumflex coronary artery. Strontium-85 microspheres were injected into the left atrium after placement of the stenosis to verify that changes in resting blood flow were only minimal. Thereafter, intravenous administration of ethyl adenosine was followed by injection of chromium-51-labeled microspheres into the left atrium and intravenous administration of thallium-201. The mean ratio of left circumflex to left anterior descending coronary arterial flow was 0.96 +/- 0.16 for the control experiment after subcritical stenosis; after administration of the vasodilator the ratio of activity levels in the two arteries was 0.43 +/- 0.09 with the chromium-51 microspheres and 0.56 +/- 0.07 with thallium-201. Imaging performed in three additional dogs after injection of microspheres in the presence of subcritical stenosis revealed a normal pattern, whereas imaging after administration of the vasodilator and thallium-201 revealed a perfusion deficit. In two additional dogs without subcritical stenosis, thallium was administered after injection of ethyl adenosine to determine that the drug alone did not cause perfusion deficits. The perfusion scans in these two dogs were normal. These studies suggest that a coronary vasodilator and thallium-201 myocardial imaging can be used to detect subcritical coronary stenosis.


Dispersion of effective refractory period during abrupt reperfusion of ischemic myocardium in dogs. Dispersion of the effective refractory period was measured in anesthetized dogs using a computerized system and bipolar epicardial electrodes or, alternatively, transmural plunge electrodes. Measurements were made at 1 minute intervals during short (5 minute) and long (15 minute) periods of coronary arterial ligation and for 3 to 5 minutes after release of the ligatures. Both transepicardial and transmural temporal dispersion of refractoriness correlated well with the increased vulnerability to spontaneous ventricular fibrillation during short periods of ligation and the relative electrical stability observed toward the end of the longer periods of ligation. During reperfusion, transmural dispersion increased somewhat after ligature release in the longer-term experiments but the increase did not appear adequate to explain the associated large incidence of spontaneous arrhythmias after release. Effective refractory periods measured at one nonischemic and five ischemic electrode sites at intervals as short as 20 seconds revealed abrupt shortening of the refractory period at all ischemic sites during the 1st minute of reperfusion, resulting in a large but short-lived electrical gradient between the ischemic and nonischemic myocardium. This increased dispersion between the ischemic and nonischemic myocardium occurred at a time of maximal vulnerability to reperfusion arrhythmias. However, this increased dispersion was greater after the 5 minute than after the 15 minute periods of ligation and thus does not fully explain the greater incidence of reperfusion arrhythmias after ligature release in the longer-term studies. Although arrhythmias of acute ischemia are associated with increased dispersion of refractoriness within theischemic segment and reperfusion arrhythmias with dispersion between ischemic and nonischemic segments, other electrophysiologic alterations probably play an important role in the genesis of the arrhythmias of reperfusion.


Contrasting effects of dopamine and isoproterenol in experimental myocardial infarction. The comparative effects of dopamine and isoproterenol on local myocardial contraction and ischemic injury after coronary occlusion were evaluated in 10 dogs. Dopamine (2.5 to 5 mug/kg per min) and isoproterenol (0.125 to 0.25 mug/kg per min) were randomly infused for 20 minutes, and segmental tension (Walton-Brodie gauge) of central ischemic, border and nonischemic myocardial zones and epicardial electrograms (10 to 12 sites) were simultaneously recorded. After coronary occlusion, tension in border zones decreased to 73.5 +/- 6.4 percent (mean +/- standard error of the mean) and tension in central zones to 60.6 +/- 9.9 percent (P less than  0.001) of control level, whereas total S-T elevation (sigmaST) rose from 10.8 +/- 1.6 to 98.4 +/- 14.0 mv and average S-T elevation (ST) from 1.6 +/- 0.2 to 10.8 +/- 1.6 mv (P less than 0.001). Isoproterenol increased heart rate from 148.7 +/- 6.9 to 170.6 +/- 7.7 beats/min (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.005) and nonischemic zone to 128.4 +/- 6.7 percent (P less than 0.02). Tension in the central zone was unchanged. However, sigmaST increased from 98.4 +/- 14.0 to 126.9 +/- 14.7 mv (P less than 0.005) and ST from 10.8 +/- 1.6 to 14.2 +/- 1.6 mv (P less than 0.001). Dopamine did not change heart rate but increased tension in the border zone from 72.4 +/- 7.9 to 124.4 +/- 16.8 percent (P less than 0.001) and tension in the nonischemic zone from 86.0 +/- 10.0 to 133.3 +/- 10.0 percent (P less than 0.01). Tension in the central zone was unimproved. However, sigmaST and ST did not increase (sigmaST from 99.8 +/- 10.8 to 97.7 +/- 13.9 mv and ST from 11.1 +/- 1.3 to 10.8 +/- 1.5 mv). Atrial pacing was used to increase heart rate during infusion of dopamine to 180.0 +/- 7.6 beats/min but neither sigmaST nor ST increased. In summary, both dopamine and isoproterenol decrease contraction abnormalities in the border and nonischemic zones after after acute coronary occlusion. Although isoproterenol increases both heart rate and S-T segment elevation, dopamine does not adversely affect either variable.


Effects of orthostatic postural changes on myocardial oxygen demands. The effects of orthostatic tilting were studied in 12 mongrel dogs anesthetized with sodium pentobarbital. Orthostasis produced significant decreases in cardiac output and left ventricular dimensions. Secondary decreases in coronary flow and myocardial oxygen consumption were also documented. These changes were attenuated when the animals were pretreated with propranolol. The upright posture may be of value in treatment of angina pectoris.


Bronchopulmonary circulation in d-transposition of the great arteries: possible role in genesis of accelerated pulmonary vascular disease. Hemodynamic and angiograhic data from 209 patients with d-transposition of the great arteries were reviewed to estimate the incidence of prominent bronchopulmonary circulation and to explore its role in the genesis of accelerated pulmonary vascular disease in these patients. The degree of bronchopulmonary circulation was assessed visually by considering the extent of the pulmonary arterial opacification and the circulation to the left atrium. An initial survey study revealed a marked degree of collateral circulation in 20 of 138 patients with d-transposition having cardiac catheterization before age 2 years at the Hospital for Sick Children, Toronto, between 1967 and 1972. Detailed analysis of 71 additional patients with d-transposition aged 1 week to 72 months (mean 17 months) studied at Children's Memorial Hospital, Chicago, between 1967 and 1974 showed collateral circulation of marked degree in 23 and of mild degree in 14. The bronchopulmonary collateral vessels were more freqently demonstrated in the patients with intact ventricular septum than in those with ventricular septal defect or left ventricular outflow tract stenosis. In a prospective study in 12 of 15 patients during cardiac catheterization the functional patency of the bronchopulmonary collateral circulation was demonstrated by obstructing pulmonary blood flow in the right or left pulmonary artery, or both, with an inflated balloon and obtaining from the pulmonary arterial segment distal to the occlusion blood with an oxygen saturation similar to that of the aorta. A hypothesis is presented concerning the role of systemic hypoxemia and local pulmonary hypoxemia induced by way of the bronchopulmonary collateral vessels and the bronchial arterial vasovasorum in promoting pulmonary vasoconstriction. It is suggested that increased pulmonary blood flow and pressure due to the physiologic features of ventricular septal defect, patent ductus arteriosus or transposition of the great vessels, in the face of this regionally increased hypoxemia results in accelerated pulmonary vascular disease.


Isolated partial anomalous pulmonary venous drainage associated with pulmonary vascular obstructive disease. Five patients with partial anomalous pulmonary venous drainage with intact atrial septum are described. In two patients, pulmonary arterial hypertension and pulmonary vascular disease developed. Both had one or more right pulmonary veins draining anomalously to the right superior vena cava. It is postulated that a combination of increased pulmonary blood flow and reflex pulmonary vascular changes contributes to the production of pulmonary vascular obstructive disease.


Afterload reduction and cardiac ouptut in infants early after intracardiac surgery. Sixteen infants less than 18 months old were studied within 3 hours of intracardiac surgery. Initial mean arterial pressure and systemic vascular resistance levels were higher than normal in each infant (99 +/- 17.2 mm Hg and 48 +/- 18.1 units'm2', respectively [mean +/- standard deviation]); cardiac index was low (1.9 +/- 0.48 liters'min-1-2) and mean left and right atrial pressures were 11.4 +/- 2.39 and 12.5 +/- 3.10 mm Hg, respectively. Mean pulmonary arterial pressure was 29 mm Hg; pulmonary vascular resistance was 8.6 units'm2'. When nitroprusside was infused to reduce mean arterial pressure to about normal, cardiac index increased 17 percent and mean left and right atrial pressures decreased 25 and 22 percent, respectively. Mean pulmonary arterial pressure decreased 31 percent. When atrial pressures returned to initial values after infusion of blood with continued infusion of nitroprusside, cardiac index increased another 24 percent. When administration of nitroprusside was discontinued, cardiac index decreased to 116 percent of the initial value and mean atrial pressure increased to 90 percent of the initial value. The study demonstrated the favorable effect on cardiac output of vasodilator therapy in combination with blood volume expansion in hypertensive infants early after intracardiac surgery. An empirical equation interrelating atrial and arterial pressures and cardiac index was derived from the data.


Relation of body weight to development of ischemic heart disease in a cohort of young North American men after a 26 year observation period: the Manitoba Study. The role of overweight as a risk factor for ischemic heart disease remains controversial. Therefore, in the Manitoba Study of a cohort of 3,983 men with a mean age at entry of 30.8 years, initial measurements of body weight, represented by body mass index (weight/height2), were compared with the 26 year incidence of ischemic heart disease. After adjustment for the effects of age and blood pressure in univariate and multivariate analysis, body mass index was a significant predictor of the 390 cases of ischemic heart disease. To elucidate this relation further, the cohort was further analyzed after categorization by age at entry, time of occurrence of disease after entry and manifestation of ischemic heart disease. The association with weight was most apparent in men less than 40 years of age and was not evident until 16 years of follow-up. A high body mass index was significantly associated with development of myocardial infarction, sudden death and coronary insufficiency or suspected myocardial infarction; the relation was strongest with sudden death. Among men who had a myocardial infarction, body mass index was more strongly associated with sudden death and was the best predictor of myocardial infarction occurring after 20 years of observation. Thus, after adjustment for the effect of age and blood pressure, overweight is a definite risk factor but primarily in younger men, after long periods of observation and for certain manifestations of ischemic heart disease.


Effect of intermittent left bundle branch block on left ventricular performance in the normal heart. The effect of left bundle branch block on left ventricular performance was studied in a patient with rate-dependent left bundle branch block and an otherwise normal heart. The timing of left heart events, hemodynamic pressures and indexes of left ventricular contractility were determined during normal intraventricular conduction and during left bundle branch block. The results indicate that in the normal heart left bundle branch block has no significant effect on left ventricular performance.


Development of the octopus cell area in the cat ventral cochlear nucleus. The octopus cell area (OCA) of the posteroventral cochlear nucleus was studied electron microscopically in kittens. The adult OCA, a region of morphologically homogeneous neurons receiving heterotypic synapses from the cochlea, was used to define the mature state. The OCA reaches cytological maturity at three weeks postnatally, after progression through four stages, defined on the basis of octopus cell cytology (including relative numbers of somatic and dendritic filopodia and spines) and the frequency, ultrastructure and location of previously defined synaptic terminals. Octopus cell size was also studied in rapid Golgi impregnations. The OCA from birth through three postnatal days (stage 1) showed small neurons, few identifiable synaptic types, small, mostly unmyelinated axons, mitotic cells and undifferentiated glia. Between the fourth and seventh postnatal days (stage 2) distinct type 1 and type 2 endings appeared and dendrites thickened, expanded peripherally and developed mature spines. During stage 3 (8-19 days) loss of filopodia, increased somatic spicules, larger somas and clearer differentiation of type 1 and type 2 synapses occurred. After three postnatal weeks (stage 4) the OCA contained morphologically mature octopus cell somas, all three synaptic types ending upon somas and thick basal dendrites, and fascicles of myelinated fibers. Although cytologically mature, the OCA at this stage (about 20-35 days) is substantially smaller than the adult OCA. This smaller size will facilitate further study of OCA synaptic organization.


Nigro-amygdaloid fiber connections in the cat. Relatively discrete unilateral lesions were made in the lateral portion of the substantia nigra of eight cats and in the medial substantia nigra of two. After a 10-day survival period the animals were killed, brains were stored in buffered 10% formalin, and frozen sections were stained for degenerating axons and terminals, or by Weil and cresyl violet methods. Electordes passed through the midial suprasylvian gyrus, pulvinar and/or posterolateral thalamic nucleus and the medial geniculate body. The stria terminalis and hippocampus were undamaged. Degeneration from the lesion followed two paths. One projected through the reticular nucleus into the internal capsule and then ventrolaterally below the putamen to enter the lateral and central amygdaloid nuclei, with degenerated terminals. The second path ran dorsolaterally in the internal capsule to enter the external capsule where some of the fibers spread into the lateral amygdaloid nucleus. It appears that some of the terminals in the lateral amygdaloid nucleus are from the external capsule. Perhaps these connections link the extrapyramidal system to the amygdaloid body.


Organization of desmosomes in Bowman's gland duct cells in a marsupial. Non-secretory cells lining the ducts of Bowman's gland in the olfactory epithelium of the bandicoot (Isoodon macrourus) are united below the duct lumen by an unusually well-organized series of desmosomes linked by conspicuous fibrillar bundles with long mitochondria aligned close to the bundles. It is suggested that these junctional specializations may help to maintain an intact duct lumen in a part of the epithelium with considerable intercellular space.


The effect of HCG on pinocytosis iwthin the canine inter-sertoli cell tight junction. A preliminary report. The role of tight junctions in permeability barriers is now well established. Other roles for this junction have been postulated but have not been demonstrated. In both adult and prepubertal dogs, stimulation with human chorionic gonadotropin (hCG) results in an  increased number of pinocytotic vesicles on the membrane faces enclosed by tight junctions within the inter-Sertoli cell junctions of the testis. It is suggested that these membranous regions, protected from the normal flow of intercellular fluids, may act as regions of selective intercellular exchange.


Stability of the intra-epithelial component of the blood-testis barrier in epinephrine-induced testicular degeneration in Syrian hamsters. Adult male Syrian hamsters were given daily intraperitoneal injections of epinephrine (1.0 mg/kg) and papaverine, a vasodilator, (60 mg/kg) for a period of ten days. After the treatment period, lanthanum and horseradish peroxidase tracer studies were used to examine the intra-epithelial component of the blood-testis barrier. Degenerating tubules often exhibited only Sertoli cells and spermatogonia, or Sertoli cells alone. Sertoli cell processes in the degenerating tubules often arched out from the main cell body to make contact with other Sertoli cell processes, forming a series of vacuole-like spaces in the germinal epithelium, adluminal to the Sertoli-Sertoli junctions. At the site of contact between these arching Sertoli cell processes one to eight tight junctions had formed with hexagonal arrays of Sertoli cell cytoplasmic filaments located immediately adjacent to these junctions. Cisternae of the Sertoli cell endoplasmic reticulum lay deep to the layer of cytoplasmic filaments. It appeared that these junctions had originated after the expulsion of the germinal elements of the seminiferous epithelium. Penetration of the tracers in the degenerating seminiferous tubules was prevented by what appeared to be normal Sertoli-Sertoli junctions located between apposed Sertoli cells, adluminal to the remaining spermatogonia when these resisted degeneration, or just adluminal to the basal lamina in those tubules in which spermatogonia were absent.


Sertoli-sertoli junctions and Sertoli-spermatid junctions after efferent ductule ligation and lanthanum treatment. Seminiferous tubules, partially dilated by ligation of the efferent ductules, were examined after treatment with lanthanum. Lanthanum penetrated the intercellular spaces of the seminiferous epithelium, but only to the level of the Sertoli-Sertoli junctions. Further penetration from the interstitial surface of the tubule was restricted by membrane fusions (tight junctions) at the junctional complex. Lanthanum also penetrated the epithelium from the luminal surface permeating the adluminal intercellular spaces, including the site of the Sertoli-spermatid junction. The lanthanum occupying the Sertoli-spermatid junctional site appeared as a slightly narrower electron-opaque zone than that found in the non-specialized intercellular areas. The findings clearly reveal that only the Sertoli-Sertoli junctional site forms a restrictive barrier. In contrast to the specializations of plasma membrane which form the tight junction, the associated filaments and cisterna of endoplasmic reticulum may be components more directly related to maintaining and regulating cell adhesion.


Age-related change in the neuronal microenvironment: penetration of ruthenium red into extracellular space of brain in young adult and senescent rats. The volume of the extracellular space, which contributes to the microenvironment of neurons, is diminished in the brains of senescent (as compared to adult) rats and an age-related change in its composition has been hypothesized. To test this hypothesis we have compared the penetration of ruthenium red, a polyanion selectively distributed in the extracellular space, into the dentate gyri of young adult and senescent Fischer 344 rats. Slices of hoppocampal formation were fixed by immersion, first in a glutaraldehyde solution containing ruthenium red, then in a solution of osmium tetroxide containind examined by electron microscopy. Dense particles of ruthenium red reaction product were readily localized in intercellular channels and synaptic clefts and the depth of penetration of ruthenium red in 25-month-old rats, as compared with 3-month-old animals, was found. These data indicate an age-related change in the charge density of the intercellular channels in the dentate gyrus of 25-month-old rats. They suggest a primary age-related change in the charg density of extracellular macromoledules, presumed to be primarily glycosaminoglycans, with a consequent change in water binding capacity and volume of the extracellular space.


Structural development of endocardial cushions. Development of chick and rat endocardial cushions (cardiac mesenchyme) was studied histologically (using Nomarski differential interference optics on living and unfixed tissue), ultrastructurally (scanning and transmission electron microscopy), cytochemically (using acidified dialyzed iron as a visual probe for polyanionic material) and autoradiographically (using 35S) to elucidate the origin of the mesenchyme, the morphologic sequences leading to cushion formation and secretion of sulfated glycosaminoglycans, if any, by migrating mesenchymal cells. Cushion formation was similar for both species. Mesenchymal cells appeared initially, in 16- to 18-somite embryos, beneath the endothelium (which lacked a basal lamina) of the future atrioventricular canal and outflow tract. The cytoplasm of cushion mesenchymal cells was structurally similar to the ensothelium; probably these cells arose by proliferation of the endothelium. Mitotic figures among the "seeded" cells were also numerous. Cushion cells were initially attached to the endothelium by desmosomes but acquired motile apparatus (pseudopodia and filopodia containing microtubules and microfilamentous bundles). Serial sectioning of successively-aged embryos (20-44 somites) indicated a centrifugal migratory direction. Interaction of the cell processes with extracellular matrix suggested that the latter was used as a migratory substrate. Contact of the advancing wedge of cushion cells with the myocardium produced no alteration in cell structure or mitotic activity. Localization of hyaluronidase-sensitive, dialyzed iron (DI) precipitates in 250-nm Golgi vacuoles and hyaluronidase-sensitive 35S-endangendered silver grains over cushion cells indicated that this tissue contributed sulfated macromolecules to the matrix. Localization of hyaluronidase-labile, DI material in coated, endocytic-like vesicles and caveolae also suggested potential modification or conditioning of the matrix by migrating mesenchymal cells. Altogether, the study established loci in developing cushions where disruption where disruption of the developmental sequence could engender valvular or septal defects.