Inhibition of calcium-dependent action potentials in mammalian myocardium by specific inhibitors of the transmembrane calcium conductivity (verapamil, D 600). Cat papillary muscles were depolarized from about -80 mV to -50 mV by addition of KCl to Tyrode's solution. This causes an inactivation of the Na-carrying system so that the remaining transmembrane inward current is due, in practice, to Ca. Such action potentials show a reduced rate of rise, a greater overshoot, and a shorter duration. These parameters vary somewhat with the strength of stimulation and, particularly, with frequency. Excitability as well as contractility of the K-depolarized fibers are completely abolished by Ca withdrawal or by addition of verapamil or D 600, which block the transmembrane Ca inward current specifically. Conversely, extra Ca or epinephrine overcomes the verapamil and C 600 effects by increasing the transmembrane Ca influx. As soon as the papillary muscles are returned to Tyrode's solution with normal K0 the Na-carrying system is reactivated. Then Ca withdrawal or Ca-antagonistic compounds lose their inhibitory influence on excitation, whereas excitation-contraction uncoupling persists.


The role of myocardial membrane leakage channels in the production of fibrillation: studies with an analog computer model. The conditions under which automatic activity and fibrillation can occur were studied through the use of an analog model. Parameters (transmembrane active and passive properties) were established from biological data of mammalian myocardial fibers. The definition of instability of membrane potential can be given by the following functions of inward and outward steady state current (I) to voltage relationships of the membrane. 1) With decreasing angle between the tangent of the slope of the Iout and (-1) Iin, instability increases at constant potential. 2) Instability is also a function of the membrane potential as related to peak inward current (nonsteady state) at a given angle. 3) Maximum peak inward current and minimum angle produced such instability as to cause fibrillation. The most likely explanation is that automaticity and/or fibrillation is induced by leakage currents which change the normal current/voltage relatiosnhip in the described manner. The membrane leakage currents could be specific to sodium or unspecific.


The ionic basis of membrane excitation in ordinary myocardial fibers: some aspects of the sodium and calcium conductance. Ionic currents in heart muscle are usually described in terms of the Hodgkin-Huxley theory for nerve fibers. Attention is paid to some aspects of the sodium and calcium conductance which seem to be specific for heart muscle: 1) recent findings indicate that repriming of the sodium and calcium conductance in heart muscle cannot be described as the reverse process of inactivation; 2) the existence of an important calcium current is well established, but controversial findings have been obtained for the time constant of inactivation; 3) Na and Ca interact in determining the slow channel current. Depending on the external Na and Ca concentration, antagonistic as well as synergistic effects may be obtained. An explanation is offered for these contradictory results.


The mechanism of supraventricular tachycardia induced by a single premature beat in the isolated left atrium of the rabbit. I. Circus movement as a consequence of unidirectional block of the premature impulse. In the isolated left atrium of the rabbit tachycardia could be elicited by a single stimulus shortly after the refractory period. The activation pattern of the preparation was mapped by means of multiple extracellular recordings. It could be demonstrated that a circus movement of the activation in a relatively small part of the atrial myocardium was responsible for the tachycardia. This phenomenon was studied on a cellular level with multiple microelectrode recordings. The impulse of the premature beat, when followed by a tachycardia, was one way only, while in the other directions the conduction failed completely or occurred with such decrement that the impulse died out. These differences in conductivity were connected with spatial differences in the refractory period. Therefore the excitability of the fibers surrounding the stimulating electrod was not restored to the same level at the moment the premature beat was elicited. Spatial dispersion in the refractory period was important for the occurrence of unidirectional block and thus for the initiation of circus movement and tachycardia.


The mechanism of supraventricular tachycardia induced by a single premature beat in the isolated left atrium of the rabbit. II. The termination of the tachycardia. Tachycardias induced by a single stimulus in the left atrium of the rabbit, are based on a circus movement of the impulse through the atrial myocardium. Circus movement often stopped spontaneously after only one beat ("coupled extrasystole") or after a small number of beats. This frequent early cessation of circus movement is explained by the relatively high conduction velocity and relatively long refractory period in the early stage of tachycardia. As an exception tachycardia lasted for a longer period. The circulating impulse then could always be interrupted by the application of a properly timed stimulus. In this case the circulating impulse will encounter the activation wave elicited by the stimulus. This resulted either in termination or resetting of the tachycardia.


Role of sympathetic excitation in generating arrhythmias in early and late phases of ectopic responses after coronary arterial occlusion in dog heart. The three phases of arrhythmias that develop within specific durations of occlusion of a coronary artery of the dog have been reviewed and characterized. The intravenous administration of practolol as described has virtually prevented the occurrence of arrhythmic activity during the first 7-8 hr after occlusion and kept the frequency at a much reduced level as compared with controls through 10 or 11 hr, but not appreciably longer. This means that first and second phase arrhythmias were almost abolished, and development of third phase ventricular tachycardia was significantly retarded, but not prevented. It is concluded that sympathetic stimulation is an important component in the effective excitation of ectopic activity during the first and second phases, but contributed no more than a minor component to the fully developed third phase activity.


Early ventricular fibrillation in the baboon: possible role of epicardial ST segment changes. The changes in epicardial ST segment and the severity of the infarct defined by the onset of primary ventricular fibrillation were monitored in baboons after ligation of the anterior descending coronary artery. Although an increase in the ratio of the total ST segment elevation over the maximal drop of isoelectric baseline appeared to precede the onset of ventricular fibrillation, further data is needed for establishing a clear relation between these parameters.


Relationship between myocardial metabolism and epicardial ST segment alterations during myocardial ischemia. Acute myocardical ischemia was produced by ligating the midlevel left anterior descending coronary artery for 17 min in anesthetized dogs. Epicardial electrocardiograms were recorded from 15 sites surrounding the area of left anterior descending coronary artery ligation with a smooth tip, rounded epicardial electrode. Sites of ST segment elevation and isoelectric sites within the grossly ischemic portion of the left ventricle were needle biopsied to obtain tissue samples of less than 6 mg wet weight to assess myocardial metabolism at these precise sites. Epicardial areas of ST segment elevation had marked lactate accumulation and high energy phosphate depletion. Isoelectric sites were areas of either no lactate accumulation or mild lactate accumulation and high energy phosphate concentrations that were greater than those found at site of ST segment elevation. Thus, the data obtained indicate that epicardial sites of ST segment elevation are locations of profound anaerobic metabolism and of both epicardial and endocardial ischemia.


Calcium-dependent depolarizations and contractions in ventricular myocardial fibers: effects of adrenaline and cardiac glycosides. Intracellular membrane potentials and contractions were recorded in ventricular trabeculae from sheep and calf hearts. Using a sucrose gap and constant current pulses of 500 msec duration, Ca-dependent depolarizations were elicited in Ca-containing Tyrode's solution + tetrodotoxin (TTX) (1-2 X 10(-5) gm/ml; [Na]e 149.2 mM) or in Na-free solution with sucrose as sodium substitute. Adrenaline (10(-8) -5 X 10(-7) gm/ml), which has been shown to enhance Ca inward current, increased (dV/dt)max and contractile force both in Na-free and in Na-containing solutions + TTX. Digitoxigenin (10(-7) -3 X 10(-7) gm/ml), however, did not change (dV/dt)max and contractions in the absence of Na. In the presence of Na (+TTX), digitoxigenin increased contractile force but decreased (dV/dt)max. Under the assumption that the Ca-dependent depolarizations are carried by Ca it is concluded 1) that in contrast to adrenaline, digitoxigenin does not increase the permeability of the myocardial cell membrane to Ca and 2) that the positive inotropic effect of digitoxigenin is not due to an enhancement in Ca inward current during depolarization.


Influence of glycosides on myocardial potassium and sodium concentration in acute and chronic potassium deficiency. The analytical assay of intracellular potassium ([Ki]) and sodium ([Nai]) concentration of guinea pig papillary muscle measured in in vitro experiments shows that: 1) 5 X 10(-7) M g-strophanthin causes a decrease of [Ki] under control conditions, in acute as well as in chronic potassium deficiency, 2) a more marked glycoside effect is seen when the extracellular potassium concentration is reduced from 4.7 to 2mEq/1; this finding, therefore, is in good agreement with the observation that glucoside binding to its receptor at the cellular membrane is enhanced when potassium concentration is decreased, 3) whereas in chronic potassium deficiency normal [Ki] and [Nai] are maintained, acute potassium deficiency is accompanied by a loss of cellular K and gain of cellular Na. Under the influence of cardioactive glycosides, in chronic potassium depletion higher intracellular potassium and lower intracellular sodium concentrations are maintained than in acute potassium depletion. It is supposed tha t the net changes which are caused by a reduction of [Ke] in acute potassium deficiency in contrast to chronical potassium deficiency predispose to glycoside toxicity. These changes may therefore be the cause of the clinical observation that acute hypokalemia is associated with a greater glycoside sensitivity than chronic potassium deficiency.


Altered tissue digoxin uptake after a toxic dose. Tissue distribution and left ventricular (LV) effects of digoxin were studied after intravenous administration of low and high doses to dogs. LV dP/dt was increased by 0.03 mg/kg digoxin in nine, group A, and digoxin-induced arrhythmias or death occurred after 0.14 mg/kg in nine others, group B. Two hours after dosing during the slow excretion phase confirmed by serial serum sampling, the animals were killed. Serum and tissue extract digoxin determinations were performed by radioimmunoassay. Digoxin levels in group A were serum 3.9 ng/ml, kidney 428 ng/gm wet wt, liver 41, pancreas 39, diaphragn 21, apex, freewall, and septum LV 117-122, right ventricle (RV) 105, left atrium (LA) 51, right atrium (RA) 50, and the serum to apex LV ration was 1:32. The tissue contents and distribution were similar to previous [3H]digoxin data. The concentrations were higher in B; for all p less than 0.001. The toxic to therapeutic concentration ratios were serum 10, kidney 2.8, liver 5.5. pancreas 5,4, diaphragm 6.5, LV 4.3, RV 4.0, LA 3.5, RA 3.4. The serum to LV ratio was lower at 1:13, p less than 0.001. Myocardial toxicity was associated with marked but apparently limited increases in tissue digoxin content in this preparation. The disproportionately high serum level suggests paralysis or saturation of kidney and other tissue binding resulting in lower serum to tissue concentration ratios. Whenever serum to tissue ratios vary from expected values, serum digoxin levels may not be linearly related to tissue content or cardiac effects.


Reversible and irreversible forms of contractile failure caused by disturbances by general anesthetics in myocardial ATP utilization. Overdoses of several volatile anesthetics (ether, chloroform, ethyl chloride, halothane, methoxyflurane) as well as of various barbiturates lead to severe contractile failure of the heart. In all cases it was found that at the stage of maximal failure the myocardial stores of ATP and phosphocreatine were increased, indicative of reduced high energy phosphate utilization. Barbiturate-induced failure can be fully reversed by the intravenous injection of CaCl2, isoproterenol, or strophanthin. Simultaneously ATP and phosphocreatine concentrations become normal. In contrast, cardiac failure caused by volatile anesthetics proved to be resistant to this therapy. Electron micrographs showed a normal structure of the transverse tubules in the case of barbiturate failure. On the other hand, after the application of volatile anesthetics, a striking dilatation of the transverse tubular system was observed. The irreversibility of this latter type of contractile failure is probably caused by permanent damage of myocardial ultrastructures involved in excitation-contraction coupling.


On the mechanism of the negative inotropic action of halothane and propanidide. 1) Halothane and propanidide reduce the contractile force of guinea pig isolated atria in a concentration-dependent manner. The approximate concentrations required to bring about a half-maximal pharmacological effect are within the same order of magnitude as the concentrations found in whole blood during general anesthesia of guinea pigs. 2) It seems most likely that the initial effect of halothane or propanidide occurs at the cell membrane. 3) Halothane and propanidide accelerate and enhance the uptake of calcium ions by the cell membrane, so that less ionized calcium will be available for excitation contraction coupling. This phenomenon readily explains the negative inotropic action of both drugs and confirms the presumption that the cell membrane is the initial site of pharmacological attack.


Outward current and electrogenic sodium pump in Purkinje fibers. The effects of metabolic inhibitors (ouabain, dihydroouabain, and 2,4-dinitrophenol (2,4-DNP) and of cooling on the membrane current of Purkinje fibers were studied by means of a voltage clamp. Within seconds after cooling or application of the drugs the outward current was found to be reduced. On longer cooling or poisoning, the potassium equilibrium potential was shifted in positive direction, the time-dependent membrane currents were depressed, and possibly the potassium conductance was altered. It is suggested that the early reduction in outward current is caused by inhibition of an electrogenic sodium pump.


Myocardial oxygen consumption in isometric contraction of various strengths due to paired stimulation and quick-release. In all of the experiments described, the oxygen consumption during isometric contraction was dependent solely upon the magnitude of active tension developed, and not on the rate of tension development or on the duration of contraction. There is a constant linear relationship between tension development and oxygen uptake. Any sudden interruption of active tension in the rising phase of the contraction terminates the energy utilization by the contractile system. These findings provide evidence to suggest that in isometric contraction of heart muscle, a rigid and constant coupling exists in the transformation of chemical energy to the mechanical tension.


Multiple measurement of intranural myocardial oxygen tension. A method was developed for measuring the intramural oxygen tension in the ventricular wall (MpO2). The 10 electrodes of intramural needles are employed simultaneously for measurement of MpO2, and, by means of the same amplifiers and registration system, of the electrogram. In this way information could be obtained about the local MpO2 and the local electrical activity obtained from over 100 points in the ventricular wall. In the normal in situ dog heart we found an MpO2 of 5-90 mm Hg (mean 32 mm Hg). When the arterial pO2 was raised, the mean value of MpO2 was decreased. Directly after the start of a period of severe hypoxia a marked fall in MpO2 could be observed, which was reversible after return to the normoxic situation, provided that the hypoxic period was short. Changes in heart rate had only transient effects on the MpO2. Heart massage of the fibrillating heart in the open-chested dog was effective in restoring the arterial pO2, but gave no significant rise in MpO2 which did not exceed 5 mm Hg.


Myocardial wall thickness as a measurement of left ventricular ischemia. Using a newly developed myocardial wall thickness gauge, the change in the left ventricular wall thickness was measured during a period of partial myocardial ischemia and compared with changes and other parameters of left ventricular function. This study revealed that major changes of systolic wall thickness occur without any significant change in left ventricular function parameters.


Transmembrane sodium movement and regulation of contraction in frog atrial muscle during the inotropic effect of veratrine. In this study, voltage clamp experiments to determine membrane conductance changes revealed that veratrine slowed considerably inactivation of the Na system, thereby greatly increasing Na inward current. The contractile response (registered simultaneously with membrane currents) was closely related to this increase: applying tetrodotoxin (TXX) or Na-free (sucrose) Ringer's solution abolished the effect of veratrine on electrical and mechanical activity almost simultaneously. With Na-free (LiCl) Ringer's solution the effect of veratrine on membrane current was obtained, but the mechanical response was unchanged. Thus transmembrane movement of Na ions is involved in regulation of contraction during the inotropic effect of veratrine. As veratrine did not substantially change the slow Ca inward current, inotropic action seems dependent on some intracellular stores of Ca ions. The possibility that intracellular Na ions govern the amount of intracellular Ca ions available for the development of the inotropic effect of veratrine is discussed.


Some factors which influence the amount of calcium stored at the superficially located sites in cardiac muscle cells. The cell membranes of cardiac muscle cells are impermeable to the trivalent rare earth element, lanthanum (La3+). Because La3+ displaces Ca2+ from its binding sites and because it does not penetrate across the cell membrane, it can be used to determine how much Ca2+ is stored at these superficially located sites. Using this technique it has been possible to study the various factors which influence the Ca2+ storing capacity of these superficially located sites. Substitution of Cl- by NO3- and Br- in the bathing fluid, and prolonged periods of perfusion reduce, whereas hyperthyroidism, an increase in the extracellular concentration of Ca2+, and a reduction in the extracellular concentration of Na+ increase the amount of Ca2+ stored at these superficially located sites. Some drugs which are negatively inotropic (verapamil and pentobarbitone) reduce, whereas others, which are positively inotropic (ouabain), increase the amount of Ca2+ which is available for displacement by La3+. Ca2+ which is stored at these sites plays an important role in regulating cardiac contractility.


Anticonvulsant activity of four oxygenated cannabidiol derivatives. A pharmacological comparison between cannabidiol (CBD) and four CBD derivatives, namely CBD-aldehyde-diacetate (I), 6-oxo-CBD-diacetate (II), 6-hydroxy-CBD-tri-acetate (III), and 9-hydroxy-CBD-triacetate (IV) was carried out in mice. Protection against maximal electroshock convulsions, potentiation of pentobarbital sleeping-time and reduction of spontaneous motor activity were the effects measured. All 5 compounds were equally potent in potentiating barbiturate sleeping time at doses ranging from 6.25 to 100 mg/kg. At 12.5 and 25 mg/kg only CBD and IV were able to decrease significantly the spontaneous motor activity. CBD, II, III and IV were also active in protecting mice against electroconvulsive shock at doses of 100-200 mg/kg, although at the larger dose CBD and compound II were the most efficient. Compound I was toxic, killing about half of the animals within 24 h after injection.


Plasma disappearance of sulfobromophthalein or indocyanine green in unconjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia as occurs in Gunn rats did not affect the plasma disappearance of sulfobromophthalein (BSP) or indocyanine green (ICG). The simultaneous injection of bilirubin and ICG decreased the plasma disappearance of ICG apparently by decreasing hepatic uptake. The data suggest that although bilirubin, ICG and BSP bind to the intracellular hepatic transport protein ligandin one cannot achieve conditions in intact rats to demonstrate effects of competitive interaction with ligandin that affect plasma kinetics of these substances.


A new approach to the treatment of sickle cell anemia. Several lines of evidence suggest that certain small molecules with a high affinity for specific sites in heme proteins may prove useful as anti-sickling agents. One agent of this group, dichloromethane, at low concentrations can prevent completely and reverse partially the aggregation of hemoglobin S. It is proposed that in the search for useful therapeutic agents attention should be given to these non-heme ligands of hemoglobin.


A theoretical analysis of the distribution of quinidine in the plasma: the relationship between protein binding and therapeutic drug levels. Quinidine is bound at two sets of sites on serum albumin. The distribution between the free and albumin bound form of the drug in plasma was analyzed by the use of a computer program using known association constants and binding capacities. The analysis was limited to concentrations of drug which ranged from subtherapeutic to toxic levels, 1 to 10 mg/L. The computations showed that 74 to 88% of the drug would be bound by serum albumin and the remainder would be free. Of the bound drug, 71-74% would be bound by the high affinity set of sites and the remainder by the low affinity set. The analysis also showed that if the concentration of protein were decreased, as in hypoalbuminemia, there would be a decrease in the amount of bound drug and an increase in the amount of free drug. The quantitative relationships between therapeutic levels of the drug and its distribution in plasma are discussed.


Antihypertensive activity of 2-amino-4-(3,4-dichlorophenyl)-2-imidazoline (MJ 10459-2) and catecholamine reduction. Antihypertensive activity of 2-amino-4-(3,4-dichlorophenyl)-2-imidazoline hydrobromide (MJ 10459-2) was assessed in conscious, spontaneously hypertensive and stress-induced hypertensive rats via indirect determination of systolic blood pressure. Subcutaneous administration of 1-4 mg/kg resulted in lowering of blood pressure that was dose related. No reductions in the content of norepinephrine, dopamine, serotonin or 5-hydroxyindoleacetic acid were noted in the cerebrum, cerebellum, midbrain or medulla/pons area of brain after 1 and 4 mg/kg of MJ 10459-2. Cardiac tissue norepinephrine was reduced to 4-6% of control values after subcutaneous doses of 0.2-20 mg/kg of MJ 10459-2 in hypertensive and normotensive rats. These data suggest that at least part of the blood pressure lowering effects of MJ 10459-2 may involve reduction of peripheral noradrenergic stores.


Dopaminergic and cholinergic influences on morphine self-administration in rats. Various doses of apomorphine, haloperidol, pilocarpine and scopolamine were administered i.p. to rats self-administering i.v. morphine (0.4 mg/kg/infusion). Apomorphine, at low doses, increased rates of morphine self-administration and, at high doses, decreased rates. Haloperidol decreased self administration rates with increasing dose. Both pilocarpine and scopolamine produced only small decreases in rates at high doses. When administered in combination, the effects of apomorphine and haloperidol were antagonistic as were the effects of pilocarpine and scopolamine; the effects of apomorphine or haloperidol predominated, however, when either drug was administered in combination with pilocarpine or scopolamine. The results are consistent with previous work implicating an important role for dopaminergic mechanisms in morphine's reinforcing property.


The action of isoproterenol on phenylthiourea induced pulmonary edema. Isoproterenol inhalation increases the pulmonary edema induced in rats by phenylthiourea. Propranolol decreases this response while phenoxybenzamine has no effect upon it. It is proposed that the observed increase in toxicity is related to the beta-adrenergic effects of the isoproterenol and that the specific mechanism responsible might be an increase in pulmonary capillary hydrostatic pressure which is secondary to an increase in pulmonary blood flow.


Microsomal O-demethylation, N-demethylation and aromatic hydroxylation in the presence of bisulfite and dithiothreitol. Microsomal O-demethylation of p-nitroanisole, N-demethylation of aminopyrine and aromatic hydroxylation of aniline, were not altered by sodium bisulfite or dithiothreitol at concentrations effective for their use as antioxidants. Incorporation of these antioxidants in microsomal metabolism studies should have general utility in preventing decomposition of readily air oxidizable compounds.


Metabolism of glutethimide in the human. Gas chromatographic and gas chromatographic-mass spectrometric techniques were used to identify metabolites of glutethimide excreted in human urine. In this study three monohydroxy metabolites, a dihydrodiol and three dihydroxy metabolites were detected after ingestion of the drug. The results indicate that the phenyl ring of glutethimide is metabolized by the epoxide-dihydrodiol pathway in the human following chronic administration of the drug.


Isolation and identification of a new metabolite of naltrexone in human blood and urine. A new metabolite of naltrexone was isolated from urine and erythrocytes of patients taking 100 mg naltrexone daily. Its tentative structure of 2-hydroxy-3-methoxy naltrexol was derived by analysis of the purified compound using gas chromatography combined with mass spectrometry, high resolution mass spectrometry and infrared spectrometry. Long bioavailability of the new metabolite is indicated by its slower excretion rate into the urine than naltrexone and beta-naltrexol. The rather high concentration of the new metabolite in the erythrocytes and its solubility in non-polar solvents like benzene demonstrate the ability of this compound to penetrate membranes. These features of the new metabolite suggest that it may contribute to naltrexone's long time course of action.


Resuscitation of patients with ischaemic heart disease before admission to hospital. This paper provides data about the efficacy of resuscitation before hospital admission of 139 patients with myocardial infarction. Successful resuscitation was effected in 43 (30.9 percent) patients, of whom 29 (20.9 percent) survived and were discharged from hospital. An organizational scheme is given for resuscitation measures before admission, in which the following teams participate: premedical, general first-aid ambulance team and specialized first-aid cardiological team (Mobile Coronary Care Unit, MCCU - definition of World Health Organization). The effectiveness of resuscitation depends upon the patient's age, and the presence and degree of circulatory insufficiency before clinical death. It proved possible to revive successfully patients of advanced age and with proceding mild or moderate acute circulatory insufficiency. Resuscitation was not successful in patients with preceding severe circulatory insufficiency. Blood electrolytes were studied in the post-resuscitation period. There was a statistically significant decline in plasma potassium ion concentration. Potassium salts should be introduced in the form of a polarizing mixture, especially to patients with an irregular cardiac rhythm in the post-resuscitation period. Problems of intracardiac injections of drugs, intubation, and pervenous electric pacing in patients with myocardial infarction during resuscitation are discussed. It has been concluded that the optimum form of resuscitation before admission of patients with myocardial infarction involves rendering maximal aid at the place of occurrence of the infarction.


A review of total brain ischaemia models in dogs and original experiments on clamping the aorta. Dog models of total brain ischaemia for the study of pathophysiological mechanisms and post-resuscitative therapy used since 1970 are reviewed. Attempts to produce isolated total cerebral ischaemia in dogs either failed to stop cerebral circulation completely because of the abundance of collateral vessels or involved complex operations with blood loss. Complete airway obstruction resulted in various periods of asphyxia preceding asystole. Total circulatory arrest by ventricular fibrillation for 12 min or longer, resulting in gross neurological deficit, required cardiopulmonary resuscitation of variable duration and often required thoracotomy to restart spontaneous circulation. An acceptable model for short-term studies was obtained by clamping the ascending aorta for 15 min. This resulted in control of perfusion pressure with precise timing of onset and termination of cerebral ischaemia, and an isoelectric electroencephalogram within a mean time of 37 (26-44) s; it retained its ability to restore spontaneous circulation promptly with special supportive therapy, and a severe neurological deficit was evident for 20 h after ischaemia. Reliable total brain ischaemia suitable for long-term survival studies could not be developed in the dog without major surgical procedures, as it has been in the rhesus monkey. Sixteen minutes of high-pressure neck occlusion with a tourniquet and special intensive care resulted in major neurological deficit with survival for at least 7 days, and proved suitable for simultaneous study of neurological, physiological and histological changes.


Correlation between acid-base status, concentrations of lactate and of pyruvate in blood and cerebrospinal fluid in patients treated in an intensive care unit. Results of examinations of 41 patients treated in an intensive care unit are reported. The patients were divided into three groups and examined on the first and twelfth days of treatment. In the first group were 15 patients who had received circulatory resuscitation, the second group was 13 patients with lesions of the central nervous system of traumatic or vascular origin and the third group was 13 patients with acute respiratory insufficiency of toxic or infective origin. The cerebrospinal fluid of patients in the second group showed the lowest pH (mean pH 7.28) and bicarbonate concentration (19.05 mequiv./1); this group also had the lowest PO2 values. Moderate respiratory alkalosis was observed in the arterial blood of patients with lesions of the central nervous system. Concentrations of lactate in the cerebrospinal fluid were increased in all three groups of patients although blood lactate concentrations were normal. The lactate/pyruvate concentration ratio was highest in the resuscitated patients.


A paediatric respiratory intensive care unit in Lagos. The respiratory Intensive Care Unit was created at the Lagos University Teaching Hospital in 1963. Experience shows that mortality has been highest in neonates who had congenital anomalies, as well as in children under 2 years of age. The predominant cause of death was preventable respiratory failure. The incidence of mortality was 43 percent. This was related to several factors: (i) the severity of illness, types of illness and antecedent period of neglect; (ii) lack of a critical care medicine programme; (iii) insufficient skilled full-time intensive care personnel, including physicians, nurses, physiotherapists and paramedical specialists; (iv) the high incidence of infection in the Intensive Care Unit.


Pulmonary oedema in chronic bronchitis - a haemodynamic study. Right heart catheterization was performed in ten patients with pulmonary oedema. Mean wedge pressures in excess of 12 mmHg above the mid-axillary line were regarded as abnormal and indicating left heart failure. If the wedge pressure was less than 12 mmHg, and pulmonary congestion was present, frusemide was given. Brief descriptions of the ten cases are given.


Effects of hyperbaric oxygenation on cerebral vasomotor tone in acute intracranial hypertension: an experimental study. The effects of hyperbaric oxygenation with 2 atm. pressure and 100 percent oxygen on cerebrovascular tone were assessed by the reactivity of the cerebral vessels to CO2 and vasomotor capacitance index (the cranial pressure divided by the mean arterial pressure) in 50 anaesthetized artifically ventilated dogs, in which intracranial pressure was raised by slow inflation of an extradural balloon. Hyperbaric oxygenation reduced the intracranial pressure only at the stage when the cerebral vessels were still responsive to CO2, as indicated by a rise in intracranial pressure of 30-70 mmHg; under these circumstances, both the reactivity of CO2 and the vasoconstrictor tone of cerebral vessels were improved by hyperbaric oxygenation. At this stage, rapid decrease of the intracranial pressure produced by deflation of the extradual balloon showed no rebound, and hyperbaric oxygenation rapidly restored the vasomotor tone. When CO2 failed to influence the intracranial pressure of about 100 mmHg hyperbaric oxygenation did not aid the recovery of the reactivity of the cerebral vessels to CO2 or the vasoconstrictor tone. In extreme intracranial hypertension (above 100 mmHg) when there was reactivity to CO2 and the electroencephalogram was flat, rapid balloon deflation was followed by a further gradual increase of intracranial pressure and hyperbaric oxygenation did not restore the cerebrovascular tone. The effect of hyperbaric oxygenation in experimental intracranial hypertension appeared to be dependent upon the vasoconstrictor tone of the cerebral vessels, which would be indicated by a vasodilator response to CO2.


Enzymes in the cerebrospinal fluid in diagnosis of brain death. The increase of enzymes in the cerebrospinal fluid is shown to indicate an adverse prognosis, with the implication of irreversibility. The massive increase of glutamate-oxaloacetate transaminase and lactate dehydrogenase and the appearance of alkaline phosphatases in a sample of cerebrospinal fluid in which the cytology is normal constitute an easy and reliable test for brain death. The increase in lactate dehydrogenase fraction V and lysozyme in cerebrospinal fluid supports the macrophagic origin of these enzymes.


The progressive response of the newborn infant to added respiratory loads. The responses of 10 normal full-term infants to 10-sec airway occlusions at functional residual capacity were studied. The responses were quantified by measuring the pressure generated on successive inspiratory efforts following occlusions in room air and 100% oxygen. The response after oxygen breathing was 30-40% less than after air breathing, indicating that hypoxia accounted for part of the response. There was an increase in the response in air from the first to the fourth day of life. Endtidal carbon dioxide tension was shown to increase during the occlusion, but the response remaining after hypoxia was eliminated may not have been due entirely to hypercapnea. We conclude that the compensatory response of the infant to added respiratory loads is in part due to hypoxia, and that the hypoxic response increases over the first week of life.


Effect of inspiratory resistance of occlusion pressure in hypoxia and hypercapnia. The authors measured ventilation and the mouth pressure developed during the first 0.1 sec of inspiratory effort against a closed airway (P 0.1) in response to normoxic hypercapnia and normocapnic hypoxia, with and without added inspiratory resistance. Hypercapneic responses were elicited by a steady-state technique, hypoxic responses by a non-steady-state technique. External resistance depressed the ventilatory response to CO2 but in general augmented the P 0.1 response. The degree of change of response was not predictable on the basis of the response in the absence of resistance. Hypoxic ventilatory response was also diminished by resistance and P 0.1 increased. The authors concluded that in normal subjects added inspiratory resistance increased inspiratory drive as assessed by P 0.1.


Tonic vagal influences on inspiratory duration. The tidal volume (VT), inspiratory (Ti) and expiratory (Te) durations were determined in anesthetized rabbits, cats and dogs under normal conditions, during continuous positive or negative pressure breathing. Elastic loads up to complete occlusion of the airways were applied in order to determine the VT-Ti and Te-Ti relationships. The larger the end-expiratory lung volume the steeper the VT-Ti relationship, the smaller the increase of Ti and the greater the increase of Te produced by the load. Hence, the larger the end-expiratory lung volume the steeper the Te-Ti relationship. In vagotomized animals airways occlusion did not affect Ti and Te. Ti of occluded breaths in vagotomized animals was longer than that of occluded breaths in intact animals, whereas Te was similar at the resting volume of the respiratory system (FRC), shorter above FRC and longer below FRC. These results show that both phasic and tonic vagal discharges determine Ti and Te.


Nitrogen exchange across the lungs in resting man. The relationship between the partial pressure of N2 in the inspired air (PIN2), and the nitrogen transfer across the lungs (VN2), has been examined in 8 resting subjects, and a study made of the effect of diet upon this relationship. Alterations in PIN2, over the range 60 mm Hg below, to 20 mm Hg above ambient PIN2, caused changes in VN2 which could be described by a linear equation. These changes agreed both in magnitude and direction with those predicted by a four-compartment electrical analogue of the body N2 stores. They were not affected by the protein content of a meal taken 3/4 hr before the start of measurements of VN2. The study has shown that any imbalance in N2 transfer across the lungs is very small and that the open-circuit method of measuring O2 consumption is valid.


Hematological and biochemical effects of chronic CO exposure on the Japanese quail. Japanese Quail were exposed to a concentration of 300 to 350 ppm CO to maintain an equilibrium carboxyhemoglobin concentration of 30% for a period of 4 weeks. Compared to a control group of birds maintained in an identical chamber, the CO-exposed quail demonstrated increases in hematocrit ratio and hemoglobin concentration. At the end of the exposure period, the CO-exposed quail had significantly larger plasma and blood volumes, slight but significant right ventricular hypertrophy and higher fasting plasma glucose concentrations than the control birds. Cardiac and skeletal muscle carbohydrate stores were not affected by chronic CO exposure.


Effect of surgical stress on the distribution of placental blood flows. The distribution of the uterine and umbilical blood flows over the surface of the placenta was measured in 9 near-term sheep in an effort to assess the effects of surgical stress. The blood flows were observed to be relatively evenly distributed over the surface of the placenta. It was determined that the heterogeneity of distributions observed in the study could have caused the transplacental clearance of a very diffusible molecule to decrease by no more than 2 0/0. It is concluded that at the macroscopic level, in both the acute and chronic conditions, the uterine and umbilical blood flows of the near-term sheep are relatively evenly distributed over the surface of the placenta and that this distribution per se does not significantly contribute to transplacental concentration gradients.


Effect of gas density and ventilatory pattern of steady-state co uptake by the lung. The steady-state uptake of carbon monoxide was measured in five normal subjects to study stratified inhomogeneity of gases in the pulmonary airways. An attempt was made to assess the effect of stratified inhomogeneity by varying the physical properties of the inspired gases and the depth and rate of ventilation by the subjects. Twelve different controlled patterns of breathing were followed by each subject on each of three gas mixtures (20% O2 with N2, He and SF6 plus 0.04% CO in each case). The experimental results show that CO uptake was significantly different when breathing the different density gases but that it was always greatest from the most dense gas SF6 and least from He. If the uptake of CO from the inspired gas across the alveolar membrane were controlled by simple molecular diffusion then as gas density decreases uptake would increase. As inspiratory flow rate was increased there was an almost linear increase in CO uptake for each gas mixture with a difference in uptake between the different-density gases which became most marked at the higher flow rates. Flow rate was increased in two ways: by maintaining tidal volume and altering breathing frequency or by maintaining frequency and altering tidal volume. The results for the two extremes, helium and SF6, indicated a difference between these methods of increasing flow rate. In the case of SF6, doubling the flow rate by increasing breathing frequency gave an uptake only marginally lower than doubling the depth of penetration. With helium, however, it was necessary to treble the frequency to obtain the increment of CO uptake achieved by doubling the depth of penetration. The experimental observations are explained by the use of a model based on Taylor dispersion in the conducting airways. The conclusion is that the results confirm the presence of significant stratified inhomogeneity in the airways of the lung.


[Intracerebral hematoma in gamma-angio-encephalography]. The radionuclide angiography, of gamma-angio-encephalography (gamma-A.E.G.), a non invasive method, is able to bring specific information for the diagnosis of intracerbral hematoma (I.C.H.). In 25 out of 32 verified cases of I.C.H. the rapid sequential imaging shows from the arterocapillary time a deeply seated avascular area, which is a quite different aspect from the defect observed in ischemic A.C.V., or malignant tumors. The transit curves confirm the regional of circulating blood pool.


[Transcortical aphasia and echolalia; problems of speech initiative]. Transcortical aphasia accompanied by echolalia occurs with malacias involving the postero-median part of the frontal lobe which includes the supplementary motor field of Penfield and is nourished by the anterior cerebral artery. The syndrome manifests itself in such cases even in fine detials in the same form as does in Pick's atrophy. The same also holds true for cases in which a tumour involves the region mentioned. Sentences or fragments of sentences are echolalised; tendency to perseveration is very marked. It is hardly, if at all, possible to evaluate the verbal understanding of these patients. Analysis of their behaviour supports the assumption that they have not lost the adaptation to some situations. Echolalia is often associated with forced grasping and other compulsory phenomena. Therefore, it may be interpreted as a sign of disinhibition of the acusticomotor reflex present during the development of the speech. Competition between the intentionality and the appearance of compulsory phenomena greatly depends on the general condition of the patient, particularly on the clarity of consciousness. The integrity of the postero-median part of the frontal lobe is indespensable for a normal reaction by speech to stimuli received from the sensory areas. The influence of the supplementary motor field on speech intention seems to be linked to the dominant hemisphere. In case lesions of the territory of the anterior cerebral artery and the cortico-bulbar neuron system are coexisting in the dominant hemisphere, the speech disturbance shifts to complete motor aphasia. In such cases the pathomechanism is analogous to that of the syndrome of Liepmann, i.e., right-sided hemiparesis with left-sided apraxia. So-called transcortical motor aphasia without echolalia can be caused by loss of stimuli from the sensory fields.


[Rapid injection technique as a routine for the IVP (results of 144 examinations with various contrast media) (author's transl)]. Report on experience with routinely used rapid injection technique for IVP's with various contrast media at present on sale. Side effects and quality of contrast are compared. The methylglutaminsalt of Ioxitalamin acid has least side-effects, but for contrast, particularly its persistence in time-consuming examinations, it is inferior to the sodium-methyl-glucamin salt mixtures (here the Ioxitalamin and Amidotrizoe-acids). The importance of routine use of the rapid injection technique for problems of hypertension and the additional information made possible are emphasized.


[Radiologic diagnosis of mega-ureter in childhood (author's transl)]. For the radiologic diagnosis of mega-ureter the degree of filling of the bladder (bladder-phenomenon) in the IVP has to be considered. A film, after emptying the bladder, prevents mistaken diagnosis. In order to prove reflux a micturition cystogram will always have to be done. The diuretic effect of the contrast medium has to be taken into account. For a differential diagnosis mega-ureter has to be distinguished from functional distension (hypotonia) in the presence of infection or increased diuresis.


[Technique, complications, possible misinterpretations and indications of retrograde renal phlebography (author's transl)]. A chronological survey is given of the gradual development of retrograde renal phlebography whereby the different techniques are contraste with each other in detail. Today's method of choice is the retrograde selective visualization of renal veins using the Seldinger procedure via the femoral vein, with or without pharmacological influence and applying larger doses of contrast medium (up to 30 ml) and higher injection pressures (up to 6 kg/cm2). Indications for simple and for pharmacophlebography are specified and exemplified by means of a scheme. Possible complications and misinterpretations are discussed.


[Radiologic diagnosis of secondaries of tumors of the testicle (author's transl)]. For the radiologic diagnosis of secondaries of testicular tumors we use conventional plain films of chest and abdomen, IVP or infusion urography, tomography of the retroperitoneal space with or without contrast media and, according to the suspected site of metastases, further special radiologic techniques like lymphography, cavography, azygography, venography of the lumbar vein or, occasionally, aortography. The techniques are described, their value and limits discussed.


[Radiologic diagnosis of retroperitoneal fibrosis (author's transl)]. The value of the various radiologic techniques for the diagnosis and follow-up of retroperitoneal fibrosis are discussed on the basis of two case reports and an analysis of 48 patients. The most important technique is the IVP with breathing and profile exposures. AP and lateral pre-operative retrograde pyelography is often essential for the diagnosis. Cavography and arteriogram should always be done in this condition, since they permit assessment of vascular compression and extension distally of the fibrosis. MDP and contrast enema should be employed, if the signs warrant it. These radiologic techniques permit, when positive, combined surgical planning by various surgical specialists.


[Aneurysmatic changes of renal arteries in the angiogram (author's transl)]. 10 out of 1600 angiographies of the kidneys or abdominal aortograms showed a renal aneurysm and in one patient an arterio-venous fistula following renal biopsy. Renal artery aneurysms are found mainly at the branching of the main renal artery. Fibromuscular dysplasia plays a large part in its development. Because of the danger of rupture every renal aneurysm should, if possible, be treated by surgery.


[Partial thoracic renal ectopy (author's transl)]. Based on a case of his own the author surveys the literature of this rare condition. He discusses its clinical importance, the differential diagnosis from a lung shadow placed on the diaphragm and the distinction between congenital and posttraumatic displacement. An IVP will settle the diagnosis. Unless there are symptoms, operative correction is not needed.


Urinary albumin excretion during exercise in juvenile diabetes. A provocation test for early abnormalities. Urinary albumin excretion during exercise was measured with a radioimmunological method in a group of 13 young male diabetic patients and in a comparable control group. The duration of diabetes was 2-18 years; they had no proteinuria (Albustix¿) and no other signs of renal disease. There was no difference in the basal albumin excretion. In the diabetics the average albumin excretion was doubled during exercise at 600 kpm/min for 20 min, from 9.1 mug/min to 18.7 mug/min (P less than 0.005). No significant change was seen in the controls. These results strongly suggest that abnormal glomerular filter properties are present in patients with relatively short duration of diabetes - that is, in patients who are known to have thickened glomerular basement membrane. The exercise provocation test may be useful in other fields of renal pathophysiology.


[131I]Hippuran renography in normal subjects and in patients with essential hypertension. Seventeen normal subjects and 21 patients with essential hypertension were examined by [131I]hippuran renography. Both groups were studied twice on the same day, first in a state of moderate dehydration and then after rehydration. From these data, four sets of reference intervals were established for several renographic parameters. Differences between the two groups were defined. The most impressive observation was a greater functional disparity between the two kidneys of one individual in the group of hypertensive patients, particularly when in a state of moderate volume depletion. This was reflected in a greater variance of certain kidney-to-kidney ratios derived from the renographic tracings. This article presents basic data to be utilized in clinical renography, as described in an accompanying article.


Diagnostic value of renography for detection of unilateral renal or renovascular disease in hypertensive patients. In an effort to find an optimal set of renographic reference parameters for the study of hypertensive patients, the renographic data from 50 hypertensive patients with unilateral renal or renovascular disease were assessed against 95% confidence intervals obtained in normal subjects and in patients with essential hypertension in two different states of hydration. The highest all-over nosographic sensitivity and specificity were obtained by using the data from hydrated normal subjects as reference parameters. The nosographic sensitivity and specificity found in the selected series of hypertensive patients were converted to the clinically relevant predictive values of a positive and a negative test by assuming the prevalence of unilateral renal or renovascular disease in hospital populations of hypertensive patients to be 5% or 10%. In these model populations the predictive value of a postive was 33% and 51%, respectively. The predictive value of a negative test was higher than 99% for both populations. We find that predictive values of that order of magnitude are satisfactory for a test to be used in the initial phase of a diagnostic process.


Cardiovascular and renal responses to acute cold exposure in water-loaded man. Changes in oxygen uptake, cardiac output, heart rate, stroke volume, central blood volume, arteriovenous oxygen difference, aortic, pulmonary arterial, and right atrial blood pressure, systemic vascular resistance, hematocrit, circulating plasma volume, urine flow, fractional sodium excretion, and free water clearance were studied in eight healthy volunteers in stable water diuresis, exposed to cold by means of air at +15 degrees C and at a speed of 0.5 m/sec. A decrease in circulating plasma volume and systemic vascular resistance was found during cold stress. Mean aortic blood pressure, sodium excretion, cardiac output, oxygen uptake, arteriovenous oxygen difference, and hematocrit increased. No changes in urine flow or in clearance of free water could be demonstrated. Heart rate, stroke volume, and central blood volume showed significant increases in cold. The results are interpreted to suggest that exposure to cold raises the arterial blood pressure by an increase in cardiac output, thereby increasing capillary hydrostatic pressure in certain vascular areas, including the renal vascular bed. This negatively affects capillary reabsorption processes in the kidney, causing a reduction in tubular sodium reabsorption, thus giving rise to a natriuresis. In other areas it seems to cause a shift of fluid towards the intersitial space.


Tubular sodium handling in cold-exposed man during inhibition of distal tubular reabsorption of sodium. In 8 healthy volunteers in stable water diuresis, exposed to cold at +15 degrees C for 60 min, changes in excretion and tubular reabsorption of sodium and osmoles were studied by the clearance technique during inhibition of distal tubular sodium reabsorption following chlorothiazide infusion at 2 mg/kg/hr. Inhibition of distal tubular sodium reabsorption by chlorothiazide increased fractional sodium excretion to 6.5% and fractional excretion of osmoles to 7.5% of the filtered amount. The superimposed cold exposure did not further increase these figures, despite a significant cold-induced increase in arterial blood pressure.


Bone mineral content in the forearm measured by photon absorptiometry. Principles and reliability. A method for estimating total bone calcium is reported. The method is based on two-dimensional scanning photon absorptiometry on the distal part of the forearm. The following factors are investigated: precision of measurements on standards and human subjects; linearity; the effect of varying bone orientation; amount of fat and soft tissue; and the relation between weight and content of calcium and phosphate. The results show that the method is eminently suitable for rapid, easy, and atraumatic measurement of local bone calcium in vivo.


Inactivation of glycogen phosphorylase of human polymorphonuclear leukocytes. Glycogen phosphorylase of human polymorphonuclear leukocytes is dephosphorylated during incubation of a gel-filtered cell extract. The dephosphorylated enzyme (b form) retains 25 per cent of the activity of the phosphoenzyme (a form) when measured without AMP but a high glucose-1-phosphate concentrations. The ratio of activity -AMP/+AMP for the a enzyme is 0.8-1.0 and for the b enzyme 0.2. Leukocyte phosphorylase is not activated by -SH groups, but the b enzyme is stimulated by 0.4 mol/1 Na2SO4. The phosphatase which catalyzes the conversion of phosphorylase a to b is inhibited by glucose-1-phosphate and AMP both a 14 degrees C and 25 degrees C. Glucose counteracts the AMP inhibition but not the glucose-1-phosphate inhibition at both temperatures. Glucose alone had no effect at 25 degrees C, but it accelerated the phosphatase reaction at 14 degrees C. Glucose-6-phosphate or glycogen alone or in the presence of AMP or glucose-1-phosphate did not affect the phosphatase reaction. From previous and present experiments it is concluded that the phosphorylase of human polymorphonuclear leukocytes is closely related to liver phosphorylase and that the inactivation of the enzyme is mainly controlled by AMP and glucose.


Rapid effect on lipoprotein lipase activity in adipose tissue of humans after carbohydrate and lipid intake. Glucose or corn oil was given perorally to fasting, young healthy volunteers, and the time course of acute effects on lipoprotein lipase activity (LLA) in adipose tissue, plasma glycerol, triglyceride, insulin, and blood glucose levels was followed. After glucose intake, adipose tissue LLA increased rapidly, reaching a maximum of 80 per cent above initial level after 2 h. Plasma glycerol, reflecting the rate of lipolysis of depot lipids, decreased rapidly, temporally well correlated to the LLA changes. After corn oil intake no significant effect on any of the parameters studied was observed except for an increase in the plasma triglyceride level caused by the influx of dietary lipid.


Oxidation of palmitate by human skeletal muscles in vitro. Method and normal values. The conditions of determination of the in vitro incorporation rate of palmitate-carbon into CO2 in human skeletal muscles were studied. Muscle biopsies were taken from 25 patients with nonmuscular diseases and incubated in a metabolic shaker with KRP as medium and palmitate as substrate. Substrate saturation was achieved beyond a palmitate concentration of 2.5 mmol/1, and the incorporation rate was linear with time for 2 hr. The activity of 3-hydroxy-acyl-CoA-dehydrogenase (ACDH), an enzyme involved in the beta-oxidation, was also determined. Both the incorporation rate of palmitate-carbon into CO2 and the activity of ACDH were higher in the leg muscles than in the abdominal muscles. Significant positive correlations were found between the incorporation rate of palmitate-carbon into CO2 and the ACDH activity, and between the incorporation rate and the phospholipid concentration in muscles. These correlations indicate that this in vitro system is valid for evaluation of the metabolism of fatty acids in skeletal muscle tissue.


Cortisol-induced accumulation of phospholipids in organ culture of human fetal lung. Lungs obtained from human fetuses with a gestational age of 17, 19, and 24 weeks were cultured as organ culture for 6 days with or without cortisol. The total phospholipid content per milligram protein in the explants incubated with cortisol increased by 56-81 per cent compared with the controls. Lecithin accounted for 62-69 per cent of the phospholipid increment in the cortisol-treated explants, whereas only 44.2 per cent of the total phospholipids in the control incubations consisted of lecithin. Cortisol increased the incorporation of [Me-3H]choline into lecithin by 118-224 per cent. The investigation shows that the human fetal lung, quite early in gestation, is capable of responding to the action of glucocorticoids by accumulating phospholipids.


Estimation of total body calcium from the bone mineral content of the forearm. The representativity of forearm in bone mineral content (BMC) measurements for estimation of total body calcium is investigated in this article. It is shown that there is a very high correlation between weight and calcium content of examined bone pieces, that there is a high correlation between weight of individual bones and BMC values, that the BMC values from various parts of the skeleton are reasonably well correlated, that the weight of individual bones is highly correlated to the weight of total skeleton, and that there is a reasonably high correlation (r=0.85) between BMC measurements in the distal part of the forearm and total weight of the skeleton. It is concluded that BMC measurements of the distal part of the forearm give an estimate of total body calcium.


Bone mineral content and estimated total body calcium in normal adults. Bone mineral content (BMC) was measured in 127 normal subjects, 54 men and 73 women, aged 21-70 years. BMC was a function of age and sex; it was therefore found relevant to give normal values in 10-year age groups for each sex. BMC was furthermore related to height, weight, surface area, and muscular strength but the biological scatter was not reduced by correction for surface area. The normal range is expressed in arbitrary units, mmol calcium/m, and calculated total body calcium in grams. Since the latter expression, after determination of the necessary proportion constants, is independent of apparatus construction and location of measurement, and is dependent on the selection of the reference population, it is recommended that the result be expressed in these grams. It is furthermore concluded that the BMC measurement is excellently suited for determining the effect of treatment on osteopenia in a group of patients but rather unsuitable for diagnosis of osteopenia in the individual patients, whereas two other conditions (as regards clinical applicability) occupy an intermediate diagnosis of osteopenia in a group of patients.


Protein concentration and hydrostatic pressure in subcutaneous tissue of rats in hypoproteinemia. Protein concentration and hydrostatic pressure were measured in subcutaneous tissue of rats during development of aminonucleoside nephrosis. Samples of interstitial fluid for protein analysis were collected from subcutaneous tissue by a wick method, and hydrostatic pressure was measured by a modified Scholander technique. When the serum protein concentration was reduced from 6.1 to 4.8 g/100 ml, interstitial fluid protein concentration fell from 3.0 to 1.1 g/100 ml. This corresponds to a reduction of calculated oncotic pressures from 18.0 to 13.0 mm Hg and from 7.8 to 3.0 mm Hg in serum and interstitial fluid, respectively, thus leaving a nearly constant net transcapillary oncotic pressure. When serum protein concentration was further reduced to 3.8 g/100 ml, interstitial fluid protein concentration was reduced to 0.5 g/100 ml, reducing net transcapillary oncotic pressure by 2-3 mm Hg. The average hydrostatic pressure in subcutis was 1.0 mm Hg subatmospheric under control conditions and did not change during hypoproteinemia. The results indicate that a reduction of interstitial protein concentration is an important factor in preventing edema formation in hypoproteinemia.


Ultrasonic measurement of sound velocity in whole blood. A comparison between an ultrasonic method and the conventional packed-cell-volume test for hematocrit determination. A new ultrasonic instrument for the determination of sound velocity in tissue is described. The instrument has been used in this investigation to measure the sound velocity in heparinized whole blood samples. The corresponding hematocrit values of the blood samples were determined by the packed cell volume test. The measurements in the hematocrit range of approx. 30-55 indicate a high degree of correlation between the hematocrit value and the respective blood sound velocity (S.E.E.=1.3 and r=0.96). Repeated measurements of the same blood samples up to 1 hr after collection of the blood show very small changes in reading of sound velocity, provided the samples were kept at a constant temperature and well stirred. The ultrasonic measurement is quick and simple to perform, and the blood specimen is not changed by the measuring process.


Serum gastrin response to food stimulation and gastric acid secretion in male patients with ileal resection. Gastric acid secretion before and after stimulation with pentagastrin and serum gastrin response to a test meal were recorded in 9 male controls and in 7 male patients from whom more than 50 cm of the terminal ileum had been resected because of Crohn's disease. The mean gastric acid secretion before and after stimulation was not found to be significantly different in the two groups. The mean fasting serum gastrin concentration and the serum gastrin response in absolute values were not different in the two groups. The MAO-BAO/'integrated gastrin response' was higher (p less than 0.05), and the gastrin response in relation to fasting level was lower in the patients than in the controls (p less than 0.05). The results indicate that an increased parietal cell sensitivity to gastrin is present after ileal resection. The negative acid feed back mechanism, however, seems to be at work. Under physiological conditions, therefore, the increased sensitivity may not result in acid hypersecretion.


Serum gastrin response to food stimulation in male azotemic patients. In 37 patients with hypertension and/or renal disease, blood from a peripheral and a renal vein was drawn during renal vein catheterization. The serum gastrin concentrations were determined and found by paired comparison to be statistically significantly (p less than 0.05) higher in the peripheral than in the renal vein. A test meal was given to 9 male controls and 7 male azotemic patients, and the serum gastrin concentration response determined. The mean fasting serum gastrin values were 173 +/- 22 pg/ml in the group of patients versus 42 +/- 5.5 pg/ml in the controls. The serum gastrin response was significantly higher and of longer duration in the azotemic patients than in the controls. The pentagastrin-stimulated gastric acid secretion was, however, equal in the two groups.


Liver disease with periportal sinusoidal dilatation. A possible complication to contraceptive steroids. Four women of fertile age on long-term treatment with contraceptive steroids developed moderate liver damage and hepatomegaly. The liver histology showed a conspicuous periportal sinusoidal dilatation as the only abnormality. The clinical course of the liver damage was benign. The aetiology and pathogenic mechanisms of these changes, which were localized predominantly to Rappaport's Zone I, are unknown. Haemodynamic studies revealed no abnormalities. The connection to possible long-term action of oestrogens and gestagens on the liver, and the relation to peliosis and benign hepatic adenomas, are discussed.


Beta-adrenergic mechanisms and ulcer formation in pylorus-ligated rats. The importance of beta-adrenergic receptor activity for ulcer formation was studied. In rats fasted for 48 hours, ulcers in the rumen were produced constantly after 17 hours of pyloric ligation. d,1,Propranolol in doses of 1 to 30 mg/kg given 4 times during 12 hours caused a dose-dependent inhibition of ulcer formation. The ulcero-protective potency of d,1,propranolol was about 20 times that of d,propranolol. No explanation of the ulcero-protective effect was observed when the gastric acid secretion was studied after 17 hours. Serum gastrin concentration after 17 hours of ligation was in all animals less than 5 pmol per liter, i.e. below one-third of the normal fasting value. For all pharmacological effects apart from beta-adrenergic blockage, d,1, and d,propranolol do not differ, while the results presented here suggest that intact beta-adrenergic receptor activity is important for the development of gastric ulcers in the pylorus-ligated rat. The mechanism behind the ulcero-protective effect of beta-adrenergic blockage remains to be solved.


Fasting serum gastrin and basal gastric acid secretion. The gastric secretion of acid was examined 30 minutes basally (BAO) and in response to stepwise increasing doses of pentagastrin in subjects with (n = 51) and without (n = 40) peptic ulcer disease. None of them showed basal anacidity. Before insertion of the gastric tube, blood was taken for radioimmunological determination of the serum gastrin concentration (SG). A significant positive correlation was found between SG and BAO in the subjects without ulcer. This was mainly due to a close correlation in 20  healthy young volunteers. When BAO and SG was expressed as proportions of calculated maximal acid response (Vmax) and half maximal dose of pentagastrin (Km), respectively, the positive correlation between SG and BAO was improved and reached significance also in the individuals with peptic ulcer disease. The findings suggest that the serum concentration of gastrin plays a role in the basal gastric secretion.


The incidence of Crohn's disease in central Sweden. In an earlier  epidemiological study covering a 12-year period from 1956-67, a gradual increase in the number of patients with Crohn's disease was found. A study of the subsequent 6 years, from 1968-73, is now presented. The mean incidence of the disease for this period is 5.0, compared with 3.1 for the preceding 6 years, 1962-67. As in the earlier 12-year series, the increasing incidence can be attributed largely to an increase in the 15-29 year age group. During the period 1956-67, the disease occurred almost as frequently in men as in women. In the 6-year period now presented, there is a predominance of women, especially over the age of 35.


Heterogeneity in susceptibility to chronic gastritis in relatives of gastric cancer patients with different histology of carcinoma. The morphological state of gastric body mucosa was examined in 269 first-degree relatives of 64 index patients with gastric carcinoma and in 142 subjects selected at random. Gastric carcinoma was divided into three groups according to histological properties: carcinoma mucocellulare, carcinoma adenomatosum, and carcinoma anaplasticum. The state of gastric body mucosa was divided into five stages: normal, superficial gastritis, slight moderate, and severe atrophic gastritis. The results were subjected to the numerical analysis based on the stochastic theory. The term 'age-adjusted score' (AAS) employed therein defines the individual susceptiability to chronic gastritis. In terms of AAS, the material could be divided into 'high' and 'low' gastritis risk families. It appeared that the subjects belonging to carcinoma mucocellulare index patient families had a significantly higher susceptibility to chronic gastritis than the other relatives examined. These families were also significantly concentrated in the group of 'high risk' families. The heterogeneity of the relatives of gastric cancer patients as regards their gastritis risk should obviously be taken into account in future epidemiological studies. These findings constitute further justification of the genetic approach in studies concerning gastritis-gastric cancer relationship.


Quantitative determination of serum bile acids using a purified 3 alpha-hydroxysteroid dehydrogenase. A specific, simple, and reliable method for the quantitative determination  of 3 alpha-hydroxy bile acids in serum in described. It is based on the specific enzymatic conversion of the 3alpha-hydroxyl group of the steroid molecule using a highly purified 3alpha-hydroxysteroid dehydrogenase and fluorimetric determination of NADH. A liquid-solid extraction employing Amberlite XAD-2 has been used. Overall recovery of the major human bile acids from normal and jaundiced serum averaged 91.2%. The range of normal values for serum bile acids was found to be 0.9-6.3 mumoles/1 (mean 3.0).


The effect of beta-adrenergic blockade upon basal and pentagastrin-stimulated gastric acid secretion and upon gastrin response to food. Beta-adrenergic blockade with 10 mg of propanolol had no significant effect upon the spontaneous gastric acid secretion, while the maximum (pentagastrin) acid secretion was depressed in healthy subjects and patients with duodenal ulcer. The gastrin response to food was significantly higher during  beta-adrenergic blockade. It is suggested that a minor part of the maximum acid secretion may be due to activation of beta-receptors, while the gastrin response to food is probably not related to activation of beta-receptors.


Fatty acid patterns of serum triglycerides and subcutaneous adipose tissues after ileal bypass in obesity. A group of 9 obese subjects with a mean body weight of 140 kg was treated for their obesity with a jejuno-ileal intestinal shunt. During the first post-operative year their mean body weight decreased to 100 kg. Fatty acid patterns of triglycerides inserum and subcutaneous adipose tissue were studied at intervals during one year after surgery. Myristic and palmitic acids' contents of serum triglycerides were found to decrease during this period of time, whereas the fatty acid pattern of triglycerides in adipose tissue was practically unchanged. Triglycerides, cholesterol, albumin, and lactate dehydrogenase in serum decreased during the first year after operation, whereas aminotransferases showed a transient elevation. It is put forward that these findings are consistent with starvation rather than liver dysfunction.


Susceptibility of the liver and biliary tract to anaerobic infection in extrahepatic biliary tract obstruction. Bacteriological investigations - an experimental study in rabbits. The influence of common duct occlusion on susceptibility to infection with anaerobic gram-negative rods was investigated in rabbits. Intravenous inoculation was performed with three B. fragilis strains isolated from human infections and with a stock culture of Fusobacterium mortiferum. Liver tissue, gallbladder, bile, and blood were investigated. Anaerobic culture procedures were based on the use of a 'glove-box' with an oxygen-free atmosphere and pre-reduced, anaerobically sterilized media. Anaerobic transport was based on flushing of samples with oxygen-free carbon dioxide and transport-time less than 30 minutes. In regard to two B. fragilis strains (ss. fragilis) and in regard to Fusobacterium mortiferum, common duct occlusion significantly increased the number of infected animals compared to a control group of inoculated animals without common duct occlusion. Spontaneous infection did not arise in a control group of animals with common duct ligation. It is concluded that: 1) in biliary tract occlusion, anaerobic bacteria are able to invade the biliary tract from the blood stream, and 2) biliary tract occlusion produces sufficient anaerobic conditions for obligate anaerobic bacteria to multiply in the bile.


Effect of vagotomy on insulin release after oral and intravenous glucose administration. In 9 non-diabetic, non-obese patients, oral and intravenous glucose tolerance tests were carried out before and after vagotomy, and the serum insulin was determined. The potentiating effect on insulin release of orally administered glucose was not abolished by total vagotomy, meaning that vagal mechanisms are not likely to play a major role in this  potentiation in man.


Healing of duodenal and prepyloric ulcers after selective and highly selective vagotomy. Thirty-six patients with duodenal or prepyloric ulcers who were treated by selective or highly selective vagotomy were followed up endoscopically. In one group of 21 patients examined 2 weeks after the operation, 67 per cent of the ulcers were healed. In another group of 15 patients endoscopy performed 2 months after the operation revealed that 93 per cent of the ulcers were healed. On comparing with previously reported endoscopical observations concerning spontaneous healing of duodenal ulcers, it can be concluded that vagotomy significantly promotes the healing of duodenal and prepyloric ulcers.


Bone marrow biopsy of the posterior iliac crest with Gidlund's instrument in malignant diseases. The bone marrow was examined on material obtained with the Gidlund trephine and with conventional cytologic bone marrow aspiration in 225 patients with malignant disease, 144 of whom had malignant lymphoma, and in 5 patients with haematological, non-malignant disease. With Gidlund's instrument, the malignant disease to 7 cases with needle biopsy. No complications were met with either technique. Bone marrow biopsy was routinely performed in the out-patient department.


Familial leukaemia: a study of 909 families. A family survey was conducted among 909 patients with leukaemia of all types, with the purpose of establishing the incidence of further cases of leukaemia among relatives. Among a total of 41,807 relatives 8,349 were deceased, and the cause of death was objectively confirmed in 5,011. 72 patients had one or more relatives with leukaemia. First degree relatives with leukaemia were much more frequent in families of patients with chronic lymphocytic than in those of patients with chronic granulocytic leukaemia. The incidence of leukaemia among first degree relatives was established to be 2.8-3.0 times, among more distant relatives about 2.3 times, and overall about 2.5 times that expected. This excess is of the order of that observed in relatives of patients with certain solid tumors. Genetic factors may have accounted for much of the excess incidence in chronic lymphocytic and acute leukaemia, but there was little evidence for a genetic background in chronic granulocytic leukaemia. With the possible exception of one family with multiple cases, a simple Mendelian mechanism did not appear to be involved in the leukaemia families investigated. It appeared more likely that a polygenic mechanism led to a heightened susceptibility to the disease in these families.


Hypercalcaemia in chronic lymphatic leukaemia. Hypercalcaemia developed in a patient with chronic lymphatic leukaemia. The hypercalcaemia did not respond to conventional treatment. At bone biopsy osteoclastic resorption was found (a photomicrograph is presented). 7 cases from the literature of hypercalcaemia and chronic lymphatic leukaemia are briefly reviewed. Possible mechanisms are discussed and it is suggested that osteoclast-stimulating factors may be of importance in the development of the hypercalcaemia.


Red cell glucose-6-phosphate dehydrogenase deficiency in Finland. Characterization of a new variant with severe enzyme deficiency. Severe red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency has been found in an 'aboriginal' Finnish family. 2 male and 9 female carriers of the variant G-6-PD were studied. The genetic pattern is consistent with x-linked recessive inheritance and the defect is associated with drug (primaquine) induced haemolysis. This was demonstrated by enzyme deficient red cell (51Cr-labelled) survival studies on a normal volunteer recipient. In addition, one of the hemizygotes studied had a slight chronic nonspherocytic haemolytic disorder. The partially purified enzyme had many of the characteristics of G-6-PD Mediterranean. The occurrence of this G-6-PD Mediterranean type variant in the Finnish population, which differs greatly from Mediterranean ethnic groups, as well as the association of slight chronic haemolysis with severe G-6-PD deficiency is discussed.


The amount of fibrin necessary to give a positive ethanol gelation test at various fibrinogen levels. The minimum fibrin-fibrinogen ratio (f-F ratio) required to give a positive ethanol gelation test at various fibrinogen concentrations was studied. Due to the fact that quantitation of soluble fibrin in plasma is difficult, highly purified fibrinogen was used. However, since a plasma milieu is required to achieve clear cut results with ethanol gelation (with purified fibrinogen alone, precipitation occurs), heat-defibrinated, dialysed and lyophilized normal plasma was added. With this artificial plasma, which in all relevant respects proved very similar to plasma obtained from healthy donors, ethanol gelation was not observed at the highest attainable fibrinogen concentration (1150 mg/100 ml). At fibrinogen levels down to 5-600 mg%, the minimum f-F ratio remained almost constant, but increased gradually by further lowering the fibrinogen concentration. At fibrinogen levels around 50 mg%, the ethanol gelation test remained negative, even in samples saturated with soluble fibrin, i.e. those containing visible fibrin threads.


Griseofulvin inhibition of polymorphonuclear leucocyte chemotaxis in Boyden chambers. Griseofulvin inhibited the chemotaxis of polymorphonuclear leucocytes (PMN's) in vitro in the concentration range 0.1-1.0 mug/ml, i.e. at concentrations comparable to those obtained in serum during peroral treatment with griseofulvin. It is suggested that PMN chemotaxis is inhibited by griseofulvin interference with the redistribution of cytoplasmic microtubules, which is thought to be essential in the direction-finding of PMNs during chemotaxis. Furthermore, it is suggested that the griseofulvin inhibition of PMN chemotaxis - together with the previously known pharmacodynamic properties of griseofulvin - may provide the rationale for griseofulvin therapy in PMN-mediated tissue injury of the gut.


ADP-induced refractory state of platelets in vitro. I. Methodological studies on aggregation in platelet rich plasma. ADP-induced aggregation was determined at various times of incubation with ADP in unstirred human platelet rich plasma (PRP) to which adenosine deaminase was added. In the early stages of incubation the shape change response was absent, the aggregation response was poor, and not reversible. These three parameters returned slowly towards normal as the incubation proceeded. Pronounced impairment of the aggregation response was present after all added ADP had been degraded in plasma. Log dose-response (rate of aggregation) curves for the platelets incubated with ADP had shifted to higher ADP concentrations and had also a small decrease in maximal height and in the slope compared to those obtained with control platelets. However, the shift in log dose response to higher ADP concentrations was far more striking, so the increase in log dose (R) necessary to obtain the same rate of aggregation as with control PRP was taken as a measure of refractoriness of aggregation towards ADP. R increased with the time of incubation to an optimal value and then decreased. The magnitude of the optimal value and the time at which optimum was reached increased with the concentration of the ADP incubated with the platelets. The variations in R during incubation did not correlate with the breakdown of added ADP. The platelets began to recover their ability to aggregate with ADP while there was still ADP in the system.


Transient impaired cell-mediated tumor immunity after acute infection with lymphocytic choriomeningitis virus. Intraperitoneal injection of nononcogenic lymphocytic choriomeningitis (LCM) virus in adult C3H mice causes a symptomless infection but stimulates specific cell-mediated and humoral immune responses. However, median survival time of virus-infected mice inoculated with syngeneic tumor cells was significantly shortened, and growth of semiallogeneic tumors was significantly enhanced. Cell-mediated cytotoxicity measured as chromium-51 release from labeled tumor cells was significantly suppressed but was recovered within 55 days after infection. The suppressed immune responsiveness could be conferreo on a normal spleen cell population when activated in virus-infected recipients. Chronically LCM virus-infected mice showed an unimpaired cell-mediated immune response to tumor allografts.


Enzymatic modification of lymphocyte receptors for antigen III. loss of antigen-responsiveness with recovery after adoptive transfer. Spleen cells from bovine serum albumin (BSA)-primed CBA mice were exposed to proteolysis by papain and pronase under conditions where cell recovery and viability were not impaired but surface Ig and antigen-binding were greatly reduced. The ability of the cells to respond to BSA was tested by a modified Farr assay of serum taken 10 days after adoptive transfer of cells to lethally irradiated syngeneic recipients. Cells not exposed to enzymes were able to respond to BSA either in vitro before adoptive transfer or in vivo after transfer. Cells exposed to papain and pronase were unable to respond in vitro, but normal antibody production was approached when the cells were exposed to antigen in vivo. Thus, after removal of much surface Ig the cells were temporarily unresponsive to antigen but were still functional, as demonstrated by their ability to recover responsiveness in vivo.


Complement dependence of localisation of aggregated IgG in germinal centres. In vivo decomplementation of mice with cobra factor completely prevented trapping of aggregated human IgG within splenic germinal centres. Observations of the intrasplenic position of the aggregated material within 8 hr of its injection into normal and decomplemented mice suggest that the early phase of localisation in germinal centres depends on binding to lymphocyte C3 receptors.


Effect of antiepileptic drugs on serum and salivary IgA. IgA, IgG, and IgM concentrations were determined in sera from 100 patients under treatment for epilepsy for at least 6 months. Low IgA was found in 25% of adult sera and in an even larger percentage of sera from children. IgM concentrations were also low, whereas there was no significant difference in the IgG concentrations compared with normal sera. IgA values were normal in untreated patients but fell during treatment with phenytoin, in one patient from 1.5 to 0.2 mg/ml within 2 months. Low or undetectable salivary IgA was a common finding, especially in gingival hyperplasia.


The incidence of hypospadias in Sweden.

The incidence of hypospadias in Sweden. In a study of the incidence of hypospadias the source material consisted of cases of hypospadias continuously reported to two central registers during the years 1965 to 1968. The material was then extended by the addition of hypospadiacs aged 5 to 9 years and admitted to departments of plastic and pediatric surgery, and in a few cases to departments of urology or surgery, who were not reported to either of the registers. During the years 1965 to 1968, 666 live male infants with hypospadias were identified among a total of 480 607 live births of both sexes in Sweden. The incidence of hypospadias was 13.9 per 10 000 of both sexes. 13.1 of these were single and 0.8 multiple malformations. A systematic grading of hypospadias showed that the mildest, glandular form was present in 62%. Early neonatal deaths with identified hypospadias was 7.


Surgical reduction of adipose tissue hypercellularity in man. Surgical removal of adipose tissue is a widely practised form of plastic surgery most often aimed at correcting cosmetic defects after extreme weight reduction such as a pendulous abdomen. However, it has not been proposed as a cure for obesity. Evidence for an interaction between the adipose tissue mass and regulation of food intake and energy balance might suggest that a reduction of body fat could favorably influence obesity. This study presents body composition data on five patients with a mean body weight of 136 kg with hyperplastic obesity who after a mean weight reduction of 46 kg by conventional therapy were subjected to extensive plastic surgery aimed at removing supernumerary fat cells. Analysis of adipose tissue cellularity revealed that 12-18% of the total number of fat cells were removed by combinations of abdominoplasty and lumbar and femoral adipectomy. There were no indications that this reduction of adipose tissue mass could prevent the recurrence of obesity in these patients, though there was no evidence for regeneration of adipose tissue in situ.


Metacarpophalangeal joint implants. I. Roentgenographic study on the silastic finger joint implant, swanson design. A roentgenographic study was carried out on 104 Silastic Finger Joint Implants, Swanson design. Sixty-two of the implants were examined in the anterio-posterior-projection (AP) from 4 months to 5 1/2 years postoperatively, a total of 116 examinations. Forty-two implants were examined in the AP-projection and in the lateral projection by tomography in maximum active extension and flexion from 9 days to 42 months postoperatively, a total of 110 examinations. Stem fractures were found in 11/104 implants: two of these preceded by a laceration of the implant surface visualized by tomography. Fragmentation of the midsection was found in 14/104 implants. Cortical erosion was seen radially in the phalanx and the metacarpal bone in some joints showing ulnar deviation, predominantly MCP joints II and III. On the tomograms a cortical erosion dorsally in the metacarpal bone could be demonstrated. Particularly around the distal stem was found an intramedullary bone lamella, varying in distance from the stem as well as in density and regularity. Bone resorption was found at the site where the midsection bore on the metacarpal bone and the proximal phalanx, resulting in a migration of the implant in a proximal and/or distal direction. The migration of the implant was evaluated on the tomograms with maximum active extension and classified into 4 Grades. Concomitant with the migration in the proximal direction a bony spur developed volarly at the resected end of the metacarpal bone, also seen in the AP-projection. The degree of maximum joint flexion was measured on the tomograms by drawing a line along the dorsal contour of each bone. In some cases flexion was found to decrease as a consequence of implant migration in the distal direction or the development of a bony spur. In several cases the range of flexion was maintained by gliding of the stems, particularly the distal one.


Metacarpophalangeal joint implants. II. Roentgenographic study of the Niebauer--Cutter Metacarpophalangeal Joint Prosthesis. A roentgenographic study was carried out on 41 Niebauer -- Cutter Metacarpophalangeal Joint Prosthesis from 1 to 36 months postoperatively, a total of 105 examinations. The examinations were performed in the AP-projection and in the lateral projection by tomography in maximum active extension and flexion. The tomographic examinations revealed implant damage of three kinds: cracking within the midsection; fragmentation of the midsection; fracture of the hinge. Cracking within the midsection was found in 8 implants between 6 and 12 months postoperatively and in 1 implant later than 12 months. Later examinations revealed fragmentation of the midsection in 2 implants previously showing cracks. Hinge fracture was observed in 22 implants. Implant damage was found in a total frequency of 26/41. Bone reaction was found on the tomograms in all the operated joints, and could not be evaluated on the AP-projections. A bony spur was found to develop on the metacarpal bone volarly at the site of the osteotomy in 35 joints. In 2 of these the bony spur reached the base of the proximal phalanx, causing anchylosis. Bone resorption was found in 23 joints, constantly dorsally in the metacarpal bone and volarly in the proximal phalanx. The mechanism of the implant damage is discussed with respect to the shearing forces in the joint and the two materials of differing elasticity constituting the implant. The bone reaction is discussed with respect to the intended fixation of the intramedullary stems.


Osteocartilaginous exostosis of the mandibular condyle. Case report. Osteochondroma of the mandibular condyle is extremely rare. An unusual case of a 32-year-old man is reported. Throughout a two-year period the patient suffered from intractable pain in the left T. M. J. region, anterior dislocation of the condylar head, malocclusion and facial asymmetry. Radiologic examination revealed that the cartilaginous cap of an overgrowth had functioned as an articular cartilage. A "pseudo articulation" was created with the prominent articular eminence and allowed an almost free movement of the mandible. Review of the seven reported cases revealed that the rare occurrence, natural history, clinical course and lack of recurrence of osteochondroma of the condylar process all substantiate the contention that this overgrowth must be considered as an osteocartilaginous exostosis rather than a neoplasm.


Metastasizing basal cell carcinoma. Case report. Three cases of metastasizing basal cell carcinoma are presented. Metastases to regional lymph nodes occurred in 2 cases, and to both the humerus and the brain in the third. In all 3 patients, local recurrence developed in spite of apparently radical surgical removal of the primary tumour, and histological examination revealed distinct aggressive growth. The presence of metastases provides further evidence of the existence of an aggressive variety of the basal cell carcinoma. In these cases it is of particular importance that initial radical treatment is performed, and that the follow-up of the patients includes a check of the regional lymph nodes.


Histological studies on granulation tissue from bipedicle tube flaps. Histological studies were performed on granulation tissue from cylinders implanted 2 to 8 weeks and 4 months in bipedicle tube flaps on rabbits. Tissue from cylinders implanted in skin folds were used as controls. Flap and control tissue showed similar changes over the weeks. At weeks 2 and 3 the tissue was rich in cells, blood vessels and collagenous fibres. At week 4 the tissue showed transitional changes to week 5, when there were zones of loosely textured tissue with fine, fragmented collagen fibres. At week 5 some of the loose tissue was replaced by fat. Macrophages and inflammatory cells had appeared. By week 7 the fatty and collagenous tissue was mature and macrophages and inflammatory cells had disappeared.


Blood vessels and connective tissue in autotransplanted free muscle grafts of the cat. After 2 weeks of denervation, whole leg muscles of adult cats were transplanted to intercostal spaces and removed at intervals from 5 days to 44 weeks after grafting. The connective tissue formation and capillary supply of the grafts were studied histologically and histochemically for connective tissue and ATPase. In addition, normal muscles, denervated muscles left in situ, and muscles transplanted without previous denervation were studied. During the denervation period of 2 weeks the capillary network increased slightly. During the first 6 weeks after grafting only a few, thick-walled, irregularly shaped capillaries were present in the grafts. At 8-12 weeks there was a pronounced increase in the vascular supply, coincident with reinnervation of the grafts, and after 40 weeks the capillary pattern appeared fairly normal. In the early stages a marked increase in perimysial and endomysial connective tissue took place. With increasing reinnervation a gradual disappearance of the endomysial connective tissue occurred and in the most mature grafts a minimal increase of perimysial connective tissue remained. In muscles transplanted without previous denervation, extensive fibrotic changes developed.


Wound strength in a clinical material.

Wound strength in a clinical material. A number of investigations on wound strength have earlier been performed, though mostly in experimental animals and on laboratory tissue; comparisons with human tissue are lacking. In this study, the breaking strength of wounds sutured with two different suture materials, polyglycolic acid (Dexon) and a synthetic polyamid (Supramid) was studied in a human material of 56 patients operated for scoliosis in two stages. Wound thickness and wound length (wound area) were considered in the determination of breaking strength. The breaking strength of a 14-day-old wound was about 57 N/cm2 wound area, a value which is quite comparable to the values obtained in experiments on wound healing in animals, such as rats and rabbits. Those experiments can thus be considered relevant also for human tissue. All wounds healed uneventfully and no difference in strength was noticed in wounds sutured with the two different suture materials.


[Disorders of hemoglobin synthesis (exclusive of iron deficiency)]. Hemoglobinopathies in the strict sense most often involve single amino acid substitutions. The clinical consequences, if any, are anemia, erythrocytosis and met-hemoglobinemia. In the thalassemias, which are characterized by microcytosis, unbalanced synthesis of normal globin chains exists and disease severity is primarily determined by the amount of relative overproduction of the unaffected chain: thus, the unstable chain tetramers precipitate and lead to ineffective erythropoiesis and hemolysis. The sideroblastic anemias are a heterogeneous group of pathological conditions, both clinically and pathogenetically. Heme synthesis appears to be regularly disturbed, but this is probably not the sole defect. Other alterations of globin and heme synthesis are listed and briefly discussed.


Virus B hepatitis in greater Glasgow.

Virus B hepatitis in greater Glasgow. During the 2-year period (1971-72), 71 patients with virus B hepatitis were studied in Greater Glasgow. In this region, virus B hepatitis is most prevalent in adult males. With the introduction of routine screening of the blood donor population for HB Ag, there has been a significant reduction (p less than 0.02) in post-transfusion hepatitis. Seventy per cent of the patients in 1972 had no obvious history of exposure to HB Ag. Twenty seven per cent of the patients in this series had severe hepatitis. For clarification of our understanding of the natural history of virus B hepatitis in Greater Glasgow, further co-ordinated study is needed.


Urinary zinc in hepatic cirrhosis.

Urinary zinc in hepatic cirrhosis. Plasma Zinc and renal clearance of Zinc have been studied in patients with various chronic hepatic disorders. Plasma Zinc levels were reduced in patients with all forms of chronic hepatic disease and were of no value in differentiating these conditions. The renal clearance of Zinc was found to be significantly higher in patients with chronic hepatic disease of alcoholic aetiology (1.25 ml./min.) compared with those of non-alcoholic aetiology (0.52 ml./min.) and normal subjects (0.33 ml./min.). The renal clearance of Zinc may be of value in identifying chronic hepatic disease in which alcohol is aetiologically involved.


Primary cardiac leiomyosarcoma with pulmonary metastases: a diagnostic problem. A case of primary cardiac leiomyosarcoma is reported. Tumour growth into the right ventricular cavity led to multiple pulmonary metastases with haemorrhage. Failure of diagnostic procedures including cardiac catheterisation, angiography and thoracotomy is noted. The incidence and presentation of primary malignant cardiac tumours is briefly discussed.


The value of ultrasonography in the diagnosis of abdominal aortic aneurysm. An evaluation of ultrasonography in early dilatation and aneurysm is presented. Fifty-nine patients with prominent abdominal pulsation were examined and aneurysm was demonstrated in 22. There was a high degree of correlation between the size of the aneurysm demonstrated by ultrasound and the size displayed at operation. It was also possible to demonstrate increasing dilatation by measurement on subsequent occasions.