Contractile effects of prostaglandin F2alpha on isolated human peripheral arteries and veins.

The effects of prostaglandin F2alpha (PGF2alpha 2.8 X 10(-7) --2.8 X 10(-5) M) on isolated segments of human peripheral arteries and veins were investigated. In both types of vessel, PGF2alpha had a concentration-dependent contracting effect. The contraction developed more slowly and had a longer relaxation time after washing than responses induced by noradrenaline or potassium. In the veins, the maximum response to the prostaglandin was 128 +/- 3.6% of that to potassium (P less than 0.01); in the arteries, the maximum amplitudes of PGF2alpha and potassium induced contractions were of similar magnitude. The arterial preparations were less responsive to PGF2alpha than to noradrenaline. On a molar basis, noradrenaline was approximately 10 times more potent than PGF2alpha. Veins, maximally contracted by noradrenaline or potassium, increased their tension further on addition of PGF2alpha. Similarly, preparations maximally contracted by PGF2alpha also showed a further increase in tension after addition of noradrenaline or potassium. The PGF2alpha induced contractions were not affected by alpha-adrenoceptor blockade (phentolamine, prazosin). The calcium antagonists verapamil and nifedipine relaxed preparations contracted by PGF2alpha, and reduced the responses in a concentration-dependent way when added 15 min. before the prostaglandin. Immersion for 30 min. in a calcium-free medium, reduced the PGF2alpha induced response in both arteries and veins. In the veins, but not in the arteries, the responses to potassium and noradrenaline were more reduced than that to PGF2alpha (P less than 0.01). Contractions induced by all agents were further depressed by verapamil and nifedipine after exposing the preparations to the calcium-free medium. It is suggested that PGF2alpha induces contraction both by enhancing the transmembrane flow of calcium, and by facilitating release of calcium from intracellular stores.


Effect of ritodrine on the bladder capacity in unanaesthetized pigs.

A cystometric investigation was carried out in unanaesthetized pigs. During intravenous infusion of ritodrine (10, 30 and 50 microgram/kg/min.) a dose-dependent and significant increase of the bladder capacity was obtained. A concomitant significant elevation of the heart rate followed the administration of the drug.


Neurotransmitted responses of smooth-muscle strips of complex sheep stomach after electrical field stimulation.

Contractile responses to stimulation of nerve elements in smooth-muscle strips of complex sheep stomach suggest the existence of inhibitory and excitatory nerve structures in preparations from all compartments. Pharmacological analysis of the responses shows that they are mediated by cholinergic excitatory, noncholinergic excitatory and nonadrenergic inhibitory nerve elements. Comparison of the distribution of the cholinergic nerve structures shows that there are no essential differences between the different compartments. Differences are observed between strips cut in the direction of the two muscle layers, the effect of the cholinergic nerve elements being more pronounced in the longitudinal strips compared with the transverse ones. Noncholinergic excitatory effects of nerve stimulation are observed in all compartments of the complex stomach. Nonadrenergic nerve structures with inhibitory effect on the muscle strips are found in all compartments of the stomach. It is assumed that in the rumen they have spontaneous activity which inhibits the capacity of the smooth muscles in this part of the stomach for spontaneous phasic contractions.


Comparative studies of colon reactivity of healthy and ionization-radiated guinea-pigs to some spasmogens and their antagonists.

Comparative studies were carried out of the contractile effects of acetylcholine (1 X 10(-6) M), histamine (1 X 10(-6) M), serotonin (1 X 10(-5) M), nicotine (1 X 10(-5) M), BaCl2 (1 X 10(-3) M) and of the influence on the induced contractions caused by the antagonists of these spasmogens, namely: atropin (1 X 10(-6) M), dipenhydramine (1 X 10(-6) M), benzyloxygramine (1 X 10(-5) M), hexamethonium (1 X 10(-5) M) and papaverine (1 x 10(-5) M) on isolated segment of guinea-pig colon. Experimental acute radiation sickness is found to induce considerable changes in the reactivity of the intestinal smooth-muscle preparation used to the spasmogens applied and to their antagonists. Depending on the nature of the pharmacological agents, the degree of development of the experimental acute radiation sickness, and on other factors, the changes in the reactivity to the drugs tested revealed very great qualitative and quantitative differences. The following more definite changes could be pointed out. The spastic effects of serotonin and BaCl2 were potentiated, while the spastic effects of histamine and nicotine showed a tendency toward decrease. Under conditions of acute radiation sickness tha antagonistic effect of atropine to acetylcholine was intensified, while the antagonistic effects of benzyloxygramine to serotonin, of hexamethonium to nicotine and of papaverine to BaCl2, grew weaker. Diphenhydramine showed potentiated antagonistic effect to histamine on the 72nd h after radiation. Certain possibilities are discussed concerning the mechanisms underlying the changes in the reactivity of the intestinal smooth muscle to pharmacological agents, induced by acute radiation sickness.


Effect of oxytocin on the blood glucose concentration.

Blood-glucose concentration is tested in male volunteers before and on the 1st, 3rd, 7th, 15th, 20th, 30th and 60th min after intravenous administration of oxytocin in doses of 0.1 IU/kg. In the first minutes after the injection there is a hypoglycaemic tendency in the changes of the blood glucose concentration, maintained in 60 per cent of the cases, while in the remaining subjects slight hyperglycaemia after the 7th min is observed. Simultaneously, hyperemia of the skin, moderate decrease in the diastolic blood pressure and tachycardia are observed. The effect of oxytocin is associated with increased influx of blood in the adipose tissue, where the glucose is metabolized with the involvement of the specific oxytocin receptors. The late hypoglycaemia is associated with oxytocin-inhibited insulin decomposition, the hyperglycaemia--with the domination of the sympathoadrenal activation in some of the subjects examined. A conclusion is reached that the effect of oxytocin on carbohydrate metabolism is physiologically unimportant.


On the vascular action of crataemon.

The vascular action of crataemon is studied. The effect of the drug on organ blood flow is examined using isotope methods. It is established that under conditions of blood loss, 10 mg/kg crataemon sharply inceases the blood supply to the myocardium and liver. Under the same conditions the blood flow in the kidneys and intestines decreases after administration of the drug. Its effect is weaker in case of normal blood pressure. In the case of perfusion of cat hind legs the flavonoid mixture studied has a biphasic effect manifested in the form of initial brief hypertension, followed by a more prolonged and stronger depressor reaction. In larger oral doses (100 and 200 mg/kg) crataemon increases the resistance of the capillaries and decreases capillary permeability in albino rats. The experiments carried out confirm the predominantly action of crataemon on some vascular regions (heart and liver). It has biphasic effect on peripheral vessels, which may be attributed to the presence of different components. The capillary-tonic action is most probably due to the presence of rutin and rutin-like flavonoids.


On the mechanism of the anti-inflammatory action of the newly-synthesized benzoylpyrazolone derivatives.

One of the basic mechanisms of action of the nonsteroid anti-inflammatory agents is associated with prostaglandin synthesis. The effects of 1-phenyl-3-methyl-4 (4)-chlorbenzoylpyrazolone-5 (No. 151) and 1-phenyl-2-benzoyl-3-methylpyrazolone-5 (No. 76) on the quantity of prostaglandins and on the invasion of polymorphonuclear leucocytes in inflammatory exudate have been studied. Experimental inflammation is induced after Higgs et al. (1976). The level of prostaglandins in the exudate is determined through cascade superfusion of isolated smooth-muscle organs. The level of prostaglandins is found to decrease in animals treated with No. 151 and indomethacine, and to increase under the effect of No. 76. The invasion of the focus with polymorphonuclear leucocytes is inhibited by No. 151 and indomethacine. On the basis of the results obtained, No. 151 is assumed to belong to the group of prostaglandin-synthetase inhibitors, according to its mechanism of action.


Pyronin--a fluorescent indicator of membrane potential of the mitochondria. Mechanism of action.

The effect of the functional state of isolated mitochondria on the fluorescence of pyronin added to the suspension is studied. It is shown experimentally that the intensity of fluorescence changes parallel to the degree of energization of the mitochondria. The magnitude and the sign of the fluorescent changes depend on the pyronin/mitochondria ratio and the length of the wave of excitating light. Model experiments show that the effects observed are probably due to the electrophoretic redistribution of pyronin between the medium, the mitochondrial membrane and the matrix, induced by the membrane potential of the mitochondria. It is assumed that pyronin acts as vector fluorescent indicator, similar to anilinonapthalenesulphonate.


Estimating the orientation of a dot pattern.

Thirty three subjects were tested to estimate the orientation of a dot pattern presented on a vertical screen. The subjects were asked to describe verbally the orientation of the pattern and afterwards to determine the point of intersection between the imaginary "line of orientation" of the dot pattern and a scale presented on the screen at some distance from the pattern. The subjects were inclined to give an integral description of the test stimulus such as "a constellation of dots" or "a cloud of dots" and to assign an orientation to this stimulus that corresponds to an invariant geometrical characteristics of the pattern--the line for which the sum of the squared distances to each dot of the pattern is minimum.


Effects of isoprenaline and cooling on histamine induced changes of capillary permeability in the rat hindquarter vascular bed.

Histamine infused intra-arterially into artificially perfused, maximally dilated rat hindquarters markedly increased fluid filtration and CFC but had essentially no effect on the diffusion capacity to small molecules. Isoprenaline largely prevented the increase in fluid filtration and CFC if infused prior to the start of the histamine infusion and, if infused after the start of the histamine infusion, promptly reduced fluid filtration and CFC to near control levels. Additionally, it was noted that severe cooling of the perfusate also largely prevented the marked increase in fluid filtration and CFC by histamine. This antagonism of histamine induced increases in macromolecular permeability represents a direct action of isoprenaline on the microvascular membrane which effectively counteracts that of histamine. The data also suggest that the large pores created by histamine are different from the large pore through which macromolecules normally transverse the microvascular membrane, and that catecholamines may exert a regulatory function in the control of microvascular permeability to macromolecules in pathophysiological states associated with massive histamine release.


Aspects of temperature regulation in harp seal pups evaluated by in vivo experiments and computer simulations.

Temperature regulation in harp seal pups (Pagophilus groenlandicus) has been studied by in vivo measurements of oxygen consumption, body temperatures and in vitro determinations of the thermal values of a fur sample. The experimental animals were restrained and exposed to natural wheather conditions. Solar irradiance above 600 W/m (global radiation) caused hyperthermia. Computer simulations based on the thermal values of the fur indicated that heat dissipation from primarily the limbs is a prerequisite for avoiding hyperthermia under natural weather conditions. Further simulations showed that the lower critical temperature of a lean newborn harp seal pup with standard metabolism is only--1 degree C while it is depressed to--59 degree C as the pup grows, aquire a 10 cm thick layer of blubber and the metabolism increases to 1.5 times standard. High metabolism and tolerance to low deep body temperatures (35 degree C) seems a prerequisite for thermal balance in the harp seal pup under cold conditions.


Antilipolytic effect of adenosine in isolated perifused fat cells.

Adenosine markedly inhibits cyclic AMP accumulation in isolated fat cells, whereas inhibitory effects of adenosine on lipopolysis have been difficult to demonstrate. The present study has been performed on isolated "perifused" fat cells where continuous monitoring of the lipolytic rate is possible and where modulating substances, such as adenosine, are not allowed to accumulate. Adenosine deaminase was ineffective as a lipolytic agent in perifused fat cells, suggesting no important background activity of adenosine in this system. Micromolar concentrations of adenosine inhibited lipolysis induced by noradrenaline (0.3--1 micrometer) and theophylline (1 mM). Theophylline was an effective lipolytic agent also in perifused fat cells suggesting that antagonism of adenosine is not the major mode of action of this drug on fat cells.


"Fast" and "slow" skeleto-fusimotor innervation in cat tenuissimus spindles; a study with the glycogen-depletion method.

The glycogen-depletion method was used to investigate the motor supply to tenuissimus with respect to the presence of fast beta axons and to assess the total proportion of both fast and slow beta-innervated spindles in this muscle. In a first series of 5 expts., groups of motor axons with conduction velocities higher than 85 m/s were repetitively stimulated so as to produce glycogen depletion in the muscle fibres they innervated. The whole muscle was then quick-frozen, serially cut, stained to demonstrate glycogen and examined for intrafusal glycogen depletion. Zones of glycogen depletion were found in 16 of the 46 examined spindles; they were most frequently located in the longest of the chain intrafusal muscle fibres. Since it is known that there are no purely fusimotor axons to tenuissimus with conduction velocities above 50 m/s, it was concluded that beta axons are present among the fastest axons to this muscle. In a second series of 5 expts. as many motor axons as possible with conduction velocities above 60 m/s were stimulated. Zones of glycogen depletion were found in 19 of the 47 examined spindles. They affected chain fibres in about half of the instances and bag1 fibers in the others. As this latter location is characteristic of slow dynamic beta axons, it was concluded that both slow and fast beta axons occur regularly in the motor supply to tenuissimus. beta-innervation is present in at least 40% of tenuissimus spindles with almost no convergence of fast and slow beta axons onto the same spindle.


Bronchial and cardiovascular actions of prostaglandin endoperoxides and an endoperoxide analogue.

Effects of PGG2, PGH2 and the endoperoxide analogue, EPA, on bronchial and vascular smooth muscle were studied in vivo and in vitro. In the cat PGG2, PGH2 and particularly EPA proved potent stimulators of airway resistance, and they were all significantly more active than PGF2 alpha. They also increased pulmonary vascular resistance but EPA alone was more active than PGF2 alpha. In guinea pigs EPA was 90--190 times more active than PGF2 alpha in increasing tracheal insufflation pressure. Human bronchi contracted in response to PGG2, PGH2 and EPA. PGG2 and PGH2 were equiactive with PGF2 alpha and EPA was more than 500 times as potent. PGG2 and PGH2 lowered systemic arterial blood pressure and increased heart rate in cats. They were as active or more active than PGE2, EPA, on the other hand, resembled PGF2 alpha in producing biphasic changes of blood pressure and heart rate or decrease of blood pressure and bradycardia in guinea pig and cat. The results obtained in this study indicate that PGG2, PGH2 and EPA are potent stimulators of bronchial and pulmonary vascular smooth muscle. The data are also consistent with the view that a significant proportion of effects resulting from prostaglandin generation in the lung is due to prostaglandin endoperoxides rather than primary prostaglandins.


The influence of supraspinal impulse activity on the intra-axonal transport of acetylcholine, choline acetyltransferase and acetylcholinesterase in rat motor neurons.

The effect of supraspinal impulse activity upon the intra-axonal transport of acetylcholine (ACh),  ACh esterase (AChE) and cholineacetyltransferase (CAT) in rat sciatic nerve has been studied. A decreased inpulse activity was obtained by spinal cord transsection (SCT) in the thoracic region 18 h, 6 days or 20 days before killing the rats. An increased neuronal activity was obtained by exercising the rats in a commercial rodent treadmill a couple of hours per day for 14 days. The amounts of substances which had accumulated in the sciatic nerve segments relative to a nerve crush performed 12 or 18 h. earlier were used to calculate the intra-axonal transport. The amounts of proximo-distal transported ACh decreased markedly with time after the SCT, while the proximo-distal transport of AChE-activity increased. Physical exercise appeared to increase ACh-transport. Thus, input to motor pericarya from supraspinal centers may regulate intra-axonal transport from the cell body of motor neurons into their axons.


Phosphoryl group transfer from Ehrlich cells prelabeled in vivo with (32P)-orthophosphate and (14C)-glucose to unlabeled glioma cells.

A transfer of (32P)-labeled phosphoryl groups has been demonstrated to occur between prelabeled Ehrlich cells (donor cells) and glioma cells (acceptor cells). The Ehrlich cells were generally prelabeled in vivo by an intraabdominal injection of (32P)-orthophosphate 24 hours prior to scarifice of the tumor-bearing mice. In some experiments two injections of (14C)-glucose were given to the animals in addition to the injection of (32P)-orthophosphate prior to sacrifice. The prelabeled Ehrlich cells were mixed with the glioma cells, that were still attached to the culture plates, and incubation took place in vitro. Labeled (32P)-phosphoryl (14C)-serine was isolated from the glioma cells as well as from the Ehrlich cells. The 32P/14C-ratio of (32P)-phosphoryl (14C)-serine of the glioma cells (acceptor cells) was significantly higher than found for the Ehrlich cells (donor cells). This was indicative of an interactive mechanism between the cells partly due to binding of membrane fragments from the Ehrlich cells on to the surface of the glioma cells and partly due to a phosphoryl group transfer between the two types of cells. Interaction experiments with a plasma membrane fraction prepared from the prelabeled Ehrlich cells vis à vis the glioma cells clearly showed that the phosphoryl group transfer mechanism between the cells was dominating and only a minor part of the interaction was due to adhesion. This transphosphorylation reaction represents a new type of interaction between cells. It was not influenced by either adenosine 3', 5'-monophosphate or adenosine 5'-diphosphate.


The distribution and secretion of kallikrein in some exocrine organs of the rat.

Extractable kallikrein was quantitated in the submandibular, sublingual, and parotid glands and in the pancreas. No kallikrein was detected in the exorbital lacrimal glands and tears. The highest kallikrein concentrations (EU/ml) were in all major salivary gland secretions seen after alpha-adrenergic stimulation, less after beta-adrenergic and least after parasympathetic stimulation. When taking into account the large variations in salivary flow rate, alpha-adrenergic stimulation was in the parotid and particularly in the submandibular gland found to result in the highest kallikrein secretory activity measured by the kallikrein secretory rate(EU/min). This shows that the kallikrein-rich granular tubular cells are selectively activated through alpha-adrenergic sympathetic receptors. The differences observed in the parotid saliva were small and not always statistically significant. However, when cervical nerve stimulation was superimposed upon parasympathetic stimulation, kallikrein secretory rate as well as kallikrein concentration increased. The large individual variations in salivary gland kallikrein content and secretion and the rather small differences observed in kallikrein secretory rate after nervous stimulation of the parotid and sublingual glands, may indicate that the kallikrein-containing striated ducts are also influenced by factors other than the secretory nerves. The kallikrein concentration and secretory rate in urine was studied. A strong positive correlation between kallikrein secretory rate and fluid volume was found in urine but not in saliva.


The effects of ureteral occlusion and renal venous constriction on kidney kallikrein-kinin and prostaglandin systems in dogs.

The intrarenal pressure was raised to 40--50 mmHg by ureteral occlusion or by renal venous constriction in anesthetized dogs loaded with 10% mannitol in saline and with a urine flow of approximately 1 ml/min/kidney. Both manoeuvres produced vasodilation and decreased urine creatinine excretion (GFR). Ureteral occlusion was associated with a marked antinatriuresis, which contrasted the variable decrements in sodium excretion during renal venous constriction. Ureteral occlusion did not affect urine excretion of kallikrein or kinins, whilst renal venous constriction decreased urinary kallikrein excretion, yet markedly increased urinary kinin excretion. Ureteral occlusion and renal venous constriction comparably increased urine prostaglandin (E-like) excretion by a presumably pressure dependent mechanism. Inhibition of prostaglandin synthesis by indomethacin abolished the vasodilation during renal venous constriction and this was accompanied by marked reductions of urinary creatinine (GFR) and kallikrein excretions, whilst the kinin excretion was enhanced as observed before the administration of indomethacin.


Release of substance P-like immunoreactivity into the antral lumen of cats.

SPLI can be detected in antral perfusates of cats. Experiments were performed in anesthetized cats provided with antral pouches. The pouches were perfused with 0.1 M HCl and 0.15 M NaCl. The concentration of SPLI in the perfusates was determined by radioimmunoassay. Basal output varied between 0--60 pg/min. Electrical vagal stimulation (2--10 Hz) caused release responses varying between 100--800 pg. Ach given i.v. or intraantrally also released SPLI into the antral lumen as well as adrenaline given i.v.


Sympathetic innervation of the urinary bladder and urethral muscle in the pig.

The sympathetic innervation of the lower urinary tract was studied in the female and male pig using a specific histochemical technique for visualization of noradrenaline containing nerves. In smooth muscle from the detrusor few evenly distributed adrenergic nerve terminals were found. A greater number of terminals were observed in the trigone, bladder neck and urethra. There was no sex difference. In smooth muscle specimens from pig detrusor and trigone sympathetic nerve terminals were more abundant than in corresponding tissue from humans.


Effect of synthetic substance P on internal carotid artery blood flow in man.

Internal carotid artery blood flow was studied by peroperative electromagnetic blood flow measurement in 7 patients following 9 intravenous infusions of synthetic Substance P, 2 ng.kg-1.min-1. The blood flow responses varied interindividually. No significant blood flow changes were observed for the whole group. The arterial mean blood pressure decreased significantly.


Abdominal radiation response modified by hypoxia after intra-aortal injection of starch microspheres. Experiments in the rat.

Degradable starch microsphers were injected in the aorta of rats above the level of the superior mesenteric artery 5 min before roentgen irradiation of the abdomen. The local hypoxia, induced by the spheres, was found to have an appreciable protective effect. The dose modification factor was estimated as 0.7.


Secretion of 99Tcm in breast milk after intravenous injection of marked macroaggregated albumin.

A nursing mother received 99Tcm-macroaggregated albumin intravenously for a lung scan. Milk was pumped out at the times when feeding normally took place for three days and the activity was determined. The 99Tcm concentration diminished almost exponentially with an effective half-life of about 4 h. The radiation dose (26-0.001 muGy) was estimated to be so small that the risk to the child may be regarded as negligible.


Thyroid carcinoma induced by irradiation for Hodgkin's disease. Report of a case.

In a 22-year-old male, who had been irradiated 16 years previously for Hodgkin's disease, a radiation-induced thyroid carcinoma developed. This was the only case with such development in a group of 207 cases with Hodgkin's disease who were treated by irradiation including the thyroid gland.


Radiation effects on the fine blood vessels in abdominal organs of mice.

The capillary networks of normal and irradiated abdominal organs of mouse were investigated by a resin cast technique. The structure of the capillary system had characteristic appearances. Radiation effects on the fine vascular structures were demonstrated from one appearances. Radiation effects on the fine vascular structures were demonstrated from one to 30 days after a single dose of 5 to 30 Gy whole body irradiation. Prominent morphologic abnormalities of the shape and distribution of the capillaries were identified, especially in the small intestine.


Catecholamines in some hypothalamic and telencephalic nuclei of food deprived rats.

The influence of 48 h food deprivation on the levels of catecholamines was investigated in different hypothalamic and telencephalic nuclei of the rat brain. There were on changes in the levels of noradrenaline (NA) and dopamine (DA) in the lateral hypothalamic area, dorsomedial nucleus, medial preoptic area and in nucleus of diagonal band (septum). On the other hand we observed a statistically significant decrease of NA and DA in the ventromedial nucleus and the decrease of NA in the arcuate nucleus.


Visual discrimination in cats: physical parameters of stimuli and effects of visual cortex ablation.

Correct reaction probability and minimum exposition time in visual form discrimination task were studied under the conditions of varying pattern parameters. The minimal exposition time depended on pattern contrast and pattern background ratio and on the number of screen position variations. However, it remained unchanged when the background luminance and pattern size varied within the suprathreshold range. The deficits of discrimination in the minimal exposition time conditions in animals with damages to the striate and parastriate cortical regions suggest that the visual cortex participates in the analysis of shortterm stimuli and is responsible for prolongation of the visual trace within the time necessary for object discrimination.


The interactions of central neurons in conditioning and the influence of some limbic structures upon them.

The interactions between the neurons in the cortex and the subcortical visual structures were studied with multimicroelectrode technique. Neurons revealing conditioned reactions were found at various levels of the brain. It is assumed that they are involved, by the conditioning, in a special cellular network: the microsystem, which is considered to be the definite functional level of brain processing mechanisms. The influence of some limbic structures on the formation of the microsystems of conditioning neurons was found. It was concluded that the elaboration or extinction of the temporary connection is performed through formation or destruction of a microsystem which takes part in the conditioning.


Lumbo-omental shunt for drainage of cerebrospinal fluid in hydrocephalus.

A new cerebrospinal fluid (CSF) shunting procedure is presented. By transposing a pedicle graft of the greater omentum to the lumbar CSF compartment, the CSF absorption capacity of the omentum is utilized. The operation is applicable to the treatment of communicating hydrocephalus. The technical problems and physiological effects of the operation have been studied earlier in dogs. This paper presents the first case of an intended clinical series. The patient was studied for 18 months postoperatively by different examinations, including psychometric tests, cisternography, computer tomography, echo-ventriculography, and carotid angiography with measurement of the cerebral blood flow. A gradual improvement in his clinical state was registered after the operation.


Microsurgery of tumours of the frontal white matter.

Seventy eight microsurgical extirpations of tumours located in the frontal white matter led to adjustment of the normal anatomy of the frontal brain according to microsurgical requirements, and also to relation with modern diagnostic procedures, especially computerized tomography (CT-scanning). The advantages of microsurgical treatment have been demonstrated. Thus, only exact comprehension of topographical anatomy allows a methodical, careful, and radical procedure. As vessels were commonly saved, postoperative courses were relatively benign because of less tendency to oedema. Out of 78 patients, 3 died while in hospital, and two recurrences were observed in the following 23 months. Postoperatively 51 patients improved, 18 stayed unchanged neurologically, and 9 patients deteriorated permanently. The usual microsurgical instruments were employed. Vascular problems were dealt with by the routine techniques used at our hospital.


Cerebral revascularization.

Cerebral vascular insufficiency due to occlusive lesions regarded as inaccessible is a common problem. The degree of cerebral dysfunction associated with such lesions is dependent in part on the amount of collateral circulation present. By anastomosing the superficial temporal artery to a branch of the middle cerebral artery an increase in collateral circulation is provided to the affected hemisphere. This report describes the results of twenty such procedures. Postoperative angiography demonstrates a 90% patency rate. There is frequent neurological improvement following surgery, and the rate of new TIA's or strokes seems less than would be expected. The most damaging complication of the procedure ist intracerebral haemorrhage. The indications for, and the complications of, such procedures are discussed.


Bilateral internal carotid artery thrombosis after closed head injury.

A case of bilateral internal carotid artery thrombosis after blunt injury to the head in a 54 years old male is described. The literature is reviewed and comment is made on the causes. Unilateral thrombosis of the internal carotid artery after closed or blunt injury to the head and neck is well known but not common. There is only one previously recorded case of bilateral internal carotid artery thrombosis after such an injury (Yashon et al. 1964).


Intracranial pressure and pressure volume relation in patients with subarachnoid haemorrhage (SAH).

The development of the intracranial pressure after a subarachnoid haemorrhage was evaluated in 21 patients. A statistically significant relation between the intracranial pressure and the neurological findings was found, whereas vasospasms did not influence the intracranial pressure. In patients in a clinically critical condition, rhythmic pressure waves of a frequency of 1/minute were repeatedly observed.


Infantile craniosynostosis: clinical, radiological, and surgical considerations based on 100 surgically treated cases.

One hundred children affected by craniosynostosis were operated on from January 1952 to February 1977. Forty-six patients were operated on within the first year of life, and only 9 after six years of age. In 27 cases only one cranial suture was synostotic (mostly the coronal: 15 cases). In 36 cases two sutures were involved (mostly coronal plus sagittal: 25 cases). In 28 cases all the cranial sutures were involved. Also included in this series are seven cases of Crouzon's, one of Apert's, and one of Carpenter's syndromes. The clinical, radiological, and surgical features of this condition are discussed, and the long-term results are reported.


Intracranial pressure in patients with diffuse cerebral arterial spasm following ruptured intracranial aneurysms.

Intracranial pressure (ICP) was recorded continuously in 12 pre-operative patients with angiographic evidence of diffuse cerebral arterial spasm due to a ruptured intracranial aneurysm. Recordings were made for 1 to 7 days, starting within 13 days after the haemorrhage. 1. An increased ICP was observed in the first week after subarachnoid haemorrhage (SAH) in 4 of the patients without any signs of angiographic arterial spasm. 2. This initial increase was regularly followed by a depression of ICP in between 7--12 days after SAH. In 11 out of 12 patients such a depression was concomitant with the beginning of arterial spasm. During the period of depressed ICP pattern, 6 patients showed little or no neurological deterioration, whereas 5 patients showed impaired consciousness or neurological deficits. 3. A secondary rise of ICP thereafter always followed due to ischaemic brain swelling or infarction, and was usually associated with a serious neurological deterioration. 4. Continuous ventricular drainage was performed to control the secondary increased ICP in 7 patients who survived, 4 of them with good clinical improvement and 3 with severe neurological deficits. 5. In the stage of depressed ICP, the administration of isoproterenol and steroids is recommended in order to try to alleviate the secondary rise of ICP.


Vasospasmogenic substance produced following subarachnoid haemorrhage, and its fate.

Fresh blood and supernatants of blood-CSF mixtures incubated for 1 to 15 days were applied to the basilar artery of adult cats, and the degree of constriction was measured with a surgical microscope. The constriction due to fresh blood was weak and transient. It seems possible to assume that serotonin isolated from platelets participates greatly in the transient vasoconstriction induced by fresh blood. Supernatants of blood-CSF mixtures incubated for three days had weak activity in comparison with the powerful and long-lasting activity of those incubated for seven days. Furthermore, mixtures incubated for 15 days had little or no activity. This change in the vasoconstrictive activity was similar to, and coincides chronologically with clinical late spasm following subarachnoid haemorrhage 34. We investigated the vasospasmogenic substance in the seventh day mixture. Heat coagulation, ultrafiltration, sephadex G-100 gel-chromatography, disc-electrophoresis, and Spectrophotography show that extracellular oxyHb has a strong spasmogenic activity. In the 15th day mixture, oxyHb is spontaneously converted to metHb. Experimentally, oxyHb has a strong vasoconstrictive activity, and metHb has no vasoconstrictive activity. We have had success in oxidizing oxyHb into metHb with sodium nitrite, thus preventing experimental vasospasm.


Position paper on RDA for protein for children.

The Recommended Dietary Allowances (RDA) by the National Academy of Sciences are revised approximately every five years. The RDA are compromise opinions of highly qualified nutritional scientists based on interpretations of available data. As with any interpretations of available data. As with any, interpretations and opinions not found on definitive information, they are subject to challenges. The RDA for protein for 7-to 9-uear-old children have been adjusted downward from 60 g in 1958 to 36 g in 1974, a 40% reduction. Data from our laboratories have shown positive apparent nitrogen balances on intakes as low as 18 g daily when no allowances were made for integumental and other nitrogen losses, however, based on accumulative data over several years we calculate the protein requirement to be 45 g daily from a typical American diet. If a safety factor of 30% is added the allowance would become 58.5 g. Currently the RDA for protein for the 7- to 10-year-old child supplies 6% of the RDA for Calories which contrasts to 8.30 and 9.20% for adult males and females, respectively. For comparison, energy from protein as a percentage of total energy for some common foods are: white bread, 12%; corn meal 10%; white rice 7%; and wheat flour 13%.


Urea as a dietary supplement for humans.

Use of urea as a nonprotein supplement in the feeding of beef cattle and other ruminant animals is a technique of practical application. Urea has also been used in human feeding studies. Its early employment was that of an added source of amino nitrogen in studies designed to determine minimum requirements of the essential amino acid. Later studies suggested that it's inclusion in diet containing sub-optimal amounts of protein supplied by various food product could result in the establishment of apparent improvement in protein nutriture. Other studies indicate that urea is not unique in this ability but is only one of many possible sources of amino nitrogen and is actually one of the least effective. Known and potential hazzards definitely prohibit the use of urea supplements to food products other than in research or clinical laboratories at the present time.


Hair as an index of protein malnutrition.

Hair samples from seven sick Ghanaian children were analyzed for amino acids. Cystine was determined by a procedure of Friedman using tributylphosphine and 2-vinylpyridine to change residues of cystine (and cysteine, if present) to S-beta-(2-pyridylethyl)-L-cysteine (2-PEC). This acid-stable derivative is released by normal acid hydrolysis and is eluted as a well-resolved peak before lysine in conventional ion-exchange amino acid analysis. The average cystine content of six children suffering from kwashiorkor or marasmic kwashiorkor was found to be about 20% less than that of the one remaining child, whose protein nutrition was judged adequate. In view of conflicting evidence of the relation of hair cystine content and nutrition, we believe further definitive studies of this subject are urgent. No other substantial difference in amino acid composition was noted.


The problem of curvature in slope assays for protein quality.

The dose-response curves in a valid slope--ratio assay must be linear and meet at the zero protein dose. However in rat bioassays at least 3 types of curvature are found when the method is applied to a wide range of samples; the types of curvature result from: 1) excessive protein 2) lysine deficiency and 3) threonine deficiency. Whole wheat flour which was limiting in lysine and threonine showed marked downward curvature after supplementation with threonine. It can be argued from these results that the slope ratio and relative protein value method underestimated the protein quality of lysine--deficient foods.


Defining dietary plant fibers in human nutrition.

Research on the nutritional aspects of dietary plant fibers in human nutrition has been plagued by many problems of definition, terminology, analytical procedures, as well as insufficient consideration of the interactions of other dietary components with the dietary fiber polymers. The use of the term non-nutritive has also led to some confusion, as many polymers of dietary fiber are digested by intestinal bacteria in humans. It appears extremely important for the orderly progress of this field that comprehensive terms be used cautiously and that perhaps a new umbrella term (such as plantix) should be introduced. The physiological effects of various polymers have been shown to differ considerably; thus the effect of dietary fiber should not be generalized. Analytical procedure should include both water-insoluble and water-soluble fractions and some consideration should be given to the non-polymeric, enzyme-indigestible compounds such as certain seed and leaf waxes.


Photosynthesis and increased production of protein.

Photosynthesis, the use of light energy in the conversion of CO2 and inorganic nutrients into plant material, is the ultimate source of the food protein necessary to man's existence. Given certain assumptions, the overall maximal theoretical photosynthetic efficiency of agricultural plants can be calculated. Actual measured maximal growth rates of plants are equivalent to efficiency levels well below that theoretical maximum. In air, C4 plants can some closer to the theoretical value than C3 plants, perhaps because C4 plants avoid the occurrence of measurable photorespiration and oxygen inhibition of photosynthesis. Alfalfa, a C3 legume, is an extremely productive protein source. Its protein yield per acre can surpass that of commonly grown C4 crops (corn, sorghum) and C3 seed crops (soybean, wheat, rice). Alfalfa leaf protein is of high nutritional quality and can apparently be used directly in the human diet, eliminating the protein loss involved in animal production. Plant protein productivity can be raised as part of an increase in overall crop yield. The growth of plants in atmospheres with elevated CO2 levels can result in increased yields. In C3 plants this is due, at least in  part, to the suppression of photorespiration and oxygen inhibition of photosynthesis. We have investigated the effect of CO2 concentration on alfalfa photosynthetic metabolism. Our results support the contention that alfalfa productivity can be increased by an environment of elevated CO2. A second approach toward increased plant protein productivity is through regulation of carbon flow during photosynthesis so as to increase portein production relative to that of other plant constituents. In particular, we have investigated whether ammonia (the form in which plants first incorporate nitrogen) can act to regulate leaf carbon metabolism. Our results indicate that NH4+, in part through stimulation of pyruvate kinase, brings about increased production of amino acids at the expense of sucrose production in alfalfa. The effect may be of considerable importance in the regulation of green leaf protein synthesis.


Control through breeding methods of factors affecting nutritional quality of cereals and grain legumes.

The comparison of nutritional quality parameters of proteins from cultivated cereal and legume species with animal proteins indicate the poor nutritional value of these plant products. The nutritive value of different cereal and legume species is very variable and large differences have also been observed coming from cultivars belonging to the same species. Many interpreting factors, such as protein content, essential amino acid composition and availability, protein digestibility and others are involved in such a highly variability. In addition, cereals as well as legumes may contain large amounts of antinutritional factors which can have serious effects under particular circumstances (e.e. tannins in a low-protein diet or phytates in a metal-deficient diet). Some legume species also contain chemicals of a different nature (i. e. lathyrogens, cyanogenetic glycosides, and others) which may be extremely toxic when ingested in significant amounts. The plant breeder attempting to develop higher-yielding, disease-resistant and nutritionally-improved crop varieties should be aware of such a complex of factors and alert to the possible production or increase of undesirable products or deleterious changes in chemical composition. Available data, although rather limited, indicate valuable breeding approaches to the improvement of nutritive value of cereal and legume grains for humans.


Methods for improving cereal protein quality.

Three methods for improving cereal protein quality are discussed. Two older methods are supplementation with limiting essential amino acids and with protein concentrates high in those amino acids. The most recent method (since 1964) is the replacement of the normal cereal grain with its high lysine mutant counterpart. Three high lysine cereals are now available, corn, barley, and sorghum. In animal feeding, least cost formulas will determine which of the three improvement methods will be used. In human nutrition, cost, availability, palatability and acceptance are all equally important factors. In animals, pounds of gain per pound of feed will be the final measure of cereal protein quality. In humans, especially preschool children, the most important criterion will be the ability of the improved cereal protein to build a strong immune defense system. Animal studies show that protein quality is more important than calories when calories are restricted to less than ad libitum consumption. It is therefore essential that children restricted in their total energy intake have the best cereal protein quality possible to protect their immune system.


Improvement of wheat protein quality and quantity by breeding.

Substantial genetic, variability for grain protein content in wheat has been identified. In appropriate combinations known genes can increase protein content of wheat grain by 5 percentage points. Productive high protein experimental lines with good agronomic traits and satisfactory processing attributes have been identified. A high protein hard red winter variety developed in Nebraska was released for commercial production in 1975 under the name "Lancota". The high protein of Lancota resides entirely in the starchy endosperm portion of the kernel and is fully transmissible to white milled flour. The high protein of Lancota results from elevated NO3 reductase activity, increased N-absorption by the roots, and more complete translocation of N to the grain. Despite strong environmental influence on wheat protein level, genes for high protein have been demonstrated to effectively increase protein content in many different production environments. Lysine % of protein decreases but lysine % of grain increases as protein is increased. Genetic variability for lysine of sufficient magnitude to overcome the normal depression of lysine % of protein as protein is increased has been uncovered. Experimental lines have been developed in the ARS-Nebraska program in which genes for high protein and high lysine were combined. The lines have been widely distributed for use in other breeding programs.


Protein quality of induced high lysine mutants in barley.

Evidence of high-lysine gene sources in barley derived from spontaneous and induced mutations has been presented. In addition barley sources considered to be "normal" also differ in lysine content. Changes in lysine concentrations invariable results in changes in other amino acids in barley protein. Protein fractions are altered in several mutant barleys and differ also in so called "normal barleys". The fractions in the normal barleys are probably more dependent upon environmental conditions than in mutant barleys. It is clearly demonstrated with chemical analyses and biological experiments with rats, poultry and pigs that high-lysine cultivars are superior in nutritive quality than their low-lysine isotypes. However, it appears that most of the lysine genotypes possess reduced grain weight and lower grain yield. This is of course unfortunate as an adequate supply of food appears to be the number one nutritional priority in the world today. This does not mean, however, that protein improvement would be of no practical value under conditions of marginal energy deprivation. The literature reviewed suggests that protein improvement would likely be of value under these conditions.


The nutritive value of mixed proteins.

Mixture of protein foods given to chickens or rats frequently result in better growth than would be expected from the performance obtained with each component of the mixture given on its own. Mixing often results in the provision of a better amino acid balance in the diet and the improved growth can be attributed to the minimising of deficiencies of particular essential amino acids in the diet. This explanation is not always possible however. Some mixtures which give better growth have lower levels of some important amino acids than the better component of the mixture, and in such cases it is suggested that the improvements are due to the achievement of better overall amino acid balance. In particular it seems clear that amino acid excesses may have a deleterious effect, and diet balancing should be designed not merely to minimise deficiencies of essential amino acids, but also to cut down excesses.


Some thoughts on amino acid supplementation of proteins in relation to improvement of protein nutriture.

Supplementation of diets with free amino acids has not routinely been beneficial and poses a potential risk. Thus, mixing proteins to increase the quality of the dietary protein is attractive. The slope-ratio technique for evaluation of protein quality has serious drawbacks, because the growth response is not linear and animals appear to adapt to the diet and thus make more efficient use of diets low in protein or low in protein quality. Apparently, the relative value of proteins is not constant, but varies with the amino acid spectrum as well as intake. Thus, evaluation of proteins or protein mixtures should be determined under the conditions (e.g. maintenance or maximum gain) of their potential use. This approach could lead to the development of a protein replacement equivalents system similar to the starch equivalents system in the evaluation of the net energy of animal feeds.


Nutritional evaluation of dry-roasted navy bean flour and mixtures with cereal proteins.

A navy bean flour prepared by dry roasting in a salt bed as a medium of heat exchange was found to have a higher PER than beans which had been autoclaved in the conventional manner. This difference was attributed to a small but significant improvement in the digestibility of the protein. The PER of the roasted beans was higher than the autoclaved beans even in the presence of supplemental methionine. When various proportions of roasted beans and corn were fed at a level of 8.3% protein in the diet, a mixture in which 40% to 60% of the protein was provided by either beans or corn had a PER essentially the same as casein. Diets containing roasted beans and various cereal grains (oats, barely, buckwheat, wheat germ, and rice) were formulated in proportions calculated to give the highest chemical scores. In most cases the PER' were not significantly different from that of casein, and, in the case of rice, the PER was higher than that of casein. Supplementation of such diets with their first limiting amino acid failed to produce a further enhancement of the PER.


Nutritional evaluation of oilseeds and legumes as protein supplements to cereals.

Several oilseed and legume protein products were fed to rats as the sole source of dietary protein, and in blends with cereals for the determination of protein efficiency ratio (PER) and biological availability of amino acids. In addition oilseed protein isolates were fed to mice for the determination of PER. Results of the mouse study revealed that the adjusted PER (casein = 100)for Target rapeseed isolate (108) was higher than  those of sunflower (74), safflower (77), soybean (86) or flax (92) isolates. Results of the rat trials revealed that the adjusted PER for Twoer rapeseed meal (88) was higher than those of fababean (21), field pea (59) and soybean meal (72). Supplementation with methionine (0.2%) resulted in improved PER for fababean (84), field pea (101) and soybean meal (97). Mustard flour and rapeseed flour gave PER of 109 and 106, respectively, while the value of sunflower flour was low (56). Protein isolates of Tower rapeseed and soybean gave PER of 92 and 80, respectively. Blending of legumes and oilseeds with wheat flour (PER = 28) gave high PER values (60--85), as also occurred in rice blends (71--88). Supplementation of wheat-legume blends with lysine (0.4%), methionine (0.2%) and threonine (0.1%) brought all PER values above 100. It appeared that differences in PER of the diets paralleled the levels of the first limiting amino acid for rat growth. Results of balance trials indicated that the availability of the limiting amino acid(s) was lower than other essential amino acids for each protein source.


The nutritive value of faba beans and low glucosinolate rapeseed meal for swine.

Faba beans may be effectively used as a partial replacement for other protein supplements in swine diets. Breeding swine appear to be particularly sensitive to the level of faba beans in their diets. The lack of response to autoclaving faba beans suggests that the trypsin inhibitor level and condensed tannin content of faba beans do not significantly influence the performance of growing-finishing swine. Supplementation of diets containing faba beans with lysine and/or methionine has not improved pig performance. The scientific selection and commercial production of low glucosinolate varieties of rape constitutes a major advance for swine nutrition. All swine experiments that have compared low glucosinolate rapessed meal with regular rapeseed meal have demonstrated the superiority of the low glucosinolate material as a protein source. Substantially larger proportions of the low glucosinolate material may be fed to all classes of swine without any significant depression in performance.


Production of animal protein from nonprotein nitrogen chemicals.

Ruminants obtain amino acids (AA) from microbial protein synthesized in the rumen and from feed proteins that escape ruminal degradation. Synthesis of microbial protein provides a mechanism for obtaining AA from NPN. Effectiveness of NPN utilization depends upon production and utilization of ammonia by rumen microbes. Because ammonia is produced from protein and NPN, feeding proteins resistant to microbial degradation forces utilization of ammonia derived from NPN. The quantity of microbial cells formed in the anaerobic rumen fermentation system is primarily dependnt upon energy supply but can be modulated by types and supplies of other nutrients (i.e. amino-N, minerals growth factors) and by growth rate of rumen bacteria. Potential quantities of NPN that can be utilized with different feed ingredients can be estimated from amounts of feed protein degraded in the rumen, and requiring transformation into protein via growth of rumen microbes, and from amounts of energy provided by feed ingredients. High energy feed ingredients with low amounts of degradable protein are most favorable for NPN utilization, but NPN has also been used successfully with high-fibrous, low energy feed materials. Growth, lactation and reproduction have been obtained on diets containing more than 97% of the nitrogen from NPN, but microbial protein alone cannot provide quantities of AA needed for high levels of productivity. Regulating ruminal degradation of dietary protein and utilizing NPN for rumen protein production is a highly desirable strategy for producing human foods with ruminants.


Analysis for availability of amino acid supplements in foods and feeds: biochemical and nutritional implications.

In formulated diets based on cereal grains, lysine and/or methionine are usually deficient as well as often being the first amino acids limiting the nutritional value of such diets. Deficiency of these two amino acids in nutritional practice is compensated by synthetic L-lysine and DL-methionine supplementation or by the introduction of various protein sources - rich in lysine and methionine. Among all essential amino acids lysine is most liable and subject to damage during the processing of foods and feeds which can cause the "deepening" of the lysine deficiency not on the total but on the physiologically-available lysine basis. Hence, the simultaneous lysine deficiency and biological "sufficiency" problem is discussed using examples of practical diets in which a balance of biologically-active substances was achieved by the formulation and optimalisation according to the needs of animals, taking into account physiological lysine "accessibility" - "availability". Growth rate, nitrogen balance data and chemical composition of the tissue in long term trials are the most valid indication justifying the quantity of amino acid supplements to the practical diets. Prediction of the practical results of dietary amino acid balance from various short-term chemical and biological tests can give misleading results. Their application in nutritional practice is restricted to particular types of foods/feeds, and to specific processing systems and test conditions. Observations of the appearances of most limiting, dietary amino acids in the blood after the meal do not provide a complete nutritional characteristics of practical rations due to complex regulatory mechanisms in protein and amino acid metabolism much of which are not yet fully understood.


N-Substituted lysines as sources of lysine in nutrition.

Twenty seven alpha-N- and epsilon-N-substituted derivatives of lysine belonging to eight different classes: (1) natural dipeptides, (2) alpha-N-acyl-, (3)epsilon-N-acyl-, (4)epsilon-N-(alpha-amino acyl)-, (5)epsilon-N-(omega-amino acyl)-, (6)alpha-N-epsilon-N-di-amino acyl-, (7)epsilon-N-acylglycyl- and (8)Schiff's bases were synthesized. The "in vitro" utilization of some of them was tested by a rat growth assay. Only the derivatives which provided biologically available lysine were hydrolysed by one or more of the intestinal mucosa, liver or kidney homogenates. It is argued that derivatives which can be split by any of the above homogenates are potential sources of lysine. The derivatives of classes (1), (4), (6) and (8) are nearly as efficient as free lysine while lysine in classes (2) and (7) is not utilized at all. From the classes (3) and (5) only some are utilized: epsilon- formyl- and epsilon-acetyl- partially and epsilon-(gamma-glutamyl)-totally. The biologically available derivatives were 4 to 7 times less reactive than free lysine in the Maillard reaction and could therefore be used to fortify foods which have to be submitted to severe heat-treatments. A cheap method of synthesis of epsilon-(gamma-glutamyl)-lysine is proposed and its metabolic transit described.


A method for improving the nutritional value of food proteins: covalent attachment of amino acids.

Casein was modified by use of a series of active N-hydroxy-succinimide esters of amino acids in order to study the effects of new covalently linked hydrophobic or hydrophilic groups on its physical and nutritional properties. Tryptophan was used to determine the best conditions for the chemical reaction and to study the stability of the newly formed amide linkage (isopeptide bond). Casein was also modified with glycine, alanine, methionine, N-acetyl-methionine and aspartic acid. In vitro hydrolysis studies using bovine chymotrypsin, pancreatine and rat bile-pancreatic juice indicated that digestibility of the modified casein derivatives was lower than that of the untreated protein. Since solubility was not significantly changed (except for tryptophyl-casein), the decreased in vitro digestibility is probably due to other factors such as steric hindrance as well as decrease in lysine residues available to trypsin in pancreatin and rat pancreatic juice. Plasma amino acid patterns for rats fed a 10% protein diet of highly modified glycyl-casein or methionyl-casein suggest that the epsilon-aminolysyl derivatives are readily hydrolyzed in vivo. This was confirmed by the growth response of rats fed the following isonitrogenous diets (protein source listed only): casein, casein + free methionine, methionyl-casein, casein + free N-acetyl-methionine, N-acety-methionyl-casein. Covalently attached methionine appeared to be as readily available as the free amino acid; bound N-acetyl-methionine was also available but to a slightly lower extent. Although this study is preliminary, the covalent attachment of amino acids  to proteins appears to be a promising method for improving the biological value of food proteins.


Microbial production of essential amino acid with Corynebacterium glutamicum mutants.

Amino acids produced by microbial process are generally L-forms. The stereospecificity of the amino acids produced by fermentation makes the process advantageous compared with synthetic process. Microorganisms employed in microbial process for amino acid production are divided into 4 classes; wild-type strain, auxotrophic mutant, regulatory mutant and auxotrophic regulatory mutant. Using such mutants of Corynebacterium glutamicum, all the essential amino acids but L-methionine are now being produced by "direct fermentation" from cheap carbon sources such as carbohydrate materials or acetic acid.


Fortification of soft drinks with protein from cottage cheese whey.

Cottage cheese whey protein concentrates, prepared by preconcentration by ultrafiltration followed by gel permeation to remove low molecular weight materials, have the solubility, stability and flavor that make them suitable for fortification of soft drinks and related products. These concentrates are characterized by high levels of "available" lysine and by amino acid compositions indicating good nutritional value. Carbonated beverages prepared with conventional beverage ingredients and containing up to 1% by weight of the total beverage of added whey protein maintained clarity, color, and flavor during 203 days storage at room temperature. Spray dried whey protein concentrates were incorporated without adverse effects into commercial "ade" type powders. Clarity of 1% protein solutions at pH 2--3.5 was not impaired by heating for 6h at 80 degree, but some structural change occurred since an average of 37% of the protein precipitated on shifting pH to 4.7. Increased stability against heat denaturation under acidic conditions was conferred by some soft drink ingredients. Added sucrose reduced protein denaturation by 1/2 but sodium saccharin had no effect. The type of acid used also altered protein denaturation rate. While properly isolated whey protein concentrates have functional properties necessary for soft drink fortification, feasibility of use will depend upon cost.


Effect on nitrogen retention by adults of different proportions of indispensable amino acids in isonitrogenous cereal-based based diets.

Nitrogen retention of adults who consumed diets in which cereals furnished 6.0 g N and 0.9 g of lysine was improved by increasing lysine to 1.8 g without altering other amino acids. In a second experiment, 70% of the 6.0 g of dietary N was supplied by rice + wheat and 30% by mixtures of amino acids so designed that the total intakes of amino acids were equivalent to those in diets containing 6.0 g N from whole egg (E), egg + potato (EP), rice + wheat (RW), rice + soy (RS), wheat + milk (WM) or corn + beans (CB). Mean N balances of young men in descending order were, g/day: E 0.69 +/- 0.23, RS 0.44 +/- 0.15, EP 0.43 +/- 0.09, WM 0.24 +/- 0.16, CB 0.16 +/- 0.13 and RW -0.02 +/- 0.10. In the same order, these diet provided, g/day: lysine 2.6, 1.9, 2.3, 1.6, 1.4 and 1.0; S-acids 2.2, 1.7, 1.6, 2.2, 1.9 and 2.3; and tryptophan 0.7, 0.4, 0.6, 0.5, 0.3 and 0.4. N balances resulting from diets E, RS and EP did not differ significantly from each other but E was superior to CB and RW (P less than 0.01). Relative amounts and propertions of the essential amino acids could be varied without altering nitrogen retention until at least one amino acid became limiting. Several patterns of indispensable amino acids therefore may be equally effective in meeting needs of adults, but both amounts and relative proportions should be considered.


Design assembly of an inexpensive, automated microbore amino acid analyzer: separation and quantitation of amino acids in physiological fluids.

An amino acid analyzer capable of separating and quantitating 0.5 to 20 n moles of each ninhydrin-positive compound in physiological fluids has been designed and assembled from commercially available components. The buffer sequence, column temperature change and sample application are controlled by an automatic programmer constructed from a series of timers. The liquid delivery protion of the instrument consists of a series of polystyrene and stainless steel chambers pressurized with argon and connected through valves and manifolds to conventional positive displacement pumps. The column is highly polished stainless steel tubing (0.21-cm ID) packed with 9-mu cation exchange resin. Micro colorimeters, equipped with appropriate interference filters and small-volume (2-8 mu 1) flow cells, are used as detectors. The sample loader is a dual 20-port automatic valve containing 25-mu1 sample loops. Small-bore teflon tubing (32 AWG), interconnected with tubing adapters and connectors, is used for buffer lines and reaction coil (100 degree C); ninhydrin lines are 1/16-inch stainless steel tubing. Separation of 42 ninhydrin positive compounds, including column equilibration, is accomplished in 5 hours. Procedures for the extraction of amino acids from physiological fluids and tissues as well as the preliminary clean-up of these extracts are also described.


Comparative protein quality as measured by human and small animal bioassays of three lines of winter wheat.

Incomplete information on factors contributing to apparent protein quality and to value of food products as sources of protein and how these factors interact necessitate the use of bioassay procedures. Ideally bioassay procedures should be done using the animal species for which the protein is intended. Practical considerations dictate the use of small animal bioassay rather than human bioassays for routine use in protein product evaluation. To be of real value for routine use in protein product evaluation. To be of real value for assays of food products designed for human use, animal bioassays must accurately predict human performance. Surprisingly little information is available on this topic. In the current project three Nebraska winter wheats of similar genetic backgrounds were evaluated for protein value and for value of the wheats as sources of proteins. Chemical, weanling mouse, adult human and growing human bioassay techniques were employed. Rankings of the grains were similar regardless of species used for protein quality evaluations. Similar rankings were found regardless of species used for protein quality/quantity evaluations. However, ranking varied between methods designed to evaluate protein quality and those designed to measure protein quality/quantity interrelationships. The results stress the importance of matching appropriate methodology with information desired. In a latter project, wheats of dissimilar genetic background were not as uniformily evaluated. This suggests that other factors known to affect protein quality and value were more variable in these wheats.


Interferon assay anomaly variation of interferon response with cell type and sialic acid content.

Human interferon derived from leukocytes and cultured fibroblast sources has been compared by assay in two human cell systems. The ratio of the activities of the two interferon preparations differed markedly in two assay systems. Neuraminidase treatment had no effect on the activity of either interferon in the more sensitive system but reduced the activity of the fibroblast material in the second system so that the resulting ratio of activities approximated that seen in the first assay system.


Interferon therapy for neoplastic diseases in man in vitro and in vivo studies.

With the object of examining the anti-tumour effect of exogenous interferon therapy in man a research programme has been initiated at the Karolinska Hospital. Established cell lines obtained from patients with Burkitt's and other types of lymphoma, leukaemia, osteosarcoma, mammary carcinoma and fibrosarcoma and from fibroblast cultures displayed a variable sensitivity to the cell multiplication inhibitory activity of interferon. All the monolayer cultures tested were found to be sensitive to interferon at concentrations between 10 and 300 units/ml. Some lymphoma cell lines were not sensitive to interferon even at concentrations as high as 10.000 units/ml, while others were sensitive at concentrations between 2 and 300 units/ml. The interferons tested appeared to show a degree of tissue specificity. Controlled studies in vivo are being performed on osteosarcoma, juvenile papilloma of the larynx, multiple myeloma and small-cell carcinoma of the lung. The clinical results of this research obtained to date, together with the results obtained in model experiments, would appear to warrant accelerated production of human interferon.


Considerations in our search for interferons for clinical use.

Interferon has yet to become the drug of choice for any clinical disease entity, but several promising uses are being pursued. Clinical trials are limited probably because interferon is so expensive. Cheaper interferon would probably stimulate more clinical trials. Demonstrated efficacy in a disease of considerable magnitude would spur the search for cheaper interferon. Possible ways to look for more, cheaper interferon are suggested. The need to understand the chemical and structural composition of interferon is pointed out especially the role played by carbohydrates. There is a need for a non-biological, yet sensitive quantitative measurement of interferon; development of an immune assay is suggested. The need to restudy ways to apply interferon to target tissues and the need for a standardized product for use in clinical trials are pointed out.


Radioimmunoassay of prostaglandins and thromboxanes.

1. Decide on what organ or other biological material to study and select the proper compound for this study from the knowledge of precursor acid metabolism. Develop the RIA for this compound or a stable derivative thereof. 2. Whichever sample type is assayed (extracted or unextracted), the possibility of the presence of nonspecific interfering factors must be constantly kept in mind. Make dilution tests and assay for parallelism; however, do not accept parallelism as an absolute criterion of absence of nonspecific influence. 3. Use two or more completely different separation techniques for comparison when validating the RIA. 4. When evaluating the RIA, do not limit the investigation to the traditional reliability criteria: sensitivity, specificity, precision, and accuracy. The RIA may seem reliable at this stage and still give completely unrealistic values when applied to biological material. The method must be evaluated by other studies as well. 5. In the experimental design, aim at following the changes in prostaglandin levels in a series of samples instead of measuring absolute levels in single samples. 6. Make comparative studies employing different quantitative methods.


Gas chromatography of the prostaglandins.

Gas chromatography is the most widely used chromatographic technique. Its strength lies in the fact that three distinct operations--separation, detection, and quantitation--can be performed on all the components of mixtures within a reasonable time, and that qualitative information about the compound identity is associated with its retention time. Despite a prominent position in other areas of biochemistry, its success in the prostaglandin field has been rather limited. The technique itself is not at fault since samples with reasonable levels of prostaglandins have been analyzed without overwhelming difficulty. However, many samples demand a sensitivity exceeding the limits of either electron capture or flame ionization detectors. Shifts in research problems have contributed to its decline, but it is fair to add that these shifts were associated with the appearance of more sensitive and accurate analytical methods. Let us not despair for gas chromatography because its competitors, radioimmunoassay and gas chromatography-mass spectroscopy, also have deficiencies. In this chapter we have described several traditional gas chromatographic methods for prostaglandin analysis and outlined their strengths and weaknesses. Hopefully, this will prevent the misapplication of a useful analytical tool and also serve as an incentive to provoke contributions to this somewhat neglected technology. In conclusion, it cannot be stressed enough that all instrumental methods are at the mercy of chemistry. Chemistry can be exploited to enhance the value of a technique, or it can be disregarded to discredit the technique. The rise of sophisticated instruments has falsely diminished the value of chemistry in analytical methods development. It is imperative that we remind ourselves of its place and use it properly.


Multidisciplinary education in geriatrics: an experimental course at the Middlesex Hospital.

For two years mixed groups of medical, nursing and physiotherapy students have taken part in an experimental course in geriatric medicine. The course organization and content are described and the students' evaluation of the course is discussed.


Suicide and parasuicide in old age: a review.

The disproportionately high suicide rate among the elderly is examined in this review. As opposed to younger age groups, a close association exists between suicide and parasuicide in old age. Factors associated with these events include a high incidence of depression, serious physical illness, as well as social factors that serve to isolate the individual and deprive him of positive support and therapeutic intervention. A high risk profile and integrative model are proposed.


Environment, temperature and death rates.

Analysis of recorded monthly deaths in England and Wales shows a close association of death rates with external temperature in most diseases other than the cancers. Analysis of daily deaths in England and Wales and in New York shows the following relationships between temperature and deaths from myocardial infarction, strokes and pneumonia. Between -10 degrees and +20 degrees C mimimum temperature there is a nearly linear fall in deaths as the temperature rises. Above 20 degrees C deaths rise steeply as the temperature rises and below -10 degrees C rise steeply as temperature falls. These associations of deaths with temperature are much stronger in the elderly than in younger subjects. Detailed analysis of the daily deaths in England and Wales from myocardial infarction, strokes and pneumonia show that short-term (1--2 days) temperature changes have little effect on death rates but medium-term (7--10 days) and longer-term (three or more weeks) changes associated with very significant changes in death rates. The three diseases vary in the time relations between temperature change and change in death rates. In all three there is an interval between the change in temperature and death and this is shortest in the case of myocardial infarction (1--2 days before death), longest in the case of pneumonia (about a week before death) and intermediate in the case of strokes (about 3--4 days before death). At low temperatures death rates increase as the duration of temperature change increases, while at high temperatures (but below +20 degrees C) death rates decrease as the period of temperature change is longer. The implications of these findings are discussed and it is postulated that there is probably causal relationship between temperature change and deaths from a wide variety of diseases. A proximal link in the chain is probably a failure of autonomic control of body temperature in the elderly leading to a change in body temperature and some humoral change which in turn leads to death. It is not appropriate to concentrate on hypothermia as the relationship between temperature and death is seen at all temperatures.


Ultra-violet irradiation and 25-hydroxy-vitamin D levels in sick old people.

Twelve elderly patients in a rehabilitation ward were given a four-week course of ultra-violet irradiation from a Vitalux lamp. They were compared with 12 controls selected from the same ward. Treatment produced a significant elevation in plasma 25-hydroxy-vitamin D (25OHD) by the end of the second week and concentrations continued to rise over the four-week period. Subject showing the greatest response were those starting with the lowest levels of plasma 25OHD. The findings suggest that ultra-violet irradiation is an effective means of treating vitamin D deficiency in old age and that patients with the greatest degree of deficiency show the greatest response.


Changing work pattern in a geriatric unit and the effect of a day hospital.

Examination of data collected during domiciliary visits is a useful research technique. It has been used to examine the changing work pattern of a Geriatric Unit over 25 years. The importance of domiciliary visiting in the efficient use of medical facilities is emphasized.


Is jejunal biopsy valuable in the elderly?

The records of the patients over 65 years undergoing jejunal biopsy in two Liverpool gastroenterology units were obtained. Biopsy failed in four of the 52 cases, diagnostic yield was 12% and only appeared to be of value in confirming the diagnosis of gluten-sensitive enteropathy (adult coeliac disease).


Picotamide: effects on coagulation, fibrinolysis and platelet aggregation during prolonged administration in the aged.

Picotamide was administered in a daily dose of 1500 mg per os for 30 days to 30 aged, arteriosclerotic subjects and as single doses of 500 mg and 1000 mg to another group of 16 subjects. A reduction of platelet aggregation (methods of Born and Breddin) was observed within 24 hours of commencement of treatment and became more evident in the subsequent days. The reduction was both consistent and significant. A marked increase in fibrinolytic activity (fibrin plate method) was observed during the first 24 hours, particularly for euglobulins with activator. The reaction and clot formation times (r and k) were prolonged and the maximal amplitude (ma) in thrombelastogram was reduced by a definite, though small amount. After the administration of a single dose the maximal effect was observed after eight hours and was still evident after 48 and, to a lesser degree, after 72 hours. The drug was in all cases well tolerated, without any significant side-effects nor untoward reactions.


Oxygen absorption in evaporating and condensing water droplets.

The amount of oxygen absorbed by individual drops of water suspended in a gas stream was measured. The water vapor content in the gas was regulated so that oxygen mass transfer could be observed under evaporation or condensation conditions. Other variables studied were oxygen concentration and exposure time. The rate of mass transfer of oxygen increased significantly with increasing water vapor and oxygen content in the gas. The relevance of mass transfer in growing aerosol systems to industrial hygiene is discussed.


In-plant evaluation of the muscle strength of workers.

The static muscular strength of the back extensors, arm flexors and hand grip were measured on industrial workers (463 men and 139 women) involved in physically demanding jobs. No significant differences in strength were found among workers on different jobs. However, strength differences were evident with respect to age and sex; women were about 60 percent as strong as men, and men below 31 years of age were stronger than men above this age.


The development of a fluorometric method for the assay of subtilisins.

An ultra-sensitive fluorometric method has been developed for quantitating subtilisins in aqueous solution. Using detergent solutions as blanks, the analytical sensitivity was estimated to be 0.002 microgram of 100% active enzyme per milliliter. The required sampling time for quantitating subtilisins in air at their TLV was estimated to be approximately two minutes.


Radiation protection philosophy: bioethical problems and priorities.

The evolution of radiation protection philosophy over the past thirty years calls attention to an urgent need to review and revise current radiation control programs with respect to the ethical problems and priorities they reflect. One problem is the environmental crisis-mentality escalating already rising expectations in our affluent society about levels of safety. A second problem is the propriety or impropriety of using cost/benefit/risk quantifications in setting priorities in public health protection. A threefold ethical justification for risk-assessment methodology challenges our government regulatory agency system as presently chartered and operationally conducted.


A new personal sampler for organic vapors.

This paper describes the evaluation of a new personal sampler for organic vapors which is totally different from traditional sampling techniques using pumps and adsorption tubes. Sampling of organic vapors is effected by collection on an adsorption substrate contained within a small passive sampler worn by the worker. The collection element is removed from the sampler and subsequently analyzed for organic vapors. The results are equated with the time-weighted-average concentration of contaminants in air. This new sampling device circumvents inherent errors generally associated with sampling pumps and tubes; e.g., changes in pumping rates and variable pressure drops across adsorption tubes. Applications of the sampler were demonstrated on various concentrations of benzene, methyl isobutyl ketone, isooctane, butyl acetate, methyl chloroform, trichloroethylene, butanol and solvent mixtures. Variables studied included the effects of temperature, charcoal lot, and air velocities. In addition, the occurrence of "breakthrough" and effect of time on sample stability were investigated.


Method for determining complex operator noise exposures.

This procedure describes a field method for determining operator noise exposures that cannot be assessed from single sound level meter readings. Noise exposures that should be evaluated by this method are those characterized by time-varying operator position sound levels--sound levels that change by three decibels or more while the meter is being read. The method is based on statistical concepts and requires multiple readings for a sample period whose length is prescribed by the desired precision of the results. This new procedure compares well with the theoretical accuracy of the best dosimeters. The actual performance of the new method has been shown to be better than the actual performance of the dosimeters.


Quantitative fit testing of personnel utilizing a mouthpiece respirator.

A respirator test facility using Refrigerant 12 as a challenge gas has been developed. More than 6000 people have received training in the effective use of mouthpiece respirators. Leakage is determined by the use of a halide detection meter analyzing the exhaled breath. The facilities have been used to provide training and quantitative fit testing for practically all types of respiratory protective equipment. An actual use investigation was made to determine the suitability of the mouthpiece respirator for use in a chlorine producing plant work situation. The mouthpiece respirator was compared with a group of half-face respirators. A clear distinction was made: the half-face respirator offered less protection than the mouthpiece respirator.


The sampling and determination of azelaic acid in air.

Air samples of azelaic acid (nonanedioic acid), were collected on polyvinyl chloride (PVC) filters, extracted with ethanol, derivatized with N, O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), containing 1% trimethylchlorosilane (TMCS) and analyzed by gas-liquid chromatography. The esterification product is the trimethylsilyl ester, which is different from the methyl ester usually chosen in the esterification processes. A calibration curve was used to determine the azelaic acid content in the filter samples. The detection limit was 1 microgram per sample. Results indicate that the analytical method can be applied to other monocarboxylic and dicarboxylic acids.


Physical state of airborne p, p'-diphenylmethane diisocyanate (MDI) and its measurement.

The current exposure standard of 0.02 ppm ceiling for MDI by definition refers to a gaseous species. The standard method, recommended by NIOSH, for measuring MDI in air, is also based on the the assumption that MDI is in the gas phase. Investigations in our Unit indicate that a major portion of airborne MDI, in working environments during spraying operations, is present as an aerosol. In view of this finding, the standard method would underestimate the MDI concentration and describing the airborne MDI concentration in "ppm" or "volume/volume unit" in invalid. A new method for calibration of the continuous reading monitors to measure airborne MDI concentration in mg/m3 unit is described.


Prolongation of cardiac conduction times by intravenous aprindine in man.

The acute electrophysiologic effects of intravenous aprindine were evaluated in 48 patients to assess the effect on conduction times and refractoriness in patients with severe cardiac disease and arrhythmias. The patients had not responded to conventional antiarrhythmic medications or had been unable to tolerate effective doses of conventional medications because of side effects. Eleven patients had an abnormal H-V interval, 9 had prolonged QRS duration and 22 had evidence of severe left ventricular dysfunction. Aprindine prolonged conduction transiently in the atria, the atrioventricular (A-V) node, the His-Purkinje system and the ventricles. The refractory times of the atria, the A-V node and the ventricles increased insignificantly, both functionally and statistically. Atrioventricular block did not develop in any patient, and side effects were minor. Thus, aprindine can be safely administered intravenously (10 to 15 mg/min) to severely ill patients with arrhythmias that are refractory to other medications even in the presence of underlying conduction system and myocardial disease.


Suppression of the repetitive ventricular response: an index of long-term antiarrhythmic effectiveness of aprindine for ventricular tachycardia in man.

The repetitive ventricular response, defined as the production of two or more ventricular premature complexes in response to a single ventricular pacing stimulus, is common in patients with serious ventricular arrhythmias. Twenty-seven patients with refractory ventricular tachycardia were studied to determine whether acute suppression of the repetitive ventricular response by aprindine predicts long-term effectiveness of this agent. Twenty-three of the 27 patients had the repetitive ventricular response before intravenous administration of aprindine, whereas only 6 had the response after aprindine. All patients were maintained on a regimen of oral aprindine and evaluated repeatedly for a mean of 12 months. Twenty of the 21 patients who had no repetitive ventricular response after intravenous aprindine manifested  clinical improvement compared with only 1 of the 6 in whom the repetitive response was present after aprindine (P less than 0.0005). Aprindine is a useful agent in refractory ventricular tachycardia, and the absence of the repetitive ventricular response after its intravenous administration predicts long-term clinical responsiveness to the oral form.


Atypical ventricular tachycardia as a manifestation of disopyramide toxicity.

An unusual ventricular tachyarrhythmia developed in a 57 year old woman with recurrent ventricular tachycardia and toxic disopyramide plasma concentrations. The rhythm was similar to the patient's previous ventricular tachycardia, but the rate was slower and the QRS complex was markedly widened, mimicking the electrocardiographic changes associated with electrolyte abnormalities. Disopyramide, which has electrophysiologic properties similar to those of quinidine, probably caused the arrhythmia and should be added to the list of drugs associated with atypical ventricular tachycardia.


Localization of pericardial effusion with wide angle phased array echocardiography.

Twenty-eight patients with proved pericardial effusions were studied in the left lateral decubitus position with an 80 degrees phased array sector scanner to determine the distribution of pericardial effusions of various sizes. Twenty-one of 28 patients were studied 2 minutes after assuming the sitting position to determine the change in the distribution of the effusions with postural change. In small volume effusions, the fluid was truly posterior at and below the atrioventricular groove. With moderate-sized effusions a more uniform distribution of the fluid was found, and with large effusions more fluid was visualized apically, posteromedially, laterally and anteriorly. Upright redistribution of the fluid was seen with moderate to large nonloculated effusions. Assumption of a uniform distribution of pericardial effusion used for M mode quantification is most valid for moderate effusions and less valid for small and large effusions. Imaging was performed in two additional patients with cardiac tamponade to assess qualitative changes in short axis ventricular volumes with respiration. The introduction of a pericardiocentesis needle was visualized. Clinical implications are discussed.


Ventricular fibrillation during programmed ventricular stimulation: incidence and clinical implications.

Ventricular fibrillation occurred in 10 (3.3 percent) of 300 patients consecutively studied with programmed ventricular stimulation. One hundred twenty-five of these patients were studied with double ventricular extrastimuli including 68 patients with and 57 patients without documented or suspected ventricular tachycardia or fibrillation, or both. Ventricular fibrillation did not develop in response to a single ventricular extrastimulus delivered during sinus rhythm, ventricular pacing or ventricular tachycardia or in response to ventricular pacing at cycle lengths of 300 msec or greater and occurred only in response to double ventricular extrastimuli. All 10 patients who manifested ventricular fibrillation during programmed stimulation were in the group of patients with suspected or documented ventricular tachycardia or fibrillation. Ventricular fibrillation was initiated in seven patients with double ventricular extrastimuli delivered during sinus rhythm or ventricular pacing and in three patients with double ventricular extrastimuli delivered during ventricular tachycardia. Four patients had spontaneous conversion to sinus rhythm and the remainder underwent defibrillation without sequelae. Recurrent ventricular fibrillation occurred clinically in 7 of the 10 patients. This study suggests that ventricular fibrillation occurs uncommonly during programmed ventricular stimulation and only in response to double ventricular extrastimuli in patients in whom spontaneous episodes are likely to occur.


Effectiveness of increasing hours of continuous ambulatory electrocardiography in detecting maximal ventricular ectopy. Continuous 48 hour study of patients with coronary heart disease and normal subjects.

The effectiveness of 1, 6, 12, 24, 36 and 48 hours of continuous ambulatory electrocardiographic examination in detecting maximal ventricular ectopy was studied in 67 patients with coronary heart disease (45 with myocardial infarction, 22 with angina pectoris) and 23 normal subjects. Two consecutive 24 hour Holter recording examinations provided 48 hours of continuous examination. Ventricular ectopy was detected in 87 percent of patients and 35 percent of normal subjects. Complex forms (multifocal or repetitive patterns) were found in 62 percent and high frequency ectopy (greater than 60/hour) in 30 percent of the patients with coronary heart disease. Examination of either the initial hour of study or an hour of dynamic activity frequently failed to reveal the maximal ventricular ectopy present, particularly with regard to complex types and high frequency. Continuous 6 and 12 hour examinations were less effective than the 24 hour examination, which detected the maximal grade of ventricular ectopy in 71 to 74 percent and the maximal frequency in 58 to 83 percent of patients with coronary heart disease. Detection of maximal complex types and high frequency of ventricular ectopy was one to three times greater with a continuous 24 hour examination than with studies of shorter duration. Patient-recorded diaries showed that 50 to 80 percent of patients were engaged in mild to moderate activity during ventricular ectopy and only 9 percent indicated symptoms during the hours of maximal ventricular ectopy.


Effects of digitalis on ventricular myocardial and His-Purkinje refractoriness and reentry in man.

The effects of digitalis on retrograde conduction and refractoriness of the His-Purkinje system, ventricular myocardium and reentry within the His-Purkinje system were studied in 17 patients using the ventricular extrastimulus (V2) technique. Studies were performed, before and 30 minutes after intravenous administration of ouabain, 0.01 mg/kg. After treatment with ouabain, there was a significant decrease in the functional refractory period (266 +/- 19 to 254 +/- 18 msec, P less than 0.001), relative refractory period (253 +/- 17 to 240 +/- 16 msec, P less than 0.001) and effective refractory period (242 +/- 23 to 231 +/- 24 msec, P less than 0.005) of the ventricular muscle. In contrast, there was no significant change in retrograde His-Purkinje conduction and refractoriness. The phenomenon of reentry within the His-Purkinje system characterized by the reentrant beat (V3) at critical retrograde conduction delays in the His-Purkinje system (V2-H2) within a narrow range of V1-V2 intervals was seen in 10 of 17 patients. Ouabain increased and shifted to the left the zone of reentry within the His-Purkinje system in 7 of 10 patients (36 +/- 23 to 55 +/- 23 msec, P less than 0.001) and decreased it by 10 to 30 msec in the remaining 3 patients. The critical V2-H2 (186 +/- 29 to 193 +/- 27 msec, difference not significant [NS]) and V1-V2 (299 +/- 30 to 294 +/- 36 msec, NS) intervals for reentry did not significantly change after ouabain. However, the minimal V1-V2 intervals (266 +/- 26 to 253 +/- 25 msec, P less than 0.025) decreased significantly, whereas the maximal V2-H2 intervals (266 +/- 40 to 239 +/- 37 msec, P less than 0.01) increased significantly. Thus, in the intact human heart, digitalis (1) significantly decreased all measures of ventricular myocardial refractoriness, (2) had no significant effect on retrograde conduction and refractoriness of the His-Purkinje system, and (3) widened the zone of reentry within the His-Purkinje system due to shortening of the functional refractory period of the ventricular muscle with attainment of longer V2-H2 delays.


Electrograms from the canine sinoatrial pacemaker recorded in vitro and in situ.

We have identified extracell potential changes associated with the electrical activity of the canine sinoatrial pacemaker. Small nonpolarizable electrodes and low frequency high gain amplification were used to record unipolar electrograms from both the epicardial and the endocardial surfaces of the canine sinus node. Initially in vitro studies were performed so that transmembrane action potential changes could be recorded simultaneously with the extracell potentials. The sinus nodal electrogram showed two characteristic potentials when the electrode was in immediate proximity to pacemaking cells: (1) During phase 4 there was a steady slope of about -30 to -100 muv/sec, and (2) during the transition from phase 4 to phase 0 of the transmembrane action potential the slope of the electrogram increased smoothly to approximately -400 to -1,000 muv/sec. These potentials were followed by high frequency deflections as cells in the surrounding atrium depolarized. Tetrodotoxin (5 mg/liter) rendered the atrial muscle inexcitable and delayed and then abolished the high frequency activity in the sinus electrogram, which then appeared as a continuous smooth tracing similar to the sinus pacemaker action potential but reversed in polarity. We then recorded these small localized potentials from the in situ canine heart. Sinus nodal electrograms could be obtained from beating hearts with hand held probes on the epicardial surface and with conventional recording catheters on the endocardial surface. The results demonstrate that the canine sinus node gives rise to detectable and characteristic changes in extracell potential and suggest that similar potentials can be recorded from man to evaluate sinus nodal function.


Superiority of practolol versus propranolol in protection against ventricular fibrillation induced by coronary occlusion.

The ability of practolol and propranolol of prevent ventricular fibrillation in experimental anterior myocardial infarction was compared in dogs subjected to ligation of the left anterior descending and first septal coronary arteries. This procedure, which causes ventricular fibrillation in 90 percent of animals within 30 minutes, was performed in control dogs and in dogs pretreated with propranolol (0.5 mg/kg body weight) or with practolol (1.5 to 2.5 mg/kg). These doses produced nearly equivalent shifts in isoproterenol-induced chronotropic dose-response curves, indicating equivalent degrees of beta adrenergic blockade. In 21 dogs with confirmed ligation, cardiogenic shock did not develop. Six of seven control dogs died with ventricular fibrillation. Six of seven dogs pretreated with propranolol also had fibrillation, whereas only one of the seven dogs pretreated with practolol manifested ventricular fibrillation during the 45 minute postligation observation period. Practolol afforded significant protection compared with no treatment or treatment with propranolol (P less than 0.05).