Search for an endogenous ligand for the opiate receptor.

It was investigated whether there is an endogenous factor in the brain which binds to the opiate receptor in neural tissue. Extracts from rat brain were processed in different ways; fractions were assayed for ability to inhibit the receptor binding of dihydromorphine. There was no evidence for high-molecular weight substances or lipid soluble substances with such ability. On the other hand, processing of an acid water extract of brain except the cerebellum (which was negative) yielded an active fraction with receptor blocking activity. This fraction was heat stable, polyionic and had an apparent molecular weight of 1000-1 200 dalton. These and other characteristics indicate that it might well be a peptide. The factor inhibited binding to the opiate receptor in synaptic plasma membranes of rat brain and to the receptor of the guinea-pig ileum although it was less effective on the latter, particularly after long-term incubation. The interaction between the factor and dihydromorphine was reversible and apparently competitive.


The release of prostaglandin-like substances during platelet aggregation and pulmonary microembolism.

During pulmonary microembolism subsequent to induced platelet aggregation in vivo, a pressor response is elicited in the lungs due to the release of vasoactive substances. During the prefusion of isolated cat lungs with whole blood, platelet aggregation induced by collagen released prostaglandin-like substances (PG-LS), and a rabbit aorta contracting substance (RCS) as measured by continuous biosassay of the venous effluent. This release occurred in parallel to the pulmonary pressor response. The same amount of PG-LS and RCS was released when the lungs were replaced by a blood filter to trap platelet aggregates. Apparently PG-LS and RCS are released from platelets during their aggregation. As E- and F-type PGs are rapidaly inactivated in the pulmonary circulation, there must either be an equal generation of PGs in the lungs themselves, or rather, the release of PGs from platelets must occur distal to the inactivation mechanism without any additional PG-release from the lungs. The exact role of PGs in the lung responses to intravascular platelet aggregation is not clear.


Influences on colonic and small intestinal motility by the cerebellar fastigial nucleus.

The fastigial influence on intestinal motility was investigated in acute experiments on chloralosed cats. Motility was recorded both from the small and large intestine. Electrical stimulation of the rostral fastigial pole produced, in combination with a blood pressure rise, increased motor activity in ileum and colon while jejunum could respond with either increased on decreased motility. The intestinal responses were neither secondary to changes in intestinal blood flow, nor to baroreceptor reflexes induced by the increased blood pressure. The excitatory responses were not due to increased parasympathetic activity since sectioning of such pathways failed to abolish the responses. Instead, interruption of adrenergic sympathetic discharge, accomplished either by guanethidine or by sectioning of relevant nerves, aid eliminate the responses, indicating that the fastigial effects were mediated by suppression of prevailing adrenergic tone. Noxious stimuli to the abdomen, including laparotomy, inhibit intestinal motility by a reflex increase in adrenergic discharge. It is suggested that fastigial influence on intestinal motility is mainly due to suppression of this reflex.


Influences on the defecation and micturition reflexes by the cerebellar fastigial nucleus.

The influence of the cerebellar fastigial nucleus on the defecation and micturition reflexes was investigated in chloralosed cats with recordings of colonic blood flow and motility, intravesical and intraabdominal pressures. Whenever effective, topical fastigial stimulation regularly suppressed both somatomotor and autonomic components of the defecation reflex, to the extent that the straining movements as well as the colnic vasodilatator and motor responses associated with defecation could be completely inhibited. Bladder motility could either be suppressed or enhanced, depending both on prevailing bladder tone and on the fastigial site stimulated. The autonomically conveyed inhibitory responses were in both cases independent of the adrenergic sympathetic pathways, since they were unaffected both by sympathetic nerve sectioning and by adrenergic blocking drugs but eliminated by pelvic nerve section. It is suggested that the mentioned fastigial inhibitory influences are exerted on the spinal parasympathetic reflexes controlling the bladder and colon. Parallels between fastigial control of autonomic somatomotor mechanisms are discussed.


Regional and single glomerular blood flow in the rat kidney prepared for micropuncture. A methodological study.

Regional renal and single glomerular blood flow was investigated in rats using 141-Ce and 85-Sr labelled microspheres. The kidneys were prepared for micropuncture and also the artery was catheterized with a steel cannula in order to make injections of 133-Xenon and vasoactive substances selectively into one kidney. The microspheres were first separated by sedimentation into a narrow fraction and then injected as a plasma suspension into the carotid arter; the two batches were infused at half an hour intervals. Single glomeruli were sampled from kidney sections with the aid of silicon rubber casts allowing the identification of the glomeruli both with respect to their localisation and their postglomerular appearance. The results showed a relatively high blood flow in the superficial and juxtamedullary glomeruli of above 100 nl/min per 100 g rat whereas in the other glomeruli the blood flow was about 70 nl/min per 100 g rat. No differences could be observed between the right untouched kidney and the left prepared for micropuncture. Futhermore no discrepancies between the results from the two injections could be found. The data on the total renal blood flow obtained by the 133-Xenon wash-out method agreed well with the microsphere method.


Release of gastrin on vagal stimulation in the cat.

Gastrin released by electrical vagal stimulation was measured in the portal blood of eviscerated cats. Blood flow was recorded by a drop chamber technique and the total gastrin output calculated. Basal peripheral gastrin levels averaged 65 pg/ml and basal portal levels 225 pg/ml. On unilateral vagal stimulation with frequencies above 3-4 Hz gastrin release rapidly increased, reaching a peak within 5-10 min. In spite of continued stimulation and independent of frequency, the gastrin levels declined and returned to basal values after a total of 2-3 000 stimuli. A new maximal response could be induced first after a recovery period of 15-30 min. In the same cat stimulation of either the left or the right vagus released equal maximal amounts of gastrin (average 32 000 pg). The maximal gastrin output on vagal stimulation corresponds to less than 1% of the total content of antral gastrin determined with radioimmunoassay.


Reflex inhibition of the slowly adapting stretch receptors in the intact abdomen of the crayfish.

The reflex inhibition of abdominal stretch receptors in crayfish was studied by controlled passive flexion of individual abdominal joints. The results are very similar to those obtained by electrical or mechanical stimulation of individual stretch receptors in immobilized abdomens. Reflex effects from posterior to anterior abdominal segments are somewhat stronger than in the opposite direction. Flexion of one abdominal joint excites the stretch receptors of that joint and inhibits the stretch receptors in neighbouring abdominal segments. Without reflex inhibition flexion of one abdominal joint excites the stretch receptors in several abdominal segments.


Optimal parameters for eliciting cardio-acceleration by electrical stimulation of the ventromedial hypothalamus.

The ventromedial hypothalamus of the unrestrained cat was stimulated electrically through permanent electrodes. The stimulation parameters, amplitude, duration and frequency of the square wave pulses were combined to produce a 20% increase of the resting heart rate value. The total electric charge for each parametric combination was calculated. The charge per stimulation (10 s) varied from about 1 to 100 micro-coulombs, depending on the parametric combination used. The response could therefore not be expressed as a function of the charge but depended on the individual parametric combinations. The relation among the stimulation parameters and the total amount of electric charge of the pulses was estimated by the correlation technique. The results suggested that about 60% of the variation in the electric charge resulting in the constant response was due to the variation of the pulse repetition frequency. The optimal parameters for eliciting cardio-acceleration in the cat by stimulation of the ventromedial hypothalamus seem to be pulse durations between 0.1 and 0.5 ms and pulse repetition frequencies below 100 P/s, with pulse amplitude as the dependent variable.


Facilitation from contralateral primary afferents of interneuronal transmission in the Ia inhibitory pathway to motoneurones.

The action of volleys in contralateral primary afferents on transmission in the Ia inhibitory pathways to motoneurones was investigated with intracellular recording from motoneurones. Ia IPSPs in flexor as well as most extensor motoneurones were regularly facilitated by volleys in contralateral high threshold muscle, cutaneous and joint afferents in spinal cats under chloralose anaesthesia. In decerebrate cats with a low pontine lesion transmission in Ia inhibitory pathways was not facilitated but rather depressed by volleys in these afferents. The recurrent effects from motor axon collaterals were investigated on inhibitory transmission from different contralateral afferents to motoneurones. Previous investigations have shown that the interneurones mediating the reciprocal Ia inhibition receive recurrent inhibition via motor axon collaterals and Renshaw cells. Now a strong positive correlation was revealed between recurrent depression of IPSPs evoked from different contralateral afferents and facilitation of Ia IPSPs by the same afferent volleys. These results suggest that the recurrent depression of IPSPs from different contralateral primary afferents depends on their excitatory convergence onto the Ia inhibitory interneurones, which then partly mediate the IPSP evoked in the motoneurone from these afferents.


Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets.

Material causing contraction of the isolated rabbit aorta (rabbit aorta contracting substance, RCS) was released from guinea pig lung following perfusion with arachidonic acid and from human blood platelets after addition of thrombin to induce aggregation. Prostaglandin endoperoxides (prostaglandins G2 and/or H2) were found both in the perfusate of guinea pig lung (1-3 ng/ml) and in the medium collected after platelet aggregation (13-37 ng/ml). The contractile response of the isolated rabbit aorta to the pure prostaglandins G2 and H2 was also determined. These data combined with the quantitative analyses of the endoperoxides released from the lungs and platelets showed that only a minor part of the rabbit aorta contracting activity was due to the prostaglandin endoperoxides. The major part of the activity consisted of very unstable material. The half life of this material was about 30 s at 37 degrees whereas at this temperature the prostaglandin endoperoxides had a half life of about 5 min.


Effect of insulin on albumin production and incorporation of 14C-leucine into proteins in isolated parenchymal liver cells from normal rats.

Parenchymal rat liver cells were isolated by a modification of the collagenase method of Quistorff, Bondesen and Grunnet. The cells secreted albumin into the medium and incorporated 14C-leucine both into cell proteins and proteins secreted into the medium. Albumin production measured from the immunologically determined increment in the incubation medium was 1.7 +/- 0.2 mug albumin/min per g liver wet wt. This is about 30% of the rate of production in the perfused liver. Addition of insulin (10(-6)-10(-10) M) enhanced albumin production (50-17%), and incorporation of 14C-leucine both into albumin (50-8%), secreted proteins (40-9%) and cell proteins (20-8%). Insulin does not increase the production of albumin by depleting the cells. The effect of insulin on albumin production is compatible with an effect on the rate of synthesis as the specific activity of albumin is unaffected by addition of insulin.


Quantitative rating of manic states. Correlation between clinical assessment and Biegel's Objective Rating Scale.

We have investigated Biegel's manic-state rating scale and found the interrater reliability high when the scale was administered both by nurses and psychiatrists. In our study of validation, we tested each item of the scale for calibration, ascending monotonicity and dispersion parallel to a global clinical assessment of the manic state. Six of the scale items were then found valid and those items differed from the valid items in studies of Biegel by including increased social contact. Like Biegel, we found a positive correlation between items concerned with depressed mood, indicating a fluctuation in the mood of manic patients during 8 hours of observation.


Pimozide in the treatment of monosymptomatic hypochondriacal psychosis.

An account is given of six cases treated with pimozide. Four of there cases fall into the diagnostic category of monosymptomatic hypochondriacal psychosis, a group with a traditionally poor prognosis. Three out of the four have responded favourably to pimozide, while the fourth showed a partial improvement. A fifth case also showed a marked degree of improvement despite a possibility of early cerebral arteriopathy. The one case which showed no improvement was suspected all along of having a personality disorder rather than a psychotic illness, and this was subsequently confirmed. It is suggested that pimozide: a) may be an effective treatment for monosymptomatic hypochondriacal psychoses whatever their aetiology; and b) may differentiate rapidly between cases of monosymptomatic hypochondriacal psychoses and dysmorphophobias due to neurotically determined factors.


Concurrence of turner's syndrome and anorexia nervosa.

The ninth known case of the concurrence of anorexia nervosa and Turner's syndrome is presented. The question whether the presence of Turner's syndrome represents a greater risk for a patient to develop anorexia nervosa is considered.


Morbidity and social mobility in an upper class educational group.

Approximately 18,000 19-year-old graduates from the high schools of Norway were followed for 50 years after graduation by means of a national case register of hospitalized psychoses. Six hundred and sixty-eight graduates were found to have been admitted to a psychiatric institution. The admission rate for male graduates was found to be 95.7 % of the expected rate, while for the female sex the percentage was 115.8. In both sexes, the number of manic-depressive cases was higher than the national average, while schizophrenia was rarer. The number of admissions related to alcohol or drug addiction was much higher in the graduates, and these admissions were concentrated mainly among members of the medical professions. A detailed study was made of 450 male and 218 female graduate patients for whom information was available about the occupation of the father as well as that of the graduate himself. The hospital admission rate was significantly higher in the graduates who had an occupation lower than that of their fathers, and vice versa. Within each social group, the rate of admission was highest in the graduates who had remained in the same occupation as their fathers: Professional sons of professional fathers had an admission rate of 109 % of the expected rate, while those who had moved to other occupations had a rate of only 87 % of the expected. It would seem that inter-generational change of occupation is associated with a lowering of psychiatric morbidity. High admission rates were found in groups which can be regarded as relative failures in relation to their level of aspiration (or that of their parents) in going to high school.


A long-term follow-up study of schizophrenia: psychiatric course of illness and prognosis.

A systematic psychiatric follow-up study of 502 schizophrenics was carried out using the same well-defined criteria to evaluate the patients throughout the investigation. After an average course of disease of 22.4 years, 22.1% of the patients showed complete psychopathological remission, 43.2% had non-characteristic types of remission and 34.7% suffered from characteristic schizophrenic deficiency syndromes. At the time of the last follow-up investigation, 86.7% of the patients were living at home, while 13.3% were permanently hospitalized. Of the entire sample, 55.9% were found to be "socially recovered". Higher education, psychoreactive provocation, depressive traits, perception of delusions, catatonic agitation, non-characteristic thought disorders and symptoms of depersonalization at the onset of the illness tended to carry with them a favorable prognosis. On the other hand, low intelligence, abnormal primary personality, premorbid disturbances in social behavior, broken homes, prolonged prodromal stages, pneumoence-phalographically measurable atrophic or dysplastic changes in the brain ventricles as well as somatic and auditory hallucinations and predominance of hebephrenic symptoms at the onset of the illness tended to lead to an unfavorable prognosis. The principle of the basic reversibility of typical schizophrenic symptoms and the extensive irreversibility of the non-characteristic defect is important for the psychopathological and social long-term prognosis.


Psychotic and borderline psychotic adolescents: frequency of psychiatric illness and treatment in childhood in 100 consecutive cases.

The first results covering the assessment period phase of a systematic study of 50 borderline psychotic and 50 psychotic adolescents are described. These 100 adolescents comprised one-third of the total number of admissions to an adolescent department during the years from 1968 to 1975. There were 58 boys and 42 girls; 53 of the 100 cases had been psychiatrically ill in childhood with evident symptoms. In 22 cases, there was positive information supporting the fact that the patients had been healthy in childhood. The rest (25 cases) were classified under "unclarified picture", showing non specific symptoms. It is concluded that in this material more than half of the adolescents had shown some instability before puberty. The illnesses described in childhood are categorised as infantile borderline psychosis, borderline psychosis probable, and other psychiatric illnesses. A shift in diagnosis is often seen in the individual case, but the symptoms in childhood and in adolescence have many similarities. The necessary treatment in childhood has not been given in one-third of the cases. The possible reasons for this are discussed. In spite of much effort in some cases and because of resistance to therapy or the proposal of inadequate therapy in others, the therapeutic possibilities in childhood have not been fully realised. It is recommended that more emphasis be placed on the emotional development in the evaluation of the children. In the treatment, development of interpersonal relationships through individual, family and/or milieu therapy should be stressed. A follow-up of children with symptoms in childhood left untreated and a teamwork between child psychiatrist and adult psychiatrist with longitudinal studies is suggested.


Manic-depressive psychosis and season of birth.

National series of psychiatric inpatients studied in Scandinavian countries and in England and Wales have all shown that compared with live births in the general population, schizophrenic patients have a significant excess of births in the early months of the year. But there has been disagreement on whether a similar birth distribution holds for manic-depression. The present paper presents new data on the seasonal distribution of births of patients born in England and Wales between 1921 and 1955. Compared with all live births, manic-depression was associated with a significant excess of births in the first quarter, and a corresponding deficiency in the third quarter of the year. Neurotic depression showed no such association. Possible reasons for the disagreement among national findings for manic-depression include difference in the proportion of first ever admissions in the series, differences in age structure, and differences in diagnostic practice and classification. The importance of the age structure of a series is considered in relation to: a) the possible effect of age on the manifestation of a disorder associated with some seasonally related constitutional damage; b) the possibility of secular variation in the severity of a seasonally related noxious factor; and c) the effect of age incidence on distorting the expected seasonal distribution of births in any series of cases.


Individual factors affecting the improvement of anxiety during a therapeutic period of 1 1/2 to 2 years.

Thirty neurotic outpatients suffering from pronounced anxiety were studied and after a therapeutic period of 1.5 to 2 years. The patients were described by means of rating scales and two perceptgenetic methods, the Meta-Contrast Technique and the Afterimage Experiment. It was possible to associate original status with improvement or non-improvement of manifest anxiety. The most positive prognostic sign was sensitivity to marginal (inner and outer) cues, whereas the most negative signs were pre-psychotic discontinuities, projection, and lack of defence mechanisms.


Orbital phlebography. IV. The carernous sinuses and adjacent venous sinuses of the skull base.

Frontal phlebography has been used to examine the cavernous sinuses and adjacent basal venous sinuses of the skull. The method has proved to be simple and effective. The normal phlebographic anatomy of the basal sinuses and their drainage has been revised in a material of 26 cases. A normal range for the transverse diameter of the pituitary fossa has been established.


Frequency of thrombosis and post-thrombotic conditions of the foot at phlebography.

In 350 consecutive ascending phlebographies thrombosis was demonstrated in 60, 6 of which were limited to the foot. The veins of the foot is an overlooked place for the origin of thrombosis and emboli.


Anatomy of the cranial nerves in the basal cisterns. A radiologic post-mortem investigation.

A post-mortem radiologic investigation of the basal cisterns has been made with special regard to the cranial nerves. The cisterns were removed in one piece together with the adjacent brain structures and the skull base. The anatomy of the cranial nerves as seen at cisternography and the frequency of their identification have been analysed. The application in clinical cisternography of the information obtained is discussed.


Meningeal reactions following myelography. Effects of detergent washing agent.

Severe acute meningeal reaction following lumbar myelography are described. Contamination of the cerebrospinal fluid with a detergent washing agent is the most probable etiology.


Congenital arteriovenous malformations of the uterus demonstrated by angiography.

Two cases of congenital arteriovenous malformations of the uterus are described, with details of their angiographic and operative identification. The condition is rare, but should be considered in cases of severe uterine haemorrhage when more routine investigations have been normal.


Liver biopsy with guidance in scanning A preliminary report.

A method to improve the accuracy of obtaining biopsy material of a lesion detected at liver scanning is presented. The site of the lesion is determined in two orthographic projections during scintigraphy and indicated on the patient's skin. With guidance of indicator fluoroscopy in two perpendicular projections percutaneous biopsy from any part of the liver may be performed.


Intensifying screens in soft tissue radiography.

Certain screen-film combinations were tested in the low voltage range (26 to 40 kV, tungsten target) and compared with an optimal non-screen industrial film. The dose reduction was of no consequence as compared with the loss in image quality. Some physical properties of the screens giving rise to the failure are discussed.


Contrast formation in fluoroscopic videodensitometry. III. Relation between roentgen tube potential and exposure rate to produce constant video level.

The exposure rate required to produce a prescribed value of the video level in a vidicon television chain during fluoroscopy was measured for water layers and copper filters of varying thickness. The reduction of the patient exposure rate was found to be so large that, in spite of a reduction of the iodine extinction to 20 to 50 per cent of the value at 40 to 50 kV, examinations of the circulatory system are recommended to be performed at 100 kV with slight copper filtering.


The pancreatographic effect during pharmacoangiography of the pancreas.

Angiography of the pancreas was performed in 55 patients after the administration of different drugs stimulating the blood flow in the pancreas and the pancreatographic effect in this group was compared with that in a series of 174 celiac angiographies without drugs. With drugs the pancreatographic effect appeared more frequently (74.5 per cent) than without (18.4 per cent). The small pancreatic arteries and veins were better demonstrated with drugs. The pancreatographic effect seems to be of value for the differential diagnosis of chronic pancreatitis and carcinoma of the pancreas.


Lymphography in the diagnosis of metastases from carcinoma of the uterine cervix stages i and ii.

The lymphographic accuracy in the diagnosis of metastasis was analysed in 300 patients with carcinoma of the uterine cervix stages Ib and II. Pelvic lymphadenectomy was performed in all patients. Lymphographic and microscopic correlation was assured by means of radiography of the lymphadenectomy specimen. The criteria of metastatic infiltration were critically evaluated.


Cavography and lymphangiography in hodgkin's disease.

In a material of 89 patients with Hodgkin's disease, 98 combined examinations, including lymphangiography, cavography and urography, were performed. Lymphangiography disclosed signs of expansive lesion 33 times, cavography 21 times and urography 17 times. The diagnostic accuracy of lymphangiography was high. Routine cavography in Hodgkin's disease is not advocated; it may be restricted to cases with equivocal lymphographic findings.


Ovarian cysts in women on chronic intermittent haemodialysis.

In a consecutive material of 42 female patients, who were treated with intermittent dialysis for chronic renal failure between May 1964 and Nov. 1971, 21 developed ovarian cysts. The cysts were found only among the 29 women, who had menstrual periods from commencement of dialysis (16 cases) or who started menstruating on dialysis after a period of secondary amenorrhoea (13 cases). No cysts were found in the remaining 13 patients, who had amenorrhoea throughout, and of whom 6 were in all probability postmenopausal. Seven of the 21 patients with ovarian cysts had pronounced symptoms, necessitating acute surgery in 4. Fourteen asymptomatic cases were diagnosed at routine gynaecological examination, which was performed at regular intervals in all patients. There is strong evidence suggesting that the development of ovarian cysts was somehow related to the dialytic treatment and neither to the uraemic state nor to the nature of the primary renal disease. The mechanism by which dialytic treatment may be opertional in the development of this hitherto undescribed complication is discussed, but no clear-cut explanation can be given.


Epidemiology of renal stones in a middle-aged male population.

The natural history of upper urinary tract stones has been studied retrospectively in 49-50 year-old men in an urban population. The prevalence of stones in 2322 men was found to be 13.7%, with the highest incidence of onset of the disease during fifth decade. Recurrences had occurred in 42% of all cases, the frequency increasing with observation time. On some occasion 23% of the patients had been admitted to hospital and 12.3% had been operated on, 94.5% of all stones passed spontaneously. A family history of kidney stones was significantly more common in stone patients than in healthy controls, and patients with a family history of stones were more prone to early and repeated recurrences. It is suggested that the raised incidence of stone disease in some families may be attributed to environmental rather than genetic factors. This could be of importance for prophylaxis. Analysis of hospital admission rates supported previous findings of a steady rise in stone incidence. The advantages of population studies for comparative analyses are pointed out.


Adult type of polycystic kidney disease in a new-born child.

A case of polycystic kidney disease in a newborn child is reported. Renal cortical necrosis due to asphyxia was the cause of death. The histopathological picture and a heavy family history support the rare diagnosis of polycystic kidney disease of adult type in a new-born child.


Plasma renin activity, blood pressure and sodium excretion during treatment with clonidine.

Clonidine, 225 mug a day, has been given orally for 3 months to 15 patients with essential hypertension. Mean BP was reduced from 159/107 to 143/87 mmHg. The antihypertensive effect of the drug was dissociated from changes in plasma renin activity (PRA) during clonidine treatment. PRA levels decreased initially in 6 patients with the highest PRA values before treatment, but then increased again. In 6 patients with lower pretreatment PRA levels, PRA rose continuously. Opposite patterns of 24-hour urinary sodium excretion were observed in these arbitrary subgroups. The antihypertensive effect of clonidine in essential hypertension appears to be independent of changes in PRA.


Dipping procedure for blood glucose determination with Dextrostix and the Eyetone reflectance meter. Assessment of a practical technique.

A dipping procedure for blood glucose determination with the Dextrastix-Eyetone system has been evaluated. The procedure involves the immersion of the Dextrostix reagent area for 1 min in a tube of whole blood followed by wash, blotting and reading as in the regular procedure. Sixty-five blood samples, covering a wide glucose concentration range, were estimated for their glucose content in random order both by the dipping procedure and a conventional Dextrostix-Eyetone procedure. An almost perfect agreement between the two methods was found, the coefficient of correlation being 0.99 and the regression line very close to the ideal line. The presence of a Dextrostix reagent area in the blood was found to bring about glycolysis. Except at high blood glucose levels, this glycolysis, however, was insignificant if the strip was correctly removed after 1 min. The dipping procedure overcomes the main technical problem of conventional procedures: the inconsistency of the drop application on the reagent area. As it is easy to perform and a reliable alternative to conventional procedures, it is recommendable in all cases where blood samples are available.


Subcutaneous administration of sodium l-thyroxine to patients with hypothyroidism.

Two patients with primary hypothyroidism are described in whom an euthyroid condition could not be achieved by oral administration of 1-thyroxine, 1-triiodothyronine or desiccated thyroid. Daily subcutaneous injections of 1-thyroxine normalized the thyroxine and triiodothyronine levels in the blood and the patients became euthyroid.


The smoking habits of men with intermittent claudication.

Smoking habits among 54 male patients with intermittent claudication (IC) and 200 healthy 50-year-old men from the same county have been studied. The prevalence of smokers at the age of 50 was 98% among the IC patients against 46% among the healthy controls. The percentage of heavy smokers and the total tobacco consumptiion were not significantly different in the two groups. However, the percentage of smokers who began to smoke before the age of 15 was significantly higher in IC patients than in the healthy group, 28% to 7%.


Studies in asymptomatic primary hyperlipidaemia, III. Physical working capacity.

One-hundred-and-sixty male and 123 female subjects with asymptomatic primary hyperlipidaemia (HLP) selected from a health control centre have been studied with a heart rate (HR) controlled exercise test. Ther serum cholesterol and/or TG at screening were above 350 mg/100 ml and 3.5 mmol/l, respectively. As a reference group 49 male and 60 female age-matched subjects from the same centre with serum cholesterol below 300 mg/100 ml and TG below 2.00 mmol/l were investigated using the same technique. Quantitative lipoprotein (LP) analyses and typing were performed on all HLP and control subjects. The subjects were divided into two age groups, 36-50 and above 50 years of age. Men with all types of HLP had lower working capacity, expressed in W170 or W150, than controls, most pronounced in the younger age group. Younger women with type II A had lower working capacity than their controls. After correction for variation in body weight and age there remained a significantly lower W150, in male types II A (11%) and IV (21%) and female type II A (11%). There was no difference in systolic BP during exercise between controls and HLP. The total exercise time and final HR did not differ in control and HLP subjects. Dynamic spirometry was performed im 102 of the male subjects and a significantly lower vital capacity was found in HLP subjects compared with controls after correction for variation in age, weight and height. No differences were found in the maximal flow values. The observed differences in working capacity between controls and HLP subjects are explained by a difference in stroke volume. The lower stroke volumes in male types II A and IV and female type II A could be explained by a lower degree of physical fitness, by a common genetic factor resulting in HLP and decreased stroke volume or by a less effective myocardial function in HLP subjects.


A postmyocardial infarction clinic in Göteborg, Sweden. A follow-up of MI patients in a specialized out-patient clinic.

The registration of all myocardial infarctions (MI) in the city of Göteborg started on Jan. 1st 1968, when a special clinic was set up for ambulatory posthospital care of infarction patients. In 1970 this clinic was expanded to cover all patients below 67 years of age with MI in the city of Göteborg, the aim being to standardize and unify patient care and therapeutic regimens to provide opportunities for the study of patient characteristics, natural history, risk factors and effects of preventive measures. Results from such studies have been published, but so far no unified description of this special out-patient unit, nor of any similar unit elsewhere. Patient recruitment, considerations concerning personnel, patient education procedures and return visit routines are covered, together with investigative methods and criteria for the treatment of complications, symptoms and risk factors. The cumulative drop-out rate up to and including 2 years follow-up was only 3%. A brief bibliography of studies originating at the Postmyocardial Infarction Clinic is included.


Creatine phosphokinase after submaximal physical exercise in untrained individuals.

Serial estimations of total serum creatine phosphokinase (CPK) have been performed before and during 18-49 hours after submaximal physical exercise in 17 untrained individuals, mean age 50 years. The maximal CPK increase after exercise was 32 mU/ml (73%). The serum CPK did not exceed the upper normal limit (130 mU/ml) except in one individual (150 mU/ml). The maximal CPK increase in patients with acute myocardial infarction (AMI) varied between 101 mU/ml (133%) and 2 260mU/ml(3 790%), mean 900 mU/ml (1 184%). As the maximal CPK elevation in AMI occurs within the same period, it seems that heavy physical work of short duration just before the onset of symptoms will very seldom impair the diagnosis of AMI with the CPK technique used.


Gaucher's disease and benign monoclonal gammapathy. A case report with immunofluorescence study of bone marrow and spleen.

A case of chronic non-neuronopathic Gaucher's disease is presented. The diagnosis was based on the finging of typical Gaucher cells in the bone marrow spleen. The patient also had a benign monoclonal gammapathy. Immunofluorescence studies of bone marrow and spleen were performed using monospecif antisera against immunoglobulin heavy and light chains. The results indicate a monoclonal plasma cell proliferation in the bone marrow, whereas the distribution of plasma cells in the spleen was polyclonal. The combination of chronic Gaucher's disease and monoclonal gammapathy was also found in the patient's brother.


Combined phytohaemagglutinin and dianhydrodulcitol treatment of lymphocytic choriomeningitis virus infection in mice.

The course of intracerebral lymphocytic choriomeningitis (LCM) virus infection was studied in mice treated simultaneously with dianhydrodulcitol (DAD) and phytohaemagglutinin (PHA). Earlier experiments revealed that DAD decreased and PHA enhanced the cellular immune response of mice to LCM virus infection. On applying the treatments simultaneously they inhibited each other and neither the decreasing effect of DAD nor the enhancing effect of PHA on the cellular immune response could be observed.


Pathogenicity of avian mycoplasma serotypes for embryonated chicken eggs.

Forty-seven strains of avian mycoplasma, representing 8 serotypes (A, B, C, E, L, M, P and R) were tested for pathogenicity to embryonated chicken eggs. Serotypes A and R were distinctly pathogenic, serotype C was slightly pathogenic wheras serotypes B, E, L, M and P were non-pathogenic.


A new fungal isolate from Paspalum scrobiculatum, Linn. with new biologically active metabolites.

A new fungal isolate from the host plant Paspalum scrobiculatum Linn., is reported. It is characterized and designated as a separate species Phomopsis paspali (n. sp.), not only for the different morphological characters as compared with the commonly occurring Phomopsis species in India, but also in view of its distinctive feature of producing biologically active new metabolites, cytochalasans. In addition, the genus Phomopsis has not been reported on this plant anywhere in the world.


New serotypes of Morganella morganii.

On the basis of 8 new O and 11 new H antigens determined in 22 strains, the Morganella morganii antigenic schema was supplemented with 8 serogroups (O35-O42) and 13 serotypes. Four strains belonged to O groups described earlier and 2 strains contained new O antigens in combination with known O antigens. Known H antigens were present in one strain as a single factor and in one strain as combination of two factors. New H antigens were demonstrated in 5 serotypes in combination with known H antigens. Six out of the 22 isolates were classified into O group 35. Two isolates contained different B-type surface antigens; these factors were not related to Escherichia coli B antigens and, unlike the latter, their living suspension gave a higher titre agglutination in OK serum as compared to the boild culture.


Functional organization of adrenal chromaffin vesicles.

The functions of the chromaffin vesicles are reflected in their molecular organization. They contain large amounts of water-soluble proteins and ATP, which act in concert with catecholamines to form a stable storage pool. The vesicles contain an ATP-driven catecholamine transport system that enables the vesicles to take up dopamine, the precursor to NE, and to recover amines that leak out of the granules. The transport system appears to be coupled to the ATPase activity of the vesicle membranes and to include an amine carrier. The enzyme DBH is present as a soluble protein within the vesicle and as a component of the membrane. However, substrates can be acted upon only after they have been transported into the vesicle. During secretion the vesicle membrane fuses with the plasma membrane, but little is known about how this occurs.


Effect of reperfusion in acute ischemia and infarction.

Physiologic concepts relating to reperfusion of ischemic areas of myocardium may be applied both to acute coronary insuficiency, manifested by angina pectoris, and to restoration of coronary blood flow by coronary bypass procedures, currently employed both in acute myocardial infarction and in chronic myocardial ischemia for relief of angina pectoris. Of the information currently available from experimental studies, much may be applicable to the clinical situation. After acutr transient coronary occlusion mechanical and electrical properties of the ischemic area rapidly return to normal, but there is prolongation of tension development and occurrence of ventricular arrhythmias; implications of these phenomena for clinical coronary ischemia deserve exploration. Following more prolonged coronary ischemia, results of experimental reperfusion appear to be variable and, although restoration of function following several hours of ischemia is possible, certain deleterious effects are often observed in the form of myocardial edema and hemorrhage. Clinical use of bypass procedures in acute myocardial infarction suggests that results may be good, but that deleterious effects are occasionally observed; occurrence of the later requires definition and explanation. Restoration of myocardial blood flow in the presence of normal left ventricular function in chronic coronary artery disease, and failure to reverse functional abnormalities when left ventricular damage has already ensued in the clinical situation, appears to be well established; however, better methods to assess the potential for recovery of function following revascularization are needed in both acute and chronic coronary artery diseases. It is anticipated that more careful exploration of pathophysiology both in the catheterization laboratory and in the operating room may aid this process.


Perioperative myocardial infarction during cardiac surgery. Diagnosis, ECG and enzyme testing.

The detection of perioperative myocardial infarction is complicated by the variety of electrocardiographic changes normally seen concomitantly with cardiac surgery. Unequivocal electrocardiographic diagnoses based on new Q wave development and evolution of ST and T segments are virtually always confirmed by inappropriately high postoperative enzyme test results. For those patients exhibiting nondiagnostic but suggestive electrocardiographic changes, enzyme testing provides a valuable adjunct in determining whether infarction has indeed taken place. Enzyme testing, similarly, in and of itself, cannot provide the dichotomous situation between those patients experiencing infarction and those who are not. SGOT and LDH appear the most reliable indicators of infarction. CPK is quite volatile with sporadic occurrences of high enzyme elevations without obvious clinical or electrocardiographic explanation. The Ck isoenzymes provide a highly specific test for myocardial damage. However, their sensitivity is sufficiently great that a relatively minor cardiac manipulation may result in uninterpretable results.


Quantification of myocardial ischemic injury.

Quantitative assessment of infarct size is becoming increasingly important, particularly since this parameter appears to be a major determinant of prognosis. Morphologic, radioisotopic and electrophysiological techniques for assessing the extent of irreversible ischemic injury entail certain unavoidable limitations. Experimental and preliminary clinical findings suggest that estimation of the extent of infarction from biochemical markers in serum is practical and useful. Furthermore, prediction of infarct size during its early evolution may improve selection of patients for interventions designed to protect ischemic myocardium and may contribute to objective assessment of their efficacy.


Management of acute myocardial infarction. Pathophysiological considerations.

Development of improved techniques for assessing infarct size in intact experimental animals and in patients has made it possible to evaluate the effectiveness of selected interventions more objectively. It is becoming increasingly apparent that infarct size is an important determinant of prognosis. Experimentally, infarct size can be modified favorably under specified conditions by interventions designed to reduce myocardial oxygen requirements or increase myocardial energy supply during the early evolution of infarction. Preliminary clinical applications of these concepts have been encouraging. The time seems to be right for carefully controlled clinical investigations to determine whether techniques designed to protect ischemic myocardium will be effective in improving survival and reducing morbidity from acute myocardial infarction. On the basis of available evidence, it seems clear that appropriate management of patients with this disorder should include careful attention to the impact of any therapeutic modality on the heart itself. It does not suffice to treat patients with beta-adrenergic agonists simply because they may elevate systemic arterial blood pressure. Hemodynamics can not be the sole criteria in guiding the physician charged with the responsibility for patient management. Rather, he must consider the potential effects of any contemplated therapeutic modality on myocardial viability as well. The ultimate place if interventions designed to protect ischemic myocardium in the therapeutic armamentarium remains to be determined. However, judicious therapy should be designed to minimize myocardial oxygen requirements and maximize myocardial energy supply as well as to prevent criti  l impairment of peripheral perfusion.


Structure and function of concanavalin A.

Lectins have been extensively used to analyze a variety of fundamental processes in cell biology. In conjuntion with our studies on the cell surface and mitosis, we have determined the amino acid sequence and three-dimensional struction of concanavalin A (Con A), the mitogenic lectin from the jack bean. Knowledge of the structure has been helpful in interpreting experiments on lymphocyte mitogenesis and the effects of Con A on cell surface receptor mobility. Con A subunits for molecular weight 25,500 are folded into dome-like structures of maximum dimensions 42 times 40 times 39 A. The domes are related by 222 symmetry to form roughly tetrahedral tetramers. Each subunit contains two large antiparallel pleated sheets, and subunits are joined to form dimers and tetramers by interactions involving one of these pleated sheets. We have examined the binding of a variety of carbohydrates to Con A and have obtained preliminary data which suggest that there are differences in the saccharide-binding behavior of Con A in solution and in the crystalline state. Dimeric chemical derivatives of Con A have been prepared and shown to have biological activities different from those of the native tetrameric protein. Under different conditions, native Con A exhibits two antagonistic activities on the lymphoid cell surface: the induction of cap formation by its own receptors and the inhibition of the mobility of a variety of receptors, including its own receptors. The dimeric derivative, succinyl-Con A, is just as effective a mitogen as the native lectin, but it lacks the ability to modulate cell surface receptor mobility. The data suggest that neither extensive immobilization of cell surface receptors nor cap formation is required for cell stimulation. Further studies on modulation of receptor translocation suggest that hypothesis that there exists a connecting network of colchicine-sensitive proteins that links receptors of different kinds and mediates their rearrangement. The degree of connectivity of this postulated network appears to be altered by changes in the state of attachment of various surface receptors to the network. Thus the network might provide the cell with a means of transmitting signals such as the stimulus for mitosis by lectins or antigens.


Studies on the combining sites of concanavalin A.

The initial event in the biological activity of concanavalin A (Con A) involves binding of the protein to cell surface receptors. The nature and mechanism whereby such binding may occur is described in terms of cell surface carbohydrates and the demonstrated specificity of the protein. Although considerable latitude is tolerated at the C-2 position of the alpha-D-hexopyranose ring system, the carbohydrate binding site of Con A appears to be complemnetary to alpha-D-mannopyranosyl residues. Hapten inhibition studies indicate that each of the hydroxyl groups of this sugar is probably involved in the binding mechanism. Of the common sugars present on cell surfaces (D-glucose, D-mannose and N-acetyl-D-glucosamine), it is probably alpha-D-mannopyranosyl residues which react with Con A. Since the latter units are primary receptors for Con A. Evidence supporting this view includes hapten inhibition studies with model oligosaccarides and preciptin studies with macromolecules containing internal 2-o-substituted alpha-D-mannopyranosyl residues. The binding to Con A of a series of oligosaccharides containing alpha-(1leads to2)-linked D-mannosyl units appears to increase up to the tetraose and then decreases; several possible explanations are considered. Acetylated Con A, although retaining its specificity, is about 50% as active as the native protein. Some biological properties of the modified protein are described. Data suggesting that Con A behaves differently in the solution phase than in the crystalline state are presented in terms of UV difference displacement studies. It is suggested that the so-called carbohydrate binding site reportedly identified in Con A crystals may not be correct.


13C NMR studies of the interaction of concanavalin A with saccharides.

The binding of alpha- and beta-methyl-D-glucopyranoside and beta-(o-iodo-pheryl)-D-glucopyranoside to concanavalin A has been studied by carbon-13 nuclear magnetic resonance techniques. The kinetics and binding orientations of these saccharides relative to the transition metal ion site in the protein have been determined.


Cytochrome P-450 in the activation and inactivation of carcinogens.

The capacity of isolate mouse liver microsomes to alter the mutagenicity for bacteria of the primary carcinogen N-methyl-N'-nitro-N-nitrosoguanisine (MNNG) and the secondary one dimethylnitrosamine (DMN) was studied. Microsomal activation of DMN and inactivation of MNNG were decreased by protein- and protein-cholinedeficient diets and were increased by pretreatment with microsomal enzyme inducers. The decrease and increase paralleled the content of cytochrome P-450 present in the different microsomal preparations. With human liver microsomes of differing cytochrome P-450 contents similar correlation was obtained, whereas normal rat liver microsomes did not activate or inactivate DMN or MNNG. Oxidative demethylation of DMN by mouse liver microsomes and the activation of DMN to a mutagen followed similar kinetics. Both reactions were inhibited by carbon monoxide and the inhibition was maximally reversed by monochromatic light at 450 nm. These observations indicate that at least some carcinogens are activated or inactivated by the unspecific cytochrome P-450 dependent enzyme system, suggesting that the extent of this biotransformation may be one factor influencing human carcinogenesis.


Increased translation as a result of elevated initation factor activity after administration of 3-methylcholanthrene.

Protein synthesis initiation factors present in a crude 0.5 M KCL microsomal wash fraction were isolated from the livers of immature rats that had been injected either 2 or 17 hours earlier with the plycyclic hydrocarbon, 3-methylcholanthrene (3MC), and then were tested for their ability to stimulate natural mRNA-directed protein synthesis in vitro. After purification of the initiation factors by means of ammonium sulfate fractionation, and DEAE-cellulose and Sephadex G-200 chromatography, M2A and M2B, but not M3 or M1, from the livers of 3MC-pretreated rats were more active than were similarly-prepared control factors in their ability to initiate the synthesis of rabbit globin polypeptides in a highly fractionated cell-free protein synthesizing system derived from rabbit reticulocytes. The greater activity of the M2A and M2B preparations from drug-treated rat liver did not appear to be due to differences in the composition of initiation factor protein extracted from the livers of control or experimental rats and occurred very early after administration of 3MC, i.e., 2 hr. The role of the protein synthesis initiation factors in the altered rates of protein synthesis which accompany cytodifferentiation and growth is discussed.


Implication of ligand modified spectra of cytochrome P-450 associated with pregnenolone synthesis in mitochondria from corpus luteum.

The implications of ligand modified spectra of cytochrome P-450 in mitochondria from corpus luteum are considered. Mitochondria from bovine corpus luteum contain a single cytochrome P-450 which oxidizes cholesterol to pregnenolone and isocaproaldehyde. These mitochondria and the cytochrome P-450 purified from these mitochondria yield Type I spectral changes with substrates, reverse Type I spectral changes with certain steroid substrates, steroid products and unrelated steroid ligands. Nitrogenous ligands yield Type II spectral changes. Mitochondrial and purified cytochrome P-450 preparations are equivalent in this study. The inhibitory effects on the cholesterol monooxygenase are directly related to the spectral changes induced by Type II ligands. Lastly, it is suggested that a similar relationship exists with reverse Type I ligands.


A possible role of copper in the regulation of heme biosynthesis through ferrochelatase.

Experiments have been performed which show that it is possible to regulate heme biosynthesis by regulating ferrochelatase activity. Treatment of rats with the transition metals, Co-++ and Mn-+-+,  has been shown to inhibit ferrochelatase activity and to produce a dose-dependent decrease in hepatic cytochrome P-450 content. Unlike other transition metals, copper stimulated ferrochelatase activity and there was an interaction between Cu-+-+ and Fe-+-+ in the system such that the Km of Fe-+-+ was dependent on the concentration of copper. After solubilizing and dialyzing hepatic mitochondrial preparations, ferrochelatase activity was lost and could be restored by the addition of copper. In addition, copper, but not iron, reversed the inhibition of ferrochelatase activity produced by Pb-+-+ or Co-+-+. This study suggest that cytochrome P-450 content may be decreased during copper deficiency due to a decrease in ferrochelatase activity and a subsequent defect in heme biosynthesis. The synthesis of other hemoproteins may also be affected by copper deficiency. For example, it is well known that copper deficiency can lead to anemias (Lee et al., 1968) which might be explained by an intracellular defect in heme biosynthesis at ferrochelatase.


Immunochemical and compositional comparison of cytochrome P-450 cam of Pseudomonas putida and P-450 lm of phenobarbital-induced rabbit liver microsomes.

Although highly purified cytochrome P-450 of Pseudomonas putida (P-450 cam), and that from phenobarbital-induced rabbit liver microsomes (P-450 LM), differ markedly in their catalytic and physical properties, they show immunological cross reaction by competitive binding and inhibition of catalytic activity, and are of similar amino acid composition. Upon treatment with cyanogen bromide they yield small heme-containing peptides of highly similar amino acid composition.


Comparison of the induction course, biophysical chemical interactions and photochemical action spectra of phenobarbital and 3-methylcholanthrene induce hepatic microsomal P-450.

A comparison has been made of the physical and chemical properties of hepatic microsomal P-450 and associated enzyme systems from rats treated with phenobarbital or with 3-methylcholanthrene and other polycyclic aryl hydrocarbons. The results of these studies, though preliminary in nature, indicate clearly that the aryl-induced mixed-function oxidase systems differ significantly from the PB-induced ones in time course of induction, spectral properties, hyroxylase and demethylase activities, CO-inhibition of these reactions and light-reversal of the inhibition. The results support and extend the findings of other investigators regarding the differential biophysical and biochemical properties of aryl-induced systems and provide an experimental design for studying these properties in greater depth at the maximum of aryl induction.


Postnatal differentiation of "presynaptic dendrites" in the lateral geniculate nucleus of the rhesus monkey.

The most characteristic synaptic arrangement in the LGN is the triadic unit, in which a retinal terminal is presynaptic to a principal cell (P cell) and to a Golgi interneuron (I cell) dendrite, which contains synaptic vesicles and is in turn presynaptic to the same P-cell element. The ontogenetic differentiation of these "presynaptic dendrites" was studied in monkey LGN by standard and quantitative electron microscopy. The dendrites and axonal arborization of I cells are well developed in the newborn monkey. Scattered synaptic vesicles are present in the dendrites, but these profiles exhibit only postsynaptic sites. The dendrodendritic synapse of the triadic arrangement is missing, although contacts between P-cell and I-cell dendrites can be observed. Conversely, the I-cell axons in the newborn establish numerous synapses with dendrites and perikarya of P cells. At about 2 weeks of age, presynaptic sites appear in the I-cell dendrites, resulting in the formation of synaptic triads. Parallel to the development of "axonal" properties in the dendrites, the number of true I-cell axonal profiles decreases sharply. These transformations become progressively more frequent with age, and beyond 8 weeks the LGN ultraarchitectonics approaches that of the mature animal. The percentage of the surface of interneuron processes occupied by presynaptic sites is similar at all developmental stages at about the 2.6% level. The relative contribution of presynaptic dendrites and of axons changes, however, so that the actual length of contacts in the mature monkey is only one-half that of the newborn for the axonal sites, and over 50 times longer for the dendritic sites. The correlation of these findings with electrophysiologic and behavioral references suggests that some but not all axonal functions may be taken over by the dendrites, that the possible inhibitory phasing of P-cell discharge would appear only after the second postnatal week, and that the triadic arrangement may not be indispensable for brightness or total luminous flux discrimination but could be required for more complex forms of visually guided behavior.


Differentiation of dendrites in the transplanted neuroblasts in the mammalian brain.

Neocortical tissue obtained from the 8-day old rat embryos was transplanted into the cerebellum of 10-day-old rats. Within these transplants various subregions were seen, some with laminated cytoarchitecture and others with nuclear organization. The laminated structures were found to contain the pyramidal nerve cells of the neocortex. The differentiation of dendrites of these pyramidal cells was studied in Golgi-Cox preparations. The sequence of dendritic growth and differentiation and the pattern of dendritic arborization were found to be very similar to those seen in the pyramidal cells of the neocortex. These two attributes of dendritic differentiation of the pyramidal cells were therefore considered to be predetermined. However, the course and the length of the apical dendrites were found to be greatly altered; therefore, these two characteristics were evaluated and found to be influenced by the milieu immediately surrounding the transplanted neuronal elements. Futhermore, the apical dendrites were found to form bundles. It was not possible to establish whether or not this characteristic of dendritic organization was predetermined. Electron microscopic evaluation revealed the presence of axodendritic and axosomatic synapses on the pyramidal cells. These observations suggested that the transplanted neuronal elements may be physiologically active, and that if trophic influences mediated by the synaptic endings had contributed to the differentiation of the pyramidal cells and their dendrites, they could not have been specific in nature.


Application of network analysis to the study of the branching patterns of dendritic fields.

The technique of network analysis has been used to define the connectivity and growth of networks generated by monochotomous, dichotomous, and trichotomous branching. The number of distinct topologic branching patterns exhibited by networks with a given number of pendant arcs is defined mathematically; when all types are represented, a complete pendant arc series is formed. The frequency of occurrence of topologic types in these series is unique for a given hypothesis of growth. The growth of the small dendritic arrays such as the basal dendritic fields of neocortical pyramids may be studied by comparing the actual frequency of topologic types with those computed according to given hypotheses. For larger dendritic networks such as those of Purkinje cells in the cerebellum it is only practicable to use the topologic types formed by the peripheral parts of the tree as a basis for comparison. Individual dendritic segments can be ordered sequentially to define their hierarchical arrangement; the frequency of orders in a given network always forms an inverse geometric series. The ratio between orders is called the "bifurcation ratio," and the relationship in a given large series between adjacent orders becomes stabilized to a fixed or "established" bifurcation ratio at the periphery of the tree only. This "established ratio" characterizes the pattern of growth of the network. In the proximal part of the tree the ratio between adjacent orders is unstable and accounts for the variability of the overall bifurcation ratio exhibited by different networks with the same fundamental growth pattern and for the deviation of the overall from the established bifurcation ratio. For a given size of network the overall bifurcation ratio may be similar regardless of the mode of growth. It is concluded that the precise definition of branching structures afforded by network analysis makes this technique well suited for the study of the connectivity, growth, and morphology of dendritic trees.


Ordering methods in quantitative analysis of branching structures of dendritic trees.

Two different ordering methods used in quantitative analysis of dendritic trees are compared with respect to the chief objective of doing the ordering, viz. grouping together those segments of a branching pattern which have similar characteristics. After describing the different properties of these two ordering methods (i.e., Strahler method and centrifugal method), criteria are given for selecting one or the other of the two methods.


Ultrastructural changes in dendrites of central neurons during axon reaction.

Retrograde atrophy of rat thalamus is marked by the appearance of profound alterations in dendrites. Concurrently, similar changes occur in parent cell somata. Electron-dense and abnormally electron-lucent dendritic profiles appear and are removed over different time courses. The morphologic features of the abnormal dendrites are detailed. Electron-dense and electron-lucent dendritic profiles are not observed in cat red nucleus after rubrospinal tractotomy. Rather, neurofilamentous hyperplasia and proliferation of smooth endoplasmic reticulum appear in affected dendrites and are identical to changes observable at the same time in the reacting parent nerve cells. The literature is reviewed and discussion is developed on the similarities of perikaryal and dendritic changes that occur in axon reaction and transneuronal degeneration.


Dendrites and neuroglia following hemisection of rat spinal cord: effects of puromycin.

Within 60 to 90 days of spinal cord hemisection or hemisection, Gelfoam, water implantation in the lesion site, ventral horn neurons 0 to 5 mm proximal to the site of lesion form varicosities along the dendrite. The varicosities form on peripheral dendrites at 10 days and progressively involve the entire dendritic shaft by 60 to 90 days. Following spinal cord hemisection and Gelfoam puromycin implantation the neurons in the ventral horn are resistant to varicosity formation. Sixty days after hemisection puromycin-treated neurons form a few varicosities on occasional peripheral dendrites with no further involvement of the dendrite by 90 days postlesion. The neuroglial reaction to hemisection is not altered by puromycin treatment. The correlation of inhibition of protein synthesis and resistance to dendritic varicosity formation is discussed.


Virions and virus-associated structures within dendrites in an experimental flavovirus encephalomyelitis.

In experimental yellow fever virus encephalomyelitis of adult albino mice, virions, and virus-associated structures were observed not only inside neuronal perikarya but also within dendrites of varied size. The finding permits the following explanations: (1) either the viral agent is synthesized in the nerve cell bodies and transported intradendritically in a proximodistal direction; or (2) virus morphogenesis takes place in neuronal perikarya and dendrites as well; or (3) both possiblities are equally valid. Some incidental findings were suggestive of virus release at postsynaptic dendrite membranes. They are discussed with reference to a hypothetical long-distance pathway of viral dissemination involving endocytosis of the agent by presynaptic axon terminals, intraaxonal virus decoating, and retrograde axoplasmic transport of the infectious nucleic acid to the cell soma.


Dendrodendritic gap junctions: a developmental approach.

Dendrodendritic gap junctions have been identified in the periaqueductal gray substance of adult rabbits and in the visual cortex of sheep fetuses. The introduction of Alcian blue as a marker substance facilitated the positive identification of gap junctions. Dendrodendritic contacts in the human fetal neocortex have been examined in freeze-cleaved specimens. The contacts are identified as gap junctions by their freeze-fracture appearance. Features of the developing dendrodendritic gap junctions are described. The possible significance of these contacts is discussed, and it is suggested that they provide electrotonic coupling of neurons belonging to the same columnar organization. In addition it is suggested that the dendrodendritic gap junctions of fetal neocortex participate in cell differentiation and morphogenesis of the cerebral wall.


Clinical value of serum alkaline phosphatase isoenzyme estimations in the elderly.

The value of the estimation of liver and bone isoenzyme of alkaline phosphatase in a series of 500 admissions to a geriatric unit is described. A raised total alkaline phosphatase was found in 40 patients and this was due to raised levels of the bone isoenzyme in about two-thirds of these. Its value in diagnosis of treatable bone disease is emphasized.


Subluxation of the shoulder in hemiplegia.

This is a study of 100 hemiplegic patients of whom 17 had downward subluxation of the shoulder joint. The mechanism of this complication is described and appropriate preventative treatment suggested.


Seasonal and short-term relationships of temperature with deaths from myocardial and cerebral infarction.

In subjects over 60, changes in temperature lasting two or more days are associated with highly significant changes in death rates from myocardial infarction and cerbral vascular accidents. In both cases, the lower the temperature the higher the death rate and vice versa. Moreover the temperatures one to four days prior to the clinical onset of infarction are more relevant than that on the day of onset, a fact which may have a bearing on prophylaxis. In the case of strokes, a high temperature on the day of onset is also associated with an increase in deaths on that day. The relevance of these findings to possible mechanisms and prophylaxis is discussed.


Metabolic studies in physically outstanding elderly men.

Forty-seven elderly men engaged in regular and vigorous exercise had significantly lower plasma insulin levels during oral glucose tolerance tests than their controls. Pasma-glucose and growth-hormone levels showed no difference. However, when the glucose tolerance test was extended to four hours follow up, for which 19 subjects of each group volunteered, the control subjects showed a blunted post-suppression recovery of growth-hormone secretion in comparison to the athletic group. This difference could be explained by differences in hypothalamic control of the pituitary.


Evaluation of vision in slow-stream wards.

Two hundred and twenty-one patients in slow-stream geriatric wards in the Portsmouth district were questioned about their vision; 159 of these were examined. It was possible to give help with vision to 21 per cent of patients and to give a further 6 percent help with other eye problems. Eighteen months later, when half the patients examined had died, 14 per cent of those still alive were continuing to enjoy their improved vision, and 6 per cent were benefitting from the help they had received with other eye problems. As a result, we recommend that all admissions should be assessed with regard to their visual ability and that all those with adequate mental faculties should be examined by an ophthalmologist or an optician on admission and when necessary therafter.


Skinfold thickness on the dorsum of the hand in the elderly.

The skinfold thickness on the dorsum of the right hand over the second metacarpal was measured with Harpenden calipers in 276 women and 152 men aged 65 and over living at home. Mean values were higher in men than women and declined with age in both sexes. Skinfold thickness was related to body size, as estimated from lean body mass, but was unrelated to the presence of osteoporosis as assessed from bone mass of the second metacarpal or the presence of vertebral fractures. The skinfold thickness was low in those subjects who had senile purpura and also in a small group of subjects on long-term steroid therapy.


Activity changes in mouse brain histidine decarboxylase.

Mice were tested for effects of various factors on histidine decarboxylase of whole brain, or major brain regions. Factors included age, sex, fasting and feeding, season of year, time of day, freezing for various time intervals, and intracerebral injection of protein synthesis inhibitors daily for 2-5 days. In the latter test, 5 day treatment with acetoxycycloheximide reduced brain histidine decarboxylase activity. In one experiment, in which a marked activity increase was observed, brain infection seemed to be the stimulus. Brain enzyme activity in normal mice showed large fluctuations over periods of several months to one year; presumably this is of some physiological significance but the causes are obscure.


Comparison of in vitro and in vivo histamine methylation by tissues.

A method for determining the histamine-methylating enzyme (HME) using crude enzyme, and minute quantities of the substrate, was applied to tissues of mice, guinea-pigs and rats. Since high levels of endogenous histamine can affect the results, tissue homogenates were dialyzed prior to incubation. Findings were compared with in vivo data on methylating ability of individual tissues; most of this in vivo data is published but a new test of guinea-pig tissues was made using amodiaquine as an inhibitor. The correlation was good, better than that obtained by other procedures. It was observed that dialysis caused an increase in HME for some guinea-pig tissues, but a loss for some mouse tissues. Possible explanations are considered. Quinacrine N-mustard, a derivative of a known HME inhibitor, was tested in mice; it altered the distribution of injected 14C-histamine but showed no evidence of HME inhibition.


p-CMB-dextran T 10. A useful tool in evaluating the functional importance of superficial SH-groups in rat adipocytes.

A large SH-blocking reagent p-CMB-dextran T 10 (MW about 10,000) was applied to isolated rat adipocytes. This compound possesses the same reactivity towards SH-groups as uncoupled p-CMB. P-CMB-Dextran T 10 did not influence the basal glucose uptake in contrast to uncoupled p-CMB. The results are discussed with respect to the usefulness of p-CMB-dextran T 10 in evaluating the role of superficial SH-groups in various membrane functions.


The evaluation of cotton twine as a new anti-inflammatory assay.

A new anti-inflammatory assay is described, utilizing a subcutaneously implanted elongated section of cotton twine to induce granuloma in rats. The cotton twine irritant is easily introduced under the abdominal skin and after seven days a well formed granuloma is established. The procedure works effectively for both steroidal and non-steroidal anti-inflammatory drug evaluation. Consistency of the cotton twine eliminates individual weighing of each section and uniformity in compactness affords reproducible results.


Structure-activity profile of substituted purines and inflammation in the delayed hypersensitivity skin reaction.

Substituted purines were tested for their effectiveness in inhibiting the delayed hypersensitivity skin reaction (DHSR) caused by tuberculin in the guinea-pig. Among the tested purines were naturally occurring derivatives of guanine and adenine, including cyclic AMP. Based on the structure-activity profile, a class of purines was identified, the members of which were very effective inhibitors of inflammatory aspects of the DHSR and are characterized by a benzyl group in position 9, an amino or alkylamino group in position 6, and various substituents in position 2. This class of 2-substituted-9-benzyladenines was more effective in the DHSR than some antimetabolites, particularly the structurally related mercaptopurines.


Substituted 9-benzyladenines: inhibitors of inflammation associated with the delayed hypersensitivity skin reaction.

Members of a group of substituted 9-benzyladenines have been identified as effective inhibitors of inflammatory aspects of the delayed hypersensitivity skin reaction in the guinea-pig. Inhibitory activity was demonstrable in the efferent arc of the cell-mediated tuberculin and contact dermatitis (2,4-dinitrochlorobenzene) reactions. One of the compounds, 2-amino-9-benzyladenine, inhibited both turpentine-induced and histamine-induced inflammation in the skin. The toxicity and inhibitory activities of some of these compounds are discussed, and reference is made to the structurally related mercaptopurines.


The optimization test in the guinea-pig. A method for the predictive evaluation of the contact allergenicity of chemicals.

Guinea-pigs were sensitized with various substances (DNCB, penicillin G, PPL, ethylaminobenzoate, formalin) by the Draize method, the maximization method and the new optimization method (intracutaneous test employing adjuvant). The advantages of the optimization method favouring its adoption as a standard sensitization test are discussed in the light of the results obtained by this method and with the two established tests.


Problem drinking in adolescence.

Diagnostic criteria for the early stages of alcoholism are unclearmaccordingly, especially in young problem drinkers, emphasis should be on symptomatic treatment and shifting environmental support away from drinking. Alcohol use is frequently a precursor and a corollary of other drug use. Active intervention by the family physician can be very effective. Starting at age 15, the medical history should include a survey of alcohol consumption.


Common problems in ophthalmic plastic surgery.

Many ophthalmic plastic surgical problems are ignored because the patient seems to be ""getting along." Frequently physicians are only vaguely aware of the constant daily discomfort their patients experience from seemingly minor problems such as endocrine exophthalmos, an ill-fitting prosthesis or baggy eyelids. As a result, too often the patient is unaware of the treatment possibilities that are available to relieve and often eliminate his problem. These conditions are often first seen by the family physician.


Bronchial reactivity to exercise in bronchial asthma.

In 65 asthmatics the behaviour of resistance during and following physical exercise was analyzed. There could be distinguished 3 types: I. Decrease of resistance during exercise. II. Decrease of resistance during exercise, but increase during recovery phase. III. Increase with a maximum of 8 to 15 min following exercise. The most frequent type was type II. Type III was characterized by lower initial values of FEV 1.0 and the highest relation between expiratory and inspiratory resistance. The strongest reaction to acetylcholine occurred in types II and III. The results speak in favour of the fact that vegetative irritability as well as mechanical factors are of special importance in exercise-induced asthma.


[Bronchial asthma: clinico-pathological study of fatalities in intensive care units].

Due to the great amount of asthmatic patients presenting complications which could endanger their lives, a revision of the possible threatening factors is carried out. The factors concurring with the base pathologic mechanism are analyzed and it is demonstrated, that some of these factors intervene independently from bronchial asthma. The study is carried out on the basis of age, sex, hospital stay duration, clinical picture, blood gases analysis, complications and pathology findings: 1) Most of the deceased patients presented various pathologies besides bronchial asthma which contributed to the decease. 2) The physician should be alert in order to establish good therapeutic procedure in these patients which could carry other important complications; these complications are responsible for the fatal outcome in a great number of patients. A complication should always be searched for, e.g. pneumothorax. 3) The vast majority of patients who passed away in status were relatively young. 4) A female predominance was found. 5) All patients before entering our Center, presented asthma crisis at least three days prior to admission. 6) The predominant hospital stay duration was 24 hours. 7) The most common pathologic findings were: pulmonary fibroemphysema, acute bronchopneumonia, bronchial mucoid plugging, atelectasia and cerebral edema. 8) Cerebral edema and compression of the amygdale were common brain pathologic findings. 9) Bronchopneumonia was a common necropsy finding. 10) Based on these findings, ICU treatment is extremely important. 11) The critical status of the patient in the moment of admission, is due to the delay in bringing him to the hospital for proper medical surveyance. This justifies the interest of the Public Health Department in ample distribution of proper information to the asthmatic patients.


The use of noninvasive methods in the evaluation of left ventricular performance in coronary artery disease. I. Relation of systolic time intervals to angiographic assessment of coronary artery disease severity.

Determination of left ventricular performance by external STI was evaluated in 113 patients with possible coronary artery disease undergoing selective coronary artery disease undergoing selective coronary arteriography and left ventriculography. Angiographically determined significant coronary artery disease was considered as 70 per cent obstruction of a coronary vessel. PEPI and PEP/LVET increased with increasing severity of coronary artery disease. LVETI decreased with increasing coronary artery involvement. Presence of prior myocardial infarction or clinically apparent congestive heart failure did not significantly alter mean STI values when groups were compared according to severity of coronary artery disease. LVETI was significantly less for patients with three-vessel coronary artery disease than for those with no significant disease; PEPI and PEP/LVET were significantly greater in those with two- or three-vessel disease than in those without significant disease. Angiographically determined LVEF correlated directly with LVETI and inversely with PEPI and PEP/LVET. Abnormal left ventricular wall motion was associated with decreased LVETI and increased PEPI and PEP/LVET. LVEDP was not significantly different in any of the groups. These findings indicate that externally determined systolic time intervals reflect abnormalities in left ventricular performance which in turn appear more pronounced with increasingly extensive coronary artery disease.


Ferrokinetic studies in acute myocardial infarction.

Serum iron levels were determined in 16 patients with AMI at different days following the event and in five patients either treated with steroids or suffering from diseases acting as stress factors. Patients with AMI showed a marked decrease in serum iron concentrations, the lowest value being recorded at day 3 after the event; serum iron returned to normal level at day 12. These alterations in iron concentration were not accompanied by changes in the 24 hour urine excretion of iron. On the other hand, a significant shortening of the half-time 59Fe plasma clearance and an early increase in 59Fe incorporation into the red blood cells were found immediately after the event. These values returned to normal in all but one patient, who had in addition polycythemia. In the five patients comprising the control group, serum iron, iron excretion in urine, and ferrokinetics were within the normal limits at all times. Since in AMI patients the 11-OHCS values were found to be significantly higher on the day following the infarction than on day 15 after the event, it is suggested that the decrease in iron concentration in these patients may be connected with changes in plasma 11-OHCS levels.


Patterns of atrioventricular conduction in children.

In this study, intracardiac electrograms were performed in 20 children--ranging in age from eight months to 18 years and without evidence of conduction disturbances on the scalar electrocardiogram--to determine the normal conduction patterns, response to atrial pacing, and values of refractory periods. Atrial pacing--18 cases--induced a prolongation al AH on increasing heart rates in all; 11 developed Wenckebach block proximal to the bundle of His at the mean pacing rate of 224 per minute +/- 45 (1 S.D.). Refractory periods were shorter than in adults. Study of the pattern of A-V conduction revealed three types of response: (1) the atrium was the limiting structure in 11 cases; (2) the delay occurred in the A-V node only in four cases; and (3) the delay occurred both in the A-V node and His-Purkinje system. This response was observed in one case only.


Stokes-Adams attacks due to acute nonspecific myocarditis.

Ten patients, all below 30 years of age (8 females and 2 males) developed Stokes-Adams attacks from complete heart block due to acute nonspecific myocarditis. Coexisting thyrotoxicosis was present in two patients and cardiogenic shock was seen in four. Temporary transvenous pacing was instituted in all but one patient. Except for two patients who developed permanent complete heart block, normal A-V conduction returned in between 1 to 12 hours after ventricular pacing in seven patients and after 12 hours of isoprenaline therapy in the final patient. The ECG returned to normal in six patients and all 10 patients survived their acute illness.


Right atrium monophasic action potentials during atrial flutter and fibrillation in man.

Monophasic action potentials recorded in two patients with atrial flutter and one patient with atrial fibrillation showed a nonuniform depolarization of the right atrial wall. In each of the two patients with atrial flutter, there was a site where two separate action potential deflections were recorded for each flutter wave. It was supposed that this was the site of re-entry for a cycling wavelet subsidiary to the main flutter wave. In the patient with atrial fibrillation, three types of electric atrial activity were found: regular activity at 180 per minute similar to that found in flutter, small irregular activity at a rate of 400 per minute, and a mixed type of the former two. The significance of these findings for the mechanism of atrial flutter and fibrillation is discussed.


Effects of tachycardia on the adequacy of subendocardial oxygen delivery in experimental aortic stenosis.

We studied the interaction of tachycardia and aortic stenosis on the adequacy of subendocardial oxygen delivery. In 18 open-chest dogs with acute supravalvular aortic stenosis, we produced subendocardial ischemia by increasing either heart rate (artrial pacing) or the severity of aortic stenosis. Ischemia was determined from ST-elevation of the intracavitary electrocardiogram. Subendocardial oxygen supply was assessed by measuring subendocardial flow (radioactive microspheres, 8 to 10 microns) and arterial oxygen content, and related to simultaneous oxygen demand [estimated from the tension time index (TTI)]. The adequacy of the supply/demand relationship in the subendocardium was estimated from the ratio DPTI times 02 content (supply)/TTI (demand). Subendocardial ischemia occurred at aortic gradients ranging from 30 to 100 mm. Hg and heart rates from 120 to 180 beats per minute. Ischemic hearts were characterized by (1) redistribution of coronary flow away from the subendocardium (endo/epi flow ratio less than 1.0), (2) reduced subendocardial oxygen delivery per unit of demand (TTI) (p less than 0.01), (3) failure to lower left ventricular end-diastolic pressure with tachycardia, and (4) supply/demand ratios (DPTI times 02 content/TTI) below 15 ( less than 0.01). These findings suggest that (1) the principal determinant of subendocardial ischemia in aortic stenosis is the unfavorable alteration of the supply/demand relationship caused by the interaction between heart rate and severity of stenosis, rather than absolute heart rate or aortic gradient and (2) the adequacy of subendocardial oxygen delivery can be assessed from readily obtained measurements of blood pressure and oxygen content.


Left main coronary artery disease. Risks of angiography, importance of coexisting disease of other coronary arteries and effects of revascularization.

To elucidate the determinants of the poor prognosis of patients with left main coronary artery disease and to assess the efficacy of diagnostic and therapeutic interventions the angiographic features and clinical course of 58 patients with left main coronary artery disease studied between September 1967 and June 1974 were analyzed. Eighty-three coronary arteriograms were obtained in these 58 patients using the Judkins technique; there were no immediate complications although one patient died 3 days after study. Previously cited predictors of left main coronary artery, unstable or nonexertional angina and marked S-T segment depression with exercise were found in a minority of patients; thus, the presence of the disease could not reliably be predicted before arteriographic study. Coexisting disease was found in either two or three other coronary arteries in 46 of 58 patients; only 2 patients had isolated left main coronary artery disease. Because the criteria for operability have changed in recent years, current criteria without knowledge of the treatment actually given or its outcome. The condition of 10 of 58 patients was judged inoperable in retrospect because of severe coexisting distal coronary artery disease (8 patients) or ventricular dysfunction (2 patients). Of 19 patients whose condition was judged operable in retrospect but who were treated without surgery, 9 died, 8 within 18 months; 10 have survived 12 to 83 months. Another 27 patients with a condition judged operable in retrospect had received saphenous vein bypass grafts. In this group, there were four operative and three late deaths. The severity of angina decreased in survivors treated surgically but was unchanged in survivors treated without surgery. The improvement in survival rates of surgically treated patients was not statistically significant. The data indicate that coronary arteriography can be performed at low risk with the Judkins technique even though preangiographic prediction of left main coronary artery disease is unreliable. Coexisting disease in oter major coronary arteries is an important determinant of the poor prognosis of patients with left main coronary artery disease and precludes surgery in 13 percent. Isolated left main coronary artery disease is uncommon. Surgical therapy relieves symptoms more effectively than nonsurgical therapy.


Oxygen delivery, anoxic metabolism and hemoglobin-oxygen affinity (P50) in patients with acute myocardial infarction and shock.

Changes in systemic oxygen delivery after acute myocardial infarction were investigated in 21 patients. In seven patients with shock, circulatory failure was characterized by a significant reduction in cardiac index, a decrease in oxygen transport and oxygen consumption and an increase in concentration of blood lactate; a decrease in the affinity of hemoglobin for oxygen (increased P50) was also noted. The P50 averaged 28.8 plus or minus 0.87 (standard error of the mean) torr in patients with shock and 26.0 plus or minus 0.45 torr (P less than 0.05) in patients without circulatory failure. However, there was no significant difference in oxygen extraction from arterial blood between the two groups. The time course of the changes in P50, cardiac index and oxygen consumption was separately examined in 12 patients. In six patients with shock, P50 increased by an average of 4.6 plus or minus 2.05 torr (P less than 0.05) and this augmentation accounted for an estimated 18 percent increase in oxygen release. Maximal P50 values were observed after 24 hours of circulatory failure. In the absence of shock, no consistent changes in P50, cardiac index or oxygen consumption were observed. These data indicate that a reduction in oxygen delivery after acute myocardial infarction is followed by a compensatory increase in P50. This change in P50 accounts for increases in oxygen availability independently of changes in cardiac output.


Measurement of S-T segment elevation in acute myocardial infarction in man. Comparison of a precordial mapping technique and the Frank vector system.

Precordial S-T segment mapping has been used to evaluate the extent of ischemic injury in patients with acute myocardial infarction. Because precordial S-T segment mapping is time-consuming and is limited to patients with anterior wall myocardial infarction, we evaluated the possibility of using the magnitude (ST-VM) and direction (ST-VD) of the S-T vector, derived from X, Y and Z leads of the Frank vector system, as a substitute for the precordial S-T segment mapping technique. Precordial S-T segment mapping and Frank system vectorcardiograms were simultaneously obtained in three groups: (1) nine normal subjects; (2) nine patients with persistent S-T segment elevation 2 to 15 months after acute anterior myocardial infarction; and (3) nine patients with acute anterior myocardial infarction studied on 41 occasions. For both systems the S-T segments were analyzed 20 and 60 msec after completion of inscription of the QRS complex. The sum of the S-T segment elevations for the 35 sites (sigma ST) and the number of sites (NST) in which S-T segment elevations exceeded 0.1 mv were computed for the precordial S-T maps. The ST-VM and ST-VD were calculated by standard formulas from X, Y and Z lead tracings of the Frank vector system. Good correlations were observed between: ST-VM and sigma ST (r = +0.818 and +0.791 at 20 and 60 msec, respectively, P less than 0.001); and ST-VM and NST (r = +0.773 and +0.705 at 20 and 60 msec, respectively, P less than 0.001). Furthermore, changes in the location of S-T segment elevations in serial precordial S-T segment maps were reflected by changes in ST-VD. Observations in patients with inferior wall myocardial infarction suggest that ST-VM and ST-VD can be serially followed in such patients. Thus, estimation of the magnitude and direction of the S-T vector is a simple alternative to standard precordial S-T segment mapping that allows for continuous monitoring of S-T segment elevations in all patients with acute myocardial infarction.


Significant sex differences in the correlation of electrocardiographic exercise testing and coronary arteriograms.

Two hundred fifty-one patients (195 male and 56 females) referred for evaluation of chest pain were studied by multistage submaximal stress testing and selective coronary arteriography. In men with positive exercise tests the incidence rate of true positive exercise test results--that is, positive tests associated with 75 percent of greater coronary stenosis--was 89 percent in contrast to a 33 percent incidence rate of true positive exercise test results in women. The incidence rate of false positive excercise test results--that is, positive tests associated with no coronary stenosis or less than 50 percent stenosis--was 8 percent in men in contrast to 67 percent in women. Conversely, the incidence rate of false negative exercise test results (that is, negative exercise tests associated with 75 percent or greater coronary stenosis) was higher in men (37 percent) than in women (12 percent). It is concluded that in men a positive multistage stress test is useful in predicting the presence of significant coronary artery disease although a negative stress test cannot be relied upon to rule out the presence of significant disease. In women, a positive exercise test is of little value in predicting the presence of significant coronary artery disease, whereas a negative test is quite useful in ruling out the presence of significant disease. New criteria should be developed for stress testing of women.


Comparison of angiographic and postmortem findings in patients with coronary artery disease.

The accuracy of coronary cineangiography in predicting the degree of stenosis in coronary arteries was evaluated by comparing autopsy and premortem cineangiographic findings in 25 patients. Coronary cineangiograms and autopsy specimens were reviewed independently by two cardiologists and two pathologists. Identical diagrams dividing the cononary  arteries into 12 segments were used by both groups to record the location and degree of stenosis observed. Cineangiographic findings were in agreement with pathologic findings (less than 25 percent difference in cross-sectional luminal area) in 178 (79 percent) of the 226 segments examined, but overestimated the degree of stenosis in 13 (6 percent) and underestimated it in 34 (15 percent). Thus, cineangiography appears to be a reliable tool in evaluating coronary artery  disease. When diagnostic errors are made, they are usually underestimations of the degree of disease; common causes of error are circumferential stenosis, eccentric lesions, obstruction of view by artifical valves and poor opacification due to severe proximal stenosis.


Effect of practolol on left ventricular dimensions during coronary occlusion.

Beta adrenergic blockade has been suggested to improve the myocardial oxygen balance during ischemic conditions. This investigation was undertaken to examine the effects of practolol, a relatively cardiospecific beta adrenergic blocking agent, on regional myocardial dimensions and shortening during acute coronary arterial occlusion in dogs. Local myocardial dimensions were measured ultrasonically in ischemic and nonischemic regions of the left ventricle. Myocardial dilatation and marked reduction in systolic shortening occurred in ischemic regions after occlusion, whereas nonischemic regions were only moderately dilated. Administration of 10 to 20 mg of practolol exerted different effects in the two ventricular regions; myocardial dilatation was reduced and the systolic shortening increased by practolol in ischemic regions, whereas further dilatation and diminished shortening occurred in nonischemic control regions. Similar results were obtained when heart rate was kept constant by atrial pacing during beta adrenergic blockade. Thus, practolol improved the function in ischemic ventricular regions, and restored ventricular stroke volume to preocclusion levels, probably as a result of improved myocardial oxygen balance.


Effect of graded reductions in regional coronary perfusion on regional and total cardiac function.

This study examines the effects of graded reduction in regional coronary perfusion and changes in arterial oxygen concentration upon regional myocardial function and left ventricular function. In 14 open chest dogs, the distal left anterior descending coronary artery was cannulated and perfused at different pressures with blood equilibrated with either 21 or 95 percent oxygen, and regional function in the perfused myocardial segment was determined by use of the pressure-length loop. The mass of perfused left ventricular myocardium was determined by injection of sodium fluorescein at a constant pressure of 100 mm Hg. Regional function decreased minimally as coronary perfusion pressure and flow were reduced to 50 to 65 mm Hg and 25 to 55 ml/min per 100 g, respectively. When pressure and flow were reduced below these critical ranges, regional function decreased sharply. Changes in left ventricular function were comparable but of lesser magnitude. The relations between regional function or left ventricular function and coronary perfusion were not affected by changing arterial oxygen concentration, except at the low range of coronary perfusion pressures (22 plus or minus 6 mm Hg), at which pressure regional function was significantly lower (P less than 0.025) in the experiments with 95 percent oxygen. Thus, the sensitivity of myocardial performance to a decrease in effective coronary perfusion pressure and flow is remarkably dependent upon whether pressure and flow are above a critical level.