Haem synthesis in the Diamond-Blackfan syndrome. The response of bone marrow to erythropoietin (EPO) from five children with the Diamond-Blackfan syndrome, also known as congenital hypoplastic anaemia (CHA), was tested in tissue culture by measurement of haem synthesis. Studies of 13 control marrows indicated that the maximum EPO effect occurred at approximately 70 h incubation using an EPO concentration of 0.2-0.3 units/ml and a nucleated cell concentration of 5 x 10(6) per culture. Under these conditions, haem synthesis was 121% greater in EPO-stimulated than in unstimulated cultures. Patients with CHA with anaemia and diminished marrow erythroids had reduced or absent haem synthesis. In one patient, haem production became normal after a spontaneous remission, and was not inhibited by autologous plasma drawn at the time of diagnosis. Plasma from three patients did not show inhibitory activity when cultured with control marrow. In contrast, plasma from an adult with acquired pure red cell aplasia produced striking inhibition of haem synthesis when cultured with control marrow. We conclude that, in comparison to some cases of the adult acquired condition, CHA is not due to inhibitors or antibodies. When present, erythroid precursors in children with CHA are capable of responding normally to EPO with increased haem synthesis.


Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias. The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.


Outflow theory and autokinetic movement: color, viewing angle, and dark adaptation. The number of reported changes in direction of autokinetic movement was assessed as a function of color of the light that served as stimulus, viewing angle (0, 30, or 60 deg of displacement from straight ahead), and dark adaptation. Color and dark adaptation had no significant main effect on the number of reported changes in direction for the red and yellow lights, but viewing angle was inversely related to the number of reported changes. For the blue-green light, atypical effects of viewing angle and dark adaptation were found.


Age differences in the associations between felt temperatures and color choices. Thirty-six subjects, twelve each at 6, 12, and 18 years of age, were asked which of four colors (blue, green, yellow, or red) they were reminded of by each of four temperatures (containers at 4, 23, 35, or 45 deg C). More 18-year-olds than expected by chance made each of the conventional associations: hot/red, warm/yellow, cool/green, cold/blue. The 12-year-olds reliably made the hot/red association but none of the others. No more 6-year-olds than expected by chance made any of the conventional associations. The results suggest that the conventional associations are founded on a loosely held cultural norm rather than on an evolutionary or physiological basis.


Stimulus selection by the retarded: list length and response requirement. Institutionalized retardates learned paired associates of redundant trigrams and double digits (e.g., DLZ/10) and were given a transfer test to measure their stimulus selection. List length (four or six items) and response requirement (recall or recognition) were both manipulated during learning. The finding of most interest was that the retardates became more efficient at cue selection as the amount of information increased. This finding suggests that, at least to some extent, these retarded persons actively tended to choose a stimulus-processing strategy that puts a low load on memory as the overall memory requirements of the paired-associate task were increased.


Cerebral biopsy and assessment of brain damage in hydrocephalus. Needle biopsies of the cerebral mantle were taken from 12 hydrocephalic children aged between 14 days and 3 years. 5 children were biopsied twice or more often during subsequent shunting operations. Histological studies of biopsies embedded in epoxy resin for light and electron microscope examination revealed more useful information than those embedded in paraffin wax. There was evidence of axonal degeneration in the white matter of patients with acute hydrocephalus. Progressive gliosis was seen in more chronic hydrocephalus together with signs of cerebral atrophy. No measurable effect of hydrocephalus on myelination was detected. This histological study of needle biopsies taken at shunt operations could be useful in assessing brain damage and thus in predicting future intellectual development in hydrocephalic children.


Urinary 5-hydroxyindoleacetic acid in 8-hour collections as an aid in diagnosis of coeliac disease. 8-hour urine excretions of 5-hydroxyindoleacetic acid (5-HIAA) were measured in 18 children with coeliac disease before treatment and the results expressed as microgram 5-HIAA/mg creatinine. Similar measurements were made on urine collections from an age-matched control group of 24 children. Significantly higher values of 5-HIAA excretion were found in children with untreated coeliac disease. Measurement of the 5-HIAA: creatinine ratio in 8-hour urine collections is therefore proposed as an aid in the diagnosis of coeliac disease.


Low birthweight babies with oesophageal atresia or tracheo-oesophageal fistula. Of 142 patients of known gestation with oesophageal atresia or tracheo-oesophageal fistula, 21% were preterm with a mean weight of 2 kg, 19% were small-for-dates with a mean weight of 2.23 kg, and the remaining 60% were born at term and weighed more than 2.5 kg. There were almost five times as many preterm and almost eight times as many small-for-date infants as in a normal population. Respiratory distress syndrome and additional severe congenital anomalies were commoner in babies of short gestational age, and pneumonia was more common in small-for-dates babies.


Effect of gestational age and intrauterine nutrition on plasma transferrin and iron in the newborn. Plasma concentrations of transferrin and iron were measured in the cord blood of babies of varying gestational age and birthweight. Tranferrin and iron concentrations rose with gestational age; values in light-for-dates babies did not differ from those in babies of appropriate weight. In the last trimester of pregnancy plasma transferrin and iron concentrations in the fetus are affected by the maturity of the pregnancy but are independent of the nutritional status of the fetus. The low transferrin levels, particularly in preterm babies, may caution the use of iron especially by the parenteral route in the neonatal period, but we are wary of abandoning on this evidence alone the well tried clinical custom of giving oral iron to preterm babies who are not breast fed.


Insulin response to intravenous glucagon in children with familial constitutional short stature. An intravenous glucagon test was performed in 8 children with familial constitutional short stature who were also lean. These children were randomly selected from a larger group of children with the same clinical manifestation and who had been shown to have a low insulin response to an oral glucose tolerance test and to an intravenous arginine test, without glucose intolerance. 7 out of 8 children showed a normal insulin response to intravenous glucagon, with a peak level of 53--180 millimicron/ml 2 minutes after the injection. It is assumed that these insulin responses represent an intact 'rapid' pool of insulin within the beta-cell, and can explain the absence of glucose intolerance in all the children so far studied.


Liver scans in cystic fibrosis.

Liver scans in cystic fibrosis. Liver scans were performed on 16 cystic fibrosis patients. Most scans were considered abnormal. In most patients, the results of serological liver function tests were normal. Liver scanning in cystic fibrosis is unlikely to make a significant contribution to an assessment of prognosis.


Hydrocephalus treated by compressive head wrapping. A simple method of applying compressive cranial wrapping for neonatal hydrocephalus is described and its beneficial use in one patient is described.


The effect of heart rate on indices of myocardial contractility in the dog. 1. Changes in heart rate were evoked by atrial pacing in anaesthetized dogs with no pretreatment and in dogs given reserpine or guanethidine for 72 h. The effect of alterations in heart rate were related to two indices of myocardial contractility: the maximal rate of change of left ventricular pressure (dp/dt), and an index which was independent of initial fibre length (dp/dt)/IIT, where IIT is integrated isometric tension. 2. An increase in heart rate in control dogs was accompanied by a rise in both dp/dt and (dp/dt)/IIT confirming that the Bowditch staircase does exist in the intact ventricle. The regression line relating heart rate to (dp/dt)/IIT was significantly steeper than that relating heart rate to dp/dt because the reduction in left ventricular preload at high heart rate tends to attenuate the rise in dp/dt. 3. Reserpine, but not guanethidine pretreatment was accompanied by either a slight decrease or no change in (dp/dt)/IIT during pacing. 4. Acute elevation of (dp/dt)/IIT by either calcium or isoprenaline infusion in reserpine pretreated dogs did not restore the Bowditch effect. 5. Acute depression of (dp/dt)/IIT by propranolol and pentobarbitone was accompanied by a greater rise in (dp/dt)/IIT with pacing in control dogs and a rise rather than a fall in reserpine-pretreated dogs.


Plasma and tissue iron changes in the rat after acute administration of ethionine. 1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle. 2. Ethionine does not cause changes in the blood parameters, including total plasma iron-binding capacity and plasma iron clearance. Erythrocytes of rats injected with ethionine show altered responses to hypertonicity. 3. Increased reticulo-endothelial activity of the spleen, indicated by increased uptake of 59Fe-labelled erythrocytes by liver and spleen, apparently contributes to plasma iron elevation. Also the liver releases iron which further raises plasma iron.


Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea-pigs. 1. Elimination rates of tritiated ouabain, digoxin and digitoxin after single intravenous administrations were investigated in guinea-pigs, the total radioactivity in whole blood being traced for a period of up to 2 weeks. 2. In the initial rapid phase of elimination between 2 and 30 min following intravenous glycoside administration, the concentration decline of radioactivity in the blood was found to be identical for the three glycosides investigated, this part of the elimination curve displaying a hyperbolic shape. 3. During this early elimination phase, rapid metabolic degradation and excretion of digoxin had already taken place. The maximum concentration of radioactivity in the bile was reached 4 min following intravenous administration of 3H-digoxin. The positive inotropic response occurred in the cat heart-lung preparation 1.5 min after intravenous injection of a therapeutic dose of digoxin, indicating a quick occupation of binding sites in the tissues. 4. The biological half-lives of tritiated ouabain, digoxin and digitoxin averaged 11 h, 2.5 days and 4.1 days, respectively, as determined by the terminal exponential elimination phase, in guinea-pigs. This terminal phase was attained 6-12, 7-24, and 24-48 h after administration of ouabain, digoxin and digitoxin, respectively. 5. The findings reveal that in guinea-pig, as has been demonstrated in man, the elimination rates of the three glycosides increase according to their hydrophobic properties. 6. The biological half-lives of tritiated ouabain, digoxin and digitoxin obtained in the guinea-pig closely resemble those found in healthy man.


State and territorial public health laboratories: the collective experience. Directors of State and Territorial Public-Health Laboratories have realized for many years that they needed to join together to compare and appraise their operations, identify common problems, and take steps leading to improvement of services provided. Before these objectives could be accomplished, a data base, built from contributions by all the laboratories, was necessary. This article is intended to give a general historical overview of the efforts at data collection and the establishment of a solid data base covering workload and activities of the laboratories which form the Association of State and Territorial Public Health Laboratories. The Consolidated Annual Report (CAR) on State and Territorial Public Health Laboratories--Fiscal Year 1973 is the 10th consecutive report of data concerning these laboratories. The annual issues of the CAR have served as a foundation from which additional documents covering position classification and pay, guide class job specifications, laboratory training activities, and relative values assigned to laboratory tests in measuring costs and workload have evolved over the past decade. Collectively, these documents provide the solid data base available today.


Absorbed heterophile and ox-cell hemolysin test in serodiagnosis of infectious mononucleosis. The accuracy of the absorbed heterophile and the ox-cell hemolysin procedures was compared by testing of 1577 sera routinely submitted to the State Laboratory of Hygiene for serodiagnosis of IM. Results of both tests were in agreement with 1369 (86.8%) sera; additional 122 (7.7%) samples yielded minor disagreements in results. Major discrepancies in results were seen with 86 sera (5.4%). On basis of clinical data peripheral blood smear findings, tests comprising our IM syndrome test battery, and additional serologic tests, we concluded that in most instances of ox-cell hemolysin positive heterophile negative findings, there was evidence to support a diagnosis of IM. Such support was lacking in a majority of cases with heterophile positive, ox-cell negative findings, and in several of these patients infection with agents other than EBV was suggested. On the basis of comparisons of sensitivity, specificity, cost and ease of performance, the ox-cell hemolysin test appears to offer several advantages over the other available IM serodiagnostic procedures for a public health laboratory performing a large number of tests.


The role of the kidney in essential hypertension. 1. Many forms of human and experimental hypertension begin with compromised renal function. Essential hypertension may be another such case. 2. The kidneys of subjects with essential hypertension excrete normal amounts of salt and water at higher-than-normal renal perfusing pressures. Other overt signs of renal dysfunction are few; renal disease is excluded by definition. However, renal blood flow and glomerular filtration rate are usually less than normal in essential hypertension. 3. Renal afferent resistance can be calculated from arterial pressure, renal blood flow, and an estimate of glomerular capillary pressure. These calculations indicate that afferent resistance is increased to two or more times normal in essential hypertension. 4. It is not clear whether afferent constriction causes hypertension or results from it. The ability of high pressure to produce vascular damage points to the latter. But, most essential hypertensives show low-to-normal plasma renin levels and a marked afferent dilation after saline loading. These observations do not suggest nephrosclerosis: they are consistent with a causal role for afferent constriction. 5. We can speculate that, in essential hypertension, there is a defect in one of the mechanisms that sets afferent resistance. Afferent constriction could result from extrinsic influences (neural or humoral) or something totally within the kidney, such as abnormal handling of information from the macula densa. 6. The effect of afferent constriction on salt-and-water excretion would theoretically be offset by elevated arterial pressure so that the actual salt-and-water excretion would be normal, but only so long as the arterial pressure remained elevated.


New medium for isolation of Corynebacterium vaginale from genital specimens. Corynebacterium vaginale was isolated from 48 (23.4%) cervical, vaginal, and urethral swabbings of 205 female outpatients. A new medium modified from peptone starch dextrose agar was used to isolate C. vaginale from most specimens. The new medium contained starch without dextrose with brom cresol purple added. With the exception of certain strains of streptococci, C. vaginale was the only organism isolated from genital specimens that grew and fermented starch on the medium. The new medium provided a rapid means of detecting and isolating C. vaginale compared to other media, and for estimating the relative predominance of the organism in mixed culture. Gram strains were used to detect clue cells in direct smears of clinical material. These cells were detected in only 12 of 48 specimens from which C. vaginale was isolated. Smears on 8 additional specimens contained clue cells but C. vaginale was not isolated. Purple broth base was superior to cystine trypticase agar for confirmatory tests with C. vaginale.


Steam sterilization: a comparison of Steam-Clox and some european biological indicators. Results of a study of the reaction of a chemical indicator (Steam-Clox) and of two biological indicators exposed to steam sterilization with varying amounts of air introduced with the steam, indicate that the chemical indicator is capable of detecting significantly smaller amounts of air than either of the biological indicators tested.


The inhibition of renin secretion in the isolated rat kidney by clonidine hydrochloride (Catapres). 1. The effect of clonidine HCl on basal and isoprenaline-stimulated renin secretion was examined in the isolated rat kidney. 2. Intrarenal infusion of clonidine at a dose level which did not increase renal perfusion pressure (1.9 nmol min-1 g-1), significantly lowered basal renin secretion without altering the stimulatory response to isoprenaline. 3. Increasing the dose of clonidine (3.4 nmol min-1 g-1) raised renal perfusion pressure, lowered perfusate flow rate and attenuated the response in renin secretion to isoprenaline. 4. Since the vasoconstrictor effect of clonidine is considered to be due to alpha-adrenergic stimulation, this observation is similar to a previous study reporting suppression of renin secretion by vasoconstrictor infusions of catecholamines (Vandongen & Peart, 1974). 5. These studies demonstrate a direct intrarenal inhibitory effect of clonidine on renin secretion. It is suggested that this may contribute to the suppression of plasma renin levels observed in vivo following administration of this drug.


Control of hindlimb vascular resistance in rats chronically sympathectomized with 6-hydroxydopamine. 1. Vascular resistance was measured after acute surgical denervation in the blood-perfused hind limbs of adult normal rats and rats which had been treated with 6-hydroxydopamine in the first 2 weeks of postnatal life. Vascular resistance was significantly higher in the limbs of 6-hydroxydopamine treated rats. 2. No excess of vasoconstrictor materials was detected when blood from 6-hydroxydopamine treated rats was used to perfuse the hind limbs of untreated rats or other 6-hydroxydopamine treated rats. 3. Hind limb blood vessels of 6-hydroxydopamine treated rats showed increased sensitivity to normal amounts of circulating vasoconstrictors of adrenal origin and to intra-arterial infusions of noradrenaline and angiotensin. 4. Infusion of desipramine into the hindlimb blood vessels of 6-hydroxydopamine treated rats did not increase vasoconstrictor responses to infused noradrenaline. Infusion of desipramine into the limbs of untreated rats increased responses to noradrenaline but these never attained the magnitude and duration of responses seen in limbs of 6-hydroxydopamine treated rats. 5. The increased sensitivity to noradrenaline of hindlimb vessels from 6-hydroxydopamine treated rats could partly be accounted for by an absence of neuronal uptake sites and partly by the development of non-specific post-junctional supersensitivity.


The effects of acute infection on blood lead, copper, and zinc levels in children. Recent reports in the literature have presented results showing a decrease in blood zinc levels accompanied by an increase in blood copper levels during acute infection. The purpose of this study was to determine possible shifts in whole blood lead as well as whole blood zinc and copper during such a stress state. The total survey population of 73 was divided into 21 children with non-infectious diseases, 40 children with acute infections and 12 asymptomatic lead poisoned children admitted for elective chelation therapy. No differences between whole blood lead levels for acute and non-infectious groups were determined. Zinc levels for controls were significantly greater than those in both the infected and the asymptomatic lead intoxicated groups. Copper levels were elevated in the infected group compared to controls but this elevation was significant only when associated with temperatures over 102 F.


Interaction between drugs and potassium-rich solutions in producing contraction in bovine tracheal smooth muscle: studies in normal and calcium-depleted tissues. 1. The contracture normally induced in isolated bovine tracheal smooth muscle by potassium-rich solution was abolished by removal of the extracellular calcium. The contraction returned when calcium was added to the solution in a concentration greater than 0.05 mmol/l. 2. The amplitudes of the potassium-contracture, and of the contractile responses to histamine and acetylcholine in normal physiological solutions, declined at low temperatures (15-25 degrees C). If drugs were added during the plateau phase of the potassium contracture, the extra tension developed above the contracture did not change with temperature. 3. Calcium-depletion reduced the responses to drugs, and repeated application of the drugs in calcium-free solution produced progressively smaller contractions, suggesting that an intracellular store of calcium was being used up. 4. Depolarization of calcium-depleted tracheal muscle by high-K+ solution without calcium produced responses to drugs which were larger than those in sodium-based calcium-free solutions. There was no potentiation in a solution in which sodium was replaced by sucrose, suggesting that potassium was not acting simply by replacing the sodium. 5. It is suggested that depolarization of the membrane by potassium makes available a fraction of bound calcium which was not available in calcium-free sodium-based solution.


Hormone metabolism and response of adenylate cyclase to parathyroid hormone in kidney. 1. Incubation of parathyroid hormone with plasma membranes from rat kidney cortex resulted in rapid loss of all hormal activity. 2. Chick kidney membranes showed no ability to inactivate parathyroid hormone even with prolonged incubation. 3. Biologically active, labelled parathyroid hormone was degraded to fragments by rat kidney membranes, but not by chick kidney. 4. Hormone-responsive adenylate cyclase activity in a mixture of rat and chick kidney membranes was additive. 5. Parathyroid hormone bound specifically to chick kidney palsma membranes. 6. It is concluded that hormone in activation during incubation has little relevance to the effectiveness of parathyroid hormone in stimulating adenylate cyclase activity in kidney, and furthermore that failure of chick kidney to metabolize the hormone is not the explanation for the greater sensitivity of this species to the hormone.


Hospital infections with pigmented water bacteria. Two types of cultures normally expected to be sterile, i.e., urine and blood, were chosen for review at a large university hospital. The bacteria isolated from urine cultures during 1966-70 and from blood cultures from 1966-73 are listed. Two organisms, Flavobacterium meningosepticum and Pseudomonas cepacia, were selected for more detailed study and review. The antibiotic susceptibility patterns for these two organisms are presented.


Microorganisms in heated nebulizers.

Microorganisms in heated nebulizers. Out of 353 heated nebulizers in actual use which were cultured in the Peter Bent Brigham Hospital, 118 (33%) were found to be contaminated. Gram-negative organisms predominated with rare micrococci and fungi. A slow-growing Vibrio was also recovered from 4 nebulizers. Heating of nebulizers above 46 C resulted in significant reduction of contamination. Types of heated nebulizers also figured significantly in the rate of contamination found. Carefully considered recommendations for the care and use of respiratory therapy equipment must be instituted and enforced. Techniques for terminal disinfection of equipment, followed by sterilization should result in the issue of sterile equipment for each patient. Rules for maintenance of equipment at the bedside are also needed.


Gram-negative water bacteria in hemodialysis systems. Gram-negative bacteria can multiply relatively fast in a variety of hospital associated fluids ranging from distilled, deionized, reverse osmosis, and softened water, which are normally considered devoid of nutrients, to intravenous solutions and fluids associated with hemodialysis. Excessive levels of these bacteria in the dialysate of artificial kidney machines can be responsible for pyrogenic reactions or sepsis or both.


Independence of oral contraceptive-induced changes in glucose tolerance and plasma cortisol levels. 1. Following a 50 g oral glucose load, plasma glucose concentrations and plasma cortisol concentrations were measured in twenty-five young healthy women. 2. When compared to controls, oral contraceptive users (OC-users) were found to show a small but significant decrease in glucose tolerance while plasma cortisol values were increased more than two-fold. 3. The decreased glucose tolerance in OC-users did not show a significant correlation with raised plasma cortisol levels.


Gonorrhea screening program in New York State. Of 171,089 mailed specimens examined for Neisseria gonorrhoeae, 88% were submitted by family planning clinics, physicians in private practice, and other non-VD clinics. To process a large volume of specimen bottles, we developed a swab-oxidase test and demonstrated it to be reliable for the initial screening of all specimens. Our protocol permitted the isolation and confirmation by sugar fermentation of 95% of all presumed N. gonorrhoeae cultures within 1 or 2 days after growth was observed. The results obtained over a 2-year period indicate that the positivity rate is directly related to the lag period between specimen collection and examination. There was no adverse effect of cold weather on the positivity rate, but, irrespective of the season, 3 to 9% of the positive specimens required incubation for 3 days before gonococcal growth appeared.


Identification of pigmented gram negative bacilli. Identification of chromogenic gram-negative bacilli on the basis of pigment production as a taxonomic criterion is unreliable. Because of this, a wide range of morphological, cultural and biochemical characteristics of bacteria in this category was examined. The salient features found to be useful for identification of pigmented bacilli, including Flavobacterium, Xanthomonas, the fluorescent pseudomonads, Pseudomonas cepacia, P. stutzeri, P. maltophilia, P. putrefaciens, and Group VE, are reviewed.


Staphylococcus aureus recoveries on various brands of membrane filters. Six commercial brands of membrane filters were compared using staphylococcus aureus obtained from pure cultures and from swimming pool water. The following brands of filters were tested: Gelman, Millipore, Nuclepore, Oxoid, Sartorius, and Selectron. Standard membrane filter (MF) procedures and m-Staphylococcus broth were used in the evaluation. Analysis of the results was performed by comparing filter recoveries to the standard plate count using the t-test and the coefficient of variation. The data revealed that recovery on Nuclepore filters was consistently lower than the other brands and showed a wider degree of variation from the mean. All organisms recovered from the pool were gram-positive cocci, and the colonies ranged from white to yellow-gold in color. Approximately 15% of both the white and yellow-gold colonies were coagulase-positive, indicating that colony color alone does not denote the presence of coagulase-positive S. aureus. Since there was no correlation between colony color of the organisms recovered on membrane filters and the presence of coagulase, the feasibility of coagulase testing only the yellow-gold colonies for bathing water analysis is questionable.


Evaluation of laboratory management training. The purpose of this study was to determine if motivation to manage increased simultaneously with planned-for cognitive learning of management. A management course designed to stimulate cognitive learning was studied. It was presented to supervisors in hospital, independent, and public health laboratories. Two groups of 22 and 26 participants, respectively, were identified to be studied. Measures of cognition and motivation were taken before and after training. The analysis revealed statistically significant increases in cognitive learning in both study groups. The analysis of motivational data did not reveal a statistically significant increase in motivation to manage for either group. It was concluded that it is possible to stimulate cognitive learning of management if such learning is consciously planned. It was also concluded that under the experimental conditions, motivation to manage does not increase when it is treated as incidental to the planned-for cognitive learning.


Variations in the level of a pregnancy-associated alpha-macroglobulin in patients with cancer. The concentration of a pregnancy-associated alpha-macroglobulin (PAM) was determined in the blood of patients with various cancers. PAM was detectable in subjects with all types of malignant disease studied, and the level of the serum protein correlated well with the course of the disease: the concentration increased before clinical recognition of metastases and decreased significantly on successful treatment. Periodic PAM determinations may allow detection of tumour recurrence while it is still at a treatable stage and could aid in the evaluation of therapy.


Fibrinolytic activity in malignant disease. Resting fibrinolytic activity and fibrinolytic capacity were compared in 31 patients with malignant disease and in 24 control subjects without malignant disease. Patients with malignant disease had a lower mean fibrinolytic activity: this was particularly marked in those with disseminated disease. In contrast, patients with malignant disease had a fibrinolytic capacity which did not differ from that of the control subjects.


Plasma erythropoietin assay in patients with chronic renal failure. Using the post-hypoxic mouse method of assay, values for erythropoietin in the plasma of patients with chronic renal failure were equal to, or greater than, normal values. Results suggest that the source of erythropoietin may be primarily extrarenal. Normal renal tissue, provided in the assay by the intact mouse, is required for activation of the hormone. There still remains to be explained the enhanced erythropoietic response to haemorrhage or hypoxia that can occur in anephric man.


Renal dysplasia in nephrectomy specimens from adolescents and adults. In a review of 156 total or partial nephrectomy specimens from patients over the age of 12 years, renal dysplasia was found 14 times. The cases were divided initially into five groups on the basis of the predominant pathological changes, namely (1) dysplasia (14 cases), (2) chronic pyelonephritis (31 cases), (3) calculous inflammation (58 cases), (4) hydronephrosis (35 cases), and (5) miscellaneous (18 cases). The diagnosis of dysplasia was made on gross and microscopic criteria and included 12 of segmental dysplasia, one of total dysplasia, and one multicystic dysplastic kidney. The principal differential diagnosis is from the irregularly scarred chronic pyelonephritic kidney. The criteria for the separation of the two are emphasized and, in particular, the distinction from those pyelonephritic kidneys with aglomerular scars. A high incidence of anomalies of drainage was found in association with dysplasia, but such were not always present. It was not thought that intrarenal reflux in infancy was an aetiological factor. Six of the cases presented with urinary infection, but only two had hypertension. It was thought that acquired glomerular damage was more important in the aetiology of hypertension than segmental glomerular agenesis.


Necropsy study on glomerulonephritis in the elderly. The necropsy reports and clinical observations of 44 cases of glomerulonephritis occurring in patients over 55 years old were reviewed. Two-thirds of the patients died from a rapidly progressive renal disease with focal necrotizing and fibrosing glomerular lesions; half of these exhibited a granulomatous splenic trabeculitis; an associated vasculitis was found in only a minority of these cases. Another important group consisted of cases of acute diffuse glomerulonephritis which, as a rule, occurred in association with a major infection. There were only four cases of chronic sclerosing glomerulonephritis.


Interpretation of respiratory tract histology in cot deaths. The degree of inflammation in the trachea, bronchi, and lungs of 139 cot deaths has been analysed and each case allocated to one of four groups. In group I the changes were considered to be serious enough to have caused death, while group II cases showed similar abnormalities but of a less severe nature, and in this group there was some doubt as to whether they were a significant cause of death. Group III lesions were very minor in type and were not considered to be serious enough to have resulted in the death of the child. There was a good correlation between the degree of inflammation in the respiratory tract, and whether or not bacteria of any type were grown. The great majority of the bacterial pathogens were isolated from the first two groups. Respiratory viruses were isolated from three of the four cases of acute bronchiolitis included in group I, and also from a group II case which showed considerable bronchiolar inflammation. One-third of the cases with minor inflammation in the lung parenchyma (group III) showed some evidence of recent virus infection.


Quantitative study of uterine curettage in the menstrual cycle. The histological appearances in 114 endometrial curettings from cases of dysfunctional bleeding have been analysed quantitatively by the method of Dunnill and Whitehead (1972) and Risdon and Keeling (1974). As applied to this type of specimen, the technique provides indices of both tubular volume and tubular surface to volume ratio. The histological diagnosis of endometrial hyperplasia is made from the increase in stromal and epithelial elements and the change in the pattern of the glands. These changes, on some occasions, can be difficult to detect. Quantitative analysis can be used to distinguish minor degrees of abnormal endometrial hyperplasia, in comparing serial endometrial changes in a given patient, and in comparing different menstrual cycles in dysfunctional uterine bleeding. Endometrial biopsies were collected and put in categories according to the clinical diagnosis. These biopsies were then examined morphometrically to find the volume/glandular surface and glandular/volume ratio. A significant change in these ratios was found.


Laboratory procedures for the isolation of chlamydia trachomatis from the human genital tract. The technique of isolating Chlamydia trachomatis from the human gential tract by centrifuging clinical specimens on to cell monolayers with subsequent incubation has been improved and simplified. Gentamicin in the media was found to be superior to streptomycin in reducing bacterial contamination of specimens. The infectivity of chlamydial suspensions of laboratory cultured material was significantly reduced by storage at +4 degrees C for more than 48 hours, and by immediate freezing to -70 degrees C. When compared with immediate processing of the specimens, freezing to -70 degrees C was found to reduce the isolation rate of C.trachomatis from men with non-gonococcal urethritis (NGU) by approximately 20%.  McCoy cells pretreated with idoxuridine were compared with irradiated McCoy cells for the isolation of C. trachomatis from clinical specimens. There was no significant difference in sensitivity between the two systems, but the former is considerably simpler. The effect of the centrifugal force used for inoculating specimens on to the cell monolayers on the isolation rate of C. trachomatis was studied in groups of men with NGU. Maximal isolation rates were obtained with forces of about 3000 G, which were not significantly raised by further increasing the force used. It is suggested that the isolation of C. trachomatis from the genital tract is now well within the capacity of any laboratory equipped with simple cell culture facilities.


Problems of nomenclature III: ambiguous abbreviations and catchwords. To avoid ambiguity, the following emendations are advocated: (1) 2H, in place of H2, to designate the second histamine receptor; (2) HN-2, in place of HN2, to designate mechlorethamine (MBA);(3) 'pre-drug', in place of 'pro-drug', to describe molecular species which must undergo biotransormation before yielding an effective drug.


Methyl derivatives of histamine; interaction with histamine metabolism. Several histamine analogs, with ring or side chain methyl groups, were tested for interaction with certain aspects of 14C-histamine metabolism. The physiological catabolite, denoted as 3-methylhistamine under the nomenclature we have adopted, is known to inhibit histamine methylation in vitro and in vivo. At low concentrations, all analogs inhibited histamine methylation by mouse brain homogenates; however 3-methylhistamine was completely ineffective against the highly active enzyme from rat didney, while 2-methylhistamine was most effective. None of the drugs showed a significant effect on in vivo formation of 14C-histamine by mouse stomach. All analogs had a definite effect on the distribution and fate of intravenously injected 14C-histamine. The 2-methyl analog was the strongest in vivo inhibitor of histamine methylation, and 3-methylhistamine next. The side chain N-methylated histamies altered uptake of 14C-histamine in some tissues but inhibited methylation weakly, if at all. Data on blood kidney and urine for 4-methylhistamine were unique, and suggested some effect on tubular reabsorption. 2-methylhistamine may prove to be the inhibitor of choice for in vivo studies on histamine methylation.


Amplification of the bradykinin response in rat uterus by pCMB-Dextran T 10. pCMB-Dextran T 10,a large, non-penetrating SH-blocking reagent caused a reversible amplification of bradykinin sensituvity in the isolated rat uterus. High concentrations of this compound (1 x 10-3 M) can evoke spontaneous uterus contraction. pCMB-Dextran T 10 did not alter the biological activity of bradykinin. It is assumed that superficial membrane SH-groups are involved in the uterus contraction mechanism.


Leucocyte migration and lysosomal enzymes release in rat carrageenin pleurisy. The time course of rat carrageenin pleurisy has been studied. The inflammatory reaction is characterized by exudate formation and massive leucocyte emigration into the pleural space both reaching peak values at 24 hours. Moreover betaglucuronidase, acid phosphatase and lactic dehydrogenase have been assayed in the exudate. The activity of lysosomal enzymes parallels the severity of the inflammatory response, while that of cytoplasmic enzyme lactic dehydrogenase resulted unmodified. Treatment of animals with indomethacin, phenylbutazone, aspirin and flufenamic acid inhibited both exudate formation and leucocyte emigration. In contrast none of these drugs was able to reduce lysosomal enzyme release.


The anti=inflammatory properties of isoxicam (4-hydroxy-2methyl-N-(5-methyl-3isoxolyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide). Isoxicam is a potent, orally active, nonsteroidal anti-inflammarory drug with prolonged activtiy in experimentally induced inflammation in rats. Isoxicam is less ulcerogenic, acutely less toxic and, therefore, appears to have a therapeutic ratio superior to other standard agents to which it was compared.


[Proceedings: A mobile coronary care unit at the Cantonal Hospital of St. Gallen]. Cardiac death after a myocardial infarction occurs most frequently within the first hour after onset of symptoms and in nearly 2/3 of cases before transfer to a hospital. Mortality therefore should be influenced by shortening of the prehospital phase. At moderate cost a mobile coronary care unit (Kardiomobil) has been introduced at the Cantonal Hospital, St. Gall. Experience and results of the first year of the service are reported. 82 out of 142 patients transported by Kardiomobil proved to have myocardial infarction. Two patients with ventricular fibrillation were defibrillated, with one longterm success. Sixteen cases of potentially life threatening arrhythmias were successfully treated. The mean period from onset of symptoms to alerting a doctor was 1 h 15 min, while the mean period from onset of infarction to entry into the hospital CCU was 3 hrs.


New alpha-substituted arylthioacetic derivatives forming analogues of clofibrate. Synthesis of some alpha-substituted arylthioacetic acids and esters forming analogues of clofibrate and of nafenopin (SU-13437) is reported and discussed. With a view to evaluating the influence of the introduction of a sulphur atom on the blood-lipid-reducing activity, preliminary pharmacological tests have been carried out on alpha-[4-(1-tetralyl)phenylthio] isobutyric acid (XIV) in parallel with its well-known phenoxy isologue. The results obtained so far, do not show any significant difference between the two compounds.


Marijuana: its meaning to a high school population. The present study investigated the meaning of the concept of marijuana as measured by both a semantic differential rating scale and a questionnaire. The responses of 100 male and female high school students (50 users, 50 nonusers) indicated that marijuana usage was primarily related to the pleasure of the high, while abstinence was associated with potential harmfulness of the drug to health and practical situational factors. The general response profile corresponded closely to that of a parallel college sample reported in an earlier study by LaDriere and Szczepkowski, suggesting that neither age and educational level nor sex constituted meaningful variables in drug use motivation. Finally the hypothesis that motivational factors specifically associated with adolescent dynamics--including needs for independence, social acceptance, and adventure--might influence the data of the high school sample was not confirmed.


Cannabis and its users in Nepal.

Cannabis and its users in Nepal. Cannabis is easily available in Nepal, large numbers of persons using it regularly. I have studied its effects on 226 persons who had been using it for a long time and in considerable amount. As a control group I used an equal number of men of matching age and education. Compared with the controls, the cannabis users had a poor work record, poor social and family relationships, a lack of interest in sex and a general loss of initiative and efficiency. However, there was no difference in crime rate between the groups.


Studies of higher nervous activity in functional phychoses. Psychiatric illnesses can be conceived of as experiments of nature, providing a variety of pathopsychological mechanisms which may elucidate normal psychological processes. Clinically the reactive psychoses are predominantly psychogenic reaction types. They present disturbances of higher nervous activity, similar to those of the neuroses. The unconditional reflex activity is practically as in normal controls, and the most outstanding finding was the large effect of psychodynamic complex structures. This is a physiological parallel to the clinical manifestations with great concern over experienced mental trauma. In the manic-depressive psychoses the most characteristic feature is a marked disturbance of unconditional reflex activity. This factor may be an important physiological mechanism underlying the more biological than psychodynamic reaction type and partly explain the changes of mood and associated interferences with sleep, body weight, sexual activity, aggression and other instinctual and vegetative functions. Schizophrenic psychoses also present changes of unconditional reflex activity, predominantly in the direction of inhibition of response. In addition there are severe dissociations within and between the three levels of unconditional reflexes and the two signaling systems. It is suggested that schizophrenia represents a functional maladaptation, which can be explained from the principles of autokinesis and schizokinesis established by Gantt in animal experiments. Prognostic models based on experimentally established impairment of performances were shown to predict long-term risks of schizophrenic defects just as well as models based on constellations of clinical symptoms. I would predict that psychophysiology and experimental psychology will become increasingly more important for establishing diagnosis and prognosis in the functional psychoses. The data of this article point toward a basis for a prophylactic psychiatry.


Male-like sexual behaviour of female rats with unilateral lesions in the hypothalamic ventromedial nuclear region. In castrated female rats treated with androgen or oestrogen a significant decrease of female sexual behaviour assocated with a significant increase of male sexual behaviour was induced by unilateral lesions of the hypothalamic ventromedial nucleus.


[Course of Trypanosoma musculi infections in NMRI mice (author's transl)]. The trypanosomes multiply during prepatency after minimal infection by a factor of 2.2-3.6 per day. During patency, increase of trypanosome number in the peripheral blood is basically non-logarithmic as the actual proliferating forms remain hidden in special vascular areas (kidney, placenta). The mean increase during patency is approximately linear, typically by 1-10 trypanosomes per 10(4) erythrocytes per day, and depends on the number of infective organisms introduced. - Length of parasitemia is 13-40 days, it is partly determined genetically. Prolonged parasitemias, very low in the later stages, were seen in mice preinfected with Trypanosoma congolense. - In 1 mouse with minimal infection, parasitemia only became patent 63 days after infection under the stress of an added infection with Trypanosoma brucei. - Parasitemia can be terminated by antiserum. Application of antiserum 3 or 4 days after infection may even suppress the development of immunity and priming. - Massive reinfection leads to parasitemia of up to 8 days duration without parasite multiplication.


Histochemical studies of renal biopsies of nephrotic children. Histopathological and histochemical studies were done on renal biopsies taken from twenty nephrotic children and thirty Albino rats of which fifteen were rendered nephrotic by the intravenous injection of nephrotoxic serum and the other fifteen served as controls. There were reduced activities of succinic dehydrogenase, alkaline phosphatase, acid phosphatase and non-specific esterases enzymes. These changes may be secondary to the insult which caused the nephrotic syndrome, or the result of the heavy proteinuria. In conclusion, a derangement in carbohydrate metabolism may underlie the disturbed metabolism of the basement membrane, the distortion of the foot-processes, and the tubular dysfunction.


[Combined clofibrate-chlorpropamide therapy in diabetes insipidus complicated with diabetes mellitus]. The authors observed the incidence of diabetes mellitus and diabetes insipidus in three cases. The combined clofibrat-chlorpropamide treatment proved to be successful. They succeeded in ceasing the daily insuline by giving the two drugs together. The daily diuresis diminished considerably in all three patients. The authors advise the combined clofibrat-chlorpropamide treatment in the incidence of the two diseases. This is especially reasonable when there is a disturbance in the lipoid metabolism.


Relationship between the dose of 1-deamino-8-d-arginine vasopressin (ddavp) and the antidiuretic response in man. A definite relationship was found between the dose of DDAVP (1-24 mug intravenously and 5-320 mug intranasally) and the antidiuretic effects (expressed in changes in free water clearance per 100 ml GFR and in urine osmolality determined in 24 hour urine collection periods) in 7 patients with diabetes insipidus. The relationship was more conspicuous when the second 12 hour antidiuretic responses were considered, indicating a dose-dependent prolongation of the antidiuretic action. Time-curves of the antidiuretic responses proved the dose-dependent prolongation of the duration of antidiuretic action. Second 12 hour antidiuretic response increased more markedly when DDAVP was given divided in two doses a day as compared to the effects of the same quantity of the drug given as a single dose; only by the administration of excessive single doses the effects of the divided doses could be reproduced.


[The mechanism of carbon isotope fractionation in the metabolic process]. The mechanism of carbon isotope fractionation in metabolic paths of autotrophic organisms is considered. The principal features of the mechanism proposed are: 1) the emergence of a one-stage kinetic isotope effect of pyruvate decarboxylation during respiration resulting in the formation of two flows of the carbon substrate with different isotope compositions; 2) the multiplication of the one-stage isotope effect by means of the repeated circulation of a light isotope fraction (C2-fragments) in lipid-carbohydrate metabolism and by the simultaneous removal of a heavy isotope carbon dioxide in the Krebs cycle. On the basis of the above mechanism carbon isotope effects are explained of CO2 assimilation and respiration as well as sequential decrease of 13C content in the series of lipids, carbohydrates and proteins. The cuase of the enrichment of the whole organisms in the light isotope in respect to the carbon dioxide of the environment is discussed.


[Middle molecules separation from uraemic serum (author's transl)]. The following method is proposed to make the serum concentration of the middle molecules evident and to isolate them: 1) Fractioning of serum by gel filtration with sephadex G 75 columns in order to eliminate proteins and other substances with mol. weight less than 3,000-3,500. 2) Collection of fractions with mol. weight greater than 3,000-3,500 their lyophilisation and their successive gel filtration by sephadex G 15 columns. The concentration of substances in the single fractions is evaluated by ultraviolet light absorption (wave length 254 nm). The peaks of the patterns show a great difference between normals and uremics. The uremic peaks are always higher than normals. The mol. weight the substances in the peaks obtained by gel filtration with sephadex G 75 and G 15 was verified by radiolabelled substances of known mol. weight added before gel filtration. The substances isolated by sephadex G 75 from 10 and 20 cases of uremics and normal controls were diafiltered by Diaflo membrane UM 05 (nominal mol. weight cut - off 500). The diafiltered substances (mol. weight between 500 and 3,500) were investigated. A great difference between uremics and normal controls of dry mol. weight was observed, while the percentage concentration of C, H, N and of amino acids evaluated after acid hydrolysis showed no difference between the two groups. The liberation of amino acids after acid hydrolysis confirmed the presence of peptides among the middle molecules. Middle molecules in the urine of uremic and normal subjects have been investigated by the same method.


[Gonadal dysgenesis, A follow-up study of 25 cases (author's transl)]. Gonadal dysgenesis (GD) is a rather frequent type of sex chromosome aberration, the rate being approximately 1 in 2000 newborn females. Many problems arise from this condition, not only in terms of symptomatology and diagnosis but mainly concerning the long term medical care. 25 patients with the "pure" GD-syndrome (cytogenetic type 45 X), or mosaicism without Y-cells, ranging in age between 4 and 35 years were studied. The data of the family- and birth history, symptoms of dysmorphism, cytogenetics, longitudinal growth, "maturation" with and without hormone therapy will be presented. From our series it could be confirmed that the full phenotype of Turner's syndrome occurs only in the 45 X-type. Mosaic cases often lack some of the Turner's-symptoms, but dwarfism was always present. Adult final height resulted between 140 and 145 cms, usually. No positive influence of hormone substitution on body-growth could be found. An important part of the study was the follow-up of psychosocial development of 6 patients between 20 and 35 years of age, who showed a better integration into normal life than anticipated. Details on all the patients from psychosocial view points can be found in the following paper of this issue, by Dr. L. Haselbacher.


[Behavior of partial oxygen pressure in the scalp of the fetus during physiological uterus contraction]. By means of a proper method for the continuous registration of tissue PO2, the behaviour of the scalp PO2 of the fetus has been investigated during physiological labour. The cases are classified in 5 types of course. A clear increase of PO2 during labour is observed in 45% of the exploited cases. Its dimension runs to 15% of the base value.


[Standardization of the peak expiratory flow rate]. Five successive measurements of the peak expiratory flow rate have been made on a large number of children and adolescents in various age groups and both sexes. The predominant part of the increase in individual performance is already achieved during the first three trials. Besides, the maximum value of the five measurements apparently does not differ essentially from the mean value of the two or three highest measurements.


The lower esophageal sphincter. Physiologic and clinical aspects. Current concepts in physiology and pathophysiology of lower esophageal sphincteric mechanism are reviewed. With recent advances in manometric method for more accurate in-vivo human studies combined with in-vivo and in-vitro studies in animal models, there is much information regarding function of this sphincter. Three components of sphincter control have been identified: specialized circular smooth muscle at esophagogastric junction, autonomic nervous system, and probable physiology effects of gastrointestinal hormones, particularly gastrin. Clinical syndromes of sphincteric dysfunction have been identified relative to these three controlling elements. Foods and drugs that adversely effect sphincter pressure have been identified and indicate that anticholinergic agents, fatty foods, chocolate, alcohol, and cigarette smoking may have a harmful effect on a patient with heartburn. Drugs that increase the antireflux sphincter barrier have been studied. Clinical effectiveness of antacids and bethanechol in therapy of heartburn is supported by controlled treatment trials. Research continues on other medications producing increases in sphincter pressure.


[Frequency of detecting bacteria of the genera Citrobacter and Hafnia in different contingents of examined adults]. A study of the incidence of bacteria of the Citrobacter and Hafnia genus in adults permitted to establish a greater occurrence of the mentioned microbes in the patients with various acute intestinal diseases in comparison with the healthy ones. Bacteria of the Citrobacter and Hafnia genus were revealed in the patients with acute intestinal diseases of obscure etiology, which often were diagnosed as gastroenteritis, enteritis, etc. Bacteria of the Citrobacter and Hafnia genus were revealed in the dysentery patients. Results of studies carried out among various healthy groups of the population indicated no significant differences in respect to the carrier state of the Citrobacter and Hafnia bacteria both within each of the groups of the persons examined and between them. Further studies directed to the investigation of the etiological role of bacteria of the Citrobacter and Hafnia genus in the pathology of enteric disturbances are necessary.


A study of curiosity, divergent thinking, and test-anxiety. A review of the literature suggested that curiosity was positively related to divergent thinking, and negatively related to test-anxiety. Subjects were male and female 9th and 10th graders (N = 67), 11th and 12th graders (N = 67), and college undergraduates (N = 69). Curiosity was measured by an 80-item self-report scale and an adjective checklist, test-anxiety by a 37-item self-report scale, and divergent thinking by two verbal paper-and-pencil test. The results showed that both measures of curiosity were positively related to divergent thinking in all three groups studied, but that test-anxiety was not significantly related to either curiosity or divergent thinking. Differences in performance by the three groups of subjects were discussed.


An appraisal of the American and British health-care systems. 1. A dispassionate comparison of the British and American systems of medical care using conventional guidelines (structure, process, and outcomes) as applied to acknowledged national problems in health and medical care (expense, quality, and distribution) has been made. 2. Dissimilarities in the size of the countries, in the attitudes of physicians, and in homogeneity of populations make it unlikely that the two countries should have identical medical-care systems. 3. The "good features" of the NHS, which by implication might benefit the American system if adopted, are seen to be overshadowed by weakness: a) Relative expensiveness or extravagance of American medicine is seen as underfinancing of the British system. b) Quality of care in Britain is threatened by lack of professional stimulation of generalists, inadequate facilities, and rationing of medical care by prolonged waiting times for elective services. c) Distribution of services is a problem in both countries which will not be corrected by administrative controls but "pegged to incentives" as is true in America. 4. Administrative change in NHS in April 1974 is evidence of internal dissatisfaction. It also demonstrates the need for continual revision of the system; a similar need is made evident by recent legislative proposals in America. 5. Dr. Beeson's final recommendation for voluntary organizational effort by the profession in America has merit.


[Viability of sandflies (Diptera, Psychodidae, Phlebotominae) after infection with promastigotes of different types of Leishmania]. Sand flies were infected with different species of promastigotes from reptiles and warm-blooded animals. Optimal doses of promastigotes were used which ensured the adaptation of Protozoa in the host's intestine. The infection with a mixed culture resulted in the death of most Sand flies: the mortality rate was the highest at the simultaneous introduction of two species and was some what lower at the subsequent infection. The survival of Sand flies infected with one species of leishmania decreased to the greatest extent if "incidental" for them strains of promastigotes were introduced: for Ph. papatasi -- cultures isolated from reptiles, for Sergentomyia arpaklensis -- those isolated from L. tropica major. Natural infection rate of the genera Phlebotomus and Sergentomyia with leishmania of different species agrees with laboratory data on the survival of sand flies. Ph. caucasicus and Ph. papatasi are infected, in general, with L. tropica major, S. arpaklensis -- with L. gymnodactyli.


Lymphocyte reactivity in patients with carcinoma of the breast and large bowel. The reactivity of lymphocytes from patients with either carcinoma of the breast or large bowel has been studied using the human to mouse normal lymphocyte transfer (NLT) reaction. It was found that, in the case of breast cancer, there was a direct correlation between the clinical stage and a reduced NLT reaction. Only patients with regional lymph node or generalized metastases showed significantly reduced lymphocyte reactivity. However, in the case of large bowel cancer there was a generalized reduction in NLT reactivity which was independent of the clinical stage. Incubation of lymphocytes from individuals without neoplastic disease in serum or plasma from breast cancer patients, showing reduced NLT reactivity, resulted in a reduced NLT reaction. This appears to be indicative of the presence of circulating "blocking factor" in such patients.


Changes in plasma amino acid concentrations in man after ingestion of an amino acid mixture simulating casein, and a tryptic hydrolysate of casein. 1. Plasma amino acid levels have been estimated at 0, 15, 30 and 45 min after ingestion of doses of (1) an amino acid mixture simulating casein and (2) a tryptic hydrolysate of casein consisting mainly of oligopeptides. Both doses contained the same amount of nitrogen. 2. After ingestion of both preparations, there was a prompt increase in plasma amino acid levels, followed by a decrease. No such change occurred in fasting subjects. There were no significant differences between increments in plasma amino acid levels after ingestion of the amino acid mixture and the corresponding increments after ingestion of the tryptic hydrolysate. 3. Correlations were found between the areas under the curves for individual amino acid concentrations, after ingestion of the two preparations, and the amino acid composition of casein. The results do not suggest that increases in plasma amino acid levels following small doses of protein digestion products are the result of circadian changes, or that such increases are 'swamped' by absorption of amino acids from endogenous protein in the lumen of the small intestine.


Absorption of L-histidine and glucose from the jejunum segment of the pig and its diurnal fluctuation. 1. Flow rate of digesta and its component in the upper jejunum, and the absorption of L-histidine and glucose from the jejunum segment were measured in pigs fitted with three simple cannulas. The pigs were fed once faily at 08.30 hours. 2. Maximum flow of digesta was obtained in the period 10.00-10.30 hours; the flow rate decreased with time after feeding, reaching a minimum in the period 22.00-22.30 hours. 3. The absorption rate for L-histidine and glucose increased in a hyperbolic manner with increasing concentrations of infused test material, which ranged from 2.5 to 20 g/1 for each material. 4. L-histidine and glucose were absorbed nearly independently when perfused in combination. The absorption rates for glucose were significantly (P less than 0.01) greater than the corresponding rates for L-histidine at each concentration of infusate. 5. The absorption of both L-histidine and glucose expressed as a percentage of the amounts in the perfusate decreased with increasing  flow rate of perfusate, from 400 to 800 ml/h. The increase in flow rate from 400 to 800 ml/h was associated with a 20% increase in L-histidine absorption rate; there was a 30% increased in glucose absorption rate when the flow rate was increased to 600 ml/h, but no further incrase at 800 ml/h. 6. The absorption of both L-histidine and glucose decreased with time after feeding; the absorption rates for L-histidine and glucose measured for the period 10.00-22-30 hours were 126 and 133%, respectively, of those measured for the period 22.00-22.30 hours.


On the role of lysophosphatides in virus-induced cell fusion and lysis. Three strains of Newcastle disease virus (NDV-HP-16, NDV-L-Kansas, and NDV-N) were propagated in chick embryo fibroblasts, equilibrium labeled with 32Pi, and the composition of phospholipid in the membranous envelope of the virions determined. A phospholipid identifed as monoacylphosphatidylserine was consistently observed in the viral strains which are listed as follows in their order of decreasing abundance of lysophosphatidylserine: NDV-HP 16greater than NDV-L-Kansas greater than NDV-N. The phosphatidylserine concentration in the virion envelopes of these strains decreased in proportion to the increase in the monoacylphosphatidylserine concentration. No other lysophosphatide was observed in significant quantity in virions of these strains. The degree of cell fusion in mouse fibroblast monolayers by each of the viral strains was independent of the lysophosphatidylserine content of the virions. The ability of the viral strains to induce fusion from within, i.e., that occurring in cells that are actively propagating virus was: NDV-L-Kansas greater than NDV-HP-16 greater than NDV-N. The ability of the viral strains to induce fusion from without, i.e., that occurring in response to incubation of cells with large quantities of irradiated virus was: NDV-HP-16 greater than NDV-N greater than NDV-L-Kansas. On the basis of these findings we conclude that there is no direct correlation between the level of lysophosphatide in the virion and its ability to induce cell membrane fusion. A direct correlation was observed, however, between the presence of high monoacylphosphatidylserine content and the ability of a strain to produce lytic infection.


Fluorescence polarization and intensity kinetic studies of antifluorescein antibody obtained at different stages of the immune response. Kinetic studies of reactions between fluorescein and antifluorescein antibody produced during early, intermediate, and late stages of the immune response have been carried out utilizing both fluorescence intensity and polarization measurements in the static (time constant similar to 5 sec) and in the stopped-flow modes (time constant similar to 5 msec). During maturation of the immune response, it was found that the "on" second-order association rate constant increased its value only by a factor of three, whereas the "off" dissociation first-order rate constant decreased by a factor of over 1000. Hence, it is the rate of dissociation which largely determines the stability of the hapten-antihapten complex. Furthermore, since second-order rate behavior was found for even heterogeneous antibody, most of the heterogeneity with respect to binding affinity occurs as a result of the heterogeneity in the rate of dissociation of the hapten-antihapten complex and not from the primary combination of hapten and antibody. Antifluorescein antibody which exhibits both high binding affinity (K similar to 5 x 10(11) M-1) and homogeneity with respect to equilibrium binding has been shown to obey second-order association kinetics over wide ranges in concentration. Despite the fact that the value of the second-order rate constant for this fluorescein-antifluorescein reaction is as large as that for most other hapten-antihapten reactions (1.4 x 10(8) M-1 sec-1), the binding reaction has an appreciable activation energy (7 kcal/mol). This is true for both divalent and univalent antibody. Furthermore, the reaction rate parameters are markedly affected by specific anions. The value of the second-order rate constant (18.5 degrees) increases according to the following scheme: salicylate less than trichloroacetate less than SCN- less than ClO4- less than Cl- less than F- less than phosphate. The activation energy increases as follows: trichloroacetate less than phosphate less than F- less than Cl- less than ClO4- less than SCN- less than salicylate, whereas estimates of the entropy of activation indicate that deltaS++ increases as follows: tricholroacetate less than phosphate similar to F- less than Cl- less than ClO4- less than SCN- less than salicylate. The same mechanism which was previously proposed by us for the antigen-antibody reaction is also consistent with the kinetics of the fluorescein-antifluorescein reaction. This mechanism postulates a bimolecular process with structural rearrangements (conformational changes and/or the loss of water) in the formation of the transition state complex. The reaction between the fluorescein hapten and its antibody hence is not diffusion limited.


Cytoplasmic nonpolysomal messenger ribonucleoprotein containing actin messenger RNA in chicken embryonic muscles. Cytoplasmic nonpolysomal mRNAs have been isolated in the form of 16-40S ribonucleoprotein particles from the postribosomal supernatant of 14-day-old chick embryonic muscles. An 8-20S RNA fraction isolated from these particles directs the synthesis of actin in a wheat germ embryo S-30 system, as judged by copurification of the products with chicken muscle actin by repeated cycles of G- to F-actin transformation; mobilities of the purified product on sodium dodecyl sulfate-polyacrylamide gels and urea gels; and analysis of the CNBr-cleaved peptides. The 16-40S particles have a buoyant density of 1.4 g/cm3 which corresponds to an RNA/protein ratio of 1:3. They do not contain detectable levels of ribosomal subunits, as judged by the absence of typical ribosomal proteins in the range of 15,000-30,000. They contain at least eight distinct polypeptide species in the molecular weight range of 44,000-100,000, including a prominent 44,000 species. The presence of these particles suggests that they may have a role in the regulation of translation in developing muscles.


Chemical and physical properties of the disulfides of bovine neurophysin-II. Bovine neurophysin-II is shown to be very susceptible to partial reduction in the absence of urea. Reduction of an average of one disulfide leads to major changes in conformation and disulfide optical activity, manifest in part by pronounced far-uv ellipticity changes, complete loss of the 248-nm ellipticity band, and a shift of the 278-nm ellipticity band to shorter wavelengths with loss of half its intensity; the reduction process generates a mixture of products and appears to be accompanied by disulfide interchange. The circular dichroism data indicate that the disulfide(s) most susceptible to reduction or interchange are either the principal contributors to the 248- and 278-nm ellipticity bands or that the optical activity of other disulfides is dependent on their integrity. Peptides that bind to the hormone-binding site of neurophysin-II protect against reduction. On reoxidation of partially reduced neurophysin-II there is only a partial return of the native circular dichroism spectrum and electrophoretic behavior. The percentage of native protein in samples reoxidized following different degrees of reduction was estimated by comparison of the circular dichroism spectra of these samples with those of the fractionated native and denatured components of monoreduced-reoxidized neurophysin. Under our reoxidation conditions, less than 50% native protein was found in monoreduced-reoxidized neurophysin and less than 10% native protein was found in completely reduced-reoxidized neurophysin. The results are interpreted with qualified reference to a model in which one or more disulfides are "strained" in the native state and in which the native protein is unstable relative to species in which the disulfides are differently paired.


Characterization and improved separation of soybean leghemoglobins. An improved separation procedure is described for isolating five leghemoglobin components from the nodules of soybean plants. After a preliminary oxidation with ferricyanide, and separation from endogenous nicotinate at pH 9.2, the ferrileghemoglobins are separated by DEAE-cellulose chromatography using gradient elution with acetate buffer (pH 5.2). The components have been characterized by their acetate and nicotinate binding affinities, gel electrophoretic, visible, and circular dichroic spectra in the ultraviolet, Soret and visible regions. Two formerly unresolved components of leghemoglobin c have indistinguishable circular dichroic, electrophoretic, and ligand binding properties, but differ in their spin states as judged by their visible spectra, their amino acid analyses, and their tryptic maps.


Cooperativity of binding of anilinonaphthalenesulfonate to serum albumin induced by a second ligand. When a ligand X is multiply bound to energetically identical, noninteracting sites of a protein, cooperative binding of this ligand can be induced by the presence of a second ligand Y. This effect should appear whenever multiple interactions exist between the bound X and Y ligands, and vanish when the concentration of Y is made sufficiently  large to ensure Y saturation at all concentrations of X. These predictions have been verified for the binding of 8-anilino-1-naphthalenesulfonate to serum albumin, when Y, the effector ion, is 3,5-dihydroxybenzoate. In the presence of 2mM dihydroxybenzoate, the Hill coefficient for anilinonaphthalenesulfonate binding rose steadily from 1 to 1.5 as the number of molecules of ligand bound increased from 1 to 3.3 per albumin molecule. The theory of interactions between isolated ligands, applied in the previous paper (D. A. Kolb and G. Weber (1975), Biochemistry, preceding paper in this issue), is extended to cases of multiple interactions, and applied here to show that the experimental results are tolerably well reproduced for a model in which four anilinonaphthalensulfonate molecules are homogeneously coupled to four molecules of dihydroxybenzoate by free energies of 3.0 and 3.5 thermal units.


Postreplication repair of DNA in chick cells: studies using photoreactivation. During replication of DNA after ultraviolet irradiation, gaps are left in the newly-synthesized DNA strands in both bacterial and animal cells and these gaps are subsequently sealed by a process known as postreplication repair. In order to test whether it is the ultraviolet-induced pyrimidine dimers which are responsible for the production of these daughter-strand gaps in animal cells, we have used chick embryo fibroblasts. In these cells the pyrimidine dimers are photoreactivable, i.e. they can be split by an enzymatic process dependent on visible or near ultraviolet light. Our results indicate that chick cells possess a postreplication repair system similar to that in mammalian cells; gaps are produced in the newly-synthesized strands and then filled in. If the ultraviolet-irradiated cells are first photoreactivated to remove most of the dimers, the number of daughter-strand gaps produced is much less than without photoreactivation. This suggests that the dimers are indeed responsible for the formation of many of the gaps in the newly-synthesized DNA. Ultraviolet light also inhibits the overall rate of DNA synthesis. This inhibition is, however, only partly overcome by photoreactivation.


A neutral protease in rheumatoid synovial fluid capable of attacking the telopeptide regions of polymeric collagen fibrils. Fluorescent-labelled polymeric collagen fibrils have been prepared which contain three fluoresein residues in the telopeptide regions and four fluorescein residues in the helical region of each tropocollagen unit within the polymer. This material has been used as a substrate for the study of enzymes present in the synovial fluid of inflamed rheumatoid joints which are capable of degrading polymeric collagen fibrils. Two enzyme systems were observed, one inhibited by EDTA and having the properties of the known synovial  collagenase, the other having the properties of a neutral protease. The neutral protease was found to be present in sonicates of the polymorphonuclear leucocytes in the synovial fluids of inflamed joints. This enzyme attacked the telopeptides of fluorescein-labelled polymeric collagen fibrils and was similar to trypsin in removing two residues of fluorescein-labelled peptides per tropocollagen molecule within the polymeric collagen fibrils but did not depolymerise the polymeric collagen fibrils.


A differential viability model for twin-pair blood group data. Much interest in human genetics studies of blood systems is focussed on the possible incompatibility of discordant twin pairs. Here we discuss a differential viability model which accounts for deviations from the standard multinomial model for twin pair data based on the Hardy-Weinberg frequencies. We discuss related estimation and testing problems, illustrating the techniques with data from the Louisville Twin Study.


Damaged DNA in lymphocytes of aplastic anemia. The size of single-stranded DNA in lymphocytes in GO stage from 22 patients with acquired primary and secondary aplastic anemia was estimated by alkaline sucrose gradient centrifugation. The average size was 9.3 (+/-0.3) times 10(7) daltons. The lymphocytes of patients contained significantly more single-strand breaks in DNA, compared to those of normal persons. The difference in size of single-stranded DNA which had been present in nontransformed lymphocytes could also be observed in transformed lymphocytes. Some characteristic differences could be observed in the sedimentation patterns of single-stranded DNA in the lymphocytes of patients with aplastic anemia and those of normal persons. The single-strand breaks in DNA suggested that the repair processes were disturbed in the DNA molecules of circulating lymphocytes from patients with acquired primary and secondary aplastic anemia.


Vasopressin release by nicotine: the site of action. 1. In cats anaesthetized with chloralose the release of neurohypophysial hormones was examined after injection of nicotine into the cerebral ventricles or cisterna magna or its topical application through perspex rings to the ventral surface of the brain stem. The release was measured by assaying the hormones in samples of venous blood. 2. Injected into a lateral or the third cerebral ventricle, nicotine (0.5 to 1 mg) produced release of vasopressin without oxytocin. When the aqueduct was cannulated, preventing access to the fourth ventricle and to the subarachnoid space, this release did not occur. 3. Vasopressin was also released without oxytocin when nicotine (0.25 to 2 mg) was injected into the subarachnoid space through the cisterna magna. With this route of administration the nicotine did not enter any part of the ventricular system. 4. Applied through paired perspex rings placed across the ventral surface of the brain stem, nicotine again produced release of vasopressin without ocytocin. The amount of nicotine placed in each ring was usually 80 mug, but a release was obtained with 10 mug and in one experiment with as little as 5 mug. 5. The bilateral region on the ventral surface of the brain stem where nicotine acts when producing release of vasopressin lies lateral to the pyramids and in a longitudinal direction, 6 to 9 mm caudal to the trapezoid bodies. 6. The vasopressin release by nicotine injected intraventricularly or intracisternally, or applied topically to the ventral surface of the brain stem was not due to absorption of nicotine into the blood stream, nor to blood pressure effects. 7. It is concluded that nicotine acts on the ventral surface of the brain stem probably by activating the central projection to the supra-optic and possibly also the paraventricular nuclei of afferent pathways in the sinus and vagus nerves which control the release of vasopressin in response to changes in blood volume or distribution.


Unit activities in the hypothalamus and midbrain during stimulation of hypothalamic attack sites. Unit activity in the hypothalamus and midbrain of unanesthetized cats was studied during electrical stimulation of the hypothalamus at sites that induced attack and at other comparable sites from which attack was not induced. The changes in the firing of units at distances from 0.7 to 1.9 mm from the site of stimulation were similar to those of units at distances from 2.0 to 5.2 mm. Although stimulation in general affected a majority of units, resulting in increases rather than in decreases of firing rates, and produced similar patterns of unit activity, stimulation at sites that induced attack affected more units, produced a greater change in unit activity and markedly increased firing rates in the lateral hypothalamus and the dorsal part of the midbrain.


Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine. Stereotaxically placed intracerebral microinjections of 6-hydroxydopamine (6-OHDA) were used to produce selective and extensive lesions of either the dopaminergic nigro-neostriatal bundle or the dorsal and ventral noradrenergic projections in the rat. The extensive damage of the noradrenergic pathways which is typically obtained after intranigral 6-OHDA injections was completely prevented by pretreatment with desipramine. Extensive depletions (85-95%) of norepinephrine (NE) in the hypothalamus, cerebral cortices and hippocampi failed to influence either spontaneous or D-amphetamine-induced locomotor activity. Neither the time course of the amphetamine response as measured by photocell cages nor the qualitative nature of the response as determined by direct observation was significantly altered by these lesions. In contrast, selective depletion (92%) of neostriatal dopamine (DA) after intranigral 6-OHDA injections severly reduced but did not abolish amphetamine-induced hyperkinesia. At the highest dose studied (2.0 mg/kg) these animals showed an initial increase in activity but, unlike controls, failed to maintain this level. This response was probably mediated by the small remaining stores of DA in the neostriatum. Pimozide (0.5 mg/kg) also severely attenuated but did not abolish amphetamine-induced locomotor activity. These data are consistent with the view that ascending DA projections are a critical substrate for amphetamine-induced hyperkinesia. They furthermore suggest that ascending NE systems do not play a role in this response.


Effects of electrical stimulation of the lateral aspect of the prefrontal cortex upon attack behavior in cats. An experiment was performed to determine the role of the lateral aspect of the prefrontal cortex upon quiet biting attack behavior elicited from the hypothalamus in the cat. The results of this experiment indicate that stimulation of 19 of 28 electrode sites sampled in the lateral prefrontal cortex produced a statistically significant inhibition of attack behavior elicited from the hypothalamus of the ipsilateral side. Stimulation of sites in the prefrontal cortex on the side contralateral to the hypothalamus from which attack was elicited had no effect upon this response. No systematic effect of prefrontal stimulation upon flight behavior was observed. Anatomical studies suggest that the lateral prefrontal cortex may inhibit attack behavior by modulating neurons in either the mediodorsal thalamic nucleus or ventral tegmental area.


Response properties and anatomical organization of pontine and medullary units responsive to vaginal stimulation in the cat. The response properties and anatomical organization in the brain stem of 234 pontine and 60 medullary genitally sensitive (GS) neurons were studied by single-unit recording in acutely prepared estrous and anestrous cats which were decerebrated under sodium pentothal or anesthetized with urethane. Pontine unit responses to vaginal probing were very pronounced and stimulus-bound, and involved a variety of response patterns. Most of the pontine GS neurons also responded to nociceptive stimuli and to a lesser degree, to innocuous somatic, extragenital visceral, and auditory stimuli. Among pontine GS cells recorded in estrous cats, responsiveness to innocuous somatosensory stimuli was more prevalent than among units in anestrous preparations (71% vs. 40%), and on the average, the units in estrous cats responded to stimulation of more regions of the body than did comparable units in anestrous animals. In recordings from the medulla in the decerebrate preparations, exclusive responsiveness to vaginal stimulation was observed in 22% of the GS neurons, contrasting with earlier results from urethane-anesthetized animals in which a greater degree of specificity was found. A close anatomical proximity existed between some medullary GS neurons and cells of nucleus ambiguus, including antidromically identified recurrent laryngeal nerve motor neurons, and between pontine cells and the trigeminal motor nuclei. Antidromic responses of GS neurons to stimulation of the brain stem revealed a projection from medullary GS neurons to the lateral tegmental field of the pons. Relatively few pontine GS neurons projected to the ipsilateral medulla. A strong synaptic influence upon medullary GS neurons, possibly or midbrain origin, descends from the lateral tegmental field of the pons.


Neuronal correlates of an encephalopathy associated with aluminum neurofibrillary degeneration. A previous study reported that the intracranial injection of a soluble aluminum salt induced an encephalopathy which may serve as a useful animal model of dementia. An early sign of the encephalopathy in cats was a progressive decrement in both the performance of a short-term visual retention task and acquisition of a conditioned avoidance response in the presence of normal visual discrimination. This study reports that 10 days following the application of aluminum (AlCl3) there was an absence in cat visual cortex of neurons with spontaneous frequencies between 7 and 12 spikes/sec. The loss was associated with neurofibrillary degeneration and aluminum concentrations in lateral gyrus between 4 and 6 mug/g dry weight. The remaining neurons decreased their variability of response to identical visual stimuli and increased their probability of response and frequency of discharge.


[Hematological and biochemical normogram and daily variations of the base parameters in the normal dog]. These experiments were designed in order to determine normal hematological and biochemical values of normal dogs living in a laboratory environment. The findings were conclusive. Serial studies of some of the basic parameters have been done in a second group of animals. After a short period of conditioning, daily changes in weight, temperature, hematocrit and hemoglobin are minimal if the methods of analysis are standardized and reproducible.


Stabilization of hog cholera virus by dimethyl sulfoxide. The stability of hog cholera virus through five freeze-thaw cycles in the presence and absence of dimethyl sulfoxide was studied. In the absence of dimethyl sulfoxide the hog cholera virus titer was reduced 52% to 91% following successive freezing and thawing cycles. However, when dimethyl sulfoxide was added to the viral suspension the virus titer appeared to remain the same after the same number of freezing and thawing cycles.


Luteinizing and ovulatory action of oestradiol in the pregnant rat. Oestradiol injection on Day 10 of pregnancy in rats, resulted in either ovulation or luteinization in 50% of cases on Day 12. Cytological data showed that the number of pituitary LH cells decreased significantly on Day 11 in all oestradiol-treated animals whether responsive or not to oestrogen by ovarian modifications, while the number of pituitary FSH cells only decreased significantly in females with characteristic ovarian signs of preovulation. Bioassay of pituitary FSH confirmed the cytological data. It is concluded that ovulation and luteinization only occurred in the pregnant rat when oestradiol triggered off a synchronous release of LH and FSH.


Cholesterol: lecithin association at molecular ratios of up to 2 : 1. X-ray diffraction studies of cholestol: egg lecithin mixtures have demonstrated that single phase systems with molecular ratios of up to 2 : 1 can be prepared from solutions in chloroform but that mixtures prepared from ethanol solutions form a single phase only up to a maximum molecular ratio of 1 : 1. The low angle X-ray patterns of the two mixtures (2 : 1 and 1 : 1) are quite distinctive but there is only a small difference in the wide angle spacings. Independent cholesterol reflections begin to appear in the X-ray diffraction pattern of the 2 : 1 mixture after a few days even when the dry sample is contained in a sealed glass capillary tube. Addition of water greatly accelerates this process. In contrast, a 2 : 1 mixture prepared from chloroform solutions can be maintained in sonicated dispersions in water for long periods.


Pharmacokinetic considerations on resistance to anticancer drugs. A model framework is discussed for a quantitative description of intercompartment drug transport in terms of individual processes involved. It permits joint consideration of blood flow, membrane transport, binding, and enzyme synthesis. Illustrations are drawn from the pharmacokinetics and pharmacodynamics of methotrexate. Special cases include flow and membrane limitation, and a simple expression is derived to estimate the time required for intracellular drug to reach the concentration of high-affinity binding sites. Transport parameters between blood and cerebrospinal fluid are inferred from new clinical data. Lumbar injection provided a reservoir effect which maintained plasma concentration for a prolonged time compared with intravenous injections.


An improved basis for enzymatic estimation of infarct size. Infarct size has been estimated from serial serum creatine phosphokinase (CPK) changes, but the contribution of noncardiac CPK may interfere. Results would also be influenced if CPK disappearance varied with hemodynamic changes. Since MB CPK is a marker more specific to myocardium. infarct size was estimated from serum MB changes in 16 patients. In addition, 21 chronically instrumented conscious dogs subjected  to tachycardia, decreased cardiac output or hepatic or renal ischemia were studied to evaluate the dependence of CPK disappearance on hemodynamics. MB CPK in human tissue extracts and serum was quantified with a new, rapid, glass bead-batch adsorption technique, verified with CPK isoenzymes prepared from human myocardium. Among tissues surveyed, only myocardium contained appreciable MB CPK. Infarct size estimated from MB correlated with total serum CPK in patients with uncomplicated myocardial infarction (r=0.97, N=12). In patients with infarction given intramusclar injections, total CPK curves were distorted but MB CPK curves were not apparently affected. Hemodynamic alterations in conscious dogs did not markedly affect the disappearance rate (kd) of intravenously injected, radioactively labeled, canine myocardial CPK, although kd was shown to depend on reticuloendothelial system activity. These findings suggest that estimation of the extent of infarction based on serum MB CPK should be useful despite hemodynamic deterioration associated with infarction or interference of noncardiac CPK.


Analysis of the effects of antitumor drugs on cell cycle kinetics. A cell cycle stage-specific multicompartmental model has been developed and used to investigate the effects of antitumor drugs on the proliferation of tumors. The drug effects simultaneously considered are (a) non-cycle-specific killing and cycle stage-specific killing of cells, (b) progression delay of cells through the cell cycle phases which may bring about an accumulation of cells in various phases of the cell cycle, and (c) prolongation of cell cycle times. These effects are analyzed in terms of possible variations in the behavior of cell kinetic parameters (namely, cell cycle times, cell loss rate, and growth fraction) and are implemented in the model specifying proper functional forms for the parameters. The time-course of drug distribution in a tumor-host system is also described by a two-compartment model and the factors affecting drug action are quantitatively formulated as a function of drug concentration. Simulation is carried out to examine the effects of BCNU, cytosine arabinoside, and methotrexate on the cell cycle and proliferation kinetics of L1210 leukemia, and the results of the simulation compare favorably with available experimental data. Also discussed are the sensitivity of drug effects to variation in dosage schedule and the different nodes of drug actions exerted on each cell cycle phase.


Effect of digitalis in patients with paroxysmal atrioventricular nodal tachycardia. Atrioventricular (A-V) conduction, ventriculo-atrial conduction and mechanism of tachycardia were studied by programmed electrical stimulation before and after the administration of ouabain in 15 patients suffering from paroxysmal supraventricular re-entrant tachycardia. In 13 patients the tachycardia circuit was confined to the A-V node. In two patients the stimulation study showed that an accessory pathway was used in a ventriculo-atrial direction during tachycardia. Ouabain lengthened the effective and functional refractory period of the A-V node and A-V nodal transmission time in all patients in whom this could be studied. Only six patients showed lengthening in ventriculo-atrial conduction time or refractory period of the ventriculo-atrial conduction system. In seven patients no tachycardia could be initiated after ouabain. The width of the zone of atrial premature beats able to initiate tachycardia (the tachycardia zone) narrowed in five patients, showed no change in two patients, and increased in one patient. In these eight patients the tachycardia zone shifted to longer premature beat intervals. Ouabain resulted in slowing of cardiac rate during tachycardia. Both patients who used an accessory pathway during tachycardia showed no change in width of their tachycardia zone following ouabain administration. Seven patients were restudied two weeks after chronic oral administration of digoxin. The results were similar to those obtained following ouabain administration. This indicates that in patients suffering from paroxysmal A-V nodal tachycardia the effect of chronic oral digoxin administration can be predicted from the study of the effect of ouabain during programmed stimulation of the heart.


Regional myocardial function in idiopathic hypertrophic subaortic stenosis. An echocardiographic study. To assess regional contractility in idiopathic hypertrophic subaortic stenosis (IHSS), a primary myopathic disorder with documented hyperdynamic ventricular contractions, systolic wall thickening and velocity of contraction of the septum and left ventricular posterior wall were measured in echocardiograms from 16 patients with IHSS and 16 normal subjects. The average thickening of the normal septum and posterior wall was 75.9+/-8.8% and 84.8+/-6.3%, respectively. The posterior wall in IHSS thickened by 75.1+/-6.8%. None of these values differed significantly. However, the increase in thickness of the IHSS septum averaged 22.5+/-2.4%, significantly less than that of either the IHSS posterior wall or the normal septum. Velocity measurements confirmed the impression of diminished septal function. The mean velocity of normal septal contraction averaged 37.0+/-2.3 mm/sec, normal posterior wall 42.3+/-2.0 mm/sec and IHSS posterior wall 55.7+/-3.5 mm/sec, whereas the septum in IHSS contracted at the rate of 26.0+/-2.5 mm/sec. Thus, the IHSS septum contracted significantly more slowly than the normal septum or IHSS posterior wall. However, the posterior wall velocity in IHSS was significantly more rapid than that measured in normal ventricles--perhaps to compensate for the septum. Normalization of all velocities for left ventricular end-diastolic internal diameter did not alter the sifnificance of the results. Consideration of IHSS as an asymmetric myopathy based on prior observations of predominantly septal hypertrophy and distorted septal cellular architecture is now supported by the above evidence of functional left ventricular asymmetry. Although the total left ventricular function in IHSS may be hyperdynamic, regional function is not uniform. The septum appears to be hypodynamic, while the contractile capacity of the posterior wall is increased.


Congenital heart malformations associated with disproportionate ventricular septal thickening. Asymmetric septal hypertrophy, or ASH, is a genetically determined myocardial disorder that is transmitted as an autosomal dominant trait. ASH is characterized by a disproportionately thickened ventricular septum that contains numerous hypertrophied, bizarrely-shaped and disorganized cardiac muscle cells. Disproportionate hypertrophy of the ventricular septum has also been observed in association with certain congenital cardiac malformations. To determine whether such congenital cardiac malformations are part of the disease spectrum of genetically determined ASH, cardiac pathologic observations were made in eight patients with disproportionate septal thickening (ventricular septal to posterobasal left ventricular free wall thickness ratios of 1.5 to 2.5) and the following three categories of associated lesions: 1) parachute deformity of the mitral valve (occurring either as an isolated lesion or with ventricular septal defect, coarctation of the aorta, supravalvular ring of the left atrium, or double outlet right ventricle); 2) complete interruption of the aortic arch; and 3) ventricular septal defect. The arrangement of cardiac muscle cells in the disproportionately thickened ventricular septum was normal in six of the eight patients; in the other two patients (one with parachute deformity of the mitral valve and one with ventricular septal defect) numerous bundles of hypertrophied cardiac muscle cells were interlaced in a disorganized fashion among more normally arranged bundles of cells. First degree relatives of six of the eight patients were studied by echocardiography and found to have normal ventricular wall thicknesses and septal-free wall ratios. It is concluded that disproportionate ventricular septal thickening may occur in patients with a variety of congenital heart malformations, but that such a finding is not necessarily a manifestation of the disease spectrum of genetically determined ASH.