Morphology and fine structure of the feline neonatal medullary raphe nuclei. A light and electron microscopic study of the caudal medullary raphe nuclei of neonatal kittens reveals that these nuclei are composed of three size classes of neurons with several possible subclasses. Internuclearly projecting dendritic arborizations in the transverse plane and intranuclear projections in the sagittal plane are common features of large and medium size class neurons of raphe nuclei magnus and obscurus though not for the cells of nucleus raphe pallidus. A positive correlation exists between neuron size and density of axosomatic and axodendritic synapses, which suggests that the large class neurons are the first to receive input in synaptogenesis, which is occurring at this time. A wide variety of synaptic forms and integration is also a characteristic feature within these nuclei, though it is not clear whether this morphological variance represents a phylogenic and/or ontogenic trend or just an expression of the multifunctional nature of this region.


Fine structure of growth cones in medullary raphe nuclei in the postnatal cat. Morphological aspects of the dynamic processes of growth cone formation and synaptogenesis have been studied in neonatal kitten (2-17 days) medullary raphe nuclei. The formation and elaboration of dendritic growth cones and primary dendritic trunks is actively taking place on the medium size class neurons (stellates) of these nuclei. The dendritic growth cones are morphologically distinctive due to their population of large dense-core vesicles and postsynaptic position. Another growth cone morphology, interpreted as axonal, is also described. This growth cone is typically found in close association or synaptic contact with the dendritic growth cones and contains, in addition to synaptic vesicles, a dense-core vesicle population distinguishable from that of the dendritic growth cone by the presence of a variety of vesicles containing an eccentrically positioned dense particle. No evidence of axo-axonic or dendrodendritic synapses has been found. Synaptogenesis was found to be occurring on somas, dendrites and dendritic growth cones throughout the medullary raphe nuclei, though this phenomenon was more apparent in indistinctly localized subnuclear spaces termed synaptogenic zones. Within these zones large class neurons are found to have greater densities of both axodendritic and axosomatic synapses than medium and small class neurons respectively. Axodendritic synaptic densities on primary and secondary dendrites of large and medium class neurons are greater than their respective axosomatic synapse densities, which may suggest that the latter forms at a later period of development.


Visual receptive fields in the lateral suprasylvian area (Clare-Bishop area) of the cat. Single units were recorded from the visual area of the lateral suprasylvian gyrus (LSSA or Clare-Bishop area) in 20 unanesthetized cats. Most LSSA units were poorly responsive to stationary visual stimuli, but they responded vigorously to moving visual stimuli. Their receptive fields appeared to be constituted of a large activating region (discharge area) often surrounded by inhibitory flanks. Relating unit behavior to changes of stimulus length, the LSSA neurons could be subdivided into 5 categories. The first category (22 out of 95 units tested, 23.16%) consisted of units showing summation inside the discharge area. Expanding the stimulus outside the discharge area did not affect the response. The second category (7.37%) was formed by units which showed summation inside the discharge area and inhibition when the stimulus was extended outside the discharge area. The third category (21.05%) consisted of units largely insensitive to the stimulus length inside the discharge area, but surrounded by inhibitory flanks. The fourth category (41.05%) consisted of units which showed inhibition of the response when the stimulus, well inside the discharge area, became longer than a certain optimal lenght. They were surrounded by inhibitory flanks. The fifth category (7.37%) was formed by units insensitive to variations of the stimulus length inside as well as outside the discharge area. Almost all units, independent of their category, were directionally specific, that is their response could be decreased 50% or more by varying the direction of movement away from that which gave the maximal response (preferred direction). Typically the response was halved when the stimulus was moved +/- 50 degrees from the preferred direction. Among the directionally specific units, 71% showed the minimal response 180 degrees away from the preferred direction (direction specificity curve type 1), 20% had the minimal response 90 degrees from the preferred direction (direction specificity curve type 2); the remaining could not be classified in this respect. Of LSSA units, 87% (all those of type 1 and many of those of type 2) were directionally selective, that is their response to movement in the preferred direction was at least double that in the opposite direction. The LSSA units usually preferred stimuli moving at rather high speeds. The optimal speed for 71% of units was 20 degrees/sec or greater. Almost all units responded over a wide range of speeds, many of them from 5-10 degrees/sec to over 100 degrees/sec. Most neurons had a low spontaneous activity and some of them remained completely silent for seconds.


Studies on field potentials and on single cells in the inferior olivary complex of the rat. Field and unitary action potentials have been recorded in the inferior olivary complex of pentobarbital anaesthetized rats. Spontaneous and antidromically evoked unitary potentials, and antidromically evoked field potentials all showed the same biphasic profile. Repetitive antidromic stimulation resulted in attenuation of the field potential with stimulation frequencies as low as 10 Hz. The latency of juxtafastigially evoked spikes was variable, and decreased with increasing stimulus strengths. Electrophoretically applied glycine, gamma-aminobutyric acid, noradrenaline, dopamine and 5-hydroxytyptamine all reduced the amplitude of the antidromic potential, but sometimes caused a transient increase preceding this decrease. Orthodromically (femoral nerve) evoked potentials were different in form and could assume one of two distinct profiles. The effects of electrophoretically applied DL-homocysteate (DLH) and the putative transmitters listed above on the form of such field potentials are described. DLH, ACh and 5-HT were tested on single olivary neurones, which had spontaneous firing rates of less than 2 Hz. These compounds had only slight effects on firing rates although marked changes were seen in action potential configuration. Spontaneous synchronous discharges of groups of olivary neurones are described. This and other findings confirm that olivary units have a tendency to both rhythmical and synchronous firing.


The effects of beta-carbolines on responses to acetylcholine, noradrenaline, 5-hydroxytryptamine and amino acids in the rat spinal cord. Various drugs have been applied electrophoretically to Renshaw cells and to unidentified spinal neurones in pentabarbitone anaesthetized or decerebrated rats. Responses to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) have not previously been described at this site and were of two types; either monophasic depression or biphasic depression-excitation. The effect of harmine on these responses was examined. Harmine and harmaline were also tested on the excitant responses to acetylcholine (ACh) and DL-homocysteate (DLH), and on the depressant responses to glycine and gamma-aminobutyric acid (GABA). On some cells harmaline antagonized ACh, but not DLH, and glycine, but not GABA, responses. Harmine caused only non-specific depression and spike configuration changes. The effects of harmine on NA and 5-HT responses were usually non-specific, and any anatagonism was usually accompanied by, or soon followed by spike changes. LSD was also tested on the amine responses. LSD itself had a clear depressant effect on neuronal firing rates. It could either antagonize or potentiate NA and 5-HT depressant responses, but the antagonism in particular was closely followed by spike changes. Somewhat more specific antagonism of the late excitation was seen.


A comparative analysis of compartmentation of metabolism in the dorsal root ganglion and ventral spinal cord gray using [U-14C]glucose, [2-14C]glucose, [6-14C]glucose, [3,4-14C]glucose, NaH14CO3, and [2-14C]pyruvate. A detailed temporal comparison of glucose metabolism, in the production of glutamate and glutamine as well as aspartate and alamine, was conducted in order to further define the uniqueness of the dorsal root ganglion compared to the ventral spinal cord gray. Experiments with injected labeled NaHCO3 and pyruvate were used in an attempt to clarify certain aspects of the above results with different [14C]glucose precursors. The glutamine/glutamate relative specific activity ratio (RSA) was consistently lower in the ganglion than in the ventral spinal cord gray, as was also true for glutamate specific activity from the same amount of injected [14C]glucose. The ganglion is characterized by a high level of alanine production from glucose and pyruvate. The NaH14CO3 experiments suggest that CO2 fixation from [3,4-14C]-glucose in the dorsal rool ganglion resul .ts in a higher glutamine/glutamate RSA when compared to results using either [6-14C] or [2-14C]glucose.


Tissue damage at the infection site after intramuscular injection of drugs in hens. 1. Injection sites were examined on the 7th d after intramuscular injection of vehicles alone or containing antibiotics or chemotherapeutics. 2. Eight out of 13 preparations caused necroses, the largest of which were seen after injection of tetracyclines and sulphonamides.


The hen's egg: independence of weight at oviposition and the sex of the chick. 1. Cockerels tend to be heavier than pullets at hatching and an experiment was therefore done to test the null hypothesis that the eggs from which cockerels hatch are, on average, at oviposition of the same weight as those from which pullets hatch. 2. The experiment did not disprove it.


The effects of exogenous oestrogen and progesterone on laying and nesting behaviour in the hen. 1. It has been shown that if oestrogen and progesterone are given to ovariectomised hens nesting behaviour will occur. Thus if these hormones are given to normal hens the excessive pacing found in some hens before laying might be reduced. 2. Experiments showed that oestrogen produced no noticeable effects and progesterone caused a high incidence of delayed oviposition and abnormal behaviour.


The chromosome number of Gallus domesticus. 1. Chromosome counts were made on 105 spermatogonial and diakinesis cells prepared from testicular tissue taken from 10 hybrid cockerels. 2. The modal numbers for the diploid chromosome and haploid chromosome complements were 78 and 39 respectively.


The use of growth and liver aspartate aminotransferase to assess the effect of source of non-essential nitrogen on pyridoxine depletion, repletion and requirements of chicks. 1. Two experiments were carried out to study the relationship between growth, liver aspartate aminotransferase (Asp AT) and dietary pyridoxine to determine the pyridoxine requirement of chicks fed on diets containing crystalline essential amino acids with glutamic acid (GA) or diammonium citrate (DAHC) as the non-essential nitrogen source. 2. In one experiment purified diets containing isolated soy-protein with 0 or 3 mg pyridoxine/kg were used. The deficient chicks were significantly lighter, coverted food less efficiently and liver Asp AT activity was decreased. When deficient chicks were offered an adequate diet performance improved and Asp AT activity rapidly increased. 3. In the second experiment diets containing crystalline amino acids GA or DAHC combined with 0, 1 or 3 mg pyridoxine/kg (GA: 0, GA: 1, GA: 3, DAHC: 1, DAHC:3) were used. Growth rates of chicks fed on GA: 1 and GA: 3 were similar, whereas chicks fed on DAHC: 1 were significantly lighter than those given DAHC: 3. The growth data indicated a pyridoxine requirement for chicks fed on the GA diets of not more than 1mg/kg and of more than 1 mg/kg in those fed on diets containing DAHC. Asp AT activity varied significantly with dietary content of pyridoxine but not with the nitrogen source. When Asp AT activity was used to assess pyridoxine requirements, there was nof difference between chicks fed on GA or DAHC diets.


Energy and nitrogen metabolism of diseased chickens: interaction of Ascaridia galli infestation and vitamin A status. 1. Effects of Ascaridia galli infection on the energy and nitrogen (N) metabolism were studied on groups of 5 cross-bred cockerels aged about 5 weeks and given a diet deficient or adequate in vitamin A at two levels of feeding in respiration chambers. 2. Metabolisability of dietary energy was 67% and N retention 33% in infected chickens compared with 71 and 41% respectively, in uninfected chickens. 3. Maintenance energy requirement of vitamin A-deficient birds was 882 kJ/kgW d compared with 998 kJ/kgW d for normal birds. N balance of the deficient chickens was also less when compared at the same energy balance. Infection did not affect maintenance energy requirement nor N balance. 4. Starvation heat production of infected chickens (619 kJ/kgW d) was higher than that of uninfected controls (586 kJ/kgW d). When infection treatments were combined, vitamin A-adequate chickens had a higher heat production (615 kJ/kg d) than the vitamin A-deficient (580 kJ/kgW d). Endogenous N excretion (mg/gW) was less in vitamin A-deficient than in adequate, starved birds. 5. Deficient chickens had undetectable liver reserves of vitamin A and only very low plasma concentrations. There was a difference in the length of larvae (17 d after infection) associated with vitamin A status, and with level of feeding.


Energy and nitrogen metabolism of diseased chickens: aflatoxicosis. 1. New Hampshire chicks were fed on diets containing 0 (control), 0-7 (A), or 1-1 (B) ppm of aflatoxin B1. In two trials 1-d-old chicks were offered ad libitum the three diets for 14 d. The gaseous exchange of five chickens from each group was measured for 3 or 4 d, the same diets being fed, at 2, 3, 4 and 5 weeks of age in two series of experiments. The controls were fed at the lower intake of the two other groups. Following each series of experiments at the various ages, birds were starved for 24 h and their heat production was re-measured over the next 24 h. 2. Mortality was highest and growth and food conversion poorest where the diet with the highest aflatoxin concentration was fed. Mortality was confined to the first 2 weeks. 3. Performance of birds in the chambers was improved in the second series due to differences in food intake. It also improved with age suggesting some resistance to the toxin. 4. Mean respiratory quotient was 0-97 for fed chickens on diet B. This was significantly different from 0-92 for the two other groups. Similarly, during starvation the RQ was 0-76 compared with 0-73. 5. birds fed on diet B generally grew better, retained more nitrogen and had a better energy balance in the respiration chambers than the other two groups. Metabolisability of dietary energy was less (68.5%) for all groups at 2 to 3 weeks than when older (70%) but availability of ME was the same (71%) for all groups. 6. Heat production (kJ/kg0-75) of starved birds on diet B was significantly lower than the other two groups, while endogenous nitrogen excretion was higher. 7. Water consumption (ml/g food and g/100 g body weight) was greatest for birds on diet B. 8. Although aflatoxin in the diet substantially reduced intake there was no indication that at these reduced levels of intake, nitrogen or energy metabolism were measurably impaired.


Variations in the red blood cell picture during growth of goslings and chickens. 1. Haematological values have been determined in 40 goslings, aged 6 to 42 d, and in 86 chickens, aged 1 to 57 d. 2. The erythrocyte number of goslings remained virtually unchanged with age but there was a decrease in the volume of circulating blood when expressed in terms of body weight. 3. In chickens the number of erythrocytes per unit volume increased with age but the size of the erythrocytes diminished with the result that there was an increase in the red blood cell total surface area per unit volume. 4. The haemoglobin content of chicken blood also rose but the haematocrit value and the mead cell haemoglobin concentration remained constant: mean cell haemoglobin decreased significantly. 5. It seems probable that the blood of goslings has a smaller oxygen carrying capability that that of the chicken and this might be reflected with their slower metabolic rate per body weight unit. There are only a few data available on the changes in haematological values of the domestic fowl after hatching (Lange, 1919; Sandreuter, 1951; Lucas and Denington, 1957; Medway and Kare, 1959) and virtually none for the goose. In this paper various haematological values for both species are presented for the first weeks of post-embryonic life.


[An unusual case of hydatid cyst].

[An unusual case of hydatid cyst]. A hydatid cyst of the spleen developed in a Greek-Canadian woman who had lived on a sheep farm. The cyst extended through the diaphragm to the left lower lobe. Splenectomy and left lower lobectomy and excision of contiguous diaphragm were performed. Histopathologic examination confirmed the presence of hydatid cysts in both spleen and lung. Postoperative course was uneventful. In Canada hydatid disease is rare and its occurrence sporadic. It is commoner among Canadian Indians and immigrants than native Canadians. Treatment is surgical; en bloc excision of tissue eliminates the possibility of anaphylaxis of dissemimination of scolices.


Primary carcinoma of the gallbladder: study of 108 cases. From 1948 through 1970, 108 causes of primary carcinoma of the gallbladder were recorded out of a total of 17 698 cases of cancer exclusive of skin cancer (incidence, 0.6%). This review indicated that the following are the chief features of this condition: Primary gallbladder carcinoma is mainly a disease of women older than 60 years; abdominal pain occurs in most patients and jaundice in more than half, and weight loss is also common; laboratory and radiographic features are nonspecific; the diagnosis is made or strongly suspected in only one-quarter and, moreover, in many patients the disease may not be discovered until pathologic examination is conducted postoperatively. Resection was possible in 41 of the 93 patients who underwent operation but treatment was conservative because it was palliative in 20, and in 20 of the other underwent cholecystectomy the disease was not recognized at operation. Overall, the 5-year survival rate was 6.4%; for those who underwent curative resection it was 33%; and for patients without visible metastases at operation the mean survival was 3 years. Improvement in survival will come from more frequent recognition of the cancer at operation so that an operation so that an operation more adequate than cholecystectomy may be performed; that is, cholecystectomy, wedge resection of liver and resection of regional lymph nodes.


Submucous lipoma of the stomach: a case report. A 54-year-old woman presented with a 4-day history of melena and a 1-day history of hematemesis. Radiographs were suggestive of a malignant gastric polyp. Gastrotomy revealed a polyp projecting from the anterior wall of the stomach. The polyp was exised and the patient has since been well. Although rare, gastric lipomas are important because they may cause hemorrhage, abdominal pain, syspepsia and pyloric obstruction; moreover, they are amenable to surgical treatment.


Acute perforation of the colon.

Acute perforation of the colon. Acute perforation of the colon causes fecal peritonitis, which is associated with high rates of morbidity and mortality. Findings in 78 patients with perforation of the colon showed that the commonest causative condition was diverticulitis (in 42%) and that the commonest site was the sigmoid colon (in 65%). The overall mortality in this series was 49%, most of the deaths being due to peritonitis; the extent of anatomic spread of peritonitis was a major factor. The form of treatment was also a factor in mortality: mortality was lowest in patients treated by diversionary colostomy (only 38%) and highest in those treated by exteriorization of perforation (71%) and in those not treated operatively (71%). With respect to postoperative complications in patients who underwent operation, wound infection and pulmonary abnormalities each occurred in 50%. This review suggests that current methods of management of patients with perforation of the colon are less than satisfactory.


Survival in breast cancer: study of 283 patients. Records of 283 women with breast cancer diagnosed from 1965 through 1973 at l'Hôpital du Saint-Sacrement were studied for survival at 3 and 5 years. These were all patients who had not previously received cancer-directed treatment. Life-table methods based on full intervals only were used to analyze survival. Adjustment for deaths from other causes was provided by computing the expected and relative survival rates. The 5-year relative survival rates (%) were 60.2+/-4.1 for the total group of 283 patients, 87.9+/-4.5 for the 142 with localized disease and 44.9+/-59 for the 118 with regional spread. Of the patients with disease that was either localized or regional, 84% underwent total mastectomy. The age of patients at entry did not differ from that of cases reported to the Quebec Tumour Registry. The significant increase over time in the proportion of patients with localized disease would be expected to reduce the Quebec death rate from breast cancer in future if the better survival of these patients is not simply a function of earlier diagnosis.


Cutaneous gangrene: a rare complication of coumarin therapy. Sodium warfarin was administered to a 59-year-old woman with congestive cardiac failure and deep vein thrombosis. After 3 days of therapy the nipple and areola of the left breast became inflamed; the entire breast then became necrotic. Gangrene spread and a simple mastectomy was performed. The patient died from pulmonary embolism 1 day after operation. Histologic examination of the breast revealed thrombi in some of the arteries and veins. The etiology of this condition is obscure, and there is no known way of preventing or effectively treating the condition. Simple mastectomy or more conservative local excision recommended.


Increasing operability and survival with intra-aortic ballon pump assist. Intra-aortic ballon pump assist (IABPA) was used over a 12-month period in the management of 41 patients: 5 patients with complications of myocardial infarction in shock whose circulation was supported by IABPA before operation immediately after angiographic and hemodynamic study (group 1); 14 patients with postcardiotomy low-output state who could not be weaned from cardiopulmonary bypass and required IABPA circulatory support either in the operating room or in the intensive care area (group 2); 19 patients with severe myocardial ischemia and unstable circulation in whom IABPA was instituted either before angiography or before saphenous vein bypass operation (group 3); and 3 patients with severe left ventricular dysfunction and left ventricular hypertrophy due to aortic valve or coronary artery disease, or both, in whom IABPA was used before, during and after cardiopulmonary bypass and a corrective operative procedure (group 4). Survival rates for patients in these groups were 2/5,8/14,18/19 and 2/3 respectively (overall survival, 73%). IABPA may increase the postoperative survival of certain high-risk patients with poor left ventricular function due to valvular disease or coronary artery disease, or both. The survival of patients with severe myocardial ischemia and complicated myocardial infarction is improved by IABPA, early angiography and appropriate surgical correction. Left ventricular ejection fraction and the estimate of subendocardial coronary flow by the ratio of the diastolic pressure time index to the tension time index appear to be significant in identifying patients who may benefit from the use of IABPA.


Circulating catecholamine levels in human and experimental hypertension. The radiometric enzymatic technique of Coyle and Henry (J. Neurochem. 21: 61-67, 1973) was adapted to the measurement of serum catecholamines. This technique requires less time than other enzymatic techniques and is sensitive to quantities as small as 25 pg. In normotensive subjects lying supine for 20 minutes serum catecholamine levels averaged 0.218 ng/ml, with no obvious sex or age difference. Under these standardized conditions, the circulating catecholamine levels for a given individual are highly reproducible on different days over a period of several months. In 22 patients with essential hypertension, circulating levels were significantly higher, with an average of 0.370 ng/ml. More than 50% of the hypertensive patients had values greater than the highest value measured in normotensives. Systolic blood pressure and heart rate were significantly higher in the hypertensive group with elevated levels of circulating catecholamines than in the hypertensive group with normal levels. In one model of experimental hypertension, produced in the rat by administration of deoxycorticosterone acetate (DOCA) and saline for 4-8 weeks, serum catecholamines were significantly elevated. These findings suggest that the sympathetic system may play an important role in maintaining an elevated blood pressure in experimental hypertension and in a significant proportion of patients with essential hypertension.


The effect of procaine amide on components of excitability in long mammalian cardiac Purkinje fibers. The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K+]0 = 4.0 mM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical observation that PA may exert both artiarrhythmic and arrhythmogenic effects. The primary mechanism by which PA modifies excitability would seem to differ considerably from that of the structurally similar local anesthetic agent lidocaine.


Distribution of myocardial blood flow in the exercising dog with restricted coronary artery inflow. The effect of a proximal coronary artery stenosis on transmural myocardial blood flow during exercise was studied in nine dogs with electromagnetic flowmeter probes and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow at rest and during treadmill exercise was estimated with radioactive microspheres 7-10 mum in diameter. Exercise studies were performed during unrestricted coronary artery inflow (control exercise) and during partial inflation of the occluder to a level which did not reduce flow at rest but which limited the increase in flow during exercise to 66 +/- 6% (mild restriction) or 44 +/- 3% (severe restriction) of the value during control exercise. Mean myocardial blood flow at rest was 0.94 +/- 0.06 ml/min per g of myocardium and increased to 2.45 +/- 0.15 ml/min per g during control exercise, with uniform distribution across the wall of the left ventricle. Flow to the subepicardial myocardium was significantly greater during exercise in the presence of a mild restriction than during control exercise, whereas flow to deeper layers of myocardium was progressively decreased below the control level. A similar pattern of redistribution of flow occurred during exercise in the presence of a severe restriction, but flow to all transmural layers was below that during mild restriction, resulting in more marked subendocardial underperfusion. Thus, exercise in the presence of stenosis resulted in transmural redistribution of myocardial blood flow with subendocardial underperfusion in proportion to the degree of restriction of coronary artery inflow.


Inhibition of prostaglandin E2 secretion. Failure to abolish autoregulation in the isolated dog kidney. We studied the role of renal prostaglandins in the regulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in the isolated dog kidney. Indomethacin or meclofenamate, 2 mg/kg of body weight, suppressed renal prostaglandin E2 (PGE2) secretion, measured by radioimmunoassay, to zero within 20 minutes; the effect persisted for the duration of the study. When renal arterial pressure (PRA) was maintained at 104 mm Hg both drugs caused a sharp decrease in sodium excretion and RBF with redistribution of flow from inner to outer cortes we examined autoregulation of GFR and RBF over the pressure ranges of 150-100 and 150-75 mm Hg, respectively, after inhibition of PGE2 secretion and under control conditions. deltaGFR/deltaPRA (ml/min per mm Hg) was 0.020 +/- 0.017 in the indomethacin group, 0.152 +/- 0.055 in the meclofenamate group, and 0.086 +/- 0.017 in the control group. The change in GFR for the indomethacin group was significantly less than that for meclofenamate (P less than 0.01) and control groups (P less than 0.025); the latter two groups were not statistically different from each other (P greater than 0.1). There was no significant difference (P greater than 0.1) between the three groups with respect to deltaRBF/deltaPRA, which measured 0.288 +/- 0.046, 0.370 +/- 0.112, and 0.438 +/- 0.123 ml/min per mm Hg in the indomethacin, meclofenamate and control groups, respectively. Renal was lowered from 150 to 75 mm Hg. The observation that inhibition of prostaglandin synthesis promotes a redistribution of RBF from inner to outer cortex suggests that renal prostaglandins may participate in the regulation of medullary blood flow. However, since autoregulation of GFR and RBF remained intact despite inhibition of prostaglandin secretion, these data argue against a role for renal prostaglandins in regulating whole kidney GFR and RBF.


Ventricular elastic modulus as a function of age in the Syrian golden hamster. Analysis of passive right and left ventricular pressure-volume curves for hearts of 72 Syrian golden hamsters studied in vitro showed increases in ventricular weight, volume, and compliance at mid-age. Both ventricles were filled by syringe pumps at a constant rate. Ventricular compliance (dV/dP) was determined by electronic differentiation of the intraventricular pressures and formation of the ratio (dV/dt)/(dP/dt) as a continuous function of intraventricular pressure between 0 and 30 mm Hg. By relating, with justification, the left ventricle to a thin-walled elastic sphere, ventricular elastic moduli, E, for different ages were compared at constant levels of myocardial wall stress, sigma. The elastic modulus E proved to be a linear function of sigma. The slope of the E-sigma plot yielded a stiffness constant, K, for each age group. Body weight, heart weight, end-diastolic volume, and dV/dP all varied by more than 200% up and then down as a function of age, but K was not a significant function of age. These results suggest that the aging heart does not normally undergo substantial alterations in passive properties that affect the muscle cells and fibers themselves, but rather that the observed changes in compliance are primarily attributable to alterations in ventricular size.


Effect of vagal stimulation on the overflow of norepinephrine into the coronary sinus during cardiac sympathetic nerve stimulation in the dog. In anesthetized dogs with the chest open, supramaximal stimulation of the left cardiac sympathetic nerves at 2 and 4 Hz produced an increase of 40-50% in ventricular contractile force (CF) and of 40-65% in coronary sinus blood flow. At these frequencies of stimulation, norepinephrine (NE) overflow into the coronary sinus was 29.8 +/- 5.1 (SE) and 54.9 +/- 13.2 ng/min, respectively. Concurrent, supramaximal vagal stimulation, at a frequency of 15 Hz, had no significant effect on coronary sinus blood flow, but caused a 25% reduction in CF and a 30% decrease in NE overflow. The changes in CF and NE overflow evoked by vagal stimulation were prevented by atropine. These results are consistent with the hypothesis that there are muscarinic receptors on the postganglionic sympathetic terminals in the walls of the ventricles. Acetylcholine released during vagal stimulation combines with these receptors, causes a reduction in the liberation of NE, and thereby attenuates the positive inotropic response.


Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. The role of a transmembrane calcium influx in hypoxic pulmonary vasoconstriction was studied in isolated, blood-perfused, rat lungs. We reasoned that, if the influx of extracellular calcium mediated the hypoxic mechanism, pressor responses to alveolar hypoxia (2.5% O2) would be susceptible to inhibition by the calcium antagonists verapamil (2 X 10(-5) to 2 X 10(-1) mM) and SKF 525A (2.6 to 260 mM). Susceptibility of hypoxic pressor responses to inhibition by these calcium antagonists was contrasted to that of pressor responses elicited by the humoral vasoconstrictors angiotensin II(1 or 0.5 mug) and prostaglandin F2alpha (10 myg). Since neither saralasin (0.5 muM), a competitive antagonist of angiotensin II, nor meclofenamate (6.8 muM), an inhibitor of prostaglandin synthesis, depressed hypoxic pressor responses, it was concluded that these humoral transmitters were not directly involved in the hypoxic mechanism, and therefore served as independent reference agonists. The order of susceptibility of pulmonary pressor responses to inhibition by verapamil was hypoxia greater than angiotensin II greater than prostaglandin F2alpha. SKF 525A also reduced pressor responses to hypoxia more readily than those to angiotensin II. The greater inhibition of hypoxic pulmonary vasoconstriction by both calcium antagonists suggested that the hypoxic mechanism was critically dependent on the transmembrane influx of extracellular calcium. Mediation of the hypoxic response by this type of excitation-contraction coupling is consistent with the idea that hypoxia has a direct depolarizing effect on the vascular smooth muscle. It also provides a unifying explanation for inhibition of the hypoxic mechanism by various agents that have depressant or stabilizing actions on membranes in addition to other pharmacological effects.


Report of the Inter-Society Commission for Heart Disease Resources. Optimal resources for examination of the chest and cardiovascular system. A hospital planning and resource guideline. Radiologic facilities for conventional x-ray examination of the heart and lungs. Catheterization-angiographic Laboratories. Radiologic resources for cardiovascular surgical operating rooms and intensive care units. This is an updated and expanded planning and oprimal resource guideline for diagnostic examinations of the cardiovascular system. Catheterization-angiographic laboratories are described and detailed specifications given for radiologic and physiologic equipment. Case loads for maintaining safe and effective performance are recommended and complication rates discussed. An optimal location for the laboratory is defined and the status of affiliated laboratories reviewed. Professional staff qualifications, relationships and requirements are enumerated and recommendations are made for organization and administration of the services. There is a protocol for electrical safety and radiation protection and a data base for assessing case loads in hospitals within a community or region. This statement also defines optimal facility and equipment criteria for conventional chest x-rays and radiologic equipment requirements for cardiovascular surgical operating rooms and intensive care units.


Sound pressure correlates of the Austin Flint murmur. An intracardiac sound study. Mitral valve motion and pressure correlates of the Austin Flint murmur (AFM) were investigated in nine patients with aortic regurgitation using high fidelity catheter tip micromanometers and the mitral valve echocardiogram (MVE). External phonocardiography demonstrated a mid-diastolic murmur (MDM) in eight subjects and a presystolic murmur (PSM) in five. Maximum intensity of both AFM components was found in the left ventricular (LV) inflow tract; the murmur was not recordable in the left atrium (LA). In two patients, an apparent AFM was recorded in the intracardiac phonocardiogram when absent externally. Only one subject had a significant late diastolic "reversed" or LV to LA gradient; in this patient, presystolic mitral regurgitation was shown angiographically but no PSM was present and MVE revealed absence of atriogenic mitral valve re-opening. In two subjects, a PSM disappeared from the external phono when a "reversed" gradient occurred during the diastolic pause following a ventricular premature systole; this LV to LA gradient was associated with diastolic mitral regurgitation recordable in the left atrial phono. In two patients, LV inflow phono showed the MDM to begin 80-120 msec after the aortic second sound and during the D to E phase of the MVE. The rate of early diastolic mitral valve closure in patients (152 +/- 24 mm/sec) was not significantly different from 13 normals (232 +/- 10 mm/sec). With regard to the genesis of the AFM, the present study concludes: 1) diastolic mitral regurgitation plays no role, and 2) antegrade mitral valve flow is required but simultaneous retrograde aortic flow may also be necessary.


Electrocardiographic manifestations of concealed junctional ectopic impulses. Thirteen episodes of concealed junctional ectopic impulses (JEI) in ten patients are described. In nine patients the JEI manifested as isolated automatic impulses and in one as a parasystolic junctional tachycardia. In addition to the previously described unexpected prolongation of the P-R, Type I and Type II A-V block, the following phenomena were recorded: 1) marked, greater than 400 msec, and persistent prolongation of the P-R interval, 2) striking changes in the duration of the P-R with an occasional sequence of R-P and P-r intervals simulating "supernormal" A-V conduction, 3) unexpected variation of the junctional escape interval explained by junctional parasystole with entrance block, 4) postponed compensatory pause, 5) concealed junctional discharge with reciprocation.


Vectorcardiographic criteria for the diagnosis of anterior myocardial infarction. Frank lead vectorcardiograms (VCG) from four carefully selected patient subgroups (226 patients) were analyzed to develop optimal criteria for the diagnosis of anterior myocardial infarction. Specificity was evaluated using 100 healthy volunteers under age 30 and 80 patients with normal left ventriculogram and normal coronary arteriograms. Sensitivity was determined using 25 patients with evolutionary ST-T wave changes (V1-2), and LDH and CPK isoenzyme evidence of acute myocardial infarction; and 21 patients with anterior wall akinesia or dyskinesia and greater than 70% occlusion of the left anterior descending coronary artery. Patients with VCG evidence of bundle branch block, left or right ventricular hypertrophy were excluded. The criterion for the diagnosis of anterior myocardial infarction which was found to give the highest sensitivity with greater than or equal to 95% specificity was: initial anterior QRS forces must not exceed 0.1 mV in maximal anterior amplitude and also must not exceed 24 msec in duration. The performance of this proposed criterion was then tested using four similarly defined patient subgroups consisting of a total of 222 patients. The incidence of false positive diagnosis in these test subgroups was less than 1% with a sensitivity of greater than 95%. The overall performance of the proposed criterion was found to be significantly superior to both the widely accepted VCG and ECG criteria for anterior myocardial infarction. Thus, this quantitative criterion using both time and duration of initial anterior forces is both a highly specific and a sensitive indicator of anterior myocardial infarction.


Statistical analysis of pacemaker follow-up data. Rate stability and reliability. In a rate-stable pacemaker, pacemaker rate reflects battery voltage level and should remain constant or be slightly depleted with time in a linear fashion until failure occurs. Linear regression techniques are therefore particularly suited to the analysis of pacemaker rate data. Data on model 8114/8114A Starr-Edwards pacemakers followed at the University of Oregon Health Sciences Center were studied. For a given pacemaker both the slope of the regression line and the standard deviation about the regression line are proportional to the original rate. Natural indices of rate depletion and rate stability for each pacemaker can therefore be calculated by dividing the slope and the standard deviation, respectively, by the inpercept of the corresponding regression line. This model pacemaker has a small average standard deviation so that significant variations from the line of regression, indicating impending pulse generator failure, can be detected in spite of random fluctuations. Emergency and prophylactic replacements can therefore be kept to a minimum so that pulse generator lifetime is maximized. Success in extending pulse generator longevity can be measured by actuarial techniques, which show this pacemaker to have a median battery depletion time of 38 months and a median replacement time of 35 months.


Alterations in ventricular contraction pattern in the Wolff-Parkinson-White syndrome. Detection by echocardiography. The effects of abnormal ventricular activation upon the contractile pattern of the ventricles in patients with the Wolff-Parkinson-White syndrome (WPW) remain uncertain. Therefore we compared the motion of the anterior right ventricular wall (RV), the interventricular septum (IVS), and left ventricular posterior wall (LVPW) on echogram in nine patients with WPW and one patient with a coronary sinus pacemaker (CSP) to 20 normal subjects. Normal subjects manifested posterior RV motion which began and reached maximal excursion at 175 and 366 msec (group mean), respectively, after the onset of the QRS complex; posterior movement of the IVS which started and peaked at 90 and 30 msec, respectively; and anterior contraction of the LVPW which began and peaked at 159 and 406 msec, respectively. Five of seven patients with Type A WPW demonstrated a localized area of premature contraction of the LVPW occuring during the initial 100 msec interval following the onset of the QRS complex which was accompanied by paradoxic anterior motion of the IVS. Thereby in Type A patients initial and maximal posterior motion of the IVS occurred later, 230 (P less than 0.001) and 400 (P less than 0.05) msec, and anterior motion of the LVPW occurred earlier, 75 (P less than 0.001) and 367 (P less than 0.05) msec as compared to normal. The amplitude and duration of early contraction could be related to the prominence of the delta wave during atrial pacing. Similar premature contraction was also observed in the patient with CSP during paced beats. One Type B WPW patient exhibited abnormal IVS motion while the additional patient manifested premature LVPW contraction similat to that seen in Type A patients. The contractile pattern of the right ventricular anterior wall was recorded in five of seven Type A Wolff-Parkinson-White patients and manifested prolongation of the interval from the onset of the QRS complex to the initial posterior movement (group mean 234 msec, P less than 0.05) as compared to normal. Thus echocardiography can be used to confirm the diagnosis and to improve understanding of the pathophysiology of the Wolff-Parkinson-White syndrome.


Cardiac imaging using a phased array ultrasound system. I. System design. A new two-dimensional, real-time, high resolution ultrasound imaging system is described. This system uses a linear array of ultrasound transducers to generate tomographic images of the heart in a circular sector format. Phased array techniques allow rapid steering of the ultrasound beam so that images are produced at the rate of 20 per second, or more, while maintaining a resolution of 2-4 mm throughout the field of view.


Cardiac imaging using a phased array ultrasound system. II. Clinical technique and application. A new two-dimensional ultrasound imaging system capable of producing high resolution tomographic images of the heart in real time has been developed. This system relies on phased array principles to rapidly steer the ultrasound beam through the structures under investigation. A hand-held linear array of 16 ultrasound transducers with overall dimensions of 14 mm at the site of contanct may be readily manipulated to image various cardiac structures. The resulting images are displayed in a circular sector format, 60 degrees in azimuth and typically 15 cm in range. At his maximum range, image frames consisting of 256 lines are generated at the rate of 20 frames/second. High azimuthal resolution throughout the field of view is assured by a focused transmit beam and by sweeping the focus of the receiver is synchrony with the range of returning echoes. Azimuthal resolution varies from 2 to 5 mm throughout the field of view while range resolution is 1.5 mm. This imaging system has proven particularly useful for the delineation of left ventricular spatial geometry by the identification of endocardium, myocardium, papillary muscles and interventricular septum. High quality images of anterior and posterior mitral leaflets, aortic root and aortic leaflets as well as left atrium and other cardiac structures have been obtained.


Echocardiographic determination of left atrial volumes in children with congenital heart disease. The feasibility of determining left atrial volumes (LAV) from LA echo dimensions was assessed in 36 children (group I) with normal cineangiographically determined LAV and 16 children (group II) with LAV overload. Conventional LA echo dimensions, obtained within 24 hours of cardiac catheterization, were compared to the angiographic LA anterior-posterior minor axes (LAmA) and LAV. There was excellent correlation betweeh the LA echo dimensions and the LAmA. In all patients, the LA echo less than LAmA, the differences being more pronounced in group II. Good correlations were found between the LAV and the LA echo, and were expressed by the equations LAV = 7.5 LA echo1.8 (r = .85) and LAV = 8.1 LA echo2.1 (r = .86) for groups I and II, respectively. Changes in LA configuration with volume overload were shown to cause a disproportionate increase in LAmA compared to the other LA dimensions and the LA echo dimension, thus necessitating the separate regression equations. Echo LA to aortic ratios were 0.86 +/- 0.11 and 1.21 +/- 0.23 (mean +/- SD) for groups I and II, respectively. This method of estimating LAV can be useful in the management of left-to-right intracardiac shunts and mitral regurgitation in infants and children.


Localization of aortic valve vegetations by echocardiography. Nine patients with anatomically documented vegetations on one or more cusps of the aortic valve had echocardiograms in which abnormal echoes were associated with the aortic leaflet echoes. The motion of the abnormal echoes during systole correlated well with the anatomic location of vegetations: a vegetation on the right coronary cusp moved anteriorly with systole while a vegetation on the noncoronary cusp moved posteriorly during systole. Our data, although inconclusive, suggest that echoes from a vegetation on the left coronary cusp maintain a mid-aortic position throughout the cardiac cycle. The echocardiographic appearance of vegetations is not specific, but in the setting of septicemia, dense mobile echoes in the region of the aortic valve are strongly suggestive of vegetation. A normal echocardiographic appearance of the aortic valve does not exclude the possibility that vegetation is present, especially if the growth is less than 5 mm in size.


Influence of acute changes in preload, afterload, contractile state and heart rate on ejection and isovolumic indices of myocardial contractility in man. To determine the sensitivity of several isovolumic and ejection phase indices of myocardial contractility to loading, inotropic stimulation and heart rate in man, 14 patients (pts) were studied during cardiac catheterization with simultaneous recordings of left ventricular (LV) pressures and ultrasound dimensions. Measurements were made of instantaneous and mean circumferential fiber shortening velocity (VCF), maximal (max) rate of LV pressure rise (dP/dt), dPHdt divided by end-diastolic circumference [(dP/dt)/C], (DP/dt)/C divided by aortic valve opening pressure [(dP/dt/CP], PEAK CONTRACTILe element velocity (VCE) using total LV pressure, VCE extrapolated to zero total pressure (Vmax), VCE at a developed pressure of 10 mm Hg (VCEDP10) and dP/dt at a common isovolumic developed pressure of 40 mm Hg [(dP/dt)/DP40]. Resulta are expressed in per cent change of the mean for the group. Acute preload increase (8.6% increase in end-diastolic circumference) with volume expansion at constant heart rate in 7 pts produced insignificant changes in VSF, an 8.3% increase in max dP/dt, no change in (dP/dt)/C, a variable response in (dP/dt)/CP, 18% reduction in peak VCE, 16% reduction in Vmax, 14% increase in VCEDP10, and a 10% increase in (dP/dt)/DP40. An acute increase in afterload produced by angiotensin in 8 pts (44% increase in peak stress) led to a 38% decrease in VCF, a 2.5% increase in max dP/dt, no significant change in (dP/dt)/C, a 26% reduction in (dP/dt)/CP, variable responses in peak VCE and Vmax, an 11% increase in VCEDP10 and minor changes in (dP/dt)/DP40. All of the contractility indices were augmented significantly by isoproterenol and atrial pacing. In a given patient, max, dP/dt appears to be useful in the assessment of acute changes in inotropic state since the magnitude of its response to abrupt changes in preload is small and to afterload insignificant. Normalizing max dP/dt for end-diastolic circumference assures better stability during loading with good sensitivity to inotropic stimulation. VCF may be used whenever changes in afterload are minimal. The isovolumic measurements of VCE (regardless of whether total or developed pressure is used) lack sufficient stability during acute changes in loading conditions to warrant their use in the quantitative assessment of acute changes in inotropic state.


Suppression of ouabain-induced ventricular rhythms with aprindine HCl. A comparison with other antiarrhythmic agents. Three groups of dogs were given ouabain (mean 60 mug/kg) until an accelerated ventricular escape (AVE) and repetitive ventricular response (RVR) followed cessation of pacing. In a group of six control dogs, the AVE and RVR were found to occur at stable escape intervals for periods of at least three hours. A second group of dogs received various antiarrhythmic agents in an attempt to suppress the AVE and RVR. Quinidine, diphenylhydration, lidocaine, procainamide, and propranolol, were successful in only 0 to 33% of trials. Potassium canrenoate, 12 mg/kg was unsuccessful in three dogs. Verapamil, by bolus, suppressed RVR in 41% and AVE in 21% of trials. KCl, infused until AVE and RVR were suppressed, was successful when the mean serum potassium rose from 3.8 mEq/L to 7.2 mEq/L. Aprindine, 2.86 mg/kg, suppressed AVE and RVR in 14 of 14 dogs. In the third group of dogs, verapamil was infused continuously and suppressed RVR and AVE at a mean cumulative dose of 2.93 mg/kg. Calcium chloride reversed aprindine and verapamil-induced suppression of RVR and AVE. This study demonstrates that RVR and AVE resist suppression by available antiarrhythmic agents in clinically-used doses. Only aprindine was 100% successful at doses used in man. The ionic pathogenesis of RVR and AVE is unknown, but some data suggest the slow current may play an important role.


Surgical repair of atrial septal defect in patients over 60 years of age. Long-term results. In order to evaluate results of surgical repair of secundum atrial septal defect (ASD) in patients 60 years of age or older, a review was made of 16 patients who had undergone such operation between January 1964 and December 1974. Before operation eight patients were in functional classification III (New York Heart Association), seven were in class II, and one was in class I. Twelve patients had a left-to-right shunt greater than 3:1. Pulmonary artery systolic pressure was greater than 40 mm Hg in 12 patients and greater than 60 mm Hg in five. Four patients had documented paradoxical emboli and were being treated with Coumadin. Before operation all patients but one were receiving digoxin. Repair was accomplished by direct suture in two patients and Dacron patch graft in 14. No deaths occurred during the postoperative period. Postoperatively, ten patients were in class I, five in class II, and one remained in class III. The hospital stay ranged from eight to 20 days (average 11 days). Two patients died one year and another (at the age of 77) five years after surgery. The remaining 13 patients are alive and well three months to 11 years after surgery. We conclude that repair of secundum ASD in patients over the age of 60 is safe, has low morbidity, and produces considerable clinical improvement.


Pulmonary perfusion abnormalities and ventilation-perfusion imbalance in children after total repair of tetralogy of Fallot. The pulmonary perfusion of 25 children who had total surgical correction of tetralogy of Fallot was evaluated by radionuclide perfusion scans. In addition, 18 had 133Xe ventilation studies. Eighteen of the children previously had palliative systemic-pulmonary shunts; 14 had aortic-pulmonary shunts (Waterston or Potts-Smith) and four had Blalock-Taussig shunts. Seven children had single stage total corrections. An asymmetric perfusion pattern was found in 13 of 18 children who previously had systemic-pulmonary shunts, including 12 of 14 with previous aortic-pulmonary shunts (P less than 0.05). The most common finding was relative hypoperfusion of the lung which had received the palliative shunt (P less than 0.001). The distribution of ventilation remained relatively symmetric, even when perfusion was markedly abnormal, and this resulted in ventilation-perfusion imbalance in several patients. Asymmetric perfusion was significantly less common in patients who had undergone single stage corrections (P less than 0.05). The findings document the frequent occurrence of residual abnormalities of pulmonary perfusion and ventilation-perfusion imbalance in patients who have palliative aortic-pulmonary shunts prior to total repair, and support the position that single stage correction is preferable to aortic-pulmonary shunting in the surgical management of tetralogy of Fallot.


Risk of new myocardial infarction in middle-aged men with manifest coronary heart disease. Men incuring coronary heart disease (CHD) during surveillance of an employed population were studied for risk factors associated with additional myocardial infarctions. The coronary-prone Type A behavior pattern measured by a test score, number of cigarettes smoked daily, and serum cholesterol were significantdiscriminators between the 67 men with recurrent CHD and the 220 with but a single clinical CHD event. Diastolic blood pressure and fasting serum triglycerides were not significant discriminators. Statistical analyses directed to possible sources of bias occasioned by the combined retrospective-prospective study design revealed that these problems are negligible and do not alter the findings observed. Type A score appears relatively unaffected by whether the measure was made before or after the initial CHD event. Multivariable discriminant function equations showed Type A score to be the strongest single predictor of recurrent CHD among the variables available. Number of cigarettes smoked and serum cholesterol accounted for additional variance. Future field trials for the secondary prevention of myocardial infarction would be strengthened by consideration of the possible role of Type A behavior.


Multivariate prediction of coronary heart disease in the Western Collaborative Group Study compared to the findings of the Framingham study. The Western Collaborative Group Study (WCGS) is a prospective epidemiological study of 3,154 initially well men, aged 39059 years at intake in 1960-61, who were employed in ten participating companies in California. Clinical coronary heart disease (CHD) occurred in 257 men during a follow-up period of eight and one-half years. Coronary heart disease risk is predicted using the additive multiple logistic model with the risk factors: age, cholesterol, systolic blood pressure, hematocrit, ECG status, smoking at intake, and relative body weight. The predicted individual CHS risk levels, using the logistic results derived from the WCGS data, are highly correlated with predicted risk levels using a Framington study (FS) equation for these same risk factors with 12-year follow-up. The observed number of CHS events in the WCGS is not significantly different from the expected number of events derived from the FS logistic equation, after correction of length of follow-up. Multiple logistic analysis of the direct association between CHD incidence and behavior pattern gives an approximate relative risk of 1.9 (P = 0.0006) and 2.1 (P = 0.0015) for Type A compared to Type B men aged 39-49 and 50-59 years, respectively. It is estimated that removal of the excess risk associated with Type A behavior would correspond to a 31% (standard error = 6.6%) reduction of coronary heart disease incidence in the Western Collaborative Group Study population.


Acute effects of increase in pulmonary vascular distending pressures on pulmonary blood volume and pulmonary extravascular fluid volume in man. The acute hemodynamic effects of supine leg exercise or atrial pacing were studied in 114 patients undergoing right and either transseptal (87 cases) or retrograde (27 cases) left heart catheterization. Seventy-one patients - 15 with coronary artery disease, 22 with aortic valve disease, and 34 with mitral valve disease - performed exercise on a bicylce ergometer. Forty-three patients, of whom 22 had coronary artery disease, nine aortic valve disease and 12 mitral valve disease, were studied during rapid atrial pacing. Cardiac index (CI), pulmonary artery mean (PAm), and left atrial mean (LAm) pressure, pulmonary blood volume (PBV) and pulmonary extravascular volume (PEV) were measured during the control state and during acute intervention. Both exercise and pacing resulted in significant elevations in PAm (range 37-65%) and LAm (range 36-43%) mean pressures in all patients. Cardiac index rose between 34 and 58% in the exercise groups, but did not change in those who were paced. During intervention both PBV and PEV increased significantly in all but the nine patients with aortic valve disease who were paced. Although volume increased occurred, they did not achieve the 5% significanc- level. For all patients the mean increment in PBV ranged between 37 and 123 ml/m2 over control, while PEV rose between 15 and 35 ml/m2. In each group the increases in PEV and PBV were proporationate, so that the ratio of PEV/PBV DID NOT CHANGE SIGNIFICANTLY BETWEEN THE CONTROL AND INTERVENTION STATES. Thus PEV and PBV increases occurred with elevations in pulmonary vascular pressures whether or not blood flow increased. Our data in patients with normal pulmonary vascular beds (i.e., coronary artery disease and aortic valve disease) strongly support the hypothesis that recruitment of vascular channels accounts for the acute changes in PEV and PBV and that the changes in PEV over a brief period of time do not necessarily reflect a "true" increase in extravascular lung water. Although pressures are higher in the lungs of patients with mitral valve disease, the data also suggest that recruitment is likely to be the mechanism for the observed proportionate increase in pulmonary extravascular volume and pulmonary blood volume.


The acute hemodynamic effects of ethacrynic acid and furosemide in patients with chronic postcapillary pulmonary hypertension. The acute hemodynamic effects of either ethacrynic acid or furosemide were studied in 27 patients who underwent diagnostic right and transseptal left heart catheterization. Twenth-three patients had postcapillary pulmonary hypertension secondary to isolated or predominant mitral stenosis. Of these, 21 patients were in New York Heart Association functional class III, and one each in class II and IV. In the remaining four patients pulmonary artery pressures were normal. Two patients had aortic stenosis and one each coronary artery disease and nonobstructive cardiomyopathy. All four patients were in class II. Cardiac index, pressures, and pulmonary blood volume (PBV) were measured in the control state and 20, 40, and 60 min after diuretic administration. Pulmonary extravascular fluid volume (PEV) was measured in the control state and at 60 min post drug infusion. A similar hemodynamic response was observed for each drug. Significant reductions in pulmonary artery and left atrial mean pressures, cardiac index, and plasma volume occurred over the one hour observation period and were accompanied by a significant duiresis. However, despite recutions in central pressures and blood flow, PBV, ev, and PEV/PBV remained unchanged, as did systemic arterial pressure. Since 23 of the subjects had postcapillary pulmonary hypertension it is postulated that the failure of PBV to decrease significantly despite significant decreases in pulmonary artery mean pressure is related to altered pressure volume characteristics in the pulmonary vascular bed in which the lung is operating on a steep portion of its pressure volume curve. The failure of the PEV to decrease supports the concept that the pulmonary extravascular space is relatively resistant to early decreases in pulmonary capillary pressure induced acutely. The failure of the pulmonary extravascular fluid volume to decrease despite a fall in plasma volume and pressures corresponds to the well recognized delay in resolution of radiologic evidence of pulmonary congestion.


De Subitaneis mortibus. XVI. Intractable tachycardia in infancy. Intractable tachycardia in a boy proved fatal at the age of one year. A cousin still living has the same problem. Special electrocardiographic studies in the boy demonstrated a consistent abnormality which included complete atrioventricular dissociation with a normal atrial rate but a ventricular rate usually about 240 beats/minute; a His bundle comples preceded each QRS and all QRS complexes were narrow and uniform in configuration without a delta wave. At postmortem examination there were changes due to congestive failure and the heart was enlarged but otherwise normal except for the His bundle. In its midportion the His bundle was split into several thin and irregular longitudinally oriented strands, within which there were many areas of focal degeneration. There was no myocarditis and no focal degeneration elsewhere in the heart. Although the etiology of this process is uncertain, some possibilities are discussed.


Echocardiography diagnosis of ruptured aneurysm of sinus of Valsalva. Report of two cases. Echocardiographic features of two cases of ruptured congenital aneurysm of Valsalva sinus with (case1) and without (case 2) a supracristal ventricular defect were studied before and after surgery by standard echocardiography. M-mode scan and two-dimensional echocardiography. Discontinuity was observed in the echo from the aneurysm wall of the Valsalva sinus in case 1 with ruptured aneurysm, but was not observed in a similar case of unruptured aneurysm. Herniation of the right coronary cusp of the aortic valve into the right ventricular outflow tract was also observed in case 1. After surgical correction the echo from the aneurysm wall and from the herniated right coronary cusp of the aortic valve disappeared. Discontinuity in the echo from the anterior aortic wall and the interventricular septum also disappeared. In case 2, discontinuity in the echo from the anterior aortic wall, and tricuspid flutter with an abnormally low early diastolic peak were observed. These abnormalities disappeared after surgery. The ability of echocardiography to detect ruptured Valsalva aneurysm is discussed.


Right ventricular growth in a case of pulmonic stenosis with intact ventricular septum and hypoplastic right ventricle. Adequate growth of the hypoplastic right ventricle in a patient with severe pulmonary stenosis with an intact ventricular septum was documented after pulmonary valvotomy in infancy. It is postulated that the growth of the ventricular chamber is largely the result of pulmonary regurgitation resulting from successful pulmonary valvotomy. Based on this and the observations of others on the growth of the hypoplastic right ventricle in pulmonary atresia (with intact septum) cases, an organized approach to eventual total surgical correction is recommended.


Convenient method for checking detector response of spectrophotometers at three wavelengths. We describe the use of a water-soluble dye, available as green food coloring, to check the linearity of detector response of spectrometers and spectrophotometers at three wavelengths. The dye has absorbance maxima at 257 nm, 410 nm, and 630 nm. The advantages of using this solution for this important instrument function check are: one solution with absorption maxima in the opposite ends of the visible spectrum as well as in the ultraviolet region; safe; inexpensive; readily available; easy to use; absorbance not dependent on pH from 2.5 to 10.0 or on temperature from 4 to 56 degrees C.


A computerized system for storage and statistical analysis of clinical amino acid data. We have developed a system of computer programs to expedite analyses of amino acid data obtained in a clinical environment. The system contains a program for building and maintaining libraries of chromatogram data, and a program for retrieval of data on the basis of any of its associated biographical characteristics. Several programs have been written that work with data drawn from the libraries. They provide for easy presentation, manipulation, or statistical analysis of the data. Included are comparison of population means and variances and intra-population correlation analyses. A minicomputer that has 12K of core storage is adequate for use with the system.


Simultaneous determination of five sex hormones in human serum by radioimmunoassay after chromatography on Lipidex-5000. We describe a method for determination of pregnenolone, progesterone, 17alpha-hydroxyprogesterone, testosterone, and 5alpha-dihydrotestosterone in 1-2 ml of serum from male or female. Using microcolumns of Lipidex-5000 (hydroxyalkoxypropyl Sephadex, 0.5 g) and light petroleum/chloroform (97/3) as the solvent during chromatography, we resolved these five steroids into four fractions, with pregnenolone and 5alpha-dihydrotestosterone eluting together. By use of selected antibodies, the latter two steroids were also determined specifically. Use of microcolumns allowed minimization of solvent volumes and sample transfers. Consequently, blank values for all the five steroids were negligible. Lowest measureable concentrations (in ng/liter) were: pregnenolone 100, progesterone 25, 17alpha-hydroxyprogesterone 50, testosterone 25, and 5alpha-dihydrotestosterone 25. Intra-assay and inter-assay coefficients of variation ranged from 5 to 9% and 10 to 15%, respectively, for the five steroids. Serum concentrations of these steroids are given for women in the follicular and luteal phases of the menstrual cycle and for women on oral contraceptives of the combination type, as well as for normal men.


Effect of time and temperature on blood P50 and 2,3-diphosphoglycerate measurements. The oxygen affinity of hemoglobin is affected by various factors, including blood pH and erythrocyte 2,3-diphosphoglycerate. The latter and blood P50 values are unchanged when aliquots of blood from normal individuals are permitted to stand at room temperature for as long as 7 h. Our data also show that equilibration in a 37 degrees C tonometer for times ranging from 0.5 to 1.5 h causes no detectable alterations in P50 values.


Organic acids in urine from human newborns. The pattern of organic acids in urine from 15 normal newborn infants was investigated by gas chromatography/mass spectrometry of trimethylsilylated derivatives. The urine contains large amounts of succinic, fumaric, 2-ketoglutaric, and 3-hydroxy-3-methylglutaric acids, which are all fairly small components of urine from adults. On the other hand, hippuric acid is a small component in the urine from newborn infants, but a large component later in life. An additional number of differences can be seen. Some previously unrecognized aliphatic dicarboxylic acids were also observed, which are present to some extent in urine from adults.


Thermodynamic aspects of some radioassays. In a number of radioimmunoassays and radiotransin assays, effective equilibrium constants have been measured at different temperatures in order to define the relative contribution of changes of entropy and enthalpy to the change in free binding energy. In systems with a large enthalpy component, the lowest possible incubation temperature maximizes sensitivity, and control of temperature throughout the assay is important. Conversely, when enthalpy change is small, a high temperature allows rapid attainment of equilibrium without loss of sensitivity. At a theoretical level, the thermodynamic characteristics of binding may allow some insight into the nature of the binding process.


Evaluation of a reagent-strip method for glucose in whole blood, as compared with a hexokinase method. The hexokinase method (I) for glucose in biological fluids, proposed by the FDA as a potential national standard method, is compared with the Eyetone/Dextrostix/Control method (II) for measurement of glucose in whole blood. I used a new, two-step calibration procedure based on a 1.30 g/liter standard for the II system. The correlation coefficient for results by the two methods was 0.99 for 142 assays in duplicate. Recovery values were near 100% (I, range 100.0 to 106.2%; II, range 100.8 to 105.1%), and the coefficients of variation were respectively +/- 4.1% and +/- 4.5%. Considering the close correlation between the two methods, together with the simplicity, speed, and convenience of II, I conclude that it has great clinical utility, particularly in emergency situations. The precision and accuracy of II depends greatly on proper calibration and control procedures and on adequate training of the operator.


Comparison of four kits for enzymatic determination of ethanol in blood. We compared results obtained with four commercially available kits for the enzymatic (alcohol dehydrogenase) determination of ethanol in blood, in a practical test in which standardized blood samples were used. Each of the kits yielded reliable results with acceptable reproducibility. A tendency to record slightly lower values in the intermediate and high alcohol range is most likely related to incomplete (inhomogeneous) deproteinization. Blood samples containing ethanol plus various concentrations of methanol and isopropanol were analyzed to evaluate the specificity of assays. Highly toxic blood concentrations of methanol (1.5 g/liter) increased apparent ethanol values only insignificantly, but even small concentrations of isopropanol (0.5 g/liter) interfered in all kits to different but substantial extents. The specific technical characteristics of the kits, their advantages and disadvantages are discussed. Costs are compared for analysis of small numbers of samples.


Atypical increase in serum creatine kinase activity in hospital patients. We use an ion-exchange column-chromatographic technique for separating creatine kinase isoenzymes in serum, and occasionally observe what appears to be sustained increase in the MB fraction. Most patients whose sera show such behavior have myocardial disease, but not necessarily a recent myocardial infarction. Electrophoretic analysis of a small sampling of such sera revealed that the apparent MB migrates atypically, appearing distinctly between isoezymes MB and MM. In another electrophoretic system, the peak might easily be mistaken for MM. This unusual isoenzyme does not appear to be "macro" creatine kinase. In laboratories that use the ion-exchange technique, the possibility of a falsely positive MB value should be considered in subjects who show persistent increases together with normal or nearly normal values for total creatine kinase activity. A suitable electrophoretic method that clearly demonstrates this unusual isoenzyme should be used in such cases, for confirmation.


Undernutrition and tetracycline half life. The plasma half life of tetracycline hydrochloride was determined in groups of well-nourished and undernourished subjects employing two dosage schedules and two routes of administration, namely oral and parenteral. Protein binding of the drug was estimated and relative volume distribution was calculated. The results indicated that in undernourished subjects, the half life of tetracycline hydrochloride, protein binding and relative volume distribution were all significantly low as compared to well-nourished subjects. The elimination rate was considerably higher in the undernourished groups, which accounted for the shorter half life. These data suggest that to maintain adequate serum concentrations of the drug in undernourished subjects, tetracycline needs to be given at more frequent intervals.


Application of an exponential curve equation for calculation of serum creatine kinase activity. A four-point scale for determination of serum creatine kinase activity is suggested and the application of an exponential curve equation is proposed for cases with this enzyme activity exceeding 177 I.U. The introduction of this modification permits the activity of creatine kinase to be determined in high-activity serum without diluting the serum before determination since this is a source of error in certain muscular diseases.


[Evolution of serum copper and zinc levels in burn patients (author's transl)]. The study of copper and zinc in 35 patients, over periods of up to 21 days following thermal injury, is marked by an important and early fall in serum copper and zinc levels. The maximum intensity of the biological disturbance appears about two days after the injury. Reversion to near normal values coincides with recovery from the large part of the lesions. The comparison of the evolution of serum levels does not permit any definite relationship to be established between copper and zinc metabolism.


Xanthelasma and hyperlipoproteinaemia.

Xanthelasma and hyperlipoproteinaemia. Ninety-eight females exhibiting xanthelasma have been examined for hyperlipoproteinaemia. Fifty-four (55.1%) have shown signs of this defect and forty-two (77.8%) of these have shown the Type II abnormality. Low cholesterol diets have shown that the hyperlipidaemia can be reversed within nine months of the patients starting the diet, and in the majority of cases, the serum lipid concentration can be kept within normal limits by diet alone. The application of low cholesterol diets to patients with xanthelasma does not cause any regression of the plaques.


4-hydroxycyclohexane-1-carboxylic acid: an unusual compound isolated from the urine of children with suspected disorders of metabolism. 1. An unknown compound has been isolated in the acidic fraction of urine samples taken from several children suspected of having metabolic disorders. 2. This unknown has been characterized using a gas chromatograph/mass spectrometer/computer system. Both the high and low resolution mass spectra have been determined and a structure proposed. 3. Authentic samples were synthesized and compared to the unknown and a final proof of structure is presented. The compound, 4-hydroxycyclohexane-1-carboxylic acid, is suspected to come from a dietary source but the actual genesis will be determined in future work.


Ornithine carbamoyl transferase activity. Use of a bovine liver extract in quality control. To obtain a pure ornithine carbamoyltransferase for quality control in clinical chemistry, the authors compared human plasma and bovine liver ornithine carbamoyltransferase. The data show that the KM of both enzymes are similar (respectively 1.03 and 1.33 mmol when ornithine is used as substrate; 1.02 and 1.06 mmol with carbamyl phosphate). The following properties are shown to be equivalent: linearity of the enzymatic reaction, inhibition by higher substrate concentrations, and temperature denaturation. The similarities between the two enzymes indicate that bovine liver ornithine carbamoyltransferase can be used in clinical chemistry quality control.


Glutaric aciduria type II: report on a previously undescribed metabolic disorder. A report is given on a hitherto undescribed metabolic disorder, characterized clinically by fatal neonatal acidosis, hypoglycemia and a strong 'sweaty-feet' odour. Biochemical features were a massive urinary excretion of glutaric and lactic acids. Isobutyric, isovaleric and alpha-methylbutyric acids were also greatly increased, followed by adipic, ethylmalonic, alpha-hydroxybutyric, n-butyric, beta-hydroxybutyric, sebacic, suberic, propionic, alpha-hydroxyisovaleric and hexanoic acids. The serum level of glutaric acid was highly elevated. In the serum there were also abnormal levels of lactic, alpha-hydroxybutyric, adipic, suberic, p-hydroxyphenyllactic, myristic, hexadecenoic, palmitic, oleic and stearic acids. Plasma lysine and valine were also elevated. Degradation of 14C-labelled glutaric acid and 14C-labelled branched-chain amino acids, alpha-ketoisovaleric and alpha-ketoisocaproic acids in intact fibroblasts was decreased, whereas that of pyruvic acid was normal. The defect was tentatively supposed to be localized at the level of the metabolism of a range of acyl-CoA compounds. The name glutaric aciduria 'type II' is proposed for the patient's disease.


Assay of an activator for lipoprotein lipase. A method is described which enables the ability of human serum to activate guinea pig lipoprotein lipase to be measured in terms of an arbitrary standard. Evidence is offered which strongly suggests that the substance measured is also the activator of human lipoprotein lipase and observations on the relative levels of activator in human sera are given.


Clinical pharmacology and pharmacokinetics of clonidine. A 300-mug oral dose of clonidine was administered to 5 normal volunteers and measurements of plasma concentration and effects upon blood pressure, heart rate, circulatory reflexes, sedation, and dry mouth were made for the following 8 hr. The plasma concentration rose to a peak of 1.02 +/- 0.52 ng/ml (SD) at 90 min and fell with a mean half-life of 12.7 hr. Blood pressure of the group fell from 111.0/77.0 to 87.2/60.4 after 3 hr and was 95.2/62.2 mm Hg at 8 hr. Heart rate in recumbency was slowed. Marked sedation and a fall in salivary flow followed the same time-course as the plasma concentration. The cold pressor response was reduced but the Valsalva overshoot was little affected.


Disposition kinetics of quinidine.

Disposition kinetics of quinidine. The disposition kinetics of quinidine in 12 hospitalized patients in whom oral quinidine therapy was to be initiated is described. Quinidine in doses of 2.6 to 5.2 mg/kg base were infused intravenously over 22 min. Plasma samples were collected during the postinfusion for 24 hr and analyzed by a specific and sensitive assay procedure. In the 12 hr after administration, postinfusion plasma quinidine concentration decay was described by a biexponential equation. Attempts to include the 24-hr data point in the fitting procedures resulted in poorer agreements between the theoretical and experimental curves. A 2-compartment open model is proposed to describe the disposition of quinidine. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.91 +/- 0.11 L/kg and 3.03 +/- 0.25 L/kg, respectively, and indicate that quinidine distribution is predominantly extravascular. Quinidine distribution was quite rapid (t1/2alpha = 7.19 +/- 0.70 min), while the apparent elimination half-life (t1/2beta) was considerably longer, 6.333 +/- 0.47 hr. Total body plasma clearance ranged from 1.49 to 7.15 ml/min/kg (mean 4.70) and is primarily associated with nonrenal mechanisms of drug elimination. Urine specimens collected for 48 hr indicated that 17% of the dose is excreted intact and that urinary excretion was essentially complete within 24 hr. Renal clearance (Clr) was 0.80 +/- 0.18 ml/min/kg. The study demonstrated that there is substantial interpatient variability with respect to quinidine disposition.


Pharmacokinetics of nalidixinic acid and oxolinic acid in healthy women. The pharmacokinetics of oral nalidixic acid (NA, 1 gm 4 times a day) and oxolinic acid (OA, 750 mg 2 times a day) administered for 7 days were studied in the same 10 healthy women on the first, third, and seventh days of the treatment. The peak concentrations of NA + OH-NA (hydroxynalidixinic acid) in serum at 2 to 3 hr were 34 mug/ml (total) and 23 mug/ml (unconjugated) on the first day and nearly two times higher on the third and seventh days; 82% to 85% of these amounts were NA. The protein-free fraction of NA + OH-NA was 8.8% to 18.3%. The total concentration of NA + OH-NA in urine was 1,220 to 2,700 mug/ml, the unconjugated concentration, 250 to 350 mug/ml, and the chemotherapeutically active concentration, 55 to 75 mug/ml. In steady state the 24-hr recovery of the total drug was 79% of the daily dose. The excretion rate in urine was 591 to 853 mg/6 hr. The OA concentration in serum was very low on the first day of the treatment, but increased to 4- to 5-fold on the third and seventh days: 6.2 to 6.4 mug/ml (total) and 3.3 to 3.6 mug/ml (unconjugated). The protein-free OA represented 19% to 23% of the total amount. The modest initial serum concentrations of OA were confirmed by the low urine concentrations on the first day. In steady state the OA concentration in urine was 570 mug/ml (total) and 35 mug/ml (unconjugated), and the 24-hr recovery, 49% and 3%, respectively. The microbiologic assay gave somewhat higher concentrations of the active drug than did the chemical assay. When taken with food, the excretion of OA in urine was retarded by 6 hr but the 48-hr recovery was not decreased.


Studies in porphyria. V. Drug oxidation rates in hereditary hepatic porphyria. The mean plasma half-life (T1/2) of antipyrine was prolonged (21.69 +/- 1.92 hr) in a group of 10 patients with hereditary hepatic porphyria, 8 of whom had acute intermittent porphyria (AIP) confirmed by decreased erythrocyte uroporphyrinogen-1-synthetase (URO-S) activities and 2 of whom had mixed hepatic porphyria, in comparison to the mean of 20 normal control subjects (12.65 +/- 0.86 hr, p less than 0.01). Antipyrine T1/2 was especially prolonged in patients with a history of more severe symptoms, but there was no correlation with the degree of elevation in urinary excretion of the porphyrin precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). In 7 completely latent carriers of the AIP gene defect who had normal urinary ALA and PBG levels, the elimination rates of antipyrine from plasma were entirely normal. Phenylbutazone T1/2s were normal in 10 porphyric patients tested. These results demonstrate that the cytochrome P-450-dependent enzyme system for oxidizing antipyrine, but not that for phenylbutazone, is impaired in some AIP individuals in whom the gene defect for the disorder is clinically expressed and that this impairment may be related to the severity of the disease. The partial decrease in URO-S activity characteristic of AIP does not result in a profound or generalized decrease in hepatic cytochrome P-450 function, however, even when there is sufficient derangement in the hepatic heme biosynthetic pathway to lead to excessive excretion of chemical intermediates in the pathway.


Erythromycin and clindamycin absorption and elimination in pregnant women. Thirty-nine pregnant women admitted for therapeutic abortions during early or mid pregnancy were given erythromycin estolate, erythromycin base, or clindamycin hydrochloride orally in single or multiple doses. Peak serum levels of clindamycin were 3.4 to 9.0 mug/ml following a single dose of 450 mg, whereas peak serum levels of erythromycin were 0.29 to 7.2 mug/ml following 500 mg in a single dose. The individual variability of serum concentrations of erythromycin was greater than that reported in normal men and nonpregnant women, whereas the serum levels of clindamycin were rather uniform, and similar to what has been reported in nonpregnant individuals. Following multiple doses of each antibiotic, high serum levels were obtained in virtually all subjects, and urine levels were also higher. Following single doses the mean urinary recovery was 2% for erythromycin and 16.8% for clindamycin.


Short-term casework: a rational-emotive approach. Time-limited casework based on the concepts of the rational-emotive school of psychotherapy can prove an effective intervention strategy by altering a client's irrational perception of his situation.


Neuropsychological testing following head injuries: prosopagnosia without visual field defect. Assessment of residual cerebral dysfunction in the post-traumatic patient poses considerable problems particularly when the neurological examination yields minimal or equivocal findings. The clinical picture is frequently complicated by emotional disturbance not easily differentiated from "post-traumatic neurosis." This report describes such a patient whose disorder was elicidated by neuropsychological testing. Numerous studies have established the validity of neuropsychological tests particularly when they are interpreted by psychologists specifically trained in their use. These procedures are also useful in differentiating patients with neurologic complaints of a nonorganic etiology from patients with similar complaints secondary to confirmed brain lesions. Although the findings reported here pertain to a patient exhibiting a rare neurologic consequence of closed head injury, the methods employed are applicable to subtle behavioral manifestations of diverse etiologies. Neurophyshological findings in a patient unable to recognize faces of familiar persons (prosopagnosia) disclosed a severe impairment of visual perception despite intact visual acuity and fields. The prosopagnosia was also associated with a pervasive memory deficit without dementia. Our results challenge current concepts of prosopagnosia and support the need for neuropsychological evaluation of post-traumatic patients.


The Vietnam veteran: the task is re-integration. The Vietnam veteran is re-integrating into the Community. Some veterans are experiencing special difficulties, and tend to cluster inot groups which are cemented by common needs, common symptoms or ideologies. At Brentwood V.A.H., the Vietnam veterans show serious psychiatric illness. The contributing factors are often complex, and include personality and social maladjustments, traumatic experiences and an impoverished family and social structure. The full range of psychiatric therapies may be appropriate, depending upon the individual problem constellation. In addition to empathic professional treatment, there is a need for community support and for a continuing open-minded clinical inquiry about both the defined and as yet unmet needs of the Vietnam veteran. Some veterans are in need of help but reject V.A. facilities. Answers to this problem are not easy. As the adolescent veteran ages, some maturation may spark a greater flexibility in attitudes and viewpoints. The V.A. as an institution is obligated to exercise its own strugles to attain a broader community base for its services. Other non-V.A. agencies have this responsibility as well. Veterans are also citizens in a wider sense. Everywhere, helping professionals have many tasks. One of these is to recognize the dangers of blurring the boundary between advocacy and therapy. The failure to attend to this confusion risks sacrificing the patient in advancing the cause.


Lithium carbonate in juvenile manic-depressive illness. A case of juvenile manic-depressive illness associated with mental retardation is reported having been treated successfully with lithium carbonate. During four years of maintenance treatment with daily doses of 600 mgs. to 900 mgs. per day of lithium carbonate, disruptive manic behavior has been controlled and a subjective leveling out of mood has allowed that patient to develop more fully her cognitive and psychomotor capacities. There was one exascerbation of disruptive behavior during the first year of treatment that was easily controlled with haloperidol together with continued lithium carbonate maintenance treatment. No measurable adverse developmental or thyroid effects have been noted. The Shaffer acquiescence scale of the MMPI correctly predicted that the patient would be a positive responder to lithium carbonate treatment.


Glucose-insulin metabolism in chronic schizophrenia. The present study deals with possible connections between the schizophrenic syndrome and alterations of the glucose-insulin metabolism. Data have been obtained in 18 patients, 9 males and 9 females, aged 22-62 years, suffering from chronic schizophrenia of 5-29 years duration. The patients were treated with Haloperidol for 30 days, 6 mg, i.m.p.d. to a total dose of 180 mg. The glucose metabolism was examined through a GTT (with a glucose load of 100 gr. per os), and an Insulin Tolerance Test (with 0.1 U/kg body weight). The insulin levels were examined under glucose load by the radioimmunological assay of Hales and Randle. The glycemic levels were examined under glucose load by an oxidative method. The psychopathological features were controlled by a Wittenborn Rating Scale. The metabolic and psychological examinations were done twice before the beginning of therapy, at 46 hrs. interval, then at 10-20-30 days of therapy. The results are probative for the presence of a chemical diabetes in a significantly high percent of patients. The significance of possible neurotransmitter impairments acting at both the biochemical and psychological levels is discussed.


[Excision and removal of multiple polyps of the colon (author's transl)]. Nowadays polyps in the gastrointestinal tract are usually removed under endoscopy, the method being highly effective and of low risk. Endoscopic removal, if necessary in several sessions, can be easily done even if there are multiple polyps of the colon. Altogether 69 polyps were removed from a 33-year-old woman, their microscopic appearance showing various degrees of proliferation. Complete removal of the polyp is of decisive importance, accomplished by enema wash-out. The diagnostic point of polypectomy lies in the histological assessment of the entire material which has been removed.


[The effect of L-tryptophan on L-dopa absorption (author's transl)]. Dopa blood levels were measured in healthy subjects after oral intake of 0.5 g L-dopa (seven subjects) as well as of 0.5 g L-dopa and 1.0 g L-tryptophan (six subjects). Combined L-dopa and L-tryptophan administration produced significantly less of a rise in dopa blood levels than L-dopa alone.


[Hairy cell leukaemia. I. Clinical features, cytochemistry, phagocytosis, establishment of permanent growing cell lines (author's transl)]. In seven patients the diagnosis of hair cell leukaemia (leukaemic reticuloendotheliosis) was confirmed cytochemically and histologically. Splenectomy, in six patients, apparently favourably influenced the course. Isoenzyme 5 of the acid phosphatase was demonstrated in the hairy cells of all patients. Reaction of alpha-naphthylacetate esterase was moderately positive in the hairy cells. Phagocytosis of latex and India-ink particles was demonstrated especially in tartrate-resistant cells of one patient. In two patients eight permanently growing cell lines were demonstrated from leucocytes and defined cytochemically. Capacity for phagocytosis of hairy cells and positive reaction of alpha-naphthylacetate esterase in the hairy cells suggest properties of monocytes. But it is not possible definitively to classify the hairy cells among B-cells or monocytes.


[Number and kinds of drug side-effects in a medical clinic (author's transl)]. All drug side-effects - definite, probable and suspected - were noted during one year in 1592 patients. The severity of the side-effects was classified into mild (15%), moderate (6.5%), and severe (1%) forms. Fatal side-effects occurred without exception only in those patients who were severely ill so that any risk of treatment had been fully justified. Among patients with renal failure, malignant haematological diseases or Hodgkin's disease there was a particularly high incidence of side-effects. Although the proportion of the latter patients was only 15% of all in-patients, they accounted for 35% of patients with side-effects.


[A new pharmacological test for diagnosing coronary artery disease (author's transl)]. In 45 patients with coronary artery disease, proven by coronary arteriography, and 15 patients without such disease 0.5 mg dipyridamole (Persantin) per kg body weight was injected i.v. over ten minutes. In 40 of the 45 patients with coronary artery disease anginal pain occurred during or immediately after dipyridamole injection and ceased immediately after intravenous administration of 0.24 g aminophylline (positive test), while in three it had stopped spontaneously without aminophylline (questionable positive test). Only in two of the 45 patients with confirmed coronary artery disease was there no anginal pain (false-negative result). None of the 15 patients without coronary artery disease had anginal pain during the test. It is concluded from these results that the "dipyridamole test", which is simple to perform and does not stress the patient significantly, is at least equivalent diagnostically to the exercise E.C.G. test.


[Testosterone-binding capacity, free-plasma testosterone fraction, and free-plasma testosterone concentration in andrological patients (author's transl)]. Testosterone-binding capacity (TeBG), free-plasma testosterone fraction (%FT), and free-plasma testosterone concentration (AFT) were measured in 24 men with primary and 14 with secondary hypogonadism of various causes, as well as in eight with coital impotence. There was a highly significant correlation between TeBG and %FT (r = minus 0.891; P less than 0.0005). TeBG and %FT did not generally differ from normal in primary hypogonadism, while AFT was normal or decreased, depending on the corresponding whole testosterone concentrations. In secondary hypogonadism there was always an increased TeBG and decreased %FT. Depending on whole testosterone concentration, AFT was low or very low. In impotent subjects TeBG, %FT and AFT were generally normal. The role of AFT determination in andrological diagnosis is discussed.


[Treatment of acute viral hepatitis with laevulose infusions (author's transl)]. Until 1962 all patients with acute viral hepatitis admitted to the Medical University Clinic at Marburg were treated with laevulose infusions. This treatment was discontinued in 1963. Follow-up examination of 109 patients with acute hepatitis who had been given laevulose infusions and 91 who had not (both groups being similar as to age and sex and average severity of the disease) revealed that there was no significant difference between the two groups with regard to the fall in transaminase levels during the first seven weeks after the onset of jaundice. Serum-bilirubin concentration was also similar. On the other hand, the abrupt fall in serum-bilirubin concentration in the second to third week of illness, so typical of the spontaneous course, occurred a week later in those who had been given laevulose infusions. Duration of the disease until normalization of transaminase and serum-bilirubin concentration was not favourably influenced by laevulose infusions. It is concluded that such infusions do not have a favourable effect on the course of acute viral hepatitis.


[Sinus tachycardia after implantation of a pacemaker for 2 : 1 A-V block with bradycardia (author's transl)]. A demand pacemaker was implanted into a 74-year-old listless woman who was in congestive heart failure, obese and had diabetes mellitus. The ECG indicated a 2 : 1 A-V block (ventricular rate 40/min). Two days after implantation a sinus tachycardia of 98/min occurred and the diabetic metabolic state deteriorated. This was probably due to hyperthyroidism in a thyroid gland of normal size but varying uptake, and was possibly precipitated by the administration of iodine contained in an anti-asthmatic medication.


[Quantification of the three-dimensional structure of jejunal mucosa in healthy subjects and patients with coeliac disease (author's transl)]. Jejunal biopsies of 10 normal subjects and 7 patients with coeliac disease were analysed quantitatively using the microdissection technique described by Clarke. Mucosal surface in the healthy upper jejunum was increased 8.3 +/- 1.1 times, the number of villi per mm2 intestine being 18.2 +/- 2.1. The ratio of the number of crypts per villi was 10.7 +/- 2.3. Mucosal transformation in coeliac disease was associated with a decrease in villi and crypts per mm2 intestine as well as in mucosal surface and an increase in crypt depth and number of mitotic figures per crypt. There was a highly significant linear correlation between villous height and mucosal surface per mm2 intestine (r = 0.93).