Symposium: Contraindications to tympanoplasty. I. Absolute and relative contraindications. A brief history of the surgical technique of tympanoplasty is provided, emphasizing the underlying principles and goals as defined by Wullstein. Based on clinical and surgical experience, a list of absolute and relative contraindications to tympanoplasty surgery is presented according to the presence or absence of active pathology.


Symposium: contraindications to tympanoplasty. III. Contraindications for tympanoplasty. Absolute and relative, systemic and regional contraindications are discussed under the topics of systemic illness, mumps, age, wet ear, traumatic perforation, only ear, perfect contralateral ear, and benefit unlikely.


Localization of implanted radioactive wires and computation of the dose distribution. A method is described for the spatial localization of implanted curved radioactive wires. The input data are obtained from two orthogonal radiographs taken on a simulator. A specially constructed double light-box is used for the determination of corresponding points on the projections of the wire in the AP and lateral radiographs. The wires are localized as a series of straight segments and formulae are derived for the computation of the segment activity in order to calculate the dose distribution for uniformly and non-uniformly activated wires. All calculations can be included as additional subprograms in a dose computation program for straight linear sources.


The sharp dissector as an aid to better surgical procedures. Various types of bone scrapers, skin scratchers and dissectors have been devised by practitioners. However, in modern operating rooms, a well sharpened general dissector is rarely seen. Experience in doing a wide range of surgical procedures indicated that well crafted dissectors with hollow-ground blades can improve the speed and accuracy of the surgeon as well as reduce the bleeding. The blades of these dissectors should be contra-angled and always kept sharp. To reduce expense, disposable round-ended blades, factory sharpened, could slide into the firmly gripping chucks of suitable handles.


Electronic stethoscope with frequency shaping and infrasonic recording capabilities. A small electronic stethoscope with variable frequency response characteristics has been developed for aerospace and research applications. The system includes a specially designed piezoelectric pickup and amplifier with an overall frequency response from 0.7 to 5,000 HZ (-3 dB points) and selective bass and treble boost or cut of up to 15 dB. A steep slope, high pass filter can be switched in for ordinary clinical auscultation without overload distortion from strong infrasonic signal inputs. A commercial stethoscope-type headset, selected for best overall response, is used which can adequately handle up to 100 mW of audio power delivered from the amplifier. The active components of the amplifier consist of only four opamp-type integrated circuits.


[Steroid metabolism in primates. XVII. Isolation of 17alpha-hydroxy-pregnenolone from adrenal venous blood of the baboon (Papio hamdryas)]. 17alpha-Hydroxypregnenolone (3beta,17alpha-dihydroxy-5-pregene-20-one) was isolated from adrenal venous blood of male healthy baboons and identified by paper chromatography, thin layer chromatography and infrared spectrometry. In 6 animals the concentration in adrenal venous blood (16--70 mug/100ml) and the secretion rate (2--5 mug/h/kg body weight) have been estimated. The results demonstrate the secretion of 17alpha-hydroxypregnenolone by the baboon adrenal.


In vitro effects of ascorbic acid and dehydroascorbic acid on diphosphopyridine nucleotide diaphorase in toad testis. The enzyme diphosphopyridine nucleotide diaphorase (DPND) was demonstrated histochemically in both the tubular and Leydig cells of the toad testis. Addition of 200 mug of dehydroascorbic acid (DHA) to 100 mg of testicular slices in the incubating medium increased the activity of DPND, while a similar dose of ascorbic acid failed to do so. The evidence indicates that DHA is involved in the oxidation of reduced DPND in toad testis.


Spacing nomograph for interstitial implants of 125I seeds. Permanent implants of 125I seeds at Memorial Sloan-Kettering Cancer Center are performed by the method of "dimension averaging" to determine the total activity to be implanted; that is, the activity (in mCi) is taken to be five times the average dimension (in cm) of the target region. A nomograph has recently been developed to permit a rapid calculation of the seed spacing required for a uniform distribution of the number of seeds specified by dimension averaging. The number of seeds is also given by the nomograph. The spacing calculation performed with the nomograph, since it involves the two-thirds power of average dimension and the one-third power of seed strength, is well beyond the reach of mental arithmetic. Elongation and shape corrections are included. The nomograph spacing result is valid for an equipartition of measured volume among seeds but must be increased by an easily determined factor if peripheral seeds are considered to define the surface of the target region.


Steroid metabolism in the gonads of a patient with testicular feminization. II. Metabolism of c19- and c18-steroids in vitro. The metabolism of C19- and C18-steroids, in particular, the aromatization of androstenedione and testosterone, the interconversion of androgens to estrogens and the 5alpha-reductase activity of a right abdominal (r) and a left inguinal (l) testis of a patient with testicular feminization, are reported. Aromatization and 5alpha-reductase activity were also evaluated in tissue from the left ductus diferens (ld). The following results were obtained: 1. aromatization of androstenedione to estrone 2.52% (r), 0.02% (l), 0.94% (ld); 2. aromatization of testosterone to estradiol 0.58% (r), 2.88% (l); 3. conversion of androstenedione to testosterone 95.65% (r), 98.07% (l); 4. conversion of testosterone to androstenedione 33.14% (r), 53.65% (l); 5. conversion of estrone to estradiol85.29% (r), 100% (l), 6. conversion of estradiol to estrone 33.12% (r), 32.33% (l); 7.5alpha-reduction of testosterone to 5alpha-dihydrotestosterone 12.01% (r), 13.64% (l) and 4.10% (ld). A lack of 5alpha-reductase activity was not found in the tissues examined as stated in the literature. Estrogen production in these testes was demonstrated by the aromatization of androstenedione and testosterone to estrone and estradiol and is reflected in the difference of the estradiol concentration measured in spermatic and peripheral blood of the same patient (168 versus 33 pg/ml).


On the evocability of a positive oestrogen feedback action on LH secretion in transsexual men and women. In transsexual men with homosexual behaviour and intact testicular function, as well as in homosexual men with normal gender identity, following a negative oestrogen feedback effect a delayed positive oestrogen feedback action on LH secretion was evoked. By contrast, in transsexual men with hypo- or asexuality and intact testes or hypergonadotrophic hypo- or agonadism, as well as in heterosexual men with normal gender identity, a negative oestrogen feedback effect was not followed by a positive feedback action on LH release. In transsexual women with homosexual behaviour and oligo- and/or hypomenorrhoea, only a weak or at best moderate positive oestrogen feedback action on LH release was evocable, similarly as in castrated and oestrogen-primed heterosexual men. By contrast, in a transsexual woman with bisexual behaviour and eumenorrhoea, a strong positive oestrogen feedback action on LH secretion was evocable, as well as in heterosexual women with normal gender identity.


Sex differences in adrenocortical structure and function. III. The effects of postpubertal gonadectomy and gonadal hormone replacement on adrenal cholesterol sidechain cleavage activity and on steroids biosynthesis by rat adrenal homogenates. In rats postpubertal orchiectomy results in an increase in the adrenal weight, testosterone replacement restores the adrenal weight to the normal level. Neither ovariectomy (8 weeks of duration) nor estradiol replacement has an effect on adrenal weight in female rats. Pregnenolone synthesis as well as corticosterone and blue tetrazolium-positive steroids secretion is significantly higher in homogenates of adrenals from female rats than from males. Orchiectomy results in a marked increase in pregnenolone biosynthesis, testosterone replacement restores the value to the normal levels. Neither ovariectomy nor estradiol replacement has an effect on pregnenolone synthesis in v i t r o. In both sexes gonadectomy causes a marked decrease in corticosterone output by adrenal homogenates, concomitantly the increase in the adrenal 5alpha-reductase activity is observed. The ratio of secreted corticosterone to pregnenolone is significantly lower in gonadectomized rats of both sexes than in control animals. Estradiol or testosterone replacement inhibits the adrenal 5alpha-reductase activity and restores the corticosterone output as well as corticosterone/pregnenolone ratio to the normal values. The above described findings show that the sex differences in steroids secretion by the rat adrenal are partially conditioned by a cholesterol sidechain cleavage activity. Testosterone inhibits this activity while estradiol under applied experimental conditions has no effect on the cholesterol sidechain cleavage activity.


The vasopressin and oxytocin content in the hypothalamus and neurohypophysis as influenced by reserpine treatment during long-term dehydration in the white rat. In dehydrated rats both neurohypophysial hormones diminished in hypothalamus as well as in the neurohypophysis. Oxytocin disappearef from the hypothalamus and neurohypophysis at a more rapid rate than vasopressin did. The minimal content of vasopressin and oxytocin in the hypothalamus was observed during 3rd--4th day, but even in extreme dehydration it was found to be relatively high: 65 per cent of vasopressin and 27 per cent of oxytocin as compared with intact animals. At that time the neurohypophysial vasopressin and oxytocin content were almost fully exhausted. In dehydrated and additionally reserpinized animals (10 mg/kg intraperitoneally, then each 48 hr 5 mg/kg of initial body weight) the vasopressin and and oxytocin hypothalamus and neurohypophysis changed in a similar manner. In some experimental groups the decrease of neurohormones in both sites was more marked under reserpine treatment. The drug seems therefore rather to potentiate the effects of physiological stimulation of osmodetectors. So the existence of monoaminergic stimulatory synapses, directly involved in the neural pathway between the osmodetector and the neurosecretory cell, appears to be hardly probable.


On electrolyte determinations in the pituitary and pineal gland: is there a diurnal rhythm? At four different times during the day determinations of the electrolyte content of the anterior and posterior pituitary as well as of the pineal had been carried out by means of atomic absorption spectroscopy. There are significant differences in the sodium and potassium content between these organs. There are also distinct changes in the adenohypophysial Na+, K+ and Mg++ content between the light and the dark period. Values are low over the day and high during the night. In the light period there is also a significant higher sodium concentration in the neurohypophysis and a greater potassium concentration of the pineal tissue. Despite a similar phylogenetic development the neurohypophysis reveals a considerably less amount of univalent cations than the pineal gland. Data from the literature, however, let suggest that there are no greater differences in the water content of neurohypophysis and pineal. The possibly resulting "hypotonicity" of neurohypophysial tissue and its possible implications for the mode of the release of hormonal substances from the neurohypophysis are discussed.


[The behavior of lipoproteins, cholesterol, triglycerides, free fatty acids and free glycerol in serum of rats with experimental hyperthyroxinemia and hypothyreosis]. In hyperthyroxinemic and hypothyreotic rats the lipoprotein level in serum was investigated using agarosegel-electrophoresis and changes in serum level of cholesterol, triglycerides, free fatty acids and glycerol were determined. In hyperthyroxinemic animals the beta-lipoproteins were found in the same level as the control animals, while the prae-beta-fraction was significantly elevated and the alpha-lipoproteins lowered. The cholesterol was significantly reduced, the triglycerides and the glycerol significantly increased. The free fatty acids were slightly elevated. In hypothyreotic animals the beta-and prae-beta-fraction of lipoproteins was significantly elevated. The alpha-lipoproteins were found diminished. Cholesterol and triglyceride values were also significantly increased. The levels of free fatty acids and glycerol did not differ in both groups of animals.


Effects of a single ethanol injection into the vas deferens on the testicular function of rats. 1. A new approach to rapid male sterilization has been studied by giving a single injection of 95% ethanol directly into the vas deferens. It produced an effective block in the lumen. The mating exposure test showed that the males were sterile. The sperm granulomas at the site of vas injection were confirmed. 2. Ethanol injection in the vas deferens caused an atrophy of the testes. Extensive necrosis and exfoliation of the seminiferous elements were conspicuous. 3. Decrease in testicular weight, seminiferous tubule diameter and RNA and sialic acid levels after 4 weeks of vas injection were associated with the histological evidence for severe degeneration of spermatogenic elements. The protein contents of testis, epididymides and seminal vesicles did not change. 4. Testicular cholesterol, total lipids and alkaline phosphatase activity was increased. 5. Low sialic acid levels in the testis, epididymides and seminal vesicles of vas-injected rats indicated an inhibition of androgen production, which was further reflected in reduced nuclear diameters of leydig cells.


Plasma glucose, insulin and free fatty acids in infants with congenital heart disease. The effect of congestive cardiac failure, hypoxia and hypoglycaemia on glucose tolerance and insulin secretion were studied in selected groups of infants with congenital heart disease. Fasting blood glucose level was significantly decreased in patients with congestive heart failure and in cyanotic infants without congestive heart failure. In the former it seemed to be correlated with the degree of malnutrition, while in cyanotic infants it was independent of the nutritional state. Plasma insulin levels were reduced in infants, with congestive cardiac failure, although their glucose tolerance test and free fatty acid concentrations were normal. It is suggested that the decreased plasma insulin concentration was a consequence of adaptation to reduced requirements. Glucose tolerance and insulin secretion were not affected by hypoxia or hypoglycaemia.


Characteristic features of antilipolytic activity of serum in relation to obesity. Antilipolytic activity (ALA) of serum of the obese and controls was tested on rat epididymal adipose tissue incubated in medium containing adrenaline; the results were compared with the effect of insulin. Serum of the obese displayed lower ALA than controls, in one third obese individuals serum potentiated the effect of adrenaline. After fasting, ALA of serum decreased. ALA value is related to the prevailing metabolic situation, an inverse relationship was observed between ALA and levels of NEFA and ketone bodies. This seems to suggest that antilipolytic effect of insulin, whose concentrations are higher in the obese, is antagonised. This effect does not apparently depend on the presence of insulin antibodies, which do not inhibit, but, on the contrary, potentiated antilipolytic effect of insulin in vitro. Investigation of fractions of native serum proteins showed the effect of fraction 10 000--50 000 MW. to differ in the obese and controls. That particular fraction of sera of the obese had an adipokinetic effect.


Metabolic effects of weight reduction in obese diabetics and nondiabetics. A weight loss of about 10 kg was acheived by means of individual periods of total fasting, hypocaloric diets and physical activity in three groups of patients: maturity-onset diabetics, patients with pathological OGTT and overweight persons with normal OGTT. Adipocyte volume decreased in all groups, glucose tolerance improved. IRI curves showed a significant overall lowering and FFA concentrations during OGTT were dimished.


Human-IgE-induced degranulation of mouse mast cells. The relations between human IgE and mouse peritoneal mast cells were studied in vitro. Non-heated human IgE sensitizes the mouse mast  cells for degranulation on challenge with anti-human IgE. This capacity is lost after heating of human IgE at 56 degrees C. The degranulation only occurs in determined quantitative IgE-anti-IgE relationships, an excess of one or the other reagent inhibiting the reaction. Sensitization is practically instanteneous, and the degranulation is independent on the order of addition of the human IgE and anti-IgE. The human IgE can be removed from mouse peritoneal mast cells by a single washing. The results show that human IgE is unable to bind firmly to mouse peritoneal mast cells in vitro. It seems to induce the formation of biologically active human IgE-anti-human IgE complexes, which act on mouse mast cells and induce their degranulation.


Evidence that C1s participates in the alternative complement pathway. Purified C1s, subcomponent of C1, induced electrophoretic conversion of factor B and consumption of hemolytic C3 and C5 in sera genetically deficient in C2 or C4. Blocking of the hemolytic activity of C1s in C2-deficient serum by F(ab')2 anti-C1s resulted in inhibition of the alternative pathway, as indicated by the failure of zymosan or cobra venom factor to induce comsumption of C3 and C6. Zymosan also failed to activate the alternative pathway when C1s was absorbed from C1r-deficient serum using a solid immunoabsorbent. These data, showing that C1s participates in the alternative pathway under certain experimental conditions, suggest the interesing possibility that C1s is important in the activation sequence of both the classical and the alternative pathway more generally.


Brain temperature in the unanaesthetized chicken: its circadian rhythm of responsiveness to light. Temperatures were recorded continuously for up to 4 days in the brain of 8 unanaesthetized, moderately restrained male chickens, kept in light-dark cycles (LD) of 30:30 or 60:60 min duration. In all cases, brain temperature was higher in L than in D. Temperatures increased or decreased immediately after the light was turned on or off, respectively, but did not reach a new level until after about 30 min. Average values of temperature obtained during the last 10 min in L and D were used for further analysis. The changes of brain temperature due to changes in light intensity were super imposed to marked circadian oscillations. The computed differences between L- and D-values were found to be a function of the circadian phase. For 4 out of the 8 chickens a uniform circadian rhythm of responsiveness to light could be demonstrated, with two maxima coinciding with the ascending and descending circadian slope, respectively. In view of the evidence suggesting brain temperature as a reliable measure of the degree of arousal, it is concluded that light has a stronger arousing effect on the chicken in the morning and in the evening than in the middle of the day or the night.


Spindle wave synchrony in the somatosensory cortex of the cat. (1) Spontaneous barbiturate spindles were recorded from the primary and secondary somatosensory cortex. The recordings were concentrated to areas surrounding several reference loci. The recording sites producing the maximal response evoked by stimulation of an exposed nerve in a contralateral limb were used as reference loci. (2) Spindles recorded at various distances from the respective reference loci were cross-correlated to spindles developing simultaneously in the latter. High correlation coefficients, indicating a considerable degree of wave synchrony, were obtained between spindles in the reference locus and spindles recorded a few millimeters from this site. The correlation coefficients decreased with increasing interelectrode distance. A relatively sharp fall in the correlation coefficients was generally found 2-3 mm from the reference locus. Small amounts of sodium pentobarbital, given intravenously at intervals of 5 min, had no effect upon this pattern. (3) The change in the correlation coefficients was followed by a parallel change in the amplitude of the evoked potentials. The iso-correlation lines of spindle wave synchrony and the iso-amplitude lines of the evoked potentials had a similar distribution and extension for each particular reference locus. (4) Lateral spread of spindle waves in the cortex seems to be of minor importance, since a vertical lesion cutting the cortico-cortical fibres did not reduce the wave synchrony of the spindles recorded from either side of the lesion. (5) The majority of the spindles recorded in the close vicinity of a reference locus started simultaneously within +/- 0.1 sec. This pattern changed with increasing distance from the reference locus and 5.6 mm away only a fraction of the spindles started simultaneously. However, within the entire primary somatosensory cortex a small but significant coupling existed between onset of the spindles.


Electrical response of glioma cells to acetylcholine. A bromodeoxyuridine resistant mutant of rat gliom line C6 grown in the presence of N6,02'-dibutyryl adenosine-3':5'-cyclic monophosphate, although inexcitable by electrical current, responds to iontophoretic application of acetylcholine by slow hyperpolarization. The sensitivity to acetylcholine is strongly reduced by excessive amounts of acetylcholine. The hyperpolarization response is inhibited by atropine or alpha-bungarotoxin, but not by D-tubocurarine. In the absence of acetylcholine some cells display spontaneous hyperpolarizations at regular intervals. The membrane resting potential is decreased if the concentration of external K+ is raised.


Brbiturate spindle activity in the association cortex of the cat and its relation to spindle activity in the somatosensory system. (1) Spontaneous barbiturate spindle activity was recorded simultaneously from nucleus ventralis poster-lateralis (VPL) of the thalamus, from the corresponding projection site in the primary somatosensory cortex (SI) and from the lateral (LAT) and middle suprasylvian (SSM) gyri. (2) Barbiturate spindles occurred more frequently in LAT and SSM than in the somatosensory cortex. Spindles in LAT and SSM were of longer duration than SI spindles while the intraspindle frequency was higher in spindles from the latter areas. The amplitude of the spindle waves was significantly higher in LAT and SSM than in SI. The largest spindle waves were recorded from the anterior part of LAT and SSM. (3) Barbiturate spindles recorded at various interelectrode distances were cross-correlated. In LAT and SSM the cross-correlation coefficients remained high up to an interelectrode distance of 4-5 mm while spindles recorded at this distance in SI gave low coefficients when cross-correlated. (4) Extensive removal of the somatosensory cortex had no effect on spindle formation in LAT or SSM. Furthermore, cutting of the cortico-cortical connections between two recording sites in either of these gyri produced no reduction in spindle wave synchrony between the recording sites. (5) Spindles in the VPL-SI only rarely started simultaneously with spindles in LAT and SSM. Those few coincident spindles which occurred were cross-correlated. The cross-correlation coefficients were invariably low suggesting that no wave synchrony existed between spindles in the VPL-SI system and those in the LAT and SSM.


Sensory requirements for the lordosis reflex in female rats. (1) Visual, auditory and olfactory input were not necessary for the performance of the lordosis reflex by female rats. Since taste is not involved in this behavior, somatosensory input must be sufficient for triggering the lordosis reflex. (2) Surgical cutaneous denervation markedly reduced the frequency and strength of lordosis. The most effective operation denervated the perineum, tailbase, posterior rump and ventral flanks. This pattern of results agrees with film observations and manual stimulation of lordosis. (3) Effects of surgical cutaneous denervation were confirmed in experiments with local anesthesia produced by subcutaneous procaine injections. (4) It is deduced that cutaneous mechanoreceptors in specific regions of hairy skin of the female rat play a crucial role in triggering the lordosis reflex.


Single unit recording in hypothalamus and preoptic area of estrogen-treated and untreated ovariectomized female rats. Single unit activity was recorded with micropipettes in the medial hypothalamus and preoptic area of urethane-anesthetized ovariectomized female rats. Some females had received long-term estradiol treatment, while others had been left untreated. In the medial preoptic region and bed nucleus of the stria terminalis, estrogen-treated rats had fewer cells (compared to untreated rats) with recordable spontaneous activity, due primarily to a loss of cells with very slow firing rates. In the basomedial hypothalamus, estrogen-treated rats had more cells (than untreated rats) with recordable spontaneous activity, due primarily to an increase in the number of cells with slow firing rates. Responsiveness of neurons to somatosensory stimulation was generally low. If present it was depressed by estrogen treatment in medial preoptic area and bed nucleus of stria terminalis, while it tended to be elevated by estrogen treatment in medial anterior hypothalamus and basomedial hypothalamus. Differences in the effects of long-term systemic estrogen treatment on medial preoptic neurons compared to basomedial hypothalamus are paralledled by differences in the control of lordosis by these neurons in female rats.


Ultrastructural changes in the vascular organ of the lamina terminalis following ovariectomy and hypophysectomy in the rat. Based on quantitative evaluations it was observed that 4 and 14 days after ovariectomy, as well as 2 months after hypophysectomy, the larger granulated vesicles (70-110 nm in diameter) in the nerve terminals of the vascular organ of the lamina terminalis (OVLT) almost disappeared. The findings are consistent with the view that the OVLT may play a role in the control of pituitary gonadotrophic function.


Serum dopamine beta-hydroxylase as an index of sympathetic nervous system activity in man. Serum dopamine beta-hydroxylase (DBH) activity was comparable in eight adrenalectomized patients and in 41 normal volunteers (37.8 +/- 3.6 vs. 40.0 +/- 4.0 IU), but were very low in four patients with severe diabetic autonomic neuropathy (6.7 +/- 4.2). These observations suggest that the major source of DBH activity in human serum is probably the sympathetic nervous system. Serum DBH activity was also significantly lower in seven patients with low renin essential hypertension than in 17 patients with normal renin hypertension (19.9 +/- 4.3 vs. 43.9 +/- 5.0 IU, P less than 0.05). Dietary sodium depletion, a stimulus for catecholamine secretion, produced only a small increase in serum DBH activity in supine normal volunteers (26.5 +/- 10.4 to 33.9 +/- 11.4, P less than 0.05; n = 7) and in five adrenalectomized patients (33.0 +/- 12.7 to 44.1 +/- 15.2, P = 0.06). Plasma renin activity increased more than 3-fold in these same subjects, and did not correlate with serum DBH activity. Similarly, 4 hours of ambulation produced only a small increase in serum DBH activity which did not correlate with plasma renin activity. The small magnitude of these responses to physiological stimuli of the sympathetic nervous system diminishes the potential clinical usefulness of measurement of serum DBH activity. Further studies utilizing direct correlation of plasma and urine catecholamines with serum DBH activity are needed to establish its relationship to sympathetic nervous system activity.


The response of atrial stretch receptors to increases in heart rate in dogs. The discharge characteristics of type B left atrial receptors were analyzed during alterations in heart rate. Recordings were made from single-fiber preparations of the left cervical vagus of pentobarbital-anesthetized, open-chest dogs. The heart was paced following a sinoatrial crush at frequencies ranging from 60 to 240 beats/min. Left atrial transmural pressure was varied at each heart rate by the intravenous infusion of warm isotonic NaCl. As heart rate was increased there was a progressive decrease in the level of peak "v" wave left atrial pressure. Concomitantly with the decrease in left atrial pressure, the number of spikes per cardiac cycle decreased as did the maximal instantaneous frequency of discharge. A significant positive relationship could be demonstrated with either the discharge per minute [(spikes per cycle) X heart rate] or discharge per cycle vs. the peak "v" wave of the left atrial pressure, regardless of heart rate. The number of impulses that entered the central nervous system per unit of time remained relatively constant at heart rates between 90 and 240/min. It is concluded from these data that the reflex effects which have been attributed in the past to atrial stretch receptor stimulation during clinical episodes of atrial tachyarrhythmias may be better correlated with some aspect of receptor discharge other than frequency or the number of discharges per cycle.


Renal cortical blood flow in glycerol-induced acute renal failure in the rat. Renal hemodynamics and renal function were evaluated in rats at 3, 24, and 48 hours and at 7 days after the induction of acute renal failure (ARF) by glycerol injection. Three hours after induction of ARF, creatinine clearance was 0.04 ml/min/100 g; renal blood flow (RBF), 1.99 ml/min/100 g; and filtration fraction, 3.7%. All were abnormally low. Although the administration of isotonic saline (total dose, 3% of body weight) to rats 3 hours after glycerol injection significantly improved creatinine clearance (0.17 ml/min/100 g), RBF (2.54 ml/min/100 g), and filtration fraction (12.9%), these values still were significantly lower than those of controls (creatinine clearance = 0.50 ml. ml/min/100 g, RBF = 4.92 ml/min/100 g, filtration fraction = 20.0%, all P values less than 0.001). Serum creatinine concentrations were significantly elevated at 24 hours (3.72% gm/100 ml), 48 hours (4.69 mg/100 ml), and 7 days (0.66 mg/100 ml) after glycerol injection compared to control (0.46 mg/100 ml, all P less than 0.01). RBF during these phases was not different from normal (4.41 ml/min/100 g). RBF 3 hours after bilateral ureteral obstruction was measured to determine the effects of tubular obstruction on renal hemodynamics. The RBF of rats with ureteral obstruction (4.12 ml/min/100 g) was not significantly different from controls (4.41 ml/min/100 g), suggesting that tubular obstruction in this model of ARF is probably not the cause of decreased RBF. The depressed glomerular filtration, as reflected by the decreased creatinine clearance that occurs during glycerol-induced ARF, is probably related to altered intrarenal vascular resistance or to changes in glomerular capillary permeability, or both.


Renal blood flow and its response to angiotensin II. An interaction between oral contraceptive agents, sodium intake, and the renin-angiotensin system in healthy young women. A variety of estrogen- and progestin-containing oral contraceptive agents reduced renal blood flow (RBF) significantly in 23 healthy, nonhypertensive young women, to a mean of 75 +/- 3.3% of the value expected for their age and dietary sodium intake (P less than 0.001). There was also significant activation of the renin-angiotensin system: renin substrate was increased approximately 3-fold in association with a striking increase in the circulating renin activity and angiotensin II levels in relation to sodium intake and excretion. Two observations suggest that the RBF reduction was directly mediated by angiotensin II. A correlation was demonstrable between circulating angiotensin II and RBF (P less than 0.01), and renal vascular responsiveness to angiotensin II infused into the renal artery was reduced significantly (P less than 0.001). Moreover, the oral contraceptive agents modified the basic relationship between sodium balance and vascular responsiveness to angiotensin II, suggesting that the agents acted through some mechanism other than alteration in the state of sodium balance. These observations provide further evidence for an important role of angiotensin II as a determinant of RBF. Renal vasoconstriction may contribute to the genesis of a number of complications, such as sodium retention and hypertension, associated with oral contraceptive use.


Atrial rhythm during ventricular fibrillation in the dog. Depolarization of the atrioventricular junctional tissues and of the atrial septum was examined in the perfused dog heart before and during ventricular fibrillation by (1) recording the potentials from the junctional tissues in the regions of the interatrial and interventricular septum and examining the relationship of activity at these sites to atrial depolarization, (2) computing histograms and autocorrelograms of atrial firing intervals to study atrial rhythmicity, and (3) plotting the sequence of atrial septal depolarization. The junctional tissue was generally randomly depolarized by the fibrillating ventricles. The histograms and autocorrelograms indicate that during ventricular fibrillation the atrial depolarization intervals do not remain constant, but vary widely. This seems to be due to the retrograde excitation from the junctional tissues. Plots of the depolarization sequences of the interatrial septum also indicate that retrograde depolarization takes place. The junctional tissues decrease the number of impulses that can pass from ventricle to atrium, and they similarly decrease the number of impulses that pass in an antegrade direction during atrial fibrillation.


Transmural distribution of myocardial blood flow during systole in the awake dog. This study was designed to quantitate transmural myocardial blood flow when coronary arterial inflow was limited to systole and during the subsequent reactive hyperemic response. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flowmeters and pneumatic occluders on the left circumflex coronary artery. Intermittent coronary perfusion, confined to the interval of left ventricular systole or an equivalent period during diastole, was effected by an R wave-triggered solenoid valve connected to the occluder. To measure regional myocardial blood flow we injected radionuclide-labeled microspheres, 7-10 mum in diameter, into the left atrium. When arterial inflow was limited to systole, flow was normal in the subepicardial layers and was decreased as a linear function of tissue depth in the subendocardial layers. When coronary arterial inflow was limited to an equivalent interval in diastole, the transmural distribution of flow was uniform. When coronary flow was confirmed to systole for more than 20 seconds, the blood flow debt incurred elicited a reactive hyperemia similar to that following a total occlusion of equivalent blood flow debt. However, regional myocardial blood flow during the peak of reactive hyperemia following systolic perfusion was preferentially directed to the subendocardium, where underperfusion was most marked, whereas reactive hyperemia flow following a total occlusion of equivalent blood flow debt was distributed more evenly across the left ventricular wall. Thus, when coronary inflow was limited to systole, ventricular contraction produced a transmural gradient in myocardial blood flow resulting in subendocardial underperfusion.


Normal myocardial contractile state in the presence of quinidine. Since quinidine is one of the few agents available to treat and prevent ventricular arrhythmias in ambulatory patients, its hemodynamic effects have been reevaluated. When given in therapeutic doses to anesthetized mongrel dogs, quinidine significantly reduced heart rate, aortic pressure and flow, but it did not significantly change the first derivative of the left ventricular pressure curve (left ventricular dp/dt) in nine dogs. A subsequent group of dogs was studied after vagotomy and practolol administration to block cardiac reflexes. This group showed significant reductions in heart rate, aortic pressure and left ventricular dp/dt, with the latter returning to predrug control values when preload, afterload and heart rate were maintained constant. These studies suggest that quinidine does not directly affect myocardial contractility when given in therapeutic doses. Furthermore, the reduction in heart rate in these animals provides support for a direct depressant effect of quinidine on the sinus node. The adverse effects of quinidine on cardiac function previously reported may be due to the use of toxic doses or are secondary to quinidine peripheral circulatory effects, rather than due to a direct reduction in cardiac contractile state.


Complication rate of coronary arteriography. A review of 5250 cases studied by a percutaneous femoral technique. Distressing rates of embolic complications from coronary arteriography performed by the percutaneous femoral approach have been reported since 1972. From 1970-1974, 5250 patients underwent coronary arteriography in our laboratory by the same percutaneous femoral technique with preformed polyethylene catheters and no systemic heparinization. Data were recorded during and for 24 hours postcatheterization. The annual mortality rate averaged 0.23% and remained relatively stable. Our incidence of embolic complications was very low. In patients with normal coronary arteries, no fatal or serious nonfatal complications occurred. Left main coronary artery disease was present in all cases of mortality and greater than or equal to 60% stenosis was shown in nine of 12 instances. Thus major risk was proportional to the severity of disease in the left coronary system. The use of more aggressive supportive measures in these high-risk cases appears essential to reduce the total complication rate from coronary arteriography significantly.


Evaluation of potassium-43 scintillation images during early myocardial ischemia in an animal model. To assess the validity of myocardial imaging with potassium-43 (43K) early after the onset of ischemia, the left anterior descending artery was occluded with a baloon tip catheter in 32 intact anesthetized dogs. 99mTechnetium ventriculograms localized the left ventricle. 43K was administered intravenously and serial images were obtained in four views using an Anger camera with a pinhole collimator. The heart was arrested after 60 minutes and removed for imaging and tissue counts to ascertain extracardiac and geometric factors. In normals (group 1) left ventricular images were relatively homogeneous, except for the thin walled apex, both in vivo and in the isolated heart. Equilibration with 43K prior to ischemia (group 2) gave similar images to group 1, associated with a small reduction in tissue count after one hour of ischemia. Group 3 was infused with 43K after initiation of ischemia. Despite a reduction of 43K counts in the ischemic area to less than one-fourth of the nonischemic site (P less than 0.001), demonstration of a "cold area" in vivo was inconstant, occurring in only 34% of studies. Lead shielding did not improve accuracy. In the isolated heart the ability to detect the cold area was improved to 73%. However, when the left ventricle was incised and spread flat, so that low and high activity areas were contiguous rather than superimposed, a widespread area of ischemia was present without exception in the anterior wall. Use of a rectilinear scanner in seven animals failed to improve diagnostic yield; areas of reduced radioactivity were seen at the apex in normals by both techniques. Thus, while detection of low flow areas in the isolated heart is feasible by isotopic imaging early after the onset of ischemia, both extracardiac and geometric factors can contribute to qualitative and quantitative errors in vivo.


Clinical, angiographic, and hemodynamic findings in patients with anomalous origin of the coronary arteries. Clinical and angiographic features of 31 patients with anomalous coronpary artery origin are reviewed. Of 17 aberrant circumflex arteries from the right sinus of Valsalva or artery, each was retro-aortic, six atherosclerotic, and seven irrigated a small area of myocardium. Of seven anomalous right coronary arteries from the left sinus of Valsalva or artery, each was ante-aortic and two atherosclerotic. Aberrant origin of the circumflex or right coronary artery was a benign anomaly. The proximal course of seven aberrant left coronary arteries from the right sinus of Valsalva or right coronary artery was related to clinical events. The anomaly was best demonstrated in the lateral view. In five cases, coronary blood flow during exercise and myocardial metabolism during pacing were assessed. Two had had a previous infarction with nonatherosclerotic arteries. Exercise coronary blood flow was normal in four and low in one patient. Pacing resulted in lactate production in two with atherosclerotic and one without atherosclerotic arteries. We conclude that anomalous left coronpary origin from the right sinus of Valsalva can result in significant myocardial ischemia and infarction.


Evaluation of left ventricular function in patients with aortic regurgitation using afterload stress. Left ventricular function was assessed in 14 patients with chronic aortic regurgitation by afterload elevation with angiotensin. Seven of 14 patients maintained their resting ejection fraction with angiotensin (group A), while the remaining seven experienced a decline of greater than 0.10 in ejection fraction (group B). Six of seven group A patients showed an appropriate rise in left ventricular stroke work index in response to the angiotensin-induced rise in left ventricular end-diastolic pressure. In contrast, six of seven group B patients showed abnormal, flat, or declining stroke work indices. Included in the seven group B patients were two patients with left ventricular dysfunction secondary to coronary artery disease. The five other group B patients, who did not have coronary diseases, exhibited similar stress-induced ventricular dysfunction, despite the absence of any significant resting hemodynamic differences from patients in group A. These five stress-induced dysfunction patients were distinctive from patients who maintained their ejection fraction level in that the former all had regurgitant fractions of greater than 0.50, whereasl all gruop A patients had regurgitant fractions of less than 0.50. Similarly, these five stress-induced dysfunction patients had significantly larger left ventricular end-diastolic volumes than did the group A patients. These data suggest that patients with pronounced aortic regurgitation measured in terms of regurgitant fraction greater than 0.50 and left ventricular end-diastolic volume of greater than 160 cm3/m2 exhibit impaired ventricular function if appropriately stressed. As most of the patients with stress-induced dysfunction had a normal ejection fraction at rest, it may be that stress-induced dysfunction represents a stage before overt resting dysfunction and cardiac failure.


The displacement cardiograph. A noninvasive technique for recording myocardial wall motion. The displacement cardiograph (DCG) is a noninvasive device employing an electromagnetic field to record tissue motion within the body. The sensing coil need not be in contact with the patient since the field penetrates air and stationary tissue without significant distortion. Disturbances in the field with result from ventricular wall motion are electronically converted to an analog output and a pattern inscribed on the paper of a physiological recorder. In an attempt to determine the reliability of the DCG in detecting regional areas of abnormal left ventricular wall motion, displacement cardiograms were obtained from 70 patients who underwent cardiac catheterization and left ventriculography. The DCG interpretations were in agreement with the ventriculographic picture of left ventricular wall motion in 67 of the 70 patients. There were two false positive and one false negative DCG diagnoses. The results indicate that the DCG can be employed as a reliable noninvasive method for repetitive assessment of the pattern of contraction of the anterior, anterolateral and posterior left ventricular wall.


Morphological development of the pulmonary vascular bed in fetal lambs. The morphological development that accompanies increasing pulmonary blood flow and decreasing pulmonary vascular resistance with advancing gestational age has not been delineated. To study this point we developed a method of comparing pulmonary arterial vessels of the same generations in fetal lambs. Pulmonary arteries were perfused with glutaraldehyde solution at pressures appropriate for gestational age and then injected with an India ink-gelatin-Micropaque mixture. Using the dissecting microscope and serially prepared sections we studied successively smaller generations of arteries. We assessed the medial width/external diameter ratio in a total of 825 vessels from six fetal lambs of 85 to 140 days gestation. In fifth generation, or resistance vessels, this ratio remained constant over the gestational period studied (N = 529, Y = 0.16, slope = 0.0003). We measured the volume of 17-34 randomly selected sections from each of the six fetuses, counted the total number of fifth and sixth generation vessels in these sections, and calculated the total number of these vessels per right lung. This number increased from 0.10 X 10(6) to 4.08 X 10(6) with increasing gestational age. The number of vessels per unit volume increased from 7.2 X 10(3)/ml to 61.8 X 10(3)/ml or right lung over this gestational period. The results indicate that increased pulmonary blood flow and decreased pulmonary vascular resistance with advancing gestation are due to an increase in the total number of vessels and increased vasomotor reactivity is related to an increase in the total amount of smooth muscle while the thickness of muscle in individual vessels remains constant.


Coronary risk factors in a community. Findings in Tecumseh, Michigan. In the Tecumseh study population examined from 1967 through 1969, 1457 men and 1607 women were separated into young (20-39 years), middle (40-54 years), and old (past 55 years) age categories. A subset of the study population, 183 men and 200 women who were repeatedly hyperglycemic according to a modified glucose tolerance test, were divided into the same age groups. Means and standard deviations of adiposity index, serum cholesterol, serum triglyceride, blood glucose, and systolic blood pressure were calculated for the total population and hyperglycemics. Correlation coefficients were determined for the relationship between adiposity index and each of the other variables and between paired variables exclusive adiposity index. Correlation coefficients for the latter relationships were recalculated after adjustment for the effect of adiposity. Means of variables were higher in middle and older age categories than in young age categories in both sexes, but the greatest incremental increases occurred between the young and middle-aged groups of men and between middle and old age groups among women. Men had significantly higher mean triglyceride and systolic blood pressure values than women in young and middle ages. Except for the cholesterol-triglyceride association, lipids, glucose, and systolic blood pressure were more highly correlated with adiposity than with each other. Correlations between variables were reduced by adjustment for adiposity. Hyperglycemics had higher mean adiposity indexes, serum lipids, and systolic blood pressures and generally higher correlations of variables than the entire study population. Much of the interrelationship of variables among hyperglycemics was associated with adiposity. Among men, higher mean triglyceride and systolic blood pressure levels, more frequent coexistence of risk factors, and a tendency to have large incremental increases in mean variables between young and middle age probably contribute to greater male susceptibility to ischemic heart disease. Levels of variables in the population and aggregation of coronary precursors in individuals are related to adiposity and hyperglycemia.


Aneurysm of the membranous ventricular septum in transposition of the great arteries. In patients with transposition of the great arteries (TGA), both the D- and L- forms, an aneurysm of the membranous ventricular septum (AMS) produces subpulmonic stenosis due to the higher right ventricular pressure which forces the aneurysm to protrude into the left ventricular, i.e., subpulmonic, outflow tract. The clinical signs and symptoms, hemodynamic findings as well as surgical results were analyzed in eight patients with TGA and AMS. The presence of an AMS should be suspected from hemodynamic data consisting of a combination of elevated left ventricular pressure, gradient across the left ventricular outflow tract and presence of a small ventricular septal defect with or without pulmonary artery hypertension. The AMS can be demonstrated by a right ventricular injection in the lateral view. The anomaly needs to be corrected at the time of the Mustard procedure. If uncorrected it may lead to postoperative death or progressive obstruction. In the presence of an aneurysm even small ventricular septal defects should be closed by a patch and the aneurysm should be excised.


Complete interruption of the aortic arch. 2. Characteristic angiographic features with emphasis on collateral circulation to the descending aorta. The angiocardiograms of 17 patients with aortic arch interruption are reviewed to emphasize the variations in arch interruption and origin of the brachiocephalic vessels, and collateral circulation to the descending aorta. Depending on the anatomical type and subtype of arch interruption, collateral flow to the descending aorta in the presence of a stenotic or closed ductus will be dependent on the development of intercostal collaterals and/or the presence of retrograde flow in all brachiocephalic vessels arising from the descending aorta. Familiarity with the potential pathways for collateral circulation may permit differentiation into types and subtypes on chest radiograph. Patients with Type I interruption may have bilateral rib notching if the right subclavian artery originates normally from the innominate artery, but will have rib notching confined to the left side if the origin of the right subclavian artery is aberrant. Type II or Type III interruption patients will have rib notching confined to the right side if the right subclavian has a normal origin, but no rib notching if the origin of the right subclavian artery is aberrant.


Dissecting aneurysm of aorta complicating aortic valvular stenosis. Six cases of classical dissecting aneurysm of the aorta complicating aortic valvular disease in which aortic stenosis was dominant are described. In three of the cases the aortic complication occurred after the natural aortic valve had been replaced by a prosthetic valve. The longest postoperative period was four months. The factor common to all reported cases in our series was cystic medial necrosis of the aorta. The authors agree with the concept of McKusick and associates that aortic dissecting aneurysm complicating aortic valvular disease is an association other than chance and is related to cystic medial necrosis of the aorta. The latter, in turn, is a consequence of the altered hemodynamics of aortic valvular disease, particularly stenosis.


Ventricular paired pacing to control rapid ventricular heart rate following open heart surgery. Observations on ectopic automaticity. Report of a case in a four-month-old patient. An unusual case is presented in which an atrioventricular (A-V) junctional tachycardia at a rate of 285 beats/min developed in the immediate postoperative period following surgical repair (a Mustard procedure) of transposition of the great vessels in a four-month-old infant. With that heart rate the systolic blood pressure bacame 35-40 mm Hg and urinary output ceased. Ventricular paired pacing was employed successfully to halve the mechanically effective ventricular rate. This resulted in a clinically effective blood pressure and return of normal urinary output. The clinical course of the A-V junctional tachycardia, plus its response to several interventions, suggested that the mechanism of the A-V junctional tachycardia was automatic rather than re-entrant. The study demonstrates that ventricular paired pacing for the control of cardiac arrhythmias is a useful clinical technique in selected cases.


Left ventricular diverticulum and mitral incompetence in asymptomatic children. Two children with congenital apical left ventricular diverticulum and significant mitral incompetence are reported. The angiographic and anatomic findings of the few previously reported patients with congenital diverticula and aneurysm were analyzed and a new classification differentiating between the two is proposed. The clinical data analyzed in apical diverticula and aneurysm are similar to those patients with anomalous origin of the left coronary artery from the pulmonary artery. Left ventriculography is the best diagnostic tool. The place of surgery in the treatment of the congenital apical diverticula with or without mitral incompetence in asymptomatic children is not clear. Further observations are needed to reveal its natural history.


An unusual form of the transposition complex. Uncorrected levo-transposition with horizontal ventricular septum: Report of two cases. A distinctive angiographic appearance is described in two patients who had uncorrected levo-transposition of the great vessels. Although levo-transposition with inversion of the ventricles usually results in physiologically corrected transposition, in these patients the anatomy was arranged in such a way as to result in an uncorrected transposition. The following elements were responsible for this physiological condition: normal atrial situs, inverted ventricles with "criss-cross" atrioventricular flow, levo-transposed great arteries. In addition, the morphological right ventricle was hypoplastic, left sided and superior to the left ventricle and the ventricular septum was horizontal in position. The two ventricles were connected via a large ventricular septal defect. The importance of accurate, detailed, preoperative angiographic demonstration of the anatomic situation is stressed.


Successful resuscitation of two near simultaneous cases of cardiac arrest with a review of fifteen cases occurring during supervised exercise. Two men with coronary heart disease experienced cardiac arrests during a recent exercise rehabilitation session. Fifteen cases of ventricular fibrillation have occurred in this program since 1968, making an average of one per six-thousand man hours of supervised exercise training. All were successfully resuscitated with no sequelae. Analysis of the patients who experience ventricular fibrillation suggests that treating patients with exercise-induced premature ventricular contractions with anti-arrhythmic drugs, proper attention to serum potassium levels, strict adherence to training pulse rates, and proper warm-up might help to prevent future similar events in an exercise program. Due to the unpredictability of ventricular fibrillation it seems preferable that individuals who have known coronary heart disease participate in exercise training under proper supervision with appropriate emergency equipment available.


Left ventricular outflow tract obstruction produced by redundant mitral valve tissue in a neonate. Clinical, angiographic, and operative findings. An unusual case of left ventricular outflow tract obstruction associated with severe left ventricular failure in a neonate is reported. The physical and laboratory data were consistent with the diagnosis of infantile valvular aortic stenosis. At operation, however, redundant gelatinous pedunculated tissue attached to the mitral valve annulus appeared to move through and obstruct the aortic valve during systole. The aortic valve showed only minimal thickening of the right and left coronary cusps. A distinct angiographic pattern was demonstrated during left ventricular cineangiography. In the frontal projection a large ovoid filling defect appeared to protrude through the aortic valve during systole and return to a subvalvular location during diastole. Recognition of this angiographic pattern should facilitate diagnosis and subsequent repair. Complete correction is possible by operative excision of the obstructing tissue without damaging the mitral valve. In contrast to isolated congenital infantile valvular aortic stenosis, a condition in which the valve leaflets are often primitive and deformed, aortic valvotomy and/or subsequent valve replacement are not necessary, resulting in a better long-term prognosis.


Sinus node function in children. Factors influencing its evaluation. Overdrive atrial stimulation was performed in 20 electrophysiologically normal children at the time of routine diagnostic cardiac catheterization, for the determination of the sinus node recovery time (SNRT). Measurements were made at pacing rates of 120, 150, 180, and 200 beats/min. The absolute recovery times demonstrated wide range of values (420-1280 msec). Expressed as a percent of the resting P-P interval, values at pacing rates of 120 and 150 beats/min were 109-166%, with significantly less overdrive suppression (P less than 0.001) occurring at the two faster pacing rates. Atropine diminished the maximum SNRT in all patients tested. This study reports normal values for the SNRT in children. Factors which influence the SNRT are the resting heart rate, the rate of overdrive, and the autonomic tone. In children, the sinus node recovery time should be expressed in terms of the resting sinus interval.


Histopathology of the conduction system in the sudden infant death syndrome. The cause of the sudden infant death syndrome (SIDS, crib death, or cot death) is unknown. Current hypotheses include lability of heart rate and/or rhythm as a pathogenetic factor. The conduction system of 50 infants coming to autopsy were examined by serial sections; the infants were from newborn to two years of age. Twenty-six were SIDS deaths and 24 were explained deaths (ED). The frequency of histologic abnormalities of the specialized tissue was almost identical in both groups of infants. Hemorrhage in or around different parts of the conduction system was present in 27% SIDS and 29% ED. There was no evidence of cell death or degeneration of conduction fibers, nor obstructive lesions of the atrioventricular (A-V) arteries. Apparent moulding of A-V node and His bundle was a universal finding in both SIDS and ED, and consisted of irregular interdigitation of A-V node and His bundle fibers with the myxoid central fibrous body (CFB). Isolated bundles of conduction fibers residing in CFB and membranous ventricular septum were seen in two SIDS, but no direct contact between these fibers and the working myocardium could be identified in serial sections in either case. Without corroborating antemortem electrophysiologic data, the functional significance of morphologic findings in the conduction system of SIDS must remain conjectural.


Effects of the pacing site on A-H conduction and refractoriness in patients with short P-R intervals. His bundle recordings were studied in four patients with short P-R and A-H intervals, and narrow QRS complexes, who had experienced several episodes of supraventricular tachyarrhythmias. The heart was paced from the high right atrium (HRA) and the coronary sinus (CS). In three patients the A-H Wenckebach phenomenon occurred at higher rates (greater than 200 pacing beats/min) when the CS was paced than when pacing was performed from the HRA. Moreover, CS stimulation produced smaller increments in the A-H interval than did pacing from HRA. The extrastimulus method of testing was done. In cases 1 and 2 the functional refractory period of the A-H tissues was 15 to 25 msec shorter during CS pacing than when pacing from the HRA. In case 3, the low right atrium (LRA) as well as the other two sites were paced. A type 1 gap was seen from HRA, a type 2 gap from CS, and both types appeared when the LRA was paced. Case 4, in which the mid-right atrium (MRA) was also stimulated, had a double pathway from HRA and CS with conduction through the accessory pathway late in the cycle and through the A-V node earlier in the cycle. However, the A-V node could not be penetrated during MRA stimulation. It appeared that the pacing site influenced the A-H conduction pattern and refractoriness, possibly by changing the site and/or mode of entry of the stimulus into the pathways that are responsible for this syndrome.


Prolonged His-Q interval in chronic bifascicular block. Relation to impending complete heart block. Although prolonged infra-His conduction time in bifascicular block is suspected of denoting trifascicular disease, adquate documentation is lacking concerning the correlation between lengthened His-Q interval (H-Q) and the risk of development of complete heart block (CHB). H-Q in conducted sinus beats in patients with bifascicular block associated with Mobitz II or intermittent CHB represents the approximation of maximal H-Q prolongation prior to onset of trifascicular block. To assess this relationship between prolongation of H-Q and trifascicular block, His bundle electrocardiography (HBE) was performed in 50 patients with chronic bifascicular block exhibiting Mobitz II block or transient CHB. Mobitz II or episodic CHB was shown in all patients: within two days prior to HBE in 45/50 patients; in 39/50 patients during HBE; and following HBE in five patients. In 49/50 patients H-Q was prolonged (greater than 55 msec) and in 47 this interval was substantially lengthened (65 msec or greater). Since marked H-Q prolongation in conducted sinus beats was documented in nearly all patients with bifascicular block associated with intermittent complete trifascicular block, we conclude that a considerably lengthened H-Q interval in bifascicular block is not only a usual prerequisite but strong evidence, for impending complete heart block.


Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction. In 12 anesthetized open-chest dogs, ventricular epicardial activation maps were constructed and electrograms were recorded from the bundle of His, left bundle branch, and subendocardial Purkinje fibers 24 hours following Harris 2-stage ligation of the left anterior descending coronary artery. All animals developed ectopic ventricular depolarizations and/or ventricular tachycardia. The earliest area of epicardial activation was located along the border of the infarct in the left ventricle in all animals. Bipolar recording from various levels of the conduction system and ventricular myocardium revealed that the earliest recorded electrical activity originated in subendocardial Purkinje fibers which had survived the acute myocardial infarction. The origin of these arrhythmias was further studied by pacing through the electrode which had recorded the early Purkinje activity and comparing the surface ECG and activation sequence with that of the spontaneous rhythm. These data tend to support the hypothesis that ventricular arrhythmias occurring 24-72 hours following acute myocardial infarction have their origin in the subendocardial Purkinje network which has survived the infarction.


Visualization of Ebstein's anomaly of the tricuspid valve by two-dimensional and standard echocardiography. Seven patients with Ebstein's anomaly were studied by two-dimensional echocardiography, with and without stop-action technique, and by standard echocardiography. Sagittal two-dimensional echocardiograms visualized a small functional right ventricle and a large atrialized right ventricle. These two parts of the chamber were separated by the anterior tricuspid leaflet and its chordae tendineae. The echocardiograms corresponded to the findings of the right ventriculogram. In horizontal two-dimensional echocardiograms a huge anterior tricuspid leaflet, atrialized right ventricle, and a displaced septal tricuspid leaflet, intervening between the functional right ventricle and the sinus portion of the functional right ventricle, were visualized. The origin of the septal tricuspid leaflet was clearly shown to be abnormal in five cases. The left ventricle was small with distinct clockwise rotation of the interventricular septum. Two-dimensional echocardiography provided information useful in evaluation of the functions of the right ventricle and the tricuspid valve and determination of what surgical procedure to follow.


Echocardiographic spectrum of Ebstein's anomaly of the tricuspid valve. Sixteen patients aged between one day to 18 years with Ebstein's malformation of the tricuspid valve were studied with ultrasound. The findings were compared with a group of 74 patients without Ebstein's malformation. Two features were considered specific for Ebstein's malformation: 1) ability to record the anterior tricuspid leaflet (ATL) farther to the left of the left sternal border than in the control group; and 2) abnormally prolonged interval between the "C" points of the tricuspid and the mitral valve echoes (McTcI). All other parameters measured were nonspecific for Ebstein's anomaly of the tricuspid valve. The sail sound was recorded in ten patients with Ebstein's malformation and occurred at the time when the anterior tricuspid leaflet was in the most posterior position. In a patient with congenital heart disease, an McTc interval greater than 0.03 sec and recording of an anterior tricuspid leaflet near the apex of the heart strongly suggest the diagnosis of Ebstein's malformation. These two criteria were not fulfilled in any patient who did not have Ebstein's malformation. Conversely, however, absence of these two features does not rule out Ebstein's anomaly of the tricuspid valve.


Echocardiographic assessment of bicuspid aortic valves. Angiographic and pathological correlates. Aortic root echocardiograms were recorded from 89 patients whose aortic valves had also been adequately defined by selective angiography or viewed surgically or at autopsy. The eccentricity index (E.I.) of the aortic leaflets was measured at the onset of diastole and an E.I. of 1.3 or greater was taken as abnormal. Of 31 patients with isolated nonobstruced or mildly obstructed bicuspid aortic valves (7 viewed previously at valvotomy and 24 diagnosed radiologically) 23 (74%) had an abnormal E.I. Varying eccentricity occurred in some of these patients. Central leaflet echoes (E.I. of 1.0 to 1.25) were present in the other eight patients. All 14 patients with nonobstructed tricuspid aortic valves had central echoes. Additional multilayered diastolic echoes were found in patients with bicuspid aortic valves as well as in two patients with abnormal tricuspid aortic valves. The valves of 13 patients with aortic stenosis or incompetence were viewed surgically and the E.I. was abnormal in all patients with a bicuspid aortic valve in this group. Aortic leaflet echo findings were not diagnostically helpful in ten patients with tetralogy of Fallot, one of whom had a normal E.I. with a surgically confirmed bicuspid aortic valve. Of 21 patients with VSD only one had a bicuspid aortic valve but six had an abnormal E.I. This false positive sign was related to a high membranous VSD, sometimes with aortic valve prolapse. It is concluded that an E.I. of greater than or equal to 1.3 in the absence of an associated VSD is diagnostic of a bicuspid aortic valve and can be expected to be found in approximately three-quarters of subjects with this abnormality.


Diagnosis of prosthetic mitral valve malfunction with combined echo-phonocardiography. Fifty-three patients were studied with combined echo-phonocardiography or phonocardiography alone following prosthetic valve replacement. In sixteen of these patients, clinical deterioration developed, and all subsequently underwent cardiac catheterization and/or surgery. Two patients came to autopsy. Included in this group of sixteen patients were five with obstructed prosthesis, six with paravalvular regurgitation, and five with left ventricular dysfunction. Measurements were made of the time interval from the aortic valve closure sound to the peak opening of the mitral prosthesis determined echocardiographically or to the mitral prosthetic opening click (A2-MVO). Echocardiographic studies of left ventricular wall motion were also performed. The A2-MVO interval was significantly shortened (P less than 0.01) with prosthetic valve obstruction (.05 +/- .02 sec) and paravalvular regurgitation (.05 +/- .01 sec) compared with normally functioning prostheses (Starr-Edwards ball valves .10 +/- .02 sec, Lillehei-Kaster tilting disc prostheses .09 +/- .01 sec). Shortening of this interval was not specific for these conditions because it was sometimes shortened with left ventricular dysfunction. Echocardiographic studies of left ventricular wall motion were helpful in distinguishing among prosthetic valve obstruction, paravalvular regurgitation and left ventricular dysfunction. The combined echo-phonocardiographic technique was especially helpful in detecting malfunction of tilting disc prostheses, because the technique enables measurement of the A2-MVO interval in the absence of an audible opening click.


Anatomically corrected malposition of the great arteries (S,L,D). The following is the first case of anatomically corrected malposition of the (S, L, D) type clinically diagnosed antemortem and only the second case recorded in the literature. The (S, L, D) notation indicates the segmental set of situs solitus of viscera and atria (S), ventricular l-loop (L), and d-malposition of the great arteries (D). This rare anomaly has the physiologic findings of complete d-transposition. Attempted surgical palliation was unsuccessful.


Resolution of pulmonary lymphangitic carcinoma of the breast. Pulmonary lymphangitic carcinomatosis, a grave complication of malignant neoplasms, usually progresses rapidly and is fatal despite all modes of therapy. We recently observed complete resolution of pulmonary lymphangitic involvement from an adenocarcinoma of the breast following both chemotherapy and bilateral oophorectomy. The patient's chest radiograph has remained clear for 1 1/2 years.


Streptococcal pancarditis.

Streptococcal pancarditis. An unusual association of pancarditis due to Streptococcus viridans is described. The pathologic findings appear to indicate that the myocardial infection and pericarditis were blood borne.


Congenital esophagobronchial fistula in a 62-year-old woman. A 62-year-old woman had symptoms of cough provoked by ingestion of liquids and radiologic changes compatible with repeated bouts of aspiration pneumonitis. A left bronchoesophageal fistula was easily demonstrated by barium esophagogram and fiberoptic bronchoscopy. Division of the fistula resulted in immediate disappearance of the symptoms, gradual resolution of the radiologic abnormalities, and marked improvement in the results of pulmonary function tests. The fistula appeared to be of congenital origin, but the reason that symptoms developed so late in life remains obscure.


Acute respiratory failure precipitated by a carbonic anhydrase inhibitor. A 60-year-old white man with chronic bronchitis was noted to develop acute respiratory failure and metabolic acidosis four days after being started on methazolamide (Neptazane) for an ophthalmologic problem. The patient was intubated with ventilator support and improved after his metabolic acidosis resolved. Caution is emphasized in the use of carbonic anhydrase inhibitors in patients with obstructive airway disease.


Recurrent thrombophlebitis and pulmonary emboli in congenital factor 5 deficiency. A case of congenital coagulation factor 5 deficiency is reported. Despite this defect in blood coagulation, this patient had frequent episodes of thrombophlebitis which were associated with pulmonary emboli on two occasions. Heparinization caused no hemorrhagic complications.


Esophageal obstruction due to intermuscular hematoma following pneumatic dilatation. A case of incomplete esophageal perforation with an intermuscular hematoma is presented. Unlike previously described submucosal or intramural perforations, this case involved mucosa, submucosa, and the inner circular muscle layer but was limited by the outer longitudinal layer. Nonsurgical treatment was followed when the clinical picture of an incomplete perforation without mediastinal soilage was considered. Surgery was done when evidence of impending extension of the process outside the esophagus developed.


Acute cardiomyopathy with recurrent pulmonary edema and hypotension following heroin overdosage. An 18-year-old man developed acute pulmonary edema following heroin overdose. Two days after initial improvement, there was recurrence of hypotension and pulmonary edema with severe hypoxemia refractory to mechanical ventilatory support utilizing positive and end-expiratory pressure. Cardiac catheterization revealed elevated pulmonary capillary wedge pressure suggestive of left ventricular failure. The use of digitalis and diuretics resulted in prompt clinical improvement and ultimate recovery. Evidence is presented indicating that this patient represents an uncommon but important syndrome of acute cardiomyopathy with left ventricular failure which complicates the clinical course of certain cases of heroin overdose. Its physiologic diagnosis is of obvious importance in the choice of proper therapy, thereby increasing the patient's chances of recovery.


Fluttering of the interventricular septum. The result of truncal insufficiency. We present a child with truncus arteriosus and truncal insufficiency who had diastolic fluttering of the anterior mitral valve leaflet and left ventricular surface of the interventricular septum on echocardiogram. Although the fluttering has been previously described in patients with aortic insufficiency, it has not been reported with truncus arteriosus.


Aortic valve atresia with a normally developed left ventricle. Aortic valve atresia is usually associated with hypoplasia of the left ventricle and mitral valve. We report a patient presenting aortic atresia with ventricular septal defect and a normally sized left ventricle. The electrocardiogram showed left axis deviation and left ventricular hypertrophy. The ventricular septal defect probably favored a normal growth of the left ventricle, allowing it to unload with systole.


Rate-dependent left bundle branch block with angina pectoris and normal coronary arteriograms. A 46-year-old man developed rate-dependent left bundle-branch block and angina pectoris with effort. Angina pectoris and left bundle-branch block could be provoked with treadmill exercise testing and right atrial pacing. Coronary arteriograms were entirely normal on two separate occasions. The syndrome of angina pectoris with normal coronary arteries can include rate-dependent left bundle-branch block.


Paradoxical motion of the interventricular septum in a patient with normal right heart hemodynamics. A 32-year-old man with paradoxical motion of the interventricular septum at the level of the chordae tendineae and with normal right heart hemodynamics is presented. It appears that, in absence of severe left ventricular dysfunction or intraventricular conduction defect, paradoxical septal motion is not entirely specific for right ventricular volume overload and may represent a rare normal variant.


Natural history six years after acute myocardial infarction. Is there a low-risk group? One hundred fifty-four survivors of acute myocardial infarction were observed for six years. Patients with anterior lesions had increased mortality in the acute phase of infarction, a trend not sustained during the long-term follow-up period. Recurrent myocardial infarction and intraventricular conduction disturbances were associated with relatively high short-term and long-term mortality. Four groups were defined. The high-risk group had congestive heart failure, major bundle-branch block, previous myocardial infarction, ventricular tachyarrhythmias, or second- or third-degree atrioventricular block. The low-risk group had none of these stigmata. Each category was divided into those under and over the age of 60. Only patients in the low-risk group, over 60 years of age, (24 percent) had a six-year survival comparable to the standard actuarial projections. Thus, 74 percent of the survivors of the acute phase of infarction had a six-year mortality far in excess of the general population. Some were particularly vulnerable during the first year. These findings may warrant reappraisal of the indications for diagnostic and surgical approaches to managing patients after myocardial infarction.


Diagnostic and therapeutic challenges following the cytologic diagnosis of in situ carcinoma of the lung. Clinical challenges associated with the cytologic detection of eight cases of occult pulmonary carcinoma are presented. The pulmonary lesions were successfully localized and resected in three of six cases encountered since the availability of flexible fiberoptic bronchoscopy and selective bronchial brushing. Two of the resected neoplasms were unequivocally in situ, while preoperative radiotherapy precluded accurate pathologic determination of invasiveness in the third. The reported experience with unequivocal in situ bronchogenic carcinoma localized and treated surgically prior to invasion through the basement membrane now totals 17 cases (15 previously reported). Forty-four additional cases (43 previously reported) have been localized and resected following early invasion. From this group totaling 61 occult carcinomas, only two patients (3 percent) are known to have died of pulmonary carcinoma during a followup ranging from 2 to 20 years.


Fiberoptic bronchoscopy in bronchial asthma. A word of caution. Three instances of intense laryngospasm and bronchospasm occurred as a result of fiberoptic bronchoscopic examination in three patients with quiescent bronchial asthma. The indications for the procedure were hemoptysis in one patient and lobar collapse in two. It is likely that vagally mediated reflex laryngospasm and bronchoconstriction occur when irritant receptors are mechanically stimulated by the bronchoscope. Therefore, in the asthmatic population with its increased airway reactivity, indications for fiberoptic bronchoscopy should be absolute, and the procedure should be performed under optimal conditions. A rationale for minimizing the risk of this procedure in patients with bronchial asthma is discussed.


Open pulmonary biopsy. Nineteen-year experience with 416 consecutive operations. Four hundred and sixteen open pulmonary biopsies through limited thoracotomies are reported. Tissue sufficient for diagnosis was obtained in all cases. Case selection, operative technique, spectrum of diagnoses, complications, and comparisons with other techniques are defined. Diagnoses by category were as follows: occupational, 105 patients (25 percent); neoplastic disease, 80 patients (19 percent); specific histologic diagnosis, (ie, sarcoidosis), 70 patients (17 percent); specific infection, 23 patients (6 percent); vascular diagnosis, 16 patients (4 percent); and nonspecific pulmonary disease, 122 patients (29 percent). Pneumothorax, minor in most cases, was the most common complication. It occurred in 97 (23 percent) of the patients, but only 24 (6 percent) required the placement of a chest tube. Pleural effusion occurred in 106 patients (25 percent) and was minor. Hemothorax occurred in two (0.5 percent) and superficial wound infection in three (0.7 percent). Overall mortality was 4.5 percent (19 patients). Only two deaths (0.4 percent) were related to the procedure. Open pulmonary biopsy remains our diagnostic method of choice in diffuse lung disease of undetermined etiology.


Respiratory symptoms related to smoking habits of family adults. A study of the effects of family smoking habits on the symptoms of other family members has shown that symptoms of household members, especially children, are related to smoking habits within the households but are not significantly so when symptoms in adults are controlled.


The spirographic "kink". A sign of emphysema. The significance of the "kink" occurring in the early portion of the forced expiratory spirogram of some patients with obstructed airflow was investigated in 153 patients with chronic obstructive pulmonary disease or asthma. The kink, which is presumably due to airway collapse, is facilitated by the presence of emphysema, which results in loss of elastic recoil, a positive pleural pressure, high bronchiolar resistance, and structural weakness in the walls of the major airways. A significant reduction of carbon-monoxide diffusing capacity was used as the indicator of the presence of significant anatomic emphysema. Eighty percent (39) of 49 patients with the spirographic kink had a low diffusing capacity, whereas only 16 of those without the kink had significantly impaired diffusion. Seventy percent (39) of the 56 patients who had emphysema by this criterion demonstrated a spirographic kink. This test is, therefore, offered as a simple, effective, and widely applicable screening procedure for detecting emphysema, with a low incidence of false-positive results.


Hemolysis in the aortic prosthetic valve. A review of the incidence and severity of hemolysis in the aortic prosthesis is presented. The noncloth-covered Starr-Edwards prosthetic series 1000, 1200, and 1260 had a 2 percent (1/54) incidence of anemia. The cloth-covered Starr-Edwards aortic prosthetic series 2300 was associated with anemia in 61 percent (28/46) of patients. The modified aortic prosthetic series 2310 and 2320 had a 34 percent (19/56) incidence. Mean lactic dehydrogenase levels for the series 1000, 1200 and 1260 were 184 units; 2300 series, 574 units; 2310 and 2320 series, 334 units; and the Bjork-Shiley aortic prosthesis, 166 units. Nine patients underwent repeat surgery because of refractory anemia in the 2300 series, and one did so in the 2310 series. Four of the patients with repeat surgery had significant cloth wearing of the valve. A transvalvular gradient in excess of 30 mm Hg was present in seven of ten anemic patients studied who had the series-2300 valve. The cloth-covered Starr-Edwards aortic prosthesis carries a significant risk of anemia. At the present time the 2310 and 2320 series cause less hemolysis and a lower incidence of anemia than the original 2300 series but in excess of the noncloth-covered Starr-Edwards prosthesis.


Swyer-James (Macleod's) syndrome. Variations in pulmonary-bronchial arterial blood flow. The Swyer-James (Macleod's) syndrome (or unilateral hyperlucency of the lung) frequently presents a diagnostic problem. Two cases of this entity are reported that demonstrate its similarity to and differentiation from pulmonary embolism and other intrapulmonic disorders. Detailed roentgenologic and physiologic studies were performed to define the diagnostic criteria of this syndrome. The reciprocal relationship of the bronchial arterial circulation in the hyperlucent lung was described.


The esophageal obturator airway. A clinical evaluation. The esophageal obturator airway (EOA) has been considered a useful ventilatory technique for cardiopulmonary resuscitation, but quantitative analysis of its clinical effectiveness is not available. We evaluated the EOA in 18 patients who had suffered prehospital cardiac arrest and who were resuscitated by mobile intensive care unit paramedics employing an EOA. Arterial blood gas determinations were obtained during ventilation with the EOA and then repeated after endotracheal intubation. Arterial oxygen tension (PaO2) greater than 64 mm Hg was achieved in 11 of 12 patients who had been converted to supraventricular rhythm, despite varying inspired oxygen concentrations. A PaO2 greater than 77 mm Hg was achieved in three of six patients still requiring external cardiac massage. There was little or no improvement in oxygenation after endotracheal intubation, implying that the failures to oxygenate were not due to the EOA. We conclude that the EOA is a useful adjunct during cardiopulmonary resuscitation when endotracheal intubation is not feasible.


Echocardiography in Marfan's syndrome.

Echocardiography in Marfan's syndrome. Echocardiographic examinations were performed in 26 patients with clinical evidence of Marfan's syndrome. Twelve patients were demonstrated to have isolated dysfunction of the mitral valvular apparatus of varying severity. Four patients demonstrated involvement of the aortic root as well as mitral valvular abnormalities, and six patients had problems involving the aortic root only. Four patients had no demonstrable cardiac abnormalities. Therapeutic decisions which could previously have been made with confidence only on the basis of cardiac catheterization with angiocardiographic studies were made by ultrasonic evaluation.


Pulmonary veno-occlusive disease. Entity or syndrome? Pulmonary veno-occlusive disease is a rare and usually fatal condition in which there is gradual obliteration of the pulmonary veins and venules. Without a lung biopsy the clinical diagnosis of this disease is difficult. If there is pulmonary hypertension with roentgenographic signs of pulmonary edema and of congestion in the absence of signs of increased left atrial pressure, the diagnosis must be considered. The morphologic picture of the lungs is characteristic. The small veins, and sometimes also the major veins, are narrowed or occluded by fibrous tissue, almost certainly on the basis of organized thrombi. Nodular areas of congestion, interstitial fibrosis, and pneumonitis are regularly present. A viral etiology has been suggested in a number of cases. If we may assume, however, that thrombosis of pulmonary veins is the initial event, the possibility has to be considered that this may be elicited by a virus in some patients and by toxic factors or by clotting disorders in others. Pulmonary veno-occlusive disease might then well be a syndrome rather than an etiologic entity.


Plasma enzyme levels in the anaesthetised dog during drainage of thoracic duct lymph. The effect of continuous removal of thoracic duct lymph on plasma activities of creatine phosphokinase (PCK), glutamic-oxaloacetic transaminase (PAST); and lactic dehydrogenase (PLDH), uas examined in pentobarbital-anaesthetised dogs over a 5.5-hour period. PCK and PAST declined relative to levels in control dogs while PLDH was unaltered. Lymph/plasma (L/P) ratios for AST and CPK were greater, and for LDH less, than the L/P ratio for total protein. It was concluded that PCK, and to some extent PAST, are normally maintained by introduction of enzyme, escaping from the intracellular compartment, into the circulating blood via the lymphatic system. PLDH and PAST appear to be maintained principally by introduction of enzyme directly from the intracellular to the plasma compartment.


A comparison of the ATP: L-methionine-S-adenosyltransferase of rat cerebral cortex and cerebellum. The ATP: L-methionine-S-adenosyltransferase of rat cerebral cortex and cerebellum was found to be differentially responsive to solubilization by sodium deoxycholate. Furthermore, the cerebellar enzyme was markedly less sensitive to inactivation by deoxycholate and to storage at 4 degrees C. The specific activity of the cerebellar enzyme was significantly higher and the two enzyme activities also exhibited differences in apparent Km values for L-methionine.


Changes in biochemical properties of myocardial lactate dehydrogenase during exposure of rats to high altitude. Exposure of normal rats to chronic natural hypoxia has shown the following effect upon catalytic properties of myocardial lactate dehydrogenase (LDH): significant increase of the two substrates pyruvate and lactate in tissue extracts; no changes in electrophoretic patterns of the enzyme; a slight enhancement of the activation energy of enzyme molecules; a significant increase in the Michaelis constant for pyruvate. Variations in biochemical properties of LDH appear after 12 ueeks of life in high altitude environment. These adjustments may be related to the stimulation of anaerobic metabolism induced by altitudinal hypoxia. Changes in LDH biochemical parameters seem adaptative.


An experimental study of acute and chronic effects of phenacetin on the rat kidney, using clinical-chemical and biochemical methods. In rats, changes in urinary enzymatic activities (AP, SP, LAP, beta-GLU, MUR) were recorded following the administration of phenacetin in acute doses (4.75 and 7.15 mmol/kg). Urinary AP and LAP activities were measured over 77 days in which 3.35 mmol phenacetin/kg were given daily. The results revealed immediate and delayed effects of phenacetin, depending upon the quality of the drug used. In the chronic series, changes in urinary enzymatic activities were less pronounced. Concomitant biochemical investigations of kidney cell fractions revealed the occurrence of mitochondrial damage under the influence of chronic phenacetin administration. Following acute doses of phenacetin, destructive alterations in the plasma membrane of kidney cells were encountered. Investigations of serum enzymatic activities 24 h after phenacetin administration did not reveal any significant changes.


Sleeping behavior and associations in a group of captive chimpanzees. The present study investigated the sleeping behavior and preferences of a group of six adolescent chimpanzees at the Delta Regional Primate Research Center in Louisiana, USA. The study sought to relate sleeping partner preferences to other aspects of social relationships. Comparative observations between those chimpanzee behaviors seen in the wild and in this group are noted.


Observations on a small group of mountain gorillas (Gorilla gorilla beringei). On the basis of a 5-month field study, data are presented on home range, patterns of daily movement and social behaviour in a small free-living gorilla group. Changes in group composition that occurred during the study are analysed with special reference to their effect on inter-individual distance. The relationships with other groups  and lone individuals whose home ranges overlapped with that of the group studied are examined on the basis of intergroup contacts.


Metastasis of cancer to cancer: report of a case. A case of primary, widely disseminated prostatic carcinoma causing bilateral urinary tract obstruction, hydronephrosis, and papillary necrosis and metastasizing in the substance of an unusual histologic variant of renal cell carcinoma and tubular adenoma of the same kidney is presented. Unusual incidental findings include isolated cardiac amyloidosis and myocardial abscesses. A brief review of the literature is presented. The peculiar tendency for renal cell carcinoma to be the host tumor for other primary carcinomas and various theories to account for this phenomenon are commented upon briefly.


Aging changes in the human aortic valve in relation to dystrophic calcification. To elucidate the pathogenesis of aging changes and their relation to age associated calcification, a morphological study of 27 human aortic valves was carried out. Nine valves were obtained from immediate autopsies and 18 valves from routine autopsies done within four hours after death. Calcium deposition was present deep in the zona fibrosa along a zone of lipid accumulation. Fibrocytes in the zona fibrosa showed predominant age associated changes, i.e., a massive accumulation of residual bodies in the cytoplasm probably derived from autophagic vacuoles. Light microscopic lipid accumulation corresponded with both intracellular accumulation of electron dense spherules and membranous vesicles derived from degenerate fibrocytes. Calcium deposition in various stages, including needle shaped hydroxyapatite crystals, was seen in close association with these cellular degradation products rather than collagen or elastic fibers. Dystrophic calcification in the aortic valve appears to result from cellular aging and death followed by petrification of cellular degradation products, which may progress to calcific aortic stenosis.


Hemangiopericytoma. An analysis of 106 cases. A series of 106 cases of hemangiopericytoma was analyzed. The neoplasms occurred principally in adults (median age, 45 years), were deep seated, and were most common in the thigh (27 cases) and the pelvic retroperitoneum (26 cases). A painless mass was the first symptom in 96 of the patients. The median size of the excised tumors was 6.5 cm. Surgical removal of the tumor was often complicated by hemorrhage because of marked dilatation of the vascular bed in the vicinity of the neoplasm, probably as the result of rapid exchange of blood from the arterial to the venous circulation within the tumor. Microscopically, benign and malignant forms could be distinguished. The latter were characterized by increased cellularity, prominent mitotic activity, and foci of necrosis or hemorrhage. Follow-up information was obtained in 93 cases. Seventy-one of the 93 patients were living (two with recurrence and four with metastasis), and 22 had died (13 as the result of recurrence or metastasis in more than two-thirds of the related causes). Recurrence preceded metastasis in more than two-thirds of the patients with evidence of metastasis. The 10 year survival rate was 70 per cent. The morphologic differences from other mesenchymal tumors showing a hemangiopericytoma-like vascular pattern are discussed, and the close resemblance of hemangiopericytoma to richly vascular forms of fibrous histiocytomas and synovial sarcoma is emphasized. Congenital or infantile hemangiopericytoma is described as a separate entity having a distinctive microscopic pattern and behavior.


Effect of room fluorescent light on the deterioration of tissue culture medium. A major cause of tissue culture medium deterioration is exposure to room fluorescent light. Riboflavin and tryptophan present in Dulbecco's modified Eagle's minimum essential medium, when exposed to light, yield toxic photoproducts responsible for loss of the ability of the medium to support clonal growth of human, mouse and Chinese hamster cell lines. Procedures for minimizing medium deterioration are discussed.


Effects of steroid hormones in fetal bovine serum on plating ang cloning of human cells in vitro. Fetal bovine sera from each of three different commercial sources were tested for their ability  to support cloning of human fibroblastoid cells in vitro. Cloning efficiencies  varied according to serum source. Serum (10 samples) from company A did not support growth, while sera (10 samples) from companies B and C provided adequate to excellent conditions for cloning and growth. Cells from neonatal foreskin or embryonic lung responded to each serum similarly. Bovine serum albumin type H7 from company C supported cell growth in media without serum. Sera containing 1.0 ng per ml or more of progesterone inhibited growth, whereas sera containing less than 1.0 ng per ml supported cloning and growth. In the low progesterone sera, the concentration of 17-beta-estradiol exceeded 100 pg per ml. Growth supporting sera could be made non-supportive by adding 0.1 mug per ml of progesterone. The addition to non-supporative sera of 0.1 mug per ml of 17-beta-estradiol or hydrocortisone made these sera supportive of cell growth. Addition of estrogen or hydrocortisone to a culture medium that inhibits growth, with subsequent reversal of the inhibitory effect, implies that these hormones competitively regulate growth of responsive cells in vitro.


Primary structure of a high potential iron-sulfur protein from the purple non-sulfur photosynthetic bacterium Rhodopseudomonas gelatinosa. The third amino acid sequence of a high potential iron-sulfur protein, that of the non-sulfur purple photosynthetic bacterium Rhodopseudomonas gelatinosa, has been determined. It consists of a single polypeptide chain of 74 amino acid residues, which is slightly smaller than the high potential iron-sulfur proteins from the sulfur purple bacteria Chromatium vinosum (85 residues) and Thiocapsa pfennigii (81 residues). The sequence of the gelatinosa protein is similar to the C. vinosum and T. pfennigii proteins with 38% and 37% identically matching residues, although six gaps are proposed for the comparison (the C. vinosum and T. pfennigii proteins have 44% identically matching residues out of 73 positions compared with only one 4-residue gap). Only 17 redisues, including the 4 cystein residues essential for binding the four-iron-sulfur chromophore, are invariant in the three known sequences. A discussion of the role of conserved residues in maintenance of the three-dimensional structure and in electron transport is presented.


Effects of anti-insulin serum, insulin, and glucose on output of triglycerides and on ketogenesis by the perfused rat liver. The rate of change of the concentration of various metabolites in blood in vivo and of the metbolism of free fatty acids by the perfused liver in vitro was sutidied as a function of time after the induction of acute insulin deficiency in rats by administration of guinea pig anti-insulin serum; the rate of reversal of these changes afte treatment of the anti-insulinserum diabetic ratss with insulin was also investigated. The concentrations of blood glucose and ketonebodies, and plasma-free fatty acids increased rapidly after injection of anti-insuli serum, while plasma triglycerides increased more slowly. These alterations were restored rapidly toward normal after treatment of the diabetic animals with insulin...