Effect of bethanechol, gastrin I, or cholecystokinin on myoelectrical activity.

The purpose of this study was to determine the effect of bethanechol, gastrin I, or the octapeptide of cholecystokinin (CCK-OP) on the smooth muscle of the isolated cat colon. Myoelectrical activity was recorded with monopolar glass-pore electrodes. Slow-wave frequency was 5.9 +/- 0.2 cycles/min during the basal period. Slow waves were generally coupled during the control period and the apparent propagation velocity was predominantly aborad at a velocity of 3.8 +/- 0.4 mm/s. Spike activity was superimposed on 11.9 +/- 1.5% of the slow waves during the control period. Bethanechol stimulated a dose-dependent increase in colonic spike activity, with a threshold concentration of 10(-7) M. Bethanechol did not alter the congruence of the colonic slow-wave frequency at any concentration. Gastrin I or CCK-OP increased colonic spike activity. The threshold concentrations for gastrin I and CCK-OP were 2 X 10(-11) M and 4 x 10(-11) M, respectively. Unlike bethanechol, gastrin I (2 X 10(-9) M - 2 X 10(-8) M) and CCK-OP (4 X 10(-9) - 4 X 10(-8) M) altered slow-wave frequency and decreased slow-wave congruence. These studies suggest that 1) bethanechol, gastrin I, or CCK-OP increases colonic spike activity, and 2) only gastrin I or CCK-OP alters the slow-wave frequency of colonic muscle. Thus neurohumoral substances may act independently on colonic spike activity and colonic slow-wave frequency.


Peristalsis in distal colon of the rabbit: an analysis of mechanical events.

The mechanical behavior of isolated segments of rabbit distal colon was studied by experimental and theoretical techniques. The isometric isovolumic preparation was adopted to obtain records of endoluminal pressure, force, and wall morphology during 59 spontaneous and 53 electrostimulated peristaltic contractions. On strips of longitudinal and circular muscle, excised from the same segments, the tension-velocity and tension-length relationships were also measured. To describe mechanical events occurring during propulsion, a mathematical model was developed that incorporates the measured characteristics of the muscle. In response to given waveforms for the activation of the two muscular coats, the solution of model equations provides the time courses of pressure, force, and wall morphology. A number of parameters measured in the experimental contractions (e.g., pressure and force peaks, time lag between the stimulus and the peaks, velocity of progression of the peristaltic wave) were compared with model outputs, and a similar pattern of response was found. Therefore the model made it possible to relate segment and strip experimental data and to investigate the temporal and quantitative relationship between the contraction of longitudinal and circular layer.


Anomalous calcium secretion in rat ileum: role of paracellular pathway.

The mechanism of apparent calcium secretion by unstripped rat ileum in vitro has been investigated using mannitol and polyethylene glycol (mol wt 900) as markers for extracellular transepithelial flux. In the absence of electrochemical gradients between the mucosal and serosal bathing media in a modified Ussing chamber, net fluxes of both mannitol and polyethylene glycol were observed from serosa to mucosa in the presence of 11 mM D-glucose. Mucosal-to-serosal calcium flux reveals a significant cellular component, but serosal-to-mucosal calcium permeability is a linear function of mannitol permeability, suggesting an exclusively extracellular route. For the mucosal-to-serosal fluxes, inhibition of calcium flux by 1 mM N-ethylmaleimide results in a calcium-to-mannitol permeability ratio indistinguishable from that measured for serosal-to-mucosal flux. This evidence suggests that the apparent calcium secretion observed at 10 mM medium calcium is not the result of a cellular secretory mechanism. It is proposed that a hydrostatic driving force generated internal to the tissue but external to the cells results in net calcium secretion at calcium conentrations that saturate the cellular absorptive mechanism.


Role of pancreatic polypeptide in canine gastric acid secretion.

The interrelationships of canine pancreatic polypeptide (cPP) and gastric acid secretion were studied in dogs following infusion of histamine or pentagastrin. Pentagastrin stimulated gastric acid release 30-fold and simultaneously increased plasma cPP secretion by an average of 120 pg/ml. Although histamine stimulated gastric acid secretion to a comparable degree, it had no effect on plasma cPP levels. Three mechanisms of inhibition of acid secretion (cimetidine, duodenal acidification, and somatostatin) had different effects on pancreatic polypeptide (PP) levels. With a background infusion of pentagastrin, cimetidine did not affect cPP levels. In contrast, somatostatin dramatically inhibited both gastric fistula output and cPP release. Finally, a 10-min duodenal irrigation with 0.1 N HCl resulted in a brief spike in cPP levels (from 266 +/- 12 to 347 +/- 31 pg/ml) at the time of greatest inhibition of histamine-stimulated acid secretion. Infusions of histamine + porcine pancreatic polypeptide (pPP) at concentrations of 1.0 and 2.25 microgram/kg per h and of pentagastrin + pPP at 2.25 microgram/kg per h closely simulated postprandial cPP levels (mean 1306 +/- 18 pg/ml at 30 min) but produced no change in gastric fistula output. These studies demonstrated that PP levels and rates of gastric acid secretion are unrelated and that at physiologic concentrations PP plays no significant role in the regulation of gastric acid secretion.


Effect of adrenal arterial infusion of P-113 on aldosterone secretion in Na-deficient sheep.

To examine the role of the renin-angiotensin system in aldosterone regulation, P-113 ([Sar1,Ala8]angiotensin II) was infused into the arterial blood supply of the transplanted adrenal gland in conscious sheep. Effects on the aldosterone response to infused angiotensin II and III in sodium-replete sheep were compared with effects of P-113 on aldosterone secretion in sodium deficiency. P-113 infusion up to 1,000 microgram/h for 1-2 h did not consistently alter aldosterone secretion in sodium-deficient sheep. However, in sodium-replete sheep P-113 infusion for 20 min at 10 microgram/h or more abolished aldosterone responses to high blood levels of angiotensin II and III produced by systemic intravenous or adrenal intra-arterial infusion. P-113 infusions alone had minor agonist activity on aldosterone secretion in sodium-replete sheep. These results indicate that the increased secretion of aldosterone in Na-depleted sheep is not simply and commensurately determined by increase of angiotensin II and III concentration in the arterial blood perfusing the adrenal gland.


Effects of parathyroid hormone on electrolyte transport in the hamster nephron.

Recollection micropuncture and clearance studies were carried out on thyroparathyroidectomized hamsters to clarify the localization of the effects of parathyroid hormone (PTH) on renal electrolyte transport. The clearance data confirmed that PTH inhibits phosphate and enhances calcium and magnesium reabsorption. These effects appeared to result from actions of the hormone in several parts of the nephron. In the proximal tubule PTH did not affect H2O reabsorption but inhibited phosphate reabsorption ((TF/P)PO4 increased from 0.46 +/- 0.04 to 0.57 +/- 0.03, P less than 0.02) and appeared to enhance calcium and magnesium reabsorption ((TF/UF)Ca decreased from 1.41 +/- 0.07 to 1.25 +/- 0.06, P less than 0.001, and (TF/UF)Mg from 1.66 +/- 0.10 to 1.51 +/- 0.08, P less than 0.05; in control animals (TF/UF)Ca increased from 1.51 +/- 0.10 to 1.65 +/- 0.11, P less than 0.01). PTH further inhibited phosphate reabsorption and enhanced calcium and magnesium reabsorption between the late proximal and early distal sites of puncture. Comparison of fractional deliveries of calcium and magnesium from the late distal tubule with their fractional excretions suggests an additional effect beyond the distal puncture site. The phosphaturic, but not the calcium- and magnesium-retaining, effects of PTH were abolished by a 16-h fast.


Renal handling of calcium: influence of parathyroid hormone and 1,25-dihydroxyvitamin D3.

The influence of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the renal Ca handling was studied in vitamin D-replete rats. The relation between plasma concentration ([Ca]P) and urinary Ca (UCaV/ml GF) was ascertained by clearance techniques over the [Ca]P range of 1.4-3.4 mM varied by infusion of Ca gluconate. Chronic thyroparathyroidectomy (TPTX) decreased the plasma Ca threshold from about 2.3 to 1.5 mM. Between [Ca]P 1.4 and 3.4 mM there was a linear increase in UCaV/ml GF corresponding to 35-50% of the increment in filtered load. In TPTX, PTH (2.5 IU/h i.v.) shifted the Ca threshold from 1.5 to 2.3 mM, without changing the slope of UCaV/ml GF on [Ca]P. The effect of TPTX on the renal Ca handling was not corrected by doses of 1,25(OH)2D3, which increased the intestinal Ca absorption of TPTX rats to normal level. In intact and TPTX rats disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given at doses which inhibit the production of 1,25(OH)2D3 did not change the tubular Ca handling. Furthermore, 1,25(OH)2D3 had no effect in EHDP-treated TPTX rats. Therefore, tubular Ca handling does not appear to be altered in response to chronic endogenous variation or physiologic supplementation of 1,25(OH)2D3 in vitamin D-replete rats. This is in contrast to the marked alteration observed after TPTX or PTH administration.


Voltage dependence of calcium transport in the thick ascending limb of Henle's loop.

Thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen-to-bath and bath-to-lumen were measured with 45Ca using different solutions that caused the transepithelial voltage to vary over a wide range. With lumen-positive voltages there was net calcium absorption from lumen to bath which varied directly with the voltage. With voltage near zero there was no measurable net flux. When the voltage was made negative, the direction of net calcium transport reversed (i.e., secretion from bath to lumen). The presence or absence of bicarbonate in the lumen did not affect the calcium fluxes. Calcium permeability, calculated from the dependence of net flux on voltage, was 7.7 x 10(-6) cm/s, which is approximately 25% of the sodium permeability previously determined in this segment. Analysis of the calcium flux ratios revealed interdependence of the bidirectional fluxes consistent with single-file diffusion but no evidence for active calcium transport. We conclude that there is an important component of passive net calcium transport driven by the voltage in this segment.


Effects of inhibitors in lumen on PAH and urate transport by isolated renal tubules.

Effects of the presence of unlabeled p-aminohippurate (PAH) or urate, probenecid, and phenol red in the lumen on labeled PAH or urate transport by isolated, perfused snake (Thamnophis spp.) proximal renal tubules were studied. Net secretion of labeled urate and luminal membrane permeability to urate were unaffected by the presence of unlabeled urate (up to 0.1 mM) or probenecid (up to 1.0 mM) in lumen only. The data are compatible with movement of urate from cells to lumen during urate secretion by a simple passive process. Net secretion of labeled PAH was rapidly and reversibly depressed to about 25-35% of control when unlabeled PAH (0.05 mM), phenol red (0.05 mM), or probenecid (0.1 mM) was added to the lumen only. During maximum depression of PAH transport, luminal membrane permeability to PAH was reduced by 60-70%. The data suggest that movement of PAH from cells to lumen down an electrochemical gradient during PAH secretion occurs by a readily inhibited, mediated process.


Effect of parathyroid hormone on bicarbonate absorption by proximal tubules in vitro.

The effect of parathyroid hormone on bicarbonate absorption was tested in rabbit proximal renal tubules perfused in vitro. In proximal straight tubules 0.05 U/ml of parathyroid hormone caused a large and reversible increase in the steady-state bicarbonate concentration in tubule fluid. Further, the rates of bicarbonate and fluid absorption (measured at faster flow rates) were inhibited approximately 50% by the hormone. We conclude that parathyroid hormone directly inhibits fluid and bicarbonate absorption by proximal straight tubules, causing an increase in the bicarbonate concentration in the tubule fluid, and we suggest that this action of the hormone contributes to the increase in renal bicarbonate excretion that is generally caused by the hormone. In proximal convoluted tubules, parathyroid hormone was previously demonstrated by other investigators to inhibit fluid and bicarbonate absorption approximately proportionally, so that there was little or no change in the bicarbonate concentration in tubule fluid. In agreement we found in the present studies that 0.05 U/ml of the hormone did not affect the steady-state bicarbonate concentration in proximal convoluted tubule fluid and that 5 U/ml caused only an equivocal increase in tubule fluid bicarbonate concentration.


Dissociation of proximal tubular glucose and Na+ reabsorption by amphotericin B.

The effect of amphotericin B on glucose and Na+ transport was studied in the Necturus proximal tubule and in microvillus membrane vesicles isolated from the rabbit renal cortex. In the Necturus experiments, the rate constants for disappearance of radiolabeled glucose (kG) and mannitol (kM) from the tubular lumen were determined by stop-flow microperfusion. Saturability and Na+-dependence of glucose reabsorption was confirmed, since kG was reduced by raising intratubular glucose from 1 to 5 mM or by replacing intratubular Na+ with choline. Neither maneuver affected kM. Intratubular amphotericin B (10 microgram/ml), previously shown to stimulate active Na+ reabsorption in the Necturus proximal tubule, inhibited kG with no effect on kM. In the membrane vesicle preparation, amphotericin inhibited the uphill glucose uptake which results from imposing a NaCl gradient from outside to inside, but had no effect on glucose uptake in either the absence of Na+ or in the presence of Na+ when there was no Na+ gradient. Amphotericin B stimulated the uptake of Na+ by the vesicles. The observed dissociation of glucose and Na+ transport by amphotericin B is consistent with the concept that proximal tubular glucose reabsorption is energized by the luminal membrane Na+ gradient and is not directly linked to active Na+ transport per se.


Amino acid content of rat renal cortex and the response to in vitro incubation.

The concentration of aspartic acid, threonine, serine, glycine, and alanine is significantly higher in newborn rat renal cortex than in the adult tissue, while phenylalanine and histidine are higher in the adult. When adult cortical slices are placed in bicarbonate buffer at room temperature for 20 min there is a 30-60% decrease in the levels of all amino acids except for lysine, which is slightly higher, and methionine and serine, which do not change. Under the same conditions, newborn cortical slices reveal a similar decrease in only glycine, tyrosine, histidine, and the branched-chain amino acids. On subsequent in vitro incubation of the cortical slices at 37 degrees C for 120 min the concentrations in adult tissue remain at the lower values observed on removal from buffer at room temperature except that glutamic acid, glycine, and lysine levels decrease further and serine increases to the concentration found in fresh tissue. Newborn tissue when incubated at 37 degrees C for 120 min shows amino acid concentrations comparable to unincubated fresh tissue for all except aspartic acid, glutamic acid, serine, and phenylalanine, which reach levels higher than unincubated tissue. The ability of newborn tissue to maintain amino acid pools may play a role in the enhanced transport of some amino acids resulting from preincubation at 37 degrees C (Reynolds et al. Science 184: 68-69, 1974; Reynolds and Segal, Biochim. Biophys. Acta 406: 513-525, 1976).


Use of mass spectrometer to measure CO2 and O2 fluxes in voltage-clamped epithelia.

A quadrupole mass spectrometer was coupled to an Ussing chamber in order to evaluate rates of oxidative metabolism in voltage-clamped epithelia. Well-defined mixing characteristics of the continuously perfused chamber allowed CO2 and O2 concentrations to be related to rates of CO2 efflux, JCO2, and oxygen influx, JO2. The use of a model tissue to simulate step changes in JCO2 validated the treatment, with response within a minute. Monitoring of metabolism was facilitated by use of a desk-top computer, which evaluated JCO2 at 6-s intervals. Concurrent measurements of electrical current and JCO2 were made in the toad urinary bladder in order to relate active sodium transport to metabolism; the use of amiloride to eliminate active transport and the associated metabolism then allowed evaluation of the rates of active Na transport (JNa) and suprabasal metabolism (JsbCO2), and their ratio JNa/JsbCO2. We report the ability to resolve a 5 pmol/s change in CO2 efflux or an 11 pmol/s change in O2 influx rates.


A new needle-type colloid osmometer for continuous determination of blood oncotic pressure.

For the purpose of facilitating measurement of colloid osmotic pressure of body fluids, a new needle-type colloid osmometer which uses a hollow fiber as a semipermeable membrane instead of a sheet ultrafilter was developed. The simple construction, easy production, and satisfactory performance of the osmometer are described in detail. Although hydrostatic pressure existing in the sample interfered a little with the accuracy of measurement, quickly interchangeable sensing probes brought great advantages in practice.


Microvascular responses to norepinephrine in renovascular and spontaneously hypertensive rats.

Closed-circuit television microscopy was used to quantitate the responses of in vivo small arteries (50-140 micrometer diam) and veins (95-265 micrometer) to topically applied norepinephrine in the cremaster muscle of four groups of urethan-chloralose anesthetized rats. The rat groups were: Sprague-Dawley control (SDC), Sprague-Dawley renovascular hypertensive (RVH), Wistar-Kyoto control (WKY), and spontaneous hypertensive (SHR). The cremaster muscle with intact circulation and innervation was suspended by sutures in a 60-ml bath of bicarbonate-buffered Krebs solution. The vascular responses to the addition of progressively higher concentrations of norepinephrine to the bath were quantitated to obtain concentration-response curves. We found that the RVH (vs. SDC) had a decreased small-artery control diameter and decreased sensitivity to norepinephrine, whereas the SHR (vs. WKY) had tachycardia and decreased small-vein control diameter. Thus, the microvascular characteristics of these two types of hypertension appear to be quite different.


Effects of sympathetic nerves on cerebral blood flow in awake dogs.

Although cerebral blood vessels are densely innervated by sympathetic nerve fibers, the functional significance of the nerves is controversial. Because previous studies have been primarily performed in anesthetized animals, it is possible that failure to observe prominent neural control of the cerebral circulation was secondary to anesthetic-induced depression of the sympathetic nervous system. Therefore, we studied sympathetic control of the cerebral circulation in 11 awake chronically instrumented dogs. Total and regional cerebral blood flow was measured with 15-micrometer microspheres at control blood pressure and during three levels of progressive hemorrhagic hypotension. Sympathetic nerves had only a small effect (11% decrease; P less than 0.05) on flow to the cerebrum during moderate hypotension (mean arterial pressure 49 +/- 2 mmHg). Also, during severe hypotension, there was a bilateral redistribution of brain blood flow that tended to preserve flow to the medulla. Although these studies suggest that sympathetic nerves have a definite constrictor effect on cerebral vessels, the data support the concept that the functional importance of sympathetic nerves to cerebral vessels is limited.


Renal effects of left atrial distension in dogs with chronic congestive heart failure.

The renal response to left atrial balloon inflation in normal dogs was compared with that in dogs with chronic congestive heart failure (CHF). CHF was induced by the production of an aortocaval fistula below the level of the renal arteries. CHF dogs showed elevated left ventricular end-diastolic pressure, enlarged hearts, a depression of myocardial contractility, pulmonary edema, ascites, and peripheral edema. They also showed significant decreases in urine flow, creatinine clearance, para-aminohippurate clearance, sodium and potassium excretion, fractional sodium excretion, osmolar clearance, arterial blood pressure, and heart rate. Balloon distension of the left atrium evoked a significant increase in urine flow and free-water clearance in the normal group. The reflex nature of this response was indicated by its blockade after bilateral cervical vagotomy. In contrast, the CHF group did not exhibit significant changes in urine flow or free-water clearance during balloon inflation. Plasma antidiuretic hormone (ADH) was significantly elevated in the CHF group; however, balloon distension reduced plasma ADH in both groups of dogs. Plasma renin activity was significantly elevated in the CHF dogs and was not changed by balloon distension in either group of dogs. It is concluded that animals with high-output CHF do not exhibit the atrial-diuretic reflex in spite of their ability to reduce ADH levels by atrial distension.


Effect of tetrodotoxin on action potentials of the conducting system in the dog heart.

Tetrodotoxin (TTX) shortens Purkinje fiber action potential duration (APD) at concentrations (greater than or equal to 3.3 x 10(-8) M) lower than that at which the maximum rate of rise decreases (approximately 10(-6) M). The shortening effect of TTX occurs either at low or high driving rate and is much greater in Purkinje fibers than in bundle branch and muscle fibers. As a result, at a TTX concentration of 1.3 x 10(-6) M, the APD is no longer statistically different all along the conducting system, i.e., the gating mechanism described by Myerburg et al. (Circ. Res. 26: 361-378, 1970) is suppressed. It is concluded that this gating mechanism is attributable, at least in part, to the existence of a TTX-sensitive inward sodium current lengthening the plateau of the Purkinje fiber action potential. Our experimental results and reconstruction of Purkinje fiber action potentials suggest that this current, which is more sensitive to TTX than the normal rapid sodium current, flows through a background sodium conductance or/and a small proportion of sodium channels with no inactivation mechanism (or inactivation mechanism different from normal). The importance of this finding for the mechanism of action of antiarrhythmic drugs is pointed out.


Cardiac performance: independent effects of inotropy and preload at high heart rate.

Linear relationships between stroke volume (SV) and heart rate (HR) were observed during right atrial pacing in open-chest dogs at control inotropy, during intravenous isoproterenol infusion and during blood volume expansion by saline infusion at HR exceeding 150 beats/min. The slope of these relationships remained constant during variations in inotropy, but rose during blood volume expansion. Myocardial chord lengths in the anterior left ventricular wall were continuously recored by ultrasonic technique to estimate left ventricular volume. When heart rate was increased, end-diastolic volume decreased more rapidly after than before blood volume expansion, explaining the increased slope of the SV/HR relationship. The end-diastolic volume and the SV/HR relationship were not influenced by changes in inotropy. After blood volume expansion by 57 +/- 13%, control end-diastolic volume was reestablished by increasing heart rate 84 +/- 20 beats/min. At identical end-diastolic volume, SV was equal at different HR. Thus, the effects on SV of changes in preload and inotropy are separable during right atrial pacing, and SV is independent of HR at constant preload and adrenergic stimulation.


Lack of fibrin formation in exercise-induced activation of coagulation.

Strenuous physical exercise leads to a significant shortening of blood clotting in various test systems. Such short times are also characteristic of those observed in sedentary patients with thrombosis or disseminated intravascular coagulation, and of those observed in experimental animals after thrombin infusion. The patients exhibit an increase in circulating fibrinopeptide A, which is attributed to thrombin action on circulating fibrinogen, and to an increase of fibrinogen degradation products, which is thought to indicate reactive fibrinolysis. To check whether physical exercise leads to fibrinemia, 10 healthy male volunteers were subjected to strenuous exercise on a bicycle ergometer. Blood samples were taken immediately before and on completion of the exercise period. Despite a significant shortening of the activated partial thromboplastin time, the thrombin time, and the Reptilase time, no increase of fibrinopeptide A could be demonstrated and the ethanol gelation test remained consistently negative. Simultaneously, the euglobulin lysis time was significantly shortened, whereas the fibrin(ogen) degradation products did not increase. The results indicate that the shortening of the coagulation times associated with physical exercise must be explained by mechanisms other than thrombin-mediated conversion of fibrinogen to fibrin.


Effect of DOCA-NaCl hypertension on pre- and postcapillary resistance in isolated hindlimbs of dogs.

Measurements of precapillary resistance (Ra), postcapillary resistance (Ra), postcapillary resistance (Rv), capillary filtration coefficient (Kf), and mean capillary hydrostatic pressure (Pci) were made during constant-flow perfusion of isolated hindlimbs from control and deoxycorticosterone acetate (DOCA)-NaCl-treated hypertensive dogs by the isogravimetric method. Both Ra and Rv were found to be significantly increased in the hypertensive group, even after maximal vasodilatation with papaverine. The net decreases in Ra and Rv following papaverine infusion were not significantly different between control and hypertensive animals. These results suggest that the observed increases in Ra and Rv were due to structural adaptation (increased wall-to-lumen ratio). Nonpapaverinized hindlimbs from hypertensive dogs exhibited a significant 40% reduction in Kf, suggesting that capillary surface area for fluid exchange was decreased. The compliance of the hindlimb vascular bed was found to be significantly decreased in the hypertensive group. Pci of both groups of hindlimbs were not different between groups and was not affected by papaverine. This result suggests that net capillary permeability to plasma proteins in this preparation was not changed by hypertension.


Cardiovascular actions of beta-phenylethylamine.

beta-Phenylethylamine increased mean aortic blood pressure, total peripheral vascular resistance, left ventricular dP/dt, and (dP/dt)/P in chloralose-anesthetized dogs. Pretreatment with phentolamine reduced the increases in aortic blood pressure and total peripheral vascular resistance produced by beta-phenylethylamine, whereas, the effects of beta-phenylethylamine on left ventricular dP/dt and (dP/dt)/P were abolished by propranolol. beta-Phenylethylamine pretreatment, but increased both after phentolamine pretreatment. Furthermore, both the cardiac and vascular effects of beta-phenylethylamine were abolished by desipramine. These results indicate that beta-phenylethylamine exerts both positive inotropic and vasoconstrictory effects, probably by releasing endogenous norepinephrine from the adrenergic nerve endings.


Prostaglandin E release from dog skeletal muscle during restricted flow exercise.

Prostaglandin E (PGE) release from the anterior calf muscles of anesthetized dogs was measured during and following exercise. Blood flow was held constant at 15.5 +/- 1.6 (SEM) ml.min-1. 100 g-1 and the muscles were stimulated for 20 min at a frequency of 4 Hz. PGE release dropped from a resting level of 11.4 +/- 3.8 ng.min-1.100 g-1 to 6.5 +/- 2.0 ng.min-1.100 g-1 during exercise (P less than 0.05). Following exercise, PGE release slowly returned to and eventually exceeded the resting level over a 60-min period. Return of vascular resistance to control was even more prolonged. Indomethacin (5 mg/kg) caused 1) an increase in resting resistance (40%), 2) a drop in PGE release (48% at rest), and 3) a more rapid return of vascular resistance to control following exercise. PGE release does not appear to contribute to the vasodilation during exercise, but can account for the portion of vascular resistance recovery not blocked by indomethacin. The remaining prolonged vasodilation could be explained by another as yet unidentified vasodilator(s). This preparation exhibits tonic prostaglandin release that causes a vasodilation at rest.


Morphological and physiological correlation of bradykinin-induced macromolecular efflux.

Bradykinin applied topically for 4 min produced marked dose-related increases in the number of fluorescent dextran (mol wt 145,000) vascular leakage sites exclusively from small postcapillary venules--evidence for an increase in macromolecular permeability. The increase in macromolecular permeability was short-lived, making repeated applications possible. The number of bradykinin-induced venular fluorescent dextran leakage sites could be greatly reduced by the simultaneous topical application of isoproterenol, and this antagonism of the increase in macromolecular permeability could be prevented by pretreatment with propranolol. The topical application of papaverine failed to antagonize the increase in the number of venular leakage sites of fluorescent dextran by bradykinin. A continuous 90-min superfusion of bradykinin elicited an initial marked increase in the number of fluorescent dextran venular leakage sites, which then waned after 20-30 min, returning to near control despite the continued superfusion with bradykinin. In canine forelimbs the bradykinin-induced increase in protein efflux, total protein transport, and lymph flow also peaked in approximately 30 min and then waned markedly despite continued local intra-arterial infusions of this agent for prolonged periods. The morphological data from the cheek pouch agrees well with the physiological data from the forelimb, suggesting that an increase in protein efflux in the canine forelimb could be readily explained by an increase in the number of large pores.


Effect of pentobarbital anesthesia on hypotension after 10% hemorrhage in the dog.

The effect of pentobarbital anesthesia, 30 mg.kg body wt-1, on the rapidly acting arterial pressure control system was studied on splenectomized dogs chronically instrumented with catheters for pressure measurement and hemorrhage and with a flow probe for measurement of aortic flow. The dogs were subjected to 10% hemorrhage in 30 s under conscious and anesthetized states before and after denervation of the carotid sinus nerves (CS) and/or the vagi (V). In the intact nerve condition, arterial pressure fall (delta AP) at 1-2 min after hemorrhage was 8.0 +/- 1.3 (mean +/- SE) mmHg in conscious dogs and 9.4 +/- 2.0 mmHg in dogs under anesthesia. There was no significant difference between these delta APs or other pairs of delta APs in conscious and anesthetized states at any stage of denervation. As long as the CS reflex was intact, heart rate and total peripheral resistance increased in response to hemorrhage as in the intact condition. In conclusion, the pentobarbital anesthesia had little effect on the rapidly acting arterial pressure control system as far as its capacity to restore mean arterial pressure after the brief 10% hemorrhage is concerned.


Digoxin-norepinephrine response and calcium blocker effects in vascular smooth muscle.

The mechanism of potentiation by digoxin of the response of vascular smooth muscle to norepinephrine was investigated in 5-cm intact segments of rabbit carotid artery. Segments were mounted in a chamber and perfused at constant pressure while flow and upstream and downstream pressures were recorded and resistance was calculated. Each vessel was perfused with a submaximal vasoconstricting concentration of norepinephrine (6 x 10(-6)M) alone, in the presence of digoxin (6 x 10(-5)M), and during exposure to both digoxin and one of the following calcium antagonists: lanthanum chloride (5 x 10(-4)M procaine hydrochloride (5 x 10(-3)M), or verapamil (5 x 10(-5)M). Digoxin potentiated the response to norepinephrine alone by 20% (P less than 0.01), to norepinephrine plus lanthanum chloride by 10% (P less than 0.001), and to norepinephrine plus procaine hydrochloride by 17% (P less than 0.001). Digoxin did not potentiate the norepinephrine response in the presence of verapamil. These data suggest that the mechanism of digoxin potentiation of the norepinephrine response in vascular smooth muscle may involve an alteration in a cellular calcium sequestration or release process. The potential cellular sites that may contribute to this phenomenon are discussed.


Choline acetyltransferase activity in rat and guinea pig heart following vagotomy.

Choline acetyltransferase (CAT), which serves as a marker for the preganglionic and postganglionic parasympathetic cholinergic neurons in heart, was measured in heart regions in rats and guinea pigs after either a right or a left unilateral cervical vagotomy or a sham operation. One day after a left vagotomy in rat, CAT activity was decreased in the region of the SA and AV nodes. In rats killed on the 2nd, 4th, and 8th day after left vagotomy, the activity of CAT in these regions increased to the control level. CAT activity in the remainder of the heart did not decrease. In guinea pig 1 wk after a left vagotomy, CAT activity was decreased in the anterior interventricular septum but not in other regions. Selective increases in enzyme activity were noted in the right atrial appendage following left vagotomy and in the superior interventricular septum following right vagotomy. These results suggest that compensatory increases in CAT activity occur that may be related to collateral sprouting similar to that observed in the frog heart.


Nerve growth factor-enhanced reinnervation of surgically denervated canine heart.

Nerve growth factor (NGF) was administered in doses of 25,000 U daily for the first 5 postoperative days to dogs subjected to cardiac denervation. These dogs and untreated cardiac-denervated dogs were killed at 1, 2, 3, and 6 mo postoperatively. Tritiated norepinephrine ([3H]NE) was administered prior to death, after which the hearts were removed and eight segments (right and left atria, right ventricular conus and sinus, left ventricular base and apex and high and low ventricular septum) analyzed to determine myocardial NE content and uptake of [3H]NE. Our data demonstrated enhanced cardiac reinnervation of the left ventricular base in NGF-treated dogs.


Increase in passive tension of spontaneously beating atria in hyperosmolar media.

Spontaneously beating rabbit atria were used for study of increases in passive tension induced by hyperosmolar Tyrode bathing media. The time course and degree of passive tension change was dependent on the level of osmolality and the osmotic agent used. The effectiveness of various agents added to Tyrode solution in increasing resting tension was in the order sucrose greater than mannitol greater than or equal to NaCl greater than glucose greater than = no change. The hyperosmotically induced "contracture" was similar to contracture induced by high Ca2+ medium, but the maximum hyperosmotic effect was greater than that of high Ca2+. In contrast to active atria, inactive atria showed no increase in passive tension in hyperosmotic solutions or in Tyrode solution containing high Ca2+. After depolarization with Tyrode medium containing high K+ or zero K+, increased Ca2+ caused contracture in inactive left atria greater than that caused by hyperosmotic media (+200 mM sucrose) in active right atria or atrial pairs. Results of the study indicate that although other factors may be involved, increased Ca2+ flux inward could largely account for the passive tension response.


Role of vagal afferents in vasodepressor effects of PGE2 in spontaneously hypertensive rats.

In anesthetized, spontaneously hypertensive rats (Okamoto-Aoki), injections of 0.75, 1.5, and 3.0 microgram/kg PGE2 into the jugular vein caused transient decreases (mean +/- SE) in arterial pressure of 21 +/- 2, 37 +/- 3, and 78 +/- 6 mmHg, respectively, before cervical vagotomy and of 1 +/- 1, 15 +/- 4, and 15 +/- 6 mmHg after cervical vagotomy. The vasodepressor effect of jugular vein injections of 3.0 microgram/kg PGE2, but not of lower doses, was depressed by vagotomy in normotensive Wistar-Kyoto and Sprague-Dawley rats. Vagotomy did not reduce the hypotensive response to intra-aortic injections of PGE2 in these hypertensive and normotensive rats. The depressor effect of PGE2 thus appears to have a significant reflex component mediated through cardiopulmonary receptors subserved by vagal afferents, with hypertensive rats exhibiting a lower threshold than normotensive rats. A vagally mediated reflex component to the depressor effect of PGE2 could not be demonstrated in normotensive rabbits or in rabbits and rats with chronic renovascular hypertension. Thus, a naturally occurring vasoactive substance can stimulate cardiopulmonary receptors subserved by vagal afferents in the rat, and spontaneously hypertensive rats appear to be especially sensitive to this effect.


An improved isolated heart preparation for external assessment of myocardial metabolism.

To facilitate characterization of myocardial metabolism with the use of positron-emitting tracers, we developed an isolated heart preparation designed to simulate physiological levels of flow and substrate extraction. Isovolumically beating hearts were perfused retrograde at 60 mmHg with modified non-recirculating Krebs-Henseleit (KH) solution with or without washed sheep red blood cells at a hematocrit of 25 or 40 (KH-RBC25, KH-RBC40). Left ventricular (LV) systolic pressure averaged 63 mmHg with KH alone, 78 with KH-RBC25, and 98 with KH-RBC40. LV dP/dt, pressure-time index, and oxygen consumption increased in an analogous fashion. Fatty acid extraction increased from 1.5% with KH to 11.8% in hearts perfused with KH-RBC40, although net uptake was not increased markedly because of the associated differences in flow (4.6 ml.g-1.min-1 with KH and 1.5 with KH-RBC40). Hearts perfused with erythrocyte-rich media exhibited functional and metabolic stability and less edema. The preparation avoids intrinsic limitations encountered with buffer-perfused hearts and should prove useful for characterization of cardiac metabolism with radiolabeled tracers relevant to positron emission transaxial tomography.


Extracorporeal circulation system for coronary artery perfusion in the closed-chest dog.

An adjustable constant-flow coronary artery perfusion system has been developed for use in the anesthetized closed-chest dog. Coronary flow and perfusion pressure measurements are obtained over the entire autoregulatory range. Coronary flow was briefly diverted to a bypass cannula and then returned to its original level. Coronary vasodilatation resulted in a fall of perfusion pressure below its preocclusion value, but recovery of vascular tone was complete in about twice the time required during unrestricted reactive hyperemia. It is concluded that no flow debt repayment is required for the restoration of vascular tone after brief occlusions. In the measurements made with this system, intramyocardial pressure distribution is not influenced by thoracotomy, pericardotomy, or positive-pressure respiration, and surgical trauma is minimal.


Development and use of a new high-frequency, low mechanical impedance strain gauge.

A low mechanical impedance strain gauge that imposed insignificant preload to the myocardial fibers was tested in vitro and in vivo. The dynamic response of the gauge to an abrupt change in length (step response) and to sinusoidal perturbation was determined. The electrical output reached 95% of maximum steady-state response within 3-5 ms after a step displacement. Frequency analysis indicated a flat response up to 80 oscillations/s. The in vivo testings of the gauges were performed on intact, working swine hearts during control and ischemic flows in a regionally perfused preparation. During control perfusion the gauges demonstrated epicardial shortening in systole and early-to-mid diastole. Relaxation was confined to late diastole. With ischemic perfusion there was a progressive loss of systolic shortening, but minimal disruption in global hemodynamics. Correlative measurements were also made with sonomicrometers positioned in subepicardial myocardium. Patterns of motion, shortening, and changes in strain were similar between the two types of gauges.


Awareness and disengagement in cancer patients.

The authors found that cancer patients (N = 44) did not differ from patients with other chronic illnesses (N = 27) with respect to awareness of their condition or ratings on an unobtrusive, nonverbal measure of disengagement. Cancer patients who were aware were more engaged than those who were not, but this was equally true for the noncancer patients. Awareness, for the cancer patients, was not associated with frequency of visiting or with living for a longer or shorter period than expected. There was a significant interaction, however, in that patients who were aware lived longer if they were engaged, whereas patients who were unaware lived longer if they were disengaged. Caution and judgment should be exercised in sharing information with terminally ill patients because awareness may be beneficial for some but not for all.


Psychiatric combat reactions during the Yom Kippur War.

The authors explore the stress of war by reporting some selected epidemiological aspects of the psychiatric combat reactions among Israeli troops during a period of intensive hostilities in the Yom Kippur War of 1973. They examined the distribution of these casualties according to intensity of fire, age, rank, sociopsychological grading, and military assignment and measured treatment outcome at the end of the war and 18 months later.


The myth of the alliance with borderline patients.

The author questions the concept of a therapeutic alliance in the psychotherapy of patients with borderline and narcissistic personality disorders. The motivating elements in their treatment are the emerging, sustaining transferences, which also allow the patients to appreciate the real qualities of their therapist. As they internalize aspects of their interactions with the therapist, including the therapist's real characteristics that are lacking in themselves, the patients gradually develop the capacity to work collaboratively with him or her. When a solid therapeutic alliance is established, the patients have reached a neurotic level of functioning.


A psychoanalyst reports at mid-career.

The author states that the current pessimistic impression of the potential of psychoanalysis as a therapy is largely due to the inclusion of a disproportionate number of inexperienced analysts in reports on groups of practitioners. To correct this bias, he summarizes his own experience of two decades as a full-time psychoanalyst, describing his successful analyses as well as his unsuccessful attempts. He concludes that the satisfaction of commitment to a psychoanalytic career comes from the fact that it confirms the usefulness of the analytic method as a means to assist others to achieve personal growth and to illuminate human mental life.


Psychiatric malpractice: the California experience.

The cost of psychiatric malpractice insurance has increased dramatically in recent years. To shed light on the extent to which this increase is justified the author polled 133 California psychiatrists who had indicated experience with some form of claims activity over the past 5 years. The 107 respondents reported 105 cases, of which 57 (54%) resulted in no more than a notification of a possible claim, 22 (21%) did not proceed beyond legal deposition, 20 (19%) were settled by dollar payment before trial, and 6 (6%) were left to the courts. The author recommends tort reform and refinement of reported claim and loss data to contain the cost of malpractice insurance.


Characteristics and disposition of persons found not guilty by reason of insanity in New York State, 1971-1976.

In order to develop an empirical profile of persons acquitted by reason of insanity from which policy could be developed, the authors studied all acquittals in New York State from 1971-1976. During this period 196 men and 29 women were found not guilty by reason of insanity. In contrast to adults admitted to state correctional facilities, the study group contained proportionately more persons who were white and older. The most frequent crimes for which subjects were tried were homicide, assault, and robbery. Most victims were acquaintances of the defendants. By 1976, 67 persons had been discharged after hospitalization ranging from 1 to 1,235 days. These defendants are still being followed after their return to the community.


Psychiatry and the rhetoric of models.

The term "medical model" has been increasingly used in discussions about the future course of psychiatry. The author examines various types of models and suggests that "medical model" is a rhetorical device which tends to obscure many important issues. He suggests that psychiatry avoid overrestricting its area of expertise.


Urinary MHPG excretion in minimal brain dysfunction and its modification by d-amphetamine.

The authors studied the excretion of 3-methoxy-4-hydroxyphenlyglycol (MHPG) in 15 hyperactive boys and 13 controls. They further examined soft neurologic signs and clinical drug response to d-amphetamine administration for two weeks in the hyperactive boys. MHPG excretion was significantly lower in the hyperactive boys than in the controls. d-Amphetamine decreased MHPG excretion significantly in the drug responders only. Pretreatment MHPG excretion did not predict clinical drug response. The responders had more soft neurologic signs than the nonresponders. Furthermore, soft neurologic signs were not related to pretreatment MHPG levels.


Amino acids in bipolar affective disorders: increased glycine levels in erythrocytes.

The authors measured the concentrations of 20 amino acids in the erythrocytes and plasma of 13 female bipolar patients and 10 female normal controls. The concentration of glycine in the erythrocyte was significantly elevated in the patient group. No differences were present in the plasma. Preliminary findings indicate that the high glycine levels were present in patients who were depressed, manic, or in remission and were unaffected by electroshock therapy.


The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.


State and trait in psychiatric practice.

The authors present a schema for conceptualizing psychiatric illness in terms of state and trait disorders. These disorders are relatively independent components, one or both of which can be present in one patient. They usually require treatment by different methods. State disorders, such as schizophrenic psychosis, mania, and depression, are time-limited and autonomous and respond better to pharmacological than psychosocial therapy. Trait disorders, such as neurotic and characterological disturbances, are long-lasting and respond better to psychosocial therapies. The authors discuss the implications of this schema for the integration of pharmacological and psychosocial treatments.


Suicide among U.S. women physicians, 1967-1972.

The authors examined AMA records of the deaths of 751 women physicians during 1967-1972. Forty-nine (6.56%) committed suicide. The suicide rate for women physicians (40.7 per 100,000 per year) was higher than for men physicians and about four times that for white American women of the same age. From the known morbid risk for suicide among women with primary affective disorder, the authors calculated that about 65% of American women physicians have primary affective disorder.


An attempt to objectify the therapeutic process: a working model.

On the basis of their observations in daily psychoanalytic work the authors developed five objective criteria for "bad" analytic hours. These criteria involve affect, intellectualization, isolation, lack of feedback, and dissatisfaction. The authors developed a formulation to help them preconsciously recognize the presence of these factors during therapeutic work and found that it was helpful in turning a potentially bad hour into a productive one.


Chlorimipramine therapy for obsessive-compulsive neurosis.

Twenty patients with a history of treatment-resistant obsessional neurosis underwent a 4-week clinical trial of chlorimipramine. Scores on the Psychiatric Questionnaire for Obsessive Compulsive Neurosis, the Leyton Obsessional Inventory, and 3 self-assessments indicated that although there was no significant change in obsessive ruminations, obsessive rituals, horrific temptations, or pervading doubt, there was a substantial significant improvement in the obsessive symptom item and severity of obsessions, as well as anxiety, depression, and phobia. Side effects were mild. The authors believe that chlorimipramine is the most promising treatment for obsessive-compulsive neurosis.


Manic-depressive variant syndrome of childhood: a preliminary report.

The author describes the specific diagnostic entity of manic-depressive variant syndrome of childhood and outlines the five essential diagnostic criteria (affective storms, family history of significant affective dysfunction, hyperactivity, chronically disturbed personal relationships, and absence of psychotic thought disorder) and the five secondary criteria (sleep disturbances, minimal brain dysfunction, abnormal EEG, enuresis, and neuropathology). In the four cases reported, the children, when properly diagnosed, responded well to lithium therapy. The author points out the need for further study of this syndrome. Precautions about the use of lithium in children under age 12 are crucial, as is the need for continuing psychotherapy for parents and child.


The elective within the required psychiatric clerkship.

Two important goals of a successful psychiatric clerkship are to maximize students' responsibility and flexibility and to provide knowledge and skills relevant to their future careers. The author describes an elective program within the required medical school psychiatric clerkship that meets these criteria. On the basis of feedback from both students and staff, the author concludes that the advantages of the elective program to students, patients, faculty, and the department far outweigh the disadvantages.


The community meeting: a comparative study.

In this study of two identical open wards, the author found that in ward 1's highly structured meetings a higher proportion of patients participated, and they distributed their participation in more direct proportion to the relative numbers of each present than in the open meetings on ward 2, where patients directed their participation disproportionately to staff. Staff on both wards disproportionately directed their participation to patients, but less so in the structured meetings. The implications of these observations are discussed in terms of the executive ego deficits of the patients involved and their need for structure in the external milieu in order to compensate for these deficits.


Impacts of the medical malpractice slowdown in Los Angeles County: January 1976.

The Los Angeles County (California) physician strike of January 1976 resulted in a partial withdrawal of physician services. Among recorded impacts were a $17.5 million loss in hospital revenues and an $8.5 million pay loss for hospital employees. Several surveys revealed no evidence of a significant impact on the general public in finding medical care. Analysis of emergency room visits and paramedical ambulance calls showed no significant increases during the strike. County mortality statistics for the strike were not affected. Eighty-eight fatalities among 2,171 patients transferred during the strike were analyzed; a Case Attributable Mortality Probability generated on 21 cases selected for final review by a five-physician multispecialist panel indicated that 29 per cent of the Attributable Mortality could be ascribed to the strike itself and 71 per cent to ongoing "patient dumping" from private sector to County hospitals. Even if sample attributable mortality rates were generalized to overall county deaths, the resultant figures are below the estimated range of 55 to 153 deaths that did not occur because of the number of elective operations not performed secondary to the strike.


Occupational health priorities for health standards: the current NIOSH approach.

Government agencies responsible for protecting the public from the adverse effects of toxic chemicals must set priorities for research, regulatory action, protocol testing, and monitoring due to the vast number of toxic chemicals and the limited resources available to these agencies. The National Institute for Occupational Safety and Health (NIOSH) must set priorities for research on hazards encountered in the workplace. Priorities are also utilized by NIOSH in preparing criteria for recommended occupational standards which are forwarded to the Occupational Safety and Health Administration (OSHA), U.S. Department of Labor, for possible promulgation. For various reasons, including rapidly changing conditions in the American workplace, NIOSH has instituted a revised priorities program. In the future, NIOSH research and recommended standards activities will focus not only on individual chemicals, but also on industries, occupations, chemical classes, and general industrial processes. NIOSH has also implemented a new program which will allow recommended control procedures for certain chemicals to be forwarded to OSHA in a shorter time period than has been experienced previously.


Drowning and near-drowning involving children: a five-year total population study from the City and County of Honolulu.

A study of all serious childhood immersion accidents (both drowned and near-drowned cases) is reported from Hawaii. This is a total population-based survey of 140 consecutive cases (0--15 years) occurring during the five-year period (1973--1977. Age-specific, sex-specific, and osmolality-specific (salt versus fresh water) data are presented both for survivors and fatalities. The overall annual drowning rate of 3.1 per 100,000 children at risk is low, for a water-oriented society. The survival rate following loss of consciousness in the water is 73 per cent. There is no evidence from this study that osmolality affected the probability of survival. The rank order of importance of drowning sites is swimming pools, surf, sheltered salt water bathing, domestic bath tubs, fresh water streams, salt water canals, and garden fish ponds. Specific accident rates, by sex, outcome, and site of immersion are also presented. No secular trend in the rate of drowning was observed in this study. Comparison with the only other available total population survey (Australia) of childhood immersions reveals common epidemiological and demographic patterns in modern urban societies and suggests that safety regulations play a role in reducing swimming accidents and fatalities in children.


Evaluation of the Tennessee Child Restraint Law.

In Tennessee a law came into force January 1, 1978 requiring parents to use child restraints properly when transporting their children who are less than four years old. Alternatively, the law permits children to be held in arms, a practice known to be hazardous rather than protective. Before and after the law went into force, observations were made of children in cars exiting from shopping centers in Knoxville and Nashville, Tennessee, and in Lexington and Louisville, Kentucky, an adjacent state not having a child restraint law. More than 80 per cent of Tennessee children observed in the fourth month the law was in force were not using child restraints anchored by seat belts, although use rates increased in Tennessee (8 to 16 per cent) to a greater extent than in Kentucky (11 to 15 per cent). Moreover, due to a large increase in children traveling in arms in Nashville, there was an increase in such travel in the two Tennessee cities studied (23 to 28 per cent) relative to a decrease in those studied in Kentucky (19 to 14 per cent).


Violent death in a metropolitan county: II. Changing patterns in suicides (1959-1974).

Suicide rates in Cuyahoga County (metropolitan Cleveland) rose from 10.2 in 1958 to 12.5 per 100,000 populations in 1974 (23 per cent increase) with the greatest rise among nonwhite males (from 5.9 to 13.1, or 122 per cent). Increased rates were observed in both the city (19 per cent increase) and suburbs (35 per cent increase). Rates increased among young non-white and white adults of both sexes aged 15--34 years, but decreased slightly among adults aged 65 years and older. These findings are consistent with national trends. Alcohol was present in the blood of one-fourth of the individuals who were "dead on arrival," and at intoxicating levels in 20 per cent. There were increasing percentages of victims with positive blood alcohol and with intoxicating levels during the study period. White male victims in the city had significantly higher frequencies of such findings than their counterparts in the suburbs. The rates of suicide committed by firearms rose among all race-sex groups, with the greatest increase among city nonwhite males (2.1 to 7.7, or 267 per cent). Suicide by chemical agents (roughly one-half being barbiturates) increased in all groups except city nonwhite males, with the greatest increase among white males and suburban white females. Firearms among males and poisoning among females displaced asphyxia as the leading modes of suicide.


The effect of outreach workers' educational efforts on disadvantaged preschool children's use of preventive services.

A special program of outreach services was implemented to assist a poverty population to appropriately use health services in the Kaiser-Permanente Medical Care Program. A study was conducted to determine the effect of outreach workers' intervention on the use of preventive services by this population. Intially, families were divided into two groups, one with and one without outreach workers. Outreach workers (neighborhood health coordinators) were trained in prevention and health education. They were then assigned to specific subgroups of the poverty population to teach the importance of preventive services and to motivate persons to use these services. This paper focuses on the effect of outreach workers' services on the use of selected preventive care services (immunizations and tine test) by preschool children from poverty families. Preschool children in families with coordinator services had higher use rates for preventive care. The sub-group for which outreach workers were specially trained to focus on preventive procedures for the pre-school group had markedly higher use rates for preventive care. The findings suggest that special intervention programs, using indigenous and nonprofessional outreach workers, can increase preventive service utilization by poverty groups.


Evaluation of an automated blood pressure measuring device intended for general public use.

Responding to Chicago newspaper reports, measurements of blood pressure by a publicly available, automated coin-operated device were compared with those of human observers using the standard cuff and auscultatory technique. One machine was examined in the laboratory, and eight others at randomly selected sites. Analysis of readings made on 100 persons in the laboratory and 227 in the field led to the following conclusions: 1) On the average, the machines measured fifth phase diastolic blood pressure at nearly the same level as did human observers; 2) The machines were more variable measuring systolic blood pressure with four differing from the average human reading by 1mm Hg or less, but two differing by 8mm Hg or more; 3) The agreement between machine-human pairs of readings was not as good as between human-human pairs, but the differences in level of agreement--both in determining the actual value and in categorizing the values as normal, borderline, or high--were small and have little practical importance; 4) Linear regression analyses of the relationship between simultaneously determined machine and human readings indicated that the average human-machine difference was the same over the range of pressures tested. Publicly available blood pressure measuring devices should be labeled concerning their purposes, capabilities, and limitations. Rules and regulations governing their use in the City of Chicago are being prepared by this city's Legal Department.


Patterns of reported rape in a tri-ethnic population: Houston, Texas, 1974--1975.

Police records of reported rape, compiled for the Federal Bureau of Investigation Uniform Crime Reports, in Houston, Texas for 1974 and 1975, were analyzed in relation to ethnicity and age of victim/offender, and time and place of occurrence. Blacks had the highest race-specific rates for both victims and offenders; the majority of all rapes were intraracial. The high-risk age group for both victims and offenders was from 20 to 24 years. Rapes increased slightly during the summer months, peaked during the hours of darkness, and were fairly evenly distributed among the days of the week. The weekend calculated as from 4:00 pm Friday to 8:00 am Monday accounted for 43.6 per cent of all rape occurrences. The majority of rape events involved the use of a lethal weapon and took place in a residence.


Interviewer effects in psychiatric epidemiology: a study of medical and lay interviewers and their impact on reported symptoms.

Utilizing data from a field study of psychiatric disorder, the study examined sex differences in patterns of response to interviewers in contrasting status positions. The dependent variables in the analysis were mean scores on nosological scales measuring three dimensions of symptomotology identified in a factor analysis. Independent variables were interviewer status and respondent sex. Three categories of interviewers were randomly assigned to administer a structured interview schedule. Strong interaction effects between interviewer status and respondent sex were noted. Women disclosed significantly fewer symptoms to the high status interviewers (identified physicians), whereas males reported most symptoms to this group. Theoretical explanations derived from the literature on sex roles were offered regarding the origins of women's response to high status figures.


The U.S. hospice movement: issues in development.

A grass-roots hospice care movement is underway in the United States modeled after recently popularized British hospice programs. Hospice care is intended to help the terminally ill maintain a personally acceptable quality of life until death. Attention should be given to ensuring the future viability of this service option by allowing for experimentation with and adaptation of existing models, and by integrating it with the overall health care system. Issues to be considered in integrating hospice care include utilization of existing resources, regional planning, standards and licensure, and reimbursement opportunities. Although hospice care may not have an immediate cost savings impact on the health care system, it could develop this capacity in the future. Such impact would not only assure a stable financial base for hospice care but would also affect bed use generally. Continuing dialogue among providers, consumers, and policy makers of various backgrounds is necessary to the effective and appropriate development of hospice care in the U.S.


Prenatal monitoring in upstate New York.

In upstate New York, birth certificates of all babies born in hospitals include response to a question on procedures used in fetal monitoring. During the first six months of 1978, some form of monitoring was reported on 47 per cent of all live births in hospitals, 33.6 per cent being monitored externally. The primary cesarean section rate in monitored women was over twice that among those not monitored.


Causes of death among laundry and dry cleaning workers.

To make a preliminary determination as to whether a potential health hazard exists for workers exposed to dry cleaning solvents (carbon tetrachloride, trichloroethylene, and tetrachloroethylene), we analyzed the causes of death of 330 deceased laundry and dry cleaning workers by the proportionate mortality method. The increased risk for malignant neoplasms resulted primarily from an excess of lung and cervical cancer and slight excesses of leukemia and liver cancer. Although the number of deaths was small, the increased risk of cancer noted in this investigation underscores the need for additional epidemiologic studies of this occupational group.


Aging of the rotator cuff.

The many years of challenge in treating athletes disabled by tendinitis stimulated a study of the aging of tendons. Autopsy specimens, representing tendons from 20-, 50-, and 70-year-old subjects, were obtained. Each specimen, consisting of a wedge of the greater tuberosity with the attached supraspinatus tendon, was examined roentgenographically to study the morphologic features of the greater tuberosity and was decalcified and stained with Safranin O to evaluate the amount of fibro-cartilage, with van Gieson to identify Sharpey's fibers, and with hematoxylin and eosin to determine cellularity, fiber integrity, and vascularity of the tendon. The comparison related to chronological age documented a morphologic change of the greater tuberosity and progressive degeneration of all elements of the tendinous structures with progressive (1) osteitis of the greater tuberosity, cystic degeneration, and irregularity of the cortical margin; (2) degenerative sulcus between the greater tuberosity and the articular surface; (3) disruption of the integrity of the attachment of the tendon to the bone by Sharpey's fibers; (4) loss of cellularity, loss of staining quality, and fragmentation of the tendon; (5) diminution of the vascularity of the tendon; and (6) diminution of fibrocartilage.


Spectrum of lesions of the anterior capsular mechanism of the shoulder.

The anterior capsular mechanism appears to be the common denominator in a number of shoulder problems ranging from the recurrent dislocation ("too loose") to the frozen shoulder ("too tight"). The shoulder region and the anterior capsular mechanism can be carefully and accurately assessed by arthrography and cineradiography. Bicipital tenosynovitis has been held accountable for shoulder problems at each extreme of the spectrum. Bicipital tenosynovitis may exist in many shoulders; however, in corrective procedures for the unstable shoulder, the biceps becomes a dynamic reinforcement of the anterior capsule. In the frozen shoulder, the biceps tendon frequently is seen as normal at surgery and the anterior capsular mechanism is identified as the site of the essential lesion. Surgery may switch the patient's problem from one side of the spectrum to the other. Shoulder problems should be investigated thoroughly and evaluated in terms of the patient's requirements for shoulder motion as well as in terms of the orthopaedic surgeon's usual criteria for recommending corrective procedures.


Hypotrophy of the soleus muscle in man after achilles tendon rupture. Discussion of findings obtained by computed tomography and morphologic studies.

Seven athletes (age range, 35 to 43 years), who sustained total subcutaneous ruptures of the Achilles tendon 2 to 5 cm above its distal insertion, were treated surgically with suturing of the tendon, immobilization of the leg and foot for 6 weeks, and cast changes so as to increase the dorsiflexion of the foot. Needle biopsies were obtained several times from the soleus muscles of both the injured and uninjured legs at a depth of about 5 cm. The cross-sectional area was measured by computed tomography at the same level the tissue was obtained by biopsy. Results of morphologic studies revealed a selective Type I fiber atrophy of the soleus muscle. Computed tomography revealed a 23% decrease in the area of the calf muscles and a 11% total reduction in the cross-sectional area of the calf (about the middle, where the gastrocnemius muscle is transformed into a tendon and where the soleus lies superficially). Mere measurement of the circumference of the calf is judged to be a poor criterion of muscle atrophy when compared with these other means of evaluation of atrophy. The evidence compiled during this study suggests that prompt surgical treatment of Achilles tendon ruptures, with cast changes several times during the period of immobilization and with tension maintained on the muscle, is the most effective treatment regimen we have found for this injury.


National football head and neck injury registry: report on cervical quadriplegia, 1971 to 1975.

Data on cervical spine injuries resulting from participation in football have been compiled by a national registry established in 1975. Information has been collected retrospectively by defined criteria since 1971. Efforts have been made to establish the mechanism of injury responsible in the majority of instances on the basis of epidemiologic evidence and recognized biomechanical principles. During the 5-year period, 77 deaths resulted from severe neck injuries. During this period, 1,275,000 players were exposed. Ninety-nine cervical fracture-dislocations resulting in permanent quadriplegia and 259 cervical fractures-dislocations occurred. There may be a "trend" towards an increase in permanent quadriplegia resulting from serious cervical spine injuries sustained while playing football. Apparently, the cause can be attributed to the helmet-face mask that has encouraged the use of the head as the primary point of contact in blocking, tackling, and head butting. The figures clearly identify defensive backs, linebackers, or specialty team members making tackles by using the head as the initial point of contact, as the individuals at greatest risk to sustain cervical spine injuries resulting in permanent quadriplegia.


Skin sensitivity of adults on the Isthmus of Panama to Mycobacterium xenopi sensitin.

A group of 106 adult Panamanian men were skin tested with a standard human tuberculin (RT 23) and three sensitins prepared from atypical mycobacteria. Two of the sensitins (prepared from Mycobacterium kansasii and Battey organism) are commonly used to detect atypical mycobacterial infections. The third (prepared from M. xenopi) had not been used in Panama previously. Skin sensitivity proved to be significantly higher to the M. xenopi sensitin than to the others. The known epidemiology of M. xenopi is briefly reviewed.


Occurrence of antibodies to Brucella canis in rural inhabitants of Corrientes and Neuquén Provinces, Argentina.

Of 1,065 persons sampled during a house-to-house survey of an area of the Department of Curuzú Cuatiá, Province of Corrientes, Argentina, 21 were seropositive to Brucella canis antibodies by the gel-diffusion test, using a saline-extracted B. ovis surface R antigen. Two positive reactors were similarly identified during a survey of rural schools in the Province of Neuquén, which included 887 persons. The findings are discussed in terms of current knowledge of this recently recognized zoonotic infection.


Secondary reconstruction of anterior cruciate ligament in athletes by using the semitendinosus tendon. Preliminary report of 78 cases.

Secondary reconstruction of the torn anterior cruciate ligament has been accomplished by semitendinosus tenodesis in 78 athletes (average age, 20 years; range, 13 to 45 years old). This series was limited to patients who had isolated tears of the ligament or tears of the anterior cruciate ligament associated with tears of one or both menisci. Meniscectomies were performed in 71 knees and reefing of the posteromedial capsular ligament in 35 knees. After an average of 11 months of follow-up (range, 6 to 29 months postoperatively), 67 (86%) of the patients have obtained significant improvement (0 to 1+ on a scale of 0 to 3+) in anteroposterior and anteromedial rotational instability of the joint. The viability and function of the reconstructed ligament was confirmed by direct visualization in three patients at 12, 25 and 26 months postoperatively. Reefing of the posteromedial capsular ligament appears to increase anteromedial rotation stability. This series will be expanded and the follow-up evaluations will continue over a period of years in an effort to determine whether or not semitendinosus tenodesis is superior to other methods of intraarticular reconstruction for a torn anterior cruciate ligament.


St. Louis encephalitis: the Chicago experience.

The largest laboratory-documented outbreak of St. Louis encephalitis (SLE) in the United States occurred in the Chicago metropolitan area in the summer and early fall of 1975. Of 1,456 illnesses investigated, 326 cases of confirmed or probable SLE and 420 cases of suspected SLE were found in the six-county area. The outbreak peaked in early September, but cases continued to occur through October. Cases clustered geographically in the southwestern suburbs. There was a direct correlation between age and attack rate, severity of illness, and mortality rate--all of which increased with successive age groups. Thirty-six persons died. Males and females were equally affected. This epidemic marked the first time that St. Louis encephalitis has been documented in the Chicago area.


Transovarial transmission of yellow fever virus by mosquitoes (Aedes aegypti).

Female Aedes aegypti mosquitoes infected with yellow fever virus by intrathoracic inoculation transmitted the virus to a small percentage of their F1 progeny. Infected offspring were obtained from surface-sterilized as well as from untreated eggs, indicating that the virus was transovarially transmitted. Vertical transmission of yellow fever virus in mosquitoes may be an alternative mechanism for biological survival of the virus during adverse periods or in the absence of susceptible vertebrate hosts.


Proximal diaphyseal fractures of the fifth metatarsal--treatment of the fractures and their complications in athletes.

Twenty-one patients (age range, 15 to 26; 18 patients 15 to 20 years old) had proximal diaphyseal fractures of the fifth metatarsal. Clinical records and radiographs for all patients were available for review. Patient treatment had been individualized and included several methods, including rest, plaster immobilization, and bone grafting. Twenty of the 21 patients were boys or men participating in athletics. Nine of the 21 fractures and 8 of the reinjuries were sustained while playing basketball. Healing required a minimum of 3 months (with bone graft) and some fractures were not radiographically healed at 20 months, although the patients were clinically asymptomatic. The fracture of the proximal shaft of the fifth metatarsal, particularly the 1.5-cm segment distal to the tuberosity, is a troublesome injury in the active athlete. The clinical course does not appear to be influenced by the usual initial conservative treatment modalities, although many of these fractures will heal if the athlete is willing to restrict activities for a prolonged period of time. In this series, bone grafting with a tibial corticocancellous graft after thorough curettage of sclerotic bone obliterating the medullary canal was the most effective treatment modality for delayed union.


Computer simulation of the effectiveness of male-linked translocations for the control of Anopheles albimanus Wiedemann.

A deterministic simulation model was used to establish the potential value of releasing male-linked translocation heterozygotes as a control measure for Anopheles albimanus Wiedemann. Theoretical population reductions exceeding 90% were obtained within 90 and 120 days after releases at initial ratios of 5 translocation males (TM): 1 normal male (NM) and 1 TM: 1 NM, respectively. Additional simulations emphasized the importance of the need for a method that would eliminate females from the release material. Releases containing 15% females were less effective than those with none. When a malaria subroutine was included in the model, the calculations showed that all the theoretical releases greatly reduced the number of malaria-infective females and therefore would have a profound effect on transmission of the disease. The number of malaria-infective females present was eliminated completely when only translocation males were released; however, a small number were present when the releases contained 15% females. Male-linked translocation males required longer periods of time to bring about population control than males that were completely sterile.


Gnathostoma spinigerum from the cervix of a woman in Jakarta.

A male Gnathostoma spinigerum was removed from the cervix of a 29-year-old Jakarta resident who suffered from chronic cervicitis. The worm was 6.7 mm in length and had eight rows of spines on the cephalic bulb. This is the third case of gnathostomiasis reported from Indonesia.


Wild reservoirs of Schistosoma mansoni from Caratinga, an endemic schistosomiasis area of Minas Gerais State, Brazil.

Among 472 small mammals trapped in the Caratinga area of Minas Gerais, Brazil, Schistosoma mansoni infection was demonstrated in 6 of 9 Procyon, 1 of 7 Didelphis, 1 of 1 Philander, 25 of 72 Nectomys, and 16 of 383 various other rodents representing 20 species. The role of Nectomys and Procyon in maintaining endemicity needs further investigation.


Clinical manifestations of cobra bite in the Thai farmer.

Twenty cases of cobra bite in farmers from the central region of Thailand are reported. Ptosis is the earliest sign of cobra bite and is an important diagnostic indication of systemic poisoning. Restlessness, irregular breathing and mental confusion are warning signs of respiratory paralysis. Antivenom for cobra bite was administered intravenously together with symptomatic and supportive treatment; 19 patients survived and 1 died from cerebral anoxia.


Giardiasis in infancy and childhood: a prospective study of 160 cases with comparison of quinacrine (Atabrine) and metronidazole (Flagyl).

The therapeutic effects of quinacrine (Atabrine) and metronidazole (Flagyl) were compared in a 3-year prospective study of 160 infants and children (86 boys and 74 girls ranging in age from 4.5 months to 13 years) with giardiasis. The most common symptom was recurrent abdominal pain. In each study group stool examinations were done 5 days, 1 month, and 6 months after treatment. There were no treatment failures with metronidazole, whereas four of those treated with quinacrine had positive stools 5 days after treatment, indicating possible failure. There were no recurrences at 1 month; after 6 months, however, Giardia infection was found in 13% of both treatment groups. These recurrences were seen mainly in children from families with other infected members. Considering the low failure rate, the minimal side effects, and the relatively more tolerable flavor, metronidazole seems to be preferrable in the treatment of giardiasis. A dosage of 15-25 mg/kg a day for 5 days is recommended.


Clinical, serologic, and epidemiologic characteristics of ocular toxocariasis.

The clinical, serologic, and epidemiologic characteristics of 17 cases of ocular toxocariasis (OT) were studied and compared with those of a control group of 15 cases of other ocular diseases whose differential diagnosis included retinoblastoma. The prevalence and mean titers of Toxocara antibody detected by enzyme-linked immunosorbent assay were greater (P less than 0.005) for patients with OT than for the control group, but not all clinically diagnosed OT cases had detectable antibody. The prevalence of pica was significantly greater in cases than in controls (P  less than 0.05). Almost all case and control patients had a history of exposure to pet dogs and cats, but recent exposure to puppies (less than 3 months old) was significantly associated with Toxocara infection in this study group.


Toxocara-specific antibody in the serum and aqueous humor of a patient with presumed ocular and visceral toxocariasis.

Rarely have concurrent ocular and systemic toxocariasis been reported in the literature. We describe a patient with serologically proven visceral toxocariasis who had a granulomatous lesion in the iris, small rod-like lesions in the retina, and in whom Toxocara-specific antibodies were also demonstrated in the aqueous humor. Two older siblings of this patient also had demonstrable serum antibody to Toxocara. The ocular manifestations resolved rapidly with corticosteroid and thiabendazole therapy and the initial leucocytosis, hepatomegaly, and elevated IgM level were normal at 3.5 months. These changes might be attributed to either the thiabendazole and prednisone therapy or to the natural history of this disease.


Eosinophilic meningitis: a suspected case of angiostrongylosis found in Shizuoka Prefecture, Honshu, Japan.

A patient with eosinophilic meningitis in Shizuoka Prefecture, Honshu, Japan had nausea, vomiting and headache on admission; laboratory examinations revealed leukocytosis with eosinophilia. Eight days later neck stiffness appeared. Lumbar puncture showed an increase of the initial pressure in association with eosinophilic pleocytosis in the spinal fluid. The possibility of angiostrongylosis was considered because the patient had eaten raw slugs for 4 years as a remedy for lumbago. Although the serum contained cross-reactive antibodies against Toxocara canis, positive reactions to Angiostrongylus cantonensis antigens were observed in all of the immunological tests made. These observations, together with results of epidemiological studies in Honshu carried out by other investigators, suggest that the present case of eosinophilic meningitis may have been caused by A. cantonensis. One previous case has been reported from Honshu Island, Japan.


Gnathostomiasis, a possible etiologic agent of eosinophilic granuloma of the gastrointestinal tract.

A 42-year-old Thai man from central Thailand came to Ramathibodi Hospital with the complaint of abdominal pain. Physical examination revealed localized tenderness in the right lower quadrant. The clinical impression was acute appendicitis and an operation was performed, revealing a large mass in the cecum. A right hemicolectomy was done for what was thought to be a carcinoma of the colon. The resected colon showed subserosal thickening on the antimesenteric side of the ascending colon with a constricted area at the middle portion. An immature adult Gnathostoma spinigerum was identified in the thickened subserosa of the cecum. Microscopic examination of the involved bowel showed a heavy infiltration of eosinophils, fibroblasts and histiocytes, and mild to moderate edema. The findings were consistent with eosinophilic granuloma of the gastrointestinal tract, and the presence of the parasite in the affected bowel suggested that it was the etiologic agent.


Subcutaneous dirofilariasis in Okinawa, Japan.

A nematode within a subcutaneous nodule excised from an elderly Okinawan man has been tentatively identified in sections as an immature Dirofilaria repens--the first to be reported from Japan.


Onchocerciasis in San Vicente Pacaya, Guatemala.

An epidemiological survey for onchocerciasis was carried out in the San Vicente Pacaya area of Guatemala. A total of 2,153 inhabitants were examined by a single skin snip, and 664 (30.8%) were positive for microfilariae. Slit lamp examination of the anterior chamber of the eye revealed microfilariae in 6.2%; the positive rate for microfilariae in the anterior chamber was proportional to the microfilarial density in the skin. The altitude-dependent character of onchocercal infection was shown in this mountainous area, suggesting that transmission occurs principally between 600 and 1,300 m. Of, 1,217 persons examined simultaneously by skin snip and by palpation for nodules, 587 were positive by one or both methods; 101 infections were detected by onchocercal nodules only and these were usually in children or persons living in areas of low endemicity. It was concluded that both the skin snip and a search for nodules are required for accurately determining the prevalence of onchocerciasis in Guatemala.


Onchocerciasis transmission potentials of four species of Guatemalan simuliidae.

Two complete days of collections and dissections of all black fly species landing on two persons infected with Onchocerca volvulus were made at monthly intervals for 13 months within a single endemic area of Guatemala. A comparison of the infective biting densities and transmission potentials showed that Simulium ochraceum was the only significant vector.


Extragenital cutaneous lesions of schistosomiasis mansoni: report of two cases.

Two cases of extragenital cutaneous lesions caused by eggs of Schistosoma mansoni are described. In one case the cutaneous involvement occurred during the acute phase of schistosomiasis; in the other the lesion appeared several years after specific treatment for schistosomiasis had been given.


Comparison of four species of snails as potential decoys to intercept schistosome miracidia.

Preliminary studies have shown that various species of aquatic snails may be used as decoys or "sponges" to intercept schistosome miracidia, thereby preventing the miracidia from reaching the snails which normally serve as their intermediate host. In this study, four species of snails were evaluated as candidate decoys for field trials: Marisa cornuarietis, Pomacea australis, Helisoma caribaeum, and Tarebia granifera. In the laboratory all four species caused considerable reductions in the proportion of Biomphalaria glabrata infected by miracidia of Schistosoma mansoni. The most effective decoys were M. cornuarietis and H. caribaeum, both of which caused experimental infection levels of 90% to decrease to 25% when five decoy snails were present for each target snail. When ten decoy snails were present for each target snail, the proportion infected decreased to 1%. M. cornuarietis was chosen as the candidate for field trials because it was found more frequently in Puerto Rico than was H. caribaeum. Initial field trials in two ponds showed that M. cornuarietis blocked infections at a ratio of 6 decoys to 1 target snail, confirming the laboratory results. Further studies in flowing water are needed before the technique can be generally evaluated in an endemic area.


Pancreatic enzyme levels in bile of patients with extrahepatic biliary tract disease.

A total of ninety three patients with biliary tract disease were studied to determine the concentration of the pancreatic enzymes, amylase and lipase, in bile obtained from the gallbladder and/or common bile duct. Of seventy gallbladder bile samples, amylase levels were higher than actual or predicted serum levels in 87 per cent, while bile lipase were higher than serum lipase values in 66 per cent. Bile obtained from the common bile duct had enzyme concentrations which fluctuated from values similar to those in serum to remarkably high levels. This suggests that pancreatic enzymes enter the biliary system through a common terminal ampulla which is known to exist in 60 to 90 per cent of human subjects. The premise is advanced that pancreatic enzymes may initiate inflammatory changes in the gallbladder and could play a role in gallstone formation by altering the constituents which maintain cholesterol in a soluble state. Biliary reflux of pancreatic enzymes could play a role in the pathogenesis of some cases of cholecystitis can cholelithiasis.


Intrahepatic lithiasis. Study of thirty-six cases and review of the literature.

In 2,700 operations for biliary tract stones, intrahepatic lithiasis (stones located proximal to the confluence of the main hepatic ducts) was discovered in 36 patients (1.3 per cent). The diagnosis of intrahepatic lithiasis was determined only via intraoperative chalangiography in thirty-two cases (88.9 er cent); in 23 per cent of our cases of intrahepatic lithiasis, jaundice was never observed. This confirms that intraoperative cholangiography should be performed routinely in every case of biliary lithiasis. The removal of stones was generally performed by an indirect approach (papillostomy and/or choledochotomy). In 16.7 per cent of our cases, a direct approach was indicated. It is extremely important, after removal of calculi, to assure ample bilioenteric flow. Our surgical approach was therefore based mostly on the caliber of the biliary tract. When the tract was dilated less that 2 cm (in 20 cases), choledochohepaticotomy with papillostomy was most often performed (12 cases, 60 per cent). When the dilatation was more that 2 cm (12 cases), Roux-en-Y hepaticojejunostomy was performed in all. There was no operative mortality, although the long-term follow-up results were poor in 9.6 per cent of the cases.


Cimetidine protects against stress-induced gastric injury augmented by mucosal barrier breakers.

An experimental rat model utilizing cold-restraint stress was employed to test the ability of an H2-receptor antagonist, cimetidine, to control gastric mucosal injury associated with stress augmented by the gastric mucosal barrier breakers, aspirin and taurocholate. Both aspirin and taurocholate, when combined with stress, caused a significant increase in gastric mucosal injury over that seen in animals receiving either stress alone or only gastric mucosal barrier breakers without stress. Pretreatment with cimetidine caused a significant reduction in gastric mucosal injury in stressed animals receiving gastric mucosal barrier breakers. This reduction was to the level of lesions seen in nonstressed animals.


rho-Shaped anastomosis: a reconstruction of the alimentary tract after total gastrectomy.

One hundred sixty-four patients underwent total gastrectomy with a rho-shaped jejunal food pouch (rho loop) and roux-en-Y jejunojejunostomy. The rate of postoperative complications was very low (9.1 per cent), and the most important problem of anastomotic failure was never encountered. Only 4 of 164 patients (2.4 per cent) died within one month of surgery, and the causes of death were pneumonia (2 patients), cerebral hemorrhage (1), and ileus (1). The function of the newly constructed passage was estimated through an elaborate barium meal examination. The test revealed that the rho-shaped jejunal food pouch has adequate reservoir and mixing functions for ingested foodstuff. No reflux of barium meal into the esophagus was observed during the examination. In a follow-up study of the patients, only a few complained of symptoms of reflux esophagitis or dumping, but none of them needed any treatment.


Antrectomy as treatment of recurrence after vagotomy for duodenal ulcer.

Sixty-eight patients antrectomized for recurrent ulcer after different types of vagotomy were reexamined two to ten years after the operation. Mortality after antrectomy for recurrent ulcer was 1.5 per cent (95 per cent confidence limits, 0.0 to 7.9 per cent), the recurrence rate 2.9 per cent (0.4 to 10.2 per cent), and total failure rate (Visick IV) 13.0 per cent (0.4 to 25.6 per cent). If these figures are applied to a series of 260 proximal gastric vagotomies recently reported from our department and compared with data from series of vagotomy-antrectomy as primary treatment of duodenal ulcer, the final surgical mortality and cure rate will be equal, whereas the final failure rate (Visick IV) probably would be less after proximal gastric vagotomy because of a lower frequency of dumping and diarrhea.


Chronic and recurrent appendicitis.

Acute appendicitis is a well known clinical entity, but many physicians are unwilling to accept appendicitis as a chronic or recurrent illness. Of 225 patients undergoing appendectomy, sixteen (7 per cent) had findings suggestive of chronic, recurrent, or subacute appendicitis. Four patients had chronic abdominal pain and histologic findings of chronic inflammation. Nine patients had previous episodes similar to that which resulted in appendectomy. All had acute suppurative appendicitis pathologically. Three patients had only one episode of abdominal pain, but had pathologic evidence of subacute inflammation. Because this study was retrospective, we suspect that the true incidence of recurrent appendicitis is significantly greater, as reported by others. Indications for operation must be strict, for unless there are specific signs and symptoms of appendiceal disease, appendectomy will often be of no benefit.


Effects of concurrent sepsis with clinically significant pulmonary embolic disease.

Forty-one patients with significant pulmonary emboli were reviewed. The presence of heart disease and obesity was found with relatively constant frequency throughout the groups presented. Postoperative infections (wounds or abscess) were frequently associated with fatal or significant pulmonary embolism, particularly after abdominal and pelvic operations. The infection rate (65 per cent) in patients in whom significant pulmonary embolism developed after abdominal and pelvic operations is particularly striking when compared to the overall infection rate of 7 per cent for major operations in our hospital. Recent studies of prophylactic minidose heparinization reveal an increased number of complications due to the heparin [24], and thus the proper selection of cases for prophylactic minidose heparin is mandatory. The data suggest that patients at high risk for the development of postoperative complications of infection are also at high risk for the development of significant pulmonary emboli and should be considered candidates for prophylactic minidose heparinization.


Survival following mastectomy for stage III breast cancer.

Patients with locally advanced breast cancer have been considered unsuitable for curative surgical therapy and are usually approached with other treatment modalities. Review of the results of radical mastectomy in 228 patients with stage III breast cancer demonstrates actuarial survival of 33 per cent at five years and 22 per cent at ten years. Treatment with preoperative or postoperative radiotherapy as employed did not lead to survival superior to that of mastectomy alone. Evidence of local or regional recurrence developed in 27 per cent of patients. In 73 per cent the first recurrence was systemic. This retrospective study suggests that the prognosis for locally advanced breast cancer is not as dismal as has been previously reported. The importance of nodal involvement is again emphasized. A randomized trial of mastectomy with adjuvant chemotherapy for locally advanced breast cancer is warranted. Such a study is in progress at our institution.


Adolescent breast masses in Nigerian Igbos.

In the Igbos of Nigeria, most adolescent breast masses were due to gynecomastia in males and to fibroadenoma in females. The peak ages for both diseases differed from those reported in a recent American series. An exotic finding was a mammary mass due to onchocerca worms. Curiously, there were as many as two cases of a rare tumor, namely, alveolar soft part sarcoma.


Feasibility of integration of modalities in melanomas and sarcomas.

Chemotherapy was administered in the immediate postoperative period to seventy patients (52 with melanomas and 18 with sarcomas) after a total of eighty-seven major operations, with no morbidity or mortality traceable to the chemotherapy. There was no apparent interference with wound healing or what would be considered a normal postoperative course. Fourteen of these patients (5 with melanomas and 9 with sarcomas) received a combination of radiation anc chemotherapy initiated in the postoperative period, and it was tolerated well. This combination appears to be safe, provided the field of radiation is not so large that is may add significantly to the myelosuppressive effect of chemotherapy and the dosage of concomitantly administered radiopotentiating agent(s) is reduced. Sixteen patients had Bacillus Calmette-Gúerin (BCG) immunotherapy in the immediate postoperative period without complications. This policy of a tight interweaving of modalities is safe, has the theoretic advantage of an earlier concerted attack on microscopic residual tumor, and appears particularly promising in sarcomas.


Pyogenic osteomyelitis of axial bones following civilian gunshot wounds.

A series of forty-five patients with low velocity gunshot wounds to the spine and pelvis were followed up for at least eight weeks to determine the incidence of pyogenic osteomyelitis and the role of debridement and fragment removal in its prevention. Four cases of osteomyelitis were found, and although debridement was not frequently done, the incidence of osteomyelitis was higher following debridement than it was without debridement. The most important cause appeared to be spread of contiguous intraabdominal abscesses into the injured paravertebral muscles and spine. If an intraabdominal abscess did not develop, the presence of gastrointestinal injury did not predispose the patient to osteomyelitis. Based on this study, we can conclude that debridement and fragment removal of the spine and pelvic bones are unnecessary for low velocity missile wounds.