Secretion of prostaglandin E2 by rabbit proximal tubules.

This study was designed to evaluate prostaglandin secretion from bath to urine in isolated perfused rabbit proximal tubules. Active prostaglandin E2 (PGE2) secretion occurred along the entire length of the proximal tubule, but the rate of net secretion was highest in the S2 segment of the proximal straight tubule. Sixteen percent of the PGE2 secreted in the proximal straight tubule was metabolized to other products. The PGE2 cell-to-bath ratio averaged 40 and the tubule fluid-to-bath ratio averaged 3.4. These findings suggest active transport of PGE2 across the peritubular membrane and passive movement across the luminal membrane. Indomethacin, probenecid, para-aminohippurate, and ouabain partially inhibited PGE2 cell accumulation and net secretion. PGE2 entered the urine of the perfused descending limb of Henle (DLH), but at a rate two orders of magnitude below that observed in the S2 segment of the proximal tubule. No evidence of active PGE2 secretion was observed in the DLH. These results suggest that PGE2 is secreted into the urine at substantial rates by the organic anion transport system of renal proximal tubules.


p-Aminohippuric acid transport into brush border vesicles isolated from flounder kidney.

p-Aminohippuric acid (PAH) transport was investigated in brush border vesicles isolated from renal proximal tubules of the winter flounder. Three characteristics of carrier-mediated transport were demonstrated: 1) unlabeled PAH inhibited the uptake of [3H]PAH; 2)[3H]PAH efflux from the vesicles was stimulated in the presence of unlabeled PAH in the extravesicular medium; and 3) PAH influx was inhibited by 2,4-dinitrophenol (DNP) and 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene (SITS). D-Glucose plus a sodium gradient stimulated PAH uptake, as did a K2SO4 gradient plus valinomycin, suggesting that PAH is transported as an anion. In contrast, PAH uptake into a membrane fraction containing mainly basal-lateral plasma membranes exhibited a larger inhibition by probenecid but a smaller inhibition by unlabeled PAH and SITS. Thus, carrier-mediated transfer of PAH driven by the electrochemical potential difference for PAH is demonstrated in the brush border membrane of the flounder kidney.


Slowly dialyzable stimulators of renal protein synthesis in urine.

Previously, we demonstrated that continuous intravenous reinfusion of half the urine output (1/2UR) in rats for 1 wk led to increased renal mass. This suggested that reduced renal excretory function, or the retention of urinary factors, was capable of stimulating renal growth. The present study was designed to examine renal protein synthesis during the early phase of this growth and to better define the nature of the stimuli. Compared with matched sham-manipulated control rats, rats subjected to 24 h of 1/2UR displayed significant increases in both the incorporation of tritiated leucine into protein and in the cellular uptake of leucine by renal cortical tissue in vitro. In addition, total protein content of the kidneys, but not of the liver, was significantly increased after 24 h of 1/2UR. Dialysis of urine prior to its reinfusion did not diminish, but rather augmented, the incorporation of leucine into renal protein. These results suggest that renal protein synthesis can be stimulated by the retention of factors in the urine that are poorly dialyzable.


Transtubular leakage of glomerular filtrate in human acute renal failure.

Ten postcardiac surgical patients with acute renal failure (ARF) were infused with inulin and dextran 40. Plasma and urine were then submitted to gel-permeation chromatography to ascertain the apparent fractional clearance profile for the dextrans. Compared to normal volunteer controls, the fractional clearance profile was substantially elevated for dextran molecules in the Einstein-Stokes radius (r) range 20-40 A. For the smaller molecules (r = 20-28 A), fractional dextran clearance in ARF was frequently in excess of unity. A simple mass conservation model which assumes that the "true" fractional dextran clearance profile for the glomerulus (in Bowman's space) in ARF is the same as that for normal controls, when applied to the experimental observations, revealed that in ARF, on the average, 50% of filtered inulin is lost by tubular backleakage. Furthermore, the model permitted an estimate of the permeability properties of the damaged tubular wall. This indicated tubular permeability not unlike that of the normal glomerulus to dextran molecules with r less than 30 A, but relative impermeability to larger dextran molecules.


Blockade of the pressor response to muscle ischemia by sensory nerve block in man.

Differential nerve block from peridural anesthesia was used to determine a) if the pressor response to muscle ischemia in man is caused by stimulation of small sensory nerve fibers and b) if these fibers contribute to cardiovascular-respiratory responses during dynamic exercise. Four men exercised at 50-100 W for 5 min. Muscle ischemia and a sustained pressor response were produced by total circulatory occlusion of both legs beginning 30 s before the end of exercise and continuing for 3 min postexercise. During regression of full motor and sensory block, motor strength recovered while sensory block continued; the pressor response was blocked as long as sensory anesthesia persisted (two subjects). During blockade of the pressor response, cardiovascular-respiratory responses to exercise gradually returned from augmented to normal (preblock) levels. Sensory blockade was incomplete in two subjects and the pressor response was not fully blocked. We conclude that stimulation of small sensory fibers during ischemia elicits the pressor response, but that these fibers appear not to contribute to cardiovascular-respiratory responses during mild dynamic exercise with adequate blood flow.


Neurohumoral regulation of blood flow to bones and marrow.

We used labeled microspheres to measure bone and marrow blood flow under control conditions and during several interventions. In dogs, blood flow to compact cortical bone (femoral diaphysis) was 2 +/- 0.1 ml.min-1. 100 g-1, and in hematopoietic marrow (femur), flow was 24 +/- 5 ml.min-1. 100 g-1. Hematopoietic cancellous bones (sternum, ilium) received substantial blood flow. We estimate that as much as 11% of cardiac output is directed to the skeleton. Bone and marrow vessels were responsive to several stimuli. During exercise, vascular resistance in bone increased two- to fourfold, in contrast to profound vasodilation in adjacent skeletal muscle. Hemmorrhage also increased bone vascular resistance. Bone and marrow vessels responded to humoral stimuli: norepinephrine increased vascular resistance and adenosine decreased resistance. Bone vessels also responded to neural stimuli: stimulation of carotid baroreceptors decreased vascular resistance, and activation of sympathetic pathways by baroreceptor deafferentation in cats increased vascular resistance. These studies indicate that bone and marrow vessels respond actively to physiological stresses and to several humoral and neurogenic stimuli


Prostaglandin E2-induced hypertension in conscious dogs.

The effects of continuous intrarenal prostaglandin E2 (PGE2) infusion (7 days) on sodium and water balance, plasma renin activity (PRA), and sodium and water balance, plasma renin activity (PRA), and mean arterial pressure (MAP) were examined in conscious, unilaterally nephrectomized dogs maintained on a fixed sodium intake of 55 meq/day. PGE2 infusion (2 microgram/min) resulted in a sustained threefold increase in both urine output and water intake without a measurable change in glomerular filtration rate. PRA increased from 0.4 +/- 0.1 during the control period to 2.2 +/- 0.9 ng AI.ml-1.h-1 on day 1 and averaged 3.6 +/- 0.5 for the remaining 6 days of PGE2 infusion. Concurrently, MAP increased from 102 +/- 3 to a maximum of 117 +/- 4 mmHg on day 5; changes in PRA and MAP were significantly correlated (r = 0.96, P less than 0.001). Sodium excretion increased from 54.5 +/- 3 to 88.0 +/- 19 meq/day on day 1, and then declined to an average of 64.8 +/- 1 meq/day for the remaining 6 days of infusion. All variables returned to the control level during the recovery period. Intravenous infusion of PGE2 (2 microgram/min) yielded directionally similar but statistically insignificant effects. It is concluded that chronic intrarenal PGE2 infusion results in marked diuresis, polydipsia, a moderate loss of sodium, enhanced PRA, and mild hypertension.


Cardiac function and morphology with aging in the spontaneously hypertensive rat.

To determine the effects of a chronic pressure load on cardiac function and morphology, spontaneously hypertensive rats (SHR) and two normotensive strains of Wistar rats (WKY and NWR) were studied under ether anesthesia at 13, 25, 52, and 90 wk of age. Although resting cardiac index of the SHR was comparable to that of WKY and NWR at all ages, the peak cardiac output and peak stroke volume per gram of left ventricle determined during a rapid intravenous infusion of Tyrode solution was markedly reduced in the SHR only at 90 wk of age. Autonomic inhibition did not alter the peak stroke volume attained, but reduced peak cardiac output at all ages in each of the strains. Absolute left ventricular dimensions in the SHR increased out of proportion to body growth, consistent with concentric hypertrophy. As peak pumping ability markedly declined from 52 to 90 wk of age in the SHR, the free wall of the left ventricle greatly thickened whereas the septum remained unchanged. At this time the right ventricle also hypertrophied. This disproportionate thickening of the walls of the left ventricle and the hypertrophy of the right ventricle were reflected in measurements of their fiber diameters. These alterations in ventricular architecture may contribute to the decrease in pumping ability observed in long-standing hypertension.


Propagation velocity and reflection of pressure waves in the canine coronary artery.

In this study the pressure wave velocity in the anterior descending branch of the left coronary artery (LADC) of the dog was measured by determining the delay time between pressure pulses along this artery. This method can only be applied if reflections of the pressure wave distal to the sites of pressure measurement are insignificant. From araldite casts of the coronary arteries the following relation between the diameter proximal to (dprox) and distal to (ddist 1, ddist 2) a bifurcation was found: dprox2.55 = ddist12.55 + ddist 22.55, indicating that reflections at a bifurcation areminimal. In dogs reflections were studied by inducing during diastole a pressure pulse in the aorta and measuring pressure and volume flow proximal to and pressure distal to a segment of the LADC at various levels of the coronary peripheral resistance. Reflection of high-frequency components (greater than 7 Hz) was found to be insignificant, allowing application of the above-mentioned method for measuring the wave-front velocity, which is insensitive to low-frequency reflection. At a pressure in the LADC of 13.3 kPa this velocity was 8.6 +/- 1.4 m.s-1 (mean +/- SD). The calculated dynamic cross-sectional stiffness (deltaP/(deltaA/A)) of the LADC was 97 +/- 11 kPa (mean +/- SE) at an arterial pressure of 13.3 kPa.


Electrocardiographic changes after bilateral carotid sinus denervation in the rat.

The effect of bilateral carotid sinus denervation (CSD) on the ECG and on the monophasic ventricular action potential (MAP) was studied in 28 and 4 rats, respectively. After CSD, T wave changes, similar to those seen in man after carotid endarterectomy, were observed and mean Q-T prolongations of 19 ms were recorded (P less than 0.001). Mean MAP increased by 10 ms (P less than 0.02). P-QRS and heart rate remained stable. Propranolol, 10 mg/kg iv, before CSD and 10 mg.kg-1.day-1 iv for 2 days prevented all ECG abnormalities. Atropine, 1 mg/kg iv, before CSD and 2.5 mg.kg-1.day-1 iv for 2 days had no effect. Isoproterenol, 0.02-0.06 microgram iv, after CSD produced further lengthening of the MAP and Q-T interval. Blood gases and electrolytes remained unchanged, and cardiac histology was unremarkable. These results suggest that CSD produces alterations in cardiac sympathetic activity in the rat leading to MAP and Q-T prolongations and to changes in the T wave form. Similar mechanisms may be operative after carotid endarterectomy in man.


Microvascular hematocrit and red cell flow in resting and contracting striated muscle.

Microvascular hematocrit and its possible relation to oxygen supply were systematically examined. We studied the red cell volume fraction (hematocrit) in arterial blood and in capillaries under a variety of circumstances. Control capillary hematocrit averaged 10.4 +/- 2.0% (SE) and arteriolar (14.2 micrometer ID) hematocrit averaged 13.9 +/- 1.2% in cremaster muscles of pentobarbital-anesthetized hamsters. Carotid artery hematocrit was 53.2 +/- 0.6%. The low microvessel hematocrit could not be entirely explained by a high red cell flux through arteriovenous channels other than capillaries (shunting). Hematocrit was not only low at rest, but varied with physiological stimuli. A 1-Hz muscle contraction increased capillary hematocrit to 18.5 +/- 2.4%, and maximal vasodilation induced a rise to 39.3 +/- 9.5%. The quantitative relations between capillary red cell flux, arterial hematocrit, and total blood flow could be explained by a two-element model of microvascular blood flow that incorporated a relatively slow-moving plasma layer (1.2 micrometer). Such a model would generate a low microvessel hematocrit and might reduce the diffusion capacity of individual capillaries, but would not reduce time-averaged red cell flux or alter steady-state vascular oxygen supply.


Experimental studies of the fibrinogen response to hemorrhage.

Rabbits were bled 20 ml/kg body wt over approximately 1 h, and the changes in hematocrit, plasma total protein, and fibrinogen concentrations, red cell and plasma volumes, and masses of total protein and fibrinogen in the plasma during and for 4 days after the hemorrhage were monitored. Ten percent of plasma fibrinogen was transferred from the interstitial fluids during the hemorrhage, and total plasma fibrinogen was raised to 140% of initial levels by 1 day later. 131I-labeled fibrinogen was given intravenously 1 day before a 20 ml/kg hemorrhage, and simulation methods described in the APPENDIX were used to define changes in the posthemorrhage fractional rates: transcapillary transfer rate (j1), lymphatic return rate (j2), and catabolic rate of fibrinogen (j3): j1 was unchanged but j2 increased and j3 briefly declined. In the day after hemorrhage fibrinogen synthetic rate increased approximately threefold to restore plasma fibrinogen concentrations to initial levels, but then returned to normal or subnormal levels. The alterations in j2 and j3 save about 20% of the synthetic work that would otherwise be required to restore plasma fibrinogen levels to normal.


Measurement of cardiac output by impedance cardiography under various conditions.

The suitability of impedance cardiography as a method to follow changes in cardiac output (CO) was investigated by comparing it with thermodilution and by measurements in conditions with predictable effects on CO. The correlation between absolute CO values obtained by impedance and thermodilution techniques was moderate (r = 0.61), but the percentage changes showed a good correlation (r = 0.84). Head-up tilting decreased CO by 25% in 5 normal subjects. Bloodletting in three subjects caused a 20% decrease, reinfusion in one subject a 16% increase. Occlusion of artificial large flow arteriovenous shunts in 6 dialysis patients caused a 12% decrease in CO, whereas the effect was less with moderate and absent with small flow shunts. Ultrafiltration caused a 28% decrease in two dialysis patients. In 20 hypertensive patients CO dropped 25% after salt depletion; propranolol administered intravenously gave a 15% decrease (n = 13), diazoxide intravenously a 30% increase (n = 6). It is concluded that, provided conditions are strictly defined, impedance cardiography is a reproducible method and suitable for the measurement of intrapatient changes in cardiac output.


Myocardial and coronary vascular responses to insulin in the diabetic lamb.

Diabetes mellitus was produced in 9 lambs by giving alloxan monohydrate, 150 mg/kg, 24 h prior to study, and these were compared with 12 control animals. Responses to insulin, 20 U/kg, were studied in each. Measurements of LV dP/dtmax, coronary sinus flow (CF) and myocardial extraction and uptake of O2, glucose and fatty acids (NEFA) were made using a hemodynamically controlled preparation described previously (Am. J. Physiol. 244: 1381, 1973). Initial arterial glucose (G) averaged 328 mg/dl in the diabetics compared with 110 mg/dl in controls. G fell to 160 mg/dl 90 min after insulin in the diabetics, and to 25 mg/dl in the controls. Initial LV dP/dtmax values were identical in both groups and showed similar increases of about 800 mmHg/s 30 min after insulin (P less than 0.001). However, initial CF was lower and resistance higher in diabetics than controls. After insulin, CF increased 50% in controls but only 10% in diabetics. Because inotropic responsiveness and O2 metabolism were the same in both groups, altered coronary vascular smooth muscle reactivity in the diabetics may explain these findings.


Myocardial performance and collateral flow after transient coronary occlusion in exercising dogs.

Fourteen dogs with prior constriction of the left circumflex (LCf) coronary artery were studied at rest and during treadmill running. Hemodynamics were measured before and after a 1-min LCf occlusion. Coronary and collateral flows were quantitated during occlusion both at rest and during exercise. Group I consisted of 4 dogs with resting collateral flow exceeding one-half (average 78%) of normal flow, and group II consisted of 10 dogs with collateral flows less than one-half (average 30%) of normal. At rest LCf occlusion caused no hemodynamic changes in group I, but stroke volume fell significantly in group II. During running, collateral flow after LCf occlusion doubled in group I, and there was only a small rise in left atrial pressure to 18 mmHg. In group II, collateral flow increased by 50% during running and actually decreased in 4 dogs. Significant cardiac failure developed as stroke volume halved, and left atrial pressure rose to an average 30 mmHg. Therefore exercise-induced depression of left ventricular function in the ischemic heart can be correlated to the amount of coronary collateral flow.


Role of cardiac sympathetics in the tonic circulatory restraint by vagal afferents.

In anesthetized cats with aortic nerves sectioned and carotid arteries occluded, we determined the role of cardiac sympathetic nerves on the tonic inhibitory restraint by cardiac vagal afferents on the cardiovascular system. The effect of afferent vagal blockade on mean arterial pressure and cardiac contractility was determined when sympathetic tone to the heart was altered. Bilateral cardiac sympathectomy produced a significant decrease in left ventricular dP/dt and attenuated the arterial pressure response to afferent vagal cold block to less than 40% of the control. The increase in dP/dt normally observed with vagal blockade was also reduced significantly. Increasing dP/dt by efferent stimulation of cardiac sympathetic nerves restored the arterial pressure response to vagal blockade to near control levels. While the vagal inhibitory activity appeared to be dependent on the resting dP/dt, left ventricular peak pressure did not seem to be contributing to the reflex. Thus, the inhibitory effects of vagally mediated reflexes from the heart which contribute to arterial pressure regulation appear to be influenced by changes in cardiac contractility induced by cardiac sympathetic nerve stimulation.


Glucose carriers at maternal and fetal sides of the trophoblast in guinea pig placenta.

Trophoblast uptake and unidirectional influx of 3H-labeled hexoses were measured relative to L-[14C]glucose (extracellular marker) using a single-circulation, paired-tracer dilution technique. Successive runs were performed in the fetal and maternal circulations of isolated dually perfused guinea pig placentas, obtained from anesthetized dams and perfused for 60--140 min. The leakiness, estimated from the percentage of the L-glucose dose that crossed the trophoblast, varied (25 +/- 3% (SE), n = 28). On the injection side the maximal sugar uptake (Umax) was measured from early venous concentration ratios, since rapid tracer backflux occurred: Umax = (1 -- 3H/14C) x 100. Umax was independent of the leakiness. In all 14 placentas studied, stereospecific saturable transport of D-glucose was demonstrated at fetal (Umax = 56 +/- 4% (SE), n = 14) and maternal (62 +/- 1% (SE), n = 14) surfaces. The mean unidirectional influxes were 3.3 and 3.5 mumol.min-1.g-1, respectively. Uptakes were inhibited by phloretin and less effectively by phlorizin. D-glucose, 3-O-methylglucose, D-mannose and D-galactose had similar Umax values, about four times that of D-fructose. Tracer backflux and transplacental flux were also equal from both sides. It is concluded that similar hexose carriers, which resemble the human erythrocyte carrier, exist at the membrane on both sides of the trophoblast. The nondestructive technique employed characterizes carriers and receptors at the blood side of cells and could be applied to the placenta or other organs in the intact animal.


Effects of two synaptic activators, calcium and ethanol, on MEPP distribution in time.

Miniature end-plate potentials (MEPPs) were recorded intracellularly from sartorius muscle of Rana esculenta. Tracings were divided into time bins whose duration approximated one-fifth of the mean interval between consecutive potentials. The observed number of bins containing 0, 1, 2, ... MEPPs was compared, by the X2 test, with the number calculated from the Poisson equation. MEPP timing was analyzed in the absence as well in the presence of Ca2+ (1 mM, 2.5 MM, and 15 mM). In half of the experiments, 0.5% ethanol was added to the bathing solution. In the absence of Ca2+, MEPP timing fitted the Poisson predictions. On adding Ca2+, the fit became poor and MEPPs showed the tendency to cluster. At 15 mM Ca2+, no experiment proved to be Poissonian. Though increasing the frequency of MEPPs similarly to Ca2+, ethanol maintained a Poissonian release of transmitter at any concentration of Ca2+. It is suggested that ethanol masks the effects of Ca2+ on MEPP timing by also inducing the discharge of transmitter outside the Ca2+-dependent sites of exocytosis in the presynaptic membrane.


Development of fatty acid esterification mechanisms in rat small intestine.

Fatty acid esterification was measured in fetal jejunal and ileal isografts implanted under the kidney capsules of adult host rats and compared to the age-controlled intestine grown in situ. Studies were conducted on the 21st, 35th, 49th, and 63rd postconceptional days, corresponding to prenatal, suckling, weaning, and weaned rats. Substantial fatty acid esterification activity was found in prenatal jejunum but not in ileum. A proximal-distal gradient of fatty acid esterification was observed in all groups grown in situ, but not in isografts. The monoglyceride pathway (MG-P) accounted for about one-third of total fatty acid esterification (TFAE) in jejunum grown in situ and remained constant through the study. In the ileum, MG-P was the major esterification pathway during the first 4 postnatal weeks, but decreased progressively after weaning to become insignificant in adult rats. TFAE fell in the jejunal isografts, whereas it increased in the ileum. MG-P remained as the major pathway in the implanted jejunum and ileum. Our studies suggest that luminal contents are probably the most important modulator for the development and maintenance of intestinal fatty acid esterification, and "fetal programming" manifested by changes in fatty acid esterification mechanisms in the isografts is less important.


Interaction of somatostatin with PTH and AVP: renal effects.

Six conscious intact dogs were studied to evaluate the interactions of somatostatin (SRIF) with exogenous antidiuretic hormone arginine vasopressin (AVP). SRIF administration caused a significant increase in free water clearance compared to a vehicle-treated group: -0.91 (+/- 0.41 SD) ml/min to 0.21 (+/- 0.32 SD) ml/min in the experimental group (P less than 0.01) versus 0.21 (+/- 0.81 SD) ml/min to -0.21 (+/- 0.68 SD) ml/min in the control (P greater than 0.5). Six conscious, thyroparathyroidectomized dogs were studied to test the interaction of SRIF and parathyroid extract (PTE). There were no significant changes in the phosphaturic and hypocalciuric effects of PTE with SRIF administration. We conclude that acute systemic SRIF administration interferes with the antidiuretic action of AVP, probably at the renal-tubular level, but does not antagonize the renal actions of PTE.


Effects of celiac and superior mesenteric ganglionectomy on interdigestive myoelectric complex in dogs.

The interdigestive myoelectrical activity of the stomach and small bowel has been studied before and after celiac and superior mesenteric ganglionectomy in four healthy, well-trained conscious dogs. The interdigestive myoelectric complex was present before and after the gangliomectomy in all dogs, but variability in the duration of its cycles was increased by ganglionectomy. The percentage of time that action potential activity was present during the interdigestive period in the stomach and orad half of the small bowel was also increased in all animals after the ganglionectomy. The duration of phase III, the activity front, was unaltered by the operation, but the timing of the other phases became more variable after ganglionectomy. The time required for migration of the complex from duodenum to terminal ileum was more variable after ganglionectomy in the three animals in which it could be measured, and in two of them the migration time was shorter. An abnormal electrical pattern occurred in all animals after ganglionectomy. Its duration ranged from 0.5--5 min. Electrically, it appeared to represent an elongated, nonmigrating activity front.


Required neural involvement in control of canine migrating motor complex.

This study evaluated the effects of muscarinic, nicotinic, and adrenergic neuronal blockade on the migrating motor complex (MMC) in four unanesthetized dogs. Circular muscle contractile activity was recorded from eight strain gauge force transducers implanted on the stomach and small intestine of each dog. Both atropine sulfate and hexamethonium bromide significantly increased the period of the MMC. When the complex returned after hexamethonium administration, the period of the succeeding complexes was significantly decreased when compared to control. Guanethidine sulfate significantly increased contractile activity on the pylorus, duodenum, and jejunum with a corresponding disruption of the MMC pattern. The migrating motor complex requires the preganglionic release of acteylcholine and possibly an inhibitory input from the sympathetic nervous system for its normal appearance.


Motor events in equine large colon.

The equine large colon is the major cellulose-fermentation locus of these species. The area of juncture of the ventral and dorsal divisions of the equine large colon was characterized, in 13 chronic unanesthetized animals and in 25 in vitro preparations, as an area of resistance to aboral flow. This is a probable pacemaker area. The reservoir function of this part of the colon is apparently facilitated by the presence of a pacemaker at this level. There was a general rise in recorded intraluminal pressure peaks during the first hour of feeding. This characteristic was not altered after resection of the extrinsic nerve supply. Electrical stimulation of the extrinsic nerve net in conscious animals at times mimicked the groups of intraluminal pressure peaks seen at the beginning of feeding.


Alkaline phosphatase in adaptation to low dietary phosphate intake.

Previous findings suggest that alkaline phosphatase (Alk Pase) may be involved in phosphate transport. Since phosphate reabsorption is enhanced in the kidney and duodenum of animals stabilized on a low-phosphorus diet (LPD), Alk Pase was measured in the kidney, small intestine, and other tissues in LPD rats. In particulate fractions from the renal cortex, intestine, renal medulla, liver, and heart ventricle from LPD rats the activity of Alk Pase was significantly increased but the activities of other plasma membrane enzymes were not different between control and LPD groups. The increased Alk Pase in the renal cortex was localized to the brush border of the proximal tubule histochemically and by measurement of Alk Pase in brush-border preparations. Also in the renal cortex, typical enzymes associated with mitochondria, lysosomes, and cytosol were unchanged with the exception of cytosolic adenosine 3',5' cyclic-monophosphate phosphodiesterase, which was increased in LPD rats. Alk Pase in the renal cortex and intestine may play a role in the enhanced phosphate reabsorption in LPD animals.


Modulation of lower esophageal sphincter relaxation in the opossum.

The relationship of lower esophageal sphincter (LES) relaxation and sphincter pressure was studied in the basal state and after neurohumoral stimulation in the anesthetized opossum. LES relaxation was induced by electrical vagal stimulation, balloon distension, and swallowing, whereas LES pressure was increased by infusions of gastrin I, histamine, phenylephrine, or bethanechol. Each agent was selected to give an approximately twofold increase in LES pressure, at the highest dosage. The lower dosage gave a submaximal increase in LES pressure. Neither gastrin nor histamine modified sphincter relaxation as induced by vagal stimulation, esophageal distension, or swallowing. Phenylephrine or bethanechol made the LES less sensitive to vagal stimulation or esophageal distension without reducing maximal LES relaxation. Only bethanechol significantly decreased sphincter relaxation in response to swallowing (P less than 0.05). The results of this study suggest that LES relaxation is not a fixed response simply dependent on the inhibitory stimulus or the resting tonic level of LES pressure, but may be modulated by both alpha-adrenergic and cholinergic drugs.


Stimulation of rabbit renal PGE2 biosynthesis by dietary sodium restriction.

Immunoreactive prostaglandin E2 (PGE2) was measured in slices of renal papilla (P), outer medulla (OM), and cortex (C) before and after 30 min of incubation (biosynthesis) in Krebs-Ringer HCO3- buffer in rabbits on low (LS), normal (NS), and high (HS) sodium diets. The 24-h urine PGE2 was also measured daily for 10 days prior to incubation. Daily urine PGE2 was significantly higher (911 +/- 54 ng) in LS, decreasing to 605 +/- 33 at NS, and 558 +/- 48 ng at HS, Initial slice PGE2 was highest in P at LS (35.5 +/- 5.1 MICROGRAMS/G), 5.1 microgram/g), decreasing to 16.9 +/- 1.3 at NS and 18.0 +/- 2.6 micrograms/g at HS. Similar patterns were observed in OM and C, which were quantitatively much lower. PGE2 biosynthesis was highest at LS (P, 139 +/- 21; OM, 58.8 +/- 5.1; C, 0.20 +/- 0.05 micrograms.G-1.30 Min-1) and lowest at HS (P, 58.9 +/- 7.4; OM, 11.8 +/- 3.1; C, 0.07 +/- 0.01 micrograms.g-1.30 min-1). Although PGE2 concentration was higher in P than in OM, the percent increase in OM PGE2 biosynthesis on LS was 3--4 times greater than in P. Since OM is 28% and P is 2% of total renal mass, these results indicate that LS markedly stimulates PGE2 biosynthesis primarily in OM and to a lesser extent in P and C, findings suggesting an important role for OM PGE2 in the renal adaptation to sodium deprivation.


Effects of kidney tubule obstruction on glomerular function in rats.

The effects of chronic blockade of single kidney tubules on glomerular capillary pressure (GCP) and blood flow were examined in anesthetized rats. Tubule blockade with castor oil for 24 h decreased GCP from 48.0 +/- 3.8 to 39.5 +/- 4.7 mmHg (P less than 0.001). The full decrease in GCP observed at 24 h was apparent by about 12 h. Bilateral ureteral obstruction for 24 h prevented a decrease in GCP. Nonradioactive microspheres (8.4 +/- 0.84 micron diam) were used to assess relative blood flow to blocked and normal nephrons. These microspheres were completely extracted by rat kidneys and had no effect on total renal blood flow. The ratio of microsphere counts in glomeruli of blocked versus normal nephrons averaged 0.61 +/- 0.21, indicating a significantly (P less than 0.001) decreased glomerular blood flow in nephrons obstructed for 24 h. Since both GCP and blood flow were reduced after tubule obstruction, afferent arteriolar constriction is involved. The data suggest a local mechanism activated by prolonged tubule blockade which shifts filtrate formation and blood flow away from blocked nephrons.


Acute reversal by saralasin of multiple intrarenal effects of angiotensin II.

Glomerular hemodynamics were measured by micropuncture technique in the plasma volume-expanded Munich-Wistar rat in 1) a control group, 2) during a pressor infusion of angiotensin II (AII), and 3) during simultaneous infusions of AII and saralasin, which returned arterial pressure to normal. Respective values obtained in the three groups studied were: nephron filtration rate: 60 +/- 2 vs. 40 +/- 2 vs. 42 +/- 2 nl.min-1.g kidney wt-1; nepphron plasma flow: 263 +/- 13 vs. 106 +/- 5 vs. 165 +/- 13 nl. min-1.g kidney wt-1; LpA, the glomerular permeability coefficient: 0.090 +/- 0.009 vs. 0.033 +/- 0.005 vs. 0.103 +/- 0.020 nl.s-1.g kidney wt-1. mmHg-1; afferent arteriolar resistance: 10.2 +/- 0.7 vs. 25.1 +/- 1.3 vs. 19.7 +/- 3.3 10(9) dyn.s.cm-5; efferent arteriolar resistance: 7.8 +/- 0.5 vs. 22.0 +/- 0.9 vs. 10.8 +/- 1.7 10(9) dyn.s.cm-5. Saralasin acutely reversed the effect of AII on both efferent resistance and LpA, suggesting that AII does not decrease LpA by inducing a fixed anatomic change. For unclear reasons, saralasin did not reverse the increase in afferent resistance associated with infusion of AII. Saralasin infusion in high AII states may acutely affect glomerular hemodynamics by decreasing efferent resistance and increasing the glomerular permeability coefficient.


Hemodynamic and excretory response of the neonatal canine kidney to acute volume expansion.

It is generally recognized that developing animals retain sodium due to an enhanced reabsorption in distal tubule segements, even when the amount administered is in excess of their needs. This study was designed to test the relationship between this relative inability to dispose of a saline load and the functional characteristics of the kidney during postnatal maturation. In addition, we explored the role played by some of the factors known to affect natriuresis in the adult subject. Measurements of sodium excretion, glomerular filtration rate (GFR), and renal blood flow (RBF) and its intrarenal distribution were made in three age groups of puppies and in adult dogs. During expansion the GFR rose rapidly and to a similar extent at all ages, but it fell thereafter, the rate of decline being much slower in adult than in developing animals (P less than 0.001). RBF and its intrarenal distribution were not altered by volume expansion. The degree of natriuresis did not reflect either the age-related or the expansion-induced changes in GFR. Fractional and absolute sodium excretion were substantially higher in 2-wk-old puppies than in either 1- or 3-wk-old animals (P less than 0.002). These findings demonstrate that the blunted renal response of the maturing animal to saline loading is due to the persistence of an enhanced tubular reabsorption rather than to a limitation in glomerular filtration.


An evaluation of large arteries compliance in man.

Cardiac output, blood pressure, and the characteristics of diastolic pressure decay were studied in 12 normal subjects and 23 sustained hypertensive patients of the same age. In normal subjects and in hypertensives, analysis of the diastolic decay showed that i) the form of the decay approximated a simple monoexponential curve during the last two-thirds of the diastolic segment, and ii) the time constant (t) of the curve was positively correlated with the total peripheral resistance (TPR), with an intercept of nearly zero. The validity of the relationship t = K x TPR was demonstrated both in groups of patients and also in individuals. Using a simple model for the vascular system, the K value was identified as the large arteries compliance and could thus be calculated in each individual. The values of arterial compliance was 1.26 +/- 0.04 ml.mmHg-1.m-2 in normal subjects and was significantly reduced in hypertensive patients (0.88 +/- 0.02 ml.mmHg=1.m-2,. P less than 0.001).


Interaction of somatic and cardiopulmonary receptors in control of renal circulation.

The purpose of this study was to determine if there is an important interaction between somatic and cardipulmonary receptors in the control of vasomotor outflow to the kidney. This interaction was examined by determining the renal vasoconstrictor responses to afferent electrical stimulation (30 V, 1 ms, 20--40 Hz) of the sectioned sciatic nerve in 8 chloralose-anesthetized dogs with sinoaortic deafferentation. During isovolemia, sciatic stimulation resulted in significant increases in arterial pressure and heart rate, and in renal vasoconstriction. Volume expansion significantly attenuated and vagotomy significantly augmented the renal vasoconstrictor responses to sciatic stimulation. These interventions did not significantly influence the arterial pressure or heart rate responses to sciatic stimulation. In 4 dogs with aortic nerves sectioned and carotid sinuses isolated and perfused at constant pressure (135 mmHg), the renal vasoconstrictor responses to stimulation were attenuated by volume expansion and augmented by vagotomy. These data show that in the absence of the arterial baroreceptors or with intermediate levels of carotid baroreceptor activation, volume expansion and, thus, augementation of discharge of cardiopulmonary receptors (vagal afferents) markedly attenuated the renal vasoconstrictor responses to somatic afferent stimulation.


Left ventricular systolic pressure-volume area correlates with oxygen consumption.

In 13 excised, cross-circulated canine hearts, we studied the correlation between left ventricular oxygen consumption per beat (MVO2) and the magnitude of a specific pressure-volume (P-V) area circumscribed by the end-systolic and end-diastolic P-V relationship curves and the systolic segment of the P-V trajectory of a left ventricular contraction. The pressure and volume load of the ventricle were changed with a volume servo pump in order to alter the P-V area, and MVO2 was measured (after each change in the pressure and volume load). In the data collected from both isovolumic and ejecting contractions of each left ventricle contracting with a stable inotropic background, we found a linear correlation between MVO2 and the P-V area. The average correlation coefficient was 0.92 +/- 0.016 (SE). Linear regression analysis yielded the formula: MVO2 (ml/beat) = alpha[P-V area (mmHg.ml/beat)] + b, where alpha, the slope coefficient, was (1.53 +/- 0.14) x 10(-5) and b, which probably represents the basal O2 consumption, was 0.019 +/- 0.003 ml/beta. We propose that the P-V area as defined above may be a good index of ventricular oxygen consumption under a given inotropic background.


Hemodynamic and plasma catecholamine responses to hyperthermic cancer therapy in humans.

Cancer patients, treated with hyperthermia (to 41.5 degrees C) under thiopental and fentanyl anesthesia, had smaller increases in heart rate and cardiac index and lesser decreases in mean arterial pressure than those reported in normal volunteers. At basal body temperature anesthesia did not alter catecholamine levels. Increasing body temperature to 39.5 degrees C and 41.5 degrees C resulted in parallel increases in heart rate and cardiac index that were directly related to the increases in plasma norepinephrine levels. At basal temperature cutaneous venous plasma norepinephrine levels exceeded those of arterial; mixed-venous plasma levels were intermediate. At 39.5 degrees C and 41.5 degrees C there were sequential increases in plasma norepinephrine. The increases in mixed-venous and arterial norepinephrine were significantly greater than in cutaneous venous blood. The differential increases in norepinephrine levels in cutaneous venous, mixed-venous, and arterial blood indicate that during hyperthermia sympathetic nerve activity in skin is decreased while that in other areas is increased, suggesting that alterations in sympathetic activity modulate the hemodynamic changes that attend hyperthermia in man.


Evidence of nonuniform sympathetic neural activity to heart regions in guinea pigs.

Central neutral activity may selectively influence cardiac regions. As an index of this, rate constants of norepinephrine turnover, KNE, in regions of guinea pig heart were determined by 1) disappearance of [3H]NE from tissues, and 2) conversion of [3H]tyrosine to [3H]NE. In sinoatrial (SA) node and right atrial appendage, KNE averaged 0.084 +/- 0.014 and 0.066 +/- 0.004 (SE) h-1, respectively (P greater than 0.05). In other specialized regions, KNE was lower than in SA node (P less than 0.05). In other contractile regions, KNE was lower than in right atrial appendage (P less than 0.05). Ganglionic blockade reduced KNE to uniform values in all heart regions. Cold stress increased KNE markedly (P less than 0.05) throughout the heart, but selectively more in SA node, AV node, proximal conduction bundles, and right atrial appendage (P less than 0.05). At room temperature, neural activity is greater to the right atrium including SA node than to other cardiac regions. At 4 degrees C, neural activity increases selectively in the right atrium and the conduction system. This suggests that central neural mechanisms contribute significantly to nonuniform cardiac regulation under conditions of progressive sympathetic activation.


Indirect measurement of instantaneous arterial blood pressure in the rat.

We devised a hydraulic servo-control system for indirect blood pressure measurement in the rat's tail, by which beat-to-beat systolic and diastolic blood pressure can be obtained. In this method the principle of "unloading vascular wall" proposed by Shirer (1962) is employed. The proposed system is composed of a transmittance photoelectric plethysmograph with an occluding cuff, a small diaphragm actuator for compressing and decompressing the segment by the hydraulic pressure, and an electromagnetic shaker driven by a volume servo circuit in accordance with the signal from the photoelectric plethysmograph. The plethysmographic signal is clamped at a proper value corresponding to the unload vascular volume by the instantaneous hydraulic servo control. The cuff pressure thus automatically controlled follows the intra-arterial pressure in the tail segment. The accuracy of this method was evaluated in comparison with direct measurement of blood pressure recorded simultaneously from 16 unanesthetized spontaneously hypertensive and normotensive rats. Close agreement between the simultaneous data from these two methods were observed.


Look at physiological integration.

Physiological integration results from cooperating processes at work within an individual. Two chief types of study are a) empirical experiments and generalizations, and b) predictive relations derived from models. In this essay the empirical type is illustrated. For example, heart rates and other circulatory properties are modified in response to messages from specific muscles, viscera, glands. In those tissues, augmented blood flow increases the supplies of oxygen and other substances at active local sites. Because specialized actions are segregated among tissues and organs, each performer evidently informs cooperating tissues of its state. Messages are transmitted at various kinds of junctions and chemical receptors. In this essay the results or actions are emphasized: in what ways do the compounded processes promote survival and advantage? Messages are sorted as they travel, certain powers of decision residing at cellular junctions. Because selected processes are corrdinated, each compound action represents an accomplishment. Thermoregulation serves as an example of relations by which several parameters yield a complex result. The multiple correlations and the intricate timing and switching are recognized.


Effect of timing of FICO2 changes on ventilatory period in domestic fowl.

These experiments were conducted to see if the pacing phenomenon found by Kunz and Miller (Respir. Physiol., 22: 167--177, 1974) in the open-loop, unidirectionally ventilated chicken is important in normally breathing birds. In this study, chickens breathed spontaneously through a tracheostomy from a gas source in which the fraction of CO2 (FICO2) could be rapidly changed. A feedback algorithm kept the FICO2 at 0.05 except for a constant duration pulse (approx 0.6 s) of low FICO2 given tau seconds after the beginning of each inspiration. In all birds tested an increase in tau resulted in a proportional increase of both inspiratory period (TI), expiratory period (TE), and the total period (Ttot). Increases in TI were from 0.5 to 1.0 times the increase in tau. Dynamic expeiments showed TI usually changed on the next breath after a step change in tau, and sinusoidal modulation of tau caused concurrent sinusoidal changes in TI, TE, and Ttot. These findings indicate that the phenomenon that produced pacing in the unidirectionally ventilated birds is important to the ventilatory pattern of normal breathing.


A two-dimensional transient mathematical model of human thermoregulation.

Current models of human thermoregulation are limited in that they fail to account for temperature distribution in any spatial direction other than radially outward from the body centerline. They are therefore incapable of accounting for nonuniform environmental conditions or nonuniform heat generation from muscles or organs within the body. However, for many situations, these nonuniform conditions are commonplace and lead to disparate skin temperatures and heat loss rates on different sides of the same body compartement. A new mathematical model of human thermoregulation that has been developed and is presented here has the capability of predicting transient temperature variations in two spatial dimensions, both radially and angularly, as measured from the body centerline. In so doing, the model accounts for nonuniform environments and internal heat generation rates. Typical results from the model are demonstrated, and comparisons with available experimental data are also presented.


Facilitation of female reproductive behavior from mesensephalic central gray in the rat.

Electrical stimulation in the mesencephalic central gray (CG) and adjacent subtectum through chronically implanted electrodes in free-moving estrogen-primed ovariectomized female rats elicited a rapid and large facilitation of the lordosis reflex in response to either male mounts or manula cutaneous stimuli. Unilateral stimulation was sufficient for this effect. The facilitation increased in a graded manner to increased stimulus intensity, and was optimally evoked by stimuli delivered at 50--150 Hz. Facilitation disappeared rapidly following the end ot electrical stimulation, and within 15 min, reflex performance returned to the prestimulation level. Lordosis facilitation appeared when no aversive responses occurred; stimulation with comparable parameters at the lateral edge of CG or in the mesencephalic reticular formation often resulted in postural changes or aversive responses but was not able to facilitate lordosis. Lordosis refelx facilitation was probably mediated by projections descending from neurons in and around the CG, and represents stimulation of a functional link between ascending somatosensory and descending motor systems for the control of lordosis behavior.


Mesencephalic mechanisms for integration of female reproductive behavior in the rat.

Placement of bilateral electrolytic lesions in the mesencephalic central gray (CG) of estrogen-primed ovariectomized female rats produced an immediate decline in performance of the lordosis reflex. Lesions that destroyed the dorsal half of the CG and the adjacent subtectal region were effective. The decrease in individual animals in terms of the lordosis reflex score ranged from 20 to 100% of the prelesion performance. Such lesions abolished the facilitation of lordosis by electrical stimulation of the ventromedial nucleus of the hypothalamus. Similar abrupt losses of lordosis followed bilateral lesions of either a) the area between CG and the cuneiform nucleus of the mesencephalic reticular formation (NCf); or b) the ventrolateral quadrant of the NCf. The difference between these two lesions was that the effect of the latter could be overridden by electrical stimulation of the CG, whereas that of the former could not. We conclude that the CG is an important supraspinal component of the circuit for lordosis behavior, constituting a link between ascending somatosensory and descending motor systems for lordosis. It probably facilitates lordosis when activated by behaviorally relevant peripheral somatosensory and/or ventromedial hypothalamic inputs.


Reversal of phosphorylase activation in muscle despite continued contractile activity.

During studies of the regulation of phosphorylase activity and glycogenolysis in contracting muscle, it was found that conversion of phosphorlyase beta to alpha is transient. Reversal of phosphorylase activation during both continuous and intermittent stimulation in the plantaris might, in part, have been due to development of fatigue. However, a complete reversal of phosphorylase activation was also evident within 5 min in the absence of fatigue in soleus muscles stimulated tetanically with 100-ms-long trains at a rate of 60/min. These muscles showed no significant decline in contractile force. Glycogen breakdown stopped in the soleus when phosphorylase reverted to the beta form, providing evidence that phosphorylase beta was not active. This lack of activity is probably explained by the finding that ATP and AMP concentrations changed little, while glucose 6-phosphate increased. Reversal of phosphorlyase activation soon after the onset of steady-state work may be a mechanism for conserving glycogen when the supply of other substrates is adequate to meet the muscles' energy needs.


Catecholamine elevation in iron deficiency.

Iron-deficient rats have increased blood and urinary catecholamines regardless of whether anemia is or is not present. The catecholamine response in both iron-deficient and control animals is largely temperature dependent, showing little difference at the isothermic temperature of 30 degrees C but a two- to threefold increase in iron-deficient animals over controls at lower temperatures. The iron-deficient rat is unable to maintain body temperature at 4 degrees C and this is independent of anemia or of food intake. When animals are run on the treadmill for 4 h, body temperatures increase but the difference observed at 4 degrees C between iron-deficient and control animals persists. The underlying abnormality in temperature regulation and in catecholamine response disappeared after 6 days of iron therapy.


Static and kinetic properties of the dolphin pupil.

In dim illumination, adult human pupil area becomes asymptotic at about 51 mm2 whereas the dolphin pupil achieves an area of about 70 mm2 under equivalent conditions. At moderate illumination levels (greater than 100 lx), the dolphin pupil becomes a horizontally oriented ellipse and develops a pronounced central constriction with additional light. The relative relationship between pupil area and illumination copmares closely with published human data. Rates of pupil response to step increments in illumination are very similar for the two species. Although the pupil has been proposed as a mechanism for correction of the dolphins' high aerial myopia, correlation of the laboratory findings on static and kinetic pupil properties with visually controlled aerial behaviors disclosed no special interdependence.


Investigation of hot flashes by ambulatory monitoring.

The unpredictability of hot flashes makes their investigation difficult. A method for continuous monitoring of subjective arousals and their objective correlates is here described and illustrated with results from one subject. Temperatures of special interest with respect to hot flashes--toe, cheek, vagina, and air--were recorded on a protable magnetic tape during routine living at home. The subject signaled the "on" and "off" of each perceived flash with a hand switch and also entered information in a notebook. She signaled 63 flashes on 5 days, during which the cheek and toe temperatures showed transient increments. Some of the flashes were labeled uncertain in the notebook. The subject also had 23 episodes of these temperature increments that she did not identify by signals as flashes. In these episodes, therefore, the mechanism of consciousness was not activated. Perceptions that coincided with transient temperature increments thus ranged as follows: subconscious, uncertain, definite but bearable, mildly distressful, and strongly distressful. Hence ambulatory monitoring can provide objective evidence of transient activation of the hypothalamic heat loss mechanism, whether perceived or not.


Endogenous nature of circadian rhythms in calcium metabolism.

Rats studied when the lights are on from 0600 to 1800 daily and fed only in the dark period displayed circadian rhythms in plasma calcium (ionized and total) and 45Ca concentrations, 6 and 8 days after 45Ca administration. In rats fed a calcium-deficient diet, the amplitude of daily variation of plasma ionized and total calcium increased markedly whereas plasma 45Ca daily fluctuation remained essentially unchanged. In the calcium-deficient rats, significant correlations between plasma calcium and 45Ca and between plasma calcium and magnesium were observed throughout the 24 h; circadian periodicity of calcium metabolism persisted in rats fasted overnight, regardless of the illumination schedule. Normal daily fluctuations in plasma 45Ca, lost after thyroparathyroidectomy (TPTX), were restored by feeding the TPTX rats a high-calcium diet. These results demonstrate clearly that circadian rhythms of calcium metabolism occurred irrespective of the light-dark schedule, the calcium supply through intestines and the thyroparathyroid system. An attractive suggestion is that circadian rhythmicity originates as a result of dynamic properties involving nonlinear processes of calcium metabolism.


Liver heat production and temperature regulation in the anesthetized dog.

Liver heat production (LHP) was measured in the anesthetized dog by a new calorimetric method. Blood flows and temperatures were measured at the same points. The method avoided damage of liver innervation and vascularization. Changes of LHP were investigated under different thermal conditions. Measurements at controlled arterial temperatures within the physiological range showed changes of LHP when arterial temperature was randomly increased or decreased. When measured LHP was compared in experiments carried out at different ambient temperatures, a negative linear correlation was found between LHP and the ambient temperature. It was concluded that liver heat production may be a factor in temperature regulation.


Zinc metabolism in humans: a kinetic model.

A quantitative model is developed that describes the kinetics of the early phases of zinc metabolism in humans. The model is based on averaged data obtained over 5 days from 17 atients with smell and/or taste dysfunction who were given 69mZn in trace amounts orally and intravenously. A function describing the rate of entry of 69mZn into systemic plasma following ingestion of the isotope is derived showing that about 37% of the ingested zinc enters plasma. Gastrointestinal absorption is essentially completed by 4 h. Sixty-seven percent of the absorbed zinc in the portal circulation is extracted by the liver before being released into the systemic circulation and agrees with the calculated extraction efficiency from the systemic circulation. There are both rapid and slow exchnage phases between plasma and liver and between plasma and red cells. The calculated steady-state zinc values for plasma, red cells, and liver agree with previously reported measured values implying there are no additional zinc pools in these tissues. The tracer data, however, account for only 10% of total body zinc, the remaining 90% in tissues whose kinetics are too slow to be resolved from a 5-day study.


Flux of labeled compounds in biochemical oscillations.

If a labeled compound (e.g., a radioisotopically or chemically labeled metabolite) is introduced into any biochemical reaction system, the label will be removed by catabolic reactions and replaced by unlabeled compound through anagolic reactions. It is shown that the removal of labeled compounds is particularly efficient if the rates of the catabolic steps are able to oscillate. This is demonstrated by comparing reaction schemes that maintain the same mean fluxes and concentrations of metabolites and the same overall chemical affinity but which differe in that the rate of catabolism is either constant or oscillates as a function of time. Simple analyses are presented for both small and large oscillations of undefined wave form and for sinusoidal oscillations. The enhanced removal of labeled compounds from oscillating reaction systems is also documented by numerical computation on a nonlinear model system. It is suggested that this ability to remove labeled compounds may have provided a selective advantage for the evolution of some biological oscillations.


Dehydration elevates osmotic threshold for salt gland secretion in the duck.

Acute salt and water balance measurements were made in two conscious salt water-acclimated Pekin ducks at and above their osmotic threshold for salt gland secretion. Intravneous infusion of 1,000 mosmol/kg H2O NaCl at 0.350 ml/min increased plasma tonicity less than 0.5% and increased secretion from nearly zero to a rate matching the infusion. Continuous secretion at a similar submaximal rate was driven by 5,600 mosmol/kg H2O NaCl infused at 0.070 ml/min. Osmolality of secreted fluid was constant for any secretion rate, so that net water loss occurred when the concentration of infusate exceeded that of secreted fluid. Threshold plasma osmolality increased by 9 mosmol/kg H2O after the loss of 77 g water (3% body wt). Solutes were always secreted at the infusion rate, even when body fluid osmolality increased while body water decreased. We conclude that the salt gland controller is sensitive to more than just extracellular fluid (ECF) tonicity, and we suggest that elevation of the osmotic threshold may occur in response to decreased ECF volume.


Noncoordinate regulation of cytoplasmic RNA in compensatory renal hypertrophy.

To examine the regulatory role of mRNA in compensatory renal hypertrophy, the accumulation and decay of [3H]orotic acid in poly(A)-containing mRNA in mouse kidney was analyzed after unilateral nephrectomy during the period of maximal rRNA accretion. The distribution of radioactivity between newly synthesized poly(A)-containing and poly(A)-lacing polysomal RNA was altered, but no differences in mRNA half-life were observed in growth compared with effects of sham nephrectomy. Radioactivity in polysomal polyadenylated RNA was diminished by approximately 25% during growth where mice were labeled after nephrectomy, but if mice were labeled 18 h before operation, no difference was noted. Thus, accumulation of newly synthesized poly(A)-containing mRNA relative to RNAs that lack poly(A) is changed early in the course of renal hypertrophy. This noncoordinate regulation may represent a control mechanism effective early in induced cell growth involving mRNAs that lack poly(A).


The medium and the message: development of videotapes for teaching psychiatry.

The author examines the issues surrounding the development and use of videotapes to teach psychiatry. She describes the special capabilities of videotaped material as well as how videotapes are produced; the structure of videotapes that use feedback techniques; the different ways medical students, psychiatric students, and experienced clinicians respond to videotapes; the special problems involved with teaching nonpsychiatric medical students about psychiatry; and the use of videotaped materials for patients and the public. She concludes that the use of videotapes to teach psychiatry, especially to teach the public, is an important area for development by psychiatrists.


Superkids: competent children of psychotic mothers.

In a follow-up study of children of psychotic mothers, the authors examined a subgroup of outstandingly talented, colorful, and competent "high-risk" children. These children and their mothers were given a variety of psychological tests and were interviewed individually. They were then compared with a control group of children whose mothers had no psychiatric illness. The 6 most socially and intellectually competent high-risk children were strikingly more competent, colorful, creative, and talented than the 6 highest functioning control children. They more often reported having a best friend and had extensive and positive contact with an extrafamilial adult. Another important variable in the prediction of high social competence among children at high risk is a warm relationship with the mother.


On schizophrenic psychoses.

The author traces the history of the concept of schizophrenic psychoses from Kraepelin's differentiation of dementia praecox from other mental illness and Bleuler's formulation of schizophrenia through the delimitation of the definition of schizophrenia to current thought on the etiology, treatment, and outcome of schizophrenic psychoses. He stresses the importance of our knowledge of both psychological and hereditary factors and urges that rather than searching only for a single, causal metabolic error we also accept the possibility that schizophrenia occurs in highly human, spiritual spheres and consider the schizophrenogenic influences in the lives and personalities of individual patients.


Combined use of molindone and guanethidine in patients with schizophrenia and hypertension.

Human sympathetic nerves have a high-affinity norepinephrine uptake system. This uptake system is inhibited competitively by chlorpromazine but not by molindone, which suggests that molindone will not interact adversely with guanethidine, an antihypertensive drug that enters sympathetic nerves via the high-affinity uptake system. Accordingly, patients with concomitant schizophrenia and hypertension were treated simultaneously with molindone and guanethidine; there was no evidence of an adverse drug interaction. The data indicate that molindone and guanethidine can be used in combination safely and effectively.


Subtypes of depression identified by the KDS-3A: a pilot study.

To devise a system of classifying depression subtypes at intake, the authors administered the Kupfer Detre Scale (KDS-3A) to depressed outpatients at intake and after one, three, and six months of treatment with tricyclic antidepressants or lithium carbonate. None of the 10 tricyclic responders scored below 8 on the 14-point chronic anxiety scale at intake while 7 of the 12 lithium responders did, suggesting that any patient scoring below 8 is a probable candidate for lithium therapy. Patients scoring 8 or above on the chronic anxiety scale fell into two categories, those who had a low impulisivity score and responded to tricyclic antidepressants and those who had a high impulsivity score, responded to lithium, and had cyclothymic disorder or emotionally unstable character disorder.


Unipolar mania: a distinct clinical entity?

Of the 241 lithium clinic patients at the New York State Psychiatric Institute with bipolar I affective disorder, 38 (15.7%) had never been hospitalized or somatically treated for depression. These "unipolar manic" patients had a significantly lower incidence of rapid cycling and suicide attempts than other bipolar I patients. No differences were found, however, in risk of illness in first-degree relatives. Lithium was an effective prophylactic agent in these patients. Some patients originally classified as "unipolar manic" were found to have depressive episodes with additional information and clinical observation. "Unipolar mania" appears to be a subgroup of bipolar I illness, but there are no data to support the hypothesis that it is a separate entity.


The right to treatment suit as an agent of change.

Right to treatment suits can serve as agents of change in the standards and function of psychiatric institutions. The author evaluated five state psychiatric institutions as an expert witness in right to treatment suits. He found that changes for the better were made in most of these institutions as a result of the suit, whether it was settled or unsettled. Although he enumerates the problems caused by such suits, he concludes that they can be a positive force for improving mental health care.


Community support programs: program evaluation and public policy.

The plight of chronic psychiatric patients in the community has led to a major federal effort to resolve fragmented and disorganized care. The Community Support Programs (CSPs) recently funded by NIMH offer the promise of reducing these difficulties by creating comprehensive human service systems at the local and state levels. However, the author points out that these demonstration projects should be evaluated lest they continue to operate on the basis of rhetoric rather than fact. He presents an evaluation framework whereby indexes pertinent to each program goal of the CSPs can be measured and the resulting data used for public policy purposes.


Intolerance and extremism in a correctional institution: a perceived ethnic relations approach.

The authors used an ecological approach to analyze the interaction of ethnicity, environment, personality, and ideology that led to racial intolerance, ethnic strife, and the existence of a self-styled neo-Nazi group in a correctional institution for youthful offenders. Staff members completed a questionnaire on which they rated the behavior of each of 320 inmates toward his own and other ethnic groups. The inmate's membership, if any, in a "power" subgroup was also noted. Results indicated a correlation between antagonistic patterns of ethnic relations and receptivity to racial propaganda and ideology. Further research focusing on the perceived ethnic relations climate is necessary to determine whether the patterns found in this institution are typical and to ascertain explanations for this correlation.


Drug abuse and criminal behavior in delinquent boys committed to a training school.

To determine drug use or drug abuse status according to DSM-III criteria, the authors interviewed 109 delinquent boys who had been committed to a training school. They categorized each boy as an offender against a person or as an offender against property only. They found that person offenders were significantly older, came from larger communities, abused a greater number of drugs, had higher asocial index scores, and had lower full-scale IQ scores than property-only offenders. The IQ score and the number of drugs abused were the most important variables predicting whether a subject belonged to the person offender or property-only offender group.


The relation of time spent in drug abuse treatment to posttreatment outcome.

The author examined follow-up outcomes in the first year after treatment in relation to time spent in treatment in the Drug Abuse Reporting Program. Follow-up interviews were completed with more than 3,000 people admitted to drug abuse treatment during 1969--1972, including clients treated with methadone maintenance, therapeutic communities, outpatient drug-free programs, and outpatient detoxification, as well as a group who completed intake procedures but did not return for treatment. Longer time in treatment was related to better posttreatment outcome, but clients who spent less than 3 months in treatment were not significantly different from the detoxification-only group or the intake-only group.


Clinical supervision of the initial interview: effects on patient care.

The authors raise the question of whether the directly supervised initial evaluation of outpatients by psychiatric residents influences the quality of patient care. The charts of 78 patients with direct supervision and 78 patients with traditional supervision were randomly selected for review four months after the initial interview. More than twice as many patients with direct supervision remained in active treatment or terminated after successful short-term treatment compared with traditionally supervised patients in the early intake period. Patients with direct supervision also received a less pathological diagnosis.


Tyramine infusions in bipolar illness: behavioral effects and longitudinal changes in pressor sensitivity.

Steady state intravenous tyramine dose pressor-response tests were administered to a patient with bipolar illness during depressed and hypomanic phases of her illness. The greatest tyramine sensitivity while unmedicated occurred when the patient was hypomanic, and the least sensitivity when she was depressed before her first switch. The data raise the possibility that changes in peripheral alpha-adrenergic receptor sensitivity accompany spontaneous mood cycles. Tyramine produced a replicable mood and cognitive alteration only in the infusion closest to the switch from hypomania to depression, suggesting that the CNS may be particularly susceptible to peripheral noradrenergic inputs at specific points in bipolar illness.


Types of psychopathology displayed by heroin addicts.

Symptom profiles of 157 male and 54 female heroin addicts based on Brief Psychiatric Rating Scale scores were compared with normative data for 6,000 psychiatric patients by using previously described schizo-depressive and coping-resignation contrast functions. Diagnostic types found among the addicts were as follows: anxious-depressive features, 35.1%; undifferentiated syndromes, 26.5%; hostile-depressive features, 16.6%; retarded depressive features, 9.5%; hostile suspicious traits, 6.6%; and blunted affect without significant depressive features, 5.7%. None of the addicts showed levels of thought disturbance comparable to those found in the psychiatric patients.


Dynamic psychotherapy with the bilingual patient.

Bilingualism is known to affect the communicative behavior of the individual. This paper describes the implications of the bilingual experience for the process of dynamic psychotherapy, and presents recommendations to psychotherapists treating the bilingual population.


Collateral therapy for the abused child and the problem parent.

Physical or sexual abuse of children is a psychopathic situation wherein both the abused child and the problem parent require collateral therapy with the eventual aim of rehabilitating the family by reinstating the child. The abusive diathesis of the parent is rooted in her or his inadequately nurtured childhood.


Psychotherapy of the psychosomatic patient.

The role of psychotherapy for psychosomatic patients is reviewed. Barriers to treatment, including special characteristics of these patients that make them poor candidates for traditional psychodynamic interventions, are discussed with implications for practice. Clinical recommendations encompass two broad preparatory phases: I, the health alliance, and II, the life alliance.


Tracking errors in psychotherapy.

Typescripts of 10-minute segments of psychotherapy sessions often reveal instances where the therapist made incorrect statements that got the patient off his track. Tracking errors are classified and their effects described. By learning to recognize such errors therapists can diminish their frequency.


Acting out in adolescence.

Adolescent individuation is frequently signified by acting out independent and dependent strivings. There can be a struggle with attachment to parents who do not acknowledge the adolescent's emerging identity. A narcissistic bond can develop between parent and adolescent that impedes individuation.


Minimal brain dysfunction and borderline personality adjustment.

Clinical experience shows that many patients diagnosed as having a borderline personality structure show a history of minimal brain dysfunction in childhood. Neurologically based dysfunctions create disruptions of drive level, perception, basic language structure, and cognition which form a constitutional basis for the distortions of early object relations. A treatment program considering both biogenic and psychogenic etiology is outlined.


Negative responses of the borderline to inpatient treatment.

The intense therapeutic encirclement maneuvers possible in long-term inpatient therapy of the borderline patient frequently stimulate emotional flooding and intense negative therapeutic reactions. Such reactions have understandable precipitants: a mixture of therapeutic goals, treatment methods, and defensive structures of the patient best conceptualized within an object-relations model.


The conquering hero quits: narcissistic factors in underachievement and failure.

In narcissistic individuals the grandiose self persists, making impossible demands for omnipotence. This often results in inability to tolerate any endeavor which requires sustained effort and repeated trial and error. Among narcissistic college students, academic failure frequently results. This dynamic applies to success neurosis in general. Treatment considerations are discussed.


Parent-child communication in widowed families.

When a parent dies the surviving parent and children are often unable to work together to cope with the loss. We propose that this situation arises from their inability to accept the finality of death. Parents and children have difficulty adjusting to life without the deceased because of their expectation that he or she will return.


Self-disclosure in therapy: marriage of the therapist.

The author presents how his interest on the general subject of self-disclosures in therapy evolved. Literature on this subject is reviewed with particular attention to intercurrent events in the therapist's life that may affect ongoing psychotherapy. Six clinical vignettes of psychotherapy cases illustrate varying reactions. The effects that planned disclosure of an intercurrent event (his marriage) had on this process are discussed.


Transsexual symptoms in a male child treated by a female therapist.

The literature on the psychodynamics and treatment of transsexualism indicates a pathological mother-son relationship, yet uniformly recommends a male therapist. A case of a six-year-old boy with transsexual symptoms treated by a female therapist is presented, and there is a discussion of the theory and implications arising from the case.


Hand and wrist injuries in the athlete.

Injuries to the hand and wrist are probably among the most common injuries incurred by the athlete. Neglect of such injuries may result in irreparable damage to the hand or wrist. This summary of the more common injuries to these areas seen in the athlete, with a description of the recognition and treatment, gives the reader insight into the multiple considerations the athlete and coach must have. Even seemingly minor injuries must be carefully evaluated and treated by a physician. Early diagnosis, accurate precise treatment, and proper rehabilitation are extremely important to regain optimal function after these injuries. They may have a significant impact not only in athletic competition but also in the athlete's selection of an occupation. It is psychologically important also that the participant be returned to his particular sport as soon as possible. Most of the injuries can be controlled by conservative means. However, when surgical repair is indicated, it is important for the surgeon to be trained and familiar with the anatomy and techniques of surgery of the hand and wrist.


Preoperative psychologic testing as a predictor of success in knee surgery. A preliminary report.

Preoperative psychologic test scores derived from the Minnesota Multiphasic Personality Inventory (MMPI) were evaluated as predictors of success after elective knee surgery. The patients were examined 1 to 3 years after surgery and were evaluated in terms of subjective improvement, pain, level of activity, work restrictions, swelling, and strength. Patients that had scored high on the hysteria and hypochondriasis scales of the MMPI showed less improvement after surgery than those patients scoring lower on these scales. The results indicate that personality factors may play an important part in the symptomatic success after elective knee surgery.


Volvulus of the cecum: choice of operation.

Although it is clear that there is a significant frequency of recurrent volvulus after cecopexy, there is no evidence from either this series or previous reports that resection is associated with a lower recurrence rate than tube cecostomy. In the absence of data suggesting a clear superiority of colon resection, it appears that tube cecostomy should be the treatment of choice for cases of cecal volvulus that are not complicated by vascular compromise.


Clinical evaluation of long-term survival after total gastrectomy.

Twenty-seven cases of long-term survival after total gastrectomy were clinically evaluated. From the standpoint of general nutrition and rehabilitation, the patients appeared to be in satisfactory condition. However, hyperchromic anemia, serum vitamin B12 deficiency, and osteoporosis were noted in some patients.


Discriminate use of antibiotic prophylaxis in gastroduodenal surgery.

In a prospective study of 107 patients undergoing surgery for gastroduodenal disease, antibiotics were withheld from a group of 24 patients defined preoperatively to be at low risk of developing postoperative infections; no wound infection occurred in this group. Perioperative cephaloridine was randomized among the remaining patients (high risk). Wound infections developed in 11 of 42 patients who did not receive cephaloridine, but in none of the 41 patients who were given cephaloridine (p less than 0.02). Coliform bacteria were grown only from swabs of the stomach mucosa of patients in the high risk group and were the main cause of wound infections. Severe preoperative lymphocytopenia was frequently associated with the development of serious postoperative sepsis. The results validate a policy of restricting antibiotic prophylaxis in gastroduodenal operations to patients at high risk of postoperative infection and suggest a new risk factor--the preoperative blood lymphocyte count.


Gastric, pancreatic, and biliary secretion and the rate of gastric emptying after parietal cell vagotomy.

We compared the gastric, pancreatic, and biliary secretory responses to a liquid test meal and the rates of gastric emptying of liquid and solid test meals in six patients at least 1 year after parietal cell vagotomy with eight unoperated subjects, one with duodenal ulcer disease and seven normal control subjects. Parietal cell vagotomy decreased gastric acid secretion to one third of normal, but total trypsin and bile salt secretion during the first 150 postcibal minutes were normal. The liquid test meal emptied from the stomach faster after parietal cell vagotomy, the pattern of emptying being exponential in the vagotomy patients and linear in the normal subjects. The rate of gastric emptying of a liquid meal, although faster than normal, was less precipitous after parietal cell vagotomy than after truncal vagotomy plus drainage or subtotal gastrectomy, and trypsin and bile salt concentrations were not diluted to abnormal levels, as occurs after these other procedures. Furthermore, emptying and dispersion of solid food remained normal after parietal cell vagotomy. These findings probably explain, at least in part, the decreased incidence of postprandial dumping and diarrhea that accompanies parietal cell vagotomy compared with the other popular operations for duodenal ulcer.


Use of ultrasound to demonstrate gallstones in symptomatic patients with normal oral cholecystograms.

Seven patients who had typical and persistent symptoms of gallbladder disease but repeatedly normal oral cholecystograms were seen in an 18 month period. Ultrasound examination of the gallbladder was diagnostic of cholelithiasis in all seven patients. Six patients were found to have gallstones at operation, and the seventh had histologically proved chronic cholecystitis. Although oral cholecystrography is a highly accurate examination, false-negative results do occur. Gray scale ultrasonography is a safe and also highly accurate means of providing objective evidence of cholelithiasis in patients clinically thought to have gallstones despite normal oral cholecystograms.


Twenty-two year experience with periampullary carcinoma at Memorial Sloan-Kettering Cancer Center.

The resectability rate was high (84 per cent) for patients with periampullary cancer. The incidence of lymph node metastases was also high, being 50 per cent for those with small tumors (2 cm or less). The 5 year cure rate was 67 per cent for patients with negative nodes but 0 per cent for those with positive nodes.


Preoperative physical assessment of thyroid glands in previously irradiated patients.

The Evanston Hospital maintains an Irradiated Thyroid Evaluation Clinic that has evaluated 695 patients since 1975. One hundred fourteen patients were retrospectively analyzed, and an attempt was made to correlate the preoperative physical examination with the pathologic specimen after thyroidectomy. There was no statistically significant difference between the incidence of carcinoma in glands containing a single nodule (23 per cent) and in multinodular glands. Postirradiation thyroiditis complicated the physical description of glands preoperatively. The categorization of physical findings served only to identify persistent thyroid abnormalities, which must be explored surgically. The overall incidence of carcinoma in the 114 available cases was 34 per cent, with nodal metastases in 18 per cent of the patients with carcinoma.


Thermal influence on the lymphocytic response of cancer patients.

A variation was noted between normal subjects and cancer patients in the response of their lymphocytes to different antigens. Raising the temperature from 37 degrees C to 40 degrees C aided in improving lymphocytic activity to the antigenic stimulation. The heat response was more noticeable in normal subjects than in cancer patients, which suggests that immunotherapy should be initiated early in patients with malignant disease before there is systemic involvement from an increasing tumor burden.


Femoropopliteal bypass grafting: predictive value of preoperative angiography.

Our experience with femoropopliteal grafting was reviewed to determine whether quantitative grading of the preoperative angiogram could be correlated with the outcome of the grafting procedure. The series consisted of 53 bypass grafts in 50 patients. The quantitative grading of the preoperative arteriogram correlated with the graft closure rate during the follow-up period of 48 months. The group with the most advanced arterial occlusive disease on angiography had a 32 per cent failure rate, while those with the least severe disease had a 6.7 per cent failure rate. The intermediate group had a 16.7 per cent closure rate. Using linear regression analysis, the data indicated a correlation between the time of graft failure in the first 18 months and the angiographic grade (p less than 0.01).


Role of angiography in the diagnosis of pancreatic neoplasms.

The vascular architecture of the pancreas has been described, but few reports indicate preoperative accuracy. During the last 3 years, selective superior mesenteric and celiac angiography was performed in 471 patients. In 35 of these patients, additional selective angiography of the superior pancreaticoduodenal and inferior pancreaticoduodenal arteries was performed to reveal the detailed vascular pattern of the pancreas and its surrounding structures. Exploratory surgery was performed in all patients except the four control subjects. The angiographic findings reflected a poorly vascularized infiltrating lesion with invasion of the blood vessels and serpiginous encasements. Peripancreatic extension of the tumor indicated nonresectability. In early pancreatitis, the pancreas showed increased vascularity and occasional stretched vessels. In more advanced pancreatitis, the arteries were prominent and irregular with increased parenchymal accumulation of contrast medium in the capillary phase. In pseudocysts of the pancreas, the only finding was stretching of the vessels around the lesion. A well circumscribed lesion with increased contrast medium in the capillary and venous phases diagnostic of pancreatic adenoma. Pancreatic angiography is an important diagnostic tool in evaluating and staging pancreatic neoplasms.


Importance of capillary perfusion.

Perfusion is more critical than oxygen in the maintenance of cell viability. A high hematocrit or high fibrinogen level increases blood viscosity and predisposes to disseminated intravascular coagulation. It is recommended that a hematocrit of about 30 be maintained in periods of circulatory stress such as shock or extracorporeal circulation.


Discrepant estrogen receptor protein levels according to surgical technique.

A marked discrepancy in the positivity rate of estrogen receptor protein assessment in breast biopsy specimens obtained by conventional scalpel dissection (53 per cent) and by electrodissection (27 per cent) raised the question of whether the latter technique was appropriate for obtaining specimens for estrogen receptor protein assay. Two cases served as their own controls to demonstrate the inherent error in obtaining tissue by electrodissection. It is now urged that the electrocautery technique be avoided when tissue is obtained for estrogen receptor protein assay.


Deficient collagen formation by obese mice in a standard wound model.

Poor healing was demonstrated in two different experimental models of diabetes mellitus. In one model, there was an absolute lack of insulin and in the other, a resistance to insulin. A review of the history of the results of surgery in diabetic patients shows that in the clinical situation, wound failure is associated with both a lack of insulin and a resistance to insulin. Thus, the causes of wound failure in diabetic patients include a failure of insulin to perform its normal role in healing. This does not exclude other causes such as "small vessel disease" as etiologic factors, but it does suggest that control of metabolic derangements is beneficial to healing in diabetic patients who undergo operation.


Pancreatic ascites: a rare complication of distal splenorenal shunt.

Ascites has become recognized as a common postoperative complication of the distal splenorenal shunt. On rare occasions the ascites has been chylous in nature. The present report is the first documented case of pancreatic ascites occurring after this operation. This complication developed in the combined setting of chronic pancreatitis and surgical trauma to the pancreas. Since the management of pancreatic ascites differs from that of cirrhotic or chylous ascites, it is recommended that this diagnosis be considered whenever a patient develops severe ascites after a distal spenorenal shunt.


Pancreatic ascites: management by caudal pancreatectomy and side-to-side pancreaticojejunostomy.

A patient with pancreatic ascites is presented who had neither a pseudocyst nor demonstrable pancreatic duct disruption, despite the presence of both calculi and strictures in a dilated duct of Wirsung. Concurrently, the patient exhibited intractable abdominal pain characteristic of end-stage chronic alcoholic pancreatitis. The pancreatic ascites responded only briefly to nonoperative management with hyperalimentation. Side-to-side pancreticojejunostomy with caudal pancreatectomy relieved the patient of both pain and ascites, suggesting that this more direct approach may be worthy of consideration in patients with similar findings.


Peutz-Jeghers syndrome and its complications. First case report from Malaysia with review of literature.

We report for the first time from Malaysia a patient with Peutz-Jeghers syndrome complicated by successive intussusceptions requiring extensive small bowel resection. Our experience is compared with that of other authors by a review of the literature highlighting important points in the diagnosis and management of complications in Peutz-Jeghers syndrome.


Congenital colonic atresia and stenosis.

Five more cases are added to the 88 reported cases of successfully treated newborns with congenital colonic atresia and stenosis. Because colonic atresia and stenosis are lethal conditions when untreated, early diagnosis and operative treatment are major requisites for survival. A two-stage procedure consisting of an emergency colostomy for decompression as the first stage and an elective resection with anastomosis a few months later is recommended. The need for thorough exploration of the abdomen is emphasized because atresias may be multiple or may be associated with additional gastrointestinal anomalies.


Peritoneal encapsulation in childhood. Case report, embryologic analysis, and review of literature.

The first reported case of peritoneal encapsulation causing mechanical small bowel obstruction in a child is described. So far, only seven asymptomatic adult patients with this anomaly have been reported on. The embryogenetic basis is discussed. Methods of operative recognition and surgical management are suggested.


Gunshot wounds of the left upper abdominal quadrant associated with multiple intraabdominal injuries.

This study reviews low velocity gunshot wounds of the left upper quadrant of the abdomen and presents four cases recently treated at Boston City Hospital. All patients sustained multiple intraabdominal organ injuries and underwent prompt exploration. Hypotension on admission seemed to be the most reliable sign for a prolonged and complicated hospital course. The essential preoperative studies in stable patients should include a chest x-ray and intravenous pyelogram. Intraoperatively, injury to the body or tail or the pancreas is best managed by distal pancreatectomy and sump drainage. Exploration of the retroperitoneum is warranted for bleeding from the kidney. Initial maneuvers should be designed to control hemorrhage from the renal pedicle. If this is unsuccessful or the renal parenchyma is badly fragmented, nephrectomy should be performed. The complications noted in our patients, infection (pneumonia and left subphrenic abscess) and hemorrhage, are comparable to those reported in most large series. Pancreatic complications (fistulas, pseudocysts, and pancreatitis) were not noted.


Continuous oculoplethysmographic monitoring during carotid endarterectomy.

Oculoplethysmography has moved from the noninvasive vascular diagnostic laboratory to the operating room and is serving a new role in monitoring internal carotid shunt blood flow during carotid endarterectomy. Temporary intraoperative shunt occlusions are instantly indicated by accurate ocular pulse delay information digitally displayed to the surgeon. Corrections in shunt placement may be made promptly and, therefore, adequate internal carotid blood flow maintained, allowing "safe" time for careful endarterectomy or vascular reconstruction. Verification of satisfactory flow after arteriorhaphy is obtained by oculoplethysmography.


Consistent, effective technique for muscle and nerve biopsy.

Muscle and nerve biopsy provides information of increasing importance in the management of neuromuscular disorders. A simplified technique is presented that yields a specimen which equals and often surpasses in quality specimens obtained by more complex methods that require specially designed clamps and forceps.


New self-retaining retractor to facilitate surgical exposure.

This new self-retaining retractor has blunt prongs that grip firmly but cause minimal trauma. A widely curved arc permits wide separation of the blades. Because the retractor is relatively long and heavy, it sits snugly within the wound, and the base is out of the surgical field. The extra length of the instrument permits considerable upward retraction of the central blade.


Methacholine and histamine inhalation challenges in asthma: relationships to age of onset, length of illness, and pulmonary functions.

Levels of airways hyperreactivity, as indexed by methacholine and histamine thresholds, were determined for hospitalized asthmatic patients using the serial concentration, constant-breath method. Airways hyperreactivity was categorized into low and high based on a split of the sample of subjects tested. These categories were unrelated to pulmonary function measurements obtained throughout hospitalization. Patients having high airways hyperreactivity to histamine or methacholine were admitted for intensive inpatient care at a young age, had an earlier age of onset, and had asthma of longer duration than patients having low airways hyperreactivity. These latter results suggested that relatively greater airways hyperreacticity is more likely to be associated with early onset of the illness.


Influence of small atmospheric ions on the airways in patients with bronchial asthma.

The influence of artificially generated atmospheric ions is studied in 15 patients with bronchial asthma. A slight but significant (at 5% level) improvement in the lung function was demonstrated in nine patients during positive as well as negative ion exposure, but the patients' subjective votings of the air quality did not show any changes due to ion exposure. No change in the histamine threshold of the airways in six patients with bronchial asthma was demonstrated during exposure to ions. Further controlled studies with electro-aerosols are needed.


Periodic respiration. The capnographic interpretation.

Different type of periodic respiration are difficult to distinguish clinically although their identification may influence the diagnosis, prognosis and treatment. Often other forms of abnormal respiration are mistaken for periodic. Four capnograms are shown illustrating (1) true Cheyne-Stokes respiration, (2) irregular "pseudo-periodic" respiration a) after fentanyl, and b) in the presence of a brain tumour and (3) regular respiration interspersed with deep sighs which was diagnosed clinically as Cheyne-Stokes respiration. A plea is made for the routine use of capnography in order to provide a visual record of respiration.


[The influence of ethanol, dithiocarb, diethylmaleate and phenobarbital on the metabolic elimination of halothane in rats (author's transl)].

Rats exposed to halothane (100 ppm) in a closed allglass-system eliminate halothane from the atmosphere of this system with a half-life (t0.5) of 0.99 h. In 24 h-fasted rats t0.5 was prolonged to 1.24 h. A single oral load of 4.8 g/kg ethanol as well as a 15% ethanol solution instead of drinking water for 28 days did not alter the metabolic elimination of halothane. On the other hand, ethanol (4.8 g/kg p.o.) applied 5 min before exposure to halothane markedly prolonged t0.5 to 3.79 h. Pretreatment with phenobarbital (80 mg/kg i.p. for 4 days) shortened t0.5 significantly to 0.79 h. Inhibition of the mixed-function oxidase system by dithiocarb (100 mg/kg i.p.) or diethyl maleate (1 ml/kg i.p.) markedly prolonged t0.5 to 7.53 and 1.57 h. respectively. The observed modifications of the halothane metabolism may be of interest in relation to the problem of halothane-induced hepatotoxicity.


[Inject-ventilation in bronchoscopy (author's transl)].

Jet ventilation initially described by Sanders has been modified and improved for use with the Storz bronchoscope. Theoretical and technical performance are discussed and the mechanical and physiological properties are dealt with e.g. FiO2, driving and endotracheal pressure, expiratory CO2 concentrations, blood gas analysis, pulmonary artery pressure and electrocardiographic changes. Using this method prolonged diagnostic and surgical procedures, such as cauterisation of bronchial adenoma, removal of foreign bodies from the airways especially of small children and bronchial toilet in status asthmaticus, are rendered free from problems for the anaesthetist. We believe that the inject ventilator is a very useful addition to endotracheal surgery.


[Effects of various anaesthetics and relaxants on vascular smooth muscle (author's transl)].

The effects of various injectable anaesthetics and relaxants on the pressure-diameter relations of isolated segments of the rat tail artery were investigated in vitro. The wall of this vessel contains about 75% smooth muscle fibres. Measurements were made before and after the induction of a virtually maximum constriction of the vascular segments which was produced by 1 mg/ml noradrenaline. When added to pure Tyrode's solution all the agents used did not markedly influence the pressure-diameter curves. However, the noradrenaline-induced constriction of the vessels was inhibited to varying degrees. This effect was most evident after thiopentone which caused the diameter to increase by 50%. After pentobarbitone, the increase in diameter was found to be less pronounced (15%). Administration of methohexitone was followed by lesser relaxation of the arterial smooth muscle resulting in a maximum increase in diameter of 7%. After alphathesin (CT 1341) and propanidid, the arterial segments dilated about 20%, after etomidate and 4-hydroxybutyrate about 10%. The muscle relaxants suxamethonium and d-tubocurarine induced dilations of 10 to 15%, alcuronium and pancuronium, however, of less than 5%. The results presented here concur with those of experiments in vivo in which the influence of narcotics and relaxants on the peripheral resistance was studied. This indicates that the dilatation of peripheral resistance vessels seen after the administration of such agents is not exclusively caused by a neurally mediated inhibition of the vascular tone. The direct action of these substances on the vascular smooth muscle may often contribute to their complex haemodynamic effects.