[Hodgkin's disease in the malignant lymphoma category atypical clinical aspects].

Various clinical and pathological features of Hodgkin's disease and its related disorders are discussed: a rare, benign form of Hodgkin's disease with skin loci only; unusual primary sites (bone, spleen, lungs and intestine---including alphs-chain disease): various paraneplastic syndromes caused by hyperparathyroidism and hypercorticism; idiopathic nephrotic syndromes of immunological origin. Reference is also made to possible relationships between lymphoma and leukaemia.


A focus on the occupational health needs of the non-white worker.

The nurse's understanding of the culture of the non-white workers is necessary if she is to work effectively with them. Her understanding of their language is vital. She must recognize the specific needs of each group. Some of these needs are psychosocial, economical, and physiological. The necessity for honesty, sincerity and humane respect is emphasized as important in successful working relationships with non-white workers. Once mutual respect has been achieved, an understanding of the cultural, physical, and psychological backgrounds of the workers will help the occupational health nurse provide the same high quality nursing care to all.


Influence of intracranial osmotic stimuli on renal nerve activity in anaesthetized cats.

In baroreceptor denervated cats one internal carotid artery (ICA) or the cerebral ventricular system (CVS) was perfused with isotonic, hypertonic and hypotonic sodium chloride solutions. Renal sympathetic activity (RSA) and blood pressure (BP) were recorded. ICA perfusion with isotonic sodium chloride (150 mM NaCl) produced no changes of RSA compared to control level,. RSA was increased from plus 30% to plus 350% in 44 tests out of 45 tests following hypertonic (425 mM NaCl) ICA perfusion. RSA was decreased following hypotonic (aqua dest.) ICA perfusion from minus 30% to minus 100% in 37 tests out of 50 tests. The degree of RSA changes was found to depend upon the osmolarity of the solutions. 425mM NaCl and aqua dest. produced greater RSA changes than 290 mM NaCl and 75 mM NaCl. CVS perfusion with isotonic sodium chloride produced a slight increase of RSA compared to control levels (plus 15%). Hypertonic sodium chloride produced a RSA increase from plus 15% to plus 135% in 10 tests out of 14 tests. Hypotonic sodium chloride produced a RSA decrease from minus 15% to minus 80% in 8 tests out of 14 tests. Changes of RSA following ICA perfusions and CVS perfusions were accompanied by changes of BP in the same direction. A quantitative correlation between delta RSA and delta BP could not be found. Results suggest that renal osmoregulatory response to osmotic stimuli in the carotid artery may not just arise in response to changing ADH levels but may also be induced by changes in RSA.


Serial observations of arterial and mixed-venous blood gases after step change in ventilation.

In 22 dogs, subjected to a step change in ventilation, serial changes in blood gas composition and lactate and pyruvate concentrations of arterial as well as mixed venous blood were studied. The change of PaCO2 was approximately 20 mm Hg both in hypo- and hyperventilation. During hypoventilation the difference in various forms of CO2 between arterial and mixed venous blood showed first a downward shift and then gradually increased, whereas during hyperventilation they progressively increased and reached a constant level within 10-20 min. This difference was assumed to be mainly due to more efficient CO2 elimination through lung ventilation in hyperventilation as compared with CO2 accumulation from tissue metabolism in hypoventilation. In vivo buffer slopes for CO2 during hypoventilation were about half those in vitro, whereas during hyperventilation both slopes were approximately the same. In vivo arterial buffer slope was higher during hypoventilation and lower during hyperventilation as compared to that of mixed venous blood in the respective state of ventilation.


The efficiency of operatnt thermoregulatory behavior in pigs as determined from the rate of oxygen consumption.

Pigs were trained to perform an operant response for a reinforcement of radiant heat and comparisons were made between oxygen consumption during sessions when extra heat was available and others when it was not. It was found that as judged by the rate of oxygen consumption the efficiency with which heat was obtained was very high when the radiation was allowed to increase air temperature, but declined when air temperature remained low. If the pig had to make several responses for a single reinforcement, there was no saving in oxygen consumption. Reducing the intensity of the heating led to a reduction in the frequency at which responses were made. When the reinforcement was a brief respite from a draught, the pigs performed a greater number of responses at low ambient temperatures, but this was not accompanied by any saving in the rate of oxygen consumption.


The effects of cholecystokinin-pancreozymin, acetylcholine and secretin on the membrane potentials of mouse pancreatic cells in vitro.

Cell membrane potentials in an in vitro preparation of mouse pancreas have been measured and the effects of cholecystokinin-pancreozymin, acetylcholine and secretin studied. The membrane potential-frequency histogram has four distinct peaks and was split into the sum of four Gaussian distributions with means of minus 14, minus 23, minus 32 and minus 41mV. The minus 32 mV peak is attributed to acinar cells which respond to cholecystokinin-pancreozymin or acetylcholine by depolarising to minus 15 to minus 20 mV, the response lasting up to 10 min. The minus 23 and minus 41 mV peaks are due to duct cells. A duct cell has a resting membrane potential of minus 23 mV and hyperpolarises to minus 41 mV in response to secretin stimulation, the response lasting for longer than 15 min. Duct cells regardless of their position in the duct system function electrophysiologically in identical fashion. The secretory sites for enzyme and electrolyte are distinct, the duct cells secrete only electrolyte while the acinar cells secrete only enzymes.


Pancreatic enzyme secretion in the conscious rat. Method and application.

1. A method for collecting duodenal juice and gastric content separately, in conscious rats, is described. Metal cannulas were implanted into the stomach fundus. For the main experiment a double lumen tube was inserted through the cannula via the pylorus into the duodenum. 2. The following secretion patterns were observed: a) In the resting state there was a constant flow rate of duodenal volume, bicarbonate, trypsin and amylase. b) Cholinergic stimuli were capable of increasing enzyme secretion as much as fourfold for a period of 30 to 40 min when administered as a single subcutaneous injection. This effect was annulled by atropine. c) Secretin and cholecystokinin-pancreozymin given together in a single injection s.c. or i.v., elicited a similarly strong response. d) Identical ranges of the secretion maxima were found with a tendency to decrease after the first hour, when the hormones were infused either s.c. or i.v. e) Doses from 0.5 to 25 U/100 g b.w. /hr showed identical responses. Doses below 0.2 U/100 g/hr were without effect. 3. Narcosis (pentobarbital) inhibited markedly the resting and stimulated enzyme secretion. 4. The method is suitable for examination of physiological and pharmacological effects on resting and stimulated enzyme secretion of the rat pancreas.


The activity of respiratory neurons before and during panting in the cat.

The effects of heating the preoptic/anterior hypothalamic (PO/AH) region on medullary respiratory neurons were studied in urethane-anesthetized, spontaneously breathing cats. The efferent phrenic nerve discharge or the pneumotachogram served as an indicator of central respiratory periodicity. In each animal, heating of the PO/AH area caused panting, defined as an increase of respiratory rate over 100 breaths per minute. During polypnea similar changes in the discharge patterns of both inspiratory and expiratory neurons were observed. There was a significant decrease in the duration of the discharge phase and the number of impulses per burst so that a reciprocal relationship existed between these parameters and respiratory rate. However, the average impulse frequency within a burst was higher during panting and could be shown to be a linear function of respiratory rate. Due to the concomitant decrease in inspiration and expiration times, the average discharge frequency per cycle time also increased in both inspiratory and expiratory medullary neurons. For continuously discharging neurons which displayed a higher frequency during the inspiration period (frequency modulated discharge), the phasic linkage remained unchanged during polypneic panting. From our results it is concluded that local heating of the PO/AH region shifts the entire respiratory system to a higher level of activity which can be correlated with ventilatory changes during panting.


An isolated guinea pig heart preparation with in vivo like features.

Hemodynamic and metabolic characteristics of an isolated guinea pig heart preparation perfused with a pyruvate fortified Krebs-Ringer-bicarbonate solution are described. The preparation is stable for more than 90 min with respect to coronary flow, heart rate, left ventricular pressure, dP/dt, oxygen consumption, and myocardial high energy phosphate levels. The changes in coronary flow induced by alterations of perfusion pressure, ischemia, and hypoxia resemble those seen under in vivo conditions. The preparation also exhibits concentration dependent and reproducible changes in coronary resistance upon administration of adenosine and papaverine. The in vivo like features of this preparation can be mainly attributed to the use of pyruvate as additional and preferentially utilized substrate. The preparation appears to be suitable for quantitative studies of myocardial metabolism and heart function as well as for investigations of the coronary system.


The radioactive microsphere method for the assessment of regional myocardial blood flow after coronary artery occlusion. Inaccuracies due to variations in the diameter distribution of the spheres.

In this study, we have tried to determine the magnitude of the inaccuracy of the radioactive microsphere method - due to variations in the diameter distribution of the spheres - for measuring regional myocardial blood flow after coronary artery occlusion. In 5 mongrel dogs, three types of 15 mum microspheres, labelled with 125I, 141Ce or 85Sr, were injected simultaneously after the descending branch of the left coronary artery had been ligated. Myocardial samples wert taken from the left ventricle and divided into four groups according to the number of spheres per sample. The radioactivity of the various isotopes per gram tissue was expressed as percentage of their activity per milliliter of the reference sample. The diameter distribution of microspheres, labelled with each of the isotopes, was determined light-microscopically in suspensions belonging to three different batches. The relative error, as determined from the difference in relative radioactivity of the various types of microspheres in the tissue samples, was higher than the theoretical error for each of the number of spheres per sample. It is very likely that this discrepancy is caused by the differences in diameter distribution of the various types of microspheres, resulting in non-random error. The smaller spheres tended to go to low flow areas and the larger ones to high flow areas. Because of the non-randomness, the error due to diameter variations in the spheres can be diminished by randomizing the order of injection of the various isotopes. The present study indicates that the relatively high degree of accuracy of the microsphere method for the determination of blood flow to large parts of the myocardium with an unimpeded coronary circulation, as was described in literature, cannot be extrapolated to the determination of regional myocardial blood flow after coronary artery occlusion, when the combination of small tissue samples, variations in the diameter distribution of the spheres and an unevenly distributed myocardial blood flow unfavourably affect the accuracy of the method.


Urea and sodium in sheep kidneys during ethacrynic acid diuresis.

The possibility of uphill transport of urea from the collecting ducts of sheep fed diets containing 14% protein (HP) and 4.9% protein (LP) was explored by measuring cortex to papilla and urine to papilla gradients of urea during ethacrynic acid diuresis. Clearance studies were done on adult, unanesthetized, hydropenic, vasopressin infused sheep. Saline was given to compensate for urine loss during ethacrynic acid diuresis. Following a period of antidiuresis, ethacrynic acid administration caused and increase in fractional water excretion to 0.33 (HP) and 0.44 (LP), an increase in fractional sodium excretion to 0.28 (HP) and 0.41 (LP), and an average increase in glomerular filtration rate of 14.7%. Fractional potassium excretion showed no consistent change. Renal concentrating ability and medullary sodium accumulation were inhibited. Antidiuretic LP and HP medullary urea accumulation patterns were lost. However, identical but small ascending cortex to papilla urea gradients remained in the LP and HP animals. There was no significant difference between the urea concentration in urine and papilla tissue water. The results fail to provide support for the presence of active urea transport from the collecting ducts of sheep fed high or low protein diets.


3H-inulin and electrolyte concentrations in Bowman's capsule in rat kidney. Comparison with artificial ultrafiltration.

Micropuncture experiments were performed on Bowman's capsules in male and female non-diuretic Munich rats. 55 samples were collected and analysed for Na, Cl, K, Ca, P, Mg and 3H-inulin contents. Their electrolyte concentrations were compared to the corresponding concentrations obtained from plasma artificial ultrafiltrates. Compared to normal Wistar rats, our Munich rats had several special characteristics: high arterial pressure (115-155 mm Hg), high concentrating ability (phi equals 2684 mOsm/1) and high NaCl reabsorption capacity. Whole kidney GFR was low in males (0.361 ml/min/kidney/100 g B.W.). 3H-Inulin concentration was the same in plasma and glomerular ultrafiltrates (GF). The corresponding ratio (GF/P) in equals 1.03 plus or minus 0.01 (N equals 55) confirmed the lack of sieving effect for inulin. GF electrolyte concentrations were, for Na, Cl, K, Ca, P, Mg respectively 139 plus or minus 0.05, 1.46 plus or minus 0.07 and 0.52 plus or minus 0.04 ml/1 (N equals 23) in females and 141 plus or minus 2, 120 plus or minus 2, 3.84 plus or minus 0.07, 1.31 plus or minus 0.03, 1.78 plus or minus 0.05 and 0.48 plus or minus 0.01 mM/1 (N equals 32) in males. Comparison of ultrafiltration trough a cuprophan membrane and glomerular ultrafiltration led to the following conclusions: For Na, Cl and P artificial and glomerular ultrafiltration produced identical results. On the other hand, for Ca and to a lesser extent for Mg and K ions, artificial ultrafiltration did not accurately reflect the true glomerular ultrafiltrate composition. The reasons for these differences are discussed below.


Micropuncture study along the proximal convoluted tubule. Electrolyte reabsorption in first convolutions.

126 micropunctures were performed on 40 Bowman's capsules as well as along the corresponding proximal convoluted tubules (PCT) on six nondiuretic rats. Capsular and tubular fluid samples (GF and TF) collected were analysed for Na, Cl, K, P, Ca Mg and 3H-Inulin concentrations by electron probe analysis and liquid scintillation. Electrolyte handling along the usually inaccessible part of the PCT, i.e. EPCT, was determined by selecting from the samples collected in the first two or three proximal loops, those having a (TF/GF) In value smaller than or equals to 1.15. Except for Na the concentration of electrolytes was significantly modified when the fluid flowed along the PCT: 1. In the EPCT, (TF/GF)Cl and K rose and (TF/GF)P dropped in correlation with (TF/GF)In. For (TF/GF)In = 1.15, (TF/GF) chloride, potassium and phosphate were respectively equal to 1.12, 1.10 and 0.72. These values were comparable to thoose obtained in the remaining length of PCT, indicating that the chemical gradient established in the first loops was maintained in the subsequent ones. Therefore proximal handling of these three ions differed depending on the PCT portion considered. The reasons for this difference are discussed further on. 2. Calcium concentration increased and reached a plateau corresponding to (TF/GF)Ca = 1.22 for (TF/GF)In values ranging from 1.31 to 1.45. 3. Magnesium was not reabsorbed for (TF/GF)In values below 1.90. Above this level slight Mg reabsorption occurred. 4. Significant correlations between (TF/GF)K, Ca and P and (TF/GF)Cl ratios were observed along the PCT, suggesting that proximal reabsorption of K, Ca and P was dependent on tubular fluid acidification.


Electrical activity in embryonic heart cell aggregates. Pacemaker oscillations.

Aggregates were formed from dissociated heart cells of 7-day chick embryos. When spontaneous action potentials were blocked with 10-8 to 10-7 g/ml tetrodotoxin (TTX) oscillatory pacemaker potentials were sometimes seen. The emergence of these pacemaker potentials was critically dependent on the external potassium concentration. In 1.3 mM potassium medium TTX suppression of action potential generation always led to a stable resting potential close to the threshold level (-55 to -50 mV). In 4.3 mM potassium TTX suppression was followed by a train of pacemaker potentials which usually gave way to a stable resting potential of about -70 mV. Raising the calcium concentration from 1.8 to 5 mM often induced long lasting (3 hrs) pacemaker oscillations of 20 to 30 mV peak to peak amplitude. These were abolished by raising the potassium concentration to 8.3 mM or upon the addition of 1.5 mM Mn2 plus. The responses of TTX-treated aggregates are discussed in terms of Noble and Tsien's pacemaker theory for Purkinje fibers. The results are well described by assuming the existence of an ik2-like potassium current in embryonic heart cells. The role of calcium is unclear but it may help provide the inward current against which the outward potassium current can function.


A new method for intratubular blockade in micropuncture experiments.

Criteria for a reliable blockade of tubular flow are generally discussed and experimental evidence is presented that solid paraffin meets all the necessary criteria in rat kidney tubules when an immobile and tight sealing intratubular blockade is requested. A special microinjection apparatus for the application of paraffin is described. Furthermore, several alternative methods and materials have been tested and have been found to be inferior to solid paraffin.


Depletion of muscle and liver glycogen during exercise. Protective effect of training.

Carbohydrate depletion during exercise was measured in the liver, in the three different types of skeletal muscle, and in the blood of exercise-trained and untrained rats. The acute exercise test consisted of 45 min of treadmill running of progressively increasing intensity. The training program consisted of 6 hrs of swimming per day, 5 days per week for 14 weeks; the training induced an increase of approximately 35 percent in the respiratory capacity of gastrocnemius muscle, and a 14 percent incrase in heart weight. Glycogen stores in fast-twitch red, fast-twitch white, and slow-twitch red types of skeletal muscle, were depleted significantly more slowly in the trained than in the untrained animals during the treadmill exercise test. Resting glycogen stores in the liver were higher and were depleted more slowly during exercise in the trained than the untrained animals. Blood lactate concentration was significantly lower in the trained than in the untrained rats at the end of the exercise test. These results provide evidence that endurance exercise training induces adaptation which protect against the depletion of glycogen from the liver and from the tree types of skeletal muscle during prolonged exercise.


The intrarenal distribution of 125I-albumin in the Syrian hamster.

The intrarenal distribution of radioiodinated human serum albumin (125RISA) after intravenous injection was studied in Syrian hamsters by scintillation counting and frozen section autoradiography. After 15, 30 and 60 min the virtual plasma albumin space in the renal cortex of the hamster represented 6.49, 7.13, and 8.06 percent respectively of the kidney tissue volume. From the cortex to the renal papilla the albumin space increased to about 30 percent of the tissue volume. In comparison to this the albumin space in the renal cortex of the rat was about 20% and in the renal papilla about 33% (11). Frozen section autoradiography indicated that the distribution of radioalbumin in the renal cortex of the Syrian hamster is limited mainly to the kidney vessels, being especially noticeable in the glomerular capillaries. Toward the papilla increasingly greater (mainly extratubular) activity could be observed not only intravascularly but also interstitially. In the cortex of the rat kidney, on the other hand, radioactive albumin was accumulated (probably by filtration and reabsorption) predominantly in the proximal tubular epithelium. Wtithin 30 min thekidneys of the rat excreted mor than 10 times as much 125I than the hamster kidneys. These results (substantially less cortical accumulation and urinary excretion of radioalbumin in the Syrian hamster) indicate that, in contrast to the rat, obviously much less albumin is filtered (and then accumulated by proximal reabsorption) by the Syrian hamster glomeruli. This suggests that the Syrian hamster kidney is more suitable than the rat kidney for determining the interstitial, cortical, albumin space.


M. Quadriceps femoris of man, a muscle with an unusual enzyme activity pattern of energy supplying metabolism in mammals.

1. The following enzyme activities were estimated in needle-biopsy samples of the lateral part of the human quadriceps femoris muscle: triosephosphate dehydrogenase (TPDH), lactate dehydrogenase (LDH), NAD : glycerol-3-phosphate dehydrogenase (GPDH), hexokinase (HK), NAD: malate dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase. 2. Although the enzyme activities in muscles of women were lesser than in those of men, no difference was found in the calculated enzyme activity ratios. There is thus no sex-dependent metabolic type-differentiation in this muscle. 3. The human quadriceps femoris is a low-activity muscle, in comparison with muscles of homoiotherm laboratory animals. The enzyme activity ratio of TPDH to CS, characterizing the glycolytic pyruvate formation to aerobic oxidative capacities, shows this muscle to be of an intermediate type in this respect, similarly as the extensor digitorum longus of the rat. The relatively very high capacity of glucose phosphorylation (HK), the high aerobic regeneration of cytoplasmic dehydrogenated NAD (GPDH) and the very low anaerobic regeneration  (LDH), show the unusually high proportion of carbohydrates (glucose) which can be broken down aerobically.


The role played by elasticity in an exercise involving movements of small amplitude.

In an exercise consisting of repetitive small jumps on both feet at a frequency of 116/min, the mechanical work performed and the O2 consumption at steady state were measured. Of the positive work performed in the jump only 40% appears to be due to the chemical transformations taking place in the contractile componenet of the muscle fibres; the remaining 60% appears to be due to the elastic energy accumulated in the elastic elements of the contracted stretched muscles of the lower limbs during the falling phase of the previous jump, when the body hits the ground.


Postprandial changes of renal blood flow. Studies on conscious dogs on a high and low sodium intake.

Postprandial renal blood flow was studied in 14 conscious dogs on a chronic high and low sodium intake on 72 days after implantation of an electromagnetic flow transducer around the left renal artery. Fasting renal blood flow was 11.7 plus or minus 3.2 ml/min with kg on high socium intake (43 days) and 11.5 plus or minus 3.3 ml/min with kg on low sodium intake (29 days). During ingestion no change of renal blood flow occurred; mean arterial pressure rose transiently. During digestion renal blood flow increased always and was, like the fasting renal blood flow of dogs on a high sodium intake was 41 plus or minus 23%, and of dogs on a low sodium intake 35 plus or minus 15% referring to fasting controls; peak increase mostly occurred between 60 and90 min postprandially and was due to a decrease of renal vascular resistance. Renal blood flow also increased after augmentation of intravascular volume by an intravenous infusion; volume receptors may be involved.


Microrheology and light transmission of blood. III. The velocity of red cell aggregate formation.

The formation of primary (rouleaux) and secondary (rouleaux networks) RCA was studied by microcinematography (12 frames/sec) and photometry in a counterrotating "rheoscope" chamber. The blood was first subjected to rapid viscometric flow (460 sec-1, all RBC dispersed and aligned in flow) and then brought abruptly to full stop. In normal human blood, primary and secondary RCA occurred simultaneously, and were completed within 8 to 10 sec after stop. Blood from pregnant women at term, known for its pronounced red cell aggregation, shows a dissociation between the formation of short primary rouleaux (initiated even before full stop and completed 1-2 see thereafter) and secondary RCA completed 3-5 see after stop. RCA increases the light transmission of blood (measured by an increase in photovoltage V), the process and its first derivative (dV/dt equals I) can be recorded. After flow stop, there is an exponential decay of I(I equals t-I-o with e-lambda-t). The half time of this decay is recorded and correlated to the kinetics of red cell aggregate formation In human blood the half time of this process varies between 1.0 and 6.0 sec. In suspensions of human RBC in artificial plasmas, t-1/2 decreases with increasing concentration of fibrinogen and/or Dextran 250000, the second component appearing at concentrations above 500 mg-%. The method lend sitself for the quantification of RCA in small blood samples (20 mul).


Microrheology and light transmission of blood. IV. The kinetics of artificial red cell aggregation induced by Dextran.

Employing both microscopic and photometric methods the rheology of pathological red cell aggregation was studied in model experiments. Suspensions of washed human red blood cells in dextran solutions containing rising concentrations of dextrans (M.W. 40000, 70000, 110000, 250000, 500000) were used. At low concentrations (less than 500 mg-%) of high molecular weight dextrans (greater than 70000) red cell suspensions formed aggregates similar to the ones found in normal human blood. At higher concentrations, the aggregates were similar to those observed in pathological human blood. The aggregates were studied under the condition of stasis, slow flow and at shear rate of their hydrodynamic dispersion. Besides, the flow behavior of the dispersed cells at high shear rates was studied. We found: 1. In all samples the rate of spontaneous aggregate re-formation in stasis (following hydrodynamic desaggregation) rose with rising dextran concentration up to 5.0 g-%. 2. The shear resistance of the aggregates, as measured by the shear stress necessary to keep them dispersed, rose up to concentrations of 2.5g-%, but fell at higher concentrations. 3. Only with dextran of a molecular weight above 110000 coarse agglomerates could be produced at high concentrations. Loose elastic meshes were rapidly produced at high concentrations of Dx 70. 4. When subjected to steady state low shear (m sec-1) only the agglomerates, but not the meshes rapidly grew in size. Most of the aggregation kinetics recorded by photometry and microscopy evaded detection by viscometry.


Time- and rate-dependence of the inotropic action of noradrenaline in the isolated guinea-pig's atrium.

The inotropic action of noradrenaline (10-6 mol/l)) was studied on a left guinea-pig's atrium which was isolated functionally by ligations and perfused during artificial stimulation (basal rhythm: 120/min) over a period of 5 to 10 hrs. Each half hour the rate was varied within a range from 60 to 300 imp/min. When modernaline is applied continuously throughout the experienment, contractility in terms of amplitude and rate of pressure development is almost maintained on the control level at the stimulation rates over at least 4 hrs of perfusion. When noradrenaline is applied at various stages of perfusion it compensates for the foregoing decay of contractility even after 8 hrs. Since contractility during normal perfusion decreases much more at a lower than at a higher rate the inotropic action of noradrenaline is minimal at a high rate in the fresh preparation (this means: under physiological conditions) and is fully developed only during later stages of perfusion at a low rate (which is far below the physiological range.


The basic requirements for the function of the isolated cell free perfused rat kidney.

We have attempt to define experimental conditions which would overcome or minimize some of the well known functional limitations of isolated single pass kidney preparations. Rat kidneys were perfused with a Krebs-Henseleit solution containing the gelatine derivative Haemaccel as colloid. Perfusion was initiated in situ via the mesenteric artery. Arterial flow rate was measured continuously from the very onset of perfusion. Effective perfusion pressure was recorded distal to the perfusion capillary in the aorta. Aliquots of the venous effluate and of an arterial bypass solution were drawn through an O-2 electrode for the calculation of Q-o-2. First it was shown that the often observed initial vasoconstriction of the preparation which occurs immediately after cannulation of the kidney can be eliminated by rapid disconnection of the autonomic nerve supply. A more delayed gradual increase of renal resistance, which we observed after 30 min could be prevented by using sterile perfusion solutions. Using glucose as the only substrate fuel, fractional Na-reabsorption decreased to 65% 3 hrs after the onset of perfusion (T Na equals 27.3 muEq/g with min). When a substrate enriched sterile solution was used containing pyruvate, lactate, oxaloacetate, and glutamate, Na conservation of the isolated kidney could be maintained at a higher level. Fractional Na-reabsorption levelled off and was still 88% after 3 hrs (T Na equals 64.4 muEq/g with min). The results demonstrate that the transport function of the isolated kidney preparation critically depends on the supply with substrate hydrogen. Thus, the present system meets the basic requirements necessary for further micropuncture evaluation of renal function under the condition of isolated single pass perfusion.


Ion conductance changes associated with spike adaptation in the rapidly adapting stretch receptor of the crayfish.

The time course of the repetitive impulse discharges has been investigated for two high intensities of maintained depolarizing currents, 30 nA and 50 nA, for which the receptor adaptation was complete within 70 msec. The changes in sodium and potassium conductance associated with the decline in spike activity have been analyzed at different instances of time by interrupting in successive experiments the various action potentials in the pulse trains either at the early phase by holding the potential at about -60 mV and recording the inward current (upstroke-gNa) or by evaluating the delayed outward current flowing as the result of a depolarizing voltage pulse which at the end of the action potential re-increased the membrane potential by  mV (after potentialgK). At the higher current intensity of 50 nA the discharge frequency was increased, while larger reductions in upstroke-gNa and after potential-gK during receptor adaptation became apparent. The progressive decrease in pulse amplitude from 99 mV to 63 or 55 mV is paralleled by a gradual reduction in upstroke-gNa from 97 mmho/cm-2 to 37 or 27.5 mmho/cm-2 and in after potential-gK from 11.5 mmho/cm-2 to about 7 mmho/cm-2. When under a stimulus of 30 nA the sodium conductance decreases to an average value of 37 mmho/cm-2 only a distorted spike can be elicited, while the spike activity was completely suppressed at upstroke-gNa equals 27.5 mmho/cm-2 was essentially the same under both conditions. The results have been interpreted in terms of the model for impulse generation formulated by Michaelis and Chaplain (1973). According to the model both sodium and potassium inactivation reduce the pulse amplitude. However, while Na-inactivation reduces the frequency of impulse discharge, the K-inactivation actually leads to an increase in spike frequency. As the frequency of the short train of pulses recorded under high-intensity current stimulation remained essentially unaltered, it is suggested that the coupling between Na- and K-inactivation actually leads to an increase in spike frequency. As the frequency of the short train of pulses recorded under high-intensity current stimulation remained essentially unaltered, it is suggested that the coupling between Na- and K-inactivation ensures a constancy of the information-carrying parameter, i.e. the average impulse density.


Biological basis for management of benign disease of the breast. The case against subcutaneous mastectomy.

The biology of breast disease abnormalities which are primarily the result of hormonal imbalance, and the action of hormones upon breast tissue are discussed. An understanding of the basic biological principles makes it possible to manage these patients more accurately. An accurate diagnosis is necessary to predict what changes will occur with the progression of time. Our reservations about subcutaneous mastectomy are stated.


Pregnancy in cactus mice: effects of prolonged copulation.

The postejaculatory copulations of cactus mice are demonstrated to function in facilitating neuroendocrine responses necessary for pregnancy. Whereas estrous cycles were altered after just 10 percent of the tests terminated after one ejaculatory series, females became either pregnant or pseudopregnant after 80 percent of tests continued at least to sexual satiety (30 minutes with no copulations).


Water recycling in lactation.

During lactation, female rodents, dingoes, and kangaroos consume urine and feces excreted by the young. Studies with tritiated water as a tracer for native water showed that roughly one-third of the water secreted as milk was returned to the mother. The results are cogent to studies of water balance of lactation and to current methods used for estimating milk production.


Chromosome-wide event accompanies the expression of recessive mutations in tetraploid cells.

Mutants resistant to 6-thioguanine were induced in pseudotetraploid hybrid Chinese hamster cells homozygous wild-type at the locus for hypoxanthine phophoribosyl transferase but heterozygous for the linked marker glucose-6-phosphate dehydrogenase. About half of these mutants had concomitantly lost the wild-type allele for glucose-6-phosphate dehydrogenase, as expected if mutation plus chromosome segregation had occurred.


Transforming potential of the anticancer drug adriamycin.

A Fischer rat embryo cell system in vitro, which had been shown to be highly accurate in identifying chemical carcinogens and to have application in the study of chemicals having anticancer properties, was used to study the anticancer drug adriamycin. At a nontoxic dose adriamycin not only did not protect the cells from transformation by the carcinogen 3-methylcholanthrene, but was found in two separate experiments to act on its own as a transforming agent.


Relationship between respiration rate and weight of loach oocytes.

It is shown that the constant k in the equation QO2 equals apk and the constant b in the equation qo2 equals aP-b change during the oogenesis of the loach. Hence, the growth of oocytes differs considerably from the growth of animals, where the constants k and b do not change with increase in weight. It is suggested that the relationship between the respiration rate and weight of the oocytes is due to the change in the amount of mitochondria in the oocytes.


The rodent ultrasound production mechanism.

Rodents produce two types of sounds, audible and ultrasonic, that differ markedly in physical structure. Studies of sound production in light gases show that whereas the audible cries appear to be produced, as in the case of most other mammals, by vibrating structures in the larynx, the ultrasonic cries are produced by a different mechanism, probably a whistle. 'Bird-call' whistles are shown to have all the properties of rodent ultrasonic cries and to mimic them in almost every detail. Thus it is concluded that rodents have two distinct sound production mechanisms, one for audible cries and one for ultrasonic cries.


Carcinoembryonic antigen test in renal cell carcinoma.

CEA (carcinoembryonic antigen) determinations were performed on 203 blood and urine samples from 23 patients with renal cell carcinoma. Neither the blood nor the urine CEA test was able to confirm the diagnosis or predict the status of the disease in more than one half of these patients. As presently constituted, the CEA test is not accurate for the diagnosis or prognosis of renal cell carcinoma.


Combined video/pressure/flow cystourethrography in female patients with voiding disturbances.

The urodynamic investigation of 152 female patients with symptoms of recurrent cystitis by synchronous video/pressure/flow cystourethrography is presented. The results fall into the following groups: (1) Normal: In 77 patients, no abnormality was found. (2) Bladder outflow obstruction: In 52 patients increased resistance to micturition was demonstrated at the level of the external sphincter. Levels of bladder pressure, flow rate, calculated urethral resistance, and cystographic appearance allow the degree of obstruction to be assessed and the urodynamic effect of treatment by dilation or urethrotomy to be appreciated. (3) Reflux: In 17 patients, reflux was demonstrated, 14 of whom showed no evidence of outflow obstruction. Postoperative assessment of reimplantation procedures are briefly discussed. (4) Systolic and unstable bladders: Six patients were in this group; the manifestations of instability are discussed together with the concept of sensory and motor urgency.


Physical growth of 5-year-old children with a low birth weight. Stature, weight, circumference of head and osseous development.

In a prospective investigation of the physical growth of children with a low birth weight, 143 unselected children who weighed less than 2500 g at birth were reviewed at 5 years of age. The children were grouped according to weight relative to gestational age. Stature and weight were compared with normal curves for Swedish children and with a control series. The circumference of the head was compared with a normal curve. Osseous development was assessed by the method of Eklöf & Ringertz and was compared with their normal values. Growth of the LBW-children was slightly retarded in respect of stature, weight and osseous development, but not regarding head circumference. The values found for stature and osseous development were low in the group small for gestational age and for twins. Those LBW-children who were appropriate for gestational age developed at a normal rate. This is true even for those with the lowest birth weight and those born long before term. Osseous development was correlated with stature, which may be due to the measuring method used. Neither maternal disease nor feeding difficulties during the first few months of life had any demonstrable effect on the physical development of the children. Socio-economic factors now surely play at most a subordinate role. Physical development of the children varied most with the mothers' stature and weight and probably with hereditary factors.


The influence of different environmental temperatures on pulmonary gas exchange and blood gas changes after birth.

The oxygen uptake (VO2) and respiratory exchange ratio (R) was determined during the first 20 min and at one and at 2 hours after birth in 16 healthy full-term newborn infants studied in different environmental temperatures. Arterial blood gases and acid-base balance were determined on repeated blood samples from the abdominal aorta. The infants were grouped in a "warm" group (n equal to 10) where efforts were made to avoid cooling after birth, and a "cold" group (n equal to 6) where a decrease in rectal temperature to a mean value of 35.4 degrees C at 2 hours occurred. Irrespective of environmental temperature, VO2 was approximately 10 ml/kg min during the first 8 min after birth, thereafter decreasing to about 6-7 ml/kg min. During the first 8 min the main increase in PaO2 occurred and about 2 ml/kg min of the VO2 was accounted for by changes in oxygen stores after birth. At 16-20 min and at 60 min after birth a negative relationship was found between VO2 and PaO2. During the period 8-120 min after birth a close relationship was found between VO2 and the degree of muscular activity. Within 4-16 min after birth, R values above 1.0 were regularly found simultaneously with the main decrease in PaO2. In infants kept "cold" a tendency to hyperventilate was found, probably elicited by cold stimuli. The rapid drop in deep body temperature regularly seen after birth could thus not be explained by a limited ability to increase pulmonary gas exchange. A high degree of evaporative heat loss, a relatively low "basal" metabolic rate and a limited response in "non-shivering thermogenesis" seem to be the main reasons for the heat loss after birth.


Serial hemodynamic observations in congenital valvular and subvalvular aortic stenosis.

The present study is an attempt to clarify the natural history of valvular and subvalvular aortic stenosis. Twenty-eight patients with isolated and uncomplicated congenital aortic stenosis who had serial hemodynamic evaluation without intervening surgery were selected. They were divided into three groups according to the severity of the peak systolic pressure gradient. At the initial study, 16 of the 28 patients had mild stenosis, 11 patients had moderate stenosis, and one patient had severe stenosis. On restudy, there were only 9 patients with mild stenosis, 12 patients with moderate stenosis, and 7 patients with severe stenosis. The cardiac index and right-sided hemodynamics were normal. The electrocardiographic and radiographic findings in relation to severity of the lesion were also observed. It is our feeling that both valvular and subvalvular aortic stenosis are progressive lesions, the subvalvular being more so than the valvular.


Acute transmural myocardial infarction associated with active Coxsackie virus B infection.

Out of a total of 233 patients suffering from transmural myocardial infarction, 20 patients were found to have serologic evidence of a concurrent active Coxsackie virus B infection. While the infection may have been coincidental, it is also possible that the virus may have played some part in the illness. Conceivably, myocarditis could be mistaken for infarction or, by some mechanism as yet unknown, the virus might precipitate infarction in susceptible subjects.


Mechanism of left ventricular outlfow obstruction in patients with obstructive asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis).

Left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis or obstructive asymmetric septal hypertrophy is due to abnormal forward motion during systole of the anterior mitral leaflet. To determine why some patients with this disease hav left ventricular outflow obstruction whereas others do not, we studied a large number of patiens with assymetric septal hypertrophy using both one- and two-dimensional echocardiography. In 100 patients with asymmetric septal hypertrophy and 22 normal subjects, mitral valve position at the onset of systole was quantitated by measuring the distance from the ventricular septum to the mitral valve and the distance from the mitral valve to the posterior left ventricular wall. None of the normal subjects and only 3 (6 percent) of 51 patients with nonobstructive asymmetric septal hypertrophy had a septal-mitral valve distance of less than 20 mm compared with 23 (66 percent) of 35 patients with obstructive asymmetric septal hypertrophy. Moreover, the mitral valve at the onset of systole was actually positioned forward in the left ventricular activity. Two-dimensional studies in 11 patients with obstructive asymmetric septal hypertrophy revealed that contraction of the malaligned papillary muscles did not cause the abnormal forward mitral valve motion. We propose that the left ventricular outflow obstruction in patients with obstructive asymmetric septal hypertrophy occurs as a result of two factors: (1) narrowing of the left ventricular outflow tract at the onset of systole, and (2) hydrodynamic forces generated by contraction on the left ventricle.


Interstitial-cell tumor of the testis. Tissue culture and ultrastructural studies.

A case of a functioning interstitial-cell tumor in a 12-year-old Negro boy is reported. The patient manifested precocious puberty, with signs of sexually aggressive behavior. The ultra-structural studies of the tumor showed features similar to those of the few cases previously reported in the literature. One characteristic finding was the presence of numerous membranous whorls within the cytoplasm. The cells grown in tissue culture were maintained for at least 9 weeks and were confirmed as testicular interstitial cells. Ultrastructurally they were similar to the cells in vivo, as evidenced by the finding of cytoplasmic organelles related to steroid synthesis.


Late effects in the vaginal and cervical epithelia after injections of diethylstilbestrol into neonatal mice.

Diethylstilbestrol, 5 mug per day for the first 5 days after birth, was injected into neonatal female NMRI mice. The animals were killed 13 months after birth. The upper vaginal part and the uterine cervix were serially sectioned. The histologic study showed extensive adenosis comprising most of the cervical wall. In some regions the glandular epithelium had undergone epidermatization. There were suggestive evidences of cancerous development from both the glandular epithelium and the epithelium in the epidermized regions. In the vaginal part, the squamous epithelium showed hyperplasia, but there were also glandular ducts penetrating far into the subepithelial tissue.


The gonadotropic hormones and their subunits in human maternal and fetal circulation at delivery.

The blood levels of HCG, LH, their alpha and beta subunits, and FSH were measured by double-antibody radioimmunoassays in 20 normal pregnanat women and in matched fetal cord arterial and venous samples at term. High levels of HCG, alpha subunit, and HCGbeta subunit, with low levels of LHbeta and FSH, were detected in maternal sera. In the fetal circulation the major detectable components were alpha subunits and presumably HCG. There was no significant arteriovenous difference in any of the hormones in the fetal circulation and no correlation between levels of hormones in maternal and fetal circulation. Column chromatography of sera confirmed that alpha subunits were present independent of intact hormones in both maternal and fetal sera.


Induction of ovulation in infertile women with pituitary tumors.

Four infertile women with pituitary adenoma were treated with human pituitary gonadotropins (HPG) in order to enable them to become pregnant. During pregnancy they contracted headache, bitemporal visual field defects, or impaired visual acuity. One woman was operated upon in the second trimester; the other three, as the symptoms were relatively moderate and no risk of permanent damage to the optic tract existed, went to term. After operation or delivery the symptoms disappeared.


Failure of stressful stimuli to inhibit embryo implantation in the rat.

The effects of stess by extreme temperature or immobilization on rat embryo implantation were investigated. One group of rats remained at 4 degrees C. at different days of progravidity. Other rats on L-3 of pregnancy remained at 39 degrees C. or immobilized. All the animals were put to death on L-6. The stressors produced no changes in either the per cent of rats implanting, the number of corpora lutea and implantation sites, or the weight of the ovaries and uteri. These results suggest that the process of nidation in the rat is resistant to several noxious environmental conditions.


Neovascularization after argon laser photocoagulation of macular lesions.

In three patients treated for macular degeneration with argon laser photocoagulation choroidal neovascularization occurred four to six weeks later at the photocoagulation site. Two of the patients were treated for angioid streaks of the macular region, the third patient was treated for disciform macular degeneration. Argon laser photocoagulation also induced neovascularization experimentally in pigmented rabbits.


Cusp size, sexual dimorphism, and heritability of cusp size in twins.

Overall measures of mandibular molars reflect the combined size contributions of the component cusps and ridges. Until now, the size hierarchy of primary and permanent mandibular molar cusps remained unclear. This paper utilizes the relative plane surface areas (basal area dimensions) of the individual molar cusps, as assays of cusp size to demonstrate cusp size variations within populations, antimere cuspal variations, sexual dimorphism, and, the heritability of cusp size. Duplicate dental casts from 199 pairs of like-sexed twins provide the raw dats. Defined anatomic landmarks on the occlusal surfaces were reduced to X-Y rectangular coordinates prior to the computation of the basal areas dimensions. The results establish a cusp size hierarchy specific for molar type, i.e., five-cusped molars with a distal fovea and distal marginal ridge (5fd), five-cusped molars without a distal fovea and without a distal marginal ridge (5o), and four-cusped molars (4c). Sexual dimorphism in cusp size is apparent in 5fd molar cusped but not in 5o molar cusps. However, males have a significantly higher frequency of 5fd molars. Females have a higher frequency of smaller 5o and 4c molars which have fewer crown components. Moreover, female 5o molars have cusps as large as or larger than 5o male molor cusps. Right-side-left-side differences exist between antimere cusps based on relatively low correlations. The mirroring of molor types occurs infrequently. When observed, most intrapair differences for cusp size, using F-ratios, indicate a low component of hereditary variability.


Sex and genetic differences in hair color changes during early childhood.

Hair color was assessed routinely from three months to six years for children participating in a longitudinal study of twins: 169 female twin pairs, 161 male pairs, and 60 opposite-sex pairs. Age trends, established by sampling only one number of every pair, showed marked changes in hair color for both sexes, but there was a consistent excess of light-haired males and dark-haired females. Within-pair concordance rates were calculated for same-sex pairs whose zygosity had been determined independently through bloodtyping. A high rate of concordance was found for MZ twins at every age in spite of the general change in hair color, indicating a strong genetic influence in the timing of color changes. The results are discussed in terms of accelerated maturation of females, and the need for genetic models of the inheritance of hair color which are age- and sex-specific.


Regulation of intestinal calcium-binding protein calcium intake in the rat.

Analytical gel electrophoresis of the vitamin D-dependent intestinal calcium-binding protein (CaBP) has demonstrated two protein bands (1 and 2) of similar molecular weight and similar specific binding activity. The mucosal concentration of CaBP, measured by a quantitative competitive binding assay, has been shown to vary reproducibly and inversely with calcium intake and the mucosal calcium concentration. These same factors also influence the relationship of bands 1 and 2. When animals on a high-calcium diet were placed on a low-calcium diet, their CaBP increased by 35% in 24 h and by 48% in 48 h and reached a level typical of animals on a low-calcium diet. Measurement of the diurnal variation of CaBP and mucosal calcium in animals allowed access to feed only at night revealed significant, but inverse, oscillations. These observations are interpreted as reflecting a regulation of CaBP by the mucosal calcium concentration, which appears to reflect absorbed calcium in transit.


Plasma renin activity during ovine pregnancy.

Chronic intravascular catheterization in maternal, fetal, and neonatal sheep was utilized to assess basal plasma renin activity (PRA) and changes in PRA in response to furosemide. Maternal PRA increased from base-line levels during the last trimester of pregnancy and remained elevated for 12 wk postpartum. Fetal basal levels of PRA were variable but usually greater than maternal levels. Intravenous administration of furosemide to pregnant ewes resulted in a prompt and significant increase in maternal PRA with inconsistent changes in fetal PRA. Fetal and neonatal animals with low basal levels showed a significant increase in PRA; maternal PRA did not change. Animals with higher basal levels did not respond to the stimulus, perhaps reflecting a maximum renin secretory rate. These data are consistent with the conclusions that fetal renin originated predominantly from the fetal kidney, that fetal PRA receives no significant contribution from the maternal circulation, and that renin does not cross the ovine placenta.


Lincomycin-curare interaction.

After observing a case of lincomycin (LCN)-induced respiratory insufficiency in a patient recovering from d-tubocurarine (DTC) administration, this interaction was studied in cats anesthetized with halothane-nitrous-oxide-oxide-oxygen. The sciatic nerve was stimulated with a 1.6-second tetanci train of 62.5 Hz every 10 seconds. The area under the contraction curve was electronically integrated and recorded. Five control cats received 0.01 mg/kg DTC every 2 minutes until time-tension integral response (TTIR) was zero. Five experimental cats received 10 mg/kg of LCN followed in 10 minutes by 0.01 mg/kg of DTC every 2 minutes until TTIR was zero. Both groups recovered to 50 per cent of control and were given 10 mg/kg of LCN. There was no difference between the slope of the y-intercept of the regression lines for the log-dose response curves for DTC in the two groups. LCN during recovery from DTC had a statist "Intermittent mandatory ventilation in the treatment of patients with chronic obstructive pulmonary disease".


A survey of the practice of anesthesiology in the U.S.--1972.

During the calendar year 1972, 46 hospitals throughout the U.S.A. participated in a survey of their anesthesia practices, using simple criteria from the "Standards of Patient Care in Anesthesiology." Eight "yes-no" questions were asked: 1. Was there written evidence of a preanesthetic evaluation by a physician? 2. Was there use of an anesthesia record? 3. Was there participation by a physician other than the surgeon in administration of anesthesia? 4. Was general anesthesia used? 5. Was the dosage or amount of anesthetic agent used during anesthesia recorded? 6. Was there evidence of postanesthesia surveillance in a recovery room? 7. Was there an identifiable postanesthesia note? 8. Did the patient live? Data from 208,868  anesthetic procedures indicated an overall mortality rate of 1.1 percent. Although affirmative responses in excess of 73 percent were noted to each condition of practice, only 50.9 percent of the cases received such a response to all five practice criteria; that is, questions 1, 2, 3, 5, and 7. A sample survey of data indicated a comparatively similar standard of practice between simple and complex operative cases.


The effects of ketamine and of Innovar anesthesia on digitalis tolerance in dogs.

In a comparison of digitalis tolerance in dogs anesthetized with ketamine, Innovar Vet, or pentobarbital, the dosage of ouabain needed to cause ventricular tachycardia was significantly higher, as was the LD50 of ouabain, with ketamine or Innovar than with pentobarbital. Ventricular tachycardia induced by ouabain was generally converted to sinus rhythm following administration of Innovar, ketamine, or droperidol but not after administration of fentayl alone or after pentobarbital.


Evaluation of manually operated self-inflating resuscitation bags.

Eight resuscitators were tested, of which five have recently been improved by the manufacturers (Air Shields Ambu, Danish-made Ambu, Pulmonator, Laerdal Resusci II, and Air Viva). One had an addition made to improve its oxygen (O2)-delivering capacity (Hope bag fitted with Blount collar) and two were new, the Air Bird, with and without high O2-concentration delivering system. The first five resuscitators were all in some way an improvement over their earlier counterparts. However, some still malfunction, some do not deliver adequate O2 concentrations for hospital use, and there is still a great variability in their performance. In some, freezing at low temperatures or clogging of valves with mucus are special hazards.


Cardiovascular effects of minimal analgesic quantities of Innovar, fentanyl, and droperidol in man.

In volunteer human subjects not undergoing surgical operations and breathing spontaneously, the cardiovascular effects of Innovar and of its components, fentanyl and droperidol, were determined when the drugs were administered in minimal amounts necessary to reach an analgesic endpoint. This amount was fentanyl 5 mcg./kg. body weight combined with droperidol 0.22 mg./kg. Innovar, or its components when administered separately, produced minimal cardiovascular changes of consequence during the time of maximum analgesia (about 15 minutes). With the passage of time after administration of a single dose of Innovar, there were some changes in cardiac output, heart rate, and stroke volume, probably representing normal changes of sedated sleep. None of the changes, acute or delayed, was clinically significant. Analgesia could be achieved only when fentanyl was combined with droperidol; and although a certain amount of respiratory depression resulted from the combined drugs, the authors concluded that the observed cardiovascular changes probably represented primary drug effects.


Case history number 82: "nonflammable" fires in the operating room.

Fires can and do occur with presumably nonflammable anesthetic technics, especially in relatively closed areas such as the oral cavity. As long as we use high concentrations of O2 and N2O in the presence of potentially flammable material and a potent source of ignition, we must remain vigilant to minimize the chance of harming our patients by fire.


Aortic valve replacement in a hemodialysis-dependent patient: anesthetic considerations--a case report.

In the anesthetic management of a hemodialysis-dependent patient undergoing aorticvalve replacement, technical and pathophysiologic problems considered included: 1. The presence of an arteriovenous hemodialysis fistula. 2. Hemodynamic alterations associated with aortic insufficiency. 3. Choice of anesthetic agents, fluid, and electrolyte balance in the presence of renal failure. 4. Postoperative management of hypertension and hyperkalemia. While there are many possible approaches, the authors present one successful technic for consideration.


Patient preference for ketamine: a case report of multiple anesthesias.

A 17-year-old underwent 17 anesthetic procedures during a period of 40 days with several different general anesthetics and declared the ketamine technic to be the most satisfactory. The authors consider subjective experiences very important in selecting anesthetic agents for patients undergoing multiple anesthesias.


Hypoventilation in a newborn following administration of succinylcholine to the mother: a case report.

Analysis of maternal and neonatal blood samples for cholinesterase-activity determination revealed a case of hypoventilation in the newborn to be apparently secondary to succinylcholine administration to the mother during obstetric anesthesia.


Malignant hyperthermia associated with enflurane anesthesia: a case report.

Malignant hyperthermia syndrome associated with various anesthetic agents has been well documented, but none has been reported with enflurane (Ethrane). This particular case is the first involving exposure for the second time to enflurane anesthesia after a six-month interval in which malignant hyperthermia resulted. A patient subject to malignant hyperthermia does not necessarily develop rigidity after succinylcholine for the intubation as noticed in this case. However, with the abnormal production of heat in the soda lime canister with tachycardia, tachypnea, rapidly rising body temperature and hypertonicity of skeletal muscles during anesthesia one should suspect malignant hyperthermia. The treatment of malignant hyperthermia involves cooling procedures, correction of acidosis, use of steroids and procainamide, and acetaminophen to facilitate lowering the body temperature.


Humidification of anesthetic systems for prolonged procedures.

The desirability of humidification of anesthesia systems for prolonged surgical procedures has been documented previously. Dry anesthetic gases damage the ciliated epithelium and cause respiratory heat loss. Chalon suggests that from 12 to 16 mg. of water/L. of gas is necessary to prevent damage to the tracheal epithelium. This study describes a method of obtaining values of from 21.5 plus or minus 0.4 to 39.3 plus or minus 0.1 mg. of water/L. by cycling the fresh gas flow through the carbon dioxide (CO2) absorber before exposure to the patient.


Vitrectomy: a new challenge for the anesthesiologist.

A new surgical procedure, virtectomy, for alleviation of blindness caused by previously intractable vitreous disease, is described. Special demands of vitrectomy upon the anesthesiologist are enumerated. Problems presented by a patient population, 83 percent of whom suffered from severe diabetes mellitus and/or hypertension with a variety of complications, are discussed. Anesthetic technic used for 47 patients undergoing vitrectomy is described.


Eyelid neoplasms of dogs.

A survey of 202 canine eyelid neoplasms was conducted to identify the prevalence of tumor types and their biological behavior. Sebaceous gland tumors, melanomas, and papillomas made up 82.1% on neoplasms studied. Sebaceous tumors were most frequently encountered, comprising 44% of canine eyelid tumors. Benign tumors (75.3%) were more prevalent than malignant forms (26.7%), and epithelium tumors outnumbered those of mesenchymal origin 134 to 23. A slightly higher percentage of neoplasms were removed from upper eyelids (40.2%) than from lower eyelids (30.2%). The average age of dogs with eyelid tumors was 8 years. Malignant tumors were comparatively larger than benign forms, but metastasis of eyelid tumors was not observed.


"Precurarization" using pancuronium.

A study comparing tubocurarine and pancuronium for precurarization indicates that either successfully attenuates fasciculation after succinylcholine administration. However, if the aim is to prevent or attenuate such side effects of succinylcholine as cardiac arrhythmias, hyperkalemia, and increased intraocular pressure, there is as yet no proof that pancuronium will be effective in these areas.


Anesthesia for jejunoileal shunt: review of 88 cases.

Experience with 88 obese pateints undergoing jejunoileal shunt is reviewed, with emphasis on preoperative preparation and assessment, conduct of anesthesia, postoperative care, and anesthesia-related complications. There was no intraoperative mortality, and postoperative morbidity was minimal. The operation can be viewed as a short-term answer to the malignancy of massive obesity, since physiologic abnormalities are reversible; however, only hospitals that can provide full surgical, medical, endocrinologic, and anesthesia services, backed by modern ancillary investigative ability, should perform this operation.


Pathologic features of chronic pneumonia in pigs with experimentally induced African swine fever.

Chronic pneumonia developed in 14 pigs inoculated with an attenuated strain of African swine fever (ASF) virus. The pathogenesis of the pneumonia was as follows: (1) Interalveolar septums became thickened by accumulation of lymphocytes and monocytes; (2) lung developed focal areas of lymphocytes and macrophages; (3) necrosis began abruptly in these foci, beginning with the cells in the alveolar lumens, developing in centrifugal direction, and eventually affecting all structures in its path; (4) necrotic tissue became calcified; and (5) a mantle of mononuclear cells (including plasma cells) and fibrous tissue formed around the necrotic area. Viremia occurred in the 14 pigs at postinoculation day (PID) 14, and precipitating antibody was increased significantly at PID 58.


Immunoferritin and immune electron microscopic study of bovine herpesvirus strain DN-599.

Intracellular antigens of strain DN-599 bovine herpesvirus were detected in the cytoplasm and the nucleus of infected bovine embryonic kidney cells by the indirect immunoferritin (IF) technique. Specific tagging was observed in viral envelope and capsids. Aggregates of viral particles heavily coated with antibody were seen by immune electron microscopy (IEM).


Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine.

Administration of either gallamine or d-tubocurarine before injecting succinylcholine diminished both the incidence and intensity of muscle fasciculations. Gallamine was more efficient than curare in this respect, 30 mg./70kg. almost entirely preventing fasciculations.


Acupuncture in obstetrics.

Electroacupuncture (ACP) during childbirth was used in 12 parturients. On the average, it produced 66 percent analgesia in 7 patients for 139 minutes while patients were in active, progressive labor. When ACP no longer could relieve pain, spinal, epidural, or double-catheter technic produced complete analgesia in all patients. ACP did not adversely affect the fetus or uterine contractions and had no harmful aftereffect on mother or neonate. However, its use as a routine method had disadvantages because analgesia was inconsistent, unpredictable, and incomplete. The technic was time-consuming, limited the patient's movement, added more wires and machinery, and interfered with electronic monitoring of the mother and fetus.


Data for peer review: acquisition and use. Results in the experimental medical care review organization program.

Nine Experimental Medical Care Review Organizations (EMCROs) review the process and outcome of medical care, using insurance billing claims or medical record abstracts as the data source. The cost of EMCRO insurance billing claims processing in 1972, including peer review, ranged from $0.47 to $2.50 per claim. Three EMCROs reviewed the necessity for elective hospital admission prospectively for $2.50, $8.50, and $10.02 per case. The EMCROs developed innovative methods for abstracting hospital, nursing home, and ambulatory medical records at a cost of $0.40 to $4.00 per abstract. These EMCRO cost estimates were not derived from uniform accounting methods. Problems of accuracy and comparability of data for peer review are discussed. The EMCRO experience may aid local implementation of Professional Standards Review Organizations (PSROs).


Characterization of hydrogen sulfide-producing bacteria isolated from meat and poultry plants.

A survey of the types of aerobic organisms able to produce H2S on peptone iron agar (Levin, 1968), and commonly occurring in meat and poultry plants, revealed that these could be divided into four distinct groups.  The ability of representative strains of each type to grow at low temperatures and cause off-odors on chicken muscle was examined.  The results are discussed in relation to the role of these organisms in the psychrophilic spoilage of meat and meat products.


Assay for lipolytic and proteolytic activity using marine substrates.

Nondestructive assay procedures for determining microbial lipolytic and proteolytic activity on marine substrates were developed and tested with 287 isolates of bacteria, filamentous fungi, and yeasts.  A definite substrate specificity was noted when the enzymatic activities on marine and nonmarine substrates was compared.  Of 170 lipolytic isolates, 14 were only active on menhaden oil, 11 could hydrolyze menhaden oil and Tween 80 and/or tributyrin, and 145 isolates could only hydrolyze one or both of the nonmarine lipids.  Of the 198 proteolytic isolates, 10 were specific for codfish extract, 152 were active against the marine substrate plus casein and/or gelatin, and 36 were specific for nonmarine substrates.


Quantitative method for the gas chromatographic analysis of short-chain monocarboxylic and dicarboxylic acids in fermentation media.

A method for the preparation and gas chromatographic analysis of the butyl esters of volatile (C-1-C-7) and nonvolatile (lactic, succinic, and fumaric) acids in microbial fermentation media is presented. Butyl esters were prepared from the dry salts of the acids. The esters were separated by temperature programming on a column of Chromosorb W coated with Dexsil 300 GC liquid phase and analyzed with a flame ionization detector. Apparent recoveries with butanol-HCl or butanol-H2SO4 as butylating agents were 80 to 90% for most acids. Chromatographic profiles of the butyl esters demonstrated that both volatile and nonvolatile acids can be detected and separated in 24 min on a single column. Standard calibration curves (peak area versus concentration) of the butyl esters were linear in the range of 5 to 40 mumol of acid per ml. The advantages of using an internal standard (heptanoic acid) for quantitating fatty acids in a mixture are given. Chromatograms of butylated fermentation media in which rumen anaerobic bacteria were grown illustrated that this method is useful for determining short-chain volatile and nonvolatile acids of toxonomic significance.


Action of water in depressing acetylene reduction by detached nodules.

Adverse effects of water on acetylene reduction by detached soybean root nodules could not be attributed to ethanol formation, but apparently were associated with nodule tissue damage caused by detachment. Intact nodules were not affected by moisture.


Polyribosomes in different stages of the life cycle of the water mold Allomyces arbuscula.

Synchronous gametogenesis in the water mold Allomyces arbuscula is blocked by actinomycin D added at the onset of the process. Formation of the male gametangium can be selectively inhibited by administering actinomycin one hr after the induction of gametogenesis. The polyribosome pattern obtained after density gradient centrifugation remains virtually unchanged throughout gametogenesis until a stage immediately preceding maturation of the gametes. When ribosome from gametes and swarming zygotes are analyzed on gradients, some RNase-sensitive materials is found to band in the heavier portion of the gradient. Its presence suggests that some messenger RNA associated with ribosomes is conserved in the swarming cells. During gametogenesis RNA is de novo synthesized and becomes associated with the polyribosomes.


Schistosomal cholecystitis.

A 51-year-old man with schistosomiasis had symptoms of cholecystitis due to Schistosoma mansoni eggs found in all layers of the gallbladder associated with all stages of inflammatory granulomatous reaction. Adult worms were found in a subserosal venule also. Why parasitism of the gallbladder by S mansoni eggs is apparently rare is not known.


A twin study of intelligence in Russia.

Twin data from prewar Russia show the same effect of family environment on intelligence as in contemporary America.


Endocarditis caused by Rhodotorula successfully treated with 5-fluorocytosine.

A 7-year-old boy suffering from aortic regurgitation and mitral stenosis and regurgitation was admitted with endocarditis caused by Rhodotorula pilimanae and was treated successfully with orally administered antifungal agent, namely 5-fluorocytosine (5-FC). A dose of 100 mg per kg body weight, divided into four equal parts, was prescribed. After a prolonged febrile period his temperature dropped to normal on the fourth day of 5-FC therapy. Review of the published reports disclosed few cases of endocarditis due to Rhodotorula spp. and this case seems to be the first treated with 5-FC. Follow-up in one year, after discharge from the hospital, revealed no evidence of relapse.


Effects upon glucose metabolism of feeding a low- or high-roughage diet at two levels of intake to sheep.

1. To determine the effect of diet and level of energy intake on glucose metabolism in sheep, four dietary treatments consisting of feeding a low-roughage (LR) and a high-roughage (HR) diet at each of two intake levels estimated to provide 586 and 1172 kJ (140 and 280 kcal) digestible energy (DE)/kg body-weight-0.75 per d were given to each of eight yearling rams in four different time periods each of 4 weeks duration. Both diets contained 140 g crude protein/kg using ground maize, mixed hay and soya-bean meal and were given in two meals/d. Estimated DE values of food were verified during the study and actual intakes of DE were within 9.5% of the estimated values. 2. To study glucose metabolism, a single intravenous injection of ]2-3H]glucose and subsequent withdrawal of nine venous blood samples with 3 h were made in each experiment. Two experiments were conducted on consecutive days for each sheep on each dietary treatment. 3. Coefficients of determination (r2) for linear regressions to measure the effect of time after a single injection of [2-3H)glucose on log specific radioactivity of plasma glucose were calculated for fifty-eight experiments. In fifty-six of the experiments, r2 values exceeding 0-95 were obtained. 4. Compared to the HR diet, the LR diet increased (P smaller than 0-05) the pool size and decreased (P smaller than 0-05) the half-life of glucose. At both intake levels, the LR diet increased (P smaller than 0-05) the plasma concentration and the entry rate of glucose compound to the HR diet but interaction (P smaller than 0-05) between diet and intake level was attributed to a greater difference obtained between diets at the higher compared to the lower level of food intake. Increasing the level of intake caused a greater (P smaller than 0-05) pool size and space, and a shorter (P smaller than 0-05) half-life of glucose. 5. It was concluded that substitution of roughage by concentrate in a ruminant's diet may increase the rate of glucose entry during a short time period after eating.


The effect of raw soya bean on in vitro active and passive accumulation by rat small intestine.

1. Sections of small intestine from rats given raw-soya-bean(RS) diets had a decreased capacity to actively accumulate L-methionine when compared to those taken from rats given heated soya bean (HS), and casein-fed controls. The extent of the reduction was small in comparison with pair-fed animals, but was statistically significant in comparison with rats restricted to the same weight gain as the RS groups. 2. The differences in the passive uptake of D-mannitol appear to be directly related to differences in gut thickness between the control and RS groups. 3. Values for water movement and intestinal transmural potentials further support the results found in the active accumulation studies. 4. From this study it was concluded that the degree of starvation directly affects the magnitude of the effect of RS diets when comparisons are made against adequately fed controls.


Concurrent studies of the flow of digesta in the duodenum and of exocrine pancreatic secretion of calves. 3. Further studies on the addition of fat to skim milk and the use of non-milk proteins in milk-substitute diets.

1. The flow of digesta through the duodenum and the concurrent secretion of the pancreas were studied in four Friesian calves given four milk-substitute diets. The diets were: reconstituted, "mildly" pre-heated, spray-dried skim-milk powder with (SKF) or without (SK) margarine fat or with 5o percent of the skim-milk powder in diet SKF replaced by soya-bean flour (ASKF) or fish-protein concentrate (BSKF), together with dried whey. The diets were given ad lib. twice daily from 13 to 37 d of age, each diet being given for 6 consecutive days. Collections of duodenal digesta and pancreatic secretions, from cannulas, were made for 12 h after feeding the 6th and 12th meals ("experimental" meals) for each diet. 2. The diets fed as "experimental" meals contained polyethylene glycol (PEG) as a fluid (whey) marker and goat's milk containing (3H)lysine as a marker for total protein; beta-carotene was added as a lipid marker to the three diets containing margarine fat. 3. Over the 12 h postprandial period, the patterns of duodenal digesta flow and secretion of pancreatic fluid did not differ markedly between the four diets. The abomasal outflow of both nitrogen and lipid in a 12 h postprandial period was related to their intakes from the "penultimate" (5th and 11th) meals for diets SKF and SK BUT TO THEIR INTAKES AT THE "EXPERIMENTAL MEALS" FOR DIETS ASKF and BSKF. Secretion of pancreatic enzyme activity was highest during the 1st hour after feeding but the main outflow from the abomasum of total N and lipid occurred 5-10 h after feeding. 4. The time required for all the whey marker (PEG) to pass through the duodenum was similar for diets SKF and SK, but only 53 and 42 percent respectively of the ingested protein marker passed through the duodenum in the 12 h after feeding. More acid appeared to be secreted by the abomasum when diet SK was given; also less undigested protein passed out of the abomasum after giving this diet. It is concluded that the physical absence of fat globules in the abomasal clot increases the degree of proteolysis. 5. The secretions of pancreatic fluid and pancreatic enzyme activity were all markedly lower for diet SK than for diet SKF. 6. With diets containing non-milk proteins (ASKF and BSKF), abomasal proteolysis was less efficient and the ingested protein passed out of the abomasum more rapidly than for diet SKF. There was no difference in the rate of abomasal outflow of the whey fluids between diets SKF, ASKF and BSKF. 7. In comparison with diet SKF, diets ASKF and BSKF tended to induce less pancreatic enzyme secretion over a 12 h postprandial period, with the exception of lipase. 8. There appeared to be no direct relationship between the quantities of any of the pancreatic enzymes secreted during a postprandial period and either the concurrent flow of duodenal digesta or the total quantities of dietary constituents passing through the duodenum.


The digestion of bulbils (Polygonum viviparum L.) and berries (Vaccinium myrtillus L. and Empetrum sp.) by captive ptarmigan (Lagopus mutus).

1. The digestion of three foods favoured by ptarmigan (Lagopus mutus) in the wild was studied using captive birds. 2. Bulbils of Polygonum viviparum L. were a good source of metabolizable energy, protein and phosphorus, but were deficient in sodium. Berries of Vaccinium myrtillus L. were the most digestible of the three foods, contained enough protein and P for maintenance, but were probably deficient in Na. A diet of Empetrum sp. berries caused the birds to be in negative nitrogen and P balance, but provided adequate Na. Both species of berries were rich sources of soluble carbohydrate. 3. In the wild, ptarmigan eat a mixed diet, which presumably provides adequate Na, protein and P. 4. The relative proportions of the various end-products of N metabolism varied according to the protein content of the food. With the diet of Vaccinium berries (11 g N/kg dry matter) roughly equal amounts of ammonium salts and urates were excreted. With Polygonum bulbils (29 g N/kg dry matter) the quantities of ammonium salts and urates excreted were similar to those with Vaccinium berries, but some urea was also excreted and about half the N in the birds' droppings was in an unidentified form. 5. When eating Empetrum berries, ptarmigan digested lignin and tannins and excreted ornithurates. The benzoic acid moiety of the ornithuric acid molecule may have been derived partly from the digested lignin and tannins.


Affinity labeling of a regulatory site of bovine liver glutamate dehydrogenase.

A new adenosine analog, 3'-p-fluorosulfonyl-benzoyladenosine (3'-FSBA), has been synthesized which reacts covalently with bovine liver glutamate dehydrogenase. Native glutamate dehydrogenase is activated by ADP and inhibited by high concentrations of DPNH. Both of these effects are irreversibly decreased upon incubation of the enzyme with the adenosine analog, 3'-p-fluorosulfonyl-benzoyladenosine (3'-FSBA), while the intrinsic enzymatic activity as measured in the absence of regulatory compounds remains unaltered. A plot of the rate constant for modification as a function of the 3'-FSBA concentration is not linear, suggesting that the adenosine derivative binds to the enzyme (Ki equals 1.0 times 10-4 M) prior to the irreversible modification. Protection against modification by 3'-FSBA is provided by ADP and by high concentrations of DPNH, but not by the inhibitor GTP, the substrate alpha-keto glutarate, the coenzyme TPNH, or low concentrations of the coenzyme DPNH. The isolated altered enzyme contains approximately 1 mol of sulfonylbenzoyladenosine per peptide chain, indicating that a single specific regulatory site has reacted with 3'-tfsba. the modified enzyme exhibits normal Michaelis constants for its substrates and is still inhibited by GTP, albeit at a higher concentration, but it is not inhibited by high concentrations of DPNH. Although ADP does not appreciably activate the modified enzyme, it does (as in the case of the native enzyme) overcome the inhibition of the modified enzyme by GTP. These results suggest that ADP can bind to the modified enzyme, but that its ability to activate is affected indirectly by the modification of the adjacent tdpnh inhibitory site. It is proposed that the regulatory sites for ADP and DPNH are partially overlapping and that 3'FSBA functions as a specific affinity label for the DPNH inhibitory site of glutamate dehydrogenase. It is anticipated that 3'-p-fluorosulfonylbenzolyadenosine may act as an affinity label of other dehydrogenases as well as of other classes of enzymes which use adenine nucleotides as substrates or regulators.


The thermodynamics of hapten and antigen binding by rabbit anti-dinitrophenyl antibody.

Rabbit anti-dinitrophenyl antibody from a serum pool was obtained as five fractions of purified specific antibody by a limiting antigen precipitation method. Each fraction had a different binding affinity for epsilon-N-2,4-dinitrophenyl-L-lysine. The free energy changes for hapten binding to the five antibody fractions varied from -8.35 to -10.0 kcal/mol. An average deltaH of -13.9 kcal/mol was measured for the fractions with a batch calorimeter. The results indicate no significant correlation between enthalpy changes and free energy changes. However, a statistically significant correlation between the free energy changes and the entropy changes was found. The enthalpy of the anti-dinitrophenyl antibody interaction with multivalent dinitrophenyl human serum albumin was determined. These are the first enthalpy measurements of an antibody antigen reaction in which the intrinsic binding enthalpy between the antibody and the determinant group is known. The deltaH for the antigen binding reaction was -10.1 kcal/mol which is 3.8 kcal/mol less exothermic than the deltaH for the hapten binding reaction. The interactions that could lead to such a difference in enthalpy are discussed.


Further characterization of bovine pancreatic lipase.

1. The amino acid composition of bovine pancreatic lipase is very similar to that of porcine lipase. 2. Bovine lipase possesses a residue of lysine at the N-terminal position and a half cystine or a cysteine at the C-terminal position. 3. Bovine lipase contains two free sulfhydryl groups of different reactivities to 5, 5'-dithiobis-(2-nitrobenzoic) acid. One of these groups is buried in the native conformation of the enzyme and is fully titrated in 1.5 M urea when reaction is performed in the presense of 1 mM EDTA.


Purification and properties of staphylocoagulase.

Staphylocoagulase, an exoprotein of coagulase-positive Staphylococci, has been purified to a state in which only trace amounts of contaminating proteins are detectable. Aspartic acid was found as a single N-terminal amino acid in this preparation. The molecular weight is 61 000; the isoelectric point lies as pH 4.53. The amino acid composition was determined.


Differential sensitivity of low molecular weight DNA polymerase to sulfhydryl-blocking reagents.

Activity of a 2.5 S mouse myeloma DNA polymerase (termed DNA polymerase II) measured with either poly(rA) or poly(dA) as template did not require sulfhydryl-reducing reagents, but was sensitive to inhibition by p-hydroxymercuribenzoate and the sulfhydryl-alkylating reagent, N-ethylmaleimide; however, the activity was much more sensitive to inhibition by p-hydroxymercuribenzoate than by the sulfhydryl-alkylating reagent. The p-hydroxymercuribenzoate inhibition appeared to involve the mercurial portion of the p-hydroxymercuribenzoate molecule because HgCl2 was an equally effective inhibitor, while p-hydroxybenzoate had little effect upon enzyme activity. The p-hydroxymercuribenzoate inhibition was reversed by an equal concentration of the sulfhydryl-reducing reagent, dithiothreitol.


The relation of thrombokinetics to bone marrow megakaryocytes in idiopathic thrombocytopenic purpura (ITP).

In 23 patients with untreated idiopathic thrombocytopenic purpura (TP), the relation of thrombokinetics to quantitative determinations of megakaryocytes in bone marrow sections was studied. The megakaryocytes were classified into maturation stages, and platelet sizes were determined. Megarkaryocyte number and volume per microliter of bone marrow were significantly higher in ITP as compared to controls. The megakaryocyte number and volume were inversely related to the peripheral platelet count. Platelet production rate was significantly increased in ITP and related to the megakaryocyte number and volume. The megakaryocytes were shifted towards more immature forms in ITP, suggesting an increased turnover rate of the expanded recognizable metakaryocyte compartment. Platelet size was significantly increased in ITP, and the mean platelet diameter was 1.6 times normal. There was a significant relationship between platelet size and platelet production rate, as well as an inverse relationship between platelet size and platelet mean life-span (MLS). There was also a significant correlation between platelet size and the proportion of young megakaryocytes.


Interaction between oxytocin and antidiuretic hormone and its effect on the milk secretion by alveoli of the mammary gland of lactating rats.

Interaction between exogenous and endogenous oxtocin and vasopressin was found to affect the mechanism of milk ejection by the alveoli of the mammary gland in lactating rats. Inhibition and stimulation of the effect of oxytocin on milk ejection by vasopressin was demonstrated. On the basis of the principles observed the concentrations fo these hormones were investigated in the plasma of dogs deprived of water for 3 days and then allowed to drink.


Effect of bacterial polysaccharide on the number of antibody-producing cells in the spleen of irradiated and unirradiated mice.

The effect of bacterial polysaccharide on the number of spleen cells producing  antibodies against sheep's red cells was investigated in irradiated and unirradiated mice. The polysaccharide increased the number of antibody-producing cells both in lethally irradiated (psi rays) and in unirradiated mice, unimmunized with sheep's red cells. This increase was connected with the stimulation of proliferative processes in the recipient by the polysaccharide.


Effect of folic acid and methotrexate on reproduction of Rauscher leukemia virus.

Folic acid was found to stimulate and its structural analog methotrexate was found to inhibit the reproduction of an oncogenic RNA-containing virus in tissue culture.


Experimental study of the functional morphology of the kinetochore in mitosis.

Chinese hamster cells in culture were blocked in prometaphase by the addition of chloral hydrate. After 2 h the chloral hydrate was removed and the ultrastructural changes in the kinetochore studied during recovery of mitosis. The kinetochore in the blocked cells is a disc measuring 300-350 nm in diameter and 30-35 nm in thickness. Imediately after recovery of mitosis the disc begins to break up and fuse with the inner nucleus of the kinetochore, when it acquires a spherical organization. On combined treatment with chloral hydrate and cobalt nitrate, inducing despiralization of the chromosomal ifbrils, the knetochore in the blocked cells becomes spherical. It is concluded that activation of the kintochore in prometaphase probably involves despiralization of the fibrils composing the disc.


Action of x-ray irradiation on DNA synthesis and mitotic activity in uterine epithelial cells at different stages of the sex cycle.

The action of x-ray irradiation on DNA synthesis and mitotic activity of the uterine epithelium was studied by autoradiography with thymidine-H-3 at different stages of the sex cycle. In response to local irradiation in a dose of 400 R the decrease in the index of labeled nuclei and in the mitotic index differed depending on the stage of the sex cycle at which irradiation was given.


The effects of implanting testosterone propionate into the central nervous system on the sexual behaviour of adrenalectomised female rhesus monkeys.

Bilateral adrenalectomy rendered ovariectomised, oestrogen-treated female rhesus monkeys sexually unreceptive. Small unilateral implants of testosterone propionate (mean weight 140 mug) into the anterior hypothalamus/preoptic area restored receptivity in 7 out of 8 of these monkeys. Cholesterol implanted into the same area, or similar amounts of testosterone propionate implanted into the posterior hypothalamus/pretectal area (4 females) or cerebral cortex/dorsal thalamus (5 monkeys) had no consistent effect on behaviour. It therefore seems likely that androgens regulate sexual receptivity in female monkeys by acting on some part of the anterior hypothalamus. Thus, though the hormonal control of receptivity in female primates differs from non-primates, the site on which hormones act to regulate this behaviour may be similar in both.


Characteristics of exaggerated sexual behavior induced by electrical stimulation of the medial preoptic area in male rats.

Twenty-two sexually experienced male rats were implanted with lateral preoptic (LPO) and medial preoptic (MPO) electrodes. Following surgery, the 22 MPO and 18 LPO electrodes were screened for the induction of stimulation-bound copulation in the presence of estrus females. Stimulation through 5 of the MPO electrodes induced highly exaggerated, stimulation-bound sexual behaviou. Ten MPO electrodes produced escape behavior, 2 electrodes aggression and one electrode induced sexual behavior intermingled with aggression. The tips of all the electrodes which effected exaggerated copulation were located within a small preoptic region, less than 1 mm lateral to the midline. LPO electrodes had either inhibitory effects on mating behavior or none at all. The increase in copulatory activity by MPO electrodes' stimulation was expressed in a great enhancement in the number of ejaculations, and marked decreases in the latency to ejaculation, the post-ejaculatory refractory period, and in the number of intromissions preceding an ejaculation. It is concluded that the electrical stimulation affected both the sexual arousal mechanism and the intromission-ejaculation mechanism involved in mating behavior.


Increased orientation to sensory stimuli following medial hypothalamic damage in rats.

After unilateral medial hypothalamic damage, rats become hyperresponsive to touch, odors, and visual stimuli presented on the side contralateral to the damage, while responding to ipsilateral stimuli remains near preoperative levels. These rats would orient their snouts more precisely to stimuli presented on the contralateral side, turn toward touch of more caudal points along that body surface, and pursue moving stimuli more vigorously on that side. Rats with unilateral damage would also viciously bite relatively weak noxious stimuli presented on the contralateral side. After injections of amphetamine, rats turned away from the side of the damage. After bilateral damage, rats showed increased responsiveness to sensory stimuli arising on either side. The rats with unilateral damage began eating more food from a container located in the contralateral sensory field than they had preoperatively. In addition, they began to attack mice more frequently and with shorter latencies when the mouse was on the side contralateral to the lesion. Just as the sensory loss after lateral hypothalamic damage contributes to the aphagia and decreased aggressive behavior of such rats, it seems that increased responsiveness to sensory stimuli plays a role in the syndrome of hyperphagia, finickiness, and increased aggressiveness seen after medial hypothalamic damage.


The possible prognostic usefulness of assessing serum proteins and cholesterol in malignancy.

Serial measurement of serum proteins, albumin, and cholesterol levels was used in attempt to assess the course and prognosis in cancer patients. This assessment is based on the fact that their declines followed first order kinetics and that these patients usually died when their levels were lower than half the initial levels. Two categories of cancer patients were identified: those in whom the initial measurements of serum albumin or cholersterol, taken soon after diagnosis, were declining (Group I), and those who showed such a decline as they entered an advanced or terminal phase (Group II). Group I included cancer of the stomach, kidney, lung (adenocarcinoma and squamous cell carcinoma), oral cavity, large intestine, breast (40%), bladder, ovary (70%), pancreas, and prostate; leukemia (acute myeloid and lymphocytic); and Hodgkin's disease (60%), all of which accounted for approximately 90% of the major causes of cancer deaths. Group II included Hodgkin's disease (40%), and cancer of the ovary (30%) and breast (60%), all of which accounted for 10% of the major causes of cancer deaths.


Breakage of a DNA-protein complex induced by 4-nitroquinoline 1-oxide, 4-nitropyridine 1-oxide, and their derivatives in cultured mouse fibroblasts.

The effects of a number of 4-nitroquinoline 1-oxide and 4-nitropyridine 1-oxide derivatives, with varying carcinogenic potencies, on the scission of proteins linking DNA were studied in cultured mouse fibroblasts, strain L-P-3. With twenty-two 4-nitroquinoline 1-oxide derivatives and twelve-4-nitroquinoline 1-oxide derivatives tested, an excellent correlation was found between the scission effect of each compound and its carcinogenicity. All carcinogens, whether strong or weak, showed positive results in the scission test. Strong carcinogens such as 4-nitroquinoline 1-oxide, 2-methyl-4-nitroquinoline 1-oxide, 6-methyl-4-nitroquinoline 1-oxide, 6-chloro-4-nitroquinoline 1-oxide,and 4-hydroxyaminoquinoline 1-oxide induced the scission at a low concentration of 1 x 10-5 M, while weak carcinogens such as 3-methyl-4-nitroquinoline 2-oxide, 6-n-butyl-4-nitroquinoline 1-oxide, 6-tert-butyl-4-nitroquinoline 1-oxide, 6-n-hexyl-4-nitroquinoline 1-oxide, and 6-carboxy-4-nitroquinoline 1-oxide only produced the same effect a dose levels higher than 5 x10-5 M. On the other hand, some noncarcinogenic derivatives such as 8-nitroquinoline  1-oxide, 4-hydoxy-quinoline 1-oxide, 4-aminoquinoline  1-oxide, and 6-nitroquinoline could not induce the scission, while other noncarcinogens such as 3-nitroquinoline 1-oxide, 5-nitroquinoline 1-oxide, and 5-nitroquinoline did induce scission at concentrations higher than 1 x 10-4 M. Throughout these tests the effective concentrations of active compounds were generally much lower than the concentration at which the compounds were cytotoxic. The implication of the results and the feasibility of the present method of analysis as a screening procedure for potential carcinogens and muagens are discussed.


Mechanism of growth inhibition by methotrexate.

The effect of methotrexate on the growth of Chinese hamster cells was examined under a variety of conditions. The experiments suggest that the important biological effects of methotrexate are the result of direct inhibition of thymidylate synthetase and one or both of the folate-dependent enzymes involved in a purine biosynthesis. In addition, analysis of the distribution of intracellular folate derivatives following methotrexate treatment gives no indication of accumulation of dihydrofolate, and accumulation that would be expected if inhibition of dihydrofolate reductase were the principal site of methotrexate action.


Elevated plasma sialyltransferase in the cancer patient.

Sialyltransferase activity was measured in plasma samples using desialated fetuin as the acceptor and cytidine 5'-phosphate-sialic acid as donor. The data show an increased enzyme level in 56 of 65 cancer patients studied, as compared with normal control values. The enzyme was not significantly elevated during lacation or in liver cirrhosis, but it was elevated in rheumtoid arthritis. Of the patients with cancer, 35 showed plasma enzyme levels above any value encountered in rheumatoid arthritis plasmas. The determinants of enzyme level in cancer appear to be complex: monitoring of plasma sialytransferase may be of value in measuring tumor progression, metatastatic involvement, or success of therapeutic programs.