In vivo absorption of phenytoin from rat small intestine and its inhibition by phlorizin.

In vivo absorption of phenytoin from the small intestine was studied by an in vivo closed segment technique. Phenytoin in concentrations of 1000, 2000, and 4000 mumol/l was administered in dissolved form. Polythylene glycol 4000 was used as a non-absorbable marker. The concentrations of phenytoin in the intestinal lumen, in the mucosa, and in cardiac blood were measured both by spectrophotometry and by gas chromatography. Phenytoin was absorbed very rapidly, and the proportion absorbed increased with increasing dose. Thus, during the first 10 min. about 85 per cent of the largest dose but only 25 per cent of the smallest dose had been absorbed. The phenytoin concentration in mucosa and serum increased in an analogous way; maximum values were observed within the first ten minutes. The concentrations in mucosa and serum were dose dependent during the first ten minutes. 0.01 mmol/l and 1 mmol/l phlorizin significantly reduced the transfer of phenytoin (4000 and 2000 mumol/l) from the gut lumen to the mucosa. No inhibition was observed when the initial phenytoin dose was 1000 mumol/l. The results suggest that an active transport mechanism, sensitive to phlorizin, is involved in the intestinal absorption of phenytoin in the rat.


Blood pressure response to ethanol in relation to acetaldehyde levels and dopamine-beta-hydroxylase activity in rats pretreated with disulfiram, cyanamide and coprine.

The blood pressure response after ethanol administration was studied in relation to blood acetaldehyde levels, aldehyde-dehydrogenase (ALDH)--and dopamine-beta-hydroxylase (DBH) activities in rats pretreated with the ethanol-sensitizing compounds disulfiram, cyanamide and coprine and the DBH-inhibitor FLA-57. Disulfiram, cyanamide and coprine, but not FLA-57, inhibited the low-Km ALDH in the liver and caused an increased acetaldehyde level in blood. Disulfiram and FLA-57, but not cyanamide and coprine, decreased the DBH-activity in the heart and the levels of norepinephrine in the heart and the brain. In disulfiram-treated rats with a low DBH-activity, a fall in blood pressure was observed at acetaldehyde levels being slightly higher than those found in control rats. In disulfiram-treated rats with a DBH-activity close to control activity and in rats pretreated with cyanamide or coprine, a fall in blood pressure were observed in rats pretreated with FLA-57. In rats pretreated with coprine + FLA-57, the fall in blood pressure was similar, or even lower, than in rats pretreated with coprine alone. The results suggest that acetaldehyde is the main determinant of the hypotension elicited by ethanol in rats pretreated with ALDH-inhibitors, and that the role of DBH in the disulfiram-ethanol reaction has been over-estimated in previous studies.


Storage of blood samples containing alcohol.

The storage of blood alcohol samples was studied. The samples were analysed and then frozen and kept at -20 degrees for 6 months before reanalysis. The results from this reanalysis did not deviate to any significant extent from those originally obtained. The process of freezing and thawing the same samples before analysis was repeated three times without any significant difference from the results with the fresh blood samples.


Cerebrovascular effects of central depressants: a study of nitrous oxide, halothane, pentobarbital and ethanol during normocapnia and hypercapnia in the rat.

The effect of the central depressants nitrous oxide, halothane, pentobarbital and ethanol upon cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2) and cerebral vascular reactivity to carbon dioxide were measured using the rapid and repetitive intraarterial 133Xenon injection technique modified for rat studies. The cerebrovascular resistance (CVR) during normocapnia in the pentobarbital group was significantly higher (P less than 0.01) than in the nitrous oxide group thus indicating a vasoconstrictor effect of pentobarbital that may be clinically important, because the ability of barbiturates to contract vessels in healthy brain regions may partly explain the protective properties of these drugs against cerebral ischemia. The results indicated that pentobarbital and ethanol may act synergistically with carbon dioxide in depressing CMRO2 and cerebral vascular reactivity. Finally, it is concluded that nitrous oxide anaesthesia (70% N2O: 30% O2) is suitable as a reference situation in rat studies of the effect of pharmocological agents on CBF, CMRO2 and cerebrovascular reactivity.


5-HT antagonism on cerebral and common carotid arteries by the 5-HT uptake inhibitors femoxetine and paroxetine.

The 5-hydroxytryptamine (5-HT) antagonism of methysergide was compared with that of the phenylpiperidine 5-HT uptake inhibitors, paroxetine and femoxetine, using two different models; the isolated cat middle cerebral artery and the common carotid artery of pithed rat perfused with the rat's own blood (autoperfusion). The extracorporeal circulation consisted of about 1.5 ml blood, which was temperature regulated to 36-38 degrees at the inlet to the carotid vessel by an automatic thermistor coupled heating system. In these experiments systemic blood pressure responses and perfusion pressure responses to 5-HT were recorded simultaneously. The 5-HT induced contractile response of the middle cerebral artery was reduced in a noncompetitive way by both uptake inhibitors at concentrations above 0.3 microM which is about 100 times the concentration needed for methysergide. In autoperfusion experiments inhibition was observed only at 5 mg/kg of both drugs. However, methysergide 0.001 mg/kg totally abolished all 5-HT responses. The uptake inhibitors can therefore be described as weak 5-HT antagonists.


Fluoride inhibition of DNA synthesis in isolated nuclei from cultured cells.

DNA synthesis in isolated nuclei from both fluoride sensitive and resistant LS cells was inhibited by fluoride at and above 3 mM. These fluoride concentrations also had an inhibitory effect on DNA synthesis in intact sensitive cells, but not in resistant cells. Due to previous findings that the intracellular fluoride concentration in the sensitive cells is only 30-40% of the extracellular, it is suggested that inhibition of DNA synthesis in intact cells is secondary to the inhibitory effect on protein synthesis.


Resetting of cardiac C-fiber endings in the spontaneously hypertensive rat.

The characteristics of 11 left atrial receptors in 9 adult male spontaneously hypertensive rats (SHR) were investigated. All the receptor afferents were non-medullated with conduction velocities from 0.5 to 1.5 m/s. Elevation of left atrial pressure during graded aortic occlusion always induced a marked increase in receptor discharge with maximal frequencies ranging from 29 to 70 Hz. The threshold for activation was from 7.5 to 13 mmHg in mean left atrial pressure (mean +/- S.E., 10.2 +/- 0.6 mmHg). Upon atrial distension all the receptors displayed a clear rhythmicity and the discharge correlated mainly with the v-wave, indicating distension as the cause of receptor activation. The relationship between the mean left atrial pressure and the frequency of discharge was constructed for all the receptors and compared with similar data obtained from normotensive control rats (NCR) (Thorén et al. 1979). It was then obvious that the left atrial receptors are reset in SHR probably secondarily to a decreased distensibility of the left atrium.


The effect of different diets and of insulin on the hormonal response to prolonged exercise.

The importance of carbohydrate availability during exercise for metabolism and plasma hormone levels was studied. Seven healthy men ran on a treadmill at 70% of individual maximal oxygen uptake having eaten a diet low (F) or high (CH) in carbohydrate through 4 days. At exhaustion the subjects were encouraged to continue to run while glucose infusion increased plasma glucose to preexercise levels. Forearm venous blood, biopsies from vastus muscle and expiratory gas were analyzed. Time to exhaustion was longer in CH- (106 +/- 5 min (S.E.)) than in F-expts. (64 +/- 6). During exercise, overall carbohydrate combustion rate, muscular glycogen depletion and glucose and lactate concentrations, carbohydrate metabolites in plasma, and estimated rate of hepatic glucose production were higher, fat metabolites lower, and the decrease in plasma glucose slower in CH- than in F-expts. Plasma norepinephrine increased and insulin decreased similarly in CH- and F-expts., whereas the increase in glucagon, epinephrine, growth hormone and cortisol was enhanced in F-expts. Glucose infusion eliminated hypoglycemic symptoms but did not substantially increase performance time. During the infusion epinephrine decreased markedly and glucagon even to preexercise levels. Infusion of insulin (to 436% of preexercise concentration) in addition to glucose in F-expts. did not change the plasma levels of the other hormones more than infusion of glucose only but reduced fat metabolites in plasma. At exhaustion muscular glycogen depletion was slow, and the glucose gradient between plasma and sarcoplasma as well as the muscular glucose 6-phosphate concentration had decreased. The preceding diet modifies the energy depots, the state of which (as regards size, receptors and enzymes) is of prime importance for metabolism during prolonged exercise. Plentiful carbohydrate stores favor both glucose oxidation and lactate production. During exercise norepinephrine increases and insulin decreases independent of plasma glucose changes whereas receptors sensitive to glucose privation but not to acute changes in insulin levels enhance the exercise-induced secretion of glucagon, epinephrine, growth hormone and cortisol. Abolition of cerebral hypoglycemia does not inevitably increase performance time, because elimination of the hypoglycemia may not abolish muscular energy lack.


Influence of muscle temperature on maximal muscle strength and power output in human skeletal muscles.

The influence of muscle temperature (Tm) on maximal muscle strength, power output, jumping, and sprinting performance was evaluated in four male subjects. In one of the subjects the electromyogram (EMG) was recorded from M. vastus lateralis, M. biceps femoris, and M. semitendinosus. Tm ranged from 30.0 degrees C to 39 degrees C. Maximal dynamic strength, power output, jumping, and sprinting performance were positively related to Tm. The changes were in the same order of magnitude for all these parameters (4-6% x degrees C-1) Maximal isometric strength decreased by 2% x degrees C-1 with decreasing Tm. The force-velocity relationship was shifted to the left at subnormal Tm. Thus in short term exercises, such as jumping and sprinting, performance is reduced at low Tm and enhanced at Tm above normal, primarily as a result of a variation in maximal dynamic strength.


Skeletal muscle metabolism, morphology and function in sedentary smokers and nonsmokers.

Smokers and nonsmokers of a homogeneous population of sedentary men have been compared with respect to skeletal muscle (vastus lateralis) morphological, metabolic and functional characteristics. The percentage type I fibres was lower and that of type IIB fibres higher in the smokers. Fibre areas were almost equal in the two groups. Muscle oxidative capacity was lowered in the smokers, as judged from decreased mitochondrial enzyme activities and a lowered fibrillar space mitochondrial volume fraction. Isometric and dynamic strengths were lower in the smokers, except at the highest velocity of movement studied. Dynamic strengths expressed in relation to isometric strength were similar at all velocities except the highest, where the smokers were relatively stronger. Muscular endurance, measured in short-term isometric and dynamic tests, was not different. It is suggested that the lowered muscle oxidative capacity and strength in the smokers may be partly a consequence of the different fibre type distribution. A possibly lower physical activity level, and tobacco smoke constituents (e.g. carbon monoxide) may also be instrumental. It is not clear whether the different fibre type distribution in the smokers is an effect of smoking per se, or if background factors are responsible.


The effect of alpha-aminoisobuturic acid and 2,4-diaminobuturic acid on mouse blastocyst outgrowth in vitro.

Blastocysts recovered from mice in a state of delay of implantation were incubated for 10 h with either alpha-aminoisobuturic acid (AIB) or 2,4-diaminobuturic acid (DAB), two non-metabolizable amino acids. The incubation medium was composed so as to maintain growth arrest of the inactive, delayed blastocysts in vitro. The blastocysts were then transferred to a complete outgrowth medium without the two non-metabolizable amino acids to test the capacity for trophoblast outgrowth. AIB, which displays saturation kinetics, was harmless to the blastocysts even at a high concentration, while DAB at a low concentration irreversibly damaged the trophoblast cells and prevented outgrowth, probably due to nonsaturation kinetics resulting in a high intracellular accumulation. The harmful effect of DAB could be abolished by concomitant incubation with L-alanine and L-methionine, which compete with DAB for the same transport system, while the D-forms of the same amino acids had little or no effect. The results suggest the presence of transport System A in mouse blastocysts growth arrested in vitro, indicating an operative carrier mechanism already during delay of implantation.


Partition of 125I-iodoantipyrine among erythrocytes, plasma, and renal cortex in the dog.

The tissue/blood partition coefficient, lambda tb, defined as the amount of blood having the same tracer content as one unit of tissue at diffusion equilibrium, was determined for 125I-iodoantipyrine (I-Ap) and tritiated water (THO) in the dog kidney cortex. Measurements were made after in vivo equilibration for 75 to 300 s and with liver circulation excluded. In 18 kidneys, lambda tb for I-Ap averaged 1.38 (S.D. 0.13) w/w (weight/weight), without significant correlation to hematocrit (range: 23-43) or to urine pH (range 5.5-8.6). The lambda tb for THO averaged 0.97 (S.D. 0.06) v/w (volume/weight), close to the relative water contents. Erythrocyte/plasma partition for I-Ap was 0.82 w/w, compared to a water partition of 0.72. Thus, at diffusion equilibrium the apparent I-Ap concentration in renal cortical and red cell water exceeds that of plasma water by 14 and 60%, respectively. It follows that I-Ap cannot be used as a general indicator for total tissue water content. When used for measurement of local blood flow and modum Kety, lambda tb must be determined for each tissue and species.


Distribution of blood flow in the dog kidney. I. Saturation rates for inert diffusible tracers, 125I-iodoantipyrine and tritiated water, versus uptake of microspheres under control conditions.

Disparate reports on intrarenal blood flow distribution prompted a direct comparison between microspheres (Ms) and inert diffusible tracers (DT). The "tissue sampling technique" for estimating local flow with DT (Kety) was adapted for the dog kidney, using 125I-iodoantipyrine (1-Ap) and tritiated water (THO). Ms (15 micron) were injected 2-3 min prior to 10-15 s DT infusion made during continuous 1 s arterial blood sampling. Tracers were measured in 7 to 20 samples from each of the following zones: Outer, middle and inner cortex (C1, C2, C3), outer and inner halves of outer medulla (OM1, OM2), and inner medulla (IM). I-Ap and THO gave closely similar flow distribution, and average total renal blood flow (RBF) of 3.90 and 3.78 as compared to 3.94 ml/min . g with Ms. Flow in C2 (ml/min . g) was similar with all tracers, and in per cent thereof average local flows were: C1 102, C3 70, OM1 34, OM2 12, and IM 2 with DT versus 117, 53, 12, 3, and 0 with Ms. Zonal flow fractions of total RBF obtained with DT were: C1 0.41, C2 0.33, and C3+medulla 0.26 versus 0.51, 0.33 and 0.16 with Ms. Thus, a Ms surplus in C1 relative to DT flow, representing 10% of total RBF, matched a Ms deficit in C3+medulla. This disparity might result from: (1) Failure of Ms to enter deep afferent arterioles in proportion to blood flow, (2) diffusion of DT from deep portions of the interlobular arteries, and/or (3) postglomerular inward flow of blood and DT.


Importance of sodium and glucose for the establishment of a villous tissue hyperosmolality by the intestinal countercurrent multiplier.

The intestinal countercurrent multiplier has earlier been shown to create an increased tissue osmolality in the villi (Jodal et al. 1978). In the present paper the importance of varying the luminal contents on the creation of the villous hyperosmolality was investigated using the cryoscopic technique described by Jodal et al. (1978). The perfusion solutions used contained 0, 25 or 147 mmol Na/l and were either provided with mannitol or glucose (30 mmol/l). It was demonstrated that sodium was of particular importance for the establishment of the villous hyperosmolality while glucose only contributed significantly at low luminal sodium concentrations. It is therefore proposed that glucose only in the absence of sodium in the luminal perfusate may effectively participate in the generation of the villous tissue hyperosmolality via the countercurrent multiplication mechanism.


Morphometry of myocardial apex in endurance-trained mice of different ages.

Mitochondrial volume density, surface density of the outer mitochondrial membrane, the mean number and size of mitochondria, and the mean surface density of crista membranes together with the volume densities of myofibrils and sarcoplasmic space were morphometrically analyzed in cardiac muscle of two groups of sedentary control mice aged 3 and 7 months, and in two groups of mice trained either 1 month rather intensely or 4 months moderately. Of the calculated mitochondrial variables only the surface density of the outer mitochondrial membrane differed between the older controls and the older trained animals, the density being slightly smaller in the trained group. The myofibrillar volume density of the order controls was smaller than that of the younger controls, while the sarcoplasmic volume density was larger. The latter difference, possibly a function of age, was also observed in the trained groups. The results suggest that at a certain steady state level of exercise-induced cardiac muscle hypertrophy the muscle cells of trained mice do not differ markedly in ultrastructural properties from those of sedentary controls.


Effects of acute hypotension and hypertension on serum TSH concentrations in male rats.

The effect of acute hypertension and hypotension on serum TSH concentration was studied in anesthetized male rats. I.v. infusions (10 and 30 min) of Na-nitroprusside and dihydralazine induced a profound hypotension, and angiotensin amide and noradrenaline increased blood pressure, but none of the treatments significantly modified serum TSH concentrations. Also clonidine and noradrenaline, when given i.p., caused hypertension, but again the increase of serum TSH levels was not consistent. When the whole material was analysed, there was a scarcely significant correlation between the change of blood pressure and the change of serum TSH level. It is inferred that the drugs affecting TSH secretion, do not exert their action solely by changing the blood pressure.


Villous tissue osmolality and intestinal transport of water and electrolytes.

The villous tissue hyperosmolality created by the intestinal countercurrent multiplier has been proposed to be of importance for fluid transport across the intestinal epithelium in vivo. This study was performed to test this hypothesis. Net transport of fluid and electrolytes (sodium, potassium and chloride), as well as unidirectional fluxes of water and sodium were determined in the small intestine of the cat. The villous osmolality was altered by varying the composition of sodium and glucose in the isotonic solutions perfusing the intestinal lumen. Net transport of fluid was correlated to tissue osmolality mainly due to an increase of the unidirectional flux of water from lumen to tissue with augmented tissue osmolality. The results are thus consistent with the view that the intestinal countercurrent multiplier is of essential importance for net water transport. A correlation was found between net water and net sodium intestinal transport. A similar correlation was also demonstrated between net sodium and net chloride absorption rates in the jejunum while in the ileum net loss of sodium into the intestinal lumen was not accompanied by any corresponding loss of chloride ions. This observation suggests the presence of a sodium independent transport mechanism for chloride in the ilium but not in the jejunum.


Influence of intravenous infusion on heart rate, sympathetic and vagal efferentation and left atrial and aortic baroreceptor activity in dogs.

The influence of 42 i.v. infusions of saline on heart rate, sympathetic and vagal cardiac efferent activity and on the aortic baroreceptor and left atrial B-type nerve impulse activity was studied in 32 morphine-chloralose anesthetized dogs. The responses in heart rate were tachycardic in 31 infusions and bradycardic in 11 infusions. In tachycardia, sympathetic activity increased in a majority of the cases but also decreases and nonsignificant changes were observed. Vagal efferentation decreased in most of the cases but also nonsignificant changes or increases in activity occurred. Sympathetic efferentation mainly decreased in bradycardic responses while vagal efferentation diverged in different directions in its nerve activity rate. The ratio of sympathetic to vagal impulses significantly correlated to the heart rate in most of the cases in tachycardia but not in bradycardia. It is concluded that sympathetic and vagal cardiac efferentation plays a significant role in heart rate regulation in volume load-induced tachycardia but in bradycardia only the changes in sympathetic cardiac efferentation are important in respect to heart rate changes. The aortic baroreceptor and left atrial B-type receptor activity rate increased both in tachycardia and bradycardia. Changes in the activities of these receptors do not explain the different heart rate responses. It is supposed that bradycardic responses result from changes in cardiac contraction associated with some reflex mechanism suppressing the excitatory influence of the activity of atrial receptors on sympathetic cardiac efferentation.


On the chromaffin system of the African lungfish, Protopterus aethiopicus.

The distribution of chromaffin tissue was studied in the African lungfish using Falck-Hillarp fluorescent histochemistry together with quantitative analysis of catecholamines in plasma and tissue extracts. Intensely fluorescent cells form chromaffin tissue in the wall of the atrium, the wall of the most anterior part of the left cardinal vein and the walls of the segmentally arranged intercostal arteries. The arrangement thus appears to be a combination of the situations in cyclostomes, elasmobranchs and teleosts. Adrenaline is present in larger quantities than noradrenaline in the intercostal arteries and the cardinal vein, while noradrenaline dominates in the atrium. During "stress" induced by physical disturbance of the animals, a strong increase in especially the noradrenaline concentration of the plasma was detected.


Adrenergic and cholinergic effects on the heart, the lung and the spleen of the African lungfish, Protopterus aethiopicus.

Effects of adrenergic and cholinergic drugs were studied on isolated preparations from the heart, the lung and the spleen of the African lungfish. In addition, a nerve-lung preparation was employed for the study of the autonomic nervous control of the lung. Falck-Hillarp fluorescent histochemistry was used in the search for adrenergic neurons in the sympathetic chain and tissues. The Protopterus lung received a cholinergic excitatory innervation via the pulmonary branches of the vagi. The presence of parasympathetic ganglia in the lung tissue is indicated. Adrenergic drugs, when producing a response, either contracted or relaxed lung strips. Spleen strips were contracted by cholinergic drugs acting on muscarinic receptors and, to a lesser extent, by adrenergic drugs. A strong negative inotropic effect was produced by carcachol on paced atrial but not ventricular strips, while adrenaline increased the contraction force in ventricular but not atrial strips. The sympathetic ganglion cells did not contain enough catecholamines to give off any visible fluorescence, nor was it possible to show any adrenergic nerve terminals in the tissues studied. It is concluded that the adrenergic control in the lungfish is mainly due to circulating catecholamines, rather than adrenergic nerve fibres, since concentrations of catecholamines in protopterus plasma are high enough to affect the spleen, lung and ventricle.


Catecholamine synthesis in the chromaffin tissue of the African lungfish, Protopterus aethiopicus.

The activities of dopamine-beta-hydroxylase (DBH, E.C. 1.14.17.1) and phenylethanol-N-methyl transferase (PNMT, E.C.1.1.1.10) were determined in tissue homogenates from the chromaffin tissue containing atrium and intercostal arteries from the African lungfish. Clearly measurable activities of DBH were found in both kinds of tissues, while PNMT activity was ascertained only in the intercostal arteries. The activity of DBH in the atrium indicates a possibility for local synthesis of the large amounts of catecholamines, especially noradrenaline, found in this tissue. Catecholamines synthetized in and released from the chromaffin tissues of Protopterus, may be of great importance for the adrenergic control in this animal in the absence of a well developed sympathetic nervous system.


Estimation of cerebral extraction of circulating compounds by the brain uptake index method: influence of circulation time, volume injection, and cerebral blood flow.

The Oldendorf "brain uptake index" method for estimating and characterizing the transport of circulating substances across the blood-brain barrier in the rat has been widely applied. The present study illustrates that minimizing the volume injected into the circulation to 10 microliters or less is necessary. Otherwise the flow artefacts, induced by the injected volume and the rate of injection, will influence the index. This principle is also relevant to techniques using intracarotid injections for the direct study of cerebral blood flow. The study also elucidates the need for reducing the circulation time after injection to about 5 sec, to avoid artefacts due to metabolism and back diffusion to the circulation of the substances studied.


The vagal control of the feline pyloric sphincter.

In acute experiments on cats in chloralose anesthesia the effects of efferent and afferent electrical stimulation of the cervical vagi on an applied constant flow of saline through the feline pylorus was studied. The motor activity of the stomach was recorded simultaneously with a volume recording technique. Efferent cervical vagal stimulation caused a decrease in the transpyloric flow and an increased gastric motor activity. In a few animals the decreased transsphincteric flow was preceded by a short period of increased flow. When the transpyloric flow was reduced by splanchnic nerve stimulation or a noradrenaline infusion, vagal nerve stimulation induced an increased flow through the pylorus indicating the presence of relaxatory fibres to the pylorus within the vagi. Electrical stimulation of the central end of the ipsilateral vagal nerve in the neck, with the contralateral vagal verve left intact, resulted in a decreased transpyloric flow and relaxation of the stomach. This response could be induced with or without intact splanchnic nerves, and disappeared when the intact contralateral vagus was cut. It is concluded that the vagi mediate both excitatory and inhibitory fibres to the pyloric sphincter in the cat. A vago-vagal excitatory reflex to the pylorus can be elicited by afferent vagal nerve stimulation together with a vago-vagal relaxatory response of the stomach.


Release of prostaglandin-like substances during elevations of left atrial pressure in the cat.

The purpose of the present work was to measure prostaglandin (PG)-like activity in arterial blood during acute pulmonary hypertension. Anesthetized cats with the chest opened and given positive pressure ventilation were used. A balloon in the left atrium was inflated to elevate hydrostatic vascular pressure in the lungs. Blood was pumped (10 ml/min) from a carotid artery to superfuse 3 smooth muscle tissues: rat stomach strip, rat colon and chick rectum: the blood was then returned to the jugular vein by gravity. The assay tissues were pretreated with antagonists against catecholamines, histamine, serotonin and acetylcholine during the experiments. They were sensitive to calibrating doses of 2 ng/ml of PGF2 alpha and 1 ng/ml of PGE2. 18 periods with elevated left atrial pressure (P LA) (21--49 mmHg), lasting 2--26 min, were applied in 9 cats. This manoevre usually also caused systemic hypotension. 14 of these PLA elevations were accompanied by increased arterial PG-like activity, which rapidly subsided when the pressure was released or when indomethacin (2 mg/kg, n = 4) was given i.v. In 3 additional experiments it was found that pulmonary degradation of PGs was unaffected during P LA elevation. I.v. infusion of angiotensin II contracted the tissues in a pattern different from that caused by pressure elevations and the PG calibrations, and these contractions were not affected by indomethacin. This indicates that the assay tissue contractions cannot be caused by angiotensin II which alone does not increase PG-like activity in arterial blood. Consequently, acute pulmonary vascular hypertension appears to stimulate PG synthesis and release in lungs of intact cats.


Excretion of metrizamide (Amipaque) in humans following lumbar subarachnoid injection.

The excretion of metrizamide through the kidneys and intestinal tract was determined in 10 patients submitted to myelography because of sciatica, for a period of 7 days following the examination. In the faeces, less than 5 per cent of the injected contrast medium was recovered during this period. Total recovery in the urine varied considerably from patient to patient, but most of the contrast medium was excreted during the first 48 hours. From the fourth day on, only small amounts were excreted, but even on the 7th day 3 to 11 mg iodine remained, which corresponds to 6 to 22 mg of metrizamide.


Role of hypertonicity in the endothelial injury caused by angiographic contrast media.

The effect of hyperosmolality on the permeability of vascular endothelium was investigated using light microscopy and silver staining of the thoracic aorta in the rat. The threshold osmolality causing significant endothelial injury was 1.41 to 1.59 tested with sodium chloride solutions. The osmolalities of ionic contrast media in clinical concentrations were at or over the osmotic threshold. Most angiographic contrast media injured the endothelium more than equiosmolal sodium chloride solutions. Hyperosmolality is only one factor contributing to the increased endothelial permeability.


Amipaque in coeliac angiography.

Coeliac angiography was performed in 12 patients using Amipaque 370 mg I/ml or Isopaque 370 mg I/ml. No significant biochemical alterations were found in serum. Amipaque improved the demonstration of small vessels in the liver and in the head of the pancreas. Amipaque caused no discomfort contrary to Isopaque, which gave moderate to severe heat during injection.


Transcatheter arterial embolization of experimental hepatic tumours in the rat.

After transcatheter arterial embolization with Spongostan (99.3% gelatin-similar to gelfoam) in a group of rats with experimental hepatic tumours, the angiographic and microscopic findings were compared with those in a group of rats with non-embolized liver tumours. Partial recanalization of the hepatic artery was demonstrated already after 2 to 6 days. Reduced vascularization of tumours could be demonstrated after embolization and in a few animals even decrease in tumour size. Microscopy revealed a significantly greater extent of tumour necrosis in embolized tumours of large size. Necrosis of normal liver tissue was found to a varying degree in the embolized rats, while no ischemic injury was evident in livers of most non-embolized animals.


Blood inflow into vascular catheters following injection of saline solution and contrast medium. Model experiments.

Using an experimental model of the arterial system, inflow of blood into polyethylene catheters following injection of two contrast media, isotonic and hypertonic saline solutions was investigated. The experiments included an analysis of the influence of the density of the solutions and the orientation of the catheter as well as the effect of single fluid injection and continuous flushing of the catheter.


Tendinography for diagnosing injuries to tendons and ligaments.

A radiographic method of tendinography is described. In rabbits no inflammatory reaction in the Achilles tendon was observed 12 to 15 days after injection of contrast medium. Effects of examination of two healthy subjects and a patient with a traumatic condition are described. Suitable amounts and concentrations of contrast medium for examinations of Achilles tendon and cruciate ligaments are discussed.


Facial bone scintigraphy. V. Differentiation of purulent from non-purulent inflammation of the maxillary sinus.

In a series of 25 patients 20 had a maxillary sinus not containing air at radiography, in 11 due to purulent and in 9 to non-purulent inflammatory lesion. At scintigraphy a definitely abnormal, high uptake of 99TcmDP was found in 10 and a probably high accumulation in one of the 11 with purulent sinuitis. Of the 9 patients with non-purulent inflammation 5 had a definitely normal and 4 a probably normal uptake. Thus, a differentiation between purulent and non-purulent sinuitis would seem to be possible by means of facial bone scintigraphy.


Relationship between clinical and radiographic findings in patients with mandibular pain or dysfunction.

The diagnosis of organic disease of the temporomandibular joint is often based on radiographic findings. The relationship between the radiographic findings in this joint and in hand joints, and clinical findings in the masticatory system, was analysed. The results showed that patients with crepitation of the temporomandibular joint frequently have radiographic abnormalities in this joint and in hand joints. Subcortical sclerosis and reduced joint space were significantly correlated with the number of occluding pairs of molar teeth.


Bronchial angiography and intraarterial chemotherapy with mitomycin-C in bronchogenic carcinoma. Anatomy, technique, complications.

Bronchial angiography and intraarterial infusion of mitomycin-C were successfully performed in 39 of 47 patients with bronchogenic carcinoma. More than one course was given to several patients. No neurologic complications occurred and the side effects were insignificant. The pertinent anatomy of the bronchial and spinal arteries is summarized and a comprehensive description of the angiography and infusion technique is given. It is important that the infused artery is not occluded by the catheter and that the drug is properly diluted to avoid complications. The method appears to be of therapeutic value in the treatment of pulmonary carcinoma.


Combined ventilation-perfusion scintigraphy for demonstratio of pulmonary embolism.

In 34 patients with suggested pulmonary emboli, ventilation scintigraphy with 133Xe and perfusion scintigraphy with 99Tcm-labelled albumin spheres were carried out. The combined ventilation-perfusion scintigraphy had a significantly higher diagnostic specificity (1.0, confidence limit 0.69-1.0) than perfusion scintigraphy alone (0.48, 0.26-0.70). Both methods had a diagnostic sensitivity of 1.0.


Venous structures of the chest and abdomen at computer tomography.

From a total of 1 560 CT examinations of the thorax and abdomen transverse sections illustrating various normal and abnormal venous structures were selected. The radiologic importance of these structures is pointed out.


Colon of the rat. An anatomic, histologic and radiographic investigation.

The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature.


Prototype ionographic imaging chamber. Construction and clinical use.

The design and construction of an experimental ionography chamber are described and the principles of this new electrostatic imaging technique are discussed. Examples of medical ionographic images taken with this simple prototype chamber are presented.


Visual evaluation of microscopic mottle.

According to Rose the resolution of an imaging system is under certain conditions limited by noise rather than by the finite geometric response as expressed by the modulation transfer function. In order to investigate whether this applies to clinical radiography as well, a technique for magnification of roentgen films has been devised, making possible visual evaluation of microscopic noise.


Significance of tortuous filling defects at lumbar myelography.

At lumbar myelography, tortuous filling defects frequently occur in the presence of a marked local narrowing of the spinal canal. This may lead to a displacement and compression of nerve roots, which may partially or completely fill the subarachnoid space. However, truly elongated nerve roots have also been observed, both at myelography and at operation. Such elongation appears to be a congenital malformation. The recognition of the true nature of tortuous filling defects is important with regard to differentiation against arteriovenous malformations and congested veins.


Scintigraphy of induced myocardial infarcts with 99Tcm-gluconate.

A new isotope compound, 99Tcm-gluconate, for detection of myocardial infarction has been tested in dogs. A close correlation was found between the isotope uptake measured in vivo with a gamma camera and the infarct weight of early irreversible myocardial infarcts.


Pulmonary systemic flow ratios in atrial septal defect assessed by ventricular volume measurements.

Twenty-eight patients with isolated secundum atrial septal defects were examined with right and left heart catheterization and cardioangiography. The radiographically assessed pulmonary-systemic stroke volume ratios and the physiologically determined pulmonary-systemic flow ratios correlated well. However, some striking discrepancies were observed the possible causes of which are discussed.


Experimental and clinical evaluation of cholangiography with xeroradiography.

Conventional screen film radiography is compared with xeroradiography in an experimental model for cholangiography. The wider exposure latitude of the xerographic technique confers certain diagnostic advantages. However, the actual clinical application presents practical difficulties, which, combined with low sensitivity, are of such a nature that the method can hardly be considered suitable at the present time. If certain improvements can be made, xeroradiography could become a superior method for radiography of the bile ducts.


Complications at balloon catheter angiography. Experiments in rabbits and dogs.

Overdistension of a balloon catheter may injure an artery and this risk increases with decreasing vessel calibre. Before balloon occlusion an estimation of the calibre of the vessel at a preliminary angiography is recommended.


Transcatheter embolization in a haemophiliac with post-traumatic renal haemorrhage. Report of a case.

Percutaneous transcatheter arterial embolization was performed in a case of severe haemophilia A to control haemorrhage secondary to renal trauma. The treatment proved to be life-saving. Eighteen months follow-up revealed no evidence of hypertension, renal failure or infection.


Radiographic appearances in Crohn's disease. I. Accuracy of radiographic methods.

Preoperative films of 176 patients operated upon for Crohn's disease were reviewed and compared with microscopic findings in the resected specimens in order to assess the accuracy of the radiographic techniques used. It was found that a diagnosis of the presence and the extent of the disease was often dependent on the demonstration of minor mucosal ulcers and less marked submucosal edema. These lesions were not adequately demonstrated by any of the techniques used for small bowel examination, but were consistently revealed by the double-contrast technique used for examination of the colon.


Hiatal incompetence and gastro-oesophageal reflux.

Gastro-oesophageal reflux and hiatal incompetence were analysed in 191 patients using a new radiographic contrast medium, polyiodostyrene, with the same density (1.0 g/cm3) as ordinary gastric contents, and correlated with supplementary oesophagoscopy and intraluminal pressure measurements. A normal hiatus seems to be an important protection against gastro-oesophageal reflux. An incompetent hiatus involves a real risk for oesophagitis. A low-density, low-viscosity contrast medium improves the roentgenologic diagnosis of gastro-oesophageal reflux.


Adrenal angiography in Sipple's syndrome.

Adrenal angiography was performed in 8 patients with Sipple's syndrome. Seven patients had pheochromocytomas and one bilateral adrenal medullary hyperplasia. In 4 cases the pheochromocytomas were bilateral. The angiographic findings are discussed and it is concluded that no typical angiographic appearance of pheochromocytoma appears to exist.


Ultrasound, angiography and fine needle aspiration biopsy in diagnosis of renal neoplasms.

The diagnostic approach to a renal mass including ultrasound, angiography and fine needle aspiration biopsy is reviewed on the basis of 23 cases. The value of the combination of these methods is emphasized especially in tumors which appear without echoes at ultrasround and avascular-hypovascular at angiography. The findings are correlated and some differential diagnostic problems discussed as well as the possible risk of spreading tumor cells at fine needle aspiration biopsy.


Percutaneous transperitoneal fluoroscopy-guided fine-needle biopsy of lymph nodes.

After lymphography from the foot, with uncertain findings, fine-needle biopsy during fluoroscopy was performed in 107 patients. In 69 patients with possible metastases, involvement was demonstrated in 46, confirmed in 43 at operation. Lymph node involvement by general lymphatic disease was suggested in 38 patients, with biopsy confirmation in 12. In metastatic disease non-representative material was obtained in only 2 patients, in general lymphatic disease in 10. No significant complications occurred, and the side effects were small.


Image enhancement by digital-analog filtration. II. Tests of filters.

The function of a device for frequency filtration of roentgenograms with digital filters has been tested with the use of different filters. The image was altered in the expected way, which means that the device is suitable for investigating the possibilities of different filters to improve the diagnostic ability. The results of the tests indicate that improvement should be achieved by low-pass filtration.


Relevance of radiographic resolution capacity.

Resolution capacity is traditionally evaluated by radiography of metal objects (lead bar grids or fine slits). These objects yield high image contrast. Resolution, then, is limited by the sideways spread of information as expressed by the MTF. However, biologic objects of fine dimensions give rise to much less image contrast than the test objects of metal. Since the amplitude of the signals thus becomes reduced the signal/noise ratio in fact limits resolution capacity much more effectively than does the sideways spread of information. Thus, the MTF expresses a property of the radiographic system which appears only rarely to affect the information capacity of clinical radiographic images.


In vitro effects of contrast media on the water content of human erythrocytes.

The effect of the concentration of the contrast media Visotrast 370, Dimer X and Adipiodon on the water content of human erythrocytes was analysed in vitro. While a concentration-dependent water discharge (shrinkage) of erythrocytes was found in the presence of Visotrast 370 and Dimer X, the application of Adipiodon caused water uptake (swelling). Possible causes of swelling of red blood cells despite the hyperosmolality of Adipiodon are discussed.


Arterial structures of the chest and abdomen at computer tomography.

Cross-sections illustrating normal and abnormal arterial structures were selected from a total of 1810 CT examinations of the chest and the abdomen. The radiologic importance of these structures is pointed out.


Mammary hamartomas.

Five cases of mammary hamartoma are described, with special reference to the radiographic features. Hamartomas are well circumscribed lesions composed of normal or dysplastic mammary tissue. They are probably more common than has been anticipated from the literature and are important because they may be confused with other well circumscribed tumors, such as cystosarcoma phyllodes. The radiographic characteristics of hamartoma allows a tentative diagnosis in most cases.


Tantalum labelling in vivo of cardiac ventricular chambers in dogs.

Demarcating fixed points in cardiac ventricles in the dog by catheter placement of tantalum coils has been shown to provide an excellent physiologic model. A new method emplying direct ventricular puncture has been developed for implanting these markers. The method has several advantages over an earlier peripheral catheter technique. Apical approach allows easier screw placement near the aortic and pulmonary valves. Peripheral vessels are left intact and pressure monitoring as well as contrast medium injection can be performed through the same catheter.


Portal pressure correlated to visceral circulation times.

Visceral angiography was performed in 7 patients with normal portal pressure and in 10 with portal hypertension. Circulation times, size of vessels and portal pressure were determined. At celiac angiography a direct correlation was found between time for maximum filling of portal vein and portal pressure, provided no vascular abnormalities existed. At superior mesenteric angiography such a correlation was not found; loss of flow by shunts in portal hypertension being one explanation. Portocaval shunts are common in the celiac system, but uncommon in the superior mesenteric system.


Pseudotumor of the renal pelvis caused by renal artery aneusysm.

Urographic abnormalities caused by renal artery aneurysms are discussed on the basis of seven cases. Angiography is the diagnostic procedure of choice to make the correct diagnosis. In cases of completely thrombosed aneurysms angiography may only demonstrate an avascular mass with displacement of vessels. At ultrasound examination renal artery aneurysms should be included in the differential diagnosis of echo-free renal masses.


Double contrast examination of the stomach compared with endoscopy.

The results of the double examination of the stomach in a series of 102 patients were compared with the findings at endoscopy. Nasogastric intubation was used to introduce the air into the stomach. Hypotonia was achieved mainly with glucagon. The radiologic error rate was 10 per cent, consisting of 7 per cent false negative and 3 per cent false positive findings. The diagnostic advantages of the double contrast technique over those of the conventional barium examination are discussed.


Angiography, ultrasound and fine-needle aspiration biopsy in the evaluation of gynecologic tumors.

The combination of angiography, ultrasound and fine-needle aspiration biopsy proved to be valuable in the preoperative evaluation of patients with a palpable mass. With ultrasound, the size, shape and origin of tumors exceeding 4 to 5 cm in diameter were correctly diagnosed, whereas angiography differentiated bettter between malignant and benign tumors.


Radiologic assessment of laryngeal carcinoma. A clinico-pathologic comparison based on whole-organ serial sections.

In 33 patients with laryngeal carcinoma operated upon with laryngectomy, a comparison has been made of the findings yielded by radiography and microlaryngoscopy and a microscopic examination using whole-organ serial sectioning. The radiographic examinations were conventional films, tomography and laryngography. Radiography supplemented in microlaryngoscopy with information of clinical importance. Surface extension of the tumour was fairly accurately assessed preoperatively whereas deep infiltration was not. Major destruction of the anterior part of the thyroid cartilage was correctly diagnosed.


Influence of microscopic mottle on the definition of small image details.

By a special technique of enlarging films, a microscopic mottle caused by quantum fluctuations was demonstrated. It was found to affect depiction of small details in such a way as to suggest that it would be of importance for determining resolution capacity, especially in high-speed radiography. Thus, the modulation transfer function appears not to be the only factor determining radiographic resolution. The resolution of high-speed screens may be improved if the film speed is reduced, which leads to a diminished microscopic mottle.


Optimised tomography for clinical use.

A technique elaborated by the present authors (1974) for the establishment of optimum tomographic movements was applied to ear tomography in order to design a movement that is not too complex, but yielding good tomographic depiction. Such a movement was found to consist of a spiral of 5 revolutions. Modern engineering appears to allow such complex movements to be carried out with satisfactory stability within a reasonable exposure time.


Tomographic localization of motion axes.

Localization of motion axes within joints and junctures in living humans has been carried out by means of roentgen stereophotogrammetry. Another technique is presented here, in which the localization of the axis is carried out by means of tomography. The field of application for this technique has been examined in a series of phantom experiments. It may be employed in certain situations where roentgen stereophotogrammetry is not useful. No other equipment is needed than a pluridirectional tomograph and conventional dark-room facilities.


Clinico-pathologic correlation in non-Hodgkin's lymphoma. I. Retrospective analysis using the Lukes and Collins classification.

A retrospective review of 302 patients with non-Hodgkin's lymphoma is presented. The tumors were classified according to a modified Lukes and Collins scheme. Clinico-pathologic correlation was analysed for the subtypes. Certain distinct features were found with respect to age, sex, clinical stage and sites of involvement at admission. Prognostically, two major groups were found with significantly differing survival curves. The pathologic and clinical significance of the modified Lukes and Collins classification is discussed.


Metastasis to neck from unknown primary tumor.

The records of 54 consecutive patients who were irradiated for metastatic disease in the neck from an unknown primary tumor were reviewed. The overall survival results are comparable to those of other reported series. Patients with high or posterior cervical lymph node involvement were irradiated with fields including the nasopharynx and oropharynx. Patients with high neck nodes had a better survival rate than those with low neck nodes. The size of the neck tumors and the local control after treatment also have prognostic significance.


Minimized irradiation volume in treatment of carcinomas of the oropharynx and hypopharynx.

Twenty-two patients with advanced squamous cell carcinoma of the oropharynx and hypopharynx (T3T4-N2N3) were irradiated with curative intention. The treatment volume was minimized as much as possible with the aim to increase tumour control and decrease morbidity. Planning and results as well as the complications during and after the irradiation are discussed.


Accumulation of 99Tcm-gluconate in isolated rat cardiac myocytes and hepatocytes during anoxia.

The accumulation of 99Tcm-gluconate in the myocardium and liver of the rat during anoxia has been investigated on the cellular level and compared with the histopathologic changes. The conclusion is drawn that the uptake of isotope runs a course similar to that registered in vivo in human myocardial infarction.


Effect of 90Sr on ovaries of foetal mice depending on time for administration during pregnancy.

Pregnant CBA-mice were injected with 3.7 x 10(5) Bq (10 muCi) 90Sr on the 8th, 11th, 13th, 16th or 19th day post coitum. The effect on the ovaries in the intrauterine-treated animals was analysed on the 28th, 56th and 84th day post partum. The result was expressed as a comparison between the number of cells in different stages of development in the treated individuals compared to untreated control animals. The reduction of the number of cells in the ovaries was strongly correlated to the time of administration of the nuclide with a more increased effect the later during foetal development the contamination occurred. The oocytes and primordial follicles were the most radiation sensitive stages. The remaining cells in the ovaries are supposed to form a numerically reduced pool of functionally normal cells.


Stroke registration in Göteborg, Sweden, 1970-75. Incidence and fatality rates.

Strokes occurring among persons between 15 and 65 years of age (population 300 000) have been registered since 1970 in Göteborg, Sweden. Control of the validity showed that less than 10% of all cases of stroke were undetected. During the period Nov. 15, 1970-May 14, 1975, 986 stroke events occurred in 941 patients, giving an annual average incidence rate of 73 (89 for men and 58 for women) per 100 000 individuals 15-65 years of age. The incidence for all ages was estimated to be about 200/100 000. The rates were higher for men than for women in all age groups. There was a female preponderance for subarachnoid haemorrhage but a male preponderance for other types of stroke. Incidence rates increased with age, most rapidly for brain infarcts and unspecified stroke. Fatality rates levelled out 3 weeks after onset of stroke; they were high for subarachnoid and intracerebral haemorrhage and low for cerebral infarction and unspecified stroke. Incidence rates were lower than those found in two similar studies from Denmark and Finland, and even greater variations were found with respect to types of stroke. Fatality rates were similar to those reported by other authors.


Risk factors for myocardial infarction in the Stockholm prospective study. A 14-year follow-up focussing on the role of plasma triglycerides and cholesterol.

A 14-year follow-up of the Stockholm prospective study is reported. A number of 130 new myocardial infarctions (MI) were found in a prospective group of men (n = 3189) and another 46, i.e. a total of 176 MI, in the total group (n = 3486). Different types of multivariate statistical analyses show that age, blood pressure, smoking, fasting plasma concentrations of cholesterol and triglycerides, ESR and Hb were independent risk factors for MI, while the weight/height index was not. Elevated BP became an important risk factor only after the age of 50. When only age, BP, smoking and the two plasma lipids were entered into the logistic multivariate analysis, plasma triglycerides were more important as a risk factor than cholesterol. Quintile analysis showed that the rate of new MIs increased more with increasing triglyceride than increasing cholesterol levels. In the prospective group, the average rate of new MIs for men below 60 years was 32 per 1000. In the bottom and top quintile these rates were 16 and 65 for plasma triglycerides and 27 and 47 for cholesterol. When the men were divided into 4 groups with regard to both plasma lipids, the rate of new MIs increased successively from group to group along this chain: both lipids normal, only cholesterol high, only triglycerides high and both plasma lipids high.


Serum ferritin during inflammation. A study on myocardial infarction.

The ferritin level in serum was investigated in 9 patients with myocardial infarction, all with a history of chest pain of less than 4 hours before admission. A significant rise in serum ferritin level was found in 8 patients. The rise was generally smaller than that seen in acute infection and not significantly correlated to the size of infarction, as estimated from changes in serum levels of myoglobin, ASAT and LDH. The rise started after a mean of 30 hours, the peak being reached within a week (M 4.3 days). Serum ferritin then fell to 120--300% (M 190) of the initial level, where it remained. An initial rise in serum iron levels was unexpectedly seen within 12 hours in 7 patients.


Clinical features in patients with recurrent myocardial infarction.

A retrospective investigation of 420 patients who had survived the acute phase of myocardial infarction revealed 63 reinfarctions (in 57 patients) within three months. Twenty-eight patients died without reinfarction during the same period, and 335 survived three months without reinfarction. The reinfarction patients were significantly more often women, had more frequently a history of previous myocardial infarction and hypertension, and their myocardial infarctions were more often non-transmural and localized to the anterior wall of the heart. The ECG of each patient that was registered nearest prior to the reinfarction during hospitalization or prior to discharge showed more often negative T-waves.


Late sudden death after surgical correction of coarctation of the aorta. Importance of aneurysm of the ascending aorta.

Follow-up studies averaging 12 years postcorrective surgery of 343 patients with coarctation of the aorta disclosed 38 late deaths, 15 of which were sudden, unexpected and probably cardiovascular. All but two patients were normotensive postoperatively, and in 4 of these the cause of death was proven dissecting aneurysm of ascending aorta. In another patient this aneurysm was repaired surgically and in 3 other patients chest X-ray had shown a dilated ascending aorta before death. At follow-up the ascending aorta was dilated angiographically in 4 survivors, who had moderate systolic hypertension and aortic valve disease. The high incidence of aneurysm of ascending aorta in patients with coarctation is probably due to hypertension during the growth period, possibly in combination with congenital weakness of the aortic wall, and to concomitant aortic valve lesion.


Oesophageal symptoms and manometry in valvular heart disease.

A possible relationship between heart disease, oesophageal dysfunction (OD) and symptomatology was studied in 47 patients with valvular heart disease. They were investigated with oesophageal manometry and oesophageal acid perfusion test. OD was found in 32 percent of the patients. A local pressure increase in the middle part of the oesophagus, probably an effect of cardiac enlargement and compression of the oesophagus, was found at manometry in 38 percent. The incidence of OD and of oesophageal symptoms was the same in patients with and without oesophageal compression. We did not find any indications that valvular disease in itself provokes OD, nor that symptoms of chest pain and cough in patients with valvular heart disease are due to OD.


Disopyramide plasma levels in cardiac patients on maintenance therapy.

The antiarrhythmic agent disopyramide, in a dosage of 200 mg/8 h, was given to 7 cardiac patients. The drug was fairly rapidly absorbed, and the mean peak plasma concentration (3.5 microgram/ml) was measured 1 h after administration of the first dose. The mean biological half-life (7.8 h) was slightly prolonged compared to that reported in normal volunteer subjects. Mean steady state plasma concentrations within the therapeutic range were attained 24--32 h after the start of medication. The fluctuations in the plasma levels were in the order or 30 percent; however, a wide spread of the values was observed. The drug was well tolerated.


Reduced vibratory perception and corneal sensitivity and metabolic disturbances following intestinal bypass surgery.

Decreased corneal sensitivity and vibratory perception suggesting a diagnosis of polyneuropathy were demonstrated in some of 26 patients who had undergone intestinal bypass surgery. Psychological tests revealed signs of disturbance of the autonomic nervous system. A deficiency of 25-hydroxyvitamin D was demonstrated, clearly related to the frequency of stools and to the weight loss. This deficiency might play a role in the pathogenesis of the polyneuropathy.


Incidence of urolithiasis leading to hospitalization in Finland.

The study population consists of 2304 urolithiasis patients discharged from all hospitals in 21 central hospital districts in 1970. The incidence rate was 50 per 100 000 inhabitants per year, 74 for men and 27 for women. The age distribution resembles the Gaussian curve, with a peak between 45 and 49 years for men and between 50 and 54 years for women. The male/female ratio was 2.7 in the entire material, about 1 in the age group 0--24 years, about 3 in the age group 25--74 years and about 1.5 in patients 75 years or older. The standardized incidence was highest in Southeastern Finland and in the archipelago of Aland, and lowest in the coastal area of Southwestern Finland. In the area with high incidence, the age distribution of urolithiasis patients differed from that in the rest of the country: in the age groups over 40 the incidence of urolithiasis did not appear to decrease. This difference was attributed to some lifelong environmental exposure. The standardized incidence of urolithiasis leading to hospitalization was higher among urban than rural residents. Seasonal variation in the hospital admissions for urolithiasis was not evident, temporal patterns of admissions were, however, dissimilar in urban and rural areas, and might reflect differences in the physical activities of urban and rural populations.


Systemic capillary leak syndrome with monoclonal IgG and complement alterations. A case report on an episodic syndrome.

A case of the rare systemic capillary leak syndrome (SCLS) is described. The patient suffered 9 attacks with muscle pain, weakness and profuse sweating. He showed increased Hct values up to 79 percent and a decreasing plasma volume to about 50 percent of normal. During the attacks the patient was in a state of shock and BP was unmeasurable. Studies with 131I-labelled albumin during attack showed an increased transcapillary escape rate to about 20 percent/hour, compared to 6 percent when he was without symptoms. A monoclonal IgG with a constant concentration of about 5g/l was found. Studies of the complement system during attack showed low C4 values, disproportions among the C1 subcomponents and C1r-C1s-C1IA complexes, suggesting a complement activation via the classic pathway. Hereditary angio-edema was excluded by normal C1IA values. The complement activation might be part of the pathogenesis of the increased macromolecular permeability in this syndrome. A short review of cases described earlier is given.


Ultrastructure of the microvessels in skeletal muscle in a case of systemic capillary leak syndrome.

The microvessels of skeletal muscle were examined electron microscopically in a case of systemic capillary leak syndrome (SCLS). One biopsy was taken in a free interval of the disease and one about 6 hours after the onset of an attack with hypovolemia. The microvascular endothelium exhibited a large number of multivesicular bodies, especially in the specimen obtained during an attack. Possibly this indicates a high heterophagic activity of the endothelium. A blebbing of the luminal surface of arteriolar endothelium was observed in the attack specimen. Since a complement activation seemed to occur during attacks, the blebbing is tentatively interpreted as a sign of a complement-mediated injury to the endothelium, leading to a breakdown of the endothelial barrier. This mechanism might explain the dramatic increase of microvascular permeability to plasma proteins during an attack of SCLS. The findings did not indicate that the increase might depend on some disturbance of the transendothelial vesicular transport function, nor could any openings of endothelial junctions, as in inflammation, be demonstrated. Regionally the periendothelial basal lamina appeared thickened, a finding which seems common in angiopathies of different kinds.


Postoperative radiation therapy in mammary carcinoma stage II. Target volume, organs at risk, absorbed dose, time-dose schedule, and dose to organs at risk in a prospective investigation.

A standardized programme for postoperative radiation therapy of carcinoma of the breast stage II is reported. The target volume and the organs at risk are defined, and the target absorbed dose and fractionation are specified. The irradiation techniques is briefly described.


Laryngeal carcinoma. I. Treatment results.

A series of 359 patients with carcinoma of the larynx was found to be very close to being representative of the northern part of Jutland, Denmark (north of Kongeåen). No unequivocal change in the disease as regards sex, age, histology, symptoms and signs, and stage of disease could be observed during the period 1963 to 1972. A not statistically significant improvement in the corrected mortality appeared. The level of complications after irradiation and secondary surgery was found to be low. A statistically significant, better prognosis was found for females than for males in the glottic group.


Effect of whole body irradiation on different tissues. Experiments with 14C leucine in the rat.

The uptake and elimination of 14C leucine were analysed in controls and in rats irradiated 2 h before injection with 8 Gy whole-body irradiation. Plasma, small intestine, kidney and skin were assayed after homogenization for TCA soluble activity curves. In highly differentiated tissues with poor proliferative activity and low protein turnover, the uptake and elimination of the tracer did not appear to be affected by irradiation. In the small intestine differences between control and irradiated animals seemed significant.


Prognistic relevance of radiation induced immune suppression in breast carcinoma.

The extent of radiation induced immune suppression was analysed in 100 patients with carcinoma of the breast. The relative changes of lymphocyte counts and stimulations by PHA and PPD were similar in patients who differed with regard to age, size of tumour and its malignancy grade or axillary node condition. Moreover, no difference in the degree of radiation induced immune suppression existed between patients who developed recurrent disease and those who remained free of disease during a follow-up period of 4 1/2 to 7 years.


Ferrous sulphate dosimetry for electrons. A re-evaluation.

A theory was developed for the perturbation correction to be applied in the calorimetric determination of the ferrous sulphate dosimeter G-value. Recent determinations of the molar extinction coefficient, epsilonm, have shown that systematic errors in epsilon may have influenced experimental G-values. With precision spectrophotometers this error is cancelled in the product epsilonm.G. It was shown that after applying the perturbation correction a very small spread was obtained in calorimetric epsilonm.G-values; the standard error of the mean being 0.2 per cent. The mean G-value is 2.3 per cent lower than that recommended in ICRU Report No. 21.


Accuracy of computerized radiation treatment planning.

The accuracy of computerized dose planning depends essentially on the computer program. The quickest and simplest way to assess the accuracy of a commercial program is to compare the results of the computer calculations with measured values. The present report deals with the accuracy of the RADPLAN dose planning program in different situations easy to control. The test methods are also applicable to other corresponding systems.


Effect of hyperthermia alone and in combination with 60Co radiation on the growth of B16 melanoma in mice.

B16 melanoma was grown in the tail of B6D2F1/BOM mice. Procedures for simultaneous local 60Co irradiation and heat treatment are described. A dose of 4 Gy had no effect on tumour growth; heat treatment at 41.5 degrees C for 200 min had a minor effect, while the combined treatment caused a marked delay in tumor growth. Heat treatment of tumours in the thigh at 41.5 degrees C for 2 hours did not influence the frequency of lung metastases.


Application of linear programming to dose optimization in intracavitary implant therapy.

Linear programming can be used to optimize intracavitary brachytherapy for carcinoma of the cervix. A method has been developed which gives meaningful output and is described. A set of reference points were necessary in addition to the standard reference points. Point A as well as an array of points for adjacent radiation sensitive normal structures were used in order to obtain isodose curves conforming to those commonly used for therapy. In addition, arbitrary upper and lower limits of dose at selected points were needed and were set to conform to systems commonly used clinically for intracavitary therapy. It was immediately evident that a wide variety of loadings can be used that deliver appropriate or improved doses to reference points while minimizing normal tissue dose. The loadings represent arrangements which are not commonly used in many clinics but offer potential for clinical use.


Vascular structure of experimental tumours. Appearances in scanning electron microscope.

The vascular structure of experimental tumours was investigated by a resin cast technique. Six characteristic types of capillaries were found: club-like, wave-like, tortuous,sinusoid-like, disorderly running and tapering. The vascular structure was correlated to the tumour growth.


Late changes in biochemistry and blood flow in rat brain locally exposed to 30, 40, or 60 Gy.

Rat brain was exposed to 30, 40 or 60 Gy of roentgen rays and different biochemical and physiologic parameters were assayed from one day to 2 years. The most important changes noted were an intermediate increase in DNA, an intermediate to late--dependent on dose--increase in collagen, a decrease in sialic acid, an early to intermediate increase in serotonin, an increase in cathepsin, an early depression, and intermediate enhancement and a late decrease in alpha amino isobutyrate uptake by brain, and an early reduction, an intermediate--and sometimes late--increase in blood flow. These changes suggest that all three principal systems 2n the brain, nerve cells, glia and vascular system, participate in late changes.


Two-dimensional echo-encephalography. 1. Acoustic properties of some tissues and the characteristics of echo patterns obtained using equipment especially adapted for detection of these tissues.

In this paper the results of measurements of ultrasound velocity in, and density of, a number of normal and pathological tissues are given. From the results it can be concluded that intracranial pathological regions will often be detectable with ultrasound techniques, but is is not possible with any degree of certainty to localise precisely the morphological boundaries of these abnormal regions. Because, in the large majority of cases, the echoes from intracranial pathological structural changes are of weak intensity, a simple electronic device is described which, in conjunction with standard echo equipment, has been shown to be of use for better detection of these weak signals.


Cranioplasty technical note.

A modification of Galicich and Hovind's method of cranioplasty is described. The prosthesis is not made on a side-table in the operation theatre. Steel wire mesh is fastened to the edge of the bone defect with stainless wires passed through drill holes. Acrylic mixture is then poured over the mesh and is cooled with saline. The technique has its main advantage in simplicity, and the result is cosmetically and functionally satisfactory.


Mechanical loading of peripheral nerves during remobilisation of the affected member after end-to-end anastomosis.

Our study involved simulating end-to-end neurorrhaphy of the sciatic nerve in a number of rabbits and analysing in vivo the mechanical loads acting on the nerve while the affected member was being remobilised. We found both the suture and mobilisation loads to be related to the size of the nerve defect. In each case, traction force, strain, and stress were proportional. The effect which these experimental findings may have on the future use of flexing neighbouring joints as a "manipulative" measure to achieve a tension-free nerve suture will be discussed.


The meningioma of the sphenoidal plane.

The present paper reports on meningioma of the sphenoidal plane. Four women and two men were investigated. All cases examined presented with impairment of visual acuity, optic atrophy, and visual field defects. The interval between onset of the disease and a noticeable space-occupying growth was 11.5 years. Frequent false diagnoses and the importance of clinical-roentgenological follow-ups at regular intervals are especially emphasized.


Outcome following head injuries in the aged.

An analysis of 420 patients 60 or more years of age showed that even very mild brain injuries may be dangerous for the aged. Only one third of 174 patients with cerebral contusion made a useful recovery; of the 101 patients with cerebral contusion unconscious for six hours or more, 78 died, and only 11 made a useful recovery. The outcome in patients with acute intracranial haematomas or depressed skull fractures was poor. Even the aged with brain injuries may benefit from an intensive effort at treatment. This effort should, however, be strictly limited in time. With the present means of treating brain injury it seems futile to use limited intensive treatment resources for an acute brain injury in a patient over 70 years of age who is unconscious on admission. In contrast to acute injuries, subacute and chronic subdural haematomas should be operated on promptly in spite of severe neurological impairment or advanced age.


Cranial extradural cyst.

A large skull defect due to an extradural collection of clear and colourless fluid in a 59-years-old man is described. Hesitantly, we consider this to be the consequence of skull erosion due to Pacchionian granulations.


A case of giant aneurysm of the basilar artery.

A case of a giant aneurysm, 66 mm across at its largest diameter, at the bifurcation of the basilar artery, with agenesis of the internal carotid artery, verified by angiography and autopsy, is reported.


Two-dimensional echo-encephalography. 2. Clinical use and reliability of two-dimensional echo-encephalography in neurology and neurosurgery.

More than two hundred patients with intracranial lesions were examined by means of B-scan echo equipment specially adapted for the detectionof weak reflections. An impression of the accuracy of the method is demonstrated by the results obtained in those patients where the diagnosis had been verified at surgery or autopsy. It appeared that B scanning is a quite reliable diagnostic method. It was found that intracranial tumours showed typical echo-patterns. Furthermore, we found that B scanning may be an important diagnostic aid in follow-up examinations of patients. However, the ultrasound technique as used by us has also a restriction: it is unsuited for the estimation of the precise extension of pathological areas and for the estimation of the nature of pathology.


The adolescent with a learning disability: a developmental perspective.

The psychosocial difficulties that usually accompany learning disabilities are examined from a framework of developmental theory, particularly that of Erik Erikson. The implications of this perspective for treatment of adolescents with learning problems is discussed, and a specific program described.


Phencyclidine use in delinquent males committed to a training school.

Delinquent males committed to a training school were interviewed to determine the extent and the effects of phencyclidine use. Nine of 109 (8%) drug using subjects knowingly had used phencyclidine in the past. These nine subjects were multiple drug abusers of other substances and had started taking drugs at an average age of 9.38 years which was significantly younger than non PCP users. Six of the nine PCP users had committed proven offenses against persons and in four cases violent actions were directly attributed to PCP use. Suicide attempts were made by five (55%) of the PCP users which was significantly more frequent than suicide attempts made by non PCP users.


Gestalt therapy in a social psychiatric setting: the 'oil & water' solution.

In this case study, a provincial government residential treatment center for mentally and emotionally disturbed adolescents, used Gestalt Therapy as its primary therapeutic and staff-development ideology. Based on participant observation, document analysis, source material Survey on Gestalt Therapy, staff-sample interview and patient sample (of diagnostic, socioeconomic status and intelligence) data, it was demonstrated that Gestalt Therapy was neither designed nor intended for treatment of young adolescents manifesting severe psychiatric or behavioral disorders, for people from lower socioeconomic status families, or of low verbal skill and intelligence. It was discovered that a disporportionately large number of the case study population were: young adolescents, from lower socioeconomic status families, and that a significant proportion were of low verbal skill and intelligence. It was further suggested th,t Gestalt criteria for: physical environment, behavioral expectations (on staff and patient) and group-living ideology were incompatible with professional, legal and treatment expectations in an institutional treatment setting.


Teenage drunkenness: warning signal, transient boisterousness, or symptom of social change?

It is important for anyone working with youngsters, including counselors, physicians, psychiatrists, social workers, school administrators, and parents to familiarize themselves with the prevalence and characteristics of youthful drunkenness. Several attitudes toward this widespread adolescent behaviour are now current--and often in conflict--in our society, including viewing teenage intoxication as a symptom of problem drinking, a warning signal of future alcoholism, a reflection of cultural norms and social changes, and an expression of youthful boisterousness. Tentative conclusions are reached regarding the validity and usefulness of each of these different perspectives of youthful drinking behavior.


Arsine (arsenic hydride) poisoning in the workplace.

The National Institute for Occupational Safety and Health (NIOSH) recommends that appropriate workpractices be implemented to reduce the risk of worker exposure to arsine (AsH3) gas. There is a high potential for the generation of arsine gas when inorganic arsenic is exposed to nascent (freshly formed) hydrogen. This recommendation is based on several reports of worker exposure to arsine resulting in severe toxic effects or death. Most of the reported cases occurred when arsine was accidently generated during an industrial process. NIOSH would like to inform the occupational health community of some of the circumstances in which workers have been poisoned by arsine, with particular emphasis on the underlying mechanisms of generating the gas. We request that producers and distributors of arsenic and materials containing arsenic transmit information to their customers and employees, and that professional associations and unions inform their members. Stibine (SbH3), another toxic gas, if formed when antimony is exposed to nascent hydrogen. In most situations where arsine can be formed if antimony is present. Therefore, similar work practices should be implemented to reduce the risk of worker exposure to stibine.


Demonstration of an antigenic component in Kveim antigen.

Anti-Kveim-antigen serum was obtained by immunizing rabbits with Kveim antigen from lymph nodes and spleen in complete Freund's adjuvant. In the Ouchterlony test and in counter-immuno electrophoresis, a precipitation band with Kveim antigen from spleen and lymph nodes was demonstrated after absorption of the antiserum with serum and extracts of normal lymph nodes and spleen.


Inhibition of luminol-dependent chemiluminescence of alveolar macrophages by possible etiological agents of byssinosis.

Aqueous extracts of cotton bracts inhibited luminol-dependent chemiluminescence of phagocytosing alveolar macrophages. The inhibitory compounds were partitioned into organic solvents. Chromotographic analysis indicated that these compounds were either lacinilene C or its 7-methyl ether and scopoletin. The fact that the inhibitory activity of these compounds was always less than that of the total extract suggests synergistic action. These compounds may function as etiological agents of byssinosis.


Retention of inhaled 2-methylfuran and 2,5-dimethylfuran.

The respiratory tract retention of 2-methylfuran and 2,5-dimethylfuran in the dog have been studied as part of a broad investigation of substances found in the vapor phase of cigarette smoke. Retention of 2-methylfuran tended to be higher that that of 2,5-dimethylfuran in the upper, lower and total respiratory tract. Uptake of 2-methylfuran ranged from 63-88% in these regions while it was only 53-62% for 2,5-dimethylfuran. Retention of 2,5-dimethylfuran was lower than any of the other compounds studied. However, the majority of either compound will be absorbed by the respiratory tract when inhalation occurs.


Environmental control in asthmatic homes. The role of cheylatus mites. Preliminary report.

Forty asthmatic patients with age ranges from 5 to 46 years were studied with three extracts in intradermal skin test: Dermatophagoides 1/10, Cheylatus 1/100 and house dust 1/500 w/v. Eighty five percent of patients were sensitive to house dust, 57.8% to Dermatophagoides and 55% to Cheylatus. Forty percent were positive to the three antigens and 12.5% were negative to these antigens. As the Cheylatus have been fed with Dermatophagoides, the positive reactions observed for the former could be influenced by this type of feeding. Therefore, Cheylatus must not be used in the patients' home for eradication of mites.


Permeation of glove materials by physiologically harmful chemicals.

The breakthrough times and permeation rates of 1,4-dichloro-2-butene, benzene, carbon tetrachloride, and 2-chloro-1,3-butadiene for eleven commercially available gloves were determined. Four methods of determining the breakthough time and permeation rate were evaluated. A wide variation in the glove material thickness and protection time was found showing that the adequate protection time can only be determined by testing the proposed glove with the chemicals to be handled.


Respirator cartridge test system and test results for benzene and acrylonitrile.

NIOSH approves organic vapor respirator cartridges based upon testing against 1000 parts per million carbon tetrachloride vapors. Data for other organic vapors are necessary for proper use of organic vapor cartridge respirators against those vapors. This paper describes a system designed to test respirator cartridges and canisters and results of cartridge tests against benzene and acrylonitrile at a variety of concentrations.


A sampling and analytical method for vinylidene chloride in air.

A sampling and analytical method for the determination of vinylidene chloride in air is presented. Vinylidene chloride can be quantitatively trapped on charcoal over a wide range of concentrations. The collected vapors are desorbed with carbon disulfide and analyzed by gas chromatography utilizing a flame ionization detector. The analytical column is packed with Durapak OPN. The lower limit for the method is approximately 7 micrograms of vinylidene chloride per sampling tube. The breakthrough volume was found to be dependent upon the concentration sampled and the relative humidity of the air sampled. The overall precision of the analytical method is 5% (relative standard deviation).


Effects of lifting frequency and technique on physical fatigue with special reference to psychophysical methodology and metabolic rate.

A laboratory study was conducted (1) to evaluate the effects of lifting frequency and technique on maximum acceptable work loads using psychophysical measurement technique, and (2) to compare the physiological fatigue criteria of 5 Kcal/min with the psychophysical fatigue criteria by measuring the metabolic rates at maximum acceptable work loads determined by subjective estimates of physical fatigue. Six male college students were required to lift from the floor to a 0.5 m height for 40 minutes. Four levels of lifting frequency (3, 6, 9 and 12 lifts/min) and three different lifting techniques (free sytle, stooped back and straight-back, bent-knee) were employed. Oxygen consumption rates were measured at maximum acceptable work loads (and were reduced to STPD). Statistical analysis showed that the maximum work loads acceptable to the workers were significantly affected by both lifting frequency and technique. Maximum acceptable work loads increased with an increase in lifting frequency. Both the subjective estimates of physical fatigue and the metabolic energy expenditure rate favored the free style lifting technique. The measured metabolic rates were in agreement with the physiological fatigue criteria of 5 Kcal/min only for six of the twelve combinations of lifting frequency and technique. Use of the physiological fatigue criteria will result in more liberal standards of work load at low work paces, especially for the stooped back and the free style lifting techniques.


Asthma problems in southern Italy: A statistical study of 2362 asthmatic patients.

In this report we have described the statistical results of a clinical study on 2362 asthmatic patients living mostly in the Naples area and observed in our Division of Respiratory Allergy from January 1976 to May 1978. All data have been analyzed by a computerized method using an Univac 1100 Computer. We have studied some aspects of the atopic syndrome in this population of Southern Italy: frequency of allergic sensitization according to endogenous and extrinsic factors (particularly Parietaria officinalis, a characteristic pollen of the Southern Italian Flora), etc. Finally we have presented the first results of our allergological investigation in Naples concerning the distribution of allergic sensitization according to air pollution of the patient's home.


The quantitative determination of acrylonitrile, acrolein, acetonitrile and acetone in workplace air.

A simple and sensitive procedure for the routine determination of personnel exposures to organic vapors in the workplace has been developed using porous polymer adsorption/thermal desorption with a subsequent analysis by gas chromatography. Detailed instructions for the packing of the adsorption tube and the operation of the thermal concentrator (flasher) are given. Calibration data obtained with both a static on tube injection procedure and a dynamic method using a permeation device are discussed. More than two years of experience with 6000 samples involving a wide variety of compounds has shown the sensitivity and versatility of the techniques. The additional equipment involved is commercially available costing about $2000.


Assessment of the respirable dust levels in the nation's underground and surface coal mining operations.

This report presents a chronological overview of the status of respirable dust exposures in underground and surface bituminous coal mines since inception of the 1969 Federal Coal Mine Health and Safety Act. Data for various intervals from 1970 through 1977, are presented for selected mining operations. Comparisons are made using data available from the mine operators' sampling program and from MSHA surveys. The data demonstrate the marked decrease that has occurred in respirable dust exposures since inception of the 1969 Act.


Recovery of acrylonitrile from charcoal tubes at low levels.

Data are presented for the recovery of acrylonitrile from charcoal tubes at levels lower than those tested in NIOSH Method S156. A 2% by volume acetone in CS2 solution is used as desorbing solvent. An injection volume of 2 muL and a 3-m long by 3.2-mm o.d. (10-ft x 1/8-in) stainless steel column filled with 20% SP-1000 on 80/100 Supelcoport gives adequate resolution of the acrylonitrile. Results indicate that recoveries are adequate for sample sizes which correspond to a 15-liter sample at 0.5 and 0.25 ppm, and that acrylonitrile collected on carbon in the absence of inhibitor is stable for at least a week.


New filter compositions for the analysis of airborne particulate and trace metals.

Characteristics are presented of various new filter materials of polyvinyl chloride--polyacrylonitrile, polyimide, polyaromatic, and of quartz fibers. These filters have been specifically developed for air sampling applications. Included in the presentation are comparative performance characteristics such as: infrared and ultraviolet spectra, inorganic and trace metals analyses, chemical compatibilities and reactivities with various liquids and gases, moisture pick-up, mass per unit area, mechanical properties (tensile strength and elongations), air flows/pressure drops, and particle retention efficiencies. Examples are presented of the increased acceptance of membrane filters in air analyses due to their simplifying tedious conventional procedures and their improvement of sensitivity, precision, and accuracies. Included are the ability of specific synthetic filters to impart optical transparency for analyses of asbestos and other fibers by transmission techniques using oil immersion or dispersion staining, the direct determination of silica on an acrylonitrile membrane by infrared, the direct determination of atmospheric particulate types and the concentrations of each. Other examples given are trace metal analyses by X-ray fluorescence, and gravimetric procedures and scanning electron microscopy techniques for analyses of suspended particulate matter.


Migration and turnover of entero-endocrine and caveolated cells in the epithelium of the descending colon, as shown by radioautography after continuous infusion of 3H-thymidine into mice.

Adult male mice were given a continuous infusion of about 0.5 muCi of 3H-thymidine per gram body weight per day for periods varying from 1 to 60 days. Semithin sections of descending colon were cut from/plastic-embedded blocks and stained by a method combining silver impregnation and iron hematoxylin, by which argentaffin entero-endocrine cells and caveolated cells could be identified. From radioautographs, the labeling index of these cells was determined. One to three days after the beginning of 3H-thymidine infusion, label is observed in some of the stained entero-endocrine cells in the bottom of the crypts; the apices of these cells reach the crypt lumen and are joined to neighboring cells by terminal bars (junctional complexes). After five to seven days, labeled entero-endocrine cells are seen on the sides of the crypts, where their base stretches along the basement membrane and their apex has lost its terminal bar connections to neighboring cells. Finally, by 13 and 24 days, labeled cells are observed within the epithelium at the mucosal surface. The turnover time, which is taken to be equal to the mean time required for migration from site of origin to site of loss on the mucosal surface, has been estimated at 23.3 days. This is much longer than the 4.6 days required by the two main cell types of the epithelium -- vacuolated-columnar and mucous cells -- to travel the same route. It is likely that, after entero-endocrine cells lose their terminal bar attachment to other epithelial cells, they migrate independently and very slowly. Labeled caveolated cells are first seen in the crypt bottom one day after the beginning of 3H-thymidine infusion. By three to five days, they are on the sides of the crypts; their base is stretched along the basement membrane, but their apex retains its attachment to neighboring cells by terminal bars. By seven days, labeled caveolated cells are on the mucosal surface. Their turnover time has been assessed at 8.2 days. This is, again, longer than for the two main types to which they are bound by terminal bars throughout migration. The discrepancy is explained by the caveolated cells arising deeper in the crypts than most vacuolated-columnar and mucous cells.


A correlated thin-section and freeze-fracture analysis of guinea pig adrenocortical cells.

Comparison of the fine structural features of guinea pig adrenocortical cells as seen in thin sections with those revealed by freeze-fracture confirms the structural appearance of steroid-secreting cells as interpreted from thin sections and reveals significant new features of the membranous organelles. Smooth-surfaced endoplasmic reticulum appears as a network of tubules, interwoven or in parallel, and as cisternae, fenestrated and non-fenestrated. These elements are tightly packed in the deeper cortical cells, excluding other organelles from their domain. Tubules and fenestrated cisternae possess randomly distributed intramembranous particles on their PF faces, while closely packed non-fenestrated cisternae possess aggregates of particles interspersed with aparticulate regions on their PF faces. These differences in particle distribution suggest functional specialization among the various forms of reticulum. Mitochondria appear as elongated structures of varying shape. Freeze-fracture reveals that all their cristae have circular origins from the inner membrane. Sinuous tubules, which appear as tubules in section, and straight tubules, which appear as lamellae in section, arise from single sites. Flattened sac-like cristae may have multiple circular origins. Definite contact points seen between inner and outer membranes may facilitate passage of molecules, including steroids, into the mitochondrial compartments. Lysosomes and peroxisomes, which are easily identified in thin sections with the aid of cytochemistry, are difficult to identify with certainty by freeze-fracture. Single membrane-bound granules of slightly smaller diameter than mitochondria may represent lysosomes. Smaller granules interconnected with the tubular reticulum, as well as dilated regions of this organelle, may represent peroxisomes. Plasma membranes show no indication of tight junctions but do have abundant gap junctions which show a zonal differentiation: small gap junctions throughout the cortex, medium-sized regularly shaped gap junctions in zona fasciculata externa, and large irregular gap junctions in zona fasciculata interna and zona reticularis. The large junctions cover planar areas as well as surfaces of projections of one cell into another. Such junctions may allow passage of ions as well as of low-molecular-weight substances between the cells, facilitating or even amplifying the response to trophic hormone stimulation.


Cyclic changes in ciliation, secretion and cell height of the oviductal epithelium in women.

Oviducts were obtained from women who elected to undergo sterilization either during a normal menstrual cycle, after the first trimester of pregnancy, or in the puerperium. The percent of ciliated cells, cell height and morphology of the fimbria and ampulla were determined and correlated with the stage of the reporductive cycle and plasma levels of the ovarian steroids. Mature ciliated and secretory cells were observed only at mid-cycle. Atrophy, deciliation and loss of secretory activity coincided with elevated levels of serum progesterone. These degenerative processes continued during pregnancy. Ciliation, hypertrophy, and restoration of secretory activity occurred when serum progesterone was essentially undetectable and estradiol relatively low. During each menstrual cycle the secretory cells were observed to undergo a complete cycle of dedifferentiation-differentiation, whereas 10--12% of the ciliated cells lost and regenerated their celia. Ciliogenic cells were frequently present in the epithelium obtained from women in the mid-follicular phase. Fibrous granules, deuterosomes, procentrioles and ciliary buds were observed in the apex of these cells. Plasma levels of estradiol were higher during periods of atrophy and deciliation than they were during periods of hypertrophy and reciliation. It appears that the serum levels of estradiol were adequate to maintain a mature epithelium at all the reproductive stages included in this study. However, progesterone, when present, blocked the growth-promoting effect of estradiol in the oviduct.


Retrograde changes in Clarke's column following neonatal hemicerebellectomy in the rat.

Long-Evans black-hooded rat pups underwent hemicerebellectomies at various postnatal ages. The animals were killed at 28 days of age and thoracolumbar segments of the spinal cord were removed and processed according to Golgi and Nissl techniques. Hemicerebellectomy at two and three days postnatally produced, in addition to cellular hypotrophy in Clarke's column, dendritic alterations which included a decrease in the number of primary dendrites and a reduction of the remaining dendrites to truncated stubs. Hemicerebellectomy at 21 days postnatally had little effect on either cell size or dendritic arborization. The role of the target nucleus in maintaining cell growth and dendritic arborization during critical developmental periods is discussed.