Toxicity of alpha-phenyl-gamma-butyrolactone, a metabolite of glutethimide in human urine.

A novel metabolite, alpha-phenyl-gamma-butyrolactone, isolated from the urine of a glutethimide overdose victim, was synthesized and tested for biological activity in mice. Interperitoneal injections of this lactone caused severe toxicity at moderate dose levels. These results point to another metabolite of glutethimide contributing toxicity to patients severely intoxicated by the parent drug. An improved synthesis as well as complete spectral data of this lactone are also presented.


Unique approach for calculation of absorption rate constant.

Several methods are employed to estimate an apparent first-order rate constant for absorption in a one-compartment model (Ka). These include curve-stripping, nonlinear least squares regression, and the Wagner-Nelson approach. The Wagner-Nelson method in particular requires extensive calculation and may be subject to error. A method for calculation of the absorption rate constant has been derived based on the relationship between area under the concentration-time curve, between time of maximum concentration (tmax) and infinity, and maximum concentration (cmax). The method obviates the need for large numbers of samples in the absorptive phase. The method also avoids extensive calculations and is less influenced by errors in data points prior to Cmax where the rate of change of concentration is very rapid and error is likely. The value for Ka is corrected for by the error found in tmax (calculated using the estimated Ka) relative to the observed tmax. The method has been tested on theoretical data with and without error generated using a range of a and KE. Errors in the estimate of Ka are proportional to error in the data.


An 125I-radioimmunoassay for the determination of the anticonvulsant agent clonazepam directly in plasma.

A simple and specific 125I-radioimmunoassay (RIA) for the determination of the anticonvulsant agent clonazepam directly in plasma has been developed using a previously reported antiserum to the drug. The 125I-radioligand was prepared by reaction of 3-aminoclonazepam with a commercially available acylating reagent, 125I-N-succinimidyl 3(4-hydroxyphenyl) propionate, of high specific activity (approximately 1500 Ci/mM). The method has a workable range between 5 and 100 ng/ml of clonazepam using a 10 mu1 sample of plasma for analysis, which is satisfactory for routine clinical monitoring. The intra and inter-assay coefficients of variation did not exceed 3 and 9% respectively. Recovery of clonazepam was quantitative when the drug was added to a pool of plasma obtained from subjects who had received a wide variety of other anticonvulsants. Clinical plasma samples from subjects receiving clonazepam chronically were assayed for clonazepam by the new 125I-RIA and a previously reported 3H-RIA. The data was subjected to linear regression analysis which gave a slope, intercept and correlation coefficient of 1,-0.33 ng/ml and 0.994 respectively and demonstrated that the two methods are equivalent. However, the 125I-RIA is more rapid and less costly for routine monitoring than the 3H-RIA.


Neurochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Wistar and Gunn rats.

Normal Wistar, heterozygous and homozygous Gunn rats were killed one week after a single intragastric dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 20 microgram/kg in acetone-olive oil. Control animals were treated similarly but without TCDD. The brain protein and RNA content were measured together with enzyme assays of lysosomal acid proteinase and soluble DT-diaphorase. Acid proteinase activity was increased in the brains of the normal Wistar rats after TCDD treatment. RNA and protein contents were lowered in the heterozygous Gunn rats whereas no changes were detected in the homozygous Gunn rats. The cerebral soluble DT-diaphorase activity was slightly enhanced (about 35%) by TCDD treatment only in normal Wistar rats. Our results may point at modified neurotoxic effects of TCDD in chronic exposure to bilirubin as in the case of Gunn rats.


Studies on the effect of tobacco smoke on the biotransformation of vasoactive substances in the isolated perfused rabbit lung. I. Prostaglandin F2alpha.

Cigarette smoke administration was previously found to have a pronounced  inhibitory effect on metabolism of nicotine and benzo[a]pyrene in the isolated perfused rabbit lung. These observations suggest the possibility of tobacco smoke inhibition of biotransformations associated with non-ventilatory pulmonary functions such as metabolic clearance of endogenous vasoactive substances. However, studies of the effect of smoke on uptake and metabolism of PGF2alpha in isolated perfused rabbit lungs provide no evidence of inhibition of these processes.


Stimulation of phospholipase activity and prostaglandin biosynthesis by melittin in cell culture and in vivo.

Melittin, a membrane-active peptide of bee venom, as well as synthetic melittin, stimulated the biosynthesis of prostaglandins by mouse transformed fibroblasts (MC5-5), human fibroblasts (D550), rabbit aorta endothelial cells (CLO), rat lung type II alveolar pneumocytes (L-2) and rabbit smooth muscle cells (R-I). The melittin peptides also stimulated the release of arachidonic acid from the cellular phospholipids of MC5-5 cells. The stimulated prostaglandin biosynthesis by MC5-5 cells was inhibited by indomethacin and dexamethasone. Dexamethasone inhibited also the release of arachidonic acid by MC5-5 cells. In mice, intraperitoneal inoculation of melittin increased 13,14-dihydro-15-keto-PGE2 levels in peripheral blood. Prior injections of the mice with indomethacin prevented the melittin-induced increase in this PGE2 metabolite.


Responses to vasectomy performed at different ages in the rat.

The weights of the liver, heart and kidneys were not influenced by vasectomy at any age whereas rats vasectomized at 50 weeks gained appreciably more (30%) in body weight than their corresponding controls. Significant atrophy of the ventral prostate occurred only in the older group of vasectomized animals but this was accompanied by slight increased in circulating testosterone. Pituitary weight was unaffected by vasectomy, but slight atrophy of the testes in the 50 week old vasectomized rats might suggest the beginnings of decline in gonadal function after vasectomy in the older animals. In addition, the accumulation of lipids in the blood and heart tissue of rats vasectomized at 50 weeks of age indicates that the older animals may be more susceptible to the effects of the surgery than their younger counterparts. There were no marked changes in fasting blood glucose and significant elevation in glucocorticoid status after vasectomy in 10 week old rats was not manifest in the older groups of animals.


Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice.

Pretreatment for four days with coenzyme Q10 (COQ10) reduced the acute toxicity in mice treated with adriamycin. In two sequential protocols, adriamycin allowed only 36 and 42% survival, respectively. Pretreatment with COQ10 allowed 80 and 86% survival, respectively. The differences are significant, p less than 0.05. The mechanism for this reduction in the acute toxicity may be based upon the prevention by the supplementary COQ10 of the inhibition caused by adriamycin to COQ10-dependent enzymes in cardiac and and other tissues. The prospect of diminishing the toxicity of adriamycin in cancer patients remains promising and important.


Alcohol-membrane interaction: calcium uptake in mitochondria.

A biphasic effect of ethanol was observed on Ca2+-uptake activity, Ca2+-uncoupled respiratory control ratio (CURCR), and State 3 oxygen uptake. At low concentrations (0.1-0.5%) ethanol enhanced these activities, probably as the result of an increase in membrane fluidity. At higher levels (0.7-4.0%) ethanol had an inhibitory influence on mitochondrial activities as the membrane macromolecules were probably disturbed due to the hydrophobic alcohol-membrane interaction.


Biphasic kinetic profile for carbamazepine epoxide formation.

The formation of the stable 10,11-epoxide from carbamazepine by rat liver microsomes was studied. A biphasic activity-substrate profile was consistently found with microsomes from both control and phenobarbital pretreated rats. These data could either indicate epoxide formation by multiple catalytic sites with differential substrate affinity or a solvent effect on the enzyme or its environment.


Evidence for a noncovalent intermolecular interaction of opiates with thiamine.

Opiate agonists and antagonists formed reversible molecular complexes with thiamine. The absorption maxima of these complexes were at wavelengths longer than those of the individual components and their intensities depended on the concentration and nature of the opiate component. The possible implications of such an interaction are discussed.


Inhibition of sympathetic neuronal transport and ouabain-induced cardiac arrhythmias.

The objective of the present investigation was to determine whether a correlation exists between the effect of ouabain to inhibit activity of the sympathetic neuronal transport system and the effect of the drug to produce cardiac arrhythmias. 3H-d,1-Metaraminol was used to monitor activity of the transport system in intact animals as well as in isolated perfused hearts. Accumulation by myocardial tissue (LV; RV), spleen (S), and gastrocnemius muscle (GM) of the guinea pig was not altered by the lowest dose of ouabain, 100 microgram/kg. A subarrhythmic dose, 150 microgram/kg, as well as the arrhythmic dose of ouabain, 212+/-24 microgram/kg, decreased accumulation by LV, RV, and S. Several different concentrations of ouabain were studied in the isolated perfused guinea pig heart preparation. Only the highest concentration, 5 X 10(-6)M was capable of decreasing accumulation of metaraminol. However, all but the lowest concentration of ouabain produced toxic arrhythmias. Thus, neither in intact animals nor in isolated perfused hearts could the dose of ouabain required to inhibit the sympathetic neuronal transport system be correlated with the dose of ouabain required to produce cardiac arrhythmias. It is concluded that ouabain inhibition of the sympathetic neuronal transport system does not play a role in the genesis of ouabain-induced cardiac arrhythmias.


Effects of phenobarbital and diazepam on imipramine-induced changes in blood pressure, heart rate and rectal temperature of rats.

To investigate the safety of anticonvulsants in doses found equipotent in suppressing imipramine induced convulsions, the effects of diazepam (1.8 mg/kg) or phenobarbital (40 mg/kg) following a toxic dose of imipramine (50 mg/kg) on heart rate, blood pressure and body temperature were examined in male Wistar rats. Administration of imipramine alone resulted in significant decreases in blood pressure, heart rate and rectal temperature. Phenobarbital or diazepam alone failed to significantly affect any of these parameters apart from a slight reduction in rectal temperature seen with phenobarbital. Diazepam given after imipramine antagonized the imipramine-induced decrease in heart rate but increased the hypotensive and hypothermic effects. Phenobarbital failed to significantly affect the imipramine-induced changes in any of the physiological parameters studied. The present data suggests that phenobarbital may be preferable to diazepam in treatment of imipramine-induced convulsions.


Specificity of amphetamine induced release of norepinephrine and serotonin from rat brain in vitro.

Incubation of normal rat cortical or brain stem tissue with 3H-NE or 3H-5-HT and subsequent exposure to amphetamine produced a concentration-related release of the transmitters from tissue stores into the incubation media. Although pretreatment with the catecholamine neurotoxin in 6-hydroxydopamine (6-OHDA) reduced the retention of 3H-NE in both of these tissues, the proportion of 3H-NE released by amphetamine was attenuated only in cortical tissue. Pretreatment with the serotonergic neurotoxin, 5,6-dihydroxytryptamine (5,6-DHT) had no effect on the retention or release of 3H-NE in cortical or brain stem tissue. Pretreatment with 5,6-DHT reduced the retention of 3H-5-HT in the cortex and brain stem, but the release of 3H-5-HT was significantly attenuated only in the latter tissue. 6-OHDA pretreatment increased the retention and proportion of cortical 3H-5-HT released by amphetamine but reduced the release of brain stem 3H-5-HT in the absence of an effect on retention. It appears that the in vitro release of 3H-NE from the cerebral cortex occurs primarily from catecholamine and not serotonergic neurons whereas the cortical release of 3H-5-HT is not an event specific to serotonergic nerve terminals. The release of 3H-5-HT from brain stem does not appear to be restricted to the serotonergic cell bodies since its release was attenuated by 5,6-DHT and 6-OHDA.


Chemiluminescence resulting from an interaction between imipramine and human polymorphonuclear leukocytes.

The addition of imipramine to a suspension of resting polymorphonuclear leukocytes (PMNs) resulted in the generation of chemiluminescence (CL) (100,000 cpm with 1 X 10(-4)M imipramine). In the presence of a particle (zymosan) capable of activating the PMNs to generate reactive oxygen species, the magnitude of CL observed with 1 X 10(4)M imipramine was greatly enhanced (greater than 1,000,000 cpm). No CL was detected upon the addition of imipramine to PMNs isolated from a chronic granulomatous child or to alveolar macrophages isolated from rats. Another tricyclic antidepressant, amitriptyline, failed to generate CL with PMNs either alone or in the presence of zymosan; however, both imipramine and amitriptyline generated CL upon addition to the xanthine oxidase-purine superoxide generating system. Although the mechanism by which this drug-cell interaction results in the generation of CL is not known, the observations are suggestive that the CL may originate, in part, from the activation of imipramine by some reactive oxygen state(s).


The effects of fructose and other substances on acetaldehyde and ethanol metabolism in the rat.

The purpose of this study was to test the comparative effectiveness of fructose, glucose, sucrose and alanine in increasing the rates of ethanol and acetaldehyde clearance. Intravenously administered fructose was found to be most effective, followed by alanine in increasing the rate of blood alcohol clearance. Administration of any one of the test substances during ethanol metabolism did not result in a significant change in the levels of blood acetaldehyde. Fructose partially prevented the ethanol-mediated changes in the concentration ratios of lactate/pyruvate and beta-hydroxybutyrate/acetoacetate. Its administration also resulted in the reversal of acetaldehyde-mediated changes in the liver. Test substances resulted in an increase in hepatic glucose levels, however, a combination of these substances with ethanol resulted in decreased hepatic glucose levels. The most pronounced effect on glucose was observed when ethanol was given in combination with glucose. During the simultaneous metabolism of fructose and ethanol, hepatic and blood levels of sorbitol increased significantly. Fructose also exerted the most pronounced antiketogenic action.


Effect of parenteral zinc on paraquat toxicity in the rat.

The purpose of this study was to determine if elevating lung zinc would prevent the lethal effect of paraquat. Several doses of zinc sulfate (20, 40, and 80 mg/kg) were administered intraperitoneally for 7 days and lung ainc measured. Only 80 mg/kg produced a significantly increase. Acute administration of 80 mg/kg zinc sulfate produced an 81% elevation in lung zinc within 4 hr. Animals were treated with zinc sulfate (80 mg/kg) followed 4 hr later by paraquat (42.5 mg/kg). They also received 2 additional doses of zinc during the next 48 hr. Zinc treated animals were not protected against the lethal effect of paraquat but, instead, had a higher fatality rate than animals treated with paraquat alone.


The reaction of 5-hydroxyindoleacetic acid with ortho-phthalaldehyde and cysteine.

The metabolite 5-hydroxyindoleacetic acid, the major metabolic product of serotonin, can be measured by reacting it with orthophthalaldehyde to form a highly fluorescent product. The inclusion of cysteine in this reaction causes an increase in the amount of fluorescence. The rate of fluorescence formation for reaction containing cysteine is much faster than the rate for the reaction without cysteine. The differences observed for both excitation and remission maxima between reaction products formed in the presence and absence of cysteine indicate that these products are different. Furthermore, the significant difference in the regression coefficients of fluorescence of the reaction products versus HC1 concentration adds further evidence that the reaction products formed in the presence and absence of cysteine are different. HC1 appears to influence the reaction of 5-HIAA, OPT and cysteine in several ways: by causing the destruction of 5-HIAA, by affecting the fluorescence of the product formed, and by influencing the amount of reaction product formed.


Influence of exercise training and exhaustion on 45Ca++ content of skeletal muscle mitochondria and fragmented sarcoplasmic reticulum.

Following a 25 muCi/Kg i/p. injection, 45Ca++ activity from the mitochondria and fragmented sarcoplasmic reticulum (FSR) of the superficial rectus femoris (FG-fibers) and combined soleus muscle (SO-fibers) of trained (T, N = 9) and untrained (UT, N = 8) male Wistar rats was determined. The FG mitochondrial 45Ca++ activity from rested animals was 3.9 (T) and 5.3 (UT) times greater than the FSR from this muscle group while the so-mitochondrial 45Ca++ activity was 13.2 (T) and 20.5 (UT) times greater when compared with the respective SO-FSR (p less than .01). The mitochondrial 45Ca++ content of the SO-fibers from rested animals was 58% UT, p less than .01) and 148% (T, p less than .001) greater than that of the FG mitochondria. After 20-26 weeks of exercise training the SO-mitochondrial 45Ca++ content of the rested-T animals was approximately 18% lower (p less than .05) while the T-FG-mitochondrial 45Ca++ content was 48% less than that of UT animals (p less than .01) with a concomitant 28% greater 45Ca++ activity in SO-FSR for the T-group as compared to UT (p less than .01). Following a rapidly exhaustive treadmill run the mitochondrial 45Ca++ content in the UT group was depressed by 21% in SO-fibers and 37% in FG-fibers (p less than .01) with no changes occurring in the T-group. Exhaustion produced no significant changes in the 45Ca++ activity of the FSR from either group of animals.


Reduction of erythropoietic toxicity to cytarabine by pentobarbital.

The erythropoietic toxicity of cytarabine was reduced when mice were maintained in the anesthetized state by pentobarbital starting 1 hr before and lasting 1 hr after a series of doses of cytarabine given over a 4 hr period. Erythropoietic toxicity was determined by injecting 59Fe 48 or 72 hr after the last dose of cytarabine and measuring 59Fe in the circulating red blood cells 24 hr later (24 hr 59Fe uptake). Although pentobarbital alone had no effect on 24 hr 59Fe uptake either 48 or 72 hr after pentobarbital, the barbiturates reduced erythropoietic toxicity when cytarabine was given as 3 doses of 50 or 100 mg/kg every 2 hr and the effect was evaluated 48 hr after the last dose. Neither single nor multiple doses of cytarabine inhibited 59Fe uptake when 24 hr 59Fe uptake was measured 72 hr after cytarabine. However, if an initial dose of cytarabine (150 mg/kg) was given 12 hr prior to the multiple doses and 24 hr 59Fe up take was measured 72 hr after drug treatment, 59Fe uptake was inhibited, suggesting that the initial dose of cytarabine induced hemopoietic stem cells in the resting GO state to go into active cell cycle. Pentobarbital also protected against these latter effects of multiple doses of cytarabine. In contrast to the above, pentobarbital did not protect against the inhibitory effects of a single dose of cytarabine on 59Fe uptake. The above data show that pentobarbital protects against the cytotoxic effect of cytarabine on pronormoblasts and hemopoietic stem cells in cell cycle.


Antiinflammatory and antiproteolytic properties of substituted-4-thiazolidones.

Eleven 3-(3,4-diamethoxy phenyl ethyl)-4-oxothiazolin-2-yl-substituted hydrozones were evaluated for antiinflammatory and antiproteolytic properties. The toxicity of the compounds was reflected by their approximate LD50 values.


Effect of p-chloroamphetamine on serotonin content of the rat pineal gland.

p-Chloroamphetamine depleted serotonin in the rat pineal gland. Unlike the effect of p-chloroamphetamine on brain serotonin in rats, the depletion in the pineal gland lasted only a few hours and was not prevented by pretreatment with fluoxetine, an uptake inhibitor.


Apparent metabolism of allopurinol by blood--a preliminary report.

Allopurinol is converted to a presently unidentified metabolite by whole blood, both in samples prepared in vitro as well as samples from subjects administered the drug. The apparent plasma concentration of allopurinol, as determined by HPLC, is dependent upon the length of time between sample preparation or sample withdrawl and the centrifugation and removal of plasma. Oxypurinol does not undergo the same conversion, nor does it affect the loss of allopurinol.


Evaluation of catheter-manometer systems for adequate intravascular blood pressure measurements in small animals.

Various catheter-manometer systems possible for intravascular blood pressure measurments on rats have been elaborated and tested in vitro and in vivo. Using a pressure-step calibrator, it was observed from in vitro studies that microtransducers had superior frequency response compared to conventional transducers. Of the catheters tested, Pe-90 tapered to a 40 mm tip with an inner diameter of 0.3 mm had the best frequency response as judged from fall and settling times. Because of the damping effect, tapering increased fall time to 1.8 ms, which was still quite acceptable. By the same token settling time was minimized to 22.4 ms. With a special calculation method the theoretical percentile fault of the recordings was estimated to be 9.66%. When the measurement error was calculated from the actual in vivo recordings, it was found to be no more than 2.7%. These results show that the technique described is adequate for continuous intravascular blood pressure recordings on small animals. Finally it is emphasized that careful handling of the catheters and avoidance of stopcocks and air bubbles are essential for obtaining accurate and reproducible values.


Effects of glucagon on liver metabolism in intact dogs.

Chloralose-anaesthesized dogs, starved for 24 hours, were used to determine the effects of 10 microgram/kg glucagon, administered i.v. as a single bolus injection, on liver substrates in situ (glycogen, glucose-1-phosphate, glucose-6-phosphate, glucose, fructose-6-phosphate, fructose-1,6-diphosphate, triose phosphates, glycerol-3-phosphate, phosphoenolypyruvate, pyruvate, lactate, citrate, malate, ATP, ADP, and AMP). liver samples were obtained by instant deep-freezing with Wollenberger clamps on four consecutive occasions at 10-minute intervals. Heart rate and blood pressure were continuously monitored. Serial liver sampling per se had no significant effects on liver metabolism or systemic haemodynamics in a group of control animals. In a second group glucagon, administered after the initial freeze-clamp sampling to obtain baseline values, led to a marked activation of the glycogenolytic pathway resulting in glucose release from the liver.


Inhibitory effects of jaundice on regenerating liver.

The effects of partial hepatectomy on the energy charge (ATP + 1/2ADP/ATP + ADP + AMP) and mitochondrial oxidative phosphorylation were studied in normal and jaundiced rats. In normal rats and energy charge levels of the remnant liver decreased only slightly with a rise in the phosphorylative activity of the mitochondria at an early stage after hepatectomy, and then rapidly returned to normal. In jaundiced rats subjected to the common bile duct ligation the energy the energy charge levels of the liver decreased to approximately 0.800 from 0.849 of normal value, though their mitochondrial oxidative phosphorylation was within normal limits. In jaundiced rats the energy charge levels of the remnant liver after partial hepatectomy decreased markedly without a return toward normal. The mitochondrial phosphorylative activity increased to only about 50% of hepatectomized normal rats after partial hepatectomy. More than 70% of jaundice rats died within 24 hours after partial hepatectomy. It was suggested that the jaundice inhibits an enhancement of ATP generation to provide sufficient energy for high energy demand rather than the enery-requiring biosynthetic process in an early process of liver regeneration.


Stored blood microfiltration. Evaluation of micro-aggregate filter composed of polyurethane foam and nylon wool.

Aggregates of amorphous material which develop during storage of banked blood have been implicated as a cause of pulmonary micro-embolism in man following massive transfusion. Such pulmonary micro-embolism may be a causal factor in the development of post traumatic pulmonary insufficiency. At present several microaggregate filters for use in massive transfusion are commercially available, and on of these is the Fenwal filter. It is composed of a screen filter which removes microclots of 250 microns and higher, a layer of polyurethane foam and a layer of nylon wool. The resistance of this device is very acceptable and the filter may be used for several blood units, but its efficiency seems less than that of Dacron wool filter.


[In-vitro formation of plasma polyps in the human placenta and their isolation by means of "inverted centrifugation" (author's transl)].

1. Histological observations on sliced human placenta shaked in Krebs-Ringer-solution showed an high plasma polyp formation by the syncytiotrophoblast without any monoidoacetate or sodiumfluoride poisoning [1]. 2. The high plasma polyp formation of placenta slices incubated with gased (96% O2, 4% CO2) Krebs-Ringer-solution and shaked at 37 degrees C decreased rapidly and lasted up to 40 min. 3. Perfusion of the placenta intervillosum with fetal serum added Krebs-Ringer-Solution gave results in plasma polyp production up to six times higher than serum free Krebs-Ringer-solution perfusions. 4. Plasma polyp isolation and concentration by one step is discribed applying the inverted centrifugation technique: Plasma polyps migrate centripetally in Krebs-Ringer-solution containing 6% Ficoll (Pharmacia) and were concentrated in the tip of a tube invertedly placed into a swing-out-rotor.


[A modified Thomas canula to create a chronic pancreatic fistula in minipigs (author's transl)].

The design of a modified Thomas canula is described. It's possible applications for investigation of exocrine pancreatic function and gastric secretion as well as gastric emptying in minipigs are discussed. The advantages of this modified canula are that it can be simply manufactured, that it is well tolerated by the tissue and that there is no risk for the animal and no need for the construction of a pouch.


[Biomechanical investigations of the liver capsule (author's transl)].

The strain properties of geometrically defined specimens of human, pig, and bovine liver capsule were analysed in vitro by applying histomechanical procedures. The dynamic relaxation correlates with the static relaxation under sinus shaped strain process after previous additional predetermined increase in length. If such a process occurs in the linear region of the stress-strain curve, the relaxation process continues on a new level even if the amplitude of the sinus length-time input function is augmented. The same experiment causes in the lower non-linear region of the stress-strain relation the so-called asymmetric amplitude phenomenon. Further histomechanical features of the liver capsule obtained after defined length-time input functions such as relaxation, static isorheological line, dynamic isorheological curve, increase of the vertices of the dynamic force-time function after static relaxation and dynamic force recovery curve are shown. The phase shift between force and lenth is pointed out. The significance of the biomechanical properties of the liver capsule under physiological and pathological conditions is discussed.


Liver fibrosis of the turkey on rapeseed products.

Sclerosis of the liver accompanied by hydropericardium of long standing was observed in turkeys fed rapeseed products for 16 weeks. Histologically, extensive increases of fibrous tissue composed predominantly of reticular fibres and centrilobular degeneration of parenchymal cells were the main pathological features. Neither prominent fatty degeneration nor the formation of pseudolobules was observed. The birds fed rapeseed products for four and 12 weeks showed continuing occurrence of multiple focal and/or solitary hepatocytic necroses preceding the process of fibrosis in the livers. Glucosinolates and their hydrolytic products were considered the most likely causative factors for the hepatocytic necrosis.


Isolation and characterisation of a murine picornavirus.

Cytopathic changes were observed in uninoculated primary cultures of mouse embryo fibroblasts. A virus resembling a picornavirus was isolated from the cultures. The virus produced cytopathic changes in mouse embryo fibroblast, chicken embryo fibroblast and Vero cell cultures. It was pathogenic for suckling mice and for chick embryos. Neutralising antibodies against the virus were present in animals of the parent colony.


Nocardia species as a possible cause of ovine abortion.

An instance of ovine abortion is described in which focal placental lesions were caused by a Gram-positive branching filamentous organism. The organism was present in well oxygenated tissues and so is thought more likely to have been a Nocardia sp than an Actinomyces sp.


Haemorrhagic liver syndrome of broiler chickens fed diets containing rapeseed products.

Haemorrhagic livers were observed in male white rock chicks of one to four weeks old, that were fed diets supplemented with 50 per cent rapeseed meal and 50 per cent rapeseed full-fat seeds. The haemorrhagic lesions were comparable to those of the laying hens except for the absence of fatty degeneration. There were no substantial fibrotic lesions. Multifocal or solitary hepatocytic necrosis was observed around the haemorrhagic lesions, although the necrotic foci did not always accompany the haemorrhage. The reticulum only of the necrotic and haemorrhagic lesions was not demonstrated with silver strain. Association of hepatocytic necrosis with liver haemorrhage and absence of argyrophilic fibres suggested that the hepatocytic necrosis was the primary contributory factor for the development of the hepatic haemorrhage.


The contribution of overwintering pasture larval infection and the spring rise as sources of Ostertagia circumcincta infection in lambs.

An investigation was made to study the acquisition of infection with Ostertagia circumcincta by lambs on land carrying residual infection, infection following the spring rise and both infections. Dry weather in June modified the usual pattern of herbage larval infection by delaying the peak of larvae derived from residual infection and cutting out the first half of the diphasic peak normally associated with the spring rise. It is suggested that prediction of the time when damaging infections develop on the herbage may be possible by a study of meteorological observations.


A comparative study of the responses of the thymus, spleen, lymph nodes and bone marrow of the albino rat to infection with Trypanosoma congolense and Trypanosoma brucei.

Using 90 albino rats, a comparison was made between the response to experimental infections of Trypanosoma brucei and T congolense of approximately three weeks duration by observation of parasitaemia, packed cell volume values, post mortem spleen and lymph weights, and histology of thymus, spleen, lymph nodes and bone marrow. In T congolense infection, phagocytosis of trypanosomes in the spleen appeared to be the main response of the host's haemopoietic tissues to the parasites, which were observed only intravascularly. In T brucei infection immunological responses occurred in the spleen and lymph nodes in addition to trypanosome phagocytosis. Trypanosomes were seen intercellularly in thymus, mediastinal tissue and lymph node sinuses and parasitaemia reached considerably higher values than in T congolense infection. Erythrophagocytosis in the spleen was the only histological feature which could account for the reduction in packed cell volume which occurred near death in both infections, medullary haemopoiesis being increased. Changes in the thymus, incorporating plasma cell production and depletion of cortical small lymphocytes, occurred in both infections.


Efficiency of praziquantel, a new cesticide, against Taenia hydatigena in the dog.

Praziquantel (2 - cyclohexylcarbonyl - 1,3,4,6,7,11b - hexahydro - 2H - pyrazino (2,1 - a) isoquinolin - 4 - one) was tested against artificially established infections of Taenia hydatigena in 39 dogs. The formulation used was a 660 mg tablet containing 50 mg of active ingredient (ai). A single oral dose at 1 mg/kg ai completely removed 14-day-old infections in all dogs. 2.5 mg/kg ai praziquantel was completely effective against 7, 14 and 28-day-old worms. 5 mg/kg ai completely removed two-day-old infestations. No side effects were seen in any treated dog.


The globule leucocyte in bovine schistosomiasis.

Globule leucocytes were detected in forestomachs, abomasum, duodenum, ileum, large intestine, lung, liver, bladder and kidney in cattle infected with Schistosoma mattheei. In animals examined seven and eight weeks after infection they were found only in the lungs. They were present in the alimentary tract from 18 weeks onwards. They were most numerous and most widely distributed in animals subjected to repeated, heavy infection. There was evidence that they were associated with the immune response of the host and that they were derived from mast cells.


Effects of storage on the methaemoglobin content of equine blood.

Equine blood containing different levels of methaemoglobin was stored under varying conditions and the methaemoglobin content was monitored during the storage period. Only under aerobic storage at 4 degrees C did the methaemoglobin content of all samples appear to remain stable.


Babesia divergens in splenectomised calves: immunogenicity of lyophilised plasma from an infected animal.

An experiment was carried out in which three groups of splenectomised calves were inoculated on three occasions at fortnightly intervals with lyophilised plasma from an animal reacting to Babesia divergens infection. Two weeks later these three groups of calves, together with three control groups, were challengpd with isologous, homologous or heterologous isolates of B divergens. Limited protection to isologous and homologous challenge was observed in the calves inoculated with plasma.


Porcine intestinal adenomatosis associated with serologically distinct Campylobacter sputorum subspecies mucosalis.

A variant of Campylobacter sputorum subspecies mucosalis which is serologically distinct from all strains previously examined is described. It has been isolated from cases of porcine intestinal adenomatosis and necrotic enteritis and in all other characteristics conforms to the description of mucosalis.


The effect of storage and handling on the activity of lactate dehydrogenase and its isoenzymes in horse serum.

The activity of lactate dehydrogenase and its isoenzymes in normal horse serum was studied under four conditions of storage. For storage periods up to three weeks freezing (-20 degrees C) was most satisfactory whereas for 24 to 48 h room temperature proved optimal. The most unsuitable temperature for lengthy storage was 4 degrees C. Storage of clotted blood for up to 48 h may result in haemolysis and unexpected rise in activity.


Experimental transmission of Babesia major by Haemaphysalis punctata.

Using a newly isolated strain of Babesia major and a clean strain of laboratory reared Haemaphysalis punctata it was shown that adult female ticks could be alimentarily infected by feeding on infected calves but that larvae and nymphae could not. All stages were able to transmit the parasite. Two syringe passages of B major resulted in a complete loss of infectivity to ticks.


Temperature-induced variations of blood acid-base status in the lugworm, Arenicola marina (L.): I. In vitro study.

Blood of the lugworm Arenicola marina studied in vitro behaved like a Rosenthal system: when temperature rose, pH decreased and PCO2 increased, whereas [HCO3] remained practically constant. pH values were low whatever the CCO2 and SO2. The temperature coefficient dpH/dt was always significantly different from the mean temperature-induced variations of the neutral pH of pure water between 0 and 30 degrees C. Consequently, the relative alkalinity of the blood, [OH-]/[H+], was very low (range, 1.53-5.06) and increased appreciably with temperature. Calculated changes in the fractional dissociation of protein imidazole groups, alphaIm, were smaller. The very variable buffer power of Arenicola hemoglobin was maximum (beta max) for a strictly defined, temperature-dependent value of pH (pH beta max), suggesting that as yet unidentified ionizable group on the hemoglobin molecule, RH, could be responsible for the pH-dependent changes of blood buffer power in Arenicola. Assuming pK'RH = PH beta max, the calculated fractional dissociation of RH, alpha RH, was constant between 0 and 30 degrees C. The nature of RH is discussed in relation with Reeves's hypothesis concerning the preeminence of protein imidazole groups in the regulation of extra- and intracellular pH.


Temperature-induced variations of blood acid-base status in the lugworm, Arenicola marina (L.): II. In vivo study.

Lugworms, Arenicola marina (L.), acclimatized at 16-17 degrees C, were acclimated at temperatures between 5.3 and 25.7 degrees C for 96 h. Whereas in vitro Arenicola blood behaves like a Rosenthal system, in vivo prebranchial blood does not: the higher the acclimation temperature, the lower the pHv and [HCO3]V, PVCO2, remaining practically constant. Nevertheless, the very low relative alkalinity of the blood in vivo ([OH-]/[H+] is less than 3), and the degree of dissociation of extra- and intracellular proteins, remain practically constant whatever the temperature. From examples in the literature together with these results, it is concluded that poikilothermic air-breathers and poikilothermic water-breathers regulate their blood pH in the face of temperature changes by contrasting mechanisms. In the first, regulation is almost instantaneous and takes place at the pulmonary level through adjustment of CO2 exchanges. In the second this regulation is slow and mainly extraventilatory, occurring through ionic exchanges. This contrast must be considered in relation with differences in blood PCO2 values, caused by the much higher O2 capacitance of air compared to water.


Placental diffusing capacity for carbon monoxide in unanesthetized guinea pigs.

In unanesthetized pregnant guinea pigs 5-7 ml of maternal blood which had been equilibrated with carbon monoxide (CO) was reinfused into the sow's carotid artery. Three serial blood samples were withdrawn from the sow and a single terminal fetal sample obtained for determination of CO content and hemoglobin  concentration. Transplacental CO uptake (VCO) was determined as the product of fetal blood CO content and fetal CO space (11.8% of fetal weight). Placental diffusing capacity (DPCO) was calculated by dividing VCO by the mean partial pressure difference between maternal and fetal blood. DPCO (ml-min(-1)/torr) increased significantly with gestational age: 45-50 days = 0.0413, 51-57 days = 0.1092 and 58-68 days = 0.1858. This increase paralleled fetal weight but was not related to placental weight.


Oxygen analyses of chicken embryo blood.

According to data obtained previously on the blood gas tensions and the oxygen dissociation curve of chicken embryos, the arteriovenous oxygen saturation difference in the allantoic circulation has been conjectured fairly large. In order to confirm this conjecture as well as to check the validity of the in vitro dissociation curve, both the blood oxygen capacity and content in allantoic artery and vein were measured. The in vivo O2 saturation measured here resulted in a similar value to that estimated from the dissociation curve. The O2 content in allantoic vein ranges from about 7 to 11.5 vol% during the 10th to the 18th days of incubation and that in artery is pronouncedly low in a range of 1 to 2.5 vol%, suggesting that the blood flow rate through the body tissues is fairly larger than that through the gas exchange capillary plexus. Then, the distribution of blood flow was estimated from the analyzed data based on a model of blood circulation and some assumptions. In connection with this estimation, the diffusing capacity for deoxygenation in the tissues was speculated to be much larger than that for oxygenation in the chorioallantoic capillaries.


Brain amino acids in conscious rats in chronic normocapnic and hypocapnic hypoxemia.

The influence of hypoxemia on the brain content of several organic acids and NH+4, AND ITS RELATIONship to the accompanying hypocapnia was studied in unanesthetized rats subjected to hypoxemia for periods ranging between 2 hours and 7 days. Under acute conditions, 'mild' hypoxemia (FO2 = 6--7%), these increases were greater and accompanied by increased gamma-aminobutyric acid (GABA) and decreased glutamic and aspartic acid levels; glutamine and NH+4 remained normal. When hypocapnia was prevented, 'severe' hypoxemia induced only a rise in GABA and slight elevations in lactic and alpha-ketoglutaric acid. During prolonged severe hypoxemia, the effects on the brain amino acids were maintained throughout, indicating that they are independent from the intracerebral pH which should progressively normalize. The effect on lactic acid gradually disappeared. The results show that during hypocapnic hypoxemia the rise in brain GABA is hypoxemia dependent, the decrease in glutamic and aspartic acid is hypocapnia dependent and the increase in lactic acid is in a large way alkalosis dependent.


[Benign multi-recurrent endothelio (?)-leukocytic meningitis].

A third of a century after the confirmation of this new entity, the author gives a current review of the clinical, general and aetio-pathogenic characteristics and course, based upon personal research and the published literature. Nothing is to be added to or subtracted from the original description but all remains to be discovered as far as aetio-pathogenesis is concerned.


[Benigne multi-recurrent meningitis (Mollaret's disease). A case in a child of 2 years and 8 months].

The authors report a case of meningitis, presenting all characteristics of the disease described in 1944 by P. Mollaret, occurring in a child aged 2 years and 8 months. They stress the rarity of cases on childhood. The cells found in the cerebrospinal fluid, photographs of which are included, are fragile and may undergo early lysis. They are present in association with lymphocytes and polynuclears, giving the slide examined a highly characteristic mottled appearance. The authors raise the question of the morphological similarity of these large cells, with their polygonal contour and small central nucleus, with an epithelium.


[Disturbances of wakefulness, sleep and respiratory function in Steinert's disease].

36 night sleep recordings were carried out on 15 patients suffering from myotonia dystrophica. 9 of these patients complained of diurnal hypersomnia. 10 patients had a disturbance of night sleep with a reduction of REM sleep sometimes associated with interruption of the recording with an increase in the light stages of sleep or alternatively with an increase of REM sleep with a reduction in the latency period of the first paradoxical sleep or with narcoleptic elements. 13 patients had abnormally early abolition of chin EMG activity, almost on falling asleep. 11 cases had pathological apnoeic episodes during sleep and in 9 of the 10 patients who underwent respiratory function studies there was a restrictive airways defect. In addition 9 had frank hypoxia without hypercapnia and 4 a right to left shunt. 3 clinically unaffected patients but with affected relatives were also investigated, 2 were found to have sleep disturbances 1 of which was associated with early abolition of tone.


[Striato-nigral degeneration. Clinical and anatomic study of a case which responded favorably to L-Dopa].

The authors have reported the case of a 65 year old woman followed for almost 4 years with an akineticrigid Parkinsonian syndrome which responded well to levodopa. Waning of response finally occurred and despite the addition of a peripheral dopa decarboxylase inhibitor the patient died suddenly. Autopsy examination revealed pure nigro-striatal degeneration without any additional pathology. The report deals primarily with purity of the Parkinsonian picture and especially with the conspicuous and prolonged effect of levodopa.


[Landouzy-Dejerine syndrome. Evolution of the concept of facio-scapulo-humeral amyotrophia].

Detailed analysis of the literature and the study of personal cases have led the authors to propose a new concept for facio-scapulo-humeral dystrophy. They consider it to be a syndrome, embracing under the same clinical picture both muscular disease (classical hereditary muscular dystrophy, congenital and acquired myopathies) and neurological disease (in particular progressive pseudomyopathic amyotrophy).


[Preoperative approach to the histologic diagnosis of cerebral tumors by combination of clinical and paraclinical examinations (EEG, computerized cerebral tomography, scintigraphy, and angiography)].

The authors present their last series of one hundred operated cerebral tumors (19 meningiomas, 16 benign gliomas, 38 malignant gliomas, 20 isolated metastasis, 8 diversified tumors) studied on the clinical, E.E.G., isotopic scanner, computorized tomographies and angiographic point of view. The comparison of these multiple exams, permits one to determinate the malignant of benign nature of a tumor in 86 p. 100 of the cases and the precise histological nature in 56 p. 100 of the cases. The biopsy effectuated in stereotaxic conditions permits to solve the problem in uncertain cases. The interest of computorized tomography is emphasized (discovery or confirmation of a suspected tumor, definition of its extension in depth), but this recent technic is incapable of constant confirmation of the histological diagnosis; it cannot replace other confirmed methods of diagnosis. The angiography remains necessary to guide the surgical gesture.


[Anatomo-clinical study of a case of "ophthalmoplegia plus" with analysis of muscular, central nervous, ocular, myocardial, and thyroid lesions].

This study deals with a case of "ophtalmoplegia plus" with histochemistry and electron microscopy of a muscle biopsy and full pathological examination in a 29 year old woman. Ragged-red fibers with abnormal mitochondria, cerebral spongiosis mostly involving white matter, perimacular pigmentary retinopathy and scattered myocardial fibrosis interrupting the Hiss'bundle were found. A goiter with hypersecretion of thyroid hormones and thyroid and ocular muscles changes characteristics of Graves' disease without any hypermetabolism occurred in her late twenties. This could be related to the absence of response from the abnormal mitochondria to the thyroid hormones.


[Bismuth myoclonic encephalopathies. Their course and lasting or definitive late complications].

Acute myoclonic encephalopathy related to the ingestion of bismuth salts has been known for 3 years and would appear to be reversible. Of a total of 41 cases, 32 were observed for an average of more than a year. Alongside the commoner benign forms, there coexist severe forms, sometimes fatal, prolonged forms and complicated forms. Permanent deterioration, affecting memory above all, tremor, marked insomnia, headache and disturbed gait are amongst the most durable complications, sometimes definitive, whilst in four cases osteo-arthropathy of the shoulders was associated with permanent invalidism.


[Senile subcortical neurofibrillary degeneration with the presence of twisted tubules and straight filaments. Atypical form of progressive supranuclear paralysis].

A case with wide-spread subcortical neurofibrillary changes, cell loss and gliosis in a 81 year old man is described. The most affected areas were both pallida, Luys subthalamic bodies, the substantia nigra and the denate nuclei of the cerebellum. The cerebral cortex contained only a few senile plaques. We interpreted this case as a variety of progressive supranuclear palsy despite the lack of the typical supranuclear ophtalmoplegia and of superior colliculi involvement. In the subthalamic body and in the substantia nigra fibrillary tangles were investigated ultrastructurally and found to consist of two kinds of fibrillary material: straight fine filaments of 100 A and twisted tubules with an average diameter of 200 A. We did not see 150 A straight filaments like those found in some cases of progressive supranuclear palsy. The possible significancy of each kind of neuro-fibrillary tangles and of their simultaneous occurrence in the subcortex of this case is discussed.


[Abnormal movements caused by L-DOPA in patients with Parkinson's disease: correlation with the plasma concentrations of DOPA and O-methyl-DOPA].

This study involved twleve parkinsonian patients exposed to abnormal movements provoked by L-DOPA. Including six patients with "mid-dose" dyskinesias and six others with "onset and end of dose" dyskinesias, Correlation between the circumstances of onset of abnormal movements and plasma concentrations of DOPA and O-methyl-DOPA, after administration of a dose of L-DOPA + IDC, gave the following results: 1) mid-dose dyskinesias appeared with the highest plasma concentrations of DOPA, at the maximum therapeutic effect; 2) onset and end of dose occurred during rise and fall in plasma levels of DOPA, coinciding with the relief and the reappearance of parkinsonian symptoms respectively; 3) no correlation could be established between plasma concentrations of O-methyl-DOPA and the duration of the period of clinical remission or of abnormal movements. These biochemical data, completed by the neuropharmacological study of one patient with onset and end of dose abnormal movements suggest the predominant role of a disturbance in central dopaminergic mechanisms in the genesis of abnormal movements, whatever their nature.


[Shy-Drager syndrome with disturbances of the respiratory rhythm and consciousness. A propos of an anatomo-clinical case].

The case, including pathological description, of a 65 year old man is presented. Severe disturbances in respiratory rhythm and consciousness occurring during wakefulness and sleep, progressing by acute exacerbations, developed after the disease had been present for 4 years and resulted in death after three months. Small degenerative lesions of the pontine nucleus, the locus coerulus, the intermedio-lateral column and the substantia nigra were seen.


[Chronic ischemia of the anterior horn of the lumbar swelling of the spinal cord. Angiographic study in a subject with herniation of the T12-L1 discs].

On the basis of a case of almost pure involvement of the anterior horn with chronic progression in an individual with a low thoracic herniated disc (T12-L1), the hypothesis is discussed of the role of ischaemia of the lumbar swelling. Angiographic arguments (displacement of the anterior spinal axis and unusual distribution of anterior spinal afferents) perhaps make it reasonable to speak of "chronic ischaemic poliomyelitis" in the absence of pathological examination.


[Water intoxication after polydipsic episodes. (8 cases)].

Eight cases of convulsive coma by water intoxication without predisposing disease in the majority of instances in psychiatric patients, added to 25 cases from the literature make it possible to describe a stereotyped picture of "psychogenic" water intoxication. This includes episodes of polydipsia preceding convulsions and altered conscious level, accompanied by severe hyponatraemia. Cure occurs spontaneously after an acute hypotonic polyuric phase. Study of free water clearances and dynamic ADH suppression tests demonstrate hypovasopressinism which is difficult to inhibit, with "lower osmoreceptor reset". This abnormality is transient and sometimes relapsing.


[Forced downward and convergent deviation of the eyes and periodic ocular movements in aneurysmal hemorrhage of the mesencephalic tegmentum].

The authors report a case of forced convergent and downward deviation of the eyes with paralysis of upward gaze and, at times, with lateral periodic alternating movements. Pathological examination disclosed a subarachnoid aneurysm behind the midbrain with a fresh hematoma within the mesencephalic tegmentum at the level of the superior colliculi. The clinical and pathological data are discussed.


[CT diagnosis and differential diagnosis of renal spaca occupying lesions (author's transl)].

In 76 patients with space occupying lesions of the kidneys CT scans were performed. Size, shape and localisation of the kidneys could well be demonstrated by this method. Space occupying lesions were clearly seen, and solid tumors could be differentiated from cysts. However differential diagnosis between either primary renal cell carcinoma and metastases or between malignant and benign mass lesions was not possible. There was no problem in the diagnosis of hydronephrosis where as a differentiation between inflammatory changes and solid masses proved to be difficult. CT scanning seems to be usefull in the diagnosis of renal space occupying lesions. As a non invavise method it should be performed previous to renal angiography, which thereby becomes unnecessary in many cases.


[Ultrasound diagnosis of the liver and gallbladder (author's transl)].

Ultrasound echography has proved a non-invasive, reproducible, harmless and, for the patient, not burdensome technique for the diagnosis of diseases of the liver and bile ducts in the right upper abdomen. Diffuse changes of the organs and disease of the bile ducts as well as cystic or tumorous solid changes in the upper abdomen are the main spheres of sonography. The use of "grey value" techniques has increased the efficiency of compound ultrasound examinations. We can expect further improvements with digital computerised evaluation of signals.


[New aspects of liver scintigraphy (author's transl)].

The development of the scintillation camera computer scintigraphy has created new chances for nuclear medicine diagnosis of the liver. With the development of new 99mTc-labeled radiopharmacenticals the effectiveness of functional scintigraphy of the liver in the differential diagnosis of parenchymal and mechanical icterus could be considerably increased. Computer perfusion scintigraphy permits proof of circulatory changes in the liver without invasive techniques. Its importance lies in early diagnosis of portal hypertension and in pre- and post-operative assessment of liver circulation after shunt surgery.


[The endoscopic retrograde cholangiography (author's transl)].

This is a report of 760 endoscopic cholangiographic procedures. 76% of all examinations answered the given clinical problem. Prepapillar stenosis of the choledochus resulting from pancreatic diseases can be found in 35% of all pathologic findings. The diagnosis of a possible stenosis of the papilla Vateri is not facilitated by a retrograde cholangiographic examination. The intravenous cholangiogram with special regard to bile drainage seems to yield more information. A common drainage hindrance of the pancreatic and bile duct in connection with a stenosis of the papilla was shown in 26%. In 65% of patients with a postcholecystectomy-syndrome organic disease could be demonstrated which made a second operation necessary.


[Results of transjugular antegrade cholangiography and retrograde portography (author's transl)].

Via the jugular approach to the liver diagnosis of the liver could be extended by transjugular cholangiography, liver biopsy and retrograde portography. Transjugular cholangiography makes possible an antegrade picture of the bile ducts - particularly when conventional techniques or retrograde measures fail. 85% of blocked bile ducts were recognized. Transjugular liver biopsy complements cholangiography. Tissue can be removed from right and left lobes of the liver. Retrograde portography makes possible assessment of hemodynamics of the liver in portal hypertension before and after shunt operations. Isolated pictures of portal circulation in the right or left lobes permits clear allocation of tumorous or parasitical disease in the respective parts of the liver. This is of special importance for surgery of the liver, a precondition of hemihepatectomy.


[Long-term control of reproducibility of automatic developers (author's transl)].

Variability of blackening of X ray films may be due to inconstant concentration or temperature of the developer. Reproducibility was examined with stepwise blackening, exposed under standard conditions and densitometrically evaluated after development. The resulting differences of blackening are without significance for the subjective assessment of X ray films, since they lie within +/- 10%.


[The so-called interstitial pulmonary diseases (author's transl)].

The so-called interstitial pulmonary diseases are considered diseases of the pulmonary parenchyma and discussed according to different pathogenesis and etiology. The disturbance of function is emphasized. On the examples of allergic alveolitis, fibrosing alveolitis, drug damage to the parenchyma and shock-lung the clinical appearances of diseases of pulmonary parenchyma are discussed. Diagnostic methods are described and the causes of faulty interpretation are examined.


[Transvenous xerotom-angiography of the pulmonary hilus (author's transl)].

Normal-size lymph-nodes and air-filled bronchi do not contribute significantly to the shadow of the normal hilus. This consists mainly in pulmonary arteries and veins of the upper lobes. Any enlargement beyond the vascular shadow has to be considered as pathologic. Xerotom-angiography following injection of contrast medium into the cubital vein shows the pulmonary vessels near the hilus more clearly. Pulmonary arteries towards the truncus are better shown. This improves the clarity of the hilus. Coincident demonstration of the superior vena cava may show pathologic processes in the upper mediastinum.


[Radio-isotope investigations in bone and joint disease (author's transl)].

Scintigraphy of the skeleton has a definite place. It is indispensable in examinations of clinically or radiologically doubtful lesions and should be routinely used for the classification of malignant tumors. Scintigrams may often provide additional information to radiographs and make possible more precise diagnosis or assessment of results of treatment.


A critical examination of distortion measurement in hearing aids.

This study was designed to examine relationships between measures of total distortion (TD) and individual 2nd and 3rd harmonic distortion in various types of hearing aids. Measures of 2nd harmonic, 3rd harmonic, and TD were determined for six instruments. Analysis of the results revealed that little additional information is obtained from a measure of TD as opposed to individual harmonic measures. Furthermore, in two instances TD measures resulted in erroneously high distortion readings because of ambient and system noise. It is recommended that in less than ideal acoustic environments, measures of 2nd and 3rd harmonic distortion be used in lieu of TD.


Influence of overstimulation on temporary threshold shift and the onset of aural overload.

This investigation sought to examine the sensitivity of pure tone thresholds and the onset of aural overload to the fatiguing effects of broad band noise. Noise levels ranging from 35 to 110 dB SPL were presented to 8 normal hearers. Post-exposure pure tone thresholds were determined for octave frequencies 500-4000 Hz while aural overload thresholds were obtained for the fundamental frequencies of 500 and 2000 Hz. Aural overload thresholds were found to decline following exposure levels insufficient to produce measurable TTS. This was particularly evident for low-frequency stimuli (below 2000 Hz). Results suggested that the aural overload test may be a more effective indication of cochlear damage than is the traditional temporary threshold shift procedure. These findings are discussed in terms of the "injured hair cell" hypothesis proffered by Wever & Lawrence (1955).


Respiration audiometry.

Since 1971 an impedance-plethysmographic method was been used to record changes in the breathing pattern of 218 high-risk infants during acoustic stimulation. The results of this technique, known as respiration audiometry, show that acoustically induced changes in the breathing pattern can be used as a hearing test for very young children. The results fall into four categories: excellent readability (45%), good readability (32%), readable (15%), not readable (8%). Respiration audiometry makes it possible in most cases to ascertain a child's hearing level. The neonatal period and early infancy are the ages best suited for investigations with respiration audiometry. The reliability of this method was found to be good.


Eustachian tube function and size of the mastoid air cell system in middle ear surgery.

Myringoplasty results in patients with poor tubal function and small cell systems are often disappointing, to both patient and surgeon. Surgical procedures to improve tubal function have been introduced but they all have the disadvantage of being rather elaborate and difficult to perform. The mastoid air cell system on the other hand does not offer the same problems of access. With the concept of creating an air-filled cavity in connection with the middle ear, mastoidectomy was performed in myringoplasty cases with poor tubal function and small (less than 9 cm2 lateral area) cell systems. Preliminary results show a healing rate of 82% in patients managed according to these principles, against 50% in corresponding cases when myringoplasty alone was done.


A quasi-free-field transducer system for high-frequency audiometry.

Previous attempts to measure human hearing capacity in the high frequencies (8 to 20 kHz) have only been met with rather limited success. Based on the results of Shaw and co-workers we have developed a free-field transducer system where the stimuli are delivered from a point source and meet the ear as plane progressive waves at a carefully chosen angle of incidence. The system can be calibrated in a precise manner by means of a specially designed coupler. Preliminary results indicate that the procedure is easily applicable also in a group of inexperienced test subjects and the test-retest variability was within such limits that are acceptable for subjective audiometric testing. These results require validation in a large group of subjects and we hope it will be possible to establish normative values for various age groups.


Electrocochleography: a comparison of action potential and behavioral thresholds.

Using the technique of electrocochleography with transtympanic electrode placement, it is possible to estimate behavioral thresholds from AP data for a acoustic stimulus. The correlation between behavioril and AP "thresholds" for the same stimulus was statistically significant and there was a better correlation for subjects with a mild hearing loss than for those with normal hearing or larger degrees of hearing loss (as determined by the pure tone average). Larger amplitudes of the AP at the maximum stimulus level tended to be associated with a more accurate threshold estimation. The AP "thresholds" showed best correlation with the pure tone audiometric thresholds at 1 000 Hz, at other tone frequencies the correlation was poorer. This agrees with the spectral contents of the click.


Listening levels through hearing aids: a difference of opinion.

The present authors find it impossible to compare their work with that of Powell & Tucker (Scand Audiol 5, 167, 1976) due to the lack of original data in the latter paper. The present authors papers were not written with the prime view of presenting predictive values but of reporting data on hearing aid users. The predictive value of our results has been largely and not very carefully inferred by Powell & Tucker. The predictive values of gain or output may be inferred from current research and the Powell & Tucker paper confirms the previous work rather than repudiates it. It is obvious that research workers should co-operate in using clearly stated methods and publishing original data in their papers. Furthermore it is important that the terminology used is of a standard form--or if not, that each new term is clearly defined.


Effect of high-pass filter on auditory brain stem responses to tone pips.

The effect of high-pass filters on the vertex-positive brain stem response to tone pips at 500, 1000, 2000 and 4000 Hz was investigated in normal adults. The tape-recorded responses were averaged through high pass filters with 3 dB attenuation at 50, 100 and 200 Hz and with a slope of 6 dB/oct, and their amplitudes were compared with those of the averaged responses without filtering. These 3 filters reduced the amplitudes of the responses to 500-Hz tone pips by 3.3, 7.1 and 10.6 dB respectively. On the other hand, the mean attenuations caused by the same series of filters on the response amplitudes at 2000 Hz were only 0.2, 2.9 and 5.4 dB respectively. The responses at 4000 Hz were similar to those at 2000 Hz. This distinct difference in the effect of the high-pass filters suggests that the dominant frequency component of the brain stem response at 500 Hz is significantly lower than that at 2000 Hz and above. The results indicate that the use of a high-pass filter with cutoff frequency over 50 Hz is not recommended for recording the slow positive deflection of the brain stem response to low frequency tones.


Factors increasing the risk for hearing loss in 'pop' musicians.

Hearing thresholds were determined in 83 'pop' musicians with an average age of 26 years, average exposure time of 9 years and average weekly exposure time of 18 hours. The following factors had a statistically significant influence (p 95) on hearing: ageing, brief exposure per session, long exposure time in years (2 kHz), participation in military service (250 Hz), listening to pop music with head phones (2 kHz).


The eustachian tube function in secretory otitis media in children: a follow-up study.

Twenty-three patients suffering from secretory otitis media were examined. The mean age of the group was 6 years. Adenoidectomy and insertion of polyethylene tympanostomy tubes was made. The tubal function was studied by measuring the middle ear pressure on the morning after operation and once a month during the following five months by using the air pressure equilibration technique. In 23 ears (79%) the pressure was considered to be normal and in 10 ears (30%) abnormal at the first measurement. After 5 months the corresponding groups were 26 (79%) and 7 (21%).


Urea and hearing in patients with menière's disease.

Transient hearing improvement was recorded in around 60% of patients with Menière's disease 2 hours after the ingestion of 20 g of urea perorally. Urea slightly increased the serum osmolality, which is thought to cause a transient reduction of the endolymphatic hydrops. Urea has no inconvenient side effects and is recommended primarily as a test substance for the verification of endolymphatic hydrops, in conformity with glycerol.


Satisfaction with fitted hearing aids. I. An analysis of technical information.

By means of a questionnaire, satisfaction with fitted hearing aids has been judged 6 months after prescription. An analysis of the information obtained, together with some audiological features of 155 patients with hearing aids is reported. The influence of the most important factors is discussed and the findings are compared with those of other surveys. The relationship between satisfaction, and the degree of hearing loss and discrimination loss is very weak. The conclusion is that the population consists of sub-populations in which different criteria apply to hearing aid satisfaction. These criteria may be more closely related to psycho-social factors than to technical aspects. A second part of the study is devoted to that subject.


The "eardrum artifact" in ipsilateral reflex measurements.

A source of error in ipsilateral reflex measurements with impedance methods is explained. It is shown that the inherent non-linearity of the cavity represented by the ear canal and tympanic membrane gives rise to an artifact in the measurement of acoustic impedance which is synchronous with the stimulus. The magnitude of the artifact increases with the intensity of the stimulus, but is relatively insensitive to the frequency of the stimulus. A practical method for measuring the magnitude of the artifact is described.


Inhibition of branched-chain amino acid degradation by ketone bodies.

The present study deals with mechanisms for the accumulation of intermediates in the catabolism of branched-chain amino acids in patients with ketoacidosis. Two different systems have been developed to measure the degradation rates of leucine and valine intermediates in rat liver mitochondria. 3-Hydroxybutyrate was found to inhibit the conversion of isobutyryl-CoA to propionyl-CoA, and this appeared to be partly due to an elevated NADH2/NAD ratio. 3-Methylcrotonyl-CoA carboxylase was strongly inhibited by acetoacetyl-CoA and to a lesser extent by the nonesterified ketone bodies. These inhibitory effects of ketone bodies may explain the accumulation of branched-chain amino acid intermediates during ketoacidosis.


Plasma renin activity, angiotensin II, and aldosterone after mental arithmetic.

Plasma renin activity (PRA) and the concentration of plasma angiotensin II and aldosterone, blood pressure, heart rate, serum electrolytes and some haematological parameters were measured in six male subjects who carried out exercises in mental arithmetic for a period of 20 min. After this mental exercise the PRA and angiotensin II values increased significantly, but plasma aldosterone showed a tendency to decrease. The highest mean increases in PRA (56.0%, P less than 0.02) and in angiotensin II (66.0%, P less than 0.001) were found 15 min after the challenge. Immediately after the mental activity systolic blood pressure was increased by 10.3% (P less than 0.005), diastolic blood pressure by 10.3% (P less than 0.02) and heart rate by 19.7% (P less than 0.001) over the pre-test values. There were no significant changes in serum electrolyte levels until 1 and 2 h after the exercises, at which time the serum potassium values were slightly, but significantly (P less than 0.005) decreased. There were no significant changes in the haematological parameters studied (blood erythrocytes, leucocytes, haemoglobin, haematocrit, and the volume, amount of haemoglobin, and haemoglobin concentration of the red cells). A positive correlation (r = 0.9389, P less than 0.01) was found between the increases observed in the PRA and in heart rate. The changes found in PRA and in the concentration of plasma angiotensin II after these exercises in mental arithmetic resemble those found previously, after physical and heat stress.


Ethanol effects of substrate utilization by the human brain.

Arterial concentrations and arterio-jugular vein differences of ethanol, acetate, glucose, lactate, pyruvate, glycerol, free fatty acids and ketone bodies were determined in seven healthy male volunteers before and during an infusion of ethanol, which gave a blood alcohol concentration of about 12 mmol/l. Arterial-jugular vein (A-JV) oxygen differences were unchanged throughout the study. Ethanol caused a small reduction in blood glucose concentration, from a mean of 5.1 to 4.7 mmol/l, and the A-JV difference fell significantly. When alcohol was given, arterial acetate concentration rose quickly to about 1 mmol/l and was unchanged thereafter. All subjects had a positive arterio-venous difference for acetate. Arterial lactate concentration was doubled by ethanol and the normal release from the brain was abolished. Arterial alanine concentration decreased significantly, from 0.19 to 0.16 mmol, when alcohol was given but no net exchange by the brain could be observed. It is concluded that: (a) acetate can be taken up by the brain and if totally oxidized, could account for 6% of the oxygen consumption; (b) glucose arterial-jugular vein difference is decreased by ethanol, suggesting an attenuation in glucose uptake; and (c) lactate net release is abolished by alcohol, probably due to the increased arterial concentration.


Studies on methods for determination of the distribution of cardiac output in the mouse.

Different techniques for determining cardiac output distribution in the mouse have been studied. The soluble indicator technique using injection of rubidium on the right side of the heart was found to give a satisfactory reproducibility which made it possible to determine cardiac output fractions in the normal mouse. The use of radioactivity-labelled microspheres, which must be injected on the side of the heart, was found to give unreliable and non-reproducible results. This was due to difficulty in depositing the microspheres into the left ventricle both when a catheter was inserted via the right carotid artery, or by means of cardiac puncture.


Relation between zinc content in saliva and blood in healthy human adults.

Measurements were made of zinc levels in saliva, whole blood and plasma as well as copper levels in plasma by atomic absorption spectrophotometry. The mean zinc concentration (in ppm) was 0.478 (n = 136) in resting mixed saliva, 0.046 (n = 36) in parotid saliva, 6.41 (n = 145) in whole blood and 0.87 (n = 145) in plasma. The whole blood zinc levels were significantly lower in females than in males (P less than 0.001). Females and blood donors (males) had a significantly (P less than 0.001) higher Cu:Zn ratio than males (non-donors). It would thus appear, first, that the local effect of salivary zinc cannot be assessed simply from the concentration of zinc in stimulated parotid saliva since about nine-tenths of the zinc in resting mixed saliva is derived from other sources and, second, that the Cu:Zn in plasma is the most eligible variable for detecting sub-clinical Zn deficiency.


Radioimmunoassay of serum-conjugated deoxycholic acid.

A specific, sensitive, and reliable radioimmunoassay for serum-conjugated deoxycholic acid has been developed with antiserum obtained after immunization of rabbits with deoxycholic acid--bovine serum albumin conjugate. The displacement curve of glyco [3H] deoxycholic acid was linear on a logit-log plot from 7.5 to 320 pmol of unlabeled glycodeoxycholic acid. At 50% displacement of bound label, the cross-reactivity of taurodeoxycholic acid was 100%, deoxycholic acid 30%, taurocholic acid 3%, and glycocholic acid 2%. No cross-reactivity was observed with free cholic acid, conjugated or free chenodeoxycholic acids and conjugated or free lithocholic acids. Fasting serum-conjugated deoxycholic acid concentrations in 10 healthy volunteers ranged from 0.18 to 0.92 mumol/1. Over a period of 5 hours following 0.5 g oral cholate administration the serum-conjugated deoxycholic acid concentration did not change in 5 fasting healthy persons, whereas an initial increase of serum cholic acid was observed.


Coagulation factors and other plasma proteins during abstinence after heavy alcohol consumption in chronic alcoholics.

Coagulation factors and other plasma proteins were studied in 19 male chronic alcoholics during the first abstinence week after a period of heavy alcohol consumption. In spite of a decade of chronic alcoholism and a daily alcohol consumption before admission of more than twice the 'normal' alcohol-metabolizing capacity, the data indicated a well-preserved protein-synthesizing capacity. In fact, the mean levels of some liver-synthesized proteins were above the upper reference limits. Minor changes within the reference ranges during the abstinence suggested a declining acute inflammatory reaction after cessation of intoxication.


Amyloidosis and Crohn's disease.

Amyloidosis associated with Crohn's disease was found in 7 patients among 85 subjected to intestinal resection for granulomatous enterocolitis. Most of the patients had symptoms of inflammatory bowel disease of relatively short duration before the diagnosis of amyloidosis was made and were without suppurative complications. Systemic involvement was seen in 6 of the patients. One died postoperatively from renal failure, and in 2 other patients kidney transplantation was performed because of deterioration of a pre-existent renal insufficiency. Six patients were alive 6 months to 10 years after amyloidosis was diagnosed. There is great risk of rapid deterioration of kidney function postoperatively in these patients. However, our experience suggests that in some cases the progression of amyloidosis may be delayed or even brought to a halt after surgical treatment of Crohn's disease.


Intestinal activities of trypsin, lipase, and phospholipase after a test meal. An evaluation of 474 examinations.

After indirect stimulation of the pancreas by means of a test meal the intestinal activities of trypsin were determined in 452 subjects, lipase in 117, and phospholipase in 57. Trypsin levels were subnormal in 88%, lipase levels in 80%, and phospholipase levels in 81% of patients with chronic pancreatic disease. The outcome of repeated tests (trypsin) was completely consistent in 20 out of 22 patients. Calculations of ratios between the enzymes studied suggested that lipase was the enzyme most susceptible to pancreatic damage. Also in cases of celiac disease and after Polya gastric resection, the decrease of the intestinal lipase concentrations was more marked than that of the other enzymes. In 9% of the cases of chronic pancreatic insufficiency the diagnosis would have been overlooked if either lipase or trypsin had been determined as the sole enzyme. In clinical practice it is recommended to estimate at least two enzymes, because abnormal ratios may be of diagnostic value and because the two different groups of enzymes provide a mutual check on the secretory capacity of pancreatic enzymes. On the whole, the test was found to be reliable, simple, physiological, and inexpensive in terms of resources, and it is highly recommended as a routine test of the pancreatic function.


Serum isoamylase pattern in obstructive pancreatic disease.

On agarose gel electrophoresis the pancreatic serum isoamylases can be separated into a main fraction and more anodally migrating minor fractions. In acute pancreatic hyperamylasemia as in normal subjects the activity of the anodally migrating pancreatic amylase does not exceed 20% of the activity of the main fraction. In patients with pancreatic main duct occlusion or stenosis with or without calculi or cysts, the anodally migrating pancreatic amylase increases proportionally more than does the main fraction, and can even be stronger than the main fraction. The majority of these patients also had abnormally increased total pancreatic serum amylase activity.


Changes in pancreatic and intestinal enzyme activities following chenodeoxycholic acid feeding.

The effect of CDCA feeding on pancreatic and intestinal enzymes was studied. Mice were fed 0.5% w/w chenodeoxycholic acid in a normal diet. Pancreatic lipase concentration was significantly increased after 3 days on the CDCA diet, while amylase and trypsin concentrations were significantly higher at 23 days when compared with the controls. At 70 days there was a significant increase in the concentrations of amylase, trypsin, and lipase. Protein concentrations paralleled the rise in enzyme levels. Amylase and lipase, when measured as specific activities, were still higher than the controls at 70 days. Intestinal amylase levels did not change during the experiments, but intestinal alpha-glucosidase activity increased significantly in the CDCA-treated animals. The results are discussed in terms of their similarity with those reported to occur after feeding soybean trypsin inhibitor.


A prospective comparative study of clinical and histological characteristics in Icelandic and Danish patients with gastric ulcer, duodenal ulcer, and X-ray negative dyspepsia. I. Design and clinical features.

Iceland (IS) and Denmark (DK) are ethnically, culturally, and economically closely related Nordic countries, but gastric cancer is much more frequent in Iceland, and other differences in the occurrence rates of gastric diseases are also suspected. Therefore a cooperative study was initiated comparing Icelandic and Danish patients with gastric ulcer (GU), duodenal ulcer (DU), and X-ray negative dyspepsia (XND) as regards clinical features, external factors of possible importance for gastritis and cancer, gastroscopic appearance, and histological gastric mucosal changes. The project lasted one year and comprised 93 Icelandic and 88 Danish patients. A large number of comparisons showed a high degree of similarity between Icelandic and Danish patients. Significant differences were found in tobacco consumption (DK greater than IS), duration of symptoms in XND (IS greater than DK), whereas the positon ratio of GU (IS less than DK) and acetylsalicylic acid consumption (DK greater than IS) showed non-significant trends. Significant difference was found between the occurrence of diffuse macroscopic changes of the gastric mucosa (IS greater than DK), which corresponds to the histological differences to be described in a subsequent article.


Inhibition of basal and pentagastrin-stimulated gastric acid secretion after treatment with benzilonium bromide and after selective proximal vagotomy.

50 consecutive patients with radiographically verified duodenal ulcer and a history of peptic ulcer disease for more than 3 years and with elevated gastric acid secretion in the basal state and after stimulation with pentagastrin were randomly allocated to two groups. The first group of 25 patients was treated with benzilonium bromide (Ulcoban Prolongatum, Parke, Davis & Co.) and the second group was subjected to selective proximal vagotomy (SPV). The patient's gastric acid secretion was determined before the start of treatment and after 1, 6, and 12 months. After one year the basal acid output had decreased by 58.2% in the group treated with benzilonium bromide and by 82.9% in the patients who had undergone SPV. The peak acid output fell by 49.4% in the benzilonium group and by 66.1% in the SPV group.


The frequency of marcroamylasemia and the diagnostic value of the amylase to creatinine clearance ratio in patients with elevated serum amylase activity.

190 patients with elevated serum amylase levels were tested for macroamylasemia and the amylase to creatinine clearance ratio. Macroamylasemia was found in 3 patients. In these patients macroamylasemia persisted after the total activity of serum amylase had fallen to nearly normal levels. The Cam/Ccr-ratios were determined 14 times in the 3 macroamylasemic patients. Only one of the 14 values was clearly less than 1%. Cam/Ccr-ratios above 4% were found in 83 patients. In 56 of them the diagnosis of acute pancreatitis could not be confirmed. 19 out of 46 patients with the established diagnosis of acute pancreatitis had Cam/Ccr-ratios below 4%. Cam/Ccr-ratios below 1% were also found in patients without macroamylasemia. It is concluded that high and low Cam/Ccr-ratios are not specific for acute pancreatitis and macroamylasemia, respectively, and--moreover--that a normal Cam/Ccr-ratio excludes neither acute pancreatitis nor macroamylesemia.


The prognosis of idiopathic proctitis.

Follow-up studies of 2 groups of patients with idiopathic proctitis show that the survival rate is little affected by the disease. The cumulative probability of extension of the inflammation to the descending colon above the left iliac crest was about 5% at 5 years and 12% at 10 years. Corresponding figures for extension to the hepatic flexure were about 4% at 5 years and 6% at 10 years. The probability of radical surgical treatment was 3--5%.


Rates and mechanisms of glucose, galactose, and xylose absorption in man in vivo.

Jejunal absorption-rates of glucose, galactose, and xylose were determined consecutively, using a double-lumen tube perfusion technique, in 6 Arab subjects in vivo; perfusion solutions contained 200 mmol/l of each monosaccharide. Mean xylose absorption rate was significantly lower than that for glucose (P less than 0.001) and galactose (P less than 0.001). In order to investigate evidence that glucose and xylose share the same jejunal transfer mechanism, their absorption-rates when given alone and together, at high concentrations, were determined in 6 other Arabs; perfusion solutions contained (1) 200 mmol/l glucose, (2) 100 mmol/l xylose, and (3) 200 mmol/l glucose + 100 mmol/l xylose. Rates of glucose and xylose absorption were not significantly influenced by the other monosaccharide. This study does not therefore confirm existence of a common transfer mechanism. A significant correlation between absorption rate of glucose and weight of xylose excreted after a 25 g oral load (P less than 0.05) was demonstrated.


The parathyroid glands in experimentally induced hypergastrinemia in the rat.

The morphology of the parathyroids in rats with hypergastrinemia, induced by antral exclusion, was compared with that of glands from untreated rats and animals from which the main source of gastrin- 17 was excluded (antral resection). Fourteen weeks after induction of hypergastrinemia the volume of the parathyroids was significantly increased owing to hyperplasia of the parenchymal cells. Removal of the antral gastrin-producing capacity of the same duration was not accompanied by any significant changes in the parathyroids. These findings suggest that hypergastrinemia could be a stimulus for the development of hyperplasia of the parathyroids, and that it may be an etiological factor in the production of hyperparathyroidism.


The influence of graded distension and carbachol on the motor response to cholecystokinin in isolated guinea-pig antrum and fundus.

Graded distension increased the motor response to cholecystokinin and acetylcholine both in antral and fundal pouches. The increase became even more obvious when the pressure responses were converted into changes in wall tension. The responses to cholecystokinin were additive with low doses (10(-7)M) of carbachol, but diminished or abolished by prestimulation with higher doses. The results indicate that the increased response to cholecystokinin after distension is due to increased smooth muscle stretch.


The role of local cholinergic pathways in the motor response to cholecystokinin and gastrin in isolated guinea-pig fundus and antrum.

Both cholecystokinin (CCK-PZ) and gastrin stimulated antral rhythmic activity and raised fundal basal pressure. The antral motor effects were significantly blocked by pretreatment with atropine or tetrodotoxin. The fundal motor responses were almost unaffected. It is concluded that CCK-PZ and gastrin exert their antral motor effects essentially through local cholinergic neural pathways, while the motor responses in the fundus are almost entirely independent of these pathways.


The CEA concentration in duodenal fluid in patients with pancreatic disease.

The CEA concentration in duodenal fluid after secretin-CCK stimulation has been investigated in 16 patients with pancreatic disease (6 with pancreatic carcinoma and 10 with chronic pancreatitis), 9 with non-pancreatic disease, and 10 control subjects. The purpose was to study whether the determination of CEA in duodenal fluid during the secretin-CCK test can give any additional information for the diagnosis of pancreatic disease and for differentiation between pancreatitis and carcinoma. We found that high values of CEA in duodenal fluid do not necessarily indicate pancreatic carcinoma. Moreover, the level may be elevated in non-pancreatic disease.


Leucocyte migration test with autologous colonic mucosa as antigen in patients with ulcerative colitis.

The leucocyte migration agarose technique (LMAT) was applied in a study of the migration of peripheral leucocytes in 16 patients with ulcerative colitis using three different autologous types of tissue as antigen: rectal mucosa, skin and buccal mucosa. In all cases the migration indices were within normal limits, and they did not differ from a group of control patients suffering from peptic ulcer, irritable colon, or haemorrhoidal tumours. The present study does not support the theory of cellular hypersensitivity against colonic mucosa in patients with ulcerative colitis.


Detection of sacro-ilitis. A comparison between profile scanning with the use of 99m Tc pertechnetate and scintigraphy with 99m Tc diphosphonate.

Comparative evaluation of the sensitivity of 99mTc pertechnetate scanning and of 99mTc diphosphonate scintigraphy in detecting sacro-iliac arthritis (S.I.) was performed in 32 patients with definite S.I., 14 with probable S.I., and 6 with inactive S.I., 14 patients without any evidence of S.I. served as controls. Greater diagnostic accuracy was obtained by 99mTc pertechnetate scanning than with 99mTc diphosphonate scintigraphy in patients with active S.I. in the early stages before radiological changes had become evident and in patients 22 years old and younger. In patients with inactive S.I. a close correlation was found between clinical, radiological, and scintigraphical results with 99mTc diphosphonate scintigraphy. An index obtained by adding the uptake values measured by both methods in each subject yielded valuable information in patients with S.I. that is clinically difficult to differentiate.


The intra-articular residual rate of 131I-fibrinogen and microautoradiographs of the synovial tissue in rheumatoid arthritis.

In this study, 131I-labeled human plasma fibrinogen (200 muCi) was injected intravenously into 21 patients with rheumatoid arthritis and 10 control patients without rheumatic diseases. The residual rates of radioiodinated fibrinogen in the knee joints were calculated by measuring with a scintillation counter the microautoradiographs of the synovial tissue obtained by punch biopsy from the knee joints. The residual rates in the knee joints without as well as with objective symptoms of RA were higher than in control patients. Radio-iodinated fibrinogen was demonstrated on the synovial villous surface, on the area of inflammatory cellular infiltration and stromal necrosis, and on the perivascular region of the synovial tissue from the knee joints of patients with RA, not only with, but also without clinical objective symptoms and histopathologic findings of fibrinoid necrosis, vascular superficial fibrinoid coating and fibrinoid degeneration of vascular wall. It is suggested that fibrinogen plays a role even in the early synovial tissue lesions of knee joints affected by RA.


Polymyalgia rheumatica and chronic lymphatic leukaemia.

A patient with polymyalgia rheumatica (PMR) is reported in whom, at the time of diagnosis, the number of lymphocytes in peripheral blood and bone marrow was normal. Lymphocytic infiltration typical of PMR was detected in renal and muscle biopsy specimens, and a liver fine-needle aspirate contained an abnormal lymphocytic infiltration, probably leukaemic. The number of lymphocytes gradually increased in bone marrow and peripheral blood until, almost 5 years after PMR had been diagnosed, a typical picture of chronic lymphatic leukaemia (CLL) was observable. The significance of the reported combination is discussed. The possibility is pointed out that a CLL in progress must be suspected when persistent lymphocytosis occurs in a patient with typical PMR, even if initially the response to treatment with corticosteroids suggests that PMR is the sole disorder.


Levels of prostaglandins F2 alpha and E2 and thromboxane B2 in joint fluid in rheumatoid arthritis.

Prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were determined by radioimmunoassay (RIA) in knee joint fluid in two groups of patients with classical or definite rheumatoid arthritis (RA). One group had no treatment for one week prior to the study. The second group consisted of patients who developed acute exudative arthritis despite the use of various non-steroidal anti-inflammatory drugs (NSAID). The main metabolites of PGF2 alpha in plasma and urine were measured in the untreated group. The conclusion to be drawn from this study are: 1) Treatment with NSAID effectively lowers PGF2 alpha and PGE2 and TXB2 levels in joint fluid. 2) Signs and symptoms of arthritis may persist in spite of lowered levels of PGF2 alpha and PGE2 in the joint fluid. 3) The main metabolites of PGF2 alpha in plasma and urine are above the low-normal limit in untreated patients. 4) The ratio TXB2/PG was low in untreated patients, suggesting that the thromboxane pathway is quantitatively minor in rheumatoid joint inflammation.


Naproxen concentrations in serum, synovial fluid, and synovium.

Naproxen levels in serum, synovial fluid and synovium of eighteen patients with "classical" or "definite" rheumatoid arthritis and chronic knee effusion were studied. After oral administration of 250 mg naproxen twice daily, naproxen levels in synovial fluid were found to be more than half as high as in serum. Even in synovium itself naproxen levels were appreciable.


Connective tissue activation by synovial fluids and synovial-tissue extracts of rheumatoid arthritis patients.

Prompted by Castor's investigations (4) on a connective-tissue-activating peptide (CTAP) we investigated the stimulative effect of synovial fluids and synovial-tissue extracts on the synthesis of collagen by incubated embryonic-chick tendon cells. The stimulative effect was greater with synovial-tissue extracts from more severe cases than with samples from patients having milder forms of the disease. There was no correlation between the stimulation by synovial fluids and synovial-tissue extracts from the same patient. The stimulative activity was lost at dialysis. A slight stimulation in the incorporation of glucosamine was also observed. Treatment of the patients with gold, chloroquine or steroids decreased the stimulating capacity. These effects seem to depend on factors different from those described by Castor. The differerences in the stimulant activity of samples from various groups cannot be entirely due to glutamine, which is one of the limiting nutrients of the embryonic-chick tendon cells.


Acid glycosaminoglycans in plasma. II. Findings in rheumatoid arthritis.

The glycosaminoglycans (GAG) directly adsorbable from undiluted plasma on DE-52 anion-exchange cellulose (free GAG) and the GAG adsorbable on AG 1 X 2 anion exchange resin after papain proteolysis (bound GAG) were determined in 35 patients suffering from active erosive rheumatoid arthritis (RA) and in 50 control subjects. Free GAG levels were significantly elevated in both female (p less than 0.001) and male (p less than 0.05) RA patients. Bound GAG levels were significantly depressed in female (p less than 0.02) but not in male RA patients. Total GAG concentrations in RA patients and in controls were fairly similar. No consistent differences in the electrophoretic patterns of the plasma GAG from RA patients and controls were discernible. The free GAG concentrations in RA plasma samples did not correlate with seropositivity or ESR.


Rheumatoid arthritis and collagen antibodies.

By using the complement fixation test, antibodies against collagen were examined. Pronase-solubilized insouble collagen served as antigen (20 degrees, 24 hours, collagen: enzyme ratio 10:1). Of 79 patients suffering from rheumatoid arthritis, the presence of collagen antibodies was demonstrated in 8 cases. 56 patients with degenerative joint disease served as the control group, in which collagen antibodies were detected in only one single patient.


[Decrease of intestinal absorption of 47-calcium in chronic alcoholism].

Intestinal 47-calcium absorption has been studied in 34 chronic alcoholics, 17 of whom were cirrhotics (group A) and 17 non-cirrhotics (group B). These patients were compared with 44 normal subjects (group C). In group C, the 47Ca 2 h plasma % of the dose showed a significant negative correlation to the total body weight (p less than 0.001) and a positive correlation with the serum albumin (p less than 0.05). The mean intestinal absorption of 47Ca expressed as 2 h plasma % of the dose multiplied by total body weight was 131 +/- SD 52 in group A and 136 +/- SD 71 in group B. These two means are significantly low (p less than 0.001 and p less than 0.002 respectively) in relation to that found in group C (168 +/- SD 32). These results suggest that intestinal calcium absorption is diminished in chronic alcoholism even in the absence of hepatic cirrhosis.