Comparative gastric antisecretory and antiulcer effects of prostaglandin E1 and its methyl ester in animals.

The influence of methyl esterification of the carboxyl group of PGE1 on the gastric antisecretory and antiulcer activities were studied. The gastric antisecretory effects of PGE1 free acid and PGE1 methyl ester (PGE1ME) were studied in the Heidenhain pouch dog. Secretion was stimulated with constant intravenous infusion of histamine dihydrochloride. When a steady-state plateau of gastric secretion had been reached, the prostaglandins were administered either by a single intravenous bolus (10.0 mug/kg) or by continuous infusion (1.0 mug/kg/min). PGE1ME was found to be slightly more potent and longer-acting than PFE1 when administered by a single i.v. bolus. PGE1ME was also shown to be more potent than PGE1 when infused intravenously for a two-hour period. PGE1ME caused a significant alteration in gastric juice concentration of hydrogen and sodium ions in an inverse relationship. Potassium and chloride concentration were not altered from pre-existing steady-state values following administration of either form of prostaglandin. Similarly, PGE1ME was also found to possess significantly greater antiulcer activity in the rat forced-exertion ulcer test. These findings support the hypothesis that methyl esterification of the prostaglandin molecule will increase some of the biological actions of PGE1 through inhibition of metabolic beta-oxidation of the carboxylic side chain.


The reaction of PGA1 with sulfhydryl groups; a component in the binding of A-type prostaglandins to proteins.

Prostaglandins of the A-type (PGAs) were found to react with cysteine or reduced glutathione to yield water-soluble adducts, an effect due to a reaction of the sulfhydryl group of cysteine with the unsaturated carbonyl function of these prostaglandins. The binding of tritiated PGA1 to the supernatant fraction of rabbit papilla homogenates reported by Attallah and Lee (4) appears to be related to this phenomenon since ethacrynic acid, a compound also highly reactive with the thiol group of cysteine, effectively competes with PGAs for the binding site in this soluble kidney preparation. Evidence is also presented to show that this binding of PGAs to the "acceptor' of the rabbit kidney is related to an interaction with a thiol group of 15-hydroxy prostaglandin dehydrogenase, the enzyme chiefly involved in the metabolism of prostaglandins.


Stimulation of bone resorption by various prostaglandins in organ culture.

The ability of E, F, A and B prostaglandins to stimulate bone resorption was demonstrated in organ culture. All of the compounds tested were able to increase the release of previously incorporated 45Ca from fetal rat bone by 60 to 135 per cent at maximally effective doses, but prostaglandins of the E series were 10- to 100- fold more potent than F, A or B prostaglandins. Compounds with two double bonds in the side chain were usually more potent than those with one double bond. PGE2 stimulation of bone resorption increased linearly with the logarithm of the medium concentration over the range of 10(-9)M to 10(-5)M, then decreased at higher concentrations. PGE2 stimulated bone resorption more slowly than did parathyroid hormone but caused complete resorption after six days in the culture system. Equilibrium dialysis studies showed no significant binding of F, and 16-34% binding of E and A prostaglandins to bovine serum albumin, which was present in the medium at 1 mg/ml. These differences in albumin binding could not account for differences in potency.


The effect of locally administered PGE2 on the contractility of the nonpregnant human uterus in vivo.

The effect of locally administered prostaglandin E2 on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied in seven women. An increase in uterine contractility in response to as little as 0.25 mug PGE2 could be observed during both the mid-proliferative and mid-secretory phases of the menstrual cycle, but around ovulation a marked decrease in sensitivity to PGE2 was noted. An inhibition of uterine motility was observed during menstruation in response to 30--40 mug PGE2. Endogenous E prostaglandin normally occurs in the secretory endometrium in levels comparable to the amount of exogenous PGE2 which elicited increased or decreased uterine activity in this study. These findings suggest that PGE2 may play an important role in the cyclical regulation of uterine motility during the menstrual cycle.


Radioimmunoassay of 13, 14-dihydro-15-keto prostaglandin F in bovine peripheral plasma.

A radioimmunoassay has been developed for 13, 14-dihydro-15-keto-prostaglandin F in bovine peripheral plasma. Acidified plasma samples were extracted with diethyl ether and the dried extract assayed for 13, 14-dihydro-15-keto-prostaglandin F using antiserum raised against a 13, 14-dihydro-15-keto-prostaglandin F2alpha-albumin complex. The tracer used for the assay was prepared enzymatically from tritiated prostaglandin F1alpha. Polyethylene glycol was employed to separate free and bound 13, 14-dihydro-15-keto-prostaglandin F. The inter-assay coefficient of variation based on 9 determinations of control plasma was 13.8%. The detection limit of the assay was 25 pg 13, 14-dihydro-15-keto-prostaglandin F/ml plasma. In 3 cows around estrus there was a complex sseries of peaks of 13, 14-dihydro-15-keto-prostaglandin F concentrations coincident with luteolysis and declining progesterone concentrations. Changes in peripheral plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F in the pregnant cow near term showed a close correlation with prostaglandin F levels in utero-ovarian venous plasma. The concentration of 13, 14-dihydro-15-keto-prostaglandin F in 12 men was 114 +/- 20 pg/ml plasma. It is concluded that the measurement of peripheral 13, 14-dihydro-15-keto-prostaglandin F concentrations may offer a simple and convenient method for monitoring uterine prostaglandin F production in the cow.


Prostaglandins and congeners. IX. The synthesis of 15-deoxy-16-, 17-, or 20-hydroxyprostaglandins and 15-deoxy-15-hydroxymethylprostaglandin E2.

Prostaglandin congeners wherein the 15-hydroxy group is moved to the C16, C17, or C20 position or is replaced by a hydroxymethyl group were prepared via the 1, 4-addition of a lithium trialkyl-trans-alkenyl alanate to an appropriate cyclopentenone. Several of the 16-hydroxy derivatives showed significant activity as constrictors of the isolated gerbil colon and in bronchodilator and anti-secretory assays.


Prostaglandin E1 and F2alpha specific binding in bovine corpora lutea: comparison with luteolytic effects.

Preliminary characterization indicated the presence of separate prostaglandin (PG)E1 and (PG)F2alpha binding sites in membrane fractions prepared from bovine corpora lutea. These differ in the rate and temperature dependence of the specific binding. Equilibrium binding data indicate the apparent dissociation constants as 1.32 x 10(-9)M and 1.1 x 10(-8)M for PGE1 and PGF2alpha, respectively. Competition of several natural prostaglandins for the PGE1 and PGF2alpha bovine luteal specific binding sites indicates specificity for the 9-keto or 9alpha-hydroxyl moiety, respectively. Differences in relative ability to inhibit 3H-PG binding were found due to sensitivity to the absence or presence of the 5, 6-cis-double bond as well. Bovine luteal function was affected following treatment of heifers with 25 mg PGF2alpha as measured by reduced estrous cycle length, decreased corpus luteum size and significantly decreased plasma progesterone levels. In contract, treatment with 25 mg PGE1 resulted in cycle lengths comparable to those of non-treated herdmates with no apparent modification in corpus luteum size. However, plasma progesterone levels were increased significantly following PGE1 treatment compared to pretreatment values. In so far as data obtained in vitro on PGF2alpha relative binding affinity to the bovine CL can be compared to data obtained independently in vitro on PGF2alpha induced luteolysis in the bovine, PGF2alpha relative binding to the CL and luteolysis appeared to be associated. By similar reasoning, there was no apparent relationship between PGE1 relative binding affinity in the luteal fractions and luteolysis in estrous cyclic cattle.


Intrauterine injection of 15(S)-15-methyl-prostaglandin F2alpha for termination of early pregnancy in out-patient.

15-me-PGF2alpha was administered as single intrauterine injection for interruption of very early pregnancy in 30 out-patients. After 2 weeks, abortion was complete in 60% induced with 125 or 200 mug and 80% induced with 300 mug. After 3 weeks, abortion was complete in 90% induced with 125 mug, in 70% induced with 200 mug and in 100% induced with 300 mug. One failure occurred in patients treated with 200 mug and 2 curettages were performed because of incompleteness of abortion. No serious complications occurred. Compared with our previous results it appears that 15-me-PGF2alpha is as effective as natural PGF2alpha in inducing abortions during very early pregnancy but causes somewhat fewer side-effects.


Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig.

Infusion of norephinephrine (NE) (1 - 3 mug/ml/min) into the isolated mesenteric vascular preparation of rabbit resulted in a rise in perfusion pressure, which was associated with the release of prostaglandin E-like substance (PGE) at a concentration of 2.81 +/- 0.65 ng/ml in terms of PGE2. Indomethacin (3 mug/ml) abolished the NE-induced release of PGE. Arachidonic acid (0.2 mug/ml) in the presence of indomethacin did not restore the NE-induced release of PGE. Hydrocortisone (10 - 30 mug/ml) and dexamethasone (2 - 5 mug/ml) also inhibited the NE-induced release of PGE. The inhibitory action of both corticosteroids was abolished by arachidonic acid (0.2 mug/ml). Antigen-induced release of a prostaglandin-like substance (PGs) (43.1 +/- 3.8 ng/ml in terms of PGE2 and a rabbit aorta contracting substance (RCS) from perfused lungs of sensitized guinea pigs was completely abolished by indomethacin (5 mug/ml) or by hydrocortisone (100 mug/ml). Indomethacin, however, increased histamine release up to 280% of the control level, which was 470 +/- 54 ng/ml, while hydrocortisone diminished histamine release down to 30% of the control level. A superimposed infusion of arachidonic acid (1 mug/ml) into the pulmonary artery reversed the hydrocortisone-induced blockade of the release of RCS and PGs. It may be concluded that corticosteroids neither inhibit prostaglandin synthetase nor influence prostaglandin transport through the membranes but they do impair the availability of the substrate for the enzyme.


Vaginally administered 16, 16-dimethyl-prostaglandin E2 as an agent for pre-operative cervical dilatation.

Twenty-one women in the 10th-12th week of pregnancy were treated prior to vacuum aspiration with vaginal suppositories containing 16, 16-dimethyl-PGE2 (free acid). An average total dose of 3.4 mg led to abortion or adequate cervical dilatation in all patients. Based upon previous experience with the compound, no prophylactic anti-emetic or anti-diarrhetic medication was given. Gastrointestinal side effects were minimal. Excessive bleeding was not observed. In two cases, slight temperature elevation was noted prior to abortion. The low incidence of side effects in combination with the effectiveness of the compound help to make this method an attractive therapeutic adjunct to vacuum aspiration beyond the 10th week of gestation. Under the experimental conditions of this study, the results suggest that vaginally administered 16, 16-dimethyl-PGE2 can be a safe and effective method for cervical dilatation before vacuum aspiration.


A possible contribution of undifferentiated cells to post-traumatic osteogenesis.

The contribution of undifferentiated cells to callus formation is difficult to observe during fracture healing and is therefore debated. In adult mongrel dogs these cells can easily be observed in a narrow space separating a freshly inserted screw from the surrounding compact bone. Undifferentiated connective tissue cells invade these spaces from the medullary and, less so, from the periosteal site. They seem to resemble histologically and more so ultrastructurally B-type lymphocytes. They migrate to the site of repair or are brought there by the blood stream. Locally these cells proliferate and differentiated into osteoblasts. The authors prefer to call these cells lymphocyte-like cells.


Studies on the biosynthesis of isocoumarins in carrot root tissues : induction by substances other than ethylene and effects of metabolic inhibitors.

Ethylene has been shown to induce carrot tissues to synthesize 8-hydroxy-6-methoxy-3-methyl-3,4-dihydroisocoumarin and 5-hydroxy-7-methoxy-2-methylchromone or eugenin. Our present data showed that the induction of isocoumarin formation could also be obtained by treating carrot slices with dinitrophenol and methylene blue. Methylene blue enhanced ethylene production, but dinitrophenol did not, therefore the action of the latter could not be mediated by ethylene. Arsenite inhibited isocoumarin synthesis, indicating the involvement of the glycolysis pathway. Assays on the pattern of derivation of isocoumarin from glucose lent support to the idea that isocoumarin is formed predominantly through the Embden-Meyerhof-Parnas pathway. Dinitrophenol-induced enhancement of both respiratory activity and isocoumarin formation indicates that the operation of the Krebs cycle and subsequently of the electron transport chain oxidations is required to provide acetate, the precursor of isocourmarin, as well as the energy necessary for the synthesizing process. The long initial lag phase as well as the mode of inhibition by cycloheximide seem to indicate that the ethylene-induced synthesis of isocoumarin is a sequential process.


[Morphometric analysis of neural tube cells in neurulating chick embryos].

Preliminary report on a morphometric study of the neuroepithelium of 1 S and 7 S -- stage chick embryos. We show first that the nucleo-cytoplasmic ratio and then, that the volume fraction of intercellular spaces, nuclei and cytoplasm as they relate to the neural tube, differ significatively from cephalic to caudal portion of the neural tube. At stage 7 S only the volume fraction of intercellular spaces, nuclei and cytoplasm in the neural tube change along the cephalo-caudal axis of the embryos. Finally, between the two stages, at the back of the head, 1) volume fraction of intercellular spaces in the neural tube remains unchanged 2) nucleo-cytoplasmic ratio increase 3) volumetric density and size of mitochondria do not change, while surface density of endoplasmic reticulum in cytoplasm increases.


The effects of swimming and running regimens on skeletal muscle glycogen in the rat.

Endurance capacity and the effects of different post-exercise states on skeletal muscle glycogen have been studied in rats trained by swimming or running and in sedentary controls. Regular endurance exercise resulted in increased skeletal muscle glycogen stores. A greater depletion was observed in trained animals than in non-trained animals after a training bout or exhaustive exercise. While muscle glycogen levels did not reflect a differential training stimulus (running vs swimming), swimming as a measure of exhaustive exercise was deemed invalid because of the ability of trained swimmers to avoid stenuous exercise by an alteration of swimming pattern.


Spontaneous dissociation of an IgG-3 paraprotein through disulfide interchange.

A paraprotein of the gamma3 subclass was observed to dissociate "spontaneously" under various experimental conditions, such as during chromatography on DEAE-cellulose and on Sephadex G-200 or on starch block electrophoresis. This phenomenon was accompanied by the formation of various complexes of higher molecular weight, displaying antigenic properties different from those of the original paraprotein. These changes did not occur in the presence of iodoacetamide, indicating that dissociation of the paraprotein was due to disulfide interchange(s) and not to the absence of interchain disulfide bridges.


Isoelectric focusing of pure rat pancreatic juice in polyacrylamide gel : possibility of concomitant estimation of radioactivity incorporated into single identified protein constituents.

A method is described for the isoelectric focusing of rat pancreatic juice on columns of polyacrylamide gel containing urea. Twenty-six bands were separated, and 6 were identified. Application of this method of separation to in vivo radioactively labelled pancreatic juice resulted in bands which could be counted with precision. This procedure allowed also the expression of radioactivity of one constituent relative to any single band, or relative to total radioactivity, concomitantly.


Cholesterol plate deposition in a pathological transport environment.

Triglycerides separated from human serum lipoprotein or triolein converted cholesterol needles to plates on equilibration in isotonic saline. Cholesterol needles equilibrated with human clear or lipemic plasma or serum were not converted to plates unless olive oil or triolein was added. Plasma phospholipid permitted and sodium lauryl sulfate (0.1-10%) prevented formation of plates from cholesterol needle-saturated olive oil in water at 38 degrees C. Cholesterol liquid crystals, formed from needles dispersed in aqueous plasma phospholipid, changed to plates on dilution with water. The cholesterol content of lipemic and high-, normal-, or low-cholesterol sera, equilibrated with cholesterol plates at 38 degrees C, was not significantly altered. In rats and mice the mobilization of injected cholesterol needles at the intrathoracic site manifested a sex-species difference. In the pathological deposition of cholesterol plates, a breakdown of a defense mechanism in plasma involving noncovalent binding of triglyceride with phospholipid and protein is indicated.


Effects of chronic guanethidine administration on cardiovascular function of dogs.

Chronic guanethidine administration 2.5 mg/kg/day for 7 to 8 months did not produce any essential changes in blood pressure and heart rate of the anesthetized dogs while there was a significant elevation of stroke volume and stroke work. There was a reduction in total peripheral resistance and an increase in cardiac output in the treated dogs in comparison with the placebo group. Ventricular function curves obtained in both the treated and placebo group were virtually identical. The data suggested that chronic guanethidine administration did not induce any adverse effect on myocardial functions.


Effects of neonatal 6-hydroxydopa treatment on monamine content of rat brain and peripheral tissues.

Treatment of rats from birth, with 6-hydroxydopa (6-OHDOPA) produced marked alterations in norepinephrine (NE) levels in the brain and spinal cord, but relatively slight changes in NE content of peripheral tissues, when rats were sacrificed at 5 weeks of age. In the neocortex, hippocampus and spinal cord 6-OHDOPA (60 mug/g i.p., 1 to 3 injections at 48 hr intervals from birth) resulted in a 20% to 85% reduction in NE. In the pons-medulla, midbrain and cerebellum, however, NE levels were elevated by 35% to 100%. Only slight alterations in NE were found in the hypothalamus, heart and spleen. Striatal levels of dopamine were unaltered by 6-OHDOPA at 5 weeks. Likewise, serotonin content of neocortex, cerebellum, pons-medulla, midbrain and hypothalamus was unchanged at 5 weeks, although slight elevations were seen in the neocortex and cerebellum at 2 weeks. The above effects indicate that neonatal 6-OHDOPA produces a relatively selective long term alteration of central stores of NE in the rat.


Antiinflammatory and antiproteolytic properties of naphthlthiosemicarbazides and cyclized oxadiazoles.

Eight 1-(naphth-1-ylacetyl)-4-substituted thiosemicarbazides and eight 2-(naphth-1-ylmethyl)-5-arylamino-1,3,4-oxadiazoles were synthesized and evaluated for antiinflammatory and antiproteolytic properties. All thiosemicarbazides (100 mg/kg) provided 14-43% protection against carrageenin-induced edema in rats. Cyclization of thiosemicarbazides to oxadiazoles resulted in significant reduction in the antiinflammatory activity. Some of these thiosemicarbazides also possessed low antiinflammatory activity against cotton-pellet-induced granuloma formation and formaldehyde-induced arthritis in rats. Hydrocortisone and oxyphenbutazone, used as reference drugs, exhibited greater antiinflammatory activity. All compounds possessed antiproteolytic activity. The in vitro protection of trypsin-induced hydrolysis of bovine serum albumin, unlike antiinflammatory activity, was greater with oxadiazoles (30-90%) than the precursor thiosemicarbazides (4-50%) at a final concentration of 1 mM.


In vitro inhibition of polyphenylalanine synthesis by bromotrichloromethane. Evidence for an oxidative mechanism.

In vitro, CBrCl3 causes a strong inhibition of phenylalanine incorporation in postmitochondrial supernatant from rat liver. Evidence is given that this inhibition mostly depends on a block of chain initiation. This block seems to be by means of an oxidative mechanism, dependent on the homolytic cleavage of CBrCl3. Some data indicate inhibition is given by free radicals, and not other products coming from the CBrCl3-induced lipid peroxidation.


Effect of aromatic molecules on the aggregation of C-phycocyanin. Quantum chemical calculations on phycocyanobilin and phycoerythrobilin.

The energies of the highest occupied and lowest empty molecular orbitals were calculated for the chromophore groups of the proteins phycocyanin and phycoerythrin. These tetrapyrrole groups on the algal proteins are shown to provide them with the potential of ating as efficient electron donors and acceptors. In addition, the pi electron charges and bond orders were also computed.


Histamine2 receptors in rat uterus.

Histamine and three histamine analogs (4-methylhistamine, 3-beta-aminoethyl 1,2,4 triazole (TD) and betazole) all produced relaxation in depolarized rat uterine strips. The rank order obtained was the same as that noted previously in the heart and gastric mucosa and the effects of the agonists were blocked by burimamide. The uterine histamine receptor thus appears to be of the H2-type. Adenylate cyclase prepared from the uterus was not stimulated by histamine. Uterine H2-receptors thus do not appear to be associated with adenylate cyclase.


Hymenoxon, a poisonous sesquiterpene lactone from Hymenoxys odorata DC. (bitterweed).

Hymenoxon (C15H22O5) was isolated from Hymenoxys odorata DC. in 0.5% yield. The structure of hymenoxon is shown to be 1. The intraperitoneal LD50 of hymenoxon in sheep is about 7 mg/kg.


Antiestrogenic activity of 4-methyl-7-hydroxy-6,8-substituted coumarins.

Eight 4-methyl-7-hydroxy-6,8-substituted coumarins were synthesized and evaluated for antiestrogenic activity. All coumarins, possessing approximate LD50 values of 500 - greater than 800 mg/kg, antagonized the uterotropic effects of diethylstilbestrol (DES) in female rats.


The glycogen-depleting effect of 1-epinephrine on the myocardium of the six and one-half day chick embryo.

The effect of 1-epinephrine, administered in ovo, on the myocardial glycogen level of the six and one-half day chick embryo has been determined. The glycogen-depleting effect of this hormone on the myocardium of the embryo was found to be both dosage-dependent and time-dependent.


Calcium-binding property of cocaine and some of its active metabolites-formation of molecular complexes.

Cocaine, benzoylecgonine, benzoylnorecgonine, norcocaine, ecgonine methyl ester but not ecgonine formed distinct molecular complexes with calcium chloride of the general formula [B. CaC12-2H20]. The particularly strong interaction observed with benzoylecgonine, benzoylnorecgonine and calcium may play a role in the potent stimulant activity of these 2 compounds observed in rats after intracisternal administration.


Effect of oral antidiabetic drugs on lipase activity in vitro.

Phenformin and metformin have a stimulating effect on lipolysis as determined by the action of mouse pancreas lipase on the dilauric (dido-decanoic) acid ester of fluorescein. Tolbutamide and chlorpropamide have an inhibitory effect.


Effect of apomorphine on serum prolactin level in the male.

Apomorphine (5 mg/kg) caused a marked lowering of serum prolactin in male rats. The apomorphine effect was reversible and could be shown without previously elevating the prolactin levels as has been customary in previous experiments. Repeated sampling of tail-vein blood without use of anesthesia was feasible and perhaps perferable to single sampling by decapitation.


Idiopathic interstitial pulmonary fibrosis with hypercapnia.

A 38-year-old patient with effort dyspnea, somnolence, cianosis and cor pulmonale is presented. Chest roentgenograms and lung function studies suggested the diagnosis of pulmonary fibrosis. The patient showed also severe hypercapnia with normal resting ventilation and ventilatory response to exercise lower than usual for this condition. Autopsy confirmed the clinical diagnosis. This subject may belong to the growing group of patients where CO2 retention is not explained by their pulmonary pathology.


Minimal increases in pulmonary wedge pressure associated with improved PaO2s in dogs.

To determine the relationship between minimal increases in pulmonary wedge pressure (PWP), arterial PO2s, single breath diffusing capacity (DLCO), and lung perfusion pattern (as determined by semiupright lung scans), we elevated PWP by 61.8+/-4.1% from baseline values of 5.5+/-0.4 mm Hg. At the end of 30 min PaO2 increased by 13.2+/-1.4% (p less than 0.001) from baseline values of 81.7+/-3.1 mm Hg; DLCO decreased by 15.5+/-1.2% (p less than 0.01) to 0.98+/-0.10 ml/min/mm Hg/kg. Lung perfusion changes in the right lung apical zone increased by 28.0+/-4.2% (p less than 0.001) and decreased in the basal zone by 6.2+/-0.8% (NS). In the left lung the apical perfusion increased by 14.9+/-1.1% (p less than 0.01) and basal perfusion decreased by 8.6/+-1.4% (NS). We conclude that minimal elevation of PWP in dogs leads to improvement in PaO2s through alterations in the lungs perfusion pattern.


Influence of lung resection on pulmonary circulation and lung function at rest and on exercise.

Since June 1972, preoperative evaluation of the pulmonary hemodynamics and lung function tests at rest and on exercise were done in patients undergoing thoracotomy with lung resection. 49 patients have been investigated postoperatively, 28 patients had pre- and postoperative rightsided heart catheterization. 80% of the patients were feeling well and more than 50% were working again. The pulmonary hemodynamics showed postoperatively already at rest an increase of the pulmonary artery pressures, the cardiac index reached on exercise no longer the preoperative values and there was an increase of PCV pressures on exercise compared to preoperative. Stroke volume, heart rate, AV difference for oxygen, oxygen uptake, PaO2, V, VD/VT, AadO2, and diffusing capacity for CO steady state on exercise showed no statistical significant changes. The extent of lung resection showed no different influence on the pulmonary circulation for the time period investigated.


[Pulmonary diffusing capacity for CO during breathing of inert gas mixtures with differing physical properties (author's transl)].

In order to study the role of diffusion limitation in alveolar space (stratification) for pulmonary gas exchange function, pulmonary diffusing capacity for CO (Dco) was comparatively measured during breathing of room air and of gas mixtures in which N2 of room air was replaced by He or Ar. Measurements in 15 healthy humans using the single breath method yielded the following mean (+/-SE) values: room air, 22.1+/-1.7; He, 25.1+/-1.3; Ar, 17.4+/-1.0 ml-min-1-Torr-1. The clear negative correlation between Dco and the molecular weight of the gases used is most easily explained on the basis of an airway diffusion resistance limiting CO transfer. For room air breathing this resistance is estimated at about 10% of the total resistance to CO uptake (1/Dco). The alveolar exchange of O2 and CO2 is expected to be affected by the diffusional resistance in airways, particularly at high metabolic levels.


[Local oversensitivity of sensoric receptors as cause of reflectoric airway obstruction (author's transl)].

The effect of local intratracheal, intrabronchial, and intravenous application of histamine, has been studied in dogs. Control studies are also carried out with saline. There is an increase in intrathoracic pressure per 100 ml of tidal volume due to locally applied histamine. This change is considered as the measure of bronchoconstriction. There is also a significant change in the bronchial sensitivity to acetylcholine inhalation. The intravenous application of the same quantity of histamine produces very little change in the bronchial sensitivity though it has produced strong and prolonged circulatory effect and even transitory respiratory arrest. The application of saline produces no change. It is concluded that the local chemical stimulus can sensitize the whole respiratory system and produces greater bronchconstriction involving some reflex path.


Chronic eosinophilic pneumonia.

An association between migratory pulmonary infiltrates and peripheral eosinophilia has been known for at least 40 years. Diagnostic challenges still exist in the classifications within this syndrome. We describe a 33-year-old female without asthma but with definite "atopy" who had a 4-year history of recurring pulmonary lesions. These were sometimes segmental, at other times dense and peripheral, and once there was lobar atelectasis due to mucoid impaction. Diagnosis by lung biopsy revealed eosinophilic pneumonia with bronchiolitis obliterans as a prominent feature. Steroid treatment resulted in promt improvement; during a 5-year follow-up the infiltrates have not recurred but there has been persistent mild obstruction.


Bradykinin and human airways.

This work explored the effects of bradykinin (BK) on human airways. Bradykinin (1 mug/kg body weight) was rapidly injected intravenously and respiratory system resistance (Rrs), closing volume (CV), forced vital capacity (FVC), expiratory volume in the first second (FEV1) maximal midexpiratory flow (MMF), and peak flow (PF) were measured. Bradykinin in normals produced no changes in Rrs or CV, but reduced the FVC. This suggests alveolar duct constriction, since no constriction of either large or small airways occurred with the decreased FVC. Bradykinin in asthmatics decreased the Rrs and CV, and increased the FEV1, MMF and PF, while the FVC did not change significantly. The absence of a significant increase in the FVC in the presence of concomitant bronchodilation, suggests that asthmatics also had alveolar duct construction. These data are consistent with animal studies which show that BK may release adrenalin (or other agents) with secondary effects, such as bronchodilation. The secondary bronchodilation seen in asthmatics but not in normals, is probably a result of the initial higher intrinsic bronchial tone of the asthmatics.


Absorption of in vivo inert gas bubbles.

The resolution rates of gas bubbles in perfused tissue are examined using a mathematical model which is consistent with transient-state and steady-state data from large gas pocket experiments. The tissue surrounding the bubble is assumed to have an infinite number of infinitesimally small capillaries (distributed sink). The time for complete disappearance of a bubble depends on initial bubble size. blood perfusion rate of the tissue, physical characteristics of the inert gas and the fraction (1-Pa/Pg), where Pa and Pg are inert gas partial pressures in the surrounding tissue and inside the bubble, respectively. Calculated time for disappearance of a nitrogen bubble of 1 mm radius in an O2-breathing man is 100-250 min, depending on blood perfusion. Breathing of air increases the time of persistence of the bubble about 10-fold. The "transient state", when gas is dissolving in the immediate surroundings of the bubble, is most influential when there is no perfusion and the partial pressure gradient gas volume is the largest. However, our major conclusion is that the initial transient state has little effect on total lifetime of the bubble in any case.


Ventilatory response of goats to transient changes in CO2 and O2 during acute hypoxia.

The authors assessed the relative sensitivity of the peripheral chemoreceptors of 4 goats to a transient decrease in inspired CO2 using a 2-breath test. This test provides a steady-state background of hypoxia and hypercapnia and then, for 2 breaths, an equally hypoxic gas mixture containing no CO2. Another type of 2-breath test, providing 2 breaths of a hyperoxic gas mixture against a background of hypoxia, was used to establish the time course of a response known to come from peripheral chemoreceptors. Seven human subjects were studied in a similar fashion to establish the validity of the procedure. Except for 2 responses, the author's human data agree with those reported previously by others. All 4 goats resembled man in responding to removal of hypoxia with a significant decrease in ventilation, but 3 of the 4 goats, unlike man, showed no significant decrease in ventilation when CO2 was removed. The authors conclude that the peripheral chemoreceptors of goats are commonly insensitive to transient changes in inspired CO2 during acute hypoxia.


Morphometric estimation of pulmonary diffusion capacity. VII. The normal Guinea pig lung.

A study of 15 normal adult guinea pig lungs fixed by instillation of fixatives via the airways is described. The morphological appearance of the guinea pig lung is similar to that of other mammals apart from quantitative differences in the mass of connective tissue in the alveolar-capillary barrier whose mean thickness was estimated at 1.59 mum. Lung volume, alveolar volume, capillary volume and the surface areas of alveoli and capillaries are shown to be linearly related to body weight. Analysis of the morphometric diffusion capacities of the alveolar-capillary membrane and of the lung shows that these are also linearly related to body weight. For a mean body weight of 429 g the lung volume was 13 ml, the alveolar surface 0.91 m2, the capillary volume 1.5 ml, the harmonic mean barrier thickness 0.42 mum, and DL 2.13 ml/min.mm Hg. These parameters are compared with those of other mammalian species and discussed in the context of normal activity levels as a probable important adaptive factor determining the size of the gas exchange apparatus.


The effect of anaphylactic shock on laryngeal calibre in rabbits.

Laryngeal resistance to airflow has been measured during anaphylactic shock in three groups of spontaneously breathing rabbits: (1) intact, (2) vagotomized and (3) vagotomized and with superior laryngeal nerves cut. In the intact animals anaphylaxis elicited large increases in expiratory laryngeal resistance. The anaphylactic constriction of the larynx did not depend on reflexes from the lungs as the responses were even more pronounced in the vagotomized animals. Cutting the superior laryngeal nerves with vagotomy lessened the size of the increase in laryngeal expiratory resistance.


The exchange of bone CO2 in vivo.

Bone 14CO2 specific activities have been measured in 10 male rats perfused for 30, 60 or 120 minutes with [14C]bicarbonate. A steady blood 14CO2 specific activity is observed from the 30th minute, whereas bone 14CO2 specific activity increased linearly with time. About 7-10% of the total activity infused may be recovered in the skeleton at any given time. Bone samples heated to constant weight lost 15% of their total CO2 content and more than 50% of the 14CO2 activity. This indicates that 14CO2 present in bone is almost exclusively located in a bicarbonate pool which may be considered as the rapidly exchangeable bone CO2 fraction. The rate of exchange between bone and blood CO2 is estimated at a maximum of 15% of the total CO2 production. It is postulated that blood flow to the skeleton is the limiting factor for bone CO2 exchange. These results lead to the conclusion that the large bone CO2 store cannot play a significant role in the buffering of extracellular fluids in acute acid-base abnormalities.


Observations on the sites of respiratory evaporation in the fowl during thermal panting.

The rate of respiratory water loss (RWL) was investigated in domestic fowls by the open-flow method, and the relative importance of the surfaces of the upper and lower respiratory tract was assessed by cannulating the trachea and by recording the temperatures at the potential evaporating sites. Birds were exposed to Ta from 20 to 40 degrees C and RWL examined at rectal temperatures (Tre) from 41 to 44 degrees C. Overall, the increase in RWL from the whole tract, and from the upper and lower divisions, was by about 1.1, 1.0 and 0.3 mg (g-hr. degrees C)-1, respectively. There was a rapid increase in V and in RWL from the whole and from the upper tract at Tre 41.5-42.5 degrees C, but no comparable change from the lower tract. Temperatures significantly below Ta and Tre (both 43 degrees C) were detected in the trachea and in the nasal and buccal cavities, but not in the air sacs. It was concluded that respiratory evaporation occurs mainly from the upper tract during panting and that the air sacs are unlikely to be involved.


Mechanisms of autonomic control of carotid chemoreceptor activity.

Single chemoreceptor fibres dissected from the cut carotid sinus nerves of cats were studied when carotid body blood flow was normal, and when it had been abruptly halted by reducing the local perfusion pressure to zero. Ten chemoreceptor fibres which, when normally supplied with blood, increased their discharge by at least 25% in response to sympathetic stimulation, and 7 fibres which, when normally supplied with blood, decreased their discharge by at least 10% in response to carotid sinus nerve stimulation, were chosen for study. The development of discharge during the period of stagnant asphyxia following stoppage of flow was reproducible in repeated control trials for each fibre investigated. Neither sympathetic nor carotid sinus nerve stimulation, commencing at the stoppage of flow and continued throughout the period of asphyxia, produced any significant alteration from the control pattern of developing chemoreceptor discharge. These experiments provide evidence that the effects of sympathetic and carotid sinus nerve stimulation on carotid chemoreceptor discharges are mediated through alterations in carotid body blood flow. When there is no flow there are no effects on discharge.


Thoracic collapse as affected by the retia thoracica in the dolphin.

The carcass of a subadult female Delphinus was placed in a hyperbaric chamber and subjected to two simulated dives each equivalent to 69.7 m. In one dive the thorax was in its natural state, and in the other 100 ml of water had been injected into each pleural cavity. Various morphometric measurements of the thorax were taken before, during, and after each dive. Results indicate that if fluid is located in the same position as the retia thoracica, the shape of the thorax is affected when submitted to diving, but not surface, pressures. The overall collapse of the chest is greater during partial infusion of the pleura, exhibiting exceptional compression in the ventral area. The engorged thoracic rete apparently affects the degree and pattern of thoracic collapse and thereby reduces the amount of displacement stress exerted upon the abdominal organs when the animal is subjected to the high ambient hydrostatic pressures encountered during normal diving.


Contribution of hypercapnic stimuli and of vagal afferents to the timing of breathing in anesthetized cats.

In tracheotomized, anesthetized cats, the authors studied the role of phasic and tonic vagal discharge and of hypercapnic stimuli on the timing of breathing. The effect of tonic vagal discharge was separated from that of the other two parameters by comparing the duration of inspiration and of expiration of control breaths with those obtained during occlusions of the airways at FRC (bulbo-pontine activity). The effect of tonic vagal discharge was then separated from that of hypercapnic stimuli by comparing the bulbo-pontine activity before and after vagotomy. Hypercapnia caused shortening of inspiratory and expiratory duration set by the bulbo-pontine pacemaker and increased sensitivity of the respiratory centers for a given phasic vagal input (displacement to the left of the tidal volume vs inspiratory duration relationship). Vagotomy did not modify the bulbo-pontine duration of inspiration nor its possibility to shorten in hypercapnia; by contrast it caused a lengthening of the expiratory time which did not shorten any more in hypercapnia, suggesting that tonic vagal discharge mainly influences the expiratory duration.


The bone CO2 compartment: evidence for a bicarbonate pool.

CO2 was measured in rat cortical bone samples with an accurate manometric technique. Bone CO2 content increased with the age of the animals. When heated to constant weight, bone samples lost 15.5% of their initial fresh CO2 content, indicating that CO2 exists in several chemical forms in the bone CO2 pool. Bone samples were exposed in vitro to atmospheres of increasing PCO2. Bone CO2 increased by 15% of its original content when exposed for 60 min. to pure CO2. CO2 uptake by bone in vitro was shown to be time- and PCO2-dependent, evoking a saturating mechanism and requiring the presence of water in bone. These findings lead to the conclusion that the bone CO2 compartment consists of 30% bicarbonate and 70% carbonate. The exact location of the bicarbonate pool and its availability as a buffer store for the whole organism are discussed.


Properties of 'irritant' receptors in canine lung.

Activity was recorded from 48 vagal afferent fibers arising from what appeared to be rapidly adapting receptors in the lungs of open-chest dogs. Most of these receptors were stimulated by hyperinflation, forced deflation and reinflation of the lungs, and their mean conduction velocity was 23.3 m/sec (n=41) compared with 32.3 m/sec(n=100) for pulmonary stretch receptors. Activity in the receptors was increased most frequently by histamine given by aerosol or intravascularly, only occasionally by ammonia vapor and cigarette smoke, and was essentially unchanged by ether vapor, CO2 and phenyl diguanide. The importance of locating presumed pulmonary receptors in the lungs is emphasized, as responses of receptors in the esophagus and pulmonary artery to ventilatory and chemical stimuli were similar to those of rapidly adapting bronchopulmonary receptors. The properties of these canine bronchopulmonary receptors are compared with those of similar receptors in other species. The lack of effect of inhaled irritants on most rapidly adapting receptors in dog lung indicates that the term 'irritant receptor' may be inappropriate.


[Optic ataxia localised in the left side of both 2 left homonymous visual hemifields].

Ocular ataxia localised to the left limbs on the left homonymous visual hemifields occurred after section of the right parieto-occipital junction zone performed to remove an intraventricular tumour. Since the right upper limb was unaffected, it must be presumed that, in man, there are two types of occipito-frontal connections, direct and crossed.


[Etiological diagnosis of spondylitis.  I. Clinical, biological and radiological aspects].

The authors compared the different elements of diagnosis contributed by the clinical examination, and by laboratory and radiological investigations in 33 cases of Pott's disease and 46 cases of non-tuberculous spondylodiscitis. They show that certain elements indicate the diagnosis of Pott's disease : associated visceral tuberculosis, and a radiogram showing in particular a centro-somatic notch, recent primary infection, absence of pain, minimum signs of medullary compression ; other elements on the other hand, indicate a diagnosis of non-tuberculous spondylodiscitis : a negative cutaneous tuberculin test, a positive haemoculture, humoral signs of melitococcosis or of typhoid fever, any indication of possible means of entry of infection in the two months before the disease, radiological signs of reconstruction in the first four months of evolution, location of the lesion in the anterior upper part of the vertebra, and to a lesser degree, the acute febrile nature of the clinical picture. The authors recall that the existence of a large abscess, of which there were no examples in the present series, is an indication in favour of tuberculosis.


[Recentering the patella in the treatment of external femoropatellar arthrosis with displacement of the patella].

The authors report their experiences of the surgical treatment of external femoro-patellar arthrosis with displacement of the kneecap, by recentering the kneecap, on knees that were not deformed as seen from the front. This recentering of the kneecap, which was monitored during the operation by radiographs with axial projection, was obtained by internal transposition of anterior tibial tuberosity and section of the external " wing " of the patella. No inert or living material was placed between the patella and the trochlea. The reduction in pain and the improvement in articular function depend on how well the patella is recentered. Twenty-two cases of external femoro-patellar arthrosis with displacement of the kneecap were treated in this way; in 18 operations, 14 results that remained favourable for more than 6 months have encouraged the authors to continue their trials and to abandon, at least for the time being, patellectomies and patelloplasties.


[Gout, hyperuricemia and femur head osteonecrosis (FHON)].

The authors report on 14 cases of osteonecrosis of the femoral head (ONFH) in patients suffering from gout. The cases of association were discovered over a period of 10 years among 232 patients with ONFH and 651 with gout. The necrosis had no particular characteristics except that there was a clear preponderence in males and a slight tendency to be bilateral; it occurred, perhaps, at a slightly earlier age. The patients with gout did not show any special clinical features ; the gout always preceded the necrosis, on average by 7 1/2 years. There was no obvious history of painful crises in the hip that could be attributed to the acute gout, except in one case. The excess of urate was detected by the baseline level of uricaemia (91 mg/litre on average), by the frequency of tophus (4 out of 14), and by the frequency of urinary lithiasis (2 out of 14), and did not appear to be any greater in the patients with gout and ONFH than it was in the whole of the population of gout patients. In those patients in whom it was estimated, the lipid analysis showed most frequently an increase in total lipids, in triglyceridaemia, and in cholesterolaemia. In the 5 patients in whom the investigations were sufficiently detailed, the dyslipidaemia was of Frederickson type II + IV (mixed hyperlipidaemia according to de Gennes' classification). Different physiopathological hypotheses are discussed by the authors, notably those concerned with micro-particulate fatty emboli (lipomicrons), which may obstruct, among others, the terminal arteries of the femoral head. Of the 6 patients for whom it was possible to obtain information, for an average period of 10 years since the onset of the necrosis, 2 had presented with untreated hyperlipidaemia and a severe general vascular illness (myocardial infarction in one case and regressive hemiplegia in the other). These findings lead to the conclusion that correction of the hyperlipidaemia by diet is indispensable to ensure the long-term survival of these patients.


[Study of blood calcium in a population of 3148 women. Variations with age. Correlation with other biological values].

The authors studied calcaemia and its correlations with other biochemical values in a population of 3,148 women. Calcaemia was 95.53 mg/litre +/- 3.54, a level equal to that found in 6,048 men. In 82 women (2.6 percent) the level of calcaemia was less than 90 mg/litre, and in 21 (0.66 percent) the level of calcaemia was less than 88 mg/litre. In 13 women (0.41 percent) the level of calcaemia was more than 105 mg/litre. Calcaemia in women decreased with age up to 50 years, increased again from 50 to 60 years and then fell again. There was a strong positive correlation between calcaemia and protidaemia (r = + 0.53) and a weak positive correlation between calcaemia and cholesterolaemia (r = + 0.19).


[Incidence of hyperuricemia and gout in coronary insufficiency from angina pectoris to myocardial infarct].

The authors try, on one hand, to estimate the role of hyperuricaemia and gout as risk factors in coronary diseases and, on the other, to decide whether the factors react in an isolated or associated fashion.


[Modification of uricemia coincident with myocardial infarct].

During myocardial infarction, uric acid values follow a very speciale evolutive curve, with 4 successive phases that might explain the occurrence of an episode of gout during an acute attack.


[Coronary insufficiency in patients with gout].

Statistics on the frequency of coronary insufficiency in patients with gout are contradictory. Nevertheless, it is shown that a correlation often exists between attacks of gout and attacks of angina or acute ischaemic episodes. Finally, these anatomo-clinical studies prove the reality of the gouty heart if only because of the discovery of deposits of intracardiac urates.


[Histomorphometric and biological data on osteoporosis due to immobilization].

The effect on the bones of immobilization was studied by means of quantitative histological methods on 34 biopsies of the iliac crest after different periods of immobilization in 28 patients, 22 of whom were immobilized by medullary lesions. At the same time a biochemical study was carried out on 68 immobilized patients over a 52-week period. This histomorphometric study included measurements of the absolute volume of trabecular bone, the volume of the osteoid matrix, the osteoclastic resorption surfaces, the size of the osteocyte lacunae, the thickness of the iliac cortical zones and the medullary adipose volume. 19 subjects received in addition double labeling with tetracycline with the object of carrying out a histodynamic study of the osteoblastic activity. The decrease in the absolute volume of the trabecular bone reached 33 percent of its original value and continued up to the 25th week, and was followed by stabilization at a value slightly higher than the vertebral fracture limit. Immobilization also led to an increase in the osteoclastic resorption surfaces and, secondarily, to an increase in the periosteocyte lacunae, a thinning of the iliac cortical zones, and a decrease in the volume of the osteoid matrix. Calciura increased as did total hydroxyprolinuria in parallel with an increase in the resorption surfaces. The histological and biochemical changes suggest a histodynamic hypothesis, according to which the longevity of the basic multicellular bone unit increases, leading to a new equilibrium characterized by very slow renewal of the bone.


[A new study on the midterm evolution of Fissinger-Leroy-Reiter syndromes seen in a military milieu (85 cases)].

Following-up a survey made in 1969 on 100 ex-soldiers suffering from the Fiessinger-Leroy-Reiter syndrome in Algeria, a new study investigated the evolution in 85 subjects, 85 percent of whom had suffered from the syndrome for 10 years or more. Those considered cured represented in the new study nor more than about 50 percent, instead of 65 percent, recurrences remained unchanged (15 cases out of 85 instead of 18 out of 100), the proportions with ankylosing spondylarthritis of the sacroiliac joints changed from 14 to 26 percent, and 5 patients remained unclassifiable. Sacro-iliac ankylosing spondylarthritis appeared in approximately half the cases in the 5 years that followed the commencement of the syndrome. Contrary to the findings in 1969, two cases of sacro-iliac ankylosing spondylarthritis were noted in patients who had experienced relapses. At present those in the cured group are those in whom the syndrome commenced the most recently and further deterioration in the figures may be expected in the years to come. Thus the long-term prognosis is difficult to evaluate from the initial symptoms. The severity of the evolution is only moderate, however, and without doubt the differences between individuals play an important role. The authors remain convinced of the principal that persons suffering from FLR are less likely to develop.


[Meniscal cysts. Therapeutic and pathogenic considerations].

The author presents a series of personal cases of meniscal cysts, compares them with other series in the literature, and draws certain conclusions. The meniscal cyst appears to be one of the manifestations of the myxoid degeneration of the meniscus-degeneration induced by small daily traumatisms. The rarity of the condition is related to the fact that movement of the myxoid substance is asymptomatic when it is towards the joint cavity. The greater frequency of the condition on the external meniscus is explained by a study of the forces applied on the knee. In contrast to the prevailing idea that surgical treatment is required, the author believes that puncture of the cyst is the most logical and simple treatment. This puncture avoids, in the long term, the risks of meniscectomy, which in 30 to 50 percent of cases, according to different authors, leads to poor results.


Conjugation of non-erythroid bilirubin in chronic experimental cholestasis in the dog.

The dynamics of conjugation of 14C-bilirubin injected intravenously during cholestasis is known from studies in rats and dogs. No studies have been performed concerning the conjugation of non-erythroid bilirbuin (NEB), i.e. the 10-20% of bilirubin synthesized from tissue haemes, mainly in the liver. This study reports the results of experiments in four dogs subjected to extra-hepatic cholestasis of 7-14 days' duration. delta-Aminolevulinic acid-5-C14HCi was injected intravenously as a NEB precursor. The appearances of unconjugated and conjugated labelled NEB as well as of the different azopigments were followed in systemic blood, liver vein blood, and thoracic duct lymph. The first NEB to appear was unconjugated; maximal concentration of unconjugated NEB in peripheral and liver vein blood was reached within one hour. The amount of conjugated NEB in both vascular compartments increased for two to three hours, after which time the degree of conjugation stabilized. The degree of conjugation was higher in liver vein than in peripheral blood for the first two hours. The same azopigments of NEB were found as for injected 14C-bilirubin. The a0 azopigment (azobilirubin) was present in higher amounts in peripheral than in liver vein blood, all the other azopigments were present in higher amounts in liver vein blood.


The role of the liver lymphatics in the transport of non-erythroid bilirubin during different stages of experimental cholestasis.

The role of the liver lymphatics in the regurgitation of bilirubin during the different stages of cholestasis has been a matter of debate. Earlier studies have shown that 14C-bilirubin injected intravenously one hour after induction of cholestasis was rapidly and completely cleared from the blood and appeared in the thoracic duct lymph in high concentration. During chronic cholestasis the injected 14C-bilirubin was delivered directly back to the blood after conjugation in the liver. The aim of the present study was to investigate the role of the lymphatics in the transport of non-erythroid bilirubin (NEB), a metabolic product of certain tissue haemes, produced mainly in the liver. The study was carried out in dogs. Five dogs were studied in the first hours following bile duct obstruction, and five others after at least one week of cholestasis. 14C-delta-aminolevulinic acid was given as a NEB precursor. In contrast to the results obtained with 14C-bilirubin injection, evidence for a delivery of conjugated labelled NEB directly to the blood during acute cholestasis was found. The concentration curves for NEB and non-NEB radioactivity in the thoracic duct lymph indicated the presence of a secondary biliolymphatic regurgitation. In chronic cholestasis no evidence for such a biliolymphatic regurgitation of NEB was found.


Sources of the serum isoamylases and their normal range of variation with age.

The isoamylases in various human tissue homogenates and body fluids were separated by agarose gel electrophoresis. Nothing suggested any significant production of amylase in the liver. Minute amounts of amylase belonging to the pancreatic group of isoamylases might be produced by the glands of the proximal duodenum. The specific group of isoamylases produced in the female genital tract could not be demonstrated in serum or urine. The activity of amylase in serum was derived from two groups of isoenzymes, one group originating from the salivary glands, the other from the pancreatic gland. The contribution of each of these two sources to the total serum amylase was determined from early foetal life to adult age. A very low activity of the salivary isoamylases was regularly found in serum from 14-week-old foetuses. The activity increased steadily with age and reached the normal adult level, about 80 U/l, at the age of 5 years. The pancreatic group of isoamylases in serum developed later; the majority of children below 3 months had no demonstrable pancreatic isoamylase activity. The activity rose slowly to reach adult level, about 80 U/l, at the age of 10 to 15 years. The activity did not vary with sex, and the diurnal variation of the isoamylase was negligible. In children with cystic fibrosis of the pancreas the activity of pancreatic isoamylases in serum was low.


Lipase and co-lipase activities of human small intestinal contents after a liquid test meal.

Methods for the determination of pancreatic lipase in small intestinal content have been re-evaluated in the light of the presence of co-lipase therein. A method is described for the determination of co-lipase in intestinal content based on its property to reactivate bile-salt-inhibited lipase. Figures are given for lipase and co-lipase activities in intestinal contents of normal humans aged 1-22. These two components originating in the pancreatic juice vary in a parallel fashion, and no variations with age were apparent. A simple diagnostic criterion is given to detect a possible specific co-lipase deficiency.


Dynamic gastric response to expansion before and after vagotomy.

The dynamic gastric pressure response to expansion by direct intragastric air insufflation, 30-50 ml/s, was studied in healthy volunteers, non-operated ulcer disease patients, and in patients operated upon with antrectomy, antrectomy and vagotomy, or proximal selective vagotomy. Non-operated individuals accepted gastric expansion without considerable increase of pressure. Antrectomized patients showed a higher basal pressure and a moderate increase of pressure during expansion. Vagotomized patients, including the ones operated upon with proximal selective vagotomy, demonstrated a marked increase of pressure during expansion. The results indicate that vagal denervation of the corpus-fundus part of the stomach is followed by an impairment of gastric resrvoir function.


Influence of a fatty acid on duodenal motility.

The duodenal transport mechanism has been studied by a method combining roentgen-fluorography and multiple pressure recordings. Three main types of motility were distinguished: propulsive, retrograde, and static. The motor pattern in the first part of the duodenum was studied in 15 individuals under basal condition and after application in the duodenal lumen of sodium myristate. The resulting inhibition of gastric emptying was found to be correlated to a significant inhibition of the propulsive movements in the duodenum. The two others types of motor activity did not change significantly.


The insulin test: negative and positive tests versus numerical values.

The result of the insulin test is commonly expressed as negative or positive according to different criteria. In 42 male duodenal ulcer patients subjected to selective vagotomy and pyloroplasty (SV + PP), negative and positive tests according to different criteria were compared with respect to the acid response to insulin and 2-deoxy-D-glucose (2DG), and to the percentage reduction of the response to insulin by SV + PP. The mean response to insulin and 2DG was smaller, and the mean reduction greater in negative than in positive tests according to any criterion. There was, however, a considerable over-lapping of the responses, or reductions, or both, between negative and positive tests. In tests negative to 4 or more criteria, insulin and 2 DG stimulated secretion by less than 0.50 mEq/30 min, but the reduction varied from 60 to 100 per cent. Accordingly, in individual patients the terms negative and positive test to most single criteria give no information about the acid response after the vagotomy nor about the effect of the vagotomy, unless the test is negative to 4 or more criteria. It is suggested that the result of the insulin or 2DG test should be reported in numerical values as basal and stimulated acid output and concentration instead of stating that the test is negative or positive.


Chronic active hepatitis. Aetiological considerations based on clinical and serological studies.

The diagnosis of chronic active (aggressive) hepatitis is based mainly on characteristic morphological changes. During a 7-year period, 85 cases were diagnosed in three medical departments in Copenhagen. This material is presented by clinical, biochemical, and serological variables at the time of diagnosis. None of the patients had simultaneously occurring Australia antigen and circulating autoantibodies. A comparison between two serologically homogeneous groups revealed significant differences in sex and age distribution onset of disease, and biochemical activity. The investigation suggests the existence of aetiologically different forms of chronic active hepatitis. Some cases are apparently caused by a persistent viral infection, while others may be due to a primary autoimmune mechanism. A considerable number of the patients stated that they had had prolonged intake of the potentially hepatotoxic laxative, oxyphenisatin. Nineteen patients were challenged with the drug and eight reacted with an increased biochemical activity in the liver disease. All these patients belonged to the group with circulating autoantibodies. It is possible that oxyphenisatin may be the primary cause of the chronic liver damage in some cases.


The effect of intragastric neutralization on the gastric acid response to antral distension in man.

The gastric acid secretion in response to graded antral distension was determined in healthy subjects and in peptic ulcer patients with water perfusion or alkaline buffer perfusion of the stomach, giving an intragastric pH of 1.8-3.0 and 6.2-8.3 respectively. Intragastric neutralization increased the basal acid secretion in healthy subjects and gastric ulcer patients but did not change the basal acid secretion in duodenal ulcer patients. Distension of the antrum produced the same secretory effect with and without intragastric neutralization: no increased acid response in healthy subjects, a slight acid response in patients with a quiescent duodenal ulcer or a gastric ulcer, and a more pronounced acid response in patients with an active ulcer, amounting to about 30% of the peak acid response to pentagastrin. The results show that: a) the peptic ulcer patients - and particularly patients with an active duodenal ulcer - are more sensitive to the acid secretory effect of antral distension than healthy subjects; b) increasing the intragastric pH above 20 does not enhance the acid response to antral distension; c) the acid secretory effect of antral distension is markedly less in man than the effect observed in the dog.


Bile flow and biliary lipid secretion following release of biliary obstruction in man.

In order to elucidate the relationship between bile acid secretion and the secretion of lecithin and cholesterol in the postcholestatic condition, five patients were studied after release of complete biliary obstruction. Ten patients operated on for uncomplicated gallstone disease served as controls. The secretion of bile acids, which constituted only newly synthesized acids, increased in the postcholestatic period 2.5-22 times. In spite of that the secretion rate of bile acids was low (less than or equal to 7.5 mumol x min-1). The pattern of the relationships between bile acid secretion and bile flow and bile acid secretion and lecithin and cholesterol secretion was the same in the postcholestatic patients as in the controls. However, the bile flow showed a higher bile acid dependency in the postcholestatic condition, and the bile-acid-independent flow varied considerably in these patients as compared with controls. Linear relations between the secretion rate of bile acids and lecithin and cholesterol secretion rates were found. Extrapolation to zero bile secretion revealed Y-intercepts, which were not statistically significantly different from origo. Calculations of bile acid - lecithin and bile acid - cholesterol relations in the controls at correspondingly low bile acid secretion rates (less than or equal to 5 mumol x min-1) gave results similar to those in the study group. The bile was supersaturated with cholesterol in all the postcholestatic patients similar to the condition in the controls at correspondingly low bile acid secretion rates. It is concluded that the bile acids are determinative for the biliary secretion of cholesterol and lecithin even at very low bile acid secretion rates. This conclusion was valid in patients with presumably normal liver function as well as in the early phase after release of severe cholestasis.


Ileorectal anastomosis in ulcerative colitis. Results in 57 patients.

The early results of colectomy and ileorectal anastomosis (IRA) in 57 patients with ulcerative colitis seemed fair. The operative mortality was relatively low (7%) also in fulminating cases (10.5%), which constituted one-third of the material. The late results were less satisfactory. Half the survivors were in need of rectal extirpation and ileostomy because of rectal dysfunction. Until now 6% have developed cancer of the rectal stump. The early diagnosis of this condition was difficult. The results regarding rectal function, stenosis, and inflammation were significantly worse in women than in men. Moreover, dyspareunia was a severe problem in more than half the women. We have abandoned IRA in the treatment of ulcerative colitis.


Distribution of disaccharidases, alkaline phosphatase, and some intracellular enzymes along the human small intestine.

The longitudinal distribution of various enzymes along the human small intestine was studied by analysis of biopsies from different parts of the small intestine, obtained from 13 patients during shunt-operation for severe obesity. Alkaline phosphatase and 3 glycolytic enzyme activities studied were rather uniformly distributed along the small intestine. Acid beta-galactosidase and hetero beta-galactosidase activities were highest in the proximal small intestine with a gradual decline throughout the intestine. The activity in the distal ileum was about half  of the maximum activity. Maltase, isomaltase, sucrase, and trehalase activity had a broad maximum in the proximal and middle small intestine with a rather sharp decrease in the distal ileum. Lactase activity had a more pronounced maximum in the middle intestine with a pronounced decrease towards the proximal and distal ends. The disaccharidase activities in surgical biopsies taken 5 cm distal to the ligament of Treitz were about 10% higher than in peroral biopsies taken just at the ligament.


Disaccharidase activities in intestinal metaplasia - contribution of lysosomal brush border enzymes.

Maltase, sucrase, and lactase were measured at pH 4 and pH 6 in normal and intestinalized gastric mucosa. In the normal mucosa the low activities of maltase and lactase seemed to be entirely due to lysosomal enzymes with acid pH-optimum. In intestinal metaplasia, brush border maltase and sucrase, but not lactase, appeared. On the other hand, there was a significant increase in lysosomal lactase (beta-galactosidase) activity.


Gastric and duodenal ulcers in the same patient.

The present prospective analysis shows that duodenal ulcers far more frequently than gastric ulcers are followed by a secondary ulcer. In patients with a gastric ulcer the cumulated 6-years probabilities of developing secondary ulcers thus was 8.8% while the corresponding risk of secondary ulcer in patients with duodenal ulcer was 3.7%. The probability of developing secondary ulcers was the same in men and women, and independent of the site and nature of the morphologic changes in the stomach and duodenum respectively. However, among patients with a gastric ulcer younger patients seem particularly apt to develop secondary ulcers. The total probability  of having both types of ulcer diagnosed in patients fulfilling the criteria of the ulcer disease was estimated at approx. 12%; but certain observations indicate an even higher frequency of the disease.


An evaluation of the 'breath test' in Crohn's disease.

The 1-(14C)-glycine-glycocholic-acid breath test was evaluated in 10 normal subjects and in 38 patients with Crohn's disease. Twelve patients were non-operated and 26 had been subjected to ileal resection (10-180 cm). In addition, coecal resection or right-sided hemicolectomy was performed on 20 patients and subtotal colectomy on six. The 14C-excretion in breath was abnormally elevated in only 16 of the 38 patients with Crohn's disease. Combining 14C-excretion in both breath and faeces, the test was found to be correlated with the activity of the disease in non-operated cases, whereas all resected patients were found to have bile acid malabsorption. It is concluded that the breath test is useless in Crohn's disease without concomitant measurement of the radioactivity in stools. The faecal 14C-excretion was correlated with the extent of ileal resection and with the extent of colonic resection, whereas the 14C-excretion in breath was independent of the type of operation performed. The breath test was found to be a more sensitive assay for ileal dysfunction than the duodenal bile acid concentration and the vitamin B12 absorption. No correlation with an elevated G/T-ratio and an abnormal bacterial growth was found.


A case of sideroblastic anaemia associated with marked elevation of erythrocytic arginase activity.

Abnormal erythrocytic arginase activity about 30 times higher than normal controls, was found in a 63-year-old male with sideroblastic anaemia. We suggest that an abnormal concentration of arginase in the erythroblasts, in this case reduces the arginine concentration and results in decreased haemoglobin synthesis.


Histamine metabolism in polycythaemia vera.

Histamine metabolism was studied in 35 patients with polycythaemia vera (PV) at different stages of their disease and compared with controls and patients with secondary polycythaemia. In addition to blood and urinary histamine the main urinary metabolites of histamine, methylhistamine (MeHi) and 1-methyl-4-imidazoleacetic acid (MeImAA) were measured. In patients with active PV the excretion of MeHi and MeImAA was significantly higher than in controls and secondary polycythaemia, indicating an increased histamine formation. The MeImAA excretion was correlated to the blood histamine level, the degree of blood basophilia, the total white blood count and the spleen volume. The blood histamine level was significantly higher in PV patients compared with controls and secondary polycythaemia. No patients with secondary polycythaemia had an increased blood histamine level. With the bio-assay technique used in this study the urinary excretion of histamine in the PV patients was within the normal range. There was no correlation between the increased histamine formation and "histamine-related symptoms". Pruritus and duodenal ulcer occurred with a similar frequency in patients with and without increased MeImAA excretion. The similarity between the disturbance of the histamine metabolism in PV and that found by other authors in chronic myeloid leukaemia is pointed out.


The in vitro and in vivo evaluation of tilorone hydrochloride as a platelet aggregation inhibitor.

Tilorone hydrochloride was tested in vitro for inhibition of platelet aggregation in the ADP, collagen, and epinephrine-induced platelet aggregation systems. Tilorone did not significantly inhibit the first phase of platelet aggregation induced by ADP, but was a very potent inhibitor of the second phase of platelet aggregation (release reaction) as illustrated by the epinephrine-induced system. When the compound was given to rats by stomach tube at 100 mg/kg for 2 doses, 24 h apart and blood taken 24 h after the second dose, an inhibition of collagen-induced platelet aggregation was found. This result is interpreted as inhibiting the release reaction and second phase platelet aggregation.


Cell separation by staphylococcal protein A-coated erythrocytes.

A method for cell separation according to cell surface markers is described. Heat-aggregated human IgG or IgG antibodies, raised to surface markers of mouse lymphocytes-for example, Ig or theta antigen-are allowed to react with the lymphocytes. When these cells are incubated with sheep erythrocytes coated with protein A of Staphylococcus aureus, rosettes are formed. These rosettes can be separated from nonrosetted lymphocytes by density gradient centrifugation. The erythrocytes of the rosettes are disrupted by complement action or by osmotic shock, and the lymphocytes are recovered. Immunoglobulin-protein A complexes are shed off the cell surfaces by cultivation. In this way cells with, as well as those without, surface markers could be obtained with high purity (up to 80%) and with high viability.


Identification of cells with monocyte markers in panhypogammaglobulinaemia.

Nonphagocytic cells bearing receptors for complement and IgGFc in blood samples from four boys with panhypogammaglobulinaemia who lacked B lymphocytes were positively stained for human macrophage antigen (HuMA) and intracellular peroxidase. Similar non-T, non-B cells were found in adult blood preparations but in lower numbers than in the four boys above and in two of three other boys with various immunodeficiencies. Because of their monocyte characteristics, it is improbable that these cells are B-lymphocyte precursors; this is consistent with our view that there is a central failure of B-cell induction in boys with panhypogammaglobulinaemia who lack lymphocytes with surface immunoglobulin.


Massive invasion of fetal lymphocytes into the mother's blood at induced abortion.

The proband, a healthy primipara, selected for study after she had asserted that she had not previously been pregnant, gave birth to a healthy girl with the karyotype 46,XX. In the 21st week of gestation, leukoagglutinin-stimulated mitoses from the proband's blood were 99% 46,XX and 1% 46,XY, the Y chromosome being identified by its quinacrine fluorescence. In two samples taken later in pregnancy no XY mitoses were found in the cultures, but on all three occasions brightly fluorescent Y chromatin in a proportion of the uncultured lymphocyte nuclei showed teh presence of XY cells in the proband's blood. High titers of cytotoxic anti-HL-A 3 were detected in the maternal serum before and after delivery. Our tentative interpretation is that the XY cells in the proband's blood emanated from a previous fetus that was legally aborted by curettage on the 10th week of an uneventful pregnancy and which the patient admitted to only after repeated questioning.


Salmonella infections in Stockholm. A 10-year review.

During the 10-year period 1963-1972 the total number of cases of salmonella infection reported to the Public Health Administration in Stockholm was 3012. The annual incidence varied between 72 (1966) and 23 (1972) per 100000 population. Peak frequencies appeared in the age groups 15-25 and 45-64 years. 101 different serotypes were diagnosed with S. typhi murium being the most common type (37%). 63% of the cases were infected during travel to foreign countries and in 19% food-borne transmission occurred. During the 6-year period 1963-1968 85% of all cases were treated in hospitals. In 1969 a new law governing infectious diseases came into force making it easier to reduce the strict measures imposed by the previous law of 1919. During the 4-year period 1969-1972 53% of the cases were hospitalized. In spite of this reduction no change in the annual pattern of secondary cases has been observed.


Persistent cerebellar symptoms after infection with Mycoplasma pneumoniae.

Mycoplasma pneumoniae infection in a 47-year-old man is reported. Symptoms of upper respiratory tract infection were followed by pneumonia and meningoencephalitis. In contrast to published cases with neurological manifestations of infection with M. pneumoniae, the patient was disabled by persistent cerebellar symptoms with generalized ataxia and atactic dysarthria. Some possible pathogenic mechanisms of the neurological manifestations of infection with M. pneumoniae are considered.


Epidemiology of hepatitis B antigen and antibody in hospital patients in Copenhagen.

A 4-year continuous screening for hepatitis B antigen (HBAg) in all patients admitted to a Copenhagen general hospital revealed 253 antigen-positive cases among 99000 patients (2.5%). 97 of the patients had acute or chronic hepatitis, while there were no signs of liver disease in 156. The "healthy" carriers showed a wavy age distribution, indicating an increased transmission of HBAg in age groups born 1920-30 and 1940-60. Hepatitis B antibody (HBAb), measured by a radioimmunoassay, occurred in 8.6% of 1000 patients. HBAb also showed an uneven age distribution with a peak prevalence of 17.5% in the age group born 1910-30. These figures indicate that the prevalence of HBAg and hence presumably also the hepatitis B virus has fluctuated within this homogeneous population, probably related to changes in the sociohygienic conditions. Determination of HBAg subtypes D and Y in 161 patients indicated that the Y-subtype is now being introduced into a formerly subtype D area by means of drug addiction, tourism or workers of East-Mediterranean origin.


Hand, foot and mouth disease associated with coxsackievirus group B.

This study from Frankfurt, although similar to other reports with respect to clinical findings, presents further evidence of a varied etiology for hand, foot and mouth disease (HFMD). Of the 6 patients with HFMD, 5 ahd virologic evidence of coxsackievirus B5 infection, and 1 had definite evidence of coxsackievirus B2 infection. Our data suggest an etiologic association of coxsackievirus group B with HFMD.


Acute viral hepatitis: a comparative study of clinical, biochemical, morphological and immunological features in patients with and without Australia Antigen.

500 consecutive patients with acute viral hepatitis verified by biopsy were divided into groups of 202 patients with detectable Australia (Au) antigen and 298 patients without antigenaemia at the time of admission to hospital. Comparison was made of the initially recorded clinical, biochemical, histological and serological variables in the two groups. Judged by both histological and biochemical criteria, the acute disease was more severe in the 202 patients with Au antigen than in the 298 patients without Au antigen. Evidence is presented that this difference is possibly due more to qualitative aetiological differences between the two groups than to the duration of antigenaemia or the time of hospitalization. Thus, the demonstration of Au antigenaemia provides not only epidemiological but also relevant clinical information.


Arthritis associated with Yersinia enterocolitica infections.

74 patients, 42 females, 32 men-all over 10 years of age, with acute arthritis associated with infection with Yersinia enterocolitica are presented. The diagnosis was based on serological evidence in all cases (an agglutinin titre of 320 or more), and in 18 of the cases also a positive culture of Y. ent. from faeces. The erythrocyte sedimentation rate was very high in most cases. Acute enteritis, sometimes with abdominal pain, preceded the acute arthritis with a latent period of about 1-14 days. In 50% of the cases only one or two joints were involved, most often large joints such as knee, ankle and wrist. The symptoms were long-standing (2 months or longer) in two-thirds of the cases. Arthritis in connection with yersiniosis must therefore be considered a serious complication to an otherwise rather benign infection.


Bacterial contamination of urine, collected in fractions from different phases of micturition. A study in healthy women.

With a special technique 4-13 consecutive fractions of urine were collected during micturition from 4 female volunteers at together 12 occasions. Quantitative bacterial cultures were performed in 78 urine fractions. Most fractions contained one or several different bacterial strains-generally in small amounts, wheras only 14% were sterile. Fractions from the end of micturition showed on average less bacterial contamination than the earlier portions. No difference was observed between the bacterial counts after cleaning the area around the urethra as compared with the counts without preparation before sampling.


Epidemiological aspects of toxoplasmosis. II. The prevalence of positive toxoplasmin reactions in naval recruits from different parts of Norway.

686 (22.5%) out of 3047 naval recruits from all parts of Norway showed positive reactions (induration greater than or equal to 2 mm) when tested with the toxoplasmin cutaneous test (TcT). The highest frequency of positive TcT was found in the south-western part of the country (34.7%). The frequency was low in the inland of Southern Norway (13.6%), and especially low in the northern part of the country (9.5%).


Some clinical, immunological and bacteriological observations in a case of pyogenic arthritis due to bacteroides fragilis.

A case of recurrent pyogenic arthritis in a knee joint and abscess formation of the lower limb is described. The infection occurred in a 70-year-old male patient treated with steroids for rheumatoid arthritis. A strain of Bacteroides fragilis was repeatedly isolated both from the knee joint and the abscess. The isolated strain was used as antigen in tube agglutination tests and significant titre changes were observed during the course of the disease. The isolated strain was initially sensitive to doxycycline but developed resistance to this drug during therapy. The sensitivity to lincomycin remained unaffected.


Criminality among female alcoholics.

The proband group consisted of 71 female alcoholics subjected to compulsory treatment by the Temperance Board in Malmö. 38 probands were recorded in the Penal Register. For a period from year 20 before to year 9 after the first compulsory treatment, 85 offences were committed. During the same period, less than one recorded criminal offence was expected, according to an age- and calendar year specific risk table for Swedish women. In relation to the expected incidence, the observed was not particularly high at the beginning of the period. From year 12 up to year 2 before the intervention, it increased to an extremely high level where it remained. The distribution of the crimes according to nature agreed with that valid for Swedish women in general. The average age at the crime debut was conspicuously high, about 30 years. Despite, this, the first criminal offence, as also the first gonorrhoeal infection, was an early sociomedical symptom; not until later did public assistance and conviction for drunkenness usually arise.


Screening--an efficient tool in outpatient endocrine care. Studies of the diagnostic process.

A screening procedure based on physical examination alone was used in the outpatient unit of a department of endocrinology and metabolism. The effectiveness, efficiency, and volume of this diagnostic process were evaluated by a study of the case records and a mail questionnaire. In 1968, 296 subjects were examined by this screening procedure; 103 of these could immediately be referred back. The percentage of confident endocrine diagnoses increased from 31 to 39%. The corresponding figure for the group of subjects immediately referred back was 100%. A considerable change in the diagnoses was also recorded. The use of the screening procedure saved approximately ately +30,000. It is concluded that diagnostic screening by an experienced endocrinologist is inexpensive, efficient and safe. The use of the screening procedure made it possible to offer highly specialized medical treatment to more people.


Arteriosclerotic and other degenerative heart diseases in Finland. I. A death certificate study of the frequency of degenerative heart diseases among males and females.

All available information recorded on the death certificates of 12973 Finnish persons who, according to the official Finnish mortality statistics, died in 1968 from arteriosclerotic and other degenerative heart diseases (ADHD, rubrics 420-422 in ICD) comprised the material of the present study. The mortality of males from ADHD analysed by age and place of residence was very high when compared with various national rates of international WHO statistics. The degree of urbanization of the domicile did not have any statistically significant effect on the mortality from ADHD. Significant differences between various provinces were found in the mortality of males from ADHD. The male population living in the eastern provinces of Finland showed a highly significantly higher mortality from degenerative heart diseases than the male population living on the west coast. A highly significant difference was found in mortality between various subgroups of the Finnish male and female populations analysed by age, place of residence, and type of community. The uniform difference between the mortality of various male and female subgroups of the Finnish population, which was obtained using the present statistical survey of death certificates, and the fairly uniform distribution of high rate of mortality of males from degenerative heart diseases in most regions of the country lend further support to the reliability of cause-of-death statistics, since certification of deaths can then be regarded to occur uniformly and with about the same accuracy in different parts of the country.


Arteriosclerotic and other degenerative heart diseases in Finland. II. A death certificate study of the examination of the cause of death from degenerative heart diseases.

A statistical survey of death certificates was made to analyse the ante-mortem and post-mortem medical and medico-legal examinations used in the determination of the cause of death of 12973 decedents who were recorded officially to have died of arteriosclerotic and other degenerative heart diseases in Finland in 1968. The relationship between the regional autopsy rate and the rate of mortality from degenerative heart diseases was studied in particular. The survey indicated that there was no systematic relationship between the type of ante-mortem and post-mortem cause-of-death examinations, including medical and medico-legal autopsies, and the rate of mortality from arteriosclerotic and other degenerative heart diseases in various groups of the Finnish population analysed by age, sex and domicile. This was concluded to be an indication of the reliability of Finnish cause-of-death statistics of degenerative heart diseases which show a generally high rate of mortality and prominent regional differences in the rate of deaths from those diseases among the Finnish male population.


Organization of a breast tumour clinic and aspects of data analysis of a clinical material.

With the aim of making it easier for patients with tumours or suspected tumours of the breast to obtain adequate medical advice and treatment, a special breast tumour clinic was established at the Department of Surgery of the University Hospital in Uppsala for women resident in the county of Uppsala. The waiting time was less than one week. In addition to palpation, fine-needle biopsy with cytological examination, mammography and xeroradiography were performed. Close co-operation between a few doctors responsible for the various diagnostic units made it possible to give the patients quick service and contributed to an efficient use of the diagnostic resources. The clinic functioned mainly within the framework of the existing medical care facilities and did not act as a screening project. Over a period of 15 months, 1244 women were examined. 116 had breast cancer, and 5 of these tumours were occult. A comparatively low mean tumour size and a low frequency of lymph node metastases would seem to indicate that the patients came under medical care at a relatively early stage. For recording of the case histories and examination findings, special medical records permitting data processing were used. This has facilitated follow-up of the patients, special checks on certain patient groups, statistical analyses and prospective investigations. We consider that, for the patient, a clinic of this kind offers considerable psychological and financial benefits, and that for the health service as a whole it means increased efficiency and a lower cost per patient. It seems probable that both the patient's and the doctor's delay are reduced.


Vitamin D and serum cholesterol.

During a mass survey for coronary heart disease in Tromsö, Norway, in 1974, 385 men aged 20 to 50 from one particular electoral district completed an additional questionnaire concering the intake of vitamin D from all sources (natural food, fortified food and vitamin D preparations). The average daily intake of vitamin D during the preceding 12 months was later related to the respective serum cholesterol levels. For the whole material, no association was found. When the men were grouped according to vitamin D intake above and below 2.5 mug and serum cholesterol levels above or below 250 mg %, a significant relationship appeared (using Yates's correction X2=10.3, P=0.0013 and the correlation coefficient 0.011 less than P less than 0.005).


Elderly people's compliance with prescriptions, and quality of medication.

We set out to examine how quality of medication influenced patients' use of drugs. 217 elderly people living in homes for the aged in Helsinki were interviewed. They used a considerable number of prescribed drugs: one-third of them had ingested at least four different prescribed drugs during the previous week. This polypharmacy largely concerned symptomatic drugs. Non-compliance with prescription instructions was common, and was more common with the symptomatic drugs. The number of deviations from the instructions correlated positively with the number of drugs, especially the number of symptomatic drugs. According to this study, non-compliance with prescription instructions is not to be condemned as such. In so far as drugs are prescribed in unreasonable large quantities, underuse is a way for the patient to avoid ingesting excessive quantities of drugs.


Detection, treatment and follow-up of hypertension in a community sample of 55-year-old men.

In connection with a population study including 703 randomly selected 55-year-old men, 20 men with the highest blood pressure were selected for a careful follow-up and treatment for 1 year. Controls without hypertension were randomly selected from the remainder of the same population. Electrocardiogram at rest and in connection with an exercise test, changes in fundus oculi, orthostatic tests, peripheral arterial blood flow, chemical analyses and other variables were recorded on three occasions during the observation year. Drug treatment was standardized. Basic treatment was induced with polythiazide, which normalized the blood pressure in the majority of the hypertensive cases. The most striking findings in the hypertensive group before treatment were, besides the high blood pressure at rest, high blood pressure during exercise, an increased peripheral blood-flow through the calves, and an increased heart rate. During treatment, the blood pressure were selected for a careful follow-up and blood-flow were almost "normalized"; the heart-rate remained elevated. The investigation shows that it is quite easy to achieve adequate reduction of blood pressure in hypertension among middle-aged men, as found in the "real world" outside the hospital. The main problem today is not to normalize the blood pressure but rather to detect hypertension and to maintain the therapy for several years. Hypertension is considered to be the cardiovascular risk factor that is probably most amenable to preventive approaches to public health.


Aortic valve replacement with frame-supported autologous fascia lata grafts. II. Clinical and laboratory findings.

Thirty-five patients with a frame-supported autologous fascia lata graft implanted in the aortic annulus were investigated 11 to 36 months after operation. The group comprised 7 patients with pure aortic stenosis, 11 with combined stenosis and incompetence and 17 with pure aortic incompetence. Seven patients had concommitant mitral valve disease. The follow-up investigation included ECG, a work test on a bicycle ergometer, dynamic spirometry, roentgenological heart volume determination and haematological "screening tests" for intravascular haemolysis. Concomitant with a marked subjective improvement of the patients, there was a considerable objective improvement, as judged by physical working capacity, ECG signs of left ventricular hypertrophy and heart volume. The serum haptoglobin values were somewhat lower postoperatively (mean value 44 mg%), but no ahaptoglobinaemia occurred. Thus, no definite signs of intravascular haemolysis were noted. No thrombo-embolism occurred within this observation period, despite the fact that none of the patients with isolated aortic valve replacement were treated with anticoagulants. This investigation shows that a frame-supported autologous fascia lata valvular graft in the aorta can function well during a period of up to 3 years.


Aortic valve replacement with frame-supported autologous fascia lata grafts. III. Haemodynamic and angiographic findings.

Thirty-two patients with a frame-supported, autologous, fascia lata graft implanted in the aortic annulus were investigated 11 to 36 months after the operation. The group comprised 7 patients with pure aortic stenosis, 10 with combined aortic stenosis and aortic incompetence and 15 with pure aortic incompetence. Six patients had concomitant mitral valve disease. The follow-up investigation included right heart and transseptal left heart catheterization, left ventricular angiocardiography through the transseptal route and a retrograde, supravalvular aortography with the cinétechnique. Cardiac output was essentially unchanged postoperatively. However, it had increased considerably in some patients in whom it was very low before the operation. Left ventricular systolic pressure decreased particularly in patients with pure aortic stenosis. Left ventricular enddiastolic pressure decreased from 12 to 7 mmHg at rest and from 25 to 18 mmHg during exercise. Left atrial (or pulmonary arterial wedge) mean pressure decreased from 14 to 2 mmHg at rest, and from 27 to 16 mmHg during exercise. In 76% of the patients a slight (grade I or II) central or paravalvular aortic regurgitation was observed on cinéangiograms. Regurgitation of grade III was found in one patient. Technical details in the construction of the valve, as well as structural changes in the fascia lata which may be responsible for stenosis and incompetence in some of these valves are discussed. Thus, although even patients with defective valves have shown considerable improvement, a close and continuous follow-up of these patients is necessary.


Accidental ventricular fibrillation of the human heart. A study of excitability levels with alternating current.

With the use of electronic equipment in medical work an electrical hazard can not be completely avoided. The danger for the patient lies in an accidental ventrical fibrillation induced by a current passing through the body. Thresholds of vulnerability for such currents were determined in dogs as well as on the human heart during cardiopulmonary bypass. Various electrode positions were tested and the minimum current of induction was measured. The lowest current producing fibrillation of the human heart was 100 muA. At the electrode surface the density of the electrical field then was 6-14 muA/mm2. In our routine procedure during open-heart surgery, the mean value for induction was found to be 600 muA.


The puzzle of blood platelets in extracorporeal circulation. Comments based on recirculation experiments.

Oozing of blood from wound tissues after some time of total body perfusion and the demonstration of microemboli have brought into focus the inevitable disappearance of platelets from the blood during extracorporeal circulation. Recirculation experiments using dog blood are reported. The effect of a bubble oxygenator and a membrane oxygenator is compared. It is concluded that in principle they both contribute to the removal of functionally active platelets.