A thermodynamic assessment of possible substrates for sulphate-reducing bacteria. A thermodynamic feasibility study was applied as a means of predicting suitable energy-yielding substrates for growth of sulphate-reducing microorganisms. The average free energy release per electron pair for a substrate-sulphate oxidoreduction may be more or less than the energy requirement for ATP synthesis from ADP and Pi. Substrates were divided into two groups on this thermodynamic basis and the division was shown to accord with previous experimental reports; those substrates which released an average of at least 8-4 kcal per electron pair (35-2 kJ per electron pair) were able to support growth whilst those releasing less than 8-4 kcal were unable to do so. It is proposed that the thermodynamic assessment could be applied to a wide range of possible substrates to predict the likelihood of their serving as sole substrates for growth of these organisms. The literature concerning the use of hydrocarbons by sulphate reducers is confused and indefinite, but inclines toward the idea that use of long-chain hydrocarbons by these organisms is possible. In contrast, however, thermodynamic analysis showed that the highest energy release is from the short-chain alkynes.


Factors in the appreciation of a prosthetic rehabilitation. 6 months after the prescription of a hearing aid, the appreciation of the aid was judged in a group of 160 patients by a questionnaire. The analysis of the answers in combination with the audiometric features is reported. The answers given in a questionnaire have a good interrelation and agree with the score given for the aid. The audiometric features also showed a good correlation for every one but only a weak relation was found with the subjects' appreciations of the aid. The implications of this hearing aid evaluation for the improvement of the fitting procedure are discussed.


Dithionite reduction in the presence of a tetrapyrrole-containing fraction from the desulfoviridin of Desulfovibrio gigas. Low-molecular-weight fractions obtained from the desulfoviridin of D. gigas and from the growth medium of Desulfovibrio sp. 10455 promoted the reduction of sodium dithionite to sulphide in the presence of reduced methylviologen. These fractions contained a tetrapyrrole of the isobacteriochlorin type which was not complexed with iron, nor was it complexed with protein. The observations are discussed in relation to the function of sulphite reductases in the sulphate-reducing bacteria.


Re-examination of the effects of periodic and aperiodic stimulation on the auditory-evoked vertex response. It has been hypothesized that aperiodic stimulation will produce larger auditory-evoked vertex responses than periodic stimulation. Attentiveness toward an acoustic stimulus by human subjects has been shown in the past to enhance the auditory-evoked response. The unpredictability of aperiodic intersignal intervals has been assumed by previous investigators to produce more attentive listening behaviour and has therefore been used clinically to obtain 'enhanced' evoked responses. In order to examine this question further, auditory-evoked vertex responses were obtained with variable-interval (aperiodic) and with fixed-interval (periodic) schedules of stimulus presentation that had geometric mean intersignal intervals of 5 or 10 s. The evoked responses were obtained from normally-hearing adults while they were engaged in a counting task and while they were reading. Tone bursts were presented at 30 and 60 dB sensation level. No significant differences in peak-to-peak amplitude measures of components with latencies shorter than 300 ms could be attributed to aperiodic stimulation. When the time-base on the signal averager was extended to include components with latencies longer than 300 ms, no significant changes in component amplitudes could be attibuted to aperiodic stimulation, even though peak-to peak amplitudes during an attentive state (counting) were nearly double those obtained during an inattentive state (reading). It was concluded that aperiodicity in intersignal intervals is not a useful technique to employ in order to produce larger and more identifiable evoked responses for clinical diagnosis.


Amino acid sequence of the smaller subunit of conglutin gamma, a storage globulin of Lupinus angustifolius. The amino acid sequence of the smaller subunit of conglutin gamma, the simplest of the three globulins from the seeds of Lupinus angustifolius cv. Uniwhite, has been determined. The subunit was homogeneous and contained 154 amino acid residues, including five sulphur-containing amino acids--a considerably higher content than is found in most other legume storage proteins. There was no indication of the complexity experienced in studies of many other legume storage proteins. This is perhaps the first sequence of a subunit of a legume storage protein to be determined.


Sulphur-selenium studies in sheep. I. The effects of varying dietary sulphate and selenomethionine on sulphur, nitrogen and selenium metabolism in sheep. Sulphur, selenium and nitrogen metabolism were studied in Merino wethers fed for 35-day periods on semipurified diets in which the sulphur content was increased to either 0-07 or 0-20% by the addition of sodium sulphate. At both levels of sulphur, additions of selenium as DL-selenomethionine increased the basal level of selenium (0-02 microgram/g) to 0-06, 0-09 and 0-67 microgram/g. Both levels of dietary sulphur supported positive sulphur balances but a reduction in sulphur intake per se resulted in a significant depression in dry matter digestibility (P less than 0-05), apparent nitrogen digestibility (P less than 0-05), nitrogen balance (P less than 0-01), sulphur balance (P less than 0-05) and plasma sulphate-sulphur (P less than 0-05) and wool (P less than 0-01) selenium levels. Selenium balance was not affected by differences in sulphate-sulphur intake. Selenium balances (P less than 0-001), plus the selenium levels in plasma (P less than 0-001), and wool (P less than 0-001) were significantly different at the different levels of selenium supplementation. A positive selenium balance was achieved when the selenium intake was approximately 37 microgram/day, regardless of sulphur treatment. The validity of using plasma and/or wool selenium levels as indices of the selenium status of sheep is questioned.


Does pop music cause hearing damage?

Does pop music cause hearing damage? Relatively few investigations have so far reported on the hearing in pop musicians. In summary, these have shown a sensorineural hearing loss in 5%. This study was carried out on 83 professionals working with pop music. Depending upon how hearing loss is defined, we found a sensorineural loss in 13-30% of the pop musicians. Hearing losses were slight. It appears that the risk for hearing damage for the audience is small. A limit for presentation of the music at 95 dB (A) is suggested as a compromise satisfying both audiologists and audience.


Biotin deficiency and the development of the fatty liver and kidney syndrome in chickens: an ultrastructural study. The structure of the tissue from the liver, kidneys, pancreas and adrenal glands of 4-week-old chickens showing symptoms of the fatty liver and kidney syndrome (FLKS) was compared with that of normal tissue and related to the amount of biotin present in the liver tissue. These birds were reared with different levels of dietary biotin and were stressed by removal of food before being killed. Birds with less than 1-5 microgram biotin/g liver were considered to be deficient in biotin. In the stressed birds the severity of FLKS increased with decreasing levels of biotin. No lesions were found in the liver and kidney tissue of the birds with severe FLKS. Large quantities of fat were accumulated in the hepatocytes and intercellular spaces of the liver tissue, but the cell contents were not disorganized. In the kidney, conspicuous fat accumulation occurred in the proximal convoluted tubule cells and some ultrastructural disorganization of the cell contents was evident. No structural changes were found in the tissue of the pancreas or the adrenal glands of chickens suffering from severe FLKS.


Measurement of extracellular fluid volume and blood volume in sheep. Methods are described for the simultaneous measurement of extracellular fluid volume (ECFV) and plasma volume (PV) in sheep using dilution of 82Br (as sodium bromide) and 131I-labelled ovine gamma globulin. Following injection of 82Br (100 micronCi), equilibrium in blood was reached after 3 h at which time only 4% of the injected dose was in rumen water. The ECFV was measured as the mean of the 2- and 3-h bromide space after correction for the relative water content of plasma, the Gibbs-Donnan factor and the loss of 82Br into red blood cells. 131I-labelled ovine gamma globulin (20 micronCi) was injected after the 3-h 82 Br space was obtained and blood samples were taken at 10, 20, 30 and 40 min. In 16 determinations in 11 sheep (25-47 kg body weight) the mean (+/- s.e.m.) ECFV was 9112 +/- 289 ml (or 245 +/- 9 ml/kg). The mean PV for 16 observations in 11 sheep measured together with ECFV was 1597 +/- 62 ml (or 42-8 +/- 1-8 ml/kg). Although there was no relationship between body weight and PV there was a significant correlation between ECFV and body weight and also significant negative correlations between body weight and ECFV or PV when these were expressed as a function of body weight. The variation in ECFV measured on four occasions over 7-10 days in four sheep was 3-5% (range 2-6-4-6%). For PV measured in two animals on two consecutive days at the same time as ECFV the coefficient of variation was 1-5 and 2-1%. Acute sodium depletion (250-670 mmol) by parotid duct cannulation in three sheep resulted in a fall in ECFV which would account for only 15-20% of the sodium deficit. The remainder is presumably derived from ruminal sodium stores.


Effect of heat acclimatization on testicular enzymes involved in androgen biosynthesis via the 5-ene pathway. The metabolism of 3beta-hydroxy-5-ene steroids by testicular homogenates of heat-acclimatized and control mice was investigated in vitro. Acclimatization was achieved by keeping the animals in a hot room (33-35 degrees C, 25-40% R.H.) for 5 weeks. The control animals were kept in a temperate environment (20-22 degrees C, 30-50% R.H.). Some of the heat-acclimatized animals were supplied with additional water in a trough placed inside each cage (HAII mice). This source of water was used by the mice mainly for body cooling. A pronounced decrease in body weight and testis weight, and a smaller decrease in the weight of seminal vesicles which was associated with atrophy of the seminiferous tubules and hyperplasia of the Leydig cells was characteristic of heat-acclimatized mice with only drinking water available (HAI), but not of HAII mice. Although body cooling abolished the adverse physiological response described, it did not prevent specific changes in enzyme activity associated with androgen production. There was increased activity of 3beta-hydroxysteroid dehydrogenase and isomerase, and of 5-ene-17beta-hydroxysteroid dehydrogenase. These data offer partial explanation for the lower peripheral blood testosterone level observed in some species of heat-acclimatized mammals.


Determination of the relatedness of the soluble surface proteins of Trypanosoma brucei and Paramecium aurelia. The soluble surface proteins isolated by Cross (1975) from Trypanosoma brucei are compared to those which occur on Paramecium aurelia. Calculations based on the amino acid residue data and the molecular weights of these surface antigens indicate that there is a considerable degree of similarity between the T. brucei and the P. aurelia proteins, and that in neither case can simple mutation be responsible for the differences of molecules within each family of antigens. The analyses are consistent with the suggestion that the P. aurelia system can serve as a model for the phenomenon of phase transformation (relapse syndrome) which occurs in trypanosomiasis.


The effect of thymectomy in guinea pigs on the lymphocyte content of central lymph. The number of lymphocytes discharged from the mesenteric lymphatic duct was measured over several days of continuous lymph drainage in adult guinea pigs which had been thymectomised at birth or as young adults. The reduced output of lymphocytes during the first few days of lymph drainage from neonatally thymectomised guinea pigs indicated that removal of the thymus at birth produced a deficiency in the mobilizable lymphocyte pool. Adult thymectomy led to a decrease in the mobilizable lymphocyte pool which did not become apparent until 35 days after removal of the thymus. This indicated that the production of lymphocytes by the thymus is important in the guinea pig for maintaining adequate numbers of recirculating lymphocytes during adult life. The concentration of lymphocytes was reduced in the peripheral blood of guinea pigs which had been thymectomised at birth. In female guinea pigs this lymphopenia was accompanied by an increase in the number of lymphocytes bearing Kurloff bodies. The concentration of lymphocytes in bone marrow was not significantly altered following neonatal thymectomy.


Endogenous histamine in rabbit thoracic aorta. A sensitive automated assay was developed for the determination of histamine. The endogenous histamine content of intact rabbit thoracic aorta, and of its separated adventitial and medial layers was determined. The histamine content of the intact aorta was found to be only partially sensitive to compound 48/80. The isolated aorta accumulated labelled histamine against a concentration gradient. The uptake was abolished by cooling to 1 degree, but was unaffected by oxygen lack. The uptake process was sensitive to a variety of agents including extraneuronal catecholamine uptake inhibitors (deoxycorticosterone acetate, normetanephrine) as well as inhibitors of catecholamine and histamine metabolism (tranylcypromine, hydrallazine). The uptake was not affected by amodiaquin, a histamine N-methyl-transferase inhibitor, by the metabolites 1,4-methylhistamine or imidazole acetic acid, by compound 48/80 or by the basic amino acid arginine.


Antibody to togaviruses in the Northern Territory and adjoining areas of Australia. Antibody to flaviviruses Murray Valley encephalitis (MVE) and Kunjin and to alphaviruses Ross River and Sindbis were found in many Aboriginal children and adults bled in central Australia in 1974 after several cases of MVE occurred there as part of a widespread epidemic. Antibody was also detected in sera taken in the period 1968 to 1973, but in a much lower proportion, suggesting both that the 1974 epidemic had caused frequent sub-clinical infection and that infection had occurred in the arid centre of Australia outside years of known togavirus activity. Evidence of frequent togavirus infection was found in sera from various species from monsoonal northern areas of Northern Territory and Western Australia, compatible with previous suggestions that togaviruses are enzootic or frequently epizootic in those areas.


Lymphocyte-like cells of the tunicate, Pyura stolonifera: binding of lectins, morphological and functional studies. In vitro investigations were carried out to determine whether lymphocyte-like (small round) cells of the tunicate Pyura stolonifera react to allogeneic cells and mitogens in a manner comparable to that of vertebrate immunocytes. The lymphocyte-like cells possessed receptors for concanavalin A, wheat germ agglutinin and soybean lectin as shown by binding of radioiodinated lectins in scintillation counting and autoradiographic assays. This binding did not induce mitogenesis. Mixtures of cells of P. stolonifera individuals taken from the same or distinct localities did not show enhanced DNA synthesis when assayed at time intervals ranging from 3 to 10 days. The small round cells of this and other tunicates are not completely similar to vertebrate lymphocytes in morphology. Our observations support the concept that these cells are not directly homologous to immunologically competent vertebrate lymphocytes, but may serve as haemopoietic stem cells as proposed by other (Endean, 1954; Freeman, 1970).


Semi-automated catecholamine assay.

Semi-automated catecholamine assay. Three semi-automated procedures are described for the estimation of the catecholamine contents of urine, tissue and plasma samples. The three procedures are based on the fluorometric tri-hydroxyindole assay which has been modified for automatic analysis. These techniques offer several advantages over currently available assays in that they are more convenient, provide for faster analysis rate and give increased sensitivity. The results of the present studies in which the catecholamine contents of urine, tissue and plasma samples were determined using the semi-automated assay provided a range of values which was identical to that obtained using other methods.


The effect of aspirin pretreatment on the sweating response of older female subjects. Seven healthy female volunteers (aged 50 to 67 years) have been subjected to a thermal stress and their sweat rates evaluated using hygrosensors on five different locations on their body surface. It was found that the sweating rate was highest on the forehead in all but one of the subjects with the chest being the next most prominent site for the response. Five of the subjects were restudied after aspirin pretreatment. In the presence of this drug, resting body temperature was lowered, sweating occurred at a lower oral temperature and the mean sweating rate at a standardized body temperature was significantly higher. These findings are consistent with aspirin's known pharmacological actions, although in this study the increased sweating rate have been demonstrated in afebrile subjects.


Lack of genetic differentiation between domestic dogs and dingoes at a further 16 loci. Clarke, Ryan and Czuppon (1975) failed to detect electrophoretic differences between domestic dogs and dingoes at 14 loci. We have found that domestic dogs and dingoes are monomorphic for the same electrophoretic alleles at a further 15 loci, and polymorphic for the same alleles at a 30th locus.


Bovine nasal granuloma (atopic rhinitis) in Victoria. Experimental reproduction by the production of immediate type hypersensitivity in the nasal mucosa. The Australian type of bovine nasal granuloma (bovine atopic rhinitis) was reproduced clinically, grossly and histopathologically in 7 of 9 experimental cattle by subjecting them to repeated acute episodes of immediate-type hypersensitivity on their nasal mucosa over periods of several months.


The use of bovine PPD tuberculin the single caudal fold test to detect tuberculosis in beef cattle. The efficiency of 2 different doses of bovine PPD tuberculin was compared using the caudal fold test for the detection of tuberculosis in beef cattle. Two matched groups of 98 cattle were selected on the basis of their reactivity to HCSM tuberculin. Cattle in each group were tested with a singl 0.1 ml dose of bovine PPD tuberculin containing either 0.1 mg or 0.2mg bovine PPD respectively. Two further groups of 100 young stock from a herd with an incidence of tuberculosis of less than 0.1% were selected as controls. Tests were interpreted subjectively by palpation and observation and objectively by caliper measurement at 48, 72 and 96h. All cattle were examined post mortem for the presence of visible lesions. The 0.2 mg dose of PPD detected 95% tuberculous cattle and caused false-positive reactions in 19% of cattle without lesions. The 0.1 mg dose detected 80% of tuberculous cattle and caused 11% false-positive reactions. No visible lesions of tuberculosis were found in either of the control groups although 11% reacted to 0.2 mg and 5% to 0.1 mg bovine PPD at 72h. The optimum time for reading tuberculin tests was found to be in the period 48 to 72h after the injection of bovine PPD and subjective interpretation was more efficient than caliper measurement as a means of detection of tuberculous cattle. The 0.2 mg dose of bovine PPD was found to be more specific than HCSM tuberculin.


Anergy to tuberculin in beef cattle.

Anergy to tuberculin in beef cattle. Various aspects associated with anergy to tuberculin were investigated in a total of 75 tuberculous cattle. Forty-six (59%) had single lesions and 32 (41%) had multiple lesions. Forty-three (55.1%) had lesions in the lungs or associated lymph nodes and 23 (29.5%) showed multiple involvement of these tissues. Nine anergic cattle had generalised tuberculosis. Histological examination of lesions from 38 animals showed that the majority were of the progressive type. When bovine PPD tuberculin was used more cattle were anergic to the 0.1 mg than to the 0.2 mg dose and fewer tuberculous cattle were detected with either dose if tests were read at 96 h rather than 72h. Other factors thought to contribute to anergy are discussed with special reference to its relative importance in cattle with pulmonary infection.


Ataxia and paralysis associated with bovine ephemeral fever infection. Three adult cattle that had been ataxic for 5 to 7 months and a bull that had been paralysed for 24 days following bovine ephemeral fever infection were studied clinically and pathologically. Severe bilaterally symmetrical Wallerian degeneration was demonstrated in the spinal cords of all 4 cattle; in 3 animals an area of primary damage was present in the first cervical segment of the cord and in the other animal it was at the level of the lumbar cord. Pressure on the cord resulting from trauma was considered to be the most likely aetiology because of the similarity of the lesion to other syndromes causing pressure on the cord and the absence of the usual inflammatory changes seen with infectious agents.


Leptospira interrogans serotype hardjo outbreak in a Victorian dairy herd and associated infection in man. Leptospirosis associated with probable L. hardjo infection was investigated in a dairy herd in a coastal district of Western Victoria. Thirty-six  of 110 cows suffered leptospiruria and mastitis characterised by flaccid udders and abnormal milk. One of two media used enabled the isolation of the organism from infected guinea pigs inoculated with fresh urine. Microscopic agglutination titres to L. hardjo were elevated during the outbreak. There was an associated human infection.


The oral toxicity for sheep of triterpene acids isolated from Lantana camara. Toxic Lantana camara taxa growing in Queensland all contain the triterpene acids lantadene A, reduced lantadene A and lantadene B. These when dosed as pure compounds orally to sheep were similarly toxic at 65 to 75, 42 to 80 and 200 to 300 mg/kg body weight respectively, causing jaundice, photosensitisation, kidney and liver lesions typical of natural and experimental lantana poisoning. Because of its comparative toxicity and abundance lantadene A is the most significant toxic principle in the plant. Reduced lantadene A because of its low concentration in the leaves (5% of lantadene A) and lantadene B because of its significantly lower toxicity are thus unlikely to be of much importance in the poisoning of ruminants following consumption of the plant. In addition, the structural features of both lantadene A and B molecules given to sheep by the oral route do not conform to the chemical structures previously reported to be required for liver damaging action of the verbenaceous triterpenes administered to rabbits by the intraperitoneal route.


Regulatory veterinary medicine in a changing environment. There is an increasing need for the veterinary profession to meet the new challenges brought about by increased and intensified livestock production. These challenges consist of control and eradication of diseases, the humane treatment of animals and the prevention of transmission of disease from animals or animal products to man. Examples are given of the contribution which regulatory medicine activities have made to the prevention/control/eradication of screw worm, foot-and-mouth disease, Venezuelan equine encephalomyelitis, Newcastle disease, bovine brucellosis, hog cholera, and certain other diseases in North America.


Infertility in the horse associated with chromosomal abnormalities. Reproductive failure was studied in 12 phenotypically normal mares (9 Arabian, 3 Quarter horses, 1 Appaloosa and 1 pony). Karyotyping was performed using lymphocytes isolated from peripheral blood by density gradient procedures, followed by standard culture methods for karyotyping. Nine mares had karyotypes of 63,XO; 1 had 63,XO/64,XX; 1 had 63,XO/64,XY and 1 had 64,XY. All mares had small, firm ovaries that when removed and examined from 4 mares, lacked germ cells and consisted of undifferentiated ovarian stroma.


Anoxia in the bovine foetus.

Anoxia in the bovine foetus. Laparohysterotomies were performed, under local analgesia, on 18 plurigravid Herefore cattle and the response of their foetuses to anoxia was examined. All control and 4 of 6 foetuses subjected to 4 minutes of anoxia survived whereas all others died when the umbilical cord was clamped for 6 or 8 minutes. Death mostly occurred just before or soon after delivery, which was undertaken immediately following release of the umbilical clamp. In 2 cases, however, the calves survived for at least 2 days before being slaughtered when death appeared imminent. During the intervening period both animals failed to suck although one was able to stand temporarily following the oral administration of glucose and milk. Studies on the blood-gas and acid-base status of the foetuses while the umbilical cord was clamped revealed a decline in pH, pO2 and standard bicarbonate levels, the development of a base deficit and an increase in pCO2 and lactate levels. Clamping of the umbilical cord usually resulted in some foetal movement and the release of meconium. Clamping of the imbilical cord also caused an almost immediate fall in the pulse rate, which gradually increased after several minutes and became irregular and weak. Post-mortem examination of foetuses or calves dying from anoxia revealed haemorrhages throughout the body, these always being found on the heart, usually in the thymus and spleen, and occasionally in other sites throughout the body.


An abattoir survey of bull genitalia.

An abattoir survey of bull genitalia. This paper describes a survey of 504 bull genitalia collected after slaughter at 3 Western Australian abattoirs over 18 months. Details of the gross pathology, histopathology, and microbiology of the genitalia, and physical dimensions of the testicles are presented. The major breeds represented were Hereford (30%), Shorthorn (16%), Friesian (14.3%), and Aberdeen Angus (13.9%). The mean age of 263 bulls (52.6%) was 4.4 years. The mean length and breadth of 469 paired testicles was 10.8 cm and 6.9 cm respectively. Pathological conditions of the testicles were present in 61/469 (13%) bulls and in the epididymides of 37/469 (7.9%) bulls. Campylobacter fetus was isolated from 20 (4%) bulls, Tritrichomonas foetus was isolated from 6 (1.2%) bulls, and infectious bovine rhinotracheitis virus was isolated from 14/158 (8.9%) bulls. Histories were supplied by stock owners for 307 (60.9%) bulls and these did not relate well to the findings of the survey. The findings of this survey were compared, in particular, to similar studies carried out in Australia.


Incidence of neurofibroma in cattle in abattoirs in New South Wales. The incidence of neurofibroma in slaughtered cattle in New South Wales during a four-year period is reported. Most of the cases were in adult Hereford females over 5 years old. In 24 of the herds to which neurofibroma cases were traced there was evidence that the disease had previously occurred in the herd. However, the data does not indicate close familial relationship among cases of neurofibroma.


Renal coccidiosis of the horse associated with Klossiella equi. Klossiella equi in the kidney of a horse is described. Gametocytic and sporogonic stages were observed in the epithelium of the collecting tubules in association with schizonts in the glomeruli and proximal convoluted tubules. The condition was asymptomatic and caused only minor renal damage and inflammation.


Myocardial blood flow distribution in miniature pigs during exercise. Total and regional myocardial blood flow was measured in miniature pigs at rest and during two levels of treadmill exercise, including maximal exercise. Exercise increased the myocardial blood flow in a linear manner with heart rate (r = 0.87). At rest the endocardial/epicardial blood flow ratio was significantly greater than unity with flow favoring the endocardium. Exercise failed to appreciably alter the distribution of coronary blood flow. Thus the myocardium was capable of further dilatation and perfusion of blood without compromising endocardial flow even during the most severe level of exercise when maximal heart rates were attained.


Ultrastructural and enzyme-histochemical studies of the prostate of the dog under the effect of estradiol. The prostate of 4 mature pure bred Beagles 12 months old was studied 3 weeks following a single i.m. injection of 1 mg estradiol/kg body weight by means of histochemistry (acid and alcaline phosphatase) and electron microscopy. Four 11 months old Beagles served as controls. Estradiol leads to a variable reaction of glandular epithelium. There is an atrophy of active secretory cells, probably due to an inhibition of the release of ICSH by the anterior pituitary lobe, that in turn leads to a deficiency of androgens. The residual secretory function is not sufficient for normal synthesis of secretory granules, recognizable through the decrease in electron density of secretory granules and the extensive loss of activity of acid phosphatase. Under physiologic conditions it corresponds in its localization to the amount of secretory granules lying in the apical portion of the cytoplasm. The basal reserve cells show an ambivalence. Normally under the predominant influence of androgen they do not show any metaplasia, but they differentiate into the secretorely active epithelial cell. Without stimulation by androgens, estradiol leads to a basal cell proliferation with squamous metaplasia particularly in the dorso-lateral lobes close to the urethra. The activity of alcaline phosphatase shows a minor decrease in the capillary endothelium under estradiol. With increasing maturation of the metaplastic squamous epithelium the activity of alcaline phosphatase increases in the upper cell layer.


Chondrosarcoma of the pulmonary artery.

Chondrosarcoma of the pulmonary artery. Primary sarcomas of the large vessels are rare. They are observed most commonly in the pulmonary artery. Up to now 28 cases of primary sarcoma of the pulmonary artery have been described in the literature. The clinical features of this disease which presents considerable diagnostic difficulties are dominated by signs of cor pulmonale. In the present paper a primary chondrosarcoma of the pulmonary artery is presented.


A comparative study on the influence of dopamine and metaproterenol on the ventricular fibrillation threshold in cats. The influence of 3-4-dihydroxyphenylethylamine (dopamine) on the VFT of the cat heart was checked with different doses in comparison to metaproterenol (Alupent). In the therapeutical doses dopamine has no significant influence on the VFT in contrast to metaproterenol. The clinical relevance of our findings seems to be that dopamine can be applied in therapeutical doses without running the risk of inducing serious cardiac arrhythmia.


Angiocardiographic volume determination of the reindeer left ventricle. A simplified single-plane angiocardiographic method for the measurement of the left ventricular volumes in the reindeer heart has been developed, on the assumption that the left ventricle forms half a revolution ellipsoid. On the basis of a study of 30 ventricular casts the following formulae were constructed for the calculation of the left ventricular volume (VLV) in end-diastole (D) and end-systole (S): VLVD = 0.60 k3a2l - 3.9 and VVLS = 0.40 k3a2l - 12 where k = magnification factor of the x-ray system, a = cross-sectional diameter of the ventricle and 1 = longitudinal diameter of the ventricle. The method was tested on the casts by comparison with biplane integration and with the single-plane ellipsoid method. In addition to this, a comparison was made in vivo by simultaneous stroke volume determination by angiocardiography and the oxygen Fick, and a good agreement was observed.


The effect of hemodilution on regional myocardial function in the presence of coronary stenosis. Hemodilution decreases blood viscosity and circulatory input impedance and thus reduces afterload. Its use in treatment of LV power failure has been advocated, but the safe limits of isovolemic hemodilution are not known. Compensation of the reduced O2-capacity of the blood was therefore studied with normal and impaired coronary reserve. In 20 dogs the LAD was stenosed to a degree just not affecting the supplied region and central and coronary hemodynamics were studied. Regional myocardial function was assessed by ultrasound transit time between transducers implanted in the LV wall. Lowering the hematocrit to 15% by isovolumic exchange of blood for Dextran 60 increased CVP (18%), PAP (47%), LAP (64%), LVedP (46%), CO (67%), and flow to the intact area (LCA: 211%). Flow in the stenosed LAD increased slightly. Enddiastolic length (EDL) of LAD dependent muscle segments rose to 120% and their contraction amplitude deltaL was decreased by 46%. Whereas non-ischemic segments showed compensatory rise in deltaL (38%) at almost constant EDL (+9%). After release of the LAD stenosis EDL and deltaL returned to normal. During progressive anemia myocardial O2-demand is not adequately met if coronary reserve capacity is depleted. Reversion of hypokinesia after removal of the stenosis shows unimpaired myocardial function at a hematocrit as low as 15% provided the coronary circulation is intact.


Electron microscopy of a ciliated cell in the human stomach. A ciliated cell was observed electron microscopically in a pyloric gland with intestinal metaplasia. This specimen was obtained from the gastric antrum of a 61-year-old man suffering from gastric cancer. The cell had flask-like contour and possessed numerous cilia protruding from the free surface of a deeply indented cytoplasm into the glandular lumen. Most cilia were similar in structure to normal kinocilia and had nine peripheral doublets and two central microtubules (9 + 2 configuration). Some cilia, however, showed varying configurations, such as 9 + 0,9 + 3, or 9 + 4. The occurrence of ciliated cell in human stomach may be related to the disturbance of cellular differentiation of the gastric primordial cells during metaplastic change.


The influence of the size of acute ischaemic myocardial lesions on coronary reserve and left ventricular function in the dog. Acute ischaemic lesions of 5 and 15% of the left ventricular mass were produced in 10 dogs by ligations of branches of the left anterior descending coronary artery. Under maximal coronary dilatation by Dipyridamole and at constant aortic pressure, an ischaemic lesion of 15% caused reductions of blood flow in the left anterior descending coronary artery of 50% (p less than 0.05), , the R. circumflexus of 36% and of total myocardial blood flow (Argon method) by 44% (p less than 0.02). Parameters of left ventricular function, dp/dtmax and Vmax fell by 26 and 27% respectively (p less than 0.02). Ischaemic lesions of 5% LV mass were detected by 133 Xenon clearance estimations, but had no effect on any of the other variables measured. There was good agreement between estimations of total myocardial blood flow (Argon) and direct measurement of coronary flow with electromagnetic flowmeters (r = 0.957).


Metabolism of arginine in lactating rat mammary gland. Significant activities of the four enzymes needed to convert arginine into proline and glutamate (arginase, ornithine aminotransferase, pyrroline-5-carboxylate reductase and pyrroline-5-carboxylate dehydrogenase) develop co-ordinately in lactating rat mammary glands in proportion to the increased production of milk. No enzymes were detected to carry out the reactions of proline oxidation or reduction of glutamate to pyrroline-5-carboxylate. Minces of the gland converted ornithine into proline and into glutamate plus glutamine. These conversions increased during the cycle of lactation in proportion to the increased milk production and to the content of the necessary enzymes. The minced gland did not convert labelled ornithine into citrulline, confirming the absence from the gland of a functioning urea cycle, and did not convert labelled proline or glutamate into ornithine. A metabolic flow of labelled arginine to proline and glutamate in mammary gland was confirmed in intact animals with experiments during which the specific radioactivity of proline in plasma remained below that of the proline being formed from labelled arginine within the gland. It was concluded that arginase in this tissue had a metabolic role in the biosynthesis of extra proline and glutamate needed for synthesis of milk proteins.


The pathway for the conversion of dihydroagnosterol into cholesterol in rat liver. Dihydroagnosterol is demethylated by a rat liver homogenate to give 4,4'-dimethylcholesta 7,9-dienol and then cholesta-7,9-dienol. The cholesta-7,9-dienol is isomerized to cholesta-8,14-dienol, which is converted into cholesterol by the normal pathway.


Faster synthesis and slower degradation of liver protein during developmental growth. A study is presented of the liver protein gain during the early stages of postnatal development. Fractional rates of protein synthesis and degradation were determined in vivo in livers of 4-day-old mice. At this age, liver protein accumulated at a rate of 18% per day. Synthesis was measured after the injection of massive amounts of radioactive leucine. Degradation was extimated as the balance between synthesis and accumulation of stable liver proteins, or from the disappearance of radioactivity from liver protein previously labelled by the administration of NaH14CO3. We found that the neonatal livers: (1) synthesize 139% as much protein per unit time and unit mass as adult tissue, which is accounted for by a higher ribosome concentration (synthesis per mg of RNA was the same); (2) retain 39% of the newly synthesized protein as stable liver components (compared with 48% in adult mice); (3) degrade protein at 56% of the rate in the adult liver. This lower rate of degradation is quantitatively the most significant difference between the growing and non-growing liver.


Formation of vitamin A in a freshwater fish. Isolation of retinoic acid. The intestines of freshly caught Saccobranchus fossilis (a freshwater fish that contains dehydroretinol) became free from carotenoids and from vitamin A when the fish were starved for about 20 days. When beta-carotene was administered to such fish, retinoic acid could be isolated from the intestines after approx. 4h. When lutein was administered to such fish, dehydroretinol and 3-hydroxyretinol could be isolated from the intestines after approx. 5h.


Permeability of the mitochondrial membrane to bicarbonate ions. Osmotic-swelling techniques show that HCO3- enters mitochondria by an electrogenic process, effectively HCO3- uniport, under non-energized conditions. This mode of translocation accounts for previous reports of non-entry of HCO3- in experiments with energy-linked Ca2+ uptake. The effects of HCO3- on mitochondrial respiration are reported and discussed.


Sulpholipid formation in rat submandibular gland. The sulphotransferase activity of rat submandibular gland differs markedly from that of testis, kidney and brain. The addition of lipid acceptors and Mn2+ (or Mg2+), which have been shown to enhance sulpholipid formation from adenosine 3'-phosphate 5'-sulphatophosphate in other tissues, has either no effect or inhibits the transfer process.


Decline in ribonucleic acid and protein synthesis with loss of viability during the early hours of imbibition of rye (Secale cereale L.) embryos. A decline in protein synthesis and slow germination accompanies loss of viability in embryos of rye (Secale cereale L.) grains. Associated with this, incorporation of precursors into all the major classes of RNA is decreased and the processing of precursor rRNA to 25S and 18S RNA is retarded. Embryos that just reach 0% viability still synthesize some low-molecular-weight non-nucleolar material, although they do not synthesize protein. It is suggested that early-synthesized RNA could play a major part in determining the extent of protein synthesis at early germination, and thereby regulate the rate at which germination can proceed.


The synthesis of hippurate from benzoate and glycine by rat liver mitochondria. Submitochondrial localization and kinetics. 1. Rat liver mitochondria make hippurate at up to 4 nmol/min per mg of protein. The rate of synthesis supported by oxidation of glutamate with exogenous Pi present is identical with that supported by ATP plus oligomycin. Lower rates were obtained with other respiratory substrates, and when glutamate was used without Pi. 2. A matrix localization for hippurate synthesis is indicated by the latency of benzoyl-CoA synthetase and glycine N-acyltransferase to their extramitochondrial substrates, failure of exogenous benzoyl-CoA to inhibit incorporation of [14C]hippurate and inhibition of hippurate synthesis supported by ATP, but not glutamate, by carboxyatractyloside. 3. The relative activities of the individual enzymes and the mitochondrial content of benzoyl-CoA in the presence and absence of glycine suggest that hippurate synthesis is rate-limited by formation of benzoyl-CoA. 4. The increases in rates of ATP hydrolysis and of O2 consumption on the addition of benzoate and glycine were in good agreement with those required to support hippurate synthesis. The increase in respiration indicates that State-4 respiration [Chance & Williams (1957) Adv. Enzymol 17, 65-134] is not used, with these conditions, for ATP synthesis.


Plasma amino acid concentrations in pregnant rats and in 21-day foetuses. Plasma amino acid concentrations were determined in virgin female rats, in pregnant rats (12 and 21 days after impregnation) and in 21-day foetuses. The total amino acid concentration in plasma decreases significantly with pregnancy, being lower at 12 than at 21 days. Alanine, glutamine+glutamate and other 'gluconeogenic' amino acids decrease dramatically by mid-term, but regain their original concentrations at the end of the pregnancy. With most other amino acids, mainly the essential ones, the trend is towards lower concentrations which are maintained throughout pregnancy. These data agree with known nitrogen-conservation schemes in pregnancy and with the important demands on amino acids provoked by foetal growth. In the 21-day foetuses, concentrations of individual amino acids are considerably higher than in their mothers, with high plasma foetal/maternal concentration ratios, especially for lysine, phenylalanine and hydroxy-proline, suggesting active protein biosynthesis and turnover. All other amino acids also have high concentration ratios, presumably owing to their requirement by the foetuses for growth. Alanine, glutamine+glutamate, asparagine+aspartate, glycine, serine and threonine form a lower proportion of the total amino acids in foetuses than in the virgin controls or pregnant rats, probably owing to their role primarily in energy metabolism in the adults. The results indicate that at this phase of foetal growth, the placental amino acid uptake is considerable and seems to be higher than immediately before birth.


Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol. 1. 19-Nor-17alpha-pregna-1,3,5(10)-trien-20-yne-3,17-diol (ethynyloestradiol) or 17beta-hydroxy-19-nor-17alpha-pregn-4-en-20-yn-3-one (norethindrone) but not 17alpha-ethyl-17beta-hydroxy-19-norandrost-4-en-3-one (norethandrolone) caused a time-dependent loss of cytochrome P-450 when incubated in vitro with rat liver microsomal fractions and NADPH-generating systems. 2. The enzyme system catalysing the norethindrone-mediated loss of cytochrome P-450 had many characteristics of the microsomal mixed-function oxidases. It required NADPH and air, and was inhibited by Co. However, it was unaffected by 1 mM-compound SKF 525A. 3. In microsomal fractions from phenobarbitone-pretreated rats the norethindrone-mediated loss of cytochrome P-450 was increased relative to controls. The norethindrone-mediated cytochrome P-450 loss was less pronounced when the animals were pretreated with 3beta-hydroxy-pregn-5-en-2-one 16alpha-carbonitrile (pregnenolone 16alpha-carbonitrile). Pretreatment with 3-methylcholanthrene rendered the animals resistant to the norethindrone effect. 4. Administration in vivo [100mg/kg, intraperitoneally] of norethindrone or ethinyl oestradiol also produced a time-dependent loss of liver cytochrome P-450. Norethandrolone had a similar, though much less-marked, effect. All three steroids lead to an induction of 5-aminolaevulinate synthase and an accumulation of porphyrins in the liver. 5. The loss of cytochrome P-450 and the accumulation of porphyrins in the liver 2 h after the administration of norethindrone to female rats was similar to that seen in males. 6. Rats pretreated with phenobarbitone and given norethindrone or ethynyloestradiol (100mg/kg, intraperitoneally) formed green pigments in their livers. These had characteristics similar to the green pigments produced in the livers of rats after the administration of 2-allyl-2-isopropylacetamide. No green pigments could be extracted from the livers of control rats or those given norethandrolone, oestradiol or progesterone.


The role of tubular reabsorption in the renal excretion of bile acids. 1. The renal excretion of bile acids was studied in an isolated rat kidney preparation perfused with a protein-free medium. 2. Tubular reabsorption exceeded 95% for both non-sulphated and sulphated bile acids at filtered loads of less than 30 nmol/min. 3. At low filtered loads the reabsorption of taurocholate and taurochenodeoxycholate was almost complete. Efficient reabsorption of taurochenodeoxycholate was maintained over a wider range of filtered loads than for taurocholate. These observations suggest that active transport may occur. 4. At high filtered loads saturation of reabsorption of taurocholate and taurochenodeoxycholate did not occur, which indicates that passive diffusion is involved in reabsorption. 5. Active proximal-tubular secretion of bile acids was not demonstrated in competition experiments with p-aminohippurate. 6. The fractional reabsorption of taurocholate, chenodeoxycholate 3,7-disulphate and chenodeoxycholate 7-monosulphate was decreased by the addition of taurochenodeoxycholate to the perfusate, so that their renal excretion was enhanced. This interaction between the bile acids for reabsorption may explain the different composition of bile acids in urine compared with that in plasma in cholestasis in man. 7. Conjugated bilirubin decreased the fractional reabsorption of both taurocholate and taurochenodeoxycholate at low filtered loads (less than 30 nmol/min) but not at high filtered loads (400 nmol/min).


Inhibition of carbon dioxide fixation by lead acetate in rat liver mitochondria. These studies were undertaken to determine the mechanism by which intravenously administered lead salts inhibit hepatic gluconeogenesis. Within 1 h after the intravenous administration of lead acetate (10 mg), there is 97% inhibition of CO2 fixation in isolated rat liver mitochondria. This effect is concentration-dependent. The induction of phosphoenolpyruvate carboxykinase activity observed with starvation was also inhibited by intravenously administered lead acetate, but the activities of pyruvate kinase, glucose 6-phosphate dehydrogenase and pyruvate carboxylase were unaffected, as was the oxidation of palmitate and palmitoyl-CoA by mitochondria from Pb2+-treated animals. The addition of reduced glutathione to mitochondria from Pb2+-treated animals had no effect on the inhibited CO2 fixation. ATP concentrations in mitochondria from Pb2+-treated animals are decreased and the dose-response relationships for the effect of Pb2+ on CO2 fixation and ATP concentrations correspond. We conclude that the decrease in mitochondrial ATP in Pb2+-treated animals is probably responsible for the marked inhibition ov CO2 fixation, and hence the impairment of gluconeogenesis from alanine, lactate and pyruvate observed by others.


Role of pyridoxal phosphate in mammalian polyamine biosynthesis. Lack of requirement for mammalian S-adenosylmethionine decarboxylase activity. 1. Polyamine concentrations were decreased in rats fed on a diet deficient in vitamin B-6. 2. Ornithine decarboxylase activity was decreased by vitamin B-6 deficiency when assayed in tissue extracts without addition of pyridoxal phosphate, but was greater than in control extracts when pyridoxal phosphate was present in saturating amounts. 3. In contrast, the activity of S-adenosylmethionine decarboxylase was not enhanced by pyridoxal phosphate addition even when dialysed extracts were prepared from tissues of young rats suckled by mothers fed on the vitamin B-6-deficient diet. 4. S-Adenosylmethionine decarboxylase activities were increased by administration of methylglyoxal bis(guanylhydrazone) (1,1'-[(methylethanediylidine)dinitrilo]diguanidine) to similar extents in both control and vitamin B-6-deficient animals. 5. The spectrum of highly purified liver S-adenosylmethionine decarboxylase did not indicate the presence of pyridoxal phosphate. After inactivation of the enzyme by reaction with NaB3H4, radioactivity was incorporated into the enzyme, but was not present as a reduced derivative of pyridoxal phosphate. 6. It is concluded that the decreased concentrations of polyamines in rats fed on a diet containing vitamin B-6 may be due to decreased activity or ornithine decarboxylase or may be caused by an unknown mechanism responding to growth retardation produced by the vitamin deficiency. In either case, measurements of S-adenosylmethionine decarboxylase and ornithine decarboxylase activity under optimum conditions in vitro do not correlate with the polyamine concentrations in vivo.


Polyamines and their biosynthetic enzymes in Ehrlich ascites-carcinoma cells. Modification of tumour polyamine pattern by diamines. 1. Ehrlich ascites-carcinoma cells contained relatively high concentrations of spermidine and spermine, but the putrescine content of the washed cells was less than 10% of that of higher polyamines. 2. Ascites-tumour cells likewise exhibited high activities of L-ornithine decarboxylase (EC 4.1.1.17), S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), spermidine synthase (EC 2.5.1.16) and spermine synthase. 3. During the first days after the inoculation, the polyamine pattern of the ascites cells was characterized by a high molar ratio of spermidine to spermine, which markedly decreased on aging of the cells. 4. Various diamines injected into mice bearing ascites cells rapidly and powerfully decreased ornithine decarboxylase activity in the carcinoma cells, apparently through a mechanism that was not a direct inhibition of the enzyme in vitro. Cadaverine (1,5-diaminopentane) and 1,6-diaminohexane were the most potent inhibitors of ornithine decarboxylase among the amines tested. 5. Chronic treatment of the mice with diamines resulted in a virtually complete disappearance of ornithine decarboxylase activity, and after 24h a significant decline in spermidine accumulation. 6. Cadaverine appeared to be an especially suitable compound for use as an inhibitor of the synthesis of higher polyamines, at least in Ehrlich ascites cells, since this diamine also acted as a competitive inhibitor for putrescine in the spermidine synthase reaction without being incorporated into the higher polyamines.


Enzymes metabolizing delta1-pyrroline-5-carboxylate in rat tissues. The direction and capacity for the metabolism of delta1-pyrroline-5-carboxylate in a number of rat tissues ere investigated by measuring the activities of delta1-pyrroline-5-carboxylate reductase, delta1-pyrroline-5-carboxylate dehydrogenase and proline oxidase. Each of these enzymes catalyzed unidirectional reactions in which delta1-pyrroline-5-carboxylate was either the substrate or product. Delta1-Pyrroline-5-carboxylate reductase activities that were much higher than any previously reported were obtained by avoiding its inactivation in the cold. delta1-Pyrroline-5-carboxylate dehydrogenase, previously said to act on both D- and L-isomers of delta1-pyrroline-5-carboxylate, acted only on the L-isomer. Proline oxidase could not be measured in two adult tissues, in which an inhibitor appeared after birth. The activity of delta1-pyrroline-5-carboxylate reductase significantly paralleled that of ornithine aminotransferase in 23 tissues, showing a widespread potential for proline synthesis from ornithine. An independently distributed potential in fewer tissues for proline degradation to alpha-oxoglutarate was shown by the significantly similar tissue distributions of proline oxidase. Delta1-pyrroline-5-carboxylate dehydrogenase and glutamate dehydrogenase. Reverse metabolism of glutamate or proline to ornithine would be atypical in rat tissues with these distributions of unidirectional enzyme reactions.


HLA and recurrent episodic arthropathy associated with rubella vaccination. The frequencies of 21 HLA antigens in 33 patients who developed recurrent, episodic arthropathy after receiving the HPV-77 DK-12 rubella vaccine have been determined and compared with those of a control population. Trends toward increased frequencies of HLA antigens B12 (P = 0.02) and B14 (P = 0.04) and of the haplotype A2, B12 (P = 0.01) did not reach significance when corrections for the number of antigen determinations were included in the statistical analysis. These data show that the syndrome of recurrent arthropathy following rubella vaccination is genetically distinct from the connective tissue diseases associated with HLA-B27.


Idiopathic or traumatic olecranon bursitis. Clinical features and bursal fluid analysis. Thirty cases of idiopathic olecranon bursitis were studied. Most had previous local trauma. The process was unilateral and often associated with nontender pitting edema in cases of short duration. Ten patients exhibited a bony spur at the olecranon process, and amorphous calcific deposits were seen in 6. The bursal fluid was hemorrhagic with a xanthochromic supernatant, and the mucin clot test was poor or fair. Leukocyte count averaged 878/mm3, predominantly mononuclears. Many cells contained inclusion bodies. Glucose, total protein, and complement (C3) concentration averaged 80, 60, and 60% of the respective serum values.


Secretion of plasminogen activator by rheumatoid and nonrheumatoid synovial cells in culture. The secretion of plasminogen activator by human synovial cultures established from explants was studied. Thirteen cultures established from patients with rheumatoid disease were hyposecretors of plasminogen activator. Seven cultures derived from patients with nonrheumatoid joint disorders all secreted high levels of this enzyme. Rheumatoid and nonrheumatoid cells contained comparable levels of intracellular activator. It is suggested that the secretion of plasminogen activator is a function of normal synovium and that a defect in this function in the rheumatoid synovium perpetuates the inflammatory process.


Pathogenesis of cervical discovertebral destruction in rheumatoid arthritis. A review of 20 cases of rheumatoid arthritis strongly supported the concept that the cervico-disco-vertebral destruction seen radiologically is a consequence of cervical instability caused by apophyseal arthritis and ligamentous laxity. It is postulated that such instability results in chronic trauma to the discovertebral joints leading to destruction of the disc cartilage and vertebral endplates. "Rheumatoid inflammation" of the disc has previously been described, but it is uncertain that such inflammation in the disc is the primary cause of these destructive lesions.


Therapeutic studies in NZB/NZW F1 mice. V. Comparison of cyclophosphamide and chlorambucil. Cyclophosphamide (Cy) has been demonstrated to be effective in treating autoimmune disease in NZB/NZW F1 mice. This study was designed to compare the efficacy of chlorambucil (Chlor) with that of a known effective drug (Cy) in the treatment of murine lupus. NZB/W female mice were treated with Cy, Chlor, or nothing on a once-a-month dosage schedule. The age of onset of proteinuria, the severity of glomerular lesions, and the median survival were compared among the three treatment groups. Cy was found to be superior to Chlor and controls in all measures.


Yersinia-related arthritis in the Pacific Northwest. Serologic evidence of Yersinia enterocolitica infection was sought by agglutination testing in serum samples from several populations, including Haida Indians, Red Cross blood donors, and Caucasian patients with rheumatoid arthritis, ankylosing spondylitis, and Reiter's syndrome. No evidence was found to indicate that yersinial infection was etiologically related to Haida spondylitis or Reiter's syndrome. Four of 28 patients with acute arthritis were diagnosed from serologic evidence as having Yersinia-related arthritis.


A new three-dimensional postmortem method to study the topography of atherosclerosis using profilometry. The examination of high resolution casts of atherosclerotic arteries with a surface profile projector provides a 3-dimensional method for the measurement of atherosclerotic lesions. Lesions recorded on casts are found to predict gross and microscopic pathology. The contrast and magnification provided afford a continuum of atherosclerotic grades from the microscopic to macroscopic range. Lesion size and grade can be related to the geometry of the arterial lumen.


Cortisol and lysosomal stability in normal and atheromatous rats. The effect of cortisol on lysosomal stability has been studied in rats fed atherogenic and normal diets. beta-Glucuronidase has been taken as a lysosomal marker enzyme. Cortisol did not significantly alter total lysosomal enzyme activity in the liver or aorta or the activity present in the hepatic nuclear fraction. However, the hormone significantly increased activity in the intact lysosome and decreased soluble activity. The ratio of soluble activity (released from the lysosomes) to activity present in the intact lysosome showed that hepatic lysosomal stability was significantly increased in rats on cortisol. Cortisol tends to restore the decreased stability observed in atheromatous rats back to that in normal rats. The rate of release of enzyme from hepatic and aortic lysosomes was reduced by cortisol in both normal and atheromatous rats. Activity of serum lysosomal enzyme was also significantly lower in rats receiving cortisol. Cortisol subsequently added in vitro after the animals had been fed a normal or an atherogenic diet caused a significant in vitro decrease in the amount of enzyme released from hepatic lysosomes. The in vitro release of enzyme from lysosomes in normal rat liver progressively fell with increasing concentration of cortisol form 10(-5)--10(-4) M. Further increase in concentration up to 5 X 10(-4) M did not significantly alter enzyme release. Since cortisol was administered as its hemisuccinate the effect of succinate on lysosomal stability was also studied. It stabilized lysosomes, but the effect was much less than with cortisol.


Aortic surface coat scanning electron-microscopic modifications after short-term hypercholesterolic diet, visualized in rabbits by con A-haemocyanin reaction. Modifications of the aortic endothelial surface coat have been visualized at SEM with the use of the Con A-haemocyanin method. After fifteen days of an atherogenic diet, a strong increase of the reactive coat was evident in areas near the orifice of the collateral branches. In other areas, the reaction appeared to be intensely diminished.


Serum and tissue lipids and glomerulonephritis in the spontaneously hypercholesterolemic (SHC) rat, with a note on the effects of gonadectomy. A spontaneously hypercholesterolemic male rat, found in the Sprague-Dawley strain, was mated with normocholesterolemic females of the same strain: the male offspring were hypercholesterolemic. By selecting rats according to their plasma cholesterol levels and repeated brother-sister mating, progeny became progressively more hypercholesterolemic--especially the males--when fed a basal low-cholesterol diet. These rats were tentatively given the short name of SHC and have at present been bred to the F14 generation. Hypercholesterolemia in male SHC rats proceeded in two stages: plasma cholesterol rose only slightly during the first stage up to the age of about 10 weeks and then increased progressively in the subsequent stage. Female SHC rats developed a high degree of hypercholesterolemia from the age of 10 months. SHC rats maintained on the basal diet were not obese, but their kidneys and livers enlarged. Histological examination showed that glomerulonephritis developed in the kidney of male SHC rats by the age of 9 months. The liver of these rats was not fatty and contained rather less lipid than usually found in the normal Sprague-Dawley rat. Male and female SHC rats were subjected to gonadectomy at the age of 4 weeks, and were then maintained on the basal diet for 18 weeks. Blood cholesterol was higher throughout the experiment in ovariectomized female SHC rats than in controls, and the renal lesion was correspondingly worse. However, gonadectomy in male SHC rats had no effect on the disease.


Relationship of advanced atherosclerosis lesions to fibrous plaques in 19 location-race groups. Aortas and coronary arteries from 23,000 autopsies of 19 location-race groups (L/R) were graded for % surface fatty streaks (FS), fibrous plaques (FP) and advanced lesions (AL = calcified, hemorrhagic, ulcerated, or thrombotic). Cases were classed by age (24-34, 35-44, 45-54, 55-64, and 65-69), sex, L/R, broad cause of death category (C/D; athero = related to atherosclerosis; basal = all other), and % surface raised lesions (RL = FP + AL). AL was converted to "advanced among lesions" (AaR = AL divided RL) because AaR was found on the average within each subgroup of subjects to hold a nearly constant ratio to RL (i.e. AaR : RL = K, an empirical constant). This ratio was different for each age (older greater than younger), C/D (athero greater than basal), and sex (M greater than F) subgroup and for coronary vs. aorta, thus requiring 5 X 2 X 2 X 2 = 40 values of K to describe the pools of subjects. The values of K were essentially same for all 19 location-race groups. If it be assumed that advanced lesions arise only be evolution from fibrous plaques, then the speed of this evolution up to each specified age is measured by K, in the sense that at a particular age larger K implies faster evolution. On the average, the rate of evolution in this sense was found to be the same in all location-race groups. Within groups a large variability of K among individuals was found, and this variation remains unexplained. However, across location-race boundaries no such variability was found, and this implies that the magnitude of K is not under control of geographically variable factors.


Effect of cholesterol feeding on arterial lipolytic activity in the rabbit. Two trioleoyl glycerol hydrolases, one of lysosomal origin as determined by a high correlation with the lysosomal marker enzyme, N-acetyl-beta-glucosaminidase, and one having the characteristics of lipoprotein lipase, were measured at varying stages of lesion development in the aortas of cholesterol-fed rabbits. Both lipases were greatly enhanced in atheromatous aortas and were linearly related to lesion severity as measured by total aortic cholesterol. Lipoprotein lipase activities of myocardium and of plasma of cholesterol-fed rabbits were also significantly increased relative to controls. The data suggest that lipoprotein lipase might be a factor regulating cholesterol deposition in the aorta.


Inhibition of cholesterol esterification in rabbit aorta by prostaglandin E2. Cholesterol esterification in the arterial wall was investigated with cell-free preparations of intima-media from control rabbits and rabbits rendered atherosclerotic by feeding a diet containing 1% cholesterol. In the presence of 2 mM ATP and 0.1 mM CoA, the major activity for esterification of [4-14C] cholesterol added in vitro was found in the 12,000 g and 105,000 g pellets. In control animals, the activity in the latter pellet was twice that in the former. After cholesterol-feeding for 6 months, the activity increased 5-fold in the 105,000 g pellet and 2-fold in the 12,000 g pellet of the atherosclerotic intima-media. Prostaglandin E2 (PGE2) in concentrations between 2 and 12 X 10(-7) M exhibited a dose-dependent inhibition of the esterifying activity in both particulate preparations. The inhibition was 97% at PGE2 concentrations greater than 1.2 X 10(-6) M in preparations from control animals. Inhibition by PGE2 in preparations from atherosclerotic rabbits was also observed. These results suggest a possible regulatory role of PGE2 in cholesterol esterification in the arterial wall.


The effect of sex hormones on glycosaminoglycan content of canine aorta and coronary arteries. Hyaluronate (HA), heparan sulfate (HS), dermatan sulfate (DS) and isomeric chondroitin sulfates (CS) were measured in vascular walls of 9-10 months old normal and hypophysectomized female beagles treated with sex hormones. Following hypophysectomy the animals were maintained for 8 weeks without any hormonal replacement therapy and then they were exposed for 3 weeks to parenteral treatment with sex hormones. One group received twice weekly 25 mg testosterone, another group was given the same amount of progesterone, and a third group received on day 1 and day 14, estrogens in 2 injections, consisting of a mixture of 10 mg short-acting estradiol-17-phenylpropionate and 2.5 mg long-acting estradiol benzoate. After 11 weeks all animals were sacrificed, coronary arteries and aortas were immediately removed and the latter were divided into three segments: arch, thoracic and abdominal. Removal of the pituitary led to a reduction of the HA content in the aortic arch and thoracic segment, but coronary arteries and abdominal aorta were not affected. The main consequence of hypophysectomy both in the entire aorta and in coronary arteries was a sharp reduction of the sulfated glycosaminoglycan (GAG) content. All three hormones produced a modest rise in the HS content of coronary arteries. A more definite response was seen in the thoracic aorta where each of the three hormones raised the low DS content to normal levels. Concerning the effect of sex hromones on aortic GAG other than DS, TESTOSTERONE RAISED THE CS content towards normal in thoracic and abdominal segments, while estrogen by doubling the normal HA concentration was particularly potent in the abdominal aorta. It is conceivable that the different sensitivity of various segments of aorta and coronary arteries to sex (and other) hormones in terms of regulating GAG metabolism may prove to be of relevance to the uneven distribution of lesions in degenerative vascular disease.


Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet. Accelerated atherosclerotic lesions are observed in genetic defects characterised by marked homocystinaemia as a result of low levels of cystathionine synthase, a pyridoxal phosphate-dependent enzyme. Attempts were therefore made to induce atherosclerosis in Macaca radiata, maintained on a high-protein, high-methionine and high-fat diet by inducing pyridoxine deficiency with deoxypyridoxine. Pyridoxine deficient monkeys failed to show any biochemical or pathological evidence of atherosclerosis, despite a significant decrease in the activity of hepatic cystathionine synthase.


The effect of centrifugal force on glycosaminoglycan production by aortic smooth muscle cells in culture. Cultured smooth muscle cells from pig aorta subjected to centrifugation (48 h at 45 g over a 72-h period) increased their production of glycosaminoglycans by approximately 50%. The sulphated components, heparan sulphate, dermatan sulphate and chondroitin sulphate, showed a relatively greater increase than hyaluronic acid (66-34%). The results are consistent with the hypothesis that mechanical stress, such as hypertension, leads to increased accumulation of glycosaminoglycans in the aortic wall and that secondary trapping of lipoproteins by sulphated glycosaminoglycans produces atherosclerotic plaques.


Linoleic acid and susceptibility to fatal ventricular fibrillation in rats. The effect of linoleic acid on the induction of fatal ventricular fibrillation by intravenous CaCl2 (10%), was studied in rats fed for a month from weaning on a diet with either a high or low content of linoleic acid. Studies were performed in the basal state and after pretreatment with noradrenaline, which increased the sensitivity to CaCl2 equally in animals from both diet groups. Despite considerable differences in the linoleic acid levels in the plasma and myocardium, the two groups did not differ in the incidence of fatal ventricular fibrillation. Our conclusions concerning the effect of linoleic acid on cardiac arrhythmias, and sudden death in particular, are compared with those from other studies.


The effect of insulin and glucose on sterol synthesis in cultured rat arterial smooth muscle cells. The smooth muscle cell plays an important role in the process of atherogenesis, proliferating in the arterial intima and becoming filled with lipid during the course of the disease. In these experiments the effect of insulin and glucose on sterol synthesis in cultured rat arterial smooth muscle cells was studied. Arterial smooth muscle cells were cultured from pieces of intima and inner media of young rat aortas. The cells were grown in Petri dishes in culture medium with foetal calf serum and when confluent were exposed to insulin or glucose for 24 hours. Insulin in concentrations of 10 micromicron-100 millimicron per ml stimulated the incorporation of sodium [2-(14)C]acetate into non-saponifiable lipids and digitonin precipitable sterols. However, insulin had no effect on the incorporation of labelled mevalonate into cell sterols. Increasing concentrations of glucose in the medium up to 140 mM had had no effect on the incorporation of isotope into sterols, but higher concentrations of glucose caused cell damage and sterol synthesis was markedly depressed. These results may have relevance to the development of atherosclerosis in diabetes and obesity.


Effect of BM 15.075 on lipoprotein concentrations in different types of hyperlipoproteinaemia. The four-week lipoprotein lowering effect of 0.2 g t.i.d. of BM 15.075 and of 0.5 g t.i.d. of clofibrate was studied in 29 subjects with different types of hyperlipoproteinaemia in a single blind crossover fashion. BM 15.075 decreased very low density lipoproteins (VLDL), triglycerides (TG) and cholesterol concentration in all types of hyperlipoproteinaemia the effect being dependent on initial lipoprotein concentrations. BM 15.075 decreased VLDL triglyceride concentrations on average 20% more than did clofibrate. BM 15.075 decreased low density lipoproteins (LDL) cholesterol concentrations in Type IIA and IIB but did not significantly affect this lipoprotein lipid in type IV hyperlipoproteinaemia. Regression analysis showed that the drug tended to decrease LDL cholesterol if initial concentrations were above 157 mg/100 ml and to increase initially lower levels. No significant differences between BM 15.075 and clofibrate was found in the effect of LDL cholesterol. High density lipoproteins (HDL) cholesterol concentrations were not influenced by BM 15.075. No subjective side effects were noted on BM 15.075. S-ASAT increased and alcaline phosphatases decreased on both treatments.


Increased pulmonary residual volume in patients with hyperlipoproteinemias. A syndrome, characterized by pulmonary hyperdistension (increased residual volume, closing capacity and Motley index), was observed in patients with hyperlipoproteinemias without without other known causes of pulmonary disease. This syndrome is mostly asymptomatic;hyperdistension is of variable degree and not directly correlated to plasma lipid levels. It is partially reversible after reduction of lipidemia. The cause of this syndrome is not known. It may explain a decreased pulmonary working capacity in asymptomatic hyperlipidemic patients.


Failure of regression of atherosclerosis in dogs with moderate cholesterolemia. Controversy exists as to whether regression occurs in atherosclerotic plaques in response to serum cholesterol reduction. In the present study, using sequential observation of canine atherosclerosis, we attempted regression in hypothyroid dogs. Animals with established lesions prior to a regression attempt were placed on a 0.05% cholesterol diet and observed up to 60 months. Weighted average cholesterols ranged from 235 to 587 mg/100 ml during the regression attempt. A control fed for the entire period of the experiment, 75 months, had an average weighted cholesterol of 435 mg/100 ml. We failed to obtain regression of atherosclerotic plaques in spite of reduction of serum cholesterol from high to moderate levels. The lesions in the experimental animals contained less lipid and more collagen and calcium than occurred in the control. Complicated plaques with aneurysm formation, stenosis of the distal aorta, and gangrene of the tail were also noted.


Inhibition of spontaneously developing arteriosclerosis in female breeder rats by adrenalectomy. In order to determine whether the adrenal glands play a primary or secondary role in the pathogenesis of the spontaneous arteriosclerosis which occurs in repeatedly bred rats, sexually mature female, Sprague-Dawley rats were adrenalectomized and maintained during four successive pregnancies. Some of the breeders were treated with deoxycorticosterone (DOCA) and 0.5% saline. The adrenalectomized breeders did not develop arteriosclerosis, beta cell degranulations, or those which has accesory or regenerated adrenal glandular tissue. Surprisingly, intact DOCA-treated breeders also showed inhibition of arterial disease but they did have fatty livers and beta cell degranulation. Body and organ weights, serum enzymes, lipids, glucose, BUN, and corticosterone were elevated in breeder rats but not to such high levels as is usual in repeatedly bred rats. These findings demonstrate that the presence of the adrenal glands is essential for the pathogenesis of the spontaneous arteriosclerosis, fatty liver, and beta cell degranulation which occurs in repeatedly bred, female rats.


Limb blood flow in treated hyperlipoproteinaemic patients with peripheral vascular disease. A preliminary report. Fourteen patients with hyperlipoproteinaemia and peripheral vascular disease have been investigated to determine the effect on limb blood flow of hypolipidaemic therapy. Satisfactory lowering of serum lipoprotein levels was achieved in the treated group. There was a significant deterioration in peak reactive blood flow measurements in the placebo group compared with the treated group. Treatment of hyperlipoproteinaemia may, therefore, be of value in preventing the progression of peripheral atherosclerosis.


Cholesterol vehicle in experimental atherosclerosis. Part 15. Randomized butter and randomized lard. Randomized lard and butter oil were conpared with native lard and butter oil for their effects on cholesterol-induced atherosclerosis in rabbits. In each experiment there was also a group fed corn oil. The diets contained 2% cholesterol and 6% fat and were fed for eight weeks. Randomization of either butter or lard had virtually no effect as regards their atherogenic potential when fed as part of a diet containing 2% cholesterol. The corn oil-containing diet was less atherogenic than any of the other fats.


Permeability in atherosclerosis: fluorescence test in green light with trypan blue. A new microscopic fluorescence method for trypan blue at 570 nm has been used to follow the entry of albumin into the atheromatous rabbit aorta. Permeability into the inner aortic wall increases before the onset of gross lesions and seems just to precede intraendothelial deposition of lipid. Thereafter, permeability of the inner wall progressively increases until streaks or small plaques develop. These raised lesions stain and fluoresce variably, some intensely so while others are almost unreactive. This variability might reflect the difference between progressive and quiescent lesions. However, a zone of increased permeability surrounds many raised lesions, suggesting that the edge is a major site of growth and progression.


Histocompatibility antigens and other genetic markers in ankylosing spondylitis and inflammatory bowel diseases. Of 118 Dutch patients suffering from ankylosing spondylitis (AS) 81-4% were found to be positive for the HLA antigen B27. The B27 frequency proved to be significantly higher in patients in whom the disease had an early onset. In addition to B27, another HLA antigen may be associated with AS; the antigen Bw 16 was found to be significantly increased in B27 negative AS patients. HLA phenotype frequencies were also determined in 109 patients with idiopathic inflammatory bwel disease (IBD). In fifty-eight ulcerative colitis (UC) patients a raised incidence of A 11 was noticed. In fifty-one patients with Crohn's disease (CD) the antigen B18 showed an increased frequency. Both deviations were statistically significant. In thirty-nine patients suffering from both AS and IBD 50% proved to be B27 positive, which is significantly diffrent from B27 frequency in patients with AS alone. In the B27 negative patients with AS and IBD and increased frequency of Bw16 was also shown.


[Isolation of viruses from urban sewage: comparison of methods]. A comparison has been made among some methods (concentration on aluminium hydroxide precipitates, polymer two-phase separation, cellulose membrane filtration, direct inoculation) for virus isolation from raw sewage. The concentration on aluminium hydroxide has given significantly better results than the other methods. No significant differences have been noted between the two-phase separation and direct inoculation method. The membrane filtration method has given no positive result. All isolated viruses belonged to the adenovirus group.


[Presence and etio-epidemiological significance of halophilic vibriones in various material]. In this work data of isolation of halophilic vibrios from coastal water of central Tyrrhenian sea are reported, and the epidemiological significance of such strains is discussed. V. Parahaemolyticus was identified in 8 out of 20 samples of sea water. V. alginolyticus was identified in 8 out of 26 samples of fishes and mussels examined and in 8 out of 20 sea water samples. Halophilic vibrios had not been isolated from 12 samples of sewage water and from 27 healthy or pathological human stool samples. From 6 different samples (sewage water and human stools included) bacteriophages active against V. parahaemolyticus were isolated. This study demonstrates that in our geographical area V. parahaemolyticus is present. The pathogenicity of such strains cannot be demonstrated because of the lack of available experimental models in vitro and/or in vivo. It is also impossible to assume their etiological rôle in human pathology, due to the absence of specific epidemics or single cases in our country.


"Immunosubtraction" electrophoresis: a simple method for identifying specific proteins producing the cellulose acetate electrophoretogram. To identify the proteins that are responsible for the electrophoretic pattern on cellulose acetate, we propose a method based on the precipitation of various individual proteins at the beginning of the electrophoretic run. Any non antibody proteins in the monospecific antisera were removed with a preliminary electrophoretic fractionation of the antiserum. Using this method, we could remove a band or a zone from the pattern, leaving the rest of the pattern unaltered. This permitted us not only to locate a protein in the pattern, but also to better interpret the electrophoretogram. The method requires no special apparatus and it is fast and cheap.


Serum zinc levels, lymphocyte counts and functions in pediatric Hodgkin's disease. Serum zinc levels, total lymphocyte counts, cutaneous reactivity to three intradermal antigens and the in vitro lymphoblastic transformation response to PHA were evaluated in 24 children with Hodgkin's disease and 20 control cases. Serum zinc level was measured by atomic absorption spectrophotometer (Perkin Elmer M 103) in Hodgkin's cases and found to be significantly decreased in the whole group of patients and reached the lowest level in LD type and the IVth stage of disease. The overall response to PHA was reduced in Hodgkin's cases. It was significantly low in the group of LD subtype. Delayed cutaneous hypersensitivity reactions were also markedly decreased in the IV stage and MC, LP subtypes of Hodgkin's patients. Our preliminary results disclosed a relationship between serum zinc level and the lymphocyte abnormalities in Hodgkin's disease.


[Immunohistological aspects of nephropathy with minimal lesions]. Renal biopsies from 32 patients, whose light microscopy showed a pattern of minimal changes nephropathy, have been submitted to immunohistological examination. On the basis of immunofluorescence pattern we separated the cases into three groups: the first group (12 cases) was characterized by absence of any glomerular deposit. The second group (9 cases) showed focal and segmental deposits of IgM and sometimes C3 on capillary walls. In the third group (11 cases) we observed slight deposits of IgM and sometimes C3 "comma like" over glomerular structures in all glomeruli. The site of these last deposits was sometimes mesangium and sometimes the capillary walls. The results of immunohistological examinations gave no information about the pathogenetic mechanisms of minimal changes nephropathy. We observed that the patients enclosed in the second group had a worse clinical prognosis, compared with the other two groups.


HLA-A3 linked C3 deficiency in multiple sclerosis. Many workers claim variations in quantity of functional activity of several components in the complement system in M.S. patients. Studies were performed in 58 M.S. patients, typing for HLA-SD specifities and C'3 complement component. We have been able to confirm a significant correlation between the hypocomplementaemic group (31.03%) with HLA-A3. In this connection we present some considerations on complement system and M.S.


[Studies of diseases caused by hepatitis B virus on the island of Favignana]. 731 serum samples were drawn from inhabitants of Favignana (Egadi Islands, total population 3,000). Presence of HBsAg and anti HBs was tested by R.I.A. Although only two cases of B Virus Hepatitis had been observed in the last 3 years, the overall positivity for HBsAg was 4.8% and for anti HBs 31.6%, showing a distribution by age and sex comparable to that observed in similar studies. The rather high prevalence of HBsAg in males over 70 deserves further investigations.


[Detection of Australia antigen (HBsAg) in an institution for the mentally retarded and its staff]. The Authors investigated HBsAg in an institution for the mentally retarded. The high incidence (8.7%) in the patients and in some categories of the hospital attendants, was related with the poor hygienic conditions of the institution. Moreover it was found an endemic spread of hepatitis between the patients.


[Coxsackie B virus infection and cardiopathies]. Neutralizing antibody activity against Coxsackie virus group B, types 1-6, was determined on paired serum samples taken from 16 hospitalized patients affected by acute heart diseases of suspected viral origin. Serum samples were also taken from 4 additional cases of pleuropericarditis observed in the course of a small outbreak of Coxsackie B2 infection. Serological evidence of virus infection was based on the occurrence of the following conditions: a) twofold or greater variation of virus neutralizing antibody; b) antibody titers equal to or greater than 1:256. Evidence of Coxsackie B2 virus infection was found in 12 patients, while Coxsackievirus B1, B3, B5 and B6 infection, respectively, could be associated with 4 cases. The advisability of performing serological examination for Coxsackie group B viruses antibodies in patients with heart diseases of suspected viral origin is emphasized.


[Blastogenetic activity of medullary blood serum of patients with various blood diseases]. Peripheral blood lymphocytes from 24 patients were cultured in vitro in the presence of autologous peripheral serum and bone marrow blood serum, with and without PHA stimulation. Bone marrow serum showed a well defined effect, in the absence of PHA stimulation, on lymphocytes from 4 patients (2 affected by acute leukaemia, 1 by megaloblastic anemia and 1 by benign idiopathic paraproteinaemia), and a less defined effect on lymphocytes from 2 donors (1 affected by iron deficiency anemia and 1 by thalassemia minor). No difference attributable to the source of blood serum was observed in PHA stimulated cultures. These results do not allow defined statements. Peripheral blood lymphocytes cultured in vitro were affected by bone marrow blood serum only in some subjects. A clear cut correlation between this effect and the clinical features of our patients was not evident.


Beta blockade in essential hypertension: an analysis of response to oxprenolol. The data from 40 patients with essential hypertension treated with oxprenolol alone have been used to analyse the falls of blood pressure and heart rate. Blood pressure and heart rate did not fall further as the daily dose was increased above 160 mg. The range of fall in mean pressure was from 0 to 40 mmHg and there was no clear separation into response groups. Pressure falls were unrelated to sex, age, initial heart rate, increase in heart rate on standing, the fall of heart rate with the drug, or the initial height of blood pressure. In the absence of predicting factors the use of oxprenolol, and, by deduction, other beta blocking agents, in hypertension remains empirical, but the simplification of the dose range allows the response to oxprenolol to be determined quickly.


Metoprolol--a new cardioselective beta-adrenoceptor blocking agent for treatment of tachyarrhythmias. The antiarrhythmic effect of the cardioselective beta-adrenoceptor blocking agent metoprolol, given intravenously, was studied in 44 patients with various tachyarrhythmias, including patients with congestive heart failure and signs of digitalis intoxication. All patients with atrial tachycardia (12 cases) reverted to normal sinus rhythm. In 3 out of 18 patients with atrial fibrillation, sinus rhythm was restored, and in the others there was a significant reduction in ventricular rate. In 6 of 10 patients with ventricular ectopic beats, and 1 of 2 patients with ventricular tachycardia, the ectopic rhythm was abolished. The drug was well tolerated, without any significant changes in blood pressure, even by patients with signs of digitalis intoxication and varying degrees of pulmonary or peripheral circulatory congestion. Metoprolol is of clinical value for treatment of tachyarrhythmias, especially those of supraventricular origin.


Mitral valve closure index. Echocardiographic index of severity of mitral stenosis. A new echocardiographic index of mitral valve diastolic closure, based on the rate of diastolic apposition of the anterior and posterior mitral leaflet echoes, was measured in 40 patients with mitral stenosis. This mitral valve closure index correlated highly significantly with the mitral valve orifice area (calculated from the Gorlin formula) (r = 0-87). Correlation between the diastolic closure rate (based) on the EF slope) and the calculated valve area was poor (r = 0-37). It is proposed that the mitral valve closure index excludes movement extraneous to the mitral apparatus and expresses the actual rate of valve closure, thus avoiding some of the factors known to contribute to the poor specificity of the diastolic closure rate. The better correlation of the mitral valve closure index with the calculated valve orifice area makes it possible to assess the severity of mitral stenosis by echocardiogram with greater accuracy and confidence.


Diagnosis of ventriculo-arterial discordance (transposition of the great arteries) by contrast echocardiography. The constant anatomical relation of the aortic arch and the pulmonary artery bifurcation permits echocardiographic differentiation of the two great arteries when viewed from the suprasternal notch. When this technique was employed with contrast echocardiography in 12 infants, 6 of whom had ventriculo-arterial discordance (transposition of the great arteries), it was possible to establish with certainty in all but 1 case which great artery was most directly connected to the systemic venous return.


Echocardiography of primitive ventricle. The angiocardiographic, echocardiographic, and, where available, the necropsy findings were correlated in 32 cases of primitive ventricle. Single probe echocardiography was shown to be a reliable and accurate technique for diagnosis of primitive ventricle; the ventricular and atrioventricular valve appearances were characteristic, and the outlet chamber was usually recognised when present, though it was not possible to say whether it was rigt or left sided. Abnormalities of the atrioventricular valves were more accurately shown by echocardiography than by angiocardiography though the two techniques were shown to be complementary in the overall diagnostic process.


What should we call the 'crista'?

What should we call the 'crista'? Review of published work concerning congenital cardiac anomalies reveals that at least four different structures have been described as the crista supraventricular, in addition to the structure which in the normally formed right ventricle separates pulmonary and tricuspid valves. Possibility of further confusion arises since at least two different structures have been described under the name 'septal band'. We suggest that this potentially confusing situation will be best resolved by reserving the term 'crista' for description of the muscle mass between inflow and outflow portions of the right ventricle when there are no additional outflow tract anomalies. We then suggest that at least three separate structures warrant description in hearts with outflow tract anomalies. The first separates the semilunar valves, the second separates a semilunar valve from an atrioventricular valve, and the third is an extensive septal trabeculation of the right ventricle. Our suggested terms for these structures are the infundibular septum, ventriculo-infundibular fold, and trabecula septomarginalis, respectively. However, we believe that such terms would be better decided and agreed upon within an internationally formulated 'Nomina Cardiologica', a terminology as yet lacking in congenital heart disease.


Normal internal calibres of ostia of great arteries and of aortic isthmus in infants and children. In order to obtain reference data, useful in paediatric cardiology and paediatric cardiovascular surgery, internal diameters of the ostia of the great arteries, of the  aortic isthmus, and of the descending aorta were determined with the aid of calibrated probes in 46 necropsy specimens of normal hearts with great vessels. Age range was from 25 weeks of gestational age up to 9 years post partum. The method used proved to be as accurate as echocardiography in vivo. The data revealed linear correlations between body length and calibres of aortic and pulmonary ostia. The correlation between the calibres of the pulmonary and the aortic ostia was also a linear one with the pulmonary ostium being slightly larger than the aortic ostium. From the cross-sectional areas of the aortic isthmus and of the descending aorta an isthmus index was calculated which indicates the presence (and degree) or absence of a narrowing (tubular hypoplasia) of the aortic isthmus. Results show that narrowing of the aortic isthmus is inconstantly present in infants younger than 10 weeks, whereas it is always absent in infants and children older than 10 weeks. No dependence of narrowing of the aortic isthmus on developmental age attained at birth has been found.


Hypertensive pulmonary vascular disease in children. Detection by radioactive nitrogen (13N) inhalation and injection. Regional lung function has been studied in 16 children with intracardiac shunts and a variety of associated cardiac anomalies using radioactive nitrogen (13N) and a gamma camera-computer system. The distribution and washout of inhaled 13N were usually normal. The distribution of intravenously injected 13N was often abnormal and could be related to local anatomy. The most important finding was delayed clearance by ventilation of intravenously injected 13N in children with an abnormally raised pulmonary/systemic vascular resistance ratio (Rp/Rs) at cardiac catheterisation. The regional localisation of this ventilation-perfusion imbalance could be related in several children to the probable distribution of hypertensive pulmonary vascular disease, predicted either from local anatomy shown at cardiac catheterisation or from the abnormal distribution of pulmonary perfusion. Abnormalities present on breathing air may be partially reversed on breathing 100 per cent oxygen.


Multifocal atrial tachycardia in two neonates. Two neonates with rapid and irregular pulse rate had an uncommon form of atrial tachycardia. The irregular heart rate was first detected during fetal monitoring. Postnatal electrocardiograms were compatible with the diagnosis of multifocal atrial tachycardia or chaotic atrial rhythm. Both patients were treated with digoxin and the rhythm gradually reverted to sinus. This may represent the first description of multifocal atrial tachycardia in the newborn.


Studies of correlation between progression of coronary artery disease, as assessed by coronary arteriography, left ventricular end-diastolic pressure, ejection fraction, and employability. The occupational status of a group of 100 male patients, 35 to 68 years of age, with chronic ischaemic heart disease was studied, and related to the severity and distribution of coronary artery stenosis seen on the arteriograms and to left ventricular function. In this series of patients 31 per cent were working, 31 per cent were recorded as temporarily sick, and 38 per cent as permanently disabled. It appears that while the type of previous occupation and physical activity associated with the job were of importance, there was no correlation between employability on the one hand and severity and distribution of coronary artery disease on the other. 'Blue-collar' workers had a higher rate of unemployment than those in 'white collar' occupations, but this could not be explained by differences in severity of coronary artery disease.


Longitudinal survey of ischaemic heart disease in randomly selected sample of older population. A group of 215 men and 272 women aged 62 to 90 forming a randomly-selected sample of the older population was studied by cardiovascular survey methods and followed for 5 years. The 5-year mortality of 28 per cent was related to age and was higher in men. Ischaemic heart disease was the certified cause of 28 per cent of the deaths. Mortality was greater in those with systolic hypertension. Among electrocardiographic features ST depression, T inversion, and atrial fibrillation increased overall and ischaemic heart disease mortality independently of their association with age. A positive response to an angina and infarct questionnaire was poorly related to subsequent mortality. Re-examination of 72 per cent of 5-year survivors was possible. Systolic and diastolic blood pressures were significantly lower and the frequency of electrocardiographic abnormalities, particularly left axis deviation, left ventricular hypertrophy, and ST and T wave changes, was increased.


Early diastolic murmurs in end-stage renal failure. An early diastolic murmur thought to indicate functional aortic regurgitation was heard in 7 of 74 consecutive patients with end-stage renal failure assessed for chronic intermittent haemodialysis and transplantation. In all 7 cases the murmur was transient and related to episodes of hypertension and fluid overload and disappeared on correction of these factors. In a further 2 patients aortic regurgitation resulted from a structural abnormality of the aortic valve. Thus, an early diastolic murmur is not uncommon in this situation and does not necessarily indicate organic aortic valve disease which might preclude selection for haemodialysis and transplantation.


Removal of AC interference from the electrocardiogram. A method is described for the removal of AC interference from the electrocardiogram in monitors which do not have isolated inputs. The patient's leads are connected to an isolation amplifier which provides isolation between the input and the output and has a high common mode rejection ratio. The output from the isolation amplifier is taken to the electrocardiographic monitor. The isolation amplifier not only provides additional patient safety but also reduces the level of AC interference without interfering with any frequency components in the electrocardiogram.


Ruptured bronchial artery aneurysm mimicking aortic dissection. A patient is presented in whom rupture of a bronchial artery aneurysm produced a clinical picture indistinguishable from an aortic dissection. This case emphasises the importance of considering alternative diagnoses when a patient presents with symptoms typical of a particular condition.


Prinzmetal's angina.

Prinzmetal's angina. A 23-year-old man had Prinzmetal's variant angina. After strenuous exercise and isoprenaline infusion the electrocardiogram remained normal and the patient asymptomatic. Coronary angiography gave normal results which remained normal after administration of ergometrine. An injection of methacholine induced an attack.