Effect of flouride varnish (Duraphat) treatment every six months compared with weekly mouthrinses with 0.2 per cent NaF solution on dental caries. Recent studies have shown a high fluorine uptake in the enamel and a considerable caries reduction following the application of varnished containing fluoride. As the application is easy to carry out it may in certain situations serve as an alternative to other topical fluoride school programmes. The aim of the present study, therefore, was to compare the caries increment in schoolchildren exposed to a fluoride varnish (Duraphat) every six months and in children receiving the conventional weekly fluoride mouthrinsing programme with 0.2 per cent sodium fluoride over a two-year period. Two hundred 14-year-old children, divided into one test and one control group took part in the study. They were clinically and radiographically examined every year. Preexperimental data revealed no differences between the groups. During the experimental period the children in the fluoride varnish group developed a statistically significant lower number of new carious lesions compared with those in the mouthrinsing group. The difference in caries increment was about 30 per cent. Further clinical studies to compare the effects of various topical fluoride programmes are recommended.


Dental caries and restoration. IV. A six-year longitudinal study of the caries increment of proximal surfaces. In order to study the progression of proximal caries lesions and the quality of restorations, a sample of individuals in Gothenburg, Sweden was radiographically examined at the ages of 16, 19 and 22. By means of an index system every proximal tooth surface was given a diagnosis and differences between examinations were evaluated by a score system. Of all decayed and filled surfaces observed at the age of 22 more than 70% were already established at the age of 16. During the 16--19 year interval more than twice as many new carious lesions were developed than during the 19--22 year interval. The decrease in the number of new lesions during the last interval was accompanied by a slower progression of already existing lesions. Both factors resulted in a lower mean value with regard to scores during the 19--22 year interval compared with the preceding one. However, great individual differences were noted and 22 percent of the individuals exhibited larger score values during the last interval than during the first. Relatively seen the number of restorations with overhanging margins was lower at the final examination than at the previous ones.


Lysozyme activity in saliva from children with various degree of gingivitis. The lysozyme activity was determined in paraffin stimulated whole saliva from 51 randomly selected children. The average age was 6.5 years. The children were divided into four groups according to their degree of gingival inflammation. An agardiffusion method was used with Micrococcus lysodeikticus as indicator of the lysozyme activity. The mean value of the lysozyme activity was determined to 48.4 microgram/ml. In the non-inflamed group the enzyme activity was 8.7 microgram/ml, whereas it was lower, 31.5 microgram/ml, in children with inflamed gingiva. The correlation coefficient (p less than 0.05) suggest that there is a negative relationship between saliva lysozyme and the degree of gingival inflammation. Furthermore this study indicates that lysozyme acts as one of the resistant-factors against gingival inflammation in young individuals.


[The pathophysiologic reactivity of the endodontium and periodontium]. The plaque-linked caries and gingivitis are attended by phlogogenic attacks to the endodontium and the periodontium. The knowledge of the morphology and pathomorphology as well as of the fundamental physiopathological reaction patterns leads to a reasonable organ-oriented diagnosis from which the regenerative power must be deducible. Experimental results are illustrated by the examples of vascularity and blood circulation. Further damage must be reduced to a minimum by sparing and safe conservative therapy.


[Myoarthropathies: findings and therapy]. Im myoarthropathies the interplay of the functions of articulation, mandibular joints, muscles and periodontium is disturbed. They are due to occlusal disorders. The oral examination is carried out according to Krogh-Poulsen. The therapeutic procedure involves three steps. Step 1 : elimination of gross occlusal disorders. Step 2: elimination of occlusal disorders after recording of the jaw relations and model analysis on the articulator. Step 3: prosthetic treatment.


[Position of the mandible, range of movement and temporomandibular joint noises in edentulous patients (proceedings)]. The authors present studies on lateral displacements and ranges of horizontal and vertical movements of the mandible. Theyy used a new device--deviatiometer (fig. 1--4)--for measuring the position and the movements of the mandible. They stated no significant differences in the frequency of temporomandibular joint noises with regard to sex, age, lateral displacement of the mandible and ranges of movements. Consequently, temporomandibular joint noises should not be overvalued in the edentulous patient.


[Mandibular positioning and movements relative to the pain dysfunction syndrome]. The movements and positions of the mandible are controlled by three guiding factors: tooth guidance, joint guidance, and muscle guidance. For this reason, the author proposes new, clearly delineated definitions for the terms "central occlusion", "central relation" and "muscle guidance". The unity of structure and function results from the harmony (biological equilibrium) between these three guiding factors. Deviations of the individual guiding factors (occlusal disorders, decentralized relations, malpositions and misguidances of the muscles) may be analyzed separately to begin with; thereupon, their interrelations will be elucidated. As not all of these three guiding factors are necessarily involved in an impairment (above all, the mandibular joints often show no abnormalities), and since pain is the principle sign in the clinical picture of a dysfunction of the orofacial organ, the author is of the opinion that the term "pain-dysfunction syndrome" (as coined by L. Schwarz) is more correct than such terms as "Costen's syndrome" or "myoarthropathy".


[Headache due to functional disorders of the masticatory organ. Headache due to tension of the masticatory muscles]. Headache in the temporal, frontal and suboccipital regions are described as to case history, findings and differential diagnosis. With due respect to possible further symptoms of dysfunction, the author indicates as principles to treatment: 1. restoration of the continuity of the rows of teeth, and of the occlusal relations; 2. restoration of correct jaw relations; 3. rehabilitation of masticatory muscles.


[Special radiographic characteristics of the temporomandibular joint in functional disorders of the masticatory organ]. The inclinations of the articular tubercles were measured on Schüller radiographs of the temporomandibular joints. They were significantly flatter in patients than in control subjects. Patients having pain showed considerably more frequently right-left different angles of inclination than patients being free from pain. The widths of the interarticular spaces were subdivided into 3 classes as suggested by Kleinrok. Again it was found that right-left dissimilarity (class III) was significantly more frequent than right-left similarity (class II) only in patients having pain.


[Occluso-articular functional diagnosis]. The guiding factors of the movements of the mandible are dealt with, and problems arising in simulating these factors on an articulator are discussed. A technique for measuring the dimensional behaviour of the mandible during moving is presented, and the influence of this phenomenon on the determination of the terminal position of the hinge axis is discussed.


[Prosthetic diagnosis within the framework of morbidity analyses]. In the framework of a morbidity analysis, the author determined in 500 subjects from the working population the frequency distribution of the various types of incomplete dentition and the proportion of actual prosthetic treatment. From this some suggestions were deduced for prosthetic treatment which should be considered in individual oral examination and treatment.


[Apicoectomy].

[Apicoectomy]. Apicectomy is a supplement to conservative therapy in those cases in which the latter fails to achieve bacteria-proof obturation. Indications for it are presented. The technique of the procedure, which has widely been standardized in the last years, is appreciated in detail. Hints at the evaluation of the results of treatment are given.


[Infectious complications in acute and chronic leukemias]. Clinical and microbiological examinations of patients with acute leucosis and chronic myelo- and lympholeucosis were carried out aiming at the elucidation of incidence, localization and causative agents of the infectious diseases along with them. The infectious complications were concluded to present a serious problem in the treatment of leucosis, due to which their diagnosis is of essential importance for their early diagnosis, timely treatment and prophylaxis.


[Partial mechanical cardiac replacement in experimental cardiogenic shock]. The importance to evaluate artificial ventricles for left heart assist under cardiogenic shock conditions is emphasized. The main cardiogenic shock models currently used for assisted circulation research are mentioned. Our own method called selective peripheral coronary embolization is presented in detail with its anatomic, pathologic-histologic and electrocardiographic pattern. Polyester fibrils are embolized selectively to the posterior wall of the heart by direct puncture of the circumflex branch of the left coronary artery. Shock hemodynamics and the effects of circulatory assist by the pneumatically driven ellipsoid ventricle (ELVAD) are demonstrated in 20 acute calf experiments. The artificial ventricle was inserted to the circulation between the natural left ventricle and the thoracic aorta in a paracorporeal and intrathoracic position. ELVAD activation was followed by a significant decrease of left ventricular pressure (-65%) and left atrial pressure (-35%). Cardiac index was increased by 10% and mean aortic pressure by 28% from their shock levels. Hemodynamics in irreversible ventricular fibrillation are analyzed in a calf experiment with a 40 hours survival only with ELVAD assist.


[Acute hypoxia and internal intensive care. IV. Results of respirator therapy in an internal intensive care unit]. In the fourth information on the topic acute hypoxia and internal intensive medicine the results of an internal intensive unit in the respiration of internal emergencies during one year are described. Issuing from this, questions of the respiration in insufficiency of the left heart, acute and chronic obstruction of the respiratory tract, restrictive disturbances of the lung, of neurological pictures of the disease, intoxications and shock lung are in the centre of the treatise.


[Difficult situations in diagnosis and therapy in nonmalignant bone tumours and similar disease (author's transl)]. Clinical and x-ray criteria for bone tumors should be analyzed very carefully. It is demonstrated that especially periosteal reactions are nor characteristic of any specific tumor but only of a certain type of stimulus upon the periost, which may be provoked by different agents such as tumor, pus, subperiosteal hematoma and others.


Prostaglandin chemistry.

Prostaglandin chemistry. The prostaglandins and some related substances of biological importance constitute a rapidly growing family of compounds, all the members of which are oxygenated derivatives of certain polyunsaturated, essential fatty acids, such as arachidonic acid. Most cell types possess the enzyme systems necessary for the conversion of the precursor fatty acids into these compounds. The first step in the conversion leads to the production of cyclic peroxides, and this step is readily inhibited by the non-steroidal anti-inflammatory drugs. The further metabolism of the endoperoxides leads to the formation of other potent compounds: the "classical" prostaglandins, the thromboxanes, and prostacyclin.


Determination of prostaglandins in body fluids and tissues. The biosynthesis of prostaglandins is a very rapid reaction. Since blood platelets, when disturbed, readily convert e.g. arachidonic acid into prostaglandin E2 and F2 alpha, those compounds cannot be quantitated in body fluids or tissues which contain platelets. When present in the circulation, primary prostaglandins are rapidly inactivated to corresponding 15-keto-13, 14-dihydro metabolites which occur in plasma in about ten times higher concentrations than the primary prostaglandins. The basal plasma levels of these metabolites are lower than 100 picog/ml. Therefore highly sensitive and specific techniques are necessary for safe quantitation of prostaglandins. The rapid inactivation of prostaglandins also makes it necessary to carefully determine which metabolite should be quantitated in a given experimental situation. The complexity of prostaglandin biochemistry and its importance for accurate monitoring of prostaglandin synthesis in different experimental situations will be discussed in this article.


Effects of the prostaglandins on the uterus. Prostaglandins and uterine contractility. The effect of intravenous and intrauterine administration of PGE1 or PGE2 and PGF2 alpha as well as oral administration of PGE2 on the sensitivity and reactivity of the nonpregnant human uterus was studied. With the use of the flaccid microballoon technique or a micro transducer catheter, uterine recordings were made at frequent intervals throughout the menstrual cycle. Independently of the route of administration and of the phase of the cycle, treatment with PGF2 alpha invariably resulted in stimulation of uterine motility. A high sensitivity to PGF2 alpha was noted during the late secretory phase both in normal and dysmenorrheic women. A marked decrease in sensitivity to both PGE2 and PGF2 alpha administered by the intrauterine route was observed in the periovulatory phase. Inhibition of uterine contractility by PGE2 following both intrauterine and oral administration was noted during active menstrual bleeding in normal as well as in dysmenorrheic women. These findings suggest that endogenous prostaglandins may play a role in the regulation of the normal uterine motility during the menstrual cycle and that the main reason for the abnormal contractility pattern seen in dysmenorrheic women during menstrual bleeding is an increased PGF2 alpha/PGE2 ratio.


Dysmenorrhea during adolescence.

Dysmenorrhea during adolescence. Different aspects of the menstrual pattern including dysmenorrhea, premenstrual tension and working performance during menstruation was studied in three different investigations. The first study includes 5458 adolescent girls aged 10 to 20. The incidence of invariably painful menstruation was 7.2 per cent during the first gynecological year and 26 per cent five years later. A correlation was found between mothers and daughters for dysmenorrhea as well as for premenstrual tension. In a second study including 331 girls aged 13 to 20 years the overall absence from school due to pain was 23.4 per cent. The frequency of dysmenorrhea increased from 36 per cent to 56.5 per cent between 13--14 years and 17--20 years. Socio-medical aspects of menstrual pattern were studied in 865 adult women. Approximately 88 per cent had premenstrual tension and almost 45 per cent had menstrual pain. Thus the treatment of menstrual distress during adolescence is of great importance and the use of modern prostaglandin synthetase inhibitors may be very useful.


Socioeconomic implications of dysmenorrhea. Dysmenorrhea constitutes only a small fraction of the causes of absence from work among women of childbearing age. Nevertheless, every second woman in two Norwegian industrial companies experienced pain during menstruation and one in three had to stay in bed at least one day per month. Many women attend their jobs in spite of reduced capacity for work during periods of discomfort. The consequence for work output and hence economy may be impossible to estimate. Socially the perimenstrual period has a negative effect on many women. Poor results at examinations, greater risk of being injured and a tendency to commit offences seem to cluster at this time. The social implications of dysmenorrhea may be as important as the econonic ones.


Standard treatment of dysmenorrhea with special reference to treatment with spasmolytics and hormones. A survey of the methods of treatment used in dysmenorrhea is given. Special importance is focused on most frequently used methods of treatment in recent years, e.g. treatment with spasmolytics and hormones. The spasmolytics are by no heans effective in all cases in treatment of dysmenorrhea and undesirable side-effects are of frequent occurrence. When oral contraceptives became available it was found that they represented an effective remedy for dysmenorrhea. Whether the Pill should be used for treatment of dysmenorrhea must depend on whether there is also a desire of contraception or not. It is not unusual that women with severe dysmenorrhea have to abandon oral contraceptives because of side-effects or possible risks of this treatment. There is a need for alternative treatment, and the new effective prostaglandin synthetase inhibitors may meet this need.


Hematological side effects from antihypertensive drugs. To sum up, some hematological side effects are seen after antihypertensive drugs. They are, however, few, usually not severe and furthermore reversible. And so, from the viewpoint of the hematologist, there are no contraindications against antihypertensive treatment. The prevalence of side effects on blood and blood-forming organs from antihypertensive drugs is low. Of certain interest are 1) the tendency of modern diuretics (thiazides) to cause a moderate and reversible thrombocytopenia and 2) the positive antiglobulin reaction (Coomb's test) sometimes seen after alpha-methyldopa therapy and in a few cases causing autoimmune hemolytic anemia. Even though case reports have appeared on leukopenia/agranulocytosis related to almost all drugs used in the treatment of hypertension, none of these drugs seem to be especially prone to cause any damage to leukocytes and/or leukocyte production.


Immunological side-effects of antihypertensive drugs. The immunological side-effects under treatment with antihypertensive drugs are mainly limited to autoimmunity and autoimmune disease caused by alpha-methyldopa and hydralazine. Autoimmune hemolytic anemia is more common during treatment with alpha-methyldopa. Hydralazine may induce antinuclear antibodies. Some patients develop a SLE-like syndrome. Its clinical picture is less severe and its prognosis is more favourable than that of spontaneous SLE. During treatment with low doses the disease develops exclusively in patients who are slow acetylators. It may appear also in rapid acetylators during the high dose treatment. The symptoms are usually reversible after withdrawal of the drug.


Granulocytic sarcoma (chloroma) of the cerebellum and meninges a case report. A 7-year-old boy, having had headache and vomiting for one month, was operated for a tumour in the left side of the posterior fossa. The tumour, weighing 52 g, infiltrated the dura mater, leptomeninges, and also, superficially, the left cerebellar hemisphere. The patient died five weeks after operation. Light and electron microscopical examination revealed a granulocytic sarcoma (chloroma). Pre- and postoperative blood examinations, together with postoperative and autopsy bone marrow examinations, showed no sign of acute myelogenous leukaemia. This is the second reported case of primary intracranial chloroma with no preceding sign of acute myelogenous leukemia, and the first case with cerebellar infiltration.


Serial studies on in vitro colony formation in patients with acute leukemia in relation to the maintenance of remission. For the purpose of preventing a relapse of acute leukemia which is currently the major problem in the successful treatment of the disease, repeated consolidation or intensification therapy during the first year following remission is important. To evaluate these therapies, we investigated the serial changes in CFU-C's of the marrow cells from 12 patients with acute nonlymphocytic leukemia in remission and tried to estimate the relationship between the intensity of consolidation or intensification therapy and the duration of remission, utilizing the degree of reduction in CFU-C's seven days after these treatments as an indicator. As a result, after 21 out of 22 courses of therapy where CFU-C's were reduced significantly after the therapy, the patients were still in remission at the time of the next intensificiation therapy (at most for about 100 days). On the other hand, after five out of ten courses where CFU-C's were not reduced significantly, the patients were in relapse at the time of the next intensification therapy. From these results, it may be inferred that cases whose CFU-C's are not reduced significantly should be treated intensively again within a short period.


Erythroleukemia: in vitro studies of erythropoiesis. We studied the growth of erythroid burst-forming units (BFU-E) and erythroid colony forming units (CFU-E) from bone marrow and blood in six patients with erythroleukemia. Five patients grew CFU-E, while BFU-E were found in the marrow of two and in the peripheral blood of only one patient. In all cases with colony growth, the numbers of colonies were markedly decreased with respect to normal controls. Patient BFU-E were composed of fewer clusters than those of controls. BFU-E and CFU-E growth was dependent on the addition of erythropoietin to the medium, and no growth was observed in absence of erythropoietin. At present it is not known if the growth obtained is derived from residual normal erythropoietic stem cells or from abnormal erythroid precursors of the leukemic cells.


[Effects of ventilation with defined formaldehyde concentrations on lung function and lung structures. Animal experiments on the noxiousness of formaldehyde residues after disinfection in the aseptor (author's transl)]. Having seen the development of fatal pneumonias in ventilated patients, the cause of which was assumed to be the presence of residual traces of formaldehyde in the air in the respirator Kilian and Haug showed in 1973 initial formaldehyde concentrations up to 0.2 ppm in the ventilatory air of respirators correctly disinfected in the Aseptor. To study the effects of formaldehyde on lung function and lung structures, 23 young pigs were automatically ventilated with defined formaldehyde concentrations during 6 hours. The concentrations used were 0.02 ppm, 0.2 ppm and 2.0 ppm (double of the maximum permissible concentration). We found no differences in lung function, as shown by compliance measurements and arterial blood gas analysis. No radiological differences were in the thorax. Histologically, there were only slight alterations in lung structure in the group ventilated with double the maximum permissible concentration of formaldehyde. We conclude that the disinfection of respirators using formaldehyde in the Aseptor will remain the method of choice.


Problems in resection of chest wall sarcomas. To illustrate the problems of reconstruction in major chest wall resection, five patients with a variety of soft tissue tumors of the chest wall, located at different sites, are presented. Patients, who underwent a lateral or posterolateral chest wall resection required removal of two to five ribs sequentially as well as the adjacent soft tissue. Those who underwent an anterior chest wall resection required resection of the manubrium or the body of sternum as well as of adjacent costal cartilages. To prevent instability of the chest, herniation, and to minimize flailing, the chest defect was bridged with the use of Marlex mesh. Whenever possible, the omentum was brought into the chest cavity to increase the vascularity of the reconstruction. Since, in most instances, the tumors involved the skin because of previous damage from radiation therapy, extensive skin coverage was planned well in advance of resection. Pedicle skin flaps or rotation flaps were used to cover the skin defect. Ventilatory support by volume respirator, was required for three to four days. In all patients, the chest wall was completeley stable after three to six weeks.


Debrancher deficiency: neuromuscular disorder in 5 adults. Five patients, 4 men and 1 woman, had adult-onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5- to 45-fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase-limit-dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired. Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult-onset hereditary myopathies.


Pyoderma gangrenosum and myeloproliferative disorders. Report of a case and review of the literature. The exact mechanism involved in the pathogenesis of pyoderma gangrenosum (PG) still remains unclear, yet there is an increasing number of reports associating PG with immunologic abnormalities. A correlation between PG and myeloproliferative disorders has also been described. We describe a patient with chronic myelocytic leukemia in whom PG developed during the course of illness. We present an immunologic analysis of this case, speculation on the pathogenesis of PG, and a review of the literature. We report the futility of current therapeutic modalities in the treatment of PG.


[Foetal antigens on leukaemia cells (author's transl)]. An antiserum against human foetal liver cells reacted in in-vitro-cytotoxic test with the leukaemia cells of 6 out of 10 children with acute lymphocytic leukaemias (ALL) and with the lymphoma cells of 1 out 2 children with lymphosarcoma (LS). No cytotoxic reactions were obtained against leukaemia cells of 5 children with acute myelogenic leukaemia (AML), leukaemia cells of 7 adults with chronic lymphocytic leukaemia (CLL), bone marrow cells of 9 children in clinical remission and lymphocytes of normal donors. The cytotoxic activity of the anti-foetalserum was removed by absorption with foetal liver but not with adult liver. The results suggest that foetal antigens may occur on ALL-cells and LS-cells.


Studies on the role of acetylhydrazine in isoniazid hepatotoxicity. Some factors affecting the metabolism of acetylhydrazine were studied in rats. This compound, a potent hepatotoxin, is a metabolite of isoniazid in man and is thought to be responsible for the hepatotoxicity of the drug. Isoniazid inhibited both the microsomal metabolism of acetylhydrazine, in vitro, and the acetylation to diacetylhydrazine in vivo. The overall effect of isoniazid in vivo was to increase metabolism of acetylhydrazine through the microsomal pathway leading to increased covalent binding of the toxic reactive intermediate to liver protein. The results suggest that the metabolism of acetylhydrazine produced as a metabolite of isoniazid may be quantitatively different from the metabolism of the compound alone. Preliminary studies in patients suffering isoniazid related liver damage indicated that acetylation of acetylhydrazine may be one of the factors involved in the hepatotoxicity of isoniazid in man.


Motility and stereotyped behaviour induced by amphetamine and apomorphine on hypophysectomized and on thyroidectomized rats. The reduction of the hypermotility and stereotyped behaviour induced by amphetamine and apomorphine was used as a criterion for the effectiveness of neuroleptics. Considering the impact of neuroleptics on the hypophysis as well as the relationship between the hypophysis and the thyroid, motility and stereotyped behaviour induced by amphetamine and apomorphine was studied in both hypophysectomized and thyroidectomized rats. In the hypophysectomized rat, amphetamine-induced hypermotility, observed between 1 and 3 hours after administration, was almost 3 times greater than in normal animals. Thyroidectomy resulted in a reversal of the motility effect induced by amphetamine. The stereotyped behaviour induced by apomorphine was practically abolished in both hypophysectomized and thyroidectomized animals.


Liver growth and tumorigenesis in rats.

Liver growth and tumorigenesis in rats. Liver enlargement is frequently reported in studies on the short-term toxicity of chemicals. In many such studies no histological evidence of damage is present but biochemically there is often an increased microsomal enzyme activity (MEA) which is interpreted to represent a type of work hypertrophy. In a few instances, the MEA in the enlarged liver is either normal or less than normal. In such instances histochemical evidence of liver damage (depression of G-6-Pase and autophagy) is found. A compound which produced the latter changes is Ponceau MX. When administered for up to 21 months at a dose-level which produces biochemical and histochemical evidence of liver injury, a series of changes were observed consisting of progerssive diminution of MEA, areas of glycogen accumulation and centrilobular fatty change and these were followed first by nodular hyperplasia and then by frank carcinoma. The protective effect of increased MEA in carcinogenesis was shown by the reduction in tumour incidence on the administration of phenobarbitone simultaneously with acetylaminofluorene, 4-dimethyl aminoazo benzene and diethylnitrosamine. But no such protective effect is seen if the phenobarbitone is administered after treatment with these carcinogens. In fact the number of tumours is enhanced presumably due to preferential stimulation of the growth of malignant cells.


Pharmacokinetic parameters influencing tissue specificity in chemical carcinogenesis. Highly and specifically (3H)-labeled trans-4-dimethylaminostilbene was orally administered to female Wistar rats in doses ranging from 5 X 10(-10) to 2.5 X 10(-4) mol/kg. The following parameters were determined: tissue index in several tissues, binding index of liver proteins, rRNA, DNA, plasma proteins and haemoglobin and stomach proteins. Up to a dose of 2.5 X 10(-6) mol/kg all parameters remained constant, i.e. binding increased proportionately with the dose. It is concluded that simple and linear kinetics prevail and that a pharmacokinetic threshold does not exist in this dose range. At higher doses deviations from linearity were observed, however, the binding index decreased rather than increased with the dose. The results indicate that reactive metabolities are involved in the acute toxic effects observed in the rat stomach and that proximate or ultimate activation products are distributed in the circulation. Their concentration in the target tissue appears not be be specifically high to account for the tissue susceptibility.


Organ specificity of induction of activating and inactivating enzymes by cigarette smoke and cigarette smoke condensate. Inhalation of cigarette smoke specifically induces the rat lung and kidney aryl hydrocarbon hydroxylase (AHH) in less than 4 h. The epoxide hydratase (EH) and the glutathione S-transferase are not significantly modified by a similar treatment in any of the rat tissues. Compared to the kidney AHH, the lung hydroxylase is 3--4 times more sensitive to small concentrations of cigarette smoke and seems to have a longer biological half-life. In both tissues, the induced AHH presents the same in vitro sensitivity to various inhibitors as a polycyclic hydrocarbon induced AHH. In primary fetal rat liver cell culture, the cigarette smoke condensate fractions (CSCF) induce both the AHH and EH activity. Nevertheless, the AHH activity responds faster and to lower concentrations of CSCF than the EH activity. The liver cell culture constitutes a unique tool for a comparative study of the AHH and EH induction mechanism. Low concentration (10 muM) of benz(a)anthracene induces only the AHH activity while trans-stilbene oxide enhances selectively the EH activity. Appropriate concentrations of CSCF or of phenobarbital (PB) determine a parallel induction of both enzymes. The results are discussed on the basis of (a) the existence of specific mechanisms of AHH regulation in the lung and in the kidney and (b) the existence of coordinated or independent biochemical control of the AHH and EH activity.


DNA repair as regulatory factor in the organotropy of alkylating carcinogens. Monofunctional alkylating agents which react predominantly at nitrogen atoms in DNA bases (e.g. alkyl methanesulphonates, dialkylsulfates) are generally weak carcinogens whereas compounds which lead extensively to oxygen alkylation (e.g. alkylnitrosoureas, dialkylnitrosamines, dialkyl-aryltriazenes) often exhibit a strong carcinogenic activity. O6-Alkylation of guanine is a promutagenic DNA modification possibly involved in the initiation of malignant transformation. O6-Alkylguanine can be enzymically excised and in the rat the induction of neural, renal and colonic tumors by alkylnitrosoureas, 3,3-dimethyll-phenyltriazene, dimethylnitrosamine and 1,2-dimethylhydrazine correlates with an excision repair deficiency in the target tissue. However, species and strain differences in the response to these carcinogens are not paralleled by differences in the excision repair capacity for O6-alkylguanine. Preliminary data suggest that in rat liver there is an inducible enzyme for the removal of O6-alkylguanine from DNA.


Modulation of the in vivo covalent binding of the carcinogen benzo(a)pyrene to rat liver DNA by selective induction of microsomal and nuclear aryl hydrocarbon hydroxylase activity. The influence of microsomal (mAHH) and nuclear (nAHH) aryl hydrocarbon hydroxylase activity on the covalent binding of tritiated benzo(a)pyrene to rat liver DNA was evaluated in vivo. Induction of mAHH was obtained after phenobarbitone treatment (180% of control), which increased DNA binding to 210%, but left the nAHH unchanged. mAHH and nAHH were slightly induced with dieldrin (130% and 120%), but the binding remained unchanged. The increasing effect of mAHH as well as the possibly decreasing effect of nAHH induction on the binding became obvious when the data of 11 individual rats were used to solve the equation Binding = aX(mAHH) + bX(nAHH) + c. Multiple linear regression analysis resulted in positive values for a and c, a negative value for b, and a multiple correlation coefficient R = 0.82. An influence of other enzymes involved in the metabolism of benzo(a)pyrene cannot be excluded. The study shows clearly that the binding of a foreign compound to DNA in vivo is not only dependent on microsomal enzyme activities but also on nuclear activities even if the latter are considerably lower than those of microsomes.


Estimation of the TCDD toxic potential in the light of the Seveso accident. Two years after the TCDD release in Sevesco from the assessment of the acute and midterm effects on the health of the population exposed to known level of contamination the following facts emerged. Chloracne appeared mainly in a small nuber of children mostly with mild severity and quick recovery. Immunoresponse remained normal and susceptibility to infectious diseases was not increased. Peripheral nervous system was not affected in these children nor were the hepatic functions and the urinary porphyrin excretion. Fetal losses and birth defects remained within the expected rates. Newborn growth and development proceeded normally. Chromosome examinations did not reveal abnormalities in number and patterns. A case of intercurrent death provided for the first time TCDD tissue levels in man 6 months after the exposure.


Biological threshold limits for benzene based on pharmacokinetics of inhaled benzene in man. Volunteers were exposed to benzene, 2--10 ppm, under controlled conditions up to 6 h a day during five consecutive days. The accumulation and elimination of benzene was measured by determination of benzene concentration -- down to 0.001 ppm -- in exhaled breath. From these observations, a multicompartment model, which approximately describes the kinetics of benzene elimination and accumulation has been designed. On the basis of this model, benzene concentrations in breath, corresponding to exposure levels of benzene, have been estimated. Thus, at a daily exposure to 10 ppm the exhaled benzene concentration in the morning after a day of exposure will not exceed 0.1 ppm.


Toxic effects of di-n-octyltin dichloride on the thymus in mice. The effects of di-n-octyltin dichloride (DOTC) on the thymus in mice were studied in dependence on the route of administration. Single administrations of 30, 60 and 120 mg/kg of DOTC i.m. induced a dose-related decrease of the thymus weight and of the number of nucleated cells in the thymus of male mice. 4 days after intravenous injection of 8 mg/kg of DOTC the thymus weight and the number of thymocytes were reduced to 50 percent of the control. In oral route of administration higher doses of DOTC (300 mg/kg) were necessary to provoke a thymus atrophy. After pretreatment of mice with carbon tetrachloride the toxic effects of orally administered DOTC were increased. The reduction of the thymus weight and of the number of thymocytes in mice after parenteral administration was accompanied by a depression of thymus-dependent antibody formation against sheep red blood cells.


Accentuation of white phosphorus induced fatty liver by phenobarbitone in male rats compared to female rats. The possible influence of a potent enzyme inducer, phenobarbitone, on white phosphorus fatty liver, was studied. Pretreatment by phenobarbitone for four days in white phosphorus poisoned rats provoked a decrease in mortality and an increase in hepatic triglycerides (fatty liver) in male rats. The activity of uridine diphosphoglucuronyl transferase (UDPGT), an inducible enzyme, is not modified by this pretreatment in white phosphorus poisoned rats. The accentuation of white phosphorus fatty liver by phenobarbitone in male rats could be explained by an increased hydroxylation of testosterone, thus counteracting the protective effect of this hormone on fatty liver.


Fatty liver induced by high doses of rifampicin in the rat: possible relation with an inhibition of RNA polymerases in eukariotic cells. The steatogenic effect on the liver of Rifampicin, a potent inhibitor of the DNA-dependent RNA polymerase in bacteria, was investigated in male and female rats which received either 200 mg or 400 mg of Rifampicin/kg/24 h for 8 days. The determination of total lipids (TL), triglycerides (TG), total cholesterol (TC) and phospholipids (PL) showed a significant increase of TL, TG and TC in the liver at a dose of 400 mg. There was better reproducibility in the male whose blood TG and PL were significantly decreased. These results showed that fatty liver can be induced by very high doses of Rifampicin in rats. A blockage of the very low density lipoproteins (VLDL) biosynthesis and/or secretion can be expected. As a potent steatogenic toxin, alpha-amanitin, is a strong inhibitor of RNA polymerase II in eukariotic cells, a relationship between the RNA polymerase inhibition induced by both of substances and a subsequent inhibition of the biosynthesis of the protein moiety of lipoproteins can be considered. Nevertheless Rifampicin is at present not considered as an inhibitor in eukariotic cells and it will be of great interest to test such a possibility with the high doses used in these experiments, in further work.


Effects of subacute toluene inhalation on its metabolism and disposition in rat. Exposure of adult male rats to 300 ppm of toluene for 1 to 15 weeks 6 h daily caused accumulation of the solvent in brain and in perirenal fat. The body solvent content tended to decrease during extended exposure which might be explained by the enhanced activity of drug-metabolizing enzymes in liver. Our findings also indicate that metabolic and functional adaptation takes place in longer exposures to low levels of toluene vapour.


Drug-nitrite interactions: species and sex differences in the formation of dimethylnitrosamine and its effects on the hepatic enzyme activities. Aminopyrine interacted with sodium nitrite in the stomachs of rats and guinea pigs forming dimethylnitrosamine, which affected the hepatic microsomal drug metabolism and certain hepatic enzyme activities. Sex and species differences in changes in the enzyme activities were observed after single or simultaneous administration of aminopyrine and sodium nitrite. A protective effect on dimethylnitrosamine formation with ascorbic acid and alpha-tocopherol was observed. The in vivo formation of dimethylnitrosamine by several antibiotics and an antihistaminic drug with tertiary amino group was also examined.


Monoamine oxidase inhibiting and toxic effects of acetyl-phenylhydrazide on rat liver in vivo. For induction of reticulocytosis, rats had been routinely treated with the haemolytic agent, acetyl-phenylhydrazide (APH), and monoamine oxidase (MAO) activity was determined in reticulocytes. Since hydrazines are known to be irreversible inhibitors of MAO, the MAO inhibiting potency of APH was assessed in vitro and in vivo. Only in vivo, an apparently organ-selective MAO inhibition was observed in rat liver; in addition, the rate of recovery of MAO activity in vivo after inhibition with APH was considerably prolonged, indicating a toxic effect of APH on this organ. However, clinical-chemical and pathohistological parameters did not reveal any signs of an overall liver parenchymal cell damage. Hence, a more specific interference of APH with mitochondrial enzyme synthesis must be postulated.


Entrance into brain of dextropropoxyphene and the toxic metabolite norpropoxyphene. Several studies show that dextropropoxyphene after oral administration is intensively biotransformed to norpropoxyphene by first pass metabolism in the liver. While dextropropoxyphene is analgesic, cardiotoxic and shows CNS toxicity with convulsions and respiratory depression, norpropoxyphene is cardiotoxic to the same degree as dextropropoxyphene, but is without analgesic or CNS-toxic effects (Lund-Jacobsen, 1978). This principal difference between the effects of dextropropoxyphene and norpropoxyphene might be due to differences in penetration into the brain. We investigated the penetration of the two compounds in 14C-labelled moities into the brain of rats by the technique originally described by Oldendorf (1970). By this method the extraction of dextropropoxyphene was found extremely high, while it was much lower for the metabolite. The extraction percentage for dextropropoxyphene after 5 and 10 S was 350 +/- 34.1 and 164 +/- 15.2, respectively, while the values for norpropoxyphene was 62 +/- 6.2 and 44 +/- 4.1 (mean +/- S.E.M.), respectively. This difference may at least partly explain the missing CNS-symptoms with the metabolite.


Prostaglandins in rat placenta following acute and chronic administration of morphine. The objective of the present study was to obtain information on prostaglandin (PG) biosynthesis in placenta following narcotic administration. PG biosynthetic capacity was determined in whole rat placenta homogenates in the presence of Na arachidonate, by evaluating net production of PGs assayed against PGE1 on rat stomach strips. An enhanced prostaglandin-like activity is shown in homogenates of placenta from rats treated subcutaneously with 10 mg/kg of morphine. This increase was prevented by naloxone pre-treatment. Continual morphine administration during gestation, results in a normalization of placental biosynthetic capacity thus suggesting the development of a tolerance to the narcotic effect.


Effects of two structurally different antispermatogenic compounds on the synthesis of steroids in rat testes. The influence of two drugs with antispermatogenic properties on steroid biosynthesis has been studied in rat testes in vitro with pregnenolone as the substrate. 20-438, an indenopyridine derivative increased the relative conversion of pregnenolone to progestins and estradiol, whilst decreasing the conversion of substrate to testosterone and androstenedione. PMHI, a pipecolinoindane derivative, reduced testosterone levels in the testes without altering the relative conversion of pregnenolone to various steroids. This suggests that the agent is partially inhibiting the biosynthesis of androgen precursors leading to a testosterone deficiency in testicular tissue which may result in reduced spermatogenesis.


Therapeutic effects of the bis-pyridinium salts HGG-12, HGG-42, and atropine, benactyzine in organophosphate poisoning of dogs. Therapeutic properties of various combinations of the bispyridinium salts HGG-12 and HGG-42 against soman and sarin poisoning were investigated in male beagles. Best therapeutic efficiency was shown by HGG-42 in a dosage of 30 muMol/kg. Also good effects were produced by the combination of both oximes in a low dosage of 3 muMol/kg for each one. In soman poisoning no significant reactivation of cholinesterase in serum or erythrocytes was observed.


Ultrastructure of intermediate lobe of the pituitary and melanocyte-stimulating hormone secretion in oestrogen-induced kidney tumours in male hamsters. One group of male Syrian hamsters was killed after various periods of diethylstilboestrol (DES) treatment, ranging from 6 to 36 weeks. All developed renal tumours by 24 weeks. DES also induced hyperplastic and neoplastic changes in the pars intermedia of the pituitary with proliferation of MSH-secreting cells and elevated serum MSH concentration. Another group of male Syrian hamsters was given DES for 36 weeks followed by cessation of hormone treatment. The animals were killed at various intervals from 12 to 36 weeks after DES withdrawal. In these animals the DES-induced renal tumours underwent regression whilst the pituitary changes persisted until the termination of the experiment. The findings suggested that the hormone MSH may be implicated in renal carcinogenesis but plays no role in the maintenance of the established tumours.


In vivo covalent binding of chemicals to DNA as a short-term test for carcinogenicity. The determination of a covalent binding of radioactive chemicals to DNA in intact mammalian organisms is proposed as a short-term test for carcinogenicity. The effectiveness of covalent binding to rat liver DNA correlates well with the hepatocarcinogenicity known from long-term bioassays. The binding indices range over more than five orders of magnitude between the strongest hepatocarcinogen aflatoxin B1 and the limit of detection of a binding with 100 muCi 14C-labelled chemical. The order of magnitude of binding is therefore a surprisingly good quantitative measure for carcinogenicity. The pattern of DNA binding sites is important especially for small alkylating agents where the determination of total binding might indicate a higher carcinogenic potency than is actually observed.


A dynamic system for long-term toxicity studies in fish under laboratory conditions. For the evaluation of possible adverse effects of compounds in fish at sublethal doses a dynamic system is required. The design of such a system is presented including the methodology of performing long-term toxicity studies in fish using selected environmental chemicals (plant protection products). Chronic studies with Diazinon, Terburyn, Phosphamidon on carp and trout comprised 28 day treatment periods followed by 28-day recovery periods. In addition to the toxicity, the residues of the applied chemicals in fish, divided into muscle tissue and viscera, and in the test medium were determined during the experimental and recovery period. The results demostrate that the chemicals accumulated to a somewhat greater extent in the viscera than in the muscle tissue of the fish during exposure. In the course of the recovery period the concentration of the substances tested decreased to the limits of detection. It was concluded that following an adequate waiting period no measurable residues were formed from these plant protection products, that are carried in the food chain.


Estrogenic partial effect of norethisterone enanthate in relation to tumor induction in rat mammary gland. The tumorigenic effect of norethisterone enanthate (NE) on mammary glands in rat and mouse may be ascribed to its own inherent estrogenicity, which is especially pronounced in these species. Because of the estrogenic partial effect, NE stimulates tubulo-alveolar growth of rat mammary gland intensively as does an estrogen-progesterone combination. Although prolactin is known as one of the essential factors needed for development of rat mammary gland, NE causes only a slight increase in serum prolactin level in the rat. In contrast with rat and mouse, NE exerts only a progestational effect in the rabbit. Since the estrogenicity of NE has not been found in many clinical studies, the estrogenic partial effect of NE seems to have no significance in humans. Such a species difference is finally due to the fact that the optimal dose ratio between estrogens and progesterone for maintenance of physiological functions of target organs is quite different from species to species.


Microsomal vinyl oxide synthetase: modification of its kinetic parameters by chemical carcinogens. The kinetic parameters of liver microsomal vinyl oxide synthetase as well as their modifications under the influence of various pretreatments have been evaluated, using 1,1,2-trichlorethylene (TCE) as a substrate. The results were correlated with those obtained using aldrin oxide synthetase and benzpyrene hydroxylase as typical cytochrome P-450 dependent enzymatic activity. The treatments of animals with chemical carcinogens selectively increase the affinity of those enzymes for their substrates.


Influence of drugs on activation and inactivation of hepatocarcinogenic nitrosamines. The alkylation of liver macromolecules following in vivo administration of dimethylnitrosamine (DMN) was diminished after phenobarbital or 3-methylcholanthrene induction of the microsomal monooxygenase system, but increased after SKF 525 A pretreatment. Determination of CH2O and CH3+formation in microsomal incubation systems revealed the same results for low DMN concentrations. An interpretation is given on the basis of spectrophotometric data and electron spinresonance (EPR) measurements, by proposing that metabolic inactivation of nitrosamines is catalysed by a reduction process in which cyt. P 450 seems to be involved.


Effect of DMN, phenobarbital and halothane on the sedimentation characteristics of rat liver DNA. Viable rat liver cells were isolated, and the velocity sedimentation characteristics of DNA centrifuged through alkaline sucrose gradients were studied following the administration in vivo of dimethylnitrosamine (DMN), phenobarbital and halothane. DMN application resulted in a strong decrease of sedimentation velocity, indicating generation of single strand breaks in DNA, whereas phenobarbital and halothane given in doses sufficient to induce liver enlargement did not alter the sedimentation behaviour of DNA from parenchymal or extraparenchymal liver cells.


Demonstration of drug-ethanol interactions by changes in activity of hepatic microsomal oxidase/oxygenase cytochrome P-450 function. "Uncoupling" of microsomal hepatic oxygenases is characterized by a situation in which microsomal monooxygenases exhibit more oxidase than oxygenase activity with an increased formation of hydrogen peroxide at the expense of O2, NADPH and substrate hydroxylation. The importance of such in vitro observations with respect to physiological conditions "in vivo" has been tested by investigating elimination kinetics of ethanol. If hexobarbital, a substrate of mixed function oxygenase as well as an "uncoupler", is given to guinea pigs together with ethanol, changes in the elimination of ethanol occur. It is suggested that this is the consequence of an increased formation of H2O2 which contributes via peroxidatic reaction of catalase to the elimination of ethanol. The results also show additional interactions of hexobarbital as well as of ethylmorphine with ethanol elimination. Both compounds increased the initial blood levels of ethanol which precede accelerated elimination, probably by a first pass effect. At low concentrations of ethanol, ethylmorphine inhibits ethanol elimination by inhibition of ADH.


Polycystic changes in rat kidney induced by biphenyl fed in different diets. Groups of rats were fed biphenyl at various dose levels in a semisynthetic diet and in a commercial chow. The effect levels for induction of polycystic kidney lesions were established by means of urinalysis, organ weight changes, light and electron microscopy, and enzyme histochemistry. The no-effect level, was less than 50 mg/kg bw./day and 300 mg/kg bw./day, when feeding the semisynthetic diet and the commercial chow respectively. This difference in effect level due to the diet is an indication that the diet is of great influence on the results of toxicological experiments.


Computer analysis and integration of animal pathology data. Computer storage of data from toxicology, biochemistry, haematology and pathology has been found necessary in our Laboratory in order to handle the vast amount of information generated by animal toxicology studies. The value of the system to pathology is enormous and its potential has not been exhausted. All finding, from organ weights and macroscopic observations made at autopsy, to the final histopathological diagnosis made by the pathologist are computerized. A modified version of the American College of Pathologists' systematized nomenclature of pathology is used. The pathologist recordtor whose role in the system is indispensable. The designation of a pathologist with special responsibility for supervising the computerisation and its scientific validity ensures its smooth running. The integration of data from haematology and clinical chemistry as a profile for each animal is available to the pathologist when making the final diagnosis. The system has resulted in a standardisation of pathological terminology, greater speed and improved accuracy in report formulation, the establishment of a readily retrievable in-house data bank and an enormous saving in the time of pathologists and secretaries.


Evaluation of the carcinogenic effects of estrogens, progestins and oral contraceptives on cervix, uterus and ovary of animals and man. Estrogens do not have the general biological effect of increasing the occurrence of cancer in various species of laboratory animals. The neoplastic effect of estrogens in animals is strain and species dependent. Estrogens may increase the incidence of uterine cervical cancer in some strains of mice, but not in other strains or other animal species. The progestins and oral contraceptives (OC) have not induced cervical cancer in animals and most studies demonstrate that the steroid anovulants do not increase the occurrence of abnormal cervical smears or cervical cancer in women. Estrogens increase the occurrence of endometrial cancer in the rabbit, occasionally in the mouse, but apparently not in other species. Case-control studies in menopausal and postmenopausal women indicate an increased risk of endometrial carcinoma (EC) associated with use of estrogen. However, in other studies estrogen has not been related to EC. Cases of EC have been reported in women using sequential OC but a causal relationship has not been established. Progestins alone may arrest progress or cause regression of EC in women. EC has not been related to use of the combination OC, and it is unlikely that use of these anovulants will lead to the development of endometrial cancer. Estrogens or OC do not induce a carcinogenic response in the ovary. A decrease in ovarian cysts, is observed during the clinical use of OC.


Neuroendocrine effects of neuropsychotropic drugs and their possible influence on toxic reactions in animals and man -- the role of the dopamine-prolactin system. As an example for the importance of the neuroendocrine system in the toxicological evaluation of neuropsychotropic drugs, the influence of functional dopaminergic agonists and antagonists on the secretion of prolactin is studied. In rats, all functional dopamine antagonists (reserpine alone or combined with alpha-methyl-p-tyrosine or benserazide, haloperidol, spiroperidol, sulpiride) increased serum PRL levels. Dopaminergic agonists (apomorphine, piribedil, d-amphetamine, L-DOPA, and the ergot derivatives bromocriptine and lisuride) all caused a decrease of serum prolactin levels. The same effect could be observed also after treatment with other ergot derivatives such as d-LSD, methergoline, methysergide and ergotamine. Also in this case, the prolactin-lowering effect seems to be related to dopaminergic activity. This was suggested by the inhibitory effect of pretreatment with the dopamine antagonist spiroperidol or with sulpiride on the prolactin-lowering effect of lisuride. In dogs, thyrotropin releasing hormone (TRH) increased and lisuride decreased serum prolactin levels determined with a new radioimmunoassay. As an example for the situation in humans, the effects of the dopamine antagonist sulpiride and of the dopamine agonist bromocriptine were described. The prolactin levels were higher in the presence of estrogens. The relevance of these neuroendocrine effects of neuropsychotropic drugs on physiological systmes in animals and man is discussed.


Adolescent dental care and the South Australian school dental programme. The problems of continuing dental care once eligibility for school care ceases have been discussed. A questionnaire of 18,976 high school students at 29 South Australian schools indicated that, compared with students with no history of school care, fewer students treated by the School Dental Service reported visiting a dentist since leaving primary school. Several programmes designed to encourage continuing dental care have been described.


The needs of the homebound and institutionalized in South Australia, 1977. A survey of 1,658 homebound and institutionalized persons suggested that about 7,000 chronically ill South Australians may need dental care and that such treatment is currently unavailable to the great majority of them.


Maxillary osteotomies.

Maxillary osteotomies. In the past decade, biological studies on the maxilla have led to variations in established maxillary osteotomy techniques. Three of these surgical innovations are presented with illustrative case histories.


The effect of carbon on the metallography of a nickel base removable partial denture casting alloy. This study has demonstrated the pattern of carbide development associated with progressive increases in carbon content in a series of six nickel chromium alloys. The carbon content is critical since it influences the production and distribution of carbides, which have been shown to alter the mechanical properties, of the nickel chromium alloys, that are dependent upon the development of gamma prime. Furthermore, it has been shown that the attainment of suitable strength is invariably associated with an unacceptable level of ductility.


Treatment of acromegaly with bromocryptine. Twelve acromegalic patients with clinical and biochemical evidence of active disease were studied whilst on bromocryptine (Sandoz) at a maximum dosage of 10--60 mg. The patients were followed for a period of 9--23 months. Clinically, ten patients showed a reduction or disappearance of sweating and seven patients had a reduction in soft tissue mass. Of the five patients who had diabetes prior to treatment, three reverted to normal glucose tolerance during treatment. Biochemically, there was no difference between mean plasma levels of growth hormone (hGH) before and on maximum therapy with bromocryptine. There was a significant difference between fasting plasma hGH before treatment with bromocryptine and following treatment for 9--23 months in five individual patients. Side effects were not disabling in this series except for a reversible paranoid psychosis in one patient. The overall results are disappointing; although some clinical features improved, plasma hGH levels returned to normal in only three patients. Bromocryptine has a limited place in the management of acromegaly for those patients in whom conventional therapy has been ineffective or is contraindicated.


Treatment of acromegaly with bromocriptine. Five men and three women with active acromegaly were treated with bromocriptine. After three months' therapy (30 mg/day) mean GH during the day decreased by 50% in six out of eight subjects. In the remaining two subjects (non-responders) GH was persistently over 100 micrograms/l. Mean GH during glucose tolerance test were not significantly decreased in three out of the eight subjects, of whom two were the nonresponders. The minimum dose of bromocriptine required to achieve maximum GH suppression ranged from 7.5 to 20 mg/day. In contrast, serum prolactin (PRL) throughout the day suppressed significantly in all subjects after 5 mg/day bromocriptine. Decreases in clinical symptoms, hand volume, urinary hydroxyproline and calcium excretion were seen in about half of the subjects. Three of the four subjects with diabetes mellitus showed improvement in glucose tolerance. Although minor side effects were uncommon, one patient died because of massive gastrointestinal haemorrhage from a duodenal ulcer.


Some properties of the colony forming cell in adult acute leukaemia. Variations in the concentration and physical characteristics of the bone marrow derived colony forming cell(CFC) have been studied in patients with acute leukaemia. Two-hundred-and-fifteen marrow samples from 83 patients provide the basis for this analysis. CFC concentration confirmed the clinical remission/relapse status and yielded some guidelines to prognosis in individual patients while the proportions of CFC in DNA synthesis also proved to be a most reliable indicator of disease status. In remission, CFC concentrations return to normal values whilst on presentation and in the relapse phase of acute leukaemia CFC numbers are reduced. Biophysical profiles of CFC established using albumin density gradient and velocity sedimentation studies also indicated the state of the leukaemic process in individual patients. By applying physical laws to the data obtained from such profiles, the mean volume, diameter, density and mass of CFC were calculated. CFC from leukaemic patients in relapse were up to twice the volume and mass although slightly less dense than CFC from normal patients. The reasons for these changes are explained and discussed.


A randomized study of factor VIII or prothrombin complex concentrate infusions in children with haemophilia and antibodies to factor VIII. In four children with haemophilia A and antibodies to factor VIII, 18 bleeding episodes were randomized for treatment with factor VIII concentrate (30 units/kg) and 18 for treatment with a prothrombin-complex concentrate (prothrombinex) given in a dose of 30 units of factor IX/kg. Treatment with prothrombinex was associated with a better clinical response, a significantly greater shortening of the kaolin partial thromboplastin time and significantly lower incidence of post-infusion increase of levels of factor VIII antibodies. Although treatment with factor VIII concentrate was clinically successful in 15 episodes, treatment failures occurred in three instances leading to parental request for withdrawal from study in two families.


Osteomalacia due to unusual causes presenting in adults. Severe osteomalacia due to causes other than malabsorption and, where renal function was impaired, disproportionate to the degree of renal failure, is described in 15 adults. Only one was younger than 46 years, the median age being 59 years. The diagnosis was not made for months in most patients. After investigation, the patients were grouped as follows: nutritional three cases, "renal" six cases, hypophosphataemia three cases, neurofibromatosis and primary hyperparathyroidism one each. The last patient was poorly nourished and had taken anticonvulsants and analgesics. Most patients responded well to treatment with calciferol. These cases indicate the need to be aware that osteomalacia may occur in previously healthy middle-aged or elderly subjects.


Multiple myeloma--prognosis, treatment and survival in an eight year study. Data are presented from an unselected group of 76 patients with multiple myeloma, diagnosed over an eight year period in Christchurch. The median survival time was 31 months from commencement of treatment. The median survival of patients with Bence Jones proteinuria (29 months) was significantly shorter than those without this feature (47 months). Patients with lambda proteinuria had a median survival of 25.5 months and those with kappa proteinuria 32 months, but this difference was not statistically significant. The correlation of presenting anaemia, azotaemia or hypoalbuminaemia with a bad prognosis was confirmed. Immunosuppression of nonmyeloma immunoglobulins in patients with IgA or IgG myeloma was associated with a significantly worse median survival. Chemotherapy was discontinued in 11 patients at a variable period after one year of remission. In six cases the disease did not relapse, but relapse occurred in four cases and in three of these control could not be reasserted. One patient developed acute myeloblastic leukaemia five months after treatment was discontinued.


Drug usage in a western Australian rural community. Drug usage in two agricultural shires, Kondinin and Kulin, was surveyed by questionnaire. Both prescription and over the counter (OTC) drugs were recorded together with age, sex, forced expiratory volume in one second (FEV1), systolic blood pressure (SBP) and body weight, and 1284 people, or 55.8% of the eligible population over six years of age, participated. Approximately 35%, 53% and 12% of people said they were taking no drugs, one to two drugs and three or more drugs respectively, a result very similar to that found in an earlier urban study (Traralgon). The interaction of all five factors on drug consumption was studied jointly by multivariate analysis; FEV1, SBP and weight were normalised using standard tables. Prescription drug usage was directly related to obesity, respiratory impairment and sex (P less than 0.01) but not to age or SBP. People taking either OTC drugs or none at all differed only in sex, with females taking more than males (P less than 0.01). There were no differences in the factors studied between prescription only and prescription plus OTC drug users.


Drug compliance in outpatients with rheumatoid arthritis. A study of drug compliance was carried out on 108 patients with rheumatoid arthritis. Thirty-nine per cent were non-compliant with their antirheumatic medication, varying from occasional to complete failure to take the prescribed drugs. Compared with those taking their medication regularly, the non-compliant patients had a significantly lower mean active joint count and average pain severity and a significantly higher proportion had not received an adequate explanation of their disease. However, drug default does not appear to be a significant problem in management of rheumatoid arthritis, as over 90% of patients were taking their medications all or most of the time. Patients with this disease appear motivated to taking their medication regularly by the presence of chronic and often severe pain.


Coronary heart disease in tribal Aborigines--the West Kimberley survey. Two-hundred-and-forty-eight full-blood tribal Aborigines from the West Kimberley region of Western Australia were surveyed for the prevalence of coronary heart disease, and compared with the known prevalence in whites in the country town of Busselton, WA. The prevalence was found to be greater among the Aborigines, with 7% of men, and 11% of women being found to have "probable" coronary heart disease. Seven per cent of the population had electrocardiographic changes characteristic of frank ischaemia. The major risk factors contributing to this high prevalence were hypertension, diabetes mellitus, and obesity. Thirty-seven per cent of the Aborigines were hypertensive, and 17% had diabetes mellitus.


Nifedipine in the treatment of life threatening Prinzmetal angina. Nifedipine is a non-nitrate vasodilator which has proved effective, in oral form, in Europe, Japan, and the USA for treatment of Prinzmetal Angina. The drug has not been used before in Australia. We report a patient with Prinzmetal's variant angina, complicated by recurrent syncopal episodes due to ventricular arrhythmias. The attacks were resistant to standard therapy except sublingual nitroglycerin but ceased completely during treatment with nifedipine.


Carbamazepine therapy complicated by nodal bradycardia and water intoxication. A case is reported of water intoxication and cardiac conduction disturbances occurring as a late complication of carbamazepine therapy for trigeminal neuralgia. These uncommon but potentially hazardous complications of therapy are reported because of the wide use of carbamazepine as the agent of choice for trigeminal neuralgia and as an anticonvulsant.


Familial relative polycythaemia due to haemoglobin Heathrow. Eleven affected members of a New Zealand family carrying the high oxygen affinity haemoglobin Heathrow are described. The detection of high oxygen affinity abnormal haemoglobins may be difficult as haemoglobin and red cell mass may both fall within the normal range and no abnormality may be detected on haemoglobin electrophoresis or by haemoglobin stability tests. The importance of oxygen affinity studies to establish the diagnosis is emphasized.


Pulmonary alveolar--septal amyloidosis associated with pulmonary tuberculosis and an unusual paraproteinaemia. A patient is described who presented with mixed obstructive and restrictive lung disease, shown to be due to deposition of amyloid in an alveolar-septal distribution. An association with a plasma cell dyscrasia and pulmonary tuberculosis is discussed, as is the need for early diagnosis and a trial of aggressive cytotoxic therapy in primary amyloidosis.


IgA deficiency, superior mediastinal tumour with unusual clinical manifestations. The clinical course of a 17-year-old man with selective IgA deficiency and anaplastic carcinoma in the superior mediastinum is described. High swinging fevers, neutrophil leucocytosis reaching 60 x 10(9)/l, polyarthralgia and skin vasodilatation were unusual manifestations of the tumour. Marked tissue reactions in the neck and polyserositis occurred with a neutrophil granulocyte tissue reaction and progressed to fibrosis. Circulating immune complexes were present and IgE levels were grossly raised. It was not established whether the unusual clinical manifestations were due solely to the tumour or were an abnormal response of an IgA-deficient host. Review of the literature of malignancy in selective IgA deficiency casts doubt upon an increased incidence of neoplasm in this immune deficiency.


Gastro-colic fistula complicating benign gastric ulcer in analgesic abusers. Two cases of gastro-colic fistula occurring in analgesic abusers are described. In both patients, the fistulous communication was diagnosed at endoscopy and subsequently verified by upper gastrointestinal tract barium studies. Gastro-colic fistula is a rare complication of benign peptic ulcer disease. Whilst salcylates and cortico-steroids have been implicated as aetiological agents, abuse of compound analgesics has not previously been reported. Since the first description of gastro-colic fistula in 1755, thirty documented cases associated with benign gastric ulcer have been reported. Most often, gastro-colic fistula occurs secondary to gastric or colonic malignancy. Barium enema examination is the most accurate diagnostic study. Endoscopy has been confined to the visual inspection of the ulcer and establishing the benign nature of these lesions.


Co-existing coeliac and inflammatory bowel disease in a patient with Turner's syndrome. A patient, aged 20, with Turner's syndrome was found to have both coeliac disease and chronic ulcerative colitis. Although a gluten-free diet restored to normal the jejunal biopsy, persisting diarrhoea was found to be due to coexisting left-sided ulcerative colitis. A search of the literature revealed only three detailed reports of chronic inflammatory bowel disease in coeliac patients, one of coeliac disease in Turner's syndrome and three of inflammatory bowel disease in Turner's syndrome. Growth failure with coeliac or inflammatory bowel disease in females, may call for a chromosomal study, even in the absence of webbing of the neck. The reason for three uncommon disorders occurring in this patient remains obscure.


Thermometerphagophilia in Münchausen syndrome. Münchausen syndrome is a medical curiosity. The presenting symptomatology is varied. An unusual presentation--thermometerphagophilia (swallowing of thermometers), is reported.


Congenital pseudarthrosis of the ulna: a case report. A case of congenital pseudarthrosis of the ulna is described. The inevitability of dislocation of the radial head in the early years of life, is pointed out. Following dislocation of the radial head, creation of a stable single-bone forearm is necessary to prevent loss of hand function due to effective shortening of the long flexors. A method of radioulnar fusion is described. Following such fusion good hand function can be anticipated, as the vital humeroulna radiocarpal joints are intact.


Congenital abduction contracture with dislocation of the shoulder in children: report of two cases. Isolated congenital contracture of the deltoid muscle in children is uncommon. There are no reports in the literature of such cases associated with anterior dislocations of the shoulder. Two young girls with deltoid contracture and associated dislocation of the shoulder are reported.


Hip problems in a battered child: a case report. A battered child with a stiff right hip, a pseudarthrosis of the left femoral neck, and a grossly shortened left femur, is described. Conservative care is suggested.


The autosuture surgical stapling instruments: preliminary experience. Stapling instruments for gastrointestinal surgery are relatively new in the surgical armamentarium of Australian surgeons. In an attempt to assess their safety and handling characteristics laboratory experience has been obtained in dogs. This has shown that these instruments are effective and easily handled, although costly in routine use. It seems likely that they will provide an appropriate alternative to certain conventional anastomotic techniques.


The technique of advancement flap haemorrhoidectomy. Surgery is still the mainstay of treatment for large, prolapsing haemorrhoids. The teaching of Sir Alan Parks, and more recently the work of W.H.F. Thompson, have shown that degeneration of the supportive tissue of the anal canal and the subsequent sliding of the anal lining, was the greatest contributing factor in the development of  haemorrhoids. The method of treatment described follows Sir Alan Park's principles of conservation of the anal canal mucosa and skin. This is then used to reline the anal canal after careful dissection and excision of the external and internal haemorrhoids. It therefore returns this prolapsed, sensitive epithelium to its original site. Wound healing is rapid and anal stenosis is avoided.


A simplified surgical approach for lumbar disc excision. A simple approach to the distal lumbar spine for disc excision is described and the relevant surgical anatomy reviewed. The approach is considered to have many advantages over formal laminectomy for the same purpose in the majority of cases. The indications and contraindications for its use are discussed.


Surgical training in France.

Surgical training in France. The French medical student does a six-year course before entering a compulsory "intern" year at the end of which he presents a thesis plus the results of all his University examinations for his medical degree. To become a surgeon he would spend four years as an "intern" in surgical posts then become a "Chef-de-Clinique" for two to four years before being accredited as a specialist. The differences and similarities of their system and ours fours years before being accredited as a specialist. The differences and similarities of their system and ours are highlighted.


The protective effect of cimetidine on stress-induced acute gastric ulceration in the rat. The effect of intraperitoneal cimetidine, an H2 receptorantagonist, has been assessed on the development of cold-restraint induced acute gastric ulcers in rats. Cimetidine in doses ranging from 20-100 mg per kg body weight significantly reduced the incidence of acute gastric ulceration compared with saline controls in this model. The protective effect of cimetidine suggests a prophylactic role for this agent in stress-induced gastric or duodenal ulceration in man.


In vitro studies of gallstone dissolution using the scanning electron microscope. Scanning electron microscope studies on cholesterol gallstones, which had been subjected to, but had not been completely dissolved by, chenodeoxycholate and deoxycholate salts, have indicated the presence of an insoluble organic matrix, probably a mucopolysaccharide. Solution of a gallstone in vitro is enhanced by the addition of heparin which dissolved this matrix, thus allowing complete dissolution of cholesterol in a gallstone.


A technique for the chronic study of the hepatic uptake and excretion of substances in the conscious pig. The pig is an ideal animal for studies of hepatic metabolism and the handling of drugs by the liver because of the many similarities in liver function to that in man. In this report we describe for the first time, in this animal, methods for the chronic implantation of sampling catheters in the major hepatic vessels and for the construction of an external biliary shunt. This model has many advantages in that it permits in the conscious animal intermittent, simultaneous and precise sampling of the hepatic uptake and clearance of substances and intermittent sampling of bile, without permanent interruption of the enterophepatic circulation. The effectiveness of this preparation has been assessed in 55 pigs. It was demonstrated that the majority of catheters remained patent for at least three days and in many cases for much longer. No significant alteration in liver function could be shown for at least seven days after surgery.


The effects of experimental division of the vascular pedicle of a transposed subcutaneous ileal loop. The effects of immediate division of the neurovascular pedicles of ileal loops implanted in the subcutaneous tissues for four weeks were studied in eight mongrel dogs. The structural and functional changes were studied by examining sections under light and electron microscopy and by comparing D-xylose absorption and motility patterns. Arteriograms were done to show the new subcutaneous collaterals supplying the loops. Of the eight dogs, four had loops showing normal histological appearances and D-xylose absorptive functions after division of the pedicles. In the remaining four dogs, the loops showed evidence of pseudomembranous changes in some areas, resulting in patching necrosis possibly due to inadequate collaterals. The absorption of D-xylose was impaired in these dogs. Perhaps a longer period of transposition and a gradual division of the vascular pedicle would improve the results. The motility pattern did not change after division of the pedicle, though the response to intravenous carbachol was significantly delayed.


Bleeding stomal ulceration.

Bleeding stomal ulceration. In a prospective study of patients with haematemesis and melaena, there were 22 admissions of patients with bleeding stomal ulceration, representing 2.5% of total admissions to the Unit. In 16 patients the bleeding was from superficial stomal lesions. These lesions, endoscopically and histologically, resembled alkaline reflux gastritis, a recently defined cause of postgastrectomy bile vomiting. Five patients presented with chronic ulceration following inadequate gastric surgery. One patient was admitted on two occasions. Nine patients received more than five units of blood and came to operation for continued bleeding. In seven of the surgical cases, the bleeding was from superficial stomal lesions. Our experience suggests that truncal vagotomy is necessary to control the bleeding in these patients. One patient presented with superficial stomal ulceration and carcinomatous change. This patient died. It is important to subject these lesions to biopsy, and biopsy with extension of a previous gastrectomy is indicated to control bleeding, and to exclude malignancy.


Acute suppurative cholecystitis: a retrospective study of 173 cases. Over a 14-year period we treated 2,290 cases of non-malignant biliary tract conditions, and among them were 173 cases of acute suppurative cholecystitis, an incidence of 7.6%. A correct preoperative diagnosis of acute suppurative cholecystitis was made in only about half the cases because features of recurrent pyogenic cholangitis dominated the clinical picture on many occasions. The diagnosis was confirmed in all cases at operation. Cholecystectomy (88%) was performed whenever this was found to be safe, and cholecystostomy (12%) was carried out only in poor-risk patients or when operative difficulties were encountered. The overall mortality of operation was 5.8%. Old age, preoperative shock, delay of operation and the presence of free perforation affected the prognosis adversely.


Retained gallstones: the choice of the method of management. The management of 26 patients with retained stones in the biliary tree after surgery is described. Various methods have been used, but intermittent rapid flushing with one litre of isotonic saline solution, together with a slow infusion of heparin solution via the T tube, was the most successful. It required no specialized equipment, and is recommended as the first choice in treatment.


Bile duct injury during cholecystectomy: causes, prevention and surgical repair in 1979. Bile duct injury during cholecystectomy is almost always a high injury of the proximal common hepatic duct, because the surgeon mistakes this duct for the cystic duct and a segment of it is removed with the gallbladder. Most of these injuries are preventable by following certain principles of careful surgical dissection of the ductal system during surgery. Surgical reconstruction is always difficult, and restricturing of the anastomosis remains the most important problem. Recent advances in surgical technique have minimized the risk of recurrent stricture formation. At present the most suitable reconstruction for the typical high common hepatic duct lesion is a hepaticojejunostomy Roux-en-Y, using transhepatic intubation and a "mucosal graft" type of procedure. Biliary reconstruction was performed on 32 patients referred to the writer during the past 13 years resulting in six recurrent strictures needing a second reconstruction. At the end of 1978, 10 patients are too early to evaluate, two are dead and 20 have obtained a good final result.


Intrapancreatic cysts associated with relapsing pancreatitis. Intrapancreatic cysts were demonstrated by endoscopic retrograde pancreatography (E.R.P.) in nine patients with a clinical diagnosis of relapsing pancreatitis. The cysts ranged in diameter from 0.6 cm to 5 cm and were frequently associated with a prolonged elevation of the serum amylase level. The complication of intracystic haemorrhage with obstructive jaundice developed in one patient requiring early surgical decompression and drainage. In four patients laparotomy was performed because of continuing abdominal pain. One patient was treated by cystogastrostomy and another by cyst aspiration, but in two patients the cyst could not be visualized or palpated. Four patients were observed without operation for periods of four to 24 months, and all showed improvement or resolution of symptoms. E.R.P. was repeated in one patient and the cyst could not be outlined, while in another an abnormal barium meal X-ray examination result reverted to normal. Intrapancreatic cysts can be managed non-operatively, since complications appear infrequent and spontaneous resolution may occur.


Colorectal cancer in New Zealand: a Wellington study. A retrospective study of three hundred patients with colorectal cancer seen during a five-year period at Wellington Hospital is presented. The age incidence, anatomical distribution, tumour stage and incidence of intestinal obstruction differ from those reported in most other series. There is no correlation between delay in presentation and Dukes stage. It is suggested that colorectal cancer is a more aggressive disease in New Zealand than it is elsewhere in the world. The dangers of translating disease satistics from one country to another are emphasized.


Mortality and complications of large-bowel resection for carcinoma. The mortality and complications of large-bowel resection for carcinoma performed at the Princess Alexandra Hospital since the Colorectal Project commenced in 1971 are reviewed and compared with the results in other published series. There were 443 patients in this prospective study, and 375 underwent resection of their tumour. The overall operative mortality was 6.4% - for colonic lesions it was 8.0% and for rectal 3.4%. The mortality for elective curative resections was 2.6%, and for emergency resections it was 10.8%. The anastomotic leak rate was 6.8%, but was higher (16.6%) when the anastomosis was done at the time of emergency resection. No patient whose anastomosis leaked but who had had a previous defunctioning proximal colostomy died. There was a wound infection rate of 15.1%.


Elective resection for diverticular disease. A series of 119 patients undergoing elective resection for diverticular disease has been reviewed. The indications for resection were classified into two major groups--those with severe infections ("complicated" diverticulitis), comprising 58 patients, and those with minimal infections, comprising 61 patients. The majority of the resections were limited to the sigmoid colon (101 patients). Fifteen patients underwent left hemicolectomy, whilst three had total colectomy. Thirty-six patients (30%) had a proximal defunctioning stoma--18 prior to resection and 19 at the time of resection. Anastomotic defects were noted in 15 patients (12.6%), but these were of clinical significance only in eight (6.7%). There were two deaths (1.7%) and 17 wound infections (14.3%). The group classified as "complicated" diverticulitis included the great majority of the patients requiring colostomy (32 out of 37), almost all those with anastomotic defects (14 out of 15), and most of the patients who had postoperative complications.


Rectal prolapse.

Rectal prolapse. One hundred and twenty-seven patients with complete rectal prolapse have been reviewed. The condition occurred more commonly in females than males (105 to 22), and at an older age in females (mean age 55 years compared with 40 years for males). Although the diagnosis is usually obvious, the importance of recognizing occult prolapse is stressed, especially in association with benign rectal ulcer, localized proctitis and colitis cystica profunda. Examination of the patient in the squatting position may assit in showing occult prolapse. Associated incontinence occurred in 33 patients (26%). Since 1971 the policy of this Unit has been to perform a Ripstein repair for complete rectal prolapse wherever possible. One hundred and two Ripstein repairs have not been performed. A minimum follow-up period of two years is available for 53 patients, of whom 50 (94%) have had their prolapse cured. Control of prolapse usually improves continence; however, seven (13%) remained incontinent despite surgery. The Ripstein repair is strongly advocated as the most effective operation for cure of complete rectal prolapse.


Hypercalcaemia in Paget's disease of bone. Albright in 1944 described a syndrome of hypercalcaemia in patients immobilized following fractures through bones affected with Paget's disease. This paper reports a further two cases in which this syndrome was considered the cause of hypercalcaemia with fatal outcome. Both patients had parathyroid adenomata. The literature is reviewed, and it is argued that no firm evidence for the existence of this syndrome has ever been put forward. The finding of hypercalcaemia in Paget's disease of bone should prompt an exhaustive search for its cause.


The accessory soleus.

The accessory soleus. The literature relating to accessory soleus muscles has been reviewed, and two further cases are here presented. The appearance of two cases in one hospital within a four-year period would suggest that the condition is, after all, not uncommon; prior awareness of it may on occasions permit an expectant approach or (if symptoms related to exertion are present) a planned and conservative surgical procedure.


Portal hypertension due to arteriovenous fistula of the gastroduodenal artery. The record is presented of a patient with severe recurrent bleeding due to portal hypertension. Surgical control of the feeding vessels of a fistulous communication between the gastroduodenal artery and its companion vein arrested the haemorrhage and controlled the portal hypertension.


Jejunal replacement of the second part of the duodenum following severe trauma. Intestine can be devitalized by crushing injuries as readily as other soft tissues. The management of a patient with severe duodenal injury is presented. The importance of resecting avascular segments, rather than hoping for the best, is stressed.


Intrarectal dermoid: report of a case.

Intrarectal dermoid: report of a case. Intrarectal dermoid is a rare clinical problem, mostly occurring in women. Though it is presumed that anterior rectal dermoids arise in the ovary and erode into the retum, up to date there has been no substantial evidence for this. A 26-year-old woman is described who presented to us with an intrarectal dermoid wherein the stalk connecting the rectal dermoid and the left ovary was clearly demonstrated.


The need for epidemiological research in road trauma. This paper discusses the application of epidemiological methods to the public health problem of road trauma. The complex nature of the system is stressed, and some consequent difficulties in the formulation of appropriate hypotheses are outlined. Examples are given. To solve these problems, the paper proposes the formation of multidisciplinary full-time epidemiological research teams.


Data needs for research in road trauma.

Data needs for research in road trauma. This paper laments the existence of widespread "instant" expertise on road trauma; postulates the need for multidisciplinary epidemiological research teams to produce a more scientific approach to this problem, based on authoritative information and analysis; and suggests that any such teams will require accessible, comprehensive, compatible data. The paper describes some problems of existing data collections associated with the source of the data, the lack of compatibility and comprehensiveness, and the absence of data on exposure and on severity of injury. It is suggested that, in the context of these deficiencies, extensive development of new data is unrealistic. Instead, the paper concludes by recommending gradual expansion of currently available data on a national basis, under the control of the Australian Bureau of Statistics. It is suggested that Section 51 of the Constitution provides the necessary head of power for this development.


Getting the evidence and using it to the best advantage. The statistical information on blood alcohol levels in road crash fatalities and casualties together with screening breath tests (evidential and non-evidential) can be used to identify drink-drivers in a high alcohol consuming society which has the second highest vehicle ownership per head of population in the world. Control of the drink driving problem can be achieved by short and long term education, plus the deterrent effect of a high predictability of detection by the enforcement of legislation providing severe penalties backed by the courts. Some positive results have been achieved in Australia, particularly in the State of Victoria, where drink driving legislation has been more extensive than in other States.


Abdominal injuries in survivors of road trauma before and since seat belt legislation in Victoria. At St Vincent's Hospital, Melbourne, the number of patients admitted annually with road crash injuries has remained almost constant for the past 14 years. Comparing admissions in the seven years before and during the seven years since enactment of seat belt legislation in Victoria, there has been no change in the proportion of those admitted with abdominal injuries, in the number of associated non-abdominal severe injuries, or in the death rate of those admitted with abdominal injuries. There has, however, been a significant increase in the number of patients admitted with injuries of the gastrointestinal tract and diaphragm. It is suggested that this increase is due to incorrect wearing of the lap component of seat belts with resulting acute abdominal compression.


The pattern of motor cycle injuries sustained by motor cyclists in Victoria in 1974 and 1975. Motor cycle injuries and fatalities (2.4% annually) represent a serious threat to the youth of Australia. This survey outlines the pattern of injuries sustained by motor cyclists and highlights of the high percentage (73%) of serious local injuries to the lower extremities. The views of motor cyclist victims on preventive safety measures are also summarized.


Arterial reconstruction with polytetrafluoroethylene: a preliminary report. Early results of arterial reconstruction with reinforced expanded polytetrafluoroethylene (PTFE) in the lower extremity have been obtained by reviewing 55 patients undergoing 59 operations - 38 femoropopliteal bypasses and 21 long bypasses distal to the popliteal artery. The one-year accumulated patency rates were 73% for the femoropopliteal bypass group and 50% for the long bypass group. Early results suggest that PTFE is superior to Dacron and is an acceptable substitute for autogenous saphenous vein when the latter is unavailable or of inadequate calibre.


Posttraumatic vascular malformations of the orbit. The close association of the external and internal carotid circulations in the orbital cavity is well recognized. Two cases are presented in which local trauma to the orbit apparently resulted in the formation of an arteriovenous fistula. These lesions progressively expanded, producing classical features of proptosis, chemosis, and bruit. The investigation by selective angiograms and the surgical management of these malformations are discussed. A further case is presented in which an early lesion was noted in angiography after a head injury, with subsequent disappearance of the lesion some weeks later.


Aneurysm of the right subclavian artery: an unusual cause of superior vena caval obstruction. A case of superior vena caval (SVC) obstruction caused by an aneurysm of the right subclavian artery is presented. Malignant conditions are the commonest aetiological factors in SVC obstruction, but benign and potentially treatable lesions account for an important minority. The importance of attempting to establish a fully documented diagnosis, including histological proof, in all patients presenting with this syndrome is emphasized.


Embolization of traumatic aneurysm of the maxillary artery. An expanding false aneurysm in the infratemporal fossa followed this patient's complicated jaw fracture. Successful Gelfoam embolization of the maxillary artery has controlled haemorrhage, treated the aneurysm, and avoided the hazards of local operative intervention. The technique of embolization has a place in the management of various difficult vascular problems.


Proximal tubular adenoma of the kidney.

Proximal tubular adenoma of the kidney. A case of proximal tubular adenoma of the kidney (renal "oncocytoma"), confirmed by electron microscopy, is reported. This benign tumour has been mistaken for renal adenocarcinoma in the past by both surgeons and pathologists.


Easier operative cholangiography.

Easier operative cholangiography. A simplified technique for operative cholangiography utilizing a cholangiogram clamp is described. The technique has been used without complications in over two hundred cholecystectomies and greatly reduces the time taken to perform an operative cholangiogram.


Severe injuries to the cervical cord and spine: neurosurgical management in the acute and early stage. The controversy of long standing in the management of cervical cord and spine injury in the acute stage ranges from an attitude of neurosurgical nihilism on the one hand, to indiscriminate, incompetent and routine "explorative" or "diagnostic" laminectomies on the other. Judicious neurosurgical management in the acute stage tends to overcome and eliminate the ill-advised extreme attitudes by careful neurological and neuroradiological diagnostic assessment. The indications and contraindications for surgical treatment are carefully weighed in each case and are based on neurosurgical criteria and experience. This communication is a summary of methods and experience evolved in the diagnostic and surgical management in the acute stage. Indications, contraindications and techniques are presented in detail.