Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds.

A human leukemic cell line (designated HL-60) has recently been established from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. This cell line displays distinct morphological and histochemical commitment towards myeloid differentiation. The cultured cells are predominantly promyelocytes, but the addition of dimethyl sulfoxide to the culture induces them to differentiate into myelocytes, metamyelocytes, and banded and segmented neutrophils. All 150 clones developed from the HL-60 culture show similar morphological differentiation in the presence of dimethyl sulfoxide. Unlike the morphologically immature promyelocytes, the dimethyl sulfoxide-induced mature cells exhibit functional maturity as exemplified by phagocytic activity. A number of other compounds previously shown to induce erythroid differentiation of mouse erythroleukemia (Friend) cells can induce analogous maturation of the myeloid HL-60 cells. The marked similarity in behavior of HL-60 cells and Friend cells in the presence of these inducing agents suggests that similar molecular mechanisms are involved in the induction of differentiation of these human myeloid and murine erythroid leukemic cells.


Modification of conditioned behavior of rats by neurohypophyseal hormones and analogues.

Vasopressin and other neurohypophyseal peptides affect various processes related to memory and/or learning. A single subcutaneous injection of vasopressin increases resistance to extinction of a pole-jumping avoidance response in rat. This test system has been applied in an attempt to relate structural aspects of neurohypophyseal peptides, analogues, and derivatives with truncated sequences to their effects on conditioned behavior. Thus far it can be concluded that there are more stringent requirements on certain residues in the 20-member covalent ring than in positions 8 and 9 of the linear peptide portion for neurohypophyseal hormones to be active. Critical are the contributions of residues in positions 2, 3, and 5; these results are reminiscent of those from conformation-activity correlations of the endocrine effects of neurohypophyseal hormones, in which the side chain of the residue in position 3 is critical for receptor binding and the side chains of residues in positions 2 and 5 are key for the activation of the receptor. Chemical modifications in position 4 yield analogues that are active and inactive in increasing the resistance to extinction of the avoidance response, depending on the particular structural substitution, similar to results from structure-activity studies of the endocrine activities of neurohypophyseal hormones. Because behavioral activities of vasopressin are more tolerant than endocrine activities to modifications of the hormone in positions 8 and 9, analogues with the most striking dissociation of potencies in learned behavior and endocrine responses are expected to be those with sequence alterations in the linear peptide portion. Peptides with linear part sequences of neurohypophyseal hormones showed little or no activity. The results obtained in this structure-activity study are compared with those of an earlier study in which the ability of various neurohypophyseal peptides to attenuate puromycin-induced amnesia in mice was evaluated.


Localization of acetylcholine receptor in excitable membrane from the electric organ of Torpedo: Evidence for exposure of receptor antigenic sites on both sides of the membrane.

Nicotinic acetylcholine receptor was localized in a receptor-rich membrane preparation from the electric organ of Torpedo californica by applying an immunoferritin technique. The membrane preparation was incubated with (Fab')2 fragments derived from specific rabbit antibodies against the purified acetylcholine receptor and subsequently with ferritin-conjugated goat antiserum to rabbit immunoglobulin. More than 50% of the vesicles were found to be labeled with ferritin while the rest remained unlabeled. Ferritin labeling on both sides of the membrane was evident in open membrane vesicles, whereas in closed vescles the labeling was confined to the outer surface due to the inability of the tracer to penetrate the membrane. These data suggest that antigenic sites of the receptor molecule are exposed on both sides of the excitable membrane, and that acetylcholine receptor may be a transmembrane protein.


Intraventricular administration of nerve growth factor induces ornithine decarboxylase in peripheral tissues of the rat.

Intraventricular administration of nerve growth factor causes an increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in liver, kidney, and adrenal as well as in brain itself. An increase in the concentration of corticosterone in the blood was also observed. Adrenalectomy, hypophysectomy, or pituitary stalk section inhibits the increase of ornithine decarboxylase activity in the peripheral tissues. Ornithine decarboxylase activity in the brain, however, responds to nerve growth factor in these animals. The data indicate that nerve growth factor causes an acitivation of the hypothalamo-hypophyseal endocrine system.


Different time course of development for high-affinity choline uptake and choline acetyltransferase in the chick retina.

Synthesis and storage of [3H]acetylcholine in isolated pieces of chick retina increased in two stages during embryogenesis. The first increase coincided with a 100-fold rise in the activity of choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), but during the second increase the activity of this enzyme remained essentially constant. The second increase instead was linked to an approximately 6-fold increase in the Vmax for high-affinity uptake of choline.


Ovarian ornithine decarboxylase regulation in the immature, the pubescent, and the pseudopregnant rat.

Ovarian ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) regulation was investigated in immature, pubescent, and pseudopregnant rats. After initial induction of the enzyme by injection of lutropin in the immature rat, continued daily injections resulted in a graded decrease in the activity of the enzyme. In the 32-day-old rat, the induction and subsequent decline in enzymic activity after a single injection of lutropin could only be partially reversed by injections of the hormone at 4-hr intervals. This decrease could not be attributed to a decrease in ovarian in vivo uptake of the hormone. In the pseudopregnant rat, ovarian ornithine decarboxylase is highly refractory to induction by either a single injection or repeated injections of lutropin. This refractoriness occurs despite a 2- to 3-fold increase in ovarian in vivo uptake of the hormone compared to that in the 32-day-old rat. It is suggested that the refractoriness observed with all three tissues is a function of cell differentiation.


The law of perceptual stability: well-definedness and validity.

Axiomatic foundations for a theory of perception have been given in a prior communication [Shiman, L. G. (1978) Proc. Natl. Acad. Sci. USA 75, 2049-2053]. The theory is based on mathematically characterized stable images. Stable images model subjective (psychological) states of observers. We showed there is a universal procedure by which such stable images can be assigned to objects of perception (icons), employing observer-dependent perceptual judgements. We construct an abstract model for an icon from the mathematical structure of a stable image that has been assigned to it. We identify the model with the icon. By identifying the model with the object of perception, we can analyze perception of the icon in terms of the mathematical properties of its associated stable images. Thus subjective phenomena, in this mathematical form, can be used to analyze the mechanisms of sensory processes. Grounds for validity of the stability law are given. The procedures are demonstrably universal. A stable image, although subjectively derived from an icon, is a mathematical entity, and has therefore objective status. Stable images give a natural and potentially complete (mathematical) classification of icons, along nontraditional lines, which includes a classification and account of many well-known "visual illusions."Extension of this (static) theory to include time-dependent (kinetic) cases is outlined. We consider grammar for vision, semantics, and the role of stability theory in constructing a unified theory of vision and natural languages.


Behavioral effects and metabolic fate of N,N-dimethyltryptamine in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), improniazid and chlorpromazine.

Behavioral aspects and metabolic fate of N,N-dimethyltryptamine (DMT) were studied in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), iproniazid or chlorpromazine (CPZ). DMT at doses of 2.5, 10.0, and 25.0 mg/kg produced several behavioral changes in a dose-related manner: inhibition of spontaneous locomotor movement, enhanced fright responses to sound stimuli, trembling, head twitching, inco-ordinated movements of hind-legs, flat or extended tail and abnormal posture with the extension of hind-legs. Pretreatment with ipromazid (153 mg/kg; 4 hr) but not SKF 525-A (50 mg/kg; 1 hr) prolonged the behavioral effects produced by 2.5 mg/kg DMT while CPZ (15 mg/kg; 0.5 hr) completely abolished the responses induced by 25 mg/kg DMT. Earlier behavioral effects generally coincided with the brain concentrations of DMT. Dose-dependent increases with rapid uptake and disappearance in the brain, plasma and hepatic levels of DMT were measured with doses of 10 and 25 mg/kg DMT. Iproniazid but not SKF 525-A markedly enhanced tissue levels of DMT. it is concluded that DMT is metabolized chiefly by monoamine oxidase rather than by drug-metabolizing hepatic microsomal enzymes and that DMT-induced behavioral effects are due to the parent compound rather than its metabolite.


[Architectural and structural craniofacial analysis (lateral view). Theoretical principles. Some example of its use in maxillofacial surgery (author's transl)].

Based upon the study of mutual equilibrium of the various bony structures of the skull and face, cranio facial architectural and structural analysis studies successively the skull (vault and base), then the face in relation to the skull and to the cranio-spinal joint. Its value lies in avoiding statistical averages rather relying upon individual measurements, influenced by the special features of each skeleton. It places the dentition within its cephalic context, thereby making it possible to demonstrate certain pathogenic factors of dento-facial dysmorphoses, not demonstrated by traditional types of orthodontic analysis. It is particularly useful to the maxillofacial surgeon in clearly demonstrating all maxillfacial amlformations and the pathological equilibria which it must transform. In the most severe types of craniofacial dysmorphosis it offers better possibilities than other methods of analysis of detecting the various cranial and facial abnormalities which characterise these conditions.


[Cleido-cranial dysplasia. Contribution to study of this disease on the basis of four cases (author's transl)].

First described in 1898 under the name of cleido-cranial dysostosis by Pierre Marie and Sainton, this hereditary disease is highly polymorphous and progressive, hence the multiplicity of its manifestations. These involve not only the skull and clavicle, but also the hands, the spine and the teeth. In fact, it is disturbance of growth rather than a dysostosis in the strict sense of the term. Its mode of transmission is dominant. Its pathogenesis is totally unknown.


[The association cleido-cranial dysplasia and a Capdepont dysplasia (author's transl)].

The authors report a rare association: that of two hereditary dysplasias transmitted in a dominant manner. Cleido-cranial dysplasia or Pierre Marie and Saniton syndrome, a congenital polymorphous disease, affecting the bones during their growth with a Capadepont dysplasia or hereditary opalescent dentine, a condition affecting both dentitons.


[Primary malignant melanoma of the parotid. One case (author's transl)].

The authors report a case of malignant melanoma of the parotid occurring in a 22-year-old man, followed by two local recurrences after surgical excision, radiotherapy and chemotherapy. The primary parotid nature of the tumour was confirmed by the absence of tumour in other sites and by the histological characteristics.


[Pulmonary-mediastinal sarcoidosis presenting as parotiditis. A report on two cases (author's transl)].

The authors report on two cases in which parotid localization enabled diagnosis of an unsuspected sarcoidosis io be made. They feel that, apart from Sjogren-Goygerot's syndrome, all patients with parotiditis, even non-specific, should be examined systematically to exclude the possibility of a latent sarcoidosis.


[Radiocrystallographic study of 46 salivary calculi. Physiopathogenic hypotheses (author's transl)].

The radiocrystallographic study of 46 salivary calculi using the Debye and Scherrer powder methods showed that such stones, whether submaxillary, parotid or "accessory" consist essentially of hydroxyapatite with the frequent presence of tricalcium and octocalcium phosphates, Whitlockite and rarely Brushite and Calcite. In order for a stone to form, the following conditions would seem to be necessary; transient supersaturation of the saliva in Ca++ and PO4--, a pH greater than normal, intracellular precepitation of amorphous tricalcium phosphate which is transformed into crystalline hydroxyapatite and, then, the fixation of crystals on a "matrix" such as desquamated cells, fibrils and collagens.


[Mandibular localization of thesaurismosis (polyvinyl-pyrrolidine) (author's transl)].

The authors report on a case of isolated mandibular localization of polyvinyl-pyrrolidine thesaurismosis. The patient, a man of 38, had been treated with injections of posterior pituitary extract, for a period of eighteen months, 10 year ago. Localization in the mandible is extremely rare, making diagnosis difficult unless a detailed anamnesis is available.


Extratympanic manometry in man. Clinical and experimental investigations of the acoustic stapedius and tensor tympani contractions in normal subjects and in patients.

New ideas and inspirations for future human investigations have emerged from the experience obtained in this study. These investigations ought to be performed for both scientific and clinical reasons. It is the author's opinion that the ETM method is extremely useful and valuable. The author intends to continue the human investigations if proper conditions are available. The ETM equipment can also be further improved for scientific and special clinical investigations. For normal clinical practice a more "simplified" ETM equipment should be developed. Clinical investigations concerning the diagnosis of brain stem disorders and the selection of noise susceptible persons will be two of the primary clinical tasks.


Discoloration of permanent front teeth in 3,157 Norwegian children due to tetracyclines and other factors.

During routine orthodontic screening in Oslo, Norway, of 3,157 children, aged 1--11 years and born in 1963/64, 36 cases (1.14%) with cosmetically marring discoloration of permanent front teeth were registered. Thirty-four of them arrived for a more exhaustive examination, which in 24 of the children revealed positive tetracycline fluorescence on exposure to ultraviolet light. In 13 (0.4%) of the children, the discolorations were diagnosed to be tetracycline-induced. Enamel hypoplasia was frequently found in teeth with positive fluorescence. Multiple exposures to various tetracyclines were reported in all children who exhibited positive fluorescence.


Caries reduction over 5 years from a single application of a fissure sealant.

This paper is a continuation of three previously published papers giving a long-term clinical evaluation of an ultraviolet light polymerizable fissure sealant method. The present findings revealed that of the 156 permanent teeth available for study 5 years after initiation, 59.6% retained the sealants in good condition, while 25.6% of the sealants were missing or partly missing. During the test period, 37 (32.2%) of the 115 sealed permanent first molars had become carious, while 92 (80.0%) of the respective paired controls had decayed. An analysis of the efficacy of the treatment on the test-control tooth pairs showed a net gain of 55 and a percentage effectiveness of 59.8%. The sealed teeth were found to be highly significantly less decayed than the respective contols (P less than 0.001). Of the individual subjects, 73.4% were found to have benefited from the treatment.


A 5-year evaluation of semipermanent composite resin crowns.

The use of composite resin crowns in the restoration of traumatized and hypoplastic permanent incisors has proved to be of great clinical and aesthetic value for the pedodontic practice. Due to the composite resin materials and the acid etch technique, an easy method of making and retaining the restorations is at hand. The present study deals with long-term observations of composite resin crowns in restoring Ellis Class II and Class III coronal fractures of traumatized permanent incisors. In all, 253 composite resin crowns were controlled every year for a minimum of 5 years. In no case was an intermediate resin layer applied on etched enamel before the restoration material was placed. Surface, marginal and "body" discoloration, marginal leakage, marginal caries, abrasion, and fractures were controlled. The study demonstrated that discoloration of the surface of the restorations, and a discoloration of the restorative material not restricted to its surface ("body" discoloration) were the most frequent causes for considering the crowns as semipermanent restorations. The other factors seemed to be of minor clinical significance.


Effect of thyroxine and growth hormone on dentin production in maxillary incisors in the rat.

Dentin production and longitudinal growth of maxillary incisors in female rats, age 60--95 d, were determined by the tetracycline technique in hypophysectomized rats after administration of growth hormone and thyroxine during age 75--95 d. Hypophysectomy was performed at age 60 d. Administration of thyroxine resulted in a considerable increase in dentin apposition and longitudinal growth of the tooth. The same effect, but somewhat lower, was registered for growth hormone. Growth hormone and thyroxine administered simultaneously had an additive synergistic effect. Compared with the effect of hypophysectomy and of hormone administration on longitudinal bone growth and cortical bone remodleing the effect on dentin production and longitudinal growth of the maxillary incisors in the same rats is less pronounced and shows a different pattern in reaction, indicating differences in sensitivity for different cell systems and difference in endocrine control.


Microbiota of gingivitis in man.

A study on the predominant cultivable microorganisms inhabiting gingival crevices affected with a chronic gingivitis was carried out using the roll tube culture technique. Samples were obtained from nine individuals 25--42 years of age. Gram-positive rods make up 29.1% of the isolates and included mainly Actinomyces naeslundii, Actinomyces israelii, and Actinomyces viscosus. Streptococcus mitis and Streptococcus sanguis together made up 26.8% of the cultivable organisms. Peptostreptococcus averaged 3.0% of the organisms recovered. Gram-negative anaerobic rods constituted 25.0% of the total isolates with Fusobacterium nucleatum, Bacteroides melaninogenicus ss. intermedius. Bacteriodes ochraceus, other Bacteroides species, Selenomonas sputigena, and Campylobacter sputorum as the most predominant isolates. Haemophilus parainfluenzae averaged about 14% and Veillonella species 4.3% of the cultivable microflora. The data presented indicate that the subgingival microflora of a chronic gingivitis differs from those of healthy periodontium and advanced adult and juvenile periodontis. This might suggest that different infectious processes may be operative in various clinical entities of periodontal disease.


Ultrastructure of salivary calculi.

Twenty-one submandibular salivary calculi from 19 patients were examined with the light and electron microscope. Adjacent to the peripheral parts of the calculi metaplastic squamous epithelium or connective tissue was seen in close contact to the mineralized matrix. Disintegrated cellular substances from these tissue components were in some cases found to condense in a peripherally located zone of the salivary calculi. The morphology of the examined salivary calculi varied extensively not only within each calculus but also from one calculus to another. High and low incidence of crystals gave rise to the lamellated pattern. In some cases the crystals were so abundant as to five a dense homogeneous appearance. In the central parts of the calculi spheroid bodies of very low electron density with a size ranging from 1 to 100micrometer were found in an amorphous matrix. The origin of these structures is discussed. In the peripheral parts of some calculi osmiophilic spherical bodies with an electron microscopical appearance similar to lipid granules as well as bacteria of cocci or coliform type were found. Degenerated bacteria might in some cases contribute in forming part of the peripheral organic matrix.


Histoquantitation on small jaw specimens.

A study is carried out to evaluate the possibility of obtaining a measure of bone mass and bone activity by histoquantitation on small jaw specimens. The material consisted of bone autopsy specimens from premolar regions of mandibles and regions above maxillary second incisors. Microradiograms of 100-micrometer-thick buccal-lingual ground sections were used. Quantitation of bone mass (bone area in percent), bone coarseness (total bone surface/bone area), and bone activity (resorption surfaces/total bone surface) was done in well-defined areas of cortical and trabecular bone by an electronic point-counting system. The analysis indicates that: (1) no further information or accuracy is obtained from measurements of large areas than of small areas of cortical or trabecular bone, (2) the bone mass in the buccal cortex anterior to the mental foramen is independent of side and state of dentition, and (3) maxillary specimens are unsuitable for quantitation of bone mass. A small bone specimen taken anterior to the mental foramen seems to be suitable for histoquantitation, when a reliable and representative measure of bone mass and bone activity in the mandible is desired for analysis of intermandibular differences.


Migration of metallic ions from screwposts into dentin and surrounding tissues.

Previous investigations have shown htat corrosion and other electrochemical processes occure when different alloys or metals are found together in the same mouth. In the present report, when teeth were restored using non-noble metallic posts, the metals diffused out to surrounding hard and soft connective tissues. The material consisted of extracted teeth with screw posts and surrounding discolored connective tissues. The screwposts had been cemented to the teeth 3--10 years earlier. The distribution of metal ions was determined by means of energy-dispersive X-ray microanalysis. Copper and zinc were found in both hard and soft tissues. Relatively high concentrations of copper ions were identified in areas of the teeth with blue-green discolorations. Zinc ions were detected in the dentin; they most probably originated from the screwposts and the cement, but zinc is also found in normal human dentin. Copper, zinc, silver and iron were found in the dark discolorations of the gingiva adjacent to the extracted teeth.


Levels of airborne particles resulting from handling alginate impression material.

The levels of airborne particles emanating from handling alginate impression powders have been surveyed. The concentrations of powders, lead and silicious particles in the aerosol have been measured after thoroughly shaking the containers before opening. The decrease of the powder concentration in the ambient air as a function of time has been estimated. The efficiency of face masks to protect against powder exposure has been investigated.


[Progress in the treatment of acute leukemias].

The most important advances achieved during the past 5 years in the diagnosis and treatment of acute leukemia are presented. It is now possible to achieve complete remission in about 60% of all patients with acute myelocytic leukemia (AML) using optimal polychemotherapy. This significant advance is in part due to improved supportive measures such as transfusions and isolation etc., which are frequently necessary during the induction phase of treatment. Unfortunately, such remissions are still of relatively short duration and seldom exceed 1 year. The treatment of relapses remains less successful. The first attempts to include immunotherapy in the treatment of AML have also been rather disappointing. Today remissions are obtained in 70% of patients with acute lymphocytic leukemia (ALL) which last, on the average, almost 1 1/2 years. These results, however, do not approach those in childhood ALL. Finally, the therapeutic possibilities for the treatment of blastic crisis in chronic myelocytic leukemia (CML) are discussed.


[When do we have to treat chronic leukemia?].

The grounds for treating or not treating chronic lymphocytic leukemias (CLL) and chronic myelocytic leukemias (CML) are discussed in the light of results in recent years. In the case of CLL, objective evaluation of treatment benefits has hitherto been difficult due to the heterogeneity of this group of diseases. A recent classification, based on hematological and clinical parameters and apparently of prognostic value, will undoubtedly help to clarify the therapeutic problem. In the case of CML, routine chemotherapy programs certainly alleviate the symptoms of the disease but have not so far achieved a significant prolongation of survival.


[The treatment of injured front teeth].

Prefabricated steel crowns have been in use up to now as a classical method of preserving of fractured front teeth. They are, however, unsatisfactory for esthetical reasons. With the introduction to the acid etch technique incisal restorations have been made with composites. They are, however, subject to some abrasion and surface staining, as the inorganic filler particles loosen from the organic matrix. The clinical experiences with the new dental filling material Isosit lead to an esthetically and functionally accurate restoration of broken teeth or hypoplasia. After one year of observation 28 traumatically damaged teeth built up with Isocap have shown no marginal discoloration, staining or material loss.


[Therapeutic considerations in maxillofacial neuralgia].

In the presence of idiopathic and neuralgiform pain in the trigeminal area, differential diagnosis will have to eliminate sinus disturbances, toothache, TMJ trouble and neuromuscular spasms derived thereof. Neuralgias unconnected to these causes are treated by electrobiological testing of the neurotoxins. Symptomatic immediate treatment was formerly done by enneural injection. Now, a special technique of auriculoacupuncture has been successful for some time.


[Aims and realizations in the manufacture of articulators].

The various designs of the most familiar articulators are described. Also the different concepts important to comprehending the stomatognathic functions are discussed. Their impact on the designs of various articulators are shown. The purpose of this study is not to given a complete review of the history and development of different articulators, rather, the purpose is to present the application of various stomatognathic philosophies to the design of various articulators.


[Abrasion-resistant MOD composite fillings made by embedding centric ceramic stops--4 year's results].

The resistance to abrasion of presently available composite restorative materials is unsatisfactory; the utilization of such materials in conventionally prepared occlusal and occluso-proximal stress-bearing restorations has been therefore contraindicated. In a private practice study carried-out between 1972-77, porous triangular-shaped ceramic inserts were polymerized into the centric-stop areas of 528 Class-II composite restorations. Clinical and electron microscopic evaluation have shown a greatly increased resistance to abrasion in the ceramic insert areas as well as no significant attrition of the antagonist cusp. 95% of the restoration were judged functionally and esthetically very satisfactory. Only 1,1% of the inserts demonstrated fracture and partial loss of ceramic material during the test period. The five-year study has shown the procedure to be relatively simple to learn and suitable for private practice application.


[Histopathology of oral precanceroses].

The nomenclature used by gynaecopathologists for precancerosis of the cervix mucosa can be used equally for the oral mucosa. Cancer usually does not develop suddenly from a normal epithelium, but through an epithelial dysplasia into a non invasive, intraepithelial carcinoma. This process of cancerization probably lasts several years. Leukoplakia must not be generally regarded as precancerosis. The criterion is the degree of epithelial dysplasia and not the accompanying acanthosis, dyskeratosis, hyper- or parakeratosis. Light and medium severe epithelial dysplasia are regarded as facultative, severe epithelial dysplasia and carcinoma in situ as true precancerosis. The cytological examination should be used more frequently as a screening method.


Histiocytosis and a leukaemoid response. A case report.

A patient with all the clinical signs of Letterer-Siwe disease is reported. The patient was unusual in that he had a severe leukaemoid reaction. To our knowledge, only 2 similar patients with reticulo-endotheliosis, histiocytic skin infiltration and leukaemoid reaction have been reported. It is possible that the disorder may represent a variant of the histiocytic proliferative disorders, characterized by both histiocytic and myeloid hyperplasia, and is thus similar to myelomonocytic leukaemia. However, it differs from the latter condition in that there is proliferation of monocytes and granulocytes in soft tissues rather than in the blood.


[Growth phenomena of jaw ameloblastomas].

Jaw ameloblastomas produce most frequently (62%) multilocular translucences. An unilocular translucence was observed in 28% of the cases. In both forms, secondary cysts were present. This radiomorphologic finding is of pathognomonic value. Conchiform or finger-shaped translucences were seen in 10% of the cases. Such radiographic changes were observed in ameloblastomas arising from the oral mucosa. The border of the radiolucent area was always sharply defined and had a lobulate or wreathed form. The ameloblastoma spreads in an expansive or invasive way. The bone destruction is in all probability caused by the acid phosphatase activity of the tumour. Bone transformation occurs simultaneously with bone destruction and might be regarded as a morphologic sign of the defence mechanism.


[Plate osteosynthesis in the mandible].

The indications for plate osteosynthesis concern above all fractures of the edentulous or partially edentulous mandible. In cases of fractures in the anterior and premolar regions, the intra-oral approach should be given preference. The technique of plate shifting complies with the rules of the Working Group on Osteosynthesis. Arched plates have proved useful.


[Wisdom teeth in the fracture line].

The evaluation of 139 mandibular fractures with wisdom teeth in the fracture line permits to draw the following conclusions: 1. Partially retained teeth in the fracture line frequently lead to infections. For this reason, they should be removed on principle prior to immobilization. 2. Retained teeth or tooth germs caused in no case an infection; consequently, they must not be removed. 3. Fully erupted teeth produced but occasionally an infection of the fracture line. In such cases, the therapy will depend on the functional value of the respective tooth.


[The varied behavior of the nasal sinuses in cleft lip and palate with differing localization of the cleft (a radio-analytical study)].

Report on 301 radiographs of the paranasal sinuses of cleft patients and on 120 radiographs of the paranasal sinuses of subjects from a control group to illustrate the development of the maxillary and frontal sinuses. In female individuals as well as in male ones, the maxillary sinuses on the left side are greater than those on the right side. Aplasia of the frontal sinuses on the right side was observed in 11.7%; aplasia of those on the left side, in 3.3%. The maxillary sinuses on the side of the cleft are greater than those on the opposite side. In patients with clefts of the secondary palate, the maxillary sinuses are significantly greater than in patients with clefts of the primary palate or with subtotal or total clefts of the secondary palate. Aplasia of the frontal sinuses on the right side was seen in 11%; aplasia of those on the left side, in 6%.


[Report on the capsule-dosage and mixing system. 4. Correctness and precision in the dosage of multi-component materials; pre-dosage in daily practice as a preliminary solution to the capsule-dosage and mixing system].

The significance of the factors "accuracy" and "precision" in the preparation of multicomponent materials is outlined with special regard to problems related to dosage. The present technological development permits to shift the responsibility for accuracy and precision to the manufacturers of dental materials. In view of the applicability of the capsule dosing and mixing system, the author presents an intermediate solution (based on the experimental verification of various dosing methods) that permits to benefit from the main advantages of the capsule system in everyday practice prior to the establishment of centralized dosing facilities.


[The prosthetic treatment of cleft patients. 1. Fixed constructions].

The difficulties encountered in the prosthetic treatment of cleft patients depend on the kind and the extent of the malformation. Modern oral surgical and orthodontic techniques offer better prerequisites than former methods. All must be done to preserve the endangered teeth as long as possible. The insertion of bridge prostheses is indicated if the defects are corrected by surgical procedures and if there is no marked pseudoprognathism.


[3 years report on endosseous implantations].

In the light of three years of experience with intra-ossal implants, the author deals with the indication and the material to be used. The significance of the patient's psychological state in establishing the indication is emphasized. Chromium-cobalt-molybdenum alloys are considered to be suited as implants. The author discussed the results from 16 cases where blade implants according to Linkow had been used.


[Orthodontic treatment in cases of mandibulo-facial dysostosis].

The author describes the clinical picture of mandibulofacial dysostosis and gives reasons for the necessity for early orthodontic treatment. Two examples are presented. The analysis of the case histories of a total of 10 patients with this syndrome showed that the responsiveness to functional orthodontic appliances is greatest in children with bilateral mandibulofacial dysostosis. The need for co-operation with other disciplines involved is pointed to.


[Modification of the tongue in the treatment of progenia].

The size, position and function of the tongue affect the surrounding jaw regions. In class III malocclusions where the tongue is involved, the treatment must be directed toward the correction of the function and the change in the oral volume proportions. These requirements are largely met by the functional prognathism appliance. Growth changes, increases in length of the upper dental arch, decreases in length of the lower dental arch and displacements of the mandible in a posterior direction were observed in the patients treated up to now.


[Cardiovascular behavior after local anesthesia in the jaw region with added vasoconstrictor agents].

The authors studied the cardiovascular behaviour after injection of different amounts of xylocitin added with adrenalin (1:80 000) and noradrenalin (1:20 000), respectively. The evaluation of the blood-pressure values, pulse rates and electrocardiograms leads to the conclusion that noradrenalin produces considerable side effects at the above-mentioned concentration. The well-known headache phenomena caused by the addition of noradrenalin are analysed.


Osteolysis in chronic myeloid leukemia.

Four patients affected by chronic myeloid leukemia who developed osteolytic lesions in the course of the disease are described. According to the literature, the appearance of these alterations seems to signify an unfavorable prognosis, since they occur slightly before or even at the same time as the blastic transformation of the disease. However, in one case bone biopsy showed a metastasis of a solid tumor, emphasizing the importance of this procedure in order to give a more precise clinical evaluation, both diagnostic and therapeutic.


Carotid angiography in Port Moresby. A report of a 5 year experience.

During a 5 year period at Port Moresby General Hospital in Papua New Guinea. 140 patients had carotid angiograms. Three quarters of the patients were male. Average age for all patients was 29 years. 44% of the patients had detectable abnormalities, the commonest being subdural haematoma and neoplasm. Other abnormalities found included aneurysm, brain abscess, tuberculoma and thrombrosed middle cerebral artery. The findings show many similarities to a reported series in Nigeria but differs from a Uganda series in which haemotoma was much more commonly found.


Sago haemolysis: clinical features and microbiological studies.

Severe, acute and sometimes fatal intravascular haemolysis has occurred on several occasions in Papua New Guinea families after the ingestion of apparently 'stale' sago. Earlier cases had been recorded only from the Maprik area; however, we now report the occurrence of two similar outbreaks, involving a total of 14 persons, in the Western Province. Several bacteria and fungi were isolated and identified in a sample of suspect sago from one of the outbreaks. None of these, however, to our knowledge, has ever been incriminated as a cause of haemolysis, and the aetiological agent(s) and mechanism of haemolysis thus remain to be elucidated. No mycotoxins were detected in one sample available for analysis. It is suggested that the eating of sago stored for a long time be discouraged; and further that, if a meal of sago tastes abnormal, additional mouthfuls should not be eaten and the remaining portion should be sent for analysis or discarded.


Port Moresby infant feeding survey.

An infant feeding survey was carried out in Port Moresby covering 136 mothers in order to determine the extent of artificial feeding in an urban area, and the effect of this method of feeding on the nutritional status of the infant. Over one third of the infants seen were artificially fed, out of which 69% were malnourished, compared with 26% of the breast fed infants. It is recommended that steps be taken by the Department of Health to control the free sale of bottles and teats to mothers.


A review of the Malaria Eradication Programme in the Solomon Islands 1975-1976.

The review outlines the developments in the Solomon Islands Malaria Eradication Programme (MEP) during the period 1975 - 1976. In most of the islands of the Solomons group MEP continues to be successful, but overall progress is hindered by persistent foci in areas of high malaria endemicity in north Guadalcanal. Some changes in the operational methodology are described, together with a report on supplementary measures carried out in the 'problem area' of north Guadalcanal.


Isoniazid-associated hepatitis in a Melanesian.

A patient with acute hepatitis associated with isoniazid therapy is described. The relevance fo isoniazid hepatotoxicity in Melanesian populations is discussed. Guidelines for recognition and management of INH-induced hepatitis are suggested.


Danger of sunburn following vaccination.

The complications of smallpox vaccination are reviewed. A case of disseminated vaccinia is presented. It is suggested that patients with sunburn may be susceptible to the complications of smallpox vaccination.


Aspiration biopsy cytology in proliferating benign mammary dysplasia.

The accuracy of the cytologic diagnosis from needle biopsy in proliferating mammary dysplasia was tested on the basis of 101 histologically proven cases of mild to severe degree. The cytomorphologic presentation in smeared aspirate is described. A reliable cytologic diagnosis of proliferating mammary dysplasia was possible in about half of the cases. This implies that the fine-needle biopsies give new possibilities for detection and intensive surveillance without surgical biopsies of women with increased risk of developing breast cancer. Study of the individual cases showed that the more severe the proliferation of the mammary epithelium, the greater the accuracy of the cytologic diagnosis. In intraductal and intracystic proliferation the accuracy was higher than in pure adenosis.


Cell clusters in urinary cytology.

Clusters of cells in cytologic preparations from the urinary tract have been commented on repeatedly. To determine their significance we studied 88 patients with documented papillary carcinomas, Grades I-IV, who had cytologic examination of their urine. We defined two distinct cluster types, "rounded", and "papillary", which were easily distinguishable from artifactual excoriated cell aggregates. By cytologic techniques 64 per cent of the specimens were positive and 18 per cent suspicious for malignancy, with the lowest sensitivity for Grade I tumors, and the highest for Grade IV tumors. Clusters were observed in 39 per cent of the cases, and also were more common in the most undifferentiated tumors. However, many cases which were cytologically positive had no clusters, and in only one case were clusters present without other cytologic features of malignancy. It appears that the presence of cell clusters is not a more sensitive indicator of papillary lesions than usual cytologic criteria applied to single cells. Clusters may indicate a higher grade tumor.


Cytologic changes associated with vaginal pessary use. With special reference to the presence of Actinomyces.

The cytopathology of Papanicolaou smears from 23 postmenopausal women with vaginal pessaries is described. The following alterations, when seen in the smear of an elderly postmenopausal woman, were found to be strongly suggestive of pessary use: cytologic atypia in the form of severe inflammatory changes in squamous cells, atypical metaplasia, and reparative changes with a background pattern of acute inflammation and prominent superficial maturation of the squamous cells. A notable additional finding in 13 of the 23 patients was the presence of filamentous organisms resembling Actinomyces and morphologically similar to organisms recently described and specifically identified as Actinomyces in patients with intrauterine devices.


Appraisal of self-collected cervical specimens in cytologic screening of uterine cancer.

Cytologic specimens were collected simultaneously by three methods on 122 patients with cervical neoplastic lesions: self-irrigated collection, self-scraped collection and physician-scraped collection. In invasive epidermoid carcinoma, the accuracy with the self-collected specimens approached the physician-scraped specimens. There was a serious defect in the detection of cervical intraepithelial neoplasia by the self-irrigation method. In carcinoma in situ and dysplasia, the self-scraping method was considerably better than the self-irrigation method. In mass screening of 89,206 females, the self-scraping positive detection rates were closer to the physican-scraping results than the self-irrigation method.


Diagnostic accuracy of endoscopy with brushing cytology and biopsy in upper gastrointestinal lesions.

Because of the high rate of diagnostic error with routine barium X-ray studies in detection of upper gastroesophageal lesions, a prospective investigation was undertaken to evaluate endoscopy together with brushing cytology and biopsy. Ninety-nine patients with recurrent upper gastrointestinal symptoms were examined during a two year period. Thirty-seven patients had cancer and 62 had benign ulcers as diagnosed by cytology and histopathology. All patients with diagnosis of carcinoma  were correctly diagnosed by a combination of the above studies as proven by subsequent surgical exploration of all 37 patients. In the benign group, 23 patients were confirmed by exploratory laparotomy and 16 patients by following up for at least 2 years with upper GI series and/or endoscopy. The highest degree of accuracy in the diagnosis of cancer was achieved by cytology alone (92% of cases) and lowest by barium study of upper gastrointestinal tract (84% of cases). Although the accuracy of endoscopy in detecting cancer of the upper gastrointestinal tract was 86 per cent, 15 per cent of benign ulcers were falsely called neoplastic by this technique. It is concluded that endoscopy with brushing cytology and biopsy is an effective diagnostic tool in distinguishing benign lesions from malignant neoplasms and can be performed with little risk to the patient.


Brushing cytology for the diagnosis of gastric cancer involving the cardia or the lower esophagus.

In 173 patients with gastric cancer involving the cardia or the lower esophagus, endoscopic biopsy and/or brushing cytology were utilized in establishing the diagnosis microscopically. Biopsy was positive in 132 of 170 patients (77.0%) while brushing was positive in 78 of 93 patients (83.8%). However, a combined use of biopsy and brushing yielded a higher diagnostic accuracy of 88.0 per cent. Further, endoscopic findings of the lower esophagus or the cardial orifice and diagnostic yields of the two methods were correlated. In patients with mucosal elevation, thick fold or a tight cardial stenosis as a pattern of esophageal involvement by gastric cancer on esophagoscopy, supplementary application of brushing increased diagnostic accuracy approximately 20 per cent compared to that of biopsy alone. It is concluded that brushing cytology should be utilized more frequently in gastric cancer involving the cardia to the lower esophagus, especially in the three types of esophageal involvement mentioned above.


From "exfoliative" to "diagnostic" cytology. A statistical evaluation of pulmonary cytology.

During the year 1975, a total of 2,877 cytologic examinations in our laboratory included 2,277 examinations on 580 patients related to pulmonary cytology. Statistical evaluation of these studies indicates that the present trend of pulmonary cytology examination is moving from "exfoliative" cytology to "diagnostic" cytology. As long as one maintains the specificity of the examination high enough by the application of stringent criteria for cytodiagnosis, further radio and/or chemotherapy can be justifiably instituted on the basis of cytologic examination along with clinical evaluation of the patients when histopathologic diagnosis is not obtainable.


Cytology of angiosarcoma of the breast. A case report.

A case of angiosarcoma of the breast nd the cytologic presentation of its unusual morphological characteristics are submitted in order to facilitate the differential diagnosis from other malignant breast tumors. This report emphasizes the necessity of needle biopsy of any breast lesion and the obvious importance of submitting pertinent clinical data to the cytopathologist at the time of cytologic diagnosis.


Characterization of glycogen in selected tissues of turkey poults with spontaneous round heart disease and furazolidone-induced cardiomyopathy.

Furazolidone (FZ) at 700 ppm was added to feed mixtures fed turkey poults 2--5 weeks after hatching to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From EKG data obtained at weekly intervals, poults were selected for sacrifice at 5 and 10 weeks of age. Poults were sacrificed by cervical dislocation and appropriate samples of tissue from the left ventricle, liver, pectoralis and tibialis cranialis muscles were removed for glycogen assays. Character of glycogen, as determined by percent of branching and number of glucose units per segment, was not significantly altered in poults with spontaneous round heart disease or FZ-induced cardiomyopathy. This suggests that the glycogen accumulation noted in these conditions most closely resembles type II glycogenosis.


Immunoblastic lymphadenopathy with pulmonary lesions and positive sputum cytology.

A case of immunoblastic lymphadenopathy is presented. The patient's diagnosis was made from his clinical findings and lymph node pathology. Of particular note are long-standing pulmonary lesions of undetermined etiology and the exfoliation in sputum specimens of large numbers of immunoblasts identical to those seen in histologic sections of lymph node. Although other cases of immunoblastic lymphadenopathy with pulmonary findings have been published, 4, 5 only the histomorphology of these lesions has been described. This is the first reported case of immunoblastic lymphadenopathy with positive pulmonary cytology. Diagnosis of this condition requires histopathologic evaluation of diagnostic lymph nodes. Immunoblasts may be identified cytologically in sputum preparations and in this context are suggestive of but not diagnostic of this entity. The use of methyl green-pyronine stain to better differentiate immunoblasts is recommended.


Improved apparatus for spinal fluid cytomorphology.

The design of an apparatus for spinal fluid cytomorphology is described. It represents an improvement over previous devices using the enhanced sedimentation principle and has given reliable clinical results over a three year period.


Corrosion of base metal alloys in vitro.

Corrosion of base metal alloys was studied by placing the alloys in artificial saliva for 2 months and then determining the concentration of metal ions in the saliva. The distribution of the attack on the surface was examined. The results indicated that the amount of metal ions in the artificial saliva could be related to the Cr content of the alloy. When the Cr content exceeded 16% very little corrosion was observed. The corrosive attack was located at Cr depleted areas, grain boundaries. The Cr depletion probably resulted from coring during solidification.


The cytology of the human peritoneal fluid.

A series of 19 human peritoneal fluids obtained by aspiration at laparoscopy and cul-de-sac punctures were analysed for their cellular content. Four types of cells were differentiated: macrophages, mesothelial cells, lymphocytes and polymorphonuclear leukocytes. The macrophages and mesothelial cells represented the two major types of cells, each group constituiting about 36 per cent of the population, while the lymphocytes and polymorphonuclears represented 18 and 7 per cent of the population, respectively. Macrophages were identified by their capacity to engulf alcohol-killed Staphylococcus albus. It appears that by this method of macrophage identification, a more accurate representation of the cellular content of peritoneal fluid can be obtained.


Maternal diabetes and changes in the hard tissues of primary teeth. III. A histologic and microradiographic study.

According to clinical studies, infants of diabetic mothers (IDM) seem to run a higher risk of mineralization disturbances in the enamel than normal healthy infants. In order to evaluate this observation at the histologic level, exfoliated primary incisors were collected from 74 IDM, representing two types of care during gestation and the perinatal period, and from 52 healthy children. The width of the neonatal line was evaluated in the enamel and the dentin by study of bucco-lingual undemineralized sections. Pre- and postnatal enamel was classified according to discolorations, deviations of prisms and hypoplasia. Microradiographic studies included measurements of the neonatal lines and classification of the degree of mineralization in the pre- and postnatal dental hard tissues. Irrespective of treatment, the IDM showed a significantly higher incidence of widened neonatal lines and also an increased frequency of postnatal disturbances compared to the controls. The observations are discussed against the background of the neonatal hypocalcemia reported in IDM.


Therapeutic pulpotomies in primary molars with the formocresol technique. A clinical and histological follow-up.

The results of therapeutic pulpotomies in primary molars with formocresol technique were studied by systematic follow-up. Of 84 primary lower molars in the clinical study, 56 became available for histological examination. The radiographic follow-up revealed periradicular osteitis in 10 per cent of the teeth treated. Internal root resorption was seen in 37 per cent of the teeth, or one-fifth of the roots treated. The histological examination revealed a very capricious diffusion of the medicament throughout the pulp tissue. Vital pulp remnants in the apical part of the treated roots showed no signs of healing. All pulps presented a varying number of inflammatory cells in the border zone adjacent to the formocresol-fixed region. In 80 per cent of the roots the histological sections revealed signs signs of internal resorption with or without incomplete repair tissue formation.


Recording of the retruded position of the mandible in patients with mandibular dysfunction.

The precision (reproducibility) of active and passive recordings of the retruded position of the mandible was studied by two examiners on 10 patients with mandibular dysfunction symptoms. The position of the mandible was recorded with an intra-oral graphic method, before and after treatment of the symptoms. The precision of the recording was highest when the retruded position was recorded by passive hinge movement and lowest when it was recorded by active hinge movement and when recording habitual closure. Both systematical and accidental errors tended to be somewhat larger among these patients than that previously found among individuals without signs or symptoms of mandibular dysfunction. The accidental errors in antero-posterior and medio-lateral directions were the same fo both examiners and of the same magnitude before and after treatment of the symptoms. Both examiners recorded the retruded position on the average 0.20 mm more posterior after treatment than before. The results showed that because of its good reproducibility the retruded position of the mandible can be recommended as a reference position in functional analysis of occlusion and for jaw recordings also in patients with TMJ muscle-pain dysfunction symptoms. During the recording the conventional technique with passive hinge movement and a posterior pressure should be used.


Osteosarcoma of the metatarsal bones. Review of the literature and report of a case.

A case of osteosarcoma affecting the third metatarsal bone is submitted. Below-knee amputation was performed, but the patient developed pulmonary metastases and died 1 year after the operation. The six cases of osteosarcoma in the metarsal bones published so far are reviewed. The prognosis for cases with this localization does not appear to differ from that for osteosarcoma in general.


Reliability of the CPRS between the disciplines of psychiatry, general practice, nursing and psychology in depressed patients.

To test the reliability and robustness of the CPRS in use by different disciplines we obtained 49 pairs of ratings on depressed patients in England and Sweden during treatment. Each rater pair consisted of a psychiatrist trained as a rater plus either a psychologist, a general practitioner, or a nurse, who had not been trained as a rater. The 17 most commonly rated items in depressive illness showed good inter-rater reliability for all groups and demonstrated the robustness of the scale even in training sessions. The implications of this for future interdisciplinary research are discussed along with suggestions for the use of the CPRS for teaching purposes.


Cross cultural studies on the use of CPRS in English and Swedish depressed patients.

54 English and 52 Swedish patients suffering from primary depressive illness were rated on the full 65 item CPRS scale to examine cross cultural differences. The correlation of the frequencies of items scored in the different patient samples was highly significant (r = 0.88). Of the most commonly scored items (occurring in more than 70% of any of the patient groups) 17 were common to both samples. The three items not in common for the two centres are compared and discussed. The inter rater reliabilities of the Swedish and English teams are compared alongside the inter rater reliabilities of a Swedish rater and an English rater on English patients and are generally good. The remarkable similarity of the psychopathology of primary depressive illness in both cultures and some of the implications are discussed.


The comprehesive psychopathological rating scale--CPRS--in patients with schizophrenic syndromes. Inter-rater reliability and in relation to Mårtens' S-scale.

In the course of a multicenter controlled trial of the effects of neuroleptic drugs on patients with schizophrenic or paranoid syndromes a comparison was made between the Swedish symptom rating scale--Mårtens' S-scale especially designed for patients with schizophrenic syndromes--and a new rating scale--the Comprehensive Psychopathological Rating Scale--CPRS. The Spearman rank correlation coefficient between the two scales was found to be 0,48 and as the inter-rater reliability for both scales was found to be quite satisfactory the validity of the scales is discussed. The CPRS scale was found to be easy to handle even for untrained doctors and in a separate study of inter-rater reliability where 5 doctors saw 16 patients a quite satisfactory reliability rk = 0,70--0.97, was found for 33 out of 39 items. In some items, espically those concerning different aspects of affective disturbances a lower inter-rater reliability was found but these items have been revised in later versions of the scale.


A comparison between "Cronholm-Ottosson depression rating scale" and variables concerned with depressive symptomatology in "the comprehensive psychopathological rating scale--CPRS".

In a study concerning 40 patients with depressive disorders the Cronholm-Ottosson depression rating scale and items concerning symptomatology from the Comprehensive Psychopathological Rating Scale--CPRS were compared. The total scores scales showed a rather satisfactory correlation (rs - 0,77). When patients were divided into two groups with depressive syndromes of a psychotic and non-psychotic dimension respectively the total scores of the items from CPRS from CPRS differed significantly for the groups while the total scores for the Cronholm-Ottosson depression rating scale showed a less pronounced, statistically non-significant difference between the groups, probably reflecting a reduced validity for the latter scale.


A CPRS subscale to assess mental symptoms in workers exposed to jet fuel--some methodological considerations.

A CPRS subscale was constructed for the assessment of mental symptoms in 30 workers exposed to jet fuel and in 30 matched non-exposed controls. All subjects were interviewed in random order by the same psychiatrist. Interviews were recorded on tapes later used for evaluation of rating-rerating and inter-rater reliability, which were in the range of rs 0.75--0.85. The average score of the exposed group exceeded significantly that of the control group. Items concerned with symptoms referred to as neurasthenic and as neurotic differentiated best between the groups. It appears that the subscale is sensitive enough differentiate between two groups of non-patient individuals and has helped establishing that occupational exposure to jet fuel may induce a psycho-organic reaction.


The comprehensive psychopathological rating scale (CPRS): communicability to, and inter-rater reliability among untrained raters.

Twenty-six, respectively twenty-three untrained Italian doctors participated in the rating of two patients with a preliminary Italian version of the CPRS. Despite an unfavourable setting, and some linguistic inaccuracies in the translation, a quite satisfactory degree of agreement was reached among the doctors. The Italian version of the CPRS has now been rewritten using a terminology more familiar to Italian psychiatrists.


Histogenesis of beryllium-induced bone tumours.

In response to beryllium treatment, irregular bone formation starts mainly in the marrow cavity of long bones, preceding neoplastic growth. Irregular medullary bone formation may be connected with the endosteum, but usually it develops in the bone marrow, independently of the endosteum. Osteogenesis in the bone marrow may be preceded by fibrosis but irregular bone may be formed also without any previous histological changes in the bone marrow. The tumour develops directly from the medullary bone. The prolonged irritation causes abnormal osteogenesis, which ultimately turns into neoplastic proliferation. Thus, the beryllium-induced bone sarcoma is, from histogenesis point of view, a hyperplaseogenic tumour. Irregular bone formation is considered a preblastomatous change, because it is closely connected with the development of the tumour and precedes it in time. The multiplicity of the tumour is explained by the "neoplastic field" theory of WILLIS.


Dietary cravings and aversions during pregnancy.

Interviews of 250 women concerning dietary changes during pregnancy were undertaken immediately after delivery. With regard to beverages, of women who regularly drank coffee or alcoholic items prior to conception, almost 30% reported a significant drop in ingestion during pregnancy. For coffee this change was attributed primarily to "endogenous" factors e.g., provocation of nausea or a loss of taste for the beverage. Concern regarding maternal or infant health was the most frequent reason for decrease in alcoholic beverages, although endogenous factors were also mentioned. Soda beverages were also ingested less frequently, predominantly because of dieting. The main increase was in milk consumption, primarily attributed to concern for the infant, but many mothers cited only a craving for the beverage. Other foods for which specific cravings were frequently cited were ice cream, sweets, and candy (particularly chocolate), fruits, and fish. Foods for which aversions outnumbered cravings were meats, poultry, and sauces flavored with oregano. Possible explanations for these changes associated with pregnancy are discussed.


The short face syndrome.

Cephalograms of twenty-seven untreated adult Caucasians, selected on the basis of a clinical impression of reduced lower facial height, were studied. Various linear and angular measurements were studied and compared to the Bolton standards. The short face syndrome SFS is a clinically recognizable facial type with reduced lower facial height as the common denominator. On the basis of the FPI (facial proportion index), the RH (ramus height), the OP-PP distance (or posterior maxillary height), and the SN:MP angle, two subgroups were distinguished in the SFS group. SFS, was characterized by a long ramus, sharply reduced SN:MP angle, an FPI close to 10, and a slightly reduced posterior maxillary height. In contrast, SFS2 was characterized by a short ramus, a slightly reduced SN:MP angle, an FPI with values around or below zero, and a sharply reduced posterior maxillary height. The latter group was designated as vertical maxillary deficiency.


Effects of cervical anchorage during and after treatment: an implant study.

Two groups of ten patients with postnormal molar relation, identical as regards facial morphology and dental stage, were treated for 8 months with cervical traction of the Kloehn type. The extraoral arch of the headgear was tilted upward in relation to the occlusal plane in one group and downward in the other. The local tooth movements were measured and related to metal implants inserted in the jaws. The movement of the implants in relation to the anterior cranial base expressed the amount and direction of the sutural and condylar growth. It was shown that a normal molar relationship was established in the shortest time with a downward tilt of the extraoral bow. A pronounced distal tipping of the molars was observed in these patients. The growth direction of the maxilla during cervical treatment was downward and backward and the mandible rotated posteriorly. The children were observed again 7 to 8 years after treatment, and it appeared that the influence of the headgear on the growth pattern of the facial skeleton was reversible, as a pronounced anterior direction of growth of the maxilla as well as of the mandible was observed in all but two subjects.


Urea peroxide solution in the treatment of gingivitis in orthodontics.

A 3-month study was conducted to determine the effect  of a 10 per cent urea peroxide solution on gingivitis and oral debris accumulation in orthodontic patients. Sixty fullybanded children (thirty-two girls, twenty-eight boys) 10 to 17 years of age were randomly placed into two groups of thirty members. The treatment group was assigned the use of the test solution and given normal oral hygiene instructions. The control group was given only the normal oral hygiene instructions. The subjects' gingival status was evaluated by means of the gingival index (GI) of O'Leary. The accumulation of oral debris was monitored by means of the oral debris index (ODI) of Greene and Vermillion as modified by Womack. Subjects were scored at the start of the study and approximately 1 and 3 months thereafter. Analysis of variance of the GI and ODI scores revealed significant treatment effects (p = 0.0013 and p = 0.0051, respectively), which substantiated the clinical observations. Rinsing with the test solution in conjunction with toothbrushing appears useful as an oral hygiene measure for orthodontic patients. No adverse reactions were experienced by any of the patients using the test solutions.


Landmark identification accuracy in xeroradiographic cephalometry.

Identification accuracy of fourteen cephalometric landmarks was compared between xeroradiographic cephalograms and conventional cephalograms. Four landmarks--point A, upper incisor tip, infradentale, and menton--were more accurately determined on the xeroradiograph, while two landmarks--point B and condylion--were more accurately determined on the conventional cephalogram. Although not conclusively demonstrated in this study, the xeroradiograph does appear to offer more clarity and detail than the conventional cephalogram. Further investigation of this new diagnostic medium will be necessary before its true significance to dentistry can be evaluated.


The importance of recognizing malignant giant cell tumor of soft parts.

Four tumors in the extremities were initially diagnosed as extraskeletal osteogenic sarcoma. Recent review of these tumors had led to their reclassification. Three of these are now recognized as malignant giant cell tumors of soft tissue and one as a malignant fibrous histiocytoma. All four patients have been cured. Some special features of malignant giant cell tumors of soft parts are described. The importance of treatment planning is stressed.


Template bleeding time and clinical hemorrhage in myeloproliferative disease.

In 32 patients with myeloproliferative disorders (MPD), correlations were made among clinical observations of hemorrhagic tendency, template Ivy bleeding time, and platelet aggregation studies. Bleeding time was commonly prolonged, particularly in myelofibrosis. In two cases, this prolongation appeared to reflect a defect in platelet function, which resulted in clinical bleeding. Prolongation of bleeding time did not correlate with degree of thrombocytosis. Two patients with thrombocytosis had serious clinical bleeding at a time when bleeding time was normal. Of the patients, 35% had abnormal findings from aggregation studies, but there was no correlation between aggregation studies and prolongation of bleeding time or clinical hemorrhage. We conclude that bleeding in MPD arises either from a defect in platelet function, which is reflected in a prolonged bleeding time, or from thrombocytosis.


Long-term hypokalemia in acute myeloid leukemia.

A 48-year-old man suffering from acute myeloid leukemia presented a hypokalemia that persisted almost constantly during 18 months despite total hematological remission. The renal investigation demonstrated a hypokalemic nephropathy with an impairment of urinary concentrating function. Light and electron microscopy showed renal lesions related to potassium depletion. We did not observe specific lesions explaining the renal potassium wasting. Metabolic studies showed persistent hyperkaluresis, which appeared to be the main kaliopenic factor. We also found hypomagnesemia and changes of the renin-aldosterone system. We observed a hyperreninism, probably due to hypokalemia and a slight hyperaldosteronism, which could have been one of the kaluretic agents.


Young Scientists Award Lecture 1977: An investigation into the value of some clinical biochemical tests in the detection of minimal changes in liver morphology and function in the rat.

Minimal liver damage was induced in groups of rats by the administration of three toxicants, viz. carbon tetrachloride, sodium phenobarbitone and orotic acid. Serial blood samples were taken from the animals during the course of the experiment and the plasma levels of a number of enzymes, substrates and metabolites were measured. Liver and kidney samples were also taken at appropriate times after dosing and examined histologically for evidence of drug induced damage. The results of the experiment show that (I) no single test gave unequivocal evidence of liver damage for all three compounds, (II) the conventional liver function tests, alanine transaminase, aspartate transaminase, and alkaline phosphatase, whose plasma activities are usually reported in toxicity studies, were not the most sensitive indicators of the minimal liver cell damage caused by the drugs used in this experiment, (III) knowledge of the intracellular location of the diagnostic enzyme makes it possible to describe, at least in part, the nature of the changes within the liver, (IV) measurement of plasma cholesterol and triglyceride levels can provide information about disruption in lipid metabolism, (V) the times at which blood samples are taken are most important if transient drug effects on the liver are to be detected.


Evaluation of food safety. National and international aspects.

Evaluation of the safety of chemicals in food have created considerable interest within the public, political, administrative, and scientific sectors in many parts o- the world. Political and administrative approaches may vary from country to country depdneing on traditions and cultural pattern. The political aims and goals of our times may be clearly defined, but they are often rather obscure seen from a scientific point of view. Health authorities are supposed to interpret the political intentions and transcribe them into practical administration. The use, by national and international health authorities, of the available scientific and technological knowledge to evaluate the safety of the food in question is discussed.


Clinical aspects of drug-induced hepatitis.

The drug reactions of the liver may be classified as to (1) reproducibility, (2) severity, (3) localization and (4) duration of the lesion. Ad 1) Few drugs give a reproducible, dose dependent, hepatic reaction (e.g. acetaminophen), a greater problem is the unpredictable, dose independent reactions caused by "indirect" hepatotoxic drugs (e.g. imipramin). Ad 2) Drug reactions may be fatal (e.g. halothane), of limited clinical importance (e.g. clorpromazin) or clinically insignificant (e.g. iopanoic acid). Ad 3) Histologically, and to some extent clinically, hepatocellular (e.g. propylthiouracil) may be distinguished from cholestatic (e.g. tolbutamide) reactions, but overlapping (e.g. phenylbutazone) and individual variations are common. Ad 4) Most drug reactions are acute, but an insiduous course, developping to cirrhosis, is increasingly recognized (e.g. oxyphenacetin). Drug reactions are usually not clinically, biochemically and morphologically distinct from other common liver diseases and are only diagnosed if this possibility is constantly kept in mind. Treatment other than withdrawal of suspected or known etiologic agents is virtually lacking. The basis for prophylaxis is careful registration of all drug reactions. Potentially hepatotoxic drugs should only be administered after thorough cost/benefit considerations.


Hepatotoxicity in patients with liver disease.

The biochemical and physiological disturbances caused by liver disease may enhance the toxicity of drugs. Besides alterations in liver blood flow and drug binding, a decreased rate of drug metabolism is an important phenomenon. Studies with phenazone, a model drug, demonstrates that the rate of microsomal drug metabolism is related to the degree of metabolic hepatic impairment. Individual dosage adjustments in patients with liver disease are complicated for many drugs, because of the counteracting influences of a decreased hepatic blood clearance and an increased free fraction of drug which may enhance drug metabolism and drug action. Moreover, many drugs owe part of their pharmacological action to active metabolites formed in the liver. Finally, little is known about altered receptor sensitivity in patients with liver disease. Non-predictable hepatotoxic reactions appear not to occur more frequently in patients with liver disease than in other patients. However, hepatotoxicity may be masked by the liver disease or by the intake of ethanol.


Halothane hepatitis.

Halothane (2-bromo-2-chloro-1:1:1-trifluoroethane) is a volatile, nonflammable anaesthetic agent which has been widely used for the last 20 years. Halothane hepatitis has been a matter of continuing controversy, but now it seems to be generally accepted as a clinical entity. Characteristically the halothane hepatitis occurs after multiple exposures to halothane within short time. The pathogenesis of the liver cell damage is obscure. It is estimated that the incidence of halothane hepatitis is about one per 8000 halothane anaesthesias and the lethality about one per 40000. Prophylaxis consists of avoiding repeated halothane anaesthesias within short time and to avoid re-exposure to halothane if otherwise unexplained liver damage has occurred after halothane.


Stimulation of DNA synthesis in mouse and rat lung following administration and butylated hydroxytoluene.

Butylated hydroxytoluene (BHT) is a widely used antioxidant in food. It has recently been reported that intraperitoneal injection of BHT to female mice produced, within 3-5 days, a hypertrophy, hyperplasia, and general disorganisation of the cellular components of the lung (Marion and Mitchell, 1972). In male mice it was shown that this effect of BHT was associated with a marked stimulation of DNA synthesis in the lung (Witschi and Saheb, 1974). Measuring the incorporation of thymidine-2-14C into DNA in lung confirmed the results reported in mice. 500 mg of BHT per kg, i.p., resulted in a 20-40 fold increase in thymidine incorporation in both male and female mice after 4 days. In similar experiments in the rat, however, a two-fold increase was observed in female rats, no effect could be demonstrated in male rats. In experiments in male and female mice using p.o. administration of BHT similar results have been obtained as following i.p. administration.


Evaluation of organ weight differences in toxicological experiments.

The most frequent measure used to interpret drug effects on organ weights in toxicological experiments is the ratio of the organ weight to the animal's bodyweight. It is shown that in general this measure is not useful and can lead to erroneous conclusions regarding drug effects, specifically for rats. In addition a new approach to the design of organ weight experiments is considered and compared to the use of relative weights using simulated data. It is concluded that this new method may be useful in the evaluation of organ weights.


Comparative cardiovascular toxicity of trazodone and imipramine in the rat.

Several authors have associated the cardiotoxicity of the tricyclic antidepressants with their capacity to potentiate the response to catecholamines. Trazodone is a psychotropic drug with a clinically proven antidepressant activity. It differes from the tricyclic antidepressants under several aspects (chemistry, pharmacology, mode and mechanism of action, etc.), including interactions with catecholamines. Contrary to the tricyclic antidepressants, it does not potentiate the response to catecholamines, but, instead, has an adrenolytic activity. We therefore decided to compare the cardiotoxicity of trazodone and of a tricyclic antidepressant, i.e. imipramine in the rat. The experiments were conducted on anaesthetized Long Evans rats, the drugs being administered by i.v. infusion until cardiac arrest occurred; ECG (lead II) and blood pressure (BP) were recorded at the same time. The primary effect of trazodone was its hypotensive action. ECG changes, consisting of a lengthening of the PR interval, were observed only when there was a marked drop in BP. The primary effect of imipramine, instead, consisted of disturbances in cardiac conduction. It is concluded that trazodone and imipramine produce different cardiovascular effects.


Liver injury and multiple drug therapy.

Analysis of the drugs used at the time of hepatic injury was carried out in a group of patients consecutively admitted to medical wards during a 10 years period (1965-1975). One drug was the possible cause in 26% of the patients and 74% of them were treated with multiple drug therapy. The most common drugs associated with liver damage have been sulphonamides, oral contraceptives, nitrofurantoin, methyldopa and phenothiazine derivatives.


Hepatotoxicity of citalopram in rats and first-pass metabolism.

A chronic oral toxicity study of citalopram in rats revealed dose dependent hepatic fatty infiltrations in male rats while female rats were unaffected. Subsequent studies demonstrated markedly reduced availability due to first-pass hepatic metabolism in male rats and roughly complete availability in females. Pretreatment of male rats with phenobarbital for 2 weeks caused increased metabolism and simultaneous administration of phenobarbital and citalopram gave more pronounced fatty infiltrations than citalopram alone. A connection is suggested between the first-pass metabolism in male rats and the hepatotoxicity, which is possibly mediated through a metabolite or intermediate formed in toxic amount during the first passage of the liver.


A new procedure for estimation of nitrovin and carbadox residues and their metabolites in food of animal origin.

In order to establishe the length of the protective period for which the animals are given food without chemical growth stimulators before slaughter two methods are proposed permitting wide use in sanitary control: 1/ A highly sensitive method of pulse-polarography has been worked out for the estimation of widely used growth stimulator nitrovin residues/ 1.5-bis/5-nitro2-furyl/1.4-pentadiene-3-on amidinohydrazone / and its metabolites. In the tissues of the experimental animals examined were found residues at a level of about 50 ppb. The limit of sensitivity of the procedure used is 10 ppb. 2/ Based upon double-electron reduction of the quinoxaline circle a simple and sufficiently sensitive polarographic method was worked out for the estimation of carbadox residues / quinoxaline-1.4-N-dioxide-2-methylcarbazate/and its main metabolite / quinoxaline-2-carboxylic acid/. With the sensitivity of the method of 0.1 ppm excretion curves were designed and residue levels were determined in tissues of pigs fed up to 56 days of age by feed containing 20 - 50 ppm of carbadox.


Covalent binding of 2,4-diaminoanisole and 2,4-diaminotoluene in vivo.

We have studied the activation of 2,4-diaminoanisole (2,4-DAA), a mutagenic hair-dye component, and 2,4-diaminotoluene (2,4-DAT), a hepatocarcinogen, to products which blind covalently to tissue macromolecules. Four hours after a dose of 100 mg/kg ring-labeled 3H-2,4-DAA, 0.30 nmol is found covalently bound per mg liver protein. This amount is increased by 83% after phenobarbital pretreatment, and by 43% after beta-naphthoflavone-pretreatment. Almost the same degree of binding is seen in kidneys. Subcellular fractionation of livers shows that most of the bound material is in the microsomal fraction. Similar levels of covalent protein binding is seen after administering ring-labeled 3H-2,4-DAT. No significant binding to DNA in vitro or in vivo could be demonstrated using 3H-2,4-DAA or 3H-2,4-DAT, whereas 3H-2,4-DAT is found to covalently bind to hepatic RNA.


Hepato- and thyreotoxicity of tifemoxone.

The oral toxicity of Tifemoxone, phenoxymethyl-6 tetrahydroxazine-1, 3 thione-2, a new potential antidepressant was studied during 6 months in rats at 30, 85 and 230 mg/kg/d and in beagle dogs at 10, 55 and 300 mg/kg/d. Thyroid hyperplasia and hypoactivity were observed in the rats and dogs plasma triiodothyronine, determined in dogs, was modified. A dose dependent hepatotoxic effect was observed in the rats and dogs. In dogs at low dose, one animal died after B.S.P. test. Water consumption and urinary volume increased, weight loss and anemia appeared at high doses in both rats and dogs. Hair loss was observed in rats and convulsions in dogs. In conclusion, Tifemoxone like tetrahydroxazine thione and some derivatives caused thyreotoxicity, hairlessness and increased in water comsumption and diuresis and in addition it had strong hepatotoxic effect especially in the dog.


Nutritional evaluation of low-erucic-acid rapeseed oils.

Detailed morphometric studies performed in heart tissue from Swiss mice and Wistar rats show that, in comparison with other edible oils, long-term feeding of the new rapeseed oils, poor in erucic acid, do not significantly affect the incidence of myocardial background lesions, in contrast to high-erucic-acid rapeseed oil. The strong predisposition of the Sprague-Dawley rat, however, to develop myocardial necrosis is re-emphasized. The factors underlying this particularity need further clarification. The data presented and the available evidence from experiments involving pigs, monkeys and poultry show that a reduction of the content of erucic acid in rapeseed lipids, as has been achieved by selective plant breeding, considerably improves the nutritional status of the cruciferous oils.


Toxicological studies on a new veterinary antibiotic turimycin.

Turimycin is a fermentation product ofStreptomyces hydroscopicus (DDR W-Patent-Nr. 84 450). It is highly active in vitro against a range of mycoplasma species and gram-positive bacteria. The acute toxicity was determined in mice, rats and dogs. In mice and rats LD50 values ranged from 750 mg/kg intraperitoneally to higher than 3000 mg/kg orally. In a chronic study on dogs oral doseas of 50 nad 125 mg/kg Turimycin were given daily in capsules for 12 months. The results showed no functional or morphological differences between treated and control animals.


Hepatic clearance and disposition of hydroxyethylrutosides.

Although salts of rutin on i-v admin. undergo insolubilization giving rise to concretions and suppurative inflammation in the liver this was not observed in respect of the vaso-active hydroxyethylrutosides (Pfeifer et al., 1970). I-v admin. of 3',4',7-tri0-(beta-hydroxy[14C]ethyl)-rutoside (tri-HR) and 7-mono0-(beta-hydroxy[14C]ethyl)rutoside (mono-HR) to mice showed rapid biliary excretion (approx. 71% within 24 h). Approx. 2/3 of the dose was subsequently excreted in faeces and ca. 25% in urine over 72 h. Autoradiography and scintilation counting showed short term concentration in the liver over the initial 4 h period but at 72 h less than 0.22% of tri-HR and 0.59% of mono-HR was detectable in hepatic tissue. Carcasses of mice killed at 72 h contained less than 7% of the initial dose which was mainly present in intestinal contents.


Changes in the hepatic copper conent after treatment with foreign compounds.

The effects of dimercaprol, CaNa2EDTA, D-penicillamine, diethyldithiocarbamate, disulfiram, pyrazole and phenobarbital on the hepatic copper content were studied. Adult male albino rats were given these compounds subcutaneously or intragastrically for 4 or 7 days, and the copper content in the hepatic crude homogenate was measured with an atomic absorption spectrophotometer. The metal chelating compounds dimercaprol, D-penicillamine and diethyldithiocarbamate only slightly decreased the level of copper in the liver. CaNa2 EDTA caused no change in the copper content. A slight decrease was found also after phenobarbital treatment. On the contrary, disulfiram and pyrazole increased the copper content 3- and 2-fold, respectively. It is suggested that the accumulation of copper in the liver is due to the cholestatic action of disulfiram and pyrazole.


Absorption and excretion of 1-amino-2-naphthol-6-sulphonic acid in rats and rabbits.

1-amino-2-naphthol-6-sulphonic acid (ANSA) and compounds of similar structure are metabolites formed by azo reduction in mammals from several commonly used food colours, e.g. Sunset Yellow FCF and Food Red 17. At our institute it has been shown that ANSA produces bile duct proliferation when given orally to rabbits. Furthermore Orange RN which by azo reduction yields ANSA (and aniline) induce the same effect in pigs (Olsen et al., 1973) but not in rats (Gaunt et al., 1971). Using 35S-labelled ANSA the absorption and excretion as well as the localisation in the liver cell of ANSA was investigated in rats and rabbits. The results after p.o. administration shows that the rabbit absorbs and excretes into the urine a significant larger amount of ANSA (30-40%) than the rat (6-13%). The results after i.v. administration shows that some 60% of the injected dose is excreted in the urine in both species. In the rat 15-20% are recovered from the faeces, while only traces (0.1-0.5%) are found in faeces of rabbits. A significant amount of ANSA was retained in the blood and the liver of both species 24 and 48 hours after administration. After differential centrifugation of liver homogenates the majority of ANSA was found in the 9000 x g supernatant.


Drug excretion into eggs. An autoradiographic study.

Ulberg's whole-body autoradiographic technic has been used to illustrate the distribution pattern, the uptake to the oocytes and the excretion into the egg-white of 14C-trimethroprim, 3H-tetracycline and 14C-urea in Japanese quails. Marked differences were found in the uptake by the follicular epithelium between the oocytes of different size. Furthermore it is observed, that the part of the compound which reaches the yolk remains there, while the rest of the compound is excreted from the body. In the oviduct, the compounds showed variations in the distribution pattern between the differen parts, apparently according to the passive diffusion concept. Some of the drugs showed peculiar localisation in high concentrations as in the retina and in the pecten of the quails eye.


Lysosomal enzymes in hepatic injury induced by bromobenzene.

In studies with bromobenzene we found increases in the activities of hepatic lysosomal enzymes. The present study was undertaken to determine how these changes are related to the development of hepatic injury after bromobenzene administration. A single intraperitoneal injection of bromobenzene (5 mmoles/kg) caused significant increases in the total activity of lysosomal N-acetyl-beta-glucosaminidase and beta-glucuronidase in rat liver within 8-12 h, whereas it did not alter the free activity of these enzymes. Enhancement of bromobenzene hepatotoxicity by the pretreatment of rats with phenobarbital was not associated with further changes in hepatic N-acetyl-beta-glucosaminidase or beta-glucuronidase activities. Cycloheximide administered prior to bromobenzene inhibited significantly the effect of bromobenzene on the total N-acetyl-beta-glucosaminidase activity. The results suggest that lysosomal enzymes are not directly involved in hepatic damage caused by bromobenzene and that the inhibition of protein synthesis may reduce this response to hepatotoxin.


Increase of hepatic and serum aldehyde dehydrogenase activity after TCDD treatment.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a contaminant of some herbicides, is an extremely potent enzyme inducer. Male albino rats of two genetically different substrains developed for the inducibility (RR) and noninducibility (rr) of aldehyde dehydrogenase by phenobarbital were given TCDD 80 microgram/kg as a single dose 6 days before analysis. rr-Animals having no induction of the hepatic soluble high-Km aldehyde dehydrogenase by phenobarbital showed an approximate 25-fold increase in activity after TCDD treatment. The increase in aldehyde dehydrogenase activity could be detected only when measured with a millimolar substrate concentration. The aldehyde dehydrogenase activity in serum was increased 3-fold after TCDD administration in both substrains.


Enhancement of cytosolic carboxylesterase by phenobarbital in the rat.

Previously suggested identity of soluble hepatic carboxylesterase and cytosolic aldehyde dehydrogenase was studied in the liver of the rr and RR rat substrains after phenobarbital administration. Results showed over 30% increase of carboxylesterase activity in all animals treated with phenobarbital. The total aldehyde dehydrogenase activity was increased only in RR substrain. These animals had no similar enhancement in the activity of carboxylesterase. The results indicate that the two enzymes are not identical.


Specific modification of the properties of the N-hydroxylase. Relationship with carcinogenesis by aromatic amides.

N-hydroxylation represents the first and limiting step in the metabolic pathway leading to the carcinogenic activity of aromatic amines and amides. Using a method recently developed by the same authors (Analytical Biochemistry, in press), the effects of pretreatment of male adult rats with N-2-acetylaminofluorene (2AAF), N-4-acetylaminofluorene (4AAF), N-4-acetyl-aminobiphenyl, (4-AABP), and phenobarbital (PB), on the kinetic parameters of the N-hydroxylase activity have been evaluated and compared. Our resutls clearly demonstrate that both hepatocarcinogenic amides, 2-AAF and 4-AABP very significantly increase the affinity of the activating enzyme towards both substrates; on the other hand, 4-AAF and PB, which are non-carcinogenic compounds slightly decrease the affinity of the enzyme. In conclusion, the carcinogenic aromatic amides seem to specifically modify the catalytic properties of the enzyme responsible for their own metabolic activation.


A very sensitive gas chromatographic method for the evaluation of styrene oxidase and styrene oxide hydratase activities.

Styrene is a compound widely used in the manufacture of polystyrenic plastics and it has recently been shown to exert mutagenic effects after metabolic activation into styrene oxide by the microsomal mixed function oxidases; this oxide is further converted into inactive styrene glycol. In order to investigate the relative importance of activation and desactivation processes of styrene, we developed a gas chromatographic method which enables us to simultaneously measure styrene oxide and styrene glycol formed after incubation of styrene with microsomal preparations from different tissues. After selective extraction of the two compounds from the incubation mixture, they are derivatized with pentafluorobenzoyl chloride and measured by gas chromatography using an electron capture detector. The high sensitivity of the method, which allows 0.01 ng of both compounds to be measured, as well as its selectiveity, has permitted us to adequately evaluate the kinetic parameters of styrene oxidase and styrene oxide hydratase activities, as well as their modifications under the influence of various pretreatments of the animals.


A gas chromatographic method for the evaluation of the vinyl epoxidase activity.

Two alternative specific and very sensitive methods for determination of vinyl epoxide synthetase activity in liver microsomes are described. Trichloroethylene, which is used as a substrate, is converted into trichloroethylene oxide by a hepatic epoxide synthetase. Chloral hydrate, the final rearrangement product of trichloroethylene oxide, is evaluated by electron capture gas chromatography, either after derivatization with pentafluorophenyl-hydrazine or after its conversion into chloroform under alcaline conditions. The kinetic parameters of the epoxidative reaction have been determined on rat hepatic microsomal suspensions.


The use of food additives in Sweden.

Recently it was demonstrated that the levels of some added colours in food sold in Sweden were such that the recommended daily intake (ADI) could easily be exceeded by the consumer (Ahlborg et al. Vår Föda, 26, 1974, 194-217). New regulations concerning the use of food colours in Sweden came into force on July 1st, 1975. The collection of information on the use of food additives in products sold on the Swedish market has not been extended to cover other food additives such as preservatives and antioxidants. This study is based upon details of about 10,000 food products containing food additives. The material is being computerised and work on the evaluation is in progress. The new investigation demonstrates that the use of food colours has decreased and that very few products now contain high levels of food colours. Data will be presented concerning the levels and total amounts of preservatives, antioxidants and other food additives used in different groups of food products.


Hemiglobin formation in vitro induced by azo dyes and their metabolites.

Azo dyes which after reduction by the intestinal flora yield aniline are known as inducers of Heinz bodies after oral intake (J.J.-P. Drake, 1975). The effect of aniline is thought to depend on its metabolic conversion to the known hemiglobin inducers, phenylhydroxylamine and o- and p-aminophenol (A. de Bruin, 1976). The azo dyes used for colouring of foods are reduced in vivo forming sulphonated primary aromatic amines, many of which are of aminonaphthol structure. Such compounds could be potential hemiglobin inducers. This possibility was investigated in vitro by incubating the following azo dyes and their metabolites, with red cells in Krebs-Ringer phosphate solution: Chrysoin S, Scharlach GN, Azorubine, Sunset Yellow FCF, Food Red 17, Orange GGN, Ponceau 4R, Amaranth, Ponceau 6R and Fast Yellow AB. The concentration in the incubate was 0.5 mmol/l and the hemiglobin formation was measured after 1 h. The effect on red cells from pigs was compared with the effect on human red cells. Only the metabolites containing amino and naphthol groups together were active. The activity depended on the number and position of the sulfonic acid groups.


Peroral toxicity of Orange RN in pigs. Early haemotological changes.

Earlier experiments with Orange RN in rats have shown several changes in the blood i.g. induction of Heinz bodies, methaemoglobinaemia and reduction of RBC (J.F. Gaunt et al., Fd. Cosmet. Toxicol., 1971, 9, 619). Similarly induction of Heinz bodies, reduction of RBC and a rise in reticulocytes were demonstrated at our institute in pigs following a few weeks administration of Orange RN (P. Olsen et al., Toxicology, 1973, 101, 249). The purpose of this study has been to investigate the degree and the induction time of Heinz bodies and changes in the number of reticulocytes and RBC in pigs during the first 18 days. After a few days marked alterations in the blood picture were seen. Heinz bodies increased from a few or none to 65% of the erythrocytes in the highest dose group (320 mg/kg bw/day) and to 30% in the lowest dose group (160 mg/kg bw/day). In addition a marked decrease in RBC and a rise in reticulocytes were seen in the highest dose group.


Toxicology of triethyllead, methylmercury and cadmium, determined in chick embryo brain cell cultures.

The toxicology of water soluble chemical compounds may be investigated in tissue culture systems. The toxicology of triethyllead chloride, methylmercury chloride and cadmium acetate was studied in chick embryo brain cell cutlures. Tetraethyllead is added to petrol as an anti-knock agent. When tetraethyllead is absorbed by the organism, it is converted to triethyllead which cause the symptoms of tetraethyllead poisoning. Chick embryo brain cell cultures derived from cerebrum of 11-day-old chick embryos developed both neurons and glial cells. The neurons formed nerve processes and synapsis in the cultures. The effect of triethyllead chloride was investigated by addition of triethyllead chloride to the nutrient medium. The median tissue culture lethal dose, TCLD50 = 1.9 mg/l, was determined as the concentration of triethyllead chloride at which the confluent layer of glial cells was destroyed in 50% of the cultures. The neurons lost their processes at even lower concentration, TCED50 = 0.57 mg/l. Electron microscopy revealed cells with swollen Golgi apparatus and dilated endoplasmic reticulum in chick embryo brain cell cultures which were treated with triethyllead chloride, 1.0 mg/l. Studies with radioactive labelled precursors revealed that triethyllead chloride inhibited the synthesis of DNA, sulfatides and cerebrosides without hydroxyfatty acids.