Isolation of the opioid heptapeptide Met-enkephalin [Arg6,Phe7] from bovine adrenal medullary granules and striatum.

Bovine adrenal chromaffin granules have been shown to contain, in addition to Met-enkephalin and Leu-enkephalin, at least three small peptides with opiate receptor activity. One of these adrenal peptides has been purified to homogeneity and its sequence was shown to be Met-enkephalin-[Arg6,Phe&]. This heptapeptide was also found in beef striatal extracts in amounts comparable to those of Leu-enkephalin.


Rhythmic patterns of discharge in hypothalamic neurosecretory neurons of cats and dogs.

Recent studies in rats suggest that vasopressin- and oxytocin-secreting neurons in supraoptic nuclei and paraventricular nuclei of the hypothalamus show two different patterns of activity: one a "bursting" or rhythmic pattern and the other, irregular continuous discharges. This possibility was investigated in cats and dogs anesthetized with chloralose or Nembutal by recording electrical activity of single supraoptic and paraventricular neurons. Only some of the "identified" neurosecretory cells showed rhythmic, intermittent discharges ("bursting" cells in rats); the majority showed an irregular continuous firing pattern. Furthermore, the pattern of discharge sometimes changed from one ot the other during long periods of observation. This occurred without apparent stimulus in certain instances; in others, the rhythmic firing was associated with fluctuation in blood pressure and heart rate and was likely to be caused by changes in baroreceptor activity. Possible origins of rhythmic discharges and the physiological importance of such patterns in terms of hormone secretion are discussed.


Mitochondrial DNA clones and matriarchal phylogeny within and among geographic populations of the pocket gopher, Geomys pinetis.

Restriction endonuclease assay of mitochondria DNA (mtDNA) and standard starch-gel electrophoresis of proteins encoded by nuclear genes have been used to analyze phylogenetic relatedness among a large number of pocket gophers (Geomys pinetis) collected throughout the range of the species. The restriction analysis clearly distinguishes two populations within the species, an eastern and a western form, which differ by at least 3% in mtDNA sequence. Qualitative comparisons of the restriction phenotypes can also be used to identify mtDNA "clones" within each form. The mtDNA clones interconnect in a phylogenetic network which represents an estimate of matriarchal phylogeny for G. pinetis. Although the protein electrophoretic data also differentiate the eastern and western forms, the data are of limited usefulness in establishing relationships among more local subpopulations. The comparison between these two data sets suggests that restriction analysis of mtDNA is probably unequalled by other techniques currently available for determining phylogenetic relationships among conspecific organisms.


[Technological aspects of agar-hydrocolloid impression materials].

Physical properties with clinical relevance has been tested on a number of agar hydrocolloid impression materials For 1 hour an almost perfect dimensional stability can be maintained when the impression is stored in water. Elasticity and strength are poor. Only the use of much bulk material may prevent damage during manipulation of the gel. The detail reproduceability meets all standards. A good compatibility with dental stone subsequently allows sharp details in the model.


[Calcifying odontogenic cyst].

Two patients have been described in which a calcifying odontogenic cyst has been removed. One patient concerned a 14-year-old girl with an impacted 24, in which a calcifying odontogenic cyst was removed in connection with a complex odontoma. The other patient concerned a 85-year-old man with a large cyst in the edentulous maxilla, which was marsupialized. This second patient is probably the oldest one reported in the literature concerning calcifying odontogenic cysts. Because of the age of the patient and his general condition, it was felt justified to just marsupialize the lesion instead of a more radical removal. The follow-up findings after one year seem to confirm the justification of the chosen treatment procedure.


Suggestion for a definition, measuring method and classification system of bristle stiffness of toothbrushes.

A definition of bristle stiffness and a measuring method are described and discussed. Sixty-six different brush models, collected worldwide, were measured according to the suggested method. Considerable differences were found between brushes of declared equal stiffness. On the basis of these findings and the method described, a classification is suggested.


Spatial position of the lateral semicircular canal in 14--60-day-old rat heads.

During growth the rat skull straightens considerably due to flexions between skull parts and individual bones. This straightening is defined as orthocephalization. Orthocephalization might also be caused by a change in head posture during growth, i.e. it may be "apparent". In order to study the significance of this phenomenon, radiographs of dried skulls of male rats, 14, 30 and 60 d of age were subjected to angular measurements between the plane of the lateral semicircular canal and the plane of foramen magnum and of the basisphenoid bone, respectively. When the plane of the lateral semicircular canal is placed horizontally, the head is claimed to be in natural position. No changes in the angulation between the lateral semicircular canal and the basisphenoid bone could be revealed, whereas the foramen magnum was shown to rotate upwards and backwards in relation to the plane of the canal. This implies that the orthocephalization which takes place between 14 and 60 d is caused only by angular changes, and that no apparent changes occur due to changes in head posture.


Concentrations of Ca, Mg, Mn, Sr and Zn in supra- and subgingival calculus.

The concentrations of Ca, Mg, Mn, Sr and Zn in supra- and subgingival calculus collected from mandibular anterior teeth mainly of the same persons were analyzed with atomic absorption spectrophotometry. The results showed highly significantly (P less than 0.001) greater Zn and Sr concentrations in subgingival samples. The mean value of Zn was 5.4 times higher in subgingival calculus than in supragingival calculus. In contrast, the concentration of Mn was significantly (P less than 0.01) higher in supragingival calculus. The difference in the concentration of Mg in supra- and subgingival calculus was highly significant (P less than 0.001) only when samples from the same person were compared. The concentration of Ca was very similar in both types of calculus and individual variations were very small.


Pulpotomy of primary molars with coronal or total pulpitis using formocresol technique.

The aim of this study was to evaluate whether formocresol can be used successfully in teeth with carious exposure and a vital pulp with clinical symptoms of chronic pulpitis. Further, the study concerned the influence on the success rate of the vehicle for formocresol. Pulpotomies were performed on 81 primary molars. Radiographic and other clinical symptoms were used to divide the material into a coronal chronic and a total chronic pulpitis group. Chosen by lot, zinc oxide-eugenol or Pharmatec (a plaster-like non-eugenol cement) was used as the vehicle for formocresol. After an observation period of 2.5 years the success rate for the whole material was 55%. No statistically significant difference in the rate of success could be demonstrated either between the two diagnostic groups or between the two vehicle groups.


Retreatment of endodontic fillings.

Effects of endodontic retreatment on quality of seal and periapical healing were assessed among 660 previously root-filled roots. The roots were divided into either of two groups according to presence or absence of pathologic alterations in the periapical area. The retreatments, which were carried out by dental students, involved a thorough chemomechanical debridement of the root-canal system aiming to control infection. Following a 2-year observation period 556 roots were reexamined clinically and radiographically. The results showed that root-fillings with technical shortcomings could, following retreatment, be markedly improved as regards effectiveness of seal and distance to the apex. A large number of lumina discernible apical to root-filling could also be treated and filled. Seventy-eight percent of the cases with pathologic lesion present periapically prior to retreatment either completely healed or displayed an obvious size-reduction of the process. Retreatments carried out because of technical inadequacies alone were successful in 94% of the cases. It was concluded that renewed endodontic treatment whenever possible is the method of choice when treating defective endodontic fillings complicated with pathologic processes periapically. Apical surgery may be attempted if no signs of healing are apparent following observation.


A method for studying epithelial-mesenchymal interactions in human oral mucosal lesions.

A system has been developed for examining connective tissue influence on keratinization of normal and leukoplakic human oral epithelia. Paired biopsy specimens of normal and leukoplakic mucosa were left intact or were incubated in 1 mM EDTA to permit epithelial-connective tissue separation and various recombinations of the epithelium and connective tissue. The tissues were transplanting to subdermal sites of "nude" (nu/nu) mice and were protected by polyethylene capsules. 44% of implants performed were recovered apparently vital. Preexisting structure was retained after epithelial-connective tissue separation and self-recombination. Cross-recombined specimens showed changes in patterns of keratinization including changes of keratinized leukoplakic epithelium to a non-keratinized type.


[Patient monitoring].

The main problems of monitoring patients on prolonged artificial respiration are discussed. These are: uninterrupted technical control of the respirator and of its clinical effects; continuous observation of the functioning of tubes, vaporizers and nebulizers; adequate tracheobronchial clearance and breathing therapy is absolutely compulsory. Intensive care units are classified into three categories according to their monitoring and surveillance capacities. The minimum, which corresponds to category I, should be performed by every intensive care unit. Category III includes additional computerized intensive care. The most important parameter for monitoring pulmonary function is blood gas analysis, which has been improved by the introduction of continuous arterial pO2 registration. Haemodynamic control serves for detection of arrhythmias and changes in pump function. The determination of pulmonary shunt flow (Qs/Qt) and of the ratio of dead space to tidal volume (VD/VT) impart information on the overall function of both systems (category II). A nomogram to simplify the calculation of pulmonary shunt is proposed which aggregates the factors contributing most to pulmonary shunt in acute respiratory failure. Its results deviate less than 1% from the calculated values if PCO2 ranges between 32 and 52 mm Hg and the error does not exceed 1.5 per cent with a PCO2 up to 82 mm Hg, unless it is combined with a very low Hb and high mixed venous saturation.


[Delayed eruption of the premolar after pathological deciduous tooth root resorption].

The behaviour of eruption of lower premolars after pathological resorption of deciduous molar roots was examined on models and X-rays. The molars of the first dentition were shed earlier after pathological resorption of deciduous molar roots. Data of absence are measured in years in the presence of occlusal bone bridges. The middle values are more than three years. Eruption of permanent teeth happens years later or they remain impacted. Eruption dates of premolars after pathological deciduous root resorption and interruption of the lamina dura, and after physiological resorption are significantly earlier than if there is an occlusal bony bridge (p less than 0.01). The therapeutic consequence is the surgical liberation of such premolars and their removal.


[Long-term clinical supervision of direct pulp capping (performed by the students of the School of Dentistry, Geneva)].

Of 123 teeth treated by direct pulp capping 110 could be rechecked clinically and radiographically after periods of 1 1/2 to 7 years, 4 on the average. In 25 cases a change in endodontic treatment has been recorded on the files: In 18 cases biopulpectomy was performed for symptomatic (pain) reasons considered as failure of the capping treatment; in 5 cases biopulpectomy was indicated for periodontal and prosthetic reasons (not considered as failure); in 5 cases of the 110 rechecked necrosis and periapical involvement was diagnosed. The rate of failure thus was 22 cases or 17%. This relatively high ratio of unfavorable results (Tab. VII) is in part due to lack of operative skill of the students while progressing tooth morbidity statistically established in the Genevan population also was taken into account. Advancing tooth ages according to graph figure 6 in accordance with other recent surveys were found to constitute no impediment for direct pulp capping. The success of this endodontic treatment is best ascertained by observing a strict selection of the case and the observance of an exacting operative procedure, namely: - Only accidentally exposed pulps without symptoms of previous spontaneous pain (Category I) are liable to successful conservation by direct pulp capping using calcium hydroxide. Previously painful pulps (Category II) according to Table VIII are either indirectly capped using corticosteroids particularly in young teeth or after exposure subject to coronal or radicular pulpotomy (Category III). Rigorous aseptical procedure and lasting hermetical sealing of the calcium hydroxide pulp dressing are additional prerequisites for success.


[Located hinge-axis or conventional hinge-axis?].

The purpose of this study is first, to evaluate the influence of locating the horizontal transverse axis of rotation of the mandible, both kinematically and conventionally, and second, to determine the influence of the thickness of the wax check-bite, as obtained in the centric relation, upon the functional analysis of the occlusion. The results show that the influence of any displacement of the horizontal transverse axis of rotation of the mandible is smaller, within a circle with a 6-mm radius, than that of the thickness of the wax check-bite obtained in the centric relation.


[Decrease in interdental bone atrophy, radiological survey; statistics from the years 1963-1976 from a Basel public dental clinic].

The material of this study consisted of 300 patients 16 to 39 years of age of the Public Dental Clinic of the City of Basle without destructive periodontal disease. The distance from the cementoenamel junction to the alveolar septum (DJS) was measured on bitewing radiographs at 8 surfaces of the lateral segment. On the radiographs made during the period 1963-1967, the average DJS ranged between 0.93 and 1.49 mm in the 5 age groups. Since 1964-1967, patients have routinely been given theoretical and repeated practical training in prevention of caries and periodontal disease. On the radiographs made during the period 1973-1976, the range of the averages was from 0.65 to 1.01 mm. The decrease of the DJS, 0.35 mm on average, was statistically significant in all 5 age groups.


[Periodontal status in a group of Swiss soldiers age 28-32 years].

139 soldiers aged 28-32 years of a medical corps unit of the Swiss army were examined for their periodontal conditions. On 3 surfaces of all teeth, plaque deposits were assessed according to the Plaque Index System (Silness and Löe, 1964) and gingival health determined according to the Gingival Index System (Löe and Silness, 1963). Calculus deposits were evaluated on the 6 representative teeth of Ramfjord (1959). On 4 surfaces of the same teeth, pocket depths and loss of attachment were measured. The mean P1I was 1.38, the mean GI 1.11. The mean pocket depth was 2.52, and the mean loss of attachment was 1.38. The results of this study were compared with those of a previous study by Curilović et al. (1972). It was concluded that periodontal disease progressed in the Swiss male population between 20 and 30 years at an annual rate of 0.18 mm loss of attachment despite all the efforts in preventive dentistry.


[Oral hygiene habits in a group of Swiss soldiers age 28-32 years].

139 medical corps soldiers (aged 28-32 years) of the Swiss army were interviewed for their oral hygiene habits. The same questionnaire as that described by Saxer et al. (1972) was used in order to compare the results of the present study with those obtained by Saxer et al. (1972) in an army basic training school in Zurich. The attitude of the soldiers towards their dentist did not change when compared to that of the recruits. However, the soldiers tended to be more "tooth conscious" than the recruits. They also showed a better attitude for oral hygiene procedures and greater knowledge concerning periodontal disease.


[Changes in dentistry].

Although collective and individual prophylactic measures have been shown to drastically reduce or totally prevent dental caries and periodontal disease, a recent survey of over a thousand twenty-year olds from all areas in Switzerland revealed an average DMFT value of 14.5, including 8.6 teeth already filled. Alarmingly, more than two thirds of all the proximal fillings examined radiographically were inadequate and therefore sources of marginal irritation. Dentistry in the future must accordingly concentrate on increased primary prevention and, where restorations are necessary, on placing restorations that will not lead to secondary caries and destructive marginal periodontitis. These goals can be most economically achieved through a team approach where the dentist delegates to his (or her) dental hygienist and specially trained chairside assistant the tasks of radiological and clinical diagnosis of caries and of marginal irritants in order to interfere with the progress of periodontal disease. The dentist, in addition, freed from administrative tasks by electronic data processing, will direct the team, and his practice will, in the future, fall into one of two large areas: preventive dentistry and/or pedodontics of curative gnathology.


[Early detection of pemphigus vulgaris: role of the dentist].

Means to detect pemphigus vulgaris at an early stage are described. Its grave evolution in absence of treatment makes an early diagnosis imperative. The first signs are frequently localized in the oral mucosa and sometimes the disease remains confined to this mucosa only. Efficient and early therapy may favourably influence the course of disease, and the dentist is in a prime position to detect the characteristic lesions.


[Age of onset of diabetes mellitus in relation to caries].

The DMF-Index of 101 children was established, regression analyses were made. It was found: -- that the D3-4MF/S was notably diminished in relation to patients with diabetes lasting a maximum of three years -- that the DMF/S of separately examined children was not reduced in spite of the diet. This may be interpreted as a sign of poor collaboration of the patient during therapy.


[Experimental study of oral hyperactivity caused by mental stress, in particular by aggression].

18 patients without stomatognathic symptoms were examined by three psychological tests (Foto-Hand test, Freiburg personal inventory, and Giessen Test). Aggression had had the strongest effect upon masticatory muscles. Various other effects were studied, like ECG, respiration, pulse, tremor, skin resistance, masseter, biceps and triceps. Because of the visible effect upon the stomatognathic system it is plausible that disease in this organic system is to be expected at an early stage.


A method for analysis of human mandibular occlusal movement.

A new method was developed to produce perspectives and maps of the top of Posselt's envelope of motion, the part that is mainly determined by occlusal tooth contact. Mandibular occlusal gliding movements were recorded in human subjects by optoelectronic tracking of infrared light emitters fixed to the subjects upper and lower teeth. Recordings were made by a commercially available electronic camera system that was extended to meet the special needs. An elaborate computer program was developed to process the information and convert it into graphic plots. Care was taken to make the system easy to use.


[Preventive dentistry, particularly in schools].

Dental caries may easily be prevented. Based on experiences extending over 20 years, several preventive programs for schoolchildren can be offered and the one best suited for the local circumstances may be selected. Two types of dental auxiliaries have proved very useful to realize preventive programs on the level of communities and/or cantons, requiring costs of only Fr. 3.--to 7.-- per year and child. Considering the excellent results already available, it should be possible to obtain cooperation even of those communities who have not yet introduced preventive programs. If salt fluoridation could also be generalized, caries levels could be reduced to a fraction of their initial values.


[Antibiotic therapy in odontogenic infections].

Antibiotic therapy for oral infections is described in the context of the determination of microorganisms involved and the formation of resistance to antibiotics. The indications are shown and in 115 cases the microorganisms responsible for the infection and their resistance are enumerated. It is alarming to know that increasingly multiple resistances to antibiotics are discovered. This increase is particularly observed in Tetracyclin and Trimethoprim-Sulfamethoxazol. Finally antibiotic therapies in oral infections are recommended.


[Relative gnotobiosis: a possibility for studying periodontal diseases in the rat].

An animal model was presented to study periodontal disease in Osborne-Mendel rats with depressed indigenous oral flora. In connection with the inoculation of an erythromycin-resistant strain A. viscosus Ny 1 E after 40 experimental days only the animals showed plaque formation, bleeding from the gingival sulcus upon gentle probing and severe alveolar bone loss. 56% sucrose in the diet counteracted the establishment of A. viscosus Ny 1 E in dental plaques. As a consequence plaque formation, gingival bleeding and bone loss diminished. Plaque formation, gingival bleeding and bone loss were correlated.


[Periodontal treatment requirements, motivation and information levels in a groups of 35-year-old Zurich residents].

A representative sample of 35-year old residents of Zurich was examined with the PTN-system to determine their periodontal treatment needs. 8.8% required no periodontal treatment. An additional 7.0% required only oral hygiene instruction and motivation to restore their gingival health. 37.1% of the sample needed removal of marginal irritants. 47.1% of the sample population had periodontal pockets in two or more quadrants, in need of surgical treatment (curettage, flap surgery). Responses to a questionnaire completed by all participants in the study revealed a strong desire on their part to retain their teeth. However, knowledge of periodontal prophylactic measures and individual oral hygiene was inadequate.


[Determination of serum and saliva concentrations of clindamycin (Dalacin C) and amoxicillin (Clamoxyl)].

The antibiotic therapy of oral infections requires bactericidal concentrations in the oral environment over sufficient time. Comparable determination of antibiotica concentration in the saliva of 8 human volunteers were made after oral application of Amoxycillin and Clindamycin. Only Clindamycin showed inhibitory concentrations.--When pharmacokinetic characteristics and the present status of resistance were considered, Clindamycin is viewed as an antibiotic of choice for oral infections.


[Presentation of a universal face-bow].

A universal face bow is reported for transferring an arbitary or located hinge axis on most articulators. Its use is simple and safe due to the rigidity of the assemblies during every step of the transfer.


[A new modular semi-adaptable articulator].

A new semi-adjustable Arcon articulator is reported. It is an evolutive device that can be set with two different types of condylar housings. - A Type: adjustable condylar guidance, preadjusted Bennett angle at 13 degrees - B Type: adjustable condylar guidance, adjustable Bennett angle. It is possible to set on this B type fossa assembly another Bennett wing with an adjustable immediate side shift This device has a double lock in centric relation and may be set with an arbitrary or localized hinge axis.


[Diagnosis, classification and therapy of cysts in the maxillary sinus region].

Cysts in the vicinity of maxillary sinuses pose special problems. In diagnosing them, it must be considered that pathophysiological processes must be considered common to both. The therapy demands knowledge of the physiology of the same anatomical sector plus considerations pertaining to the later necessary seat of the maxillary prosthesis. Methods of diagnosis and therapy are shown.


[Measurement of the consequences of characteristic occlusal relations of the temporomandibular joint].

The occlusion of the dental arches determines the positioning of the mandible through intercuspidation. This intercuspidal position may force the condyles into a displaced position. Purpose of this paper is to show how to obtain a proper diagnosis of the cranio-mandibular relationship with a new instrument, the mandibular positions indicator.


Experimental secondary caries around amalgam, composite and glass ionomer cement fillings in human teeth.

It was the aim of this in vitro study to examine secondary caries occurring in enamel and dentin adjacent to different filling materials and after different filling methods. The materials used were: amalgam, composite and glass ionomer cement. The highest rate of secondary caries was found on the crown surface as well as root surface of teeth which were conventionally treated with amalgam and composite materials. The preliminary treatment with a copal-ether varnish (Copalite) was of insignificant value. Fluoridation of the cavity walls with a fluoride solution (Elmex-Fluid) resulted a significant cariostatic effect with amalgam- or composite fillings in enamel and in root surfaces. Zones of inhibition of demineralization could be found. The addition of 5% NaF to composite material also produced an inhibition of demineralization, manifesting itself in a reduction of the secondary caries rate and increased percentage of tight margins of the fillings. Although glass ionomer cement has adherent properties to enamel and dentin, a larger percentage of filling-margins, especially of those applied to dentin, were found to be untight. Nevertheless, the demineralizations were not very pronounced and significant zones of inhibition of demineralization were found in the cavity walls and tooth surfaces adjacent to the fillings. The amounts of fluoride released by silicate cement, glass ionomer cement and composites containing 5% NaF were compared. The glass ionomer cement showed higher values than the composite and silicate materials. After 10 days of storage in water, the dosis of fluoride released--by all materials--was 7-20 times less than on the first day.


Polishing effect and abrasion of five toothpastes on dental enamel.

Prepared enamel samples were polished with one of 5 different toothpastes, dulled by acid treatment and repolished with the same toothpaste. The lustre change was measured by reflectometry and the micromorphological aspects of abrasion on enamel were investigated with the scanning electron microscope.


[20 years of fluoridation in the German Democratic Republic].

Caries-statistical data obtained from cross-sectional studies on more than 240,000 individuals having an age range from 3 to 18 years, at Karl-Marx-Stadt (where the drinking water contains 1 p.p.m. of fluoride) and several towns with low levels of fluoride content the repercussions of the caries reduction achieved on the system of organized paedodontic care. Due to further development on a legal basis, 1,3 million inhabitants (13%) of the GDR are at present provided with fluoridated water for caries-protective reasons. It is aimed at serving 50% of the inhabitants by 1990.


[Continung results of the Berlin morbidity study 1972. 4. DMF index, educational status and stomatological health education].

The general educational level and the dental health knowledge are negatively correlated with the DMF index and its M component. They are positively correlated with the number of primarily sound teeth. No correlations could be established between the aforementioned criteria and the D component.


[Fluorescence microscopic studies on the beginning of the mineralization of rat incisors].

Histologic and fluorescence microscopic studies were performed on labelled calcium complexes to determine the beginning of the mineralization of rat incisors. The period of the first indications of tooth mineralization at the end of the 20th day of embryonic life is described in detail, special attention being paid to single hard tissue components.


[Clinical studies for the evaluation of the composite filling material Evicrol].

339 Evicrol fillings were clinically re-examined 0,52 to 2 years after insertion. The comparison of the results obtained with those from silicate cement fillings (Hildisch) evidenced that the properties of Evicrol are better. In assessing Evicrol for a prolonged period, special attention must be paid to the higher percentage (18--33%) of discolourations appearing already within 1--2 years.


[The correlation between color change, swelling and iodine reaction in gingivitis].

The use of an index with separate evaluation of colour change, swelling and iodine reaction (in accordance with a classification into 4 degrees) and separate determination of the P, M and A units corresponds to the conditions in practice and yields reproducible results. Correlations between colour, swelling and iodine reaction could be established which were most marked for colour and iodine reaction.


[The use of alpha-chymotrypsin in traumatology].

Due to its fibrinolytic activity, alpha-chymotrypsin should be applied, even in doses of 5 and 10 mg (as indicated in the List of Drugs) only for postoperative oedema and haematoma prophylaxis, with due regard to the simultaneous effect on haemostasis. The maximum of fibrinolytic activity was observed 6 to 9 hours after intramuscular injection. These findings are consistent with clinical observation. The authors dissuade from uncontrolled use because, in spite of many separate experimental studies and clinical trials, there are still numerous questions that must be considered unsettled.


[Limits and potentials of modern functional diagnosis of chronic arterial insufficiency of the extremities (CAIE)].

A survey is made of the angiologic methods for ChAIE investigations. The role and the potentialities of some of the non-invasive present-day methods are discussed in details, implemented lately in the clinical practice: determination of muscular Xenon 133 clearance, venous obturation pletismography (VOP) and US Doppler flowmetry. VOP is one of the few methods, enabling the quantitative assessment of the functional state of peripheral circulation. US Doppler flowmetry, as a relatively easy to apply and adequate method for wide clinical application and for scientific investigations, gives a valuable diagnostic information about CHAIE and enables the accurate dynamic control of the vascular-reconcstructive and conservative therapy. An original classification system is proposed for the assessment of the potentialities of the various angiologic methods in ChAIE diagnosties.


[Determination of serum vitamin B12 in hematologic diseases].

By means of a test set of the Isocommerz (GDR) determinations of vitamin B12 in the serum were carried out according to the principle of the competitive protein binding. The normal values lie between 200 and 1,000 pg/ml serum. Clearly decreased levels of vitamin B12 are found in the pernicious anaemia, in other megaloblastic anaemias and in disturbances of the resorption after resection of the stomach. Increased values can be stated in the untreated chronic myelosis and in the blast episode. Under Busulphan-therapy a significant decrease of the values of vitamin B12 develops. The method seems to be practically important for the well-timed recognition of deficiency conditions of vitamin B12 in beginning pernicious anaemia, in disturbances of intestinal resorption after resection of the stomach and for the observation of the course of the chronic myelosis.


Fine needle aspiration of ovarian masses. II. Correlative cytologic and histologic study of nonneoplastic cysts and noncelomic epithelial neoplasms.

A wide variety of neoplasms and nonneoplastic cysts involves the ovary. Seventy-seven ovarian masses were aspirated using fine needles. They included 32 nonneoplastic cysts of various types, 29 celomic epithelial neoplasms, 10 germ cell neoplasms and 6 other neoplasms. The study was performed in order to elucidate the cytologic features of aspirates from these lesions and correlate them with the histologic features. Material aspirated from malignant neoplasms resulted in abundantly cellular specimens while aspirates from benign neoplasms and nonneoplastic cysts showed only scanty cells. Follicular cysts and corpus luteum cysts showed similar cell types but with various degrees of cellularity and incidence of cell types. Cysts lined by a single layer of cuboidal cells, such as paraovarian and paratubal cysts, were very similar cytologically. The three types of germ cell neoplasms encountered showed features which were diagnostic of each entity. It was difficult to discriminate between some of the types of the sex cord and mesenchymal neoplasms. Aspiration cytology can achieve a satisfactory classification of ovarian masses. It has a specific role to play especially in young patients, in whom preservation of ovarian function is advisable.


The cytopathology of mesothelioma.

Fifty-seven cases of mesothelioma from the Toronto General Hospital during the period 1965 to 1976 have been reviewed. Pleural effusions or ascites were present in 34 patients. The value of cytologic examination of effusion specimens was assessed, and the criteria for cytologic diagnosis were elucidated. It appears that patients with predominantly fibrous or sarcomatous mesothelioma were not prone to develop pleural effusions or ascites; few tumor cells, if any, from these mesotheliomas were exfoliated into effusions. Cytologic examinations of effusion specimens were positive in 12 of 14 cases of carcinomatous mesothelioma and in three of four cases of undifferentiated mesothelioma. However, only four of seven casee of benign mesothelioma (mostly epithelial type) showed positive results, as did two of four cases of sarcomatous mesothelioma. It appears that cytologic diagnosis of mesothelioma is more useful for the carcinomatous and undifferentiated types. The cytomorphologic features of the various types of mesothelioma are different, and by cytologic examination of effusion specimens, typing of mesothelioma is possible and correlates well with the histologic typing.


The cytology of a giant-cell, osteoclastoma-like malignant thyroid neoplasms. A case report.

The cytologic findings on aspirated material in a rare giant-cell, "osteoclastoma-like," malignant neoplasm of the thyroid are reported.


Sputum cytology of giant cell interstitial pneumonia.

The purpose of this case report is to illustrate the cytologic findings from a patient who had clinical, radiologic and morphologic evidence of giant cell interstitial pneumonia. Of additional interest is the fact that this patient had had histologically proven desquamative interstitial pneumonia approximately seven years prior to his current admission. A discussion of the relationship between these two entities is also presented. Furthermore, it is emphasized that the presence of multinucleated giant cells alone is a nonspecific finding. However, with proper correlation with clinical history, radiology and other pertinent laboratory studies, one can often minimize the differential diagnosis. This case report points out the usefulness of such an approach in arriving at a specific diagnosis.


Needle aspiration of 310 thyroid lesions.

Needle aspirations of benign and malignant epithelial lesions of the thyroid were investigated in 265 patients. An 18-gauge needle connected to a 20-cc glass syringe was used to puncture each tumoral mass. Smears were stained by the Wright-Giemsa method. The material obtained consisted of 180 nontoxic goiters, 18 toxic goiters, 15 cases of thyroiditis and 52 malignant lesions. Aspirations taken from 21 patients (8%) were either blank or contained only blood and insufficient material for diagnosis. Results were correlated with clinical findings and laboratory tests. Biopsies were obtained only in selected patients to establish the final diagnosis. One false positive and one false negative were recorded. Although well-preserved follicular patterns can be seen on the cytologic specimens, the differentiation of thyroid adenoma from early follicular carcinoma based on cytologic criteria only if fraught with many difficulties. Cell density, nuclear structure and presence of nucleoli are sometimes helpful in making the cytologic diagnosis of thyroid carcinoma.


Spectral characteristics of human leukocytes and their relevance to automated cell identification. III. Eosinophils, neutrophils and lymphocytes.

The spectral characteristics of various normal cell types from human blood were examined in respect to an automated, rapid-flow photometric identification system after staining for peroxidase activity. It was found that a plot of light loss against light scatter gave a separation of eosinophils, neutrophils and lymphocytes comparable in accuracy to visual separations. This staining was not useful for the segregation of monocytes and basophils, for which other stains have proven useful in the sytsem under study. It is concluded that automated, rapid-flow photometric identification of blood cell types can produce differential cell counts with good confidence levels.


Basic studies on repair, especially histology, cytology and microspectrophotometry of DNA contents.

We studied epithelial regeneration from its cytologic, histologic and microspectrophotometric aspects. In the squamous region of the uterine cervix, repair cells which have characteristic atypia appear approximately seven days after injury. Thereafter, these repair cells resemble normal squamous cells or metaplastic cells. In the vaginal region, the reparative processes are no different from those in the squamous region of the uterine cervix. Repair cells in the cervical columnar region are most prominent and atypical two weeks after cryosurgery. From the standpoint of clinical cytology, the differential diagnosis of repair cells from malignant cells is possible through follow-up of repeated smears.


Cytologic description of squamous cell papilloma of the respiratory tract.

A patient with squamous cell papilloma of the respiratory tract, reported on herein, provides an opportunity to describe the cytologic and histologic picture associated with this disease. We find both cytologic and histologic similarities between squamous cell papilloma and condyloma accuminatum.


Light and electron microscopic observations of blastomyces dermatitidis in sputum.

Freshly expectorated sputum from a 52-year-old man with extensive pulmonary blastomycosis was examined by light and electron microscopy. Wet preparations of the sputum, stained with 1% aqueous cresyl violet, revealed numerous thick-walled, spherical blastospores and occasional budding forms. Ultrastructurally, the blastospores revealed a double-layered cell wall, the peripheral portion of which consisted of a thick, densely staining lamellar material of variable thickness, suggestive of the glycocalyx of bacterial cells. Mitochrondria and other organelles were easily recognized, but distinct nuclei were not observed. Retraction of the cell membrane and cytoplasmic mass from the cell wall was a common finding. Results of this case study suggest that electron microscopy of sputum may serve as an important adjunct to conventional staining techniques for the presumptive diagnosis of blastomycosis. Similar studies of other fungi in respiratory tract secretions may be helpful in providing more precise morphologic identification.


The proliferative behavior of the human adult mammary epithelium.

Normal, human, resting, breast tissue was cultured in the defined culture medium 199 with and without insulin. DNA synthesis was assessed by use of autoradiography. A labeling index (LI) showed a different sensitivity in terms of DNA synthesis in the three basic segments of the mammary tree: intralobular ductules, terminal ducts and large ducts. The LI increased significantly after six hours in the terminal ducts, both in the basic unenriched 199 medium and in the presence of 1 microgram/ml insulin. Cumulative LIs were representative of the interlobular ducts, the most active part of breast epithelium.


Description of the population and ultrastructure of cells on IUDs.

We looked at the cell population and individual cell ultrastructure in samples from the surfaces of removed IUDs. The women had worn the devices for 48 hours to eight years prior to removal. The layer of cells which covers IUDs two days after insertion was found to consist of macrophages and neutrophils. The macrophages were exceptionally active, but fragments of sperm were observed in their phagosomes only rarely. All observed free sperm were degenerated. The fibrous tissue which was formed on IUDs later contained numerous lymphoid cells.


Diagnostic cytology and electron microscopy of fine needle aspirates of retroperitoneal lymph nodes in the diagnosis of metastatic pelvic neoplasms.

Ten patients with abnormal pelvic lymphangiograms underwent fluoroscopically directed percutaneous fine needle aspiration biopsy of retroperitoneal lymph nodes. In all cases, the primary diagnosis had already been established by biopsy or resection. In nine cases, aspiration cytology was positive for the same cell type identified in the primary neoplasm. In one of these nine cases, electron microscopy was utilized to further study the malignant cells in the aspirate. In the tenth case, the aspirate was negative for tumor, and the patient continues to be followed. Cytologic confirmation of lymphangiographically positive or suggestive nodes is useful in pelvic neoplasms and may obviate exploratory surgery in assessing the extent of disease and aid in planning therapy.


Fine needle aspiration cytology in gynecologic oncology. II. Morphologic aspects.

This study was based on the evaluation of 140 fine-needle spirations from gynecologic lesion. Cytologic criteria for the diagnosis of benign and malignant lesions and cellular changes due to irradiation and chemotherapy are presented. For accurate evaluation of fine-needle aspiration specimens from the pelvis, the exact location of the sampling must be known, clinical data must be available, and the patholgist must have an intimate knowledge of anatomy, histology and pathology of benign and malignant lesions in this area. Fine-needle aspiration cytology provided a high degree of accuracy in the diagnosis of gynecologic lesions.


Cytopathologic presentation of cerebral histiocytosis.

Histiocytoses involving the central nervous system are rare, and those in which the brain and meninges are the the only systems affected are rarer still. This paper presents such a case, in which cytologic study of cerebrospinal fluid during life showed large numbers of abnormal histiocytes and necropsy showed infiltration of brain and meninges by masses of similar cells, without other systems being involved. The cytologic features and differential diagnosis are discussed.


Cytologic changes in the respiratory tract in children smokers.

Cytologic investigation was carried out on sputum of 45 children who were cigarette smokers and in a control group of nonsmoking children matched for age and environment. All but one of the children smokers were able to produce sputa whereas none of the controls could do so. Abnormal columnar cells were frequent, and squamous metaplasia was noted in 15.5% of the 45 patients. Atypical metaplasia was not found. The rate of metaplasia was much lower in children than in adult smokers. It is possible that the respiratory epithelium of children is resistant to the noxious effects of cigarette smoke.


Cytomorphologic and cytochemical aspects of malignant histiocytosis with spindle-cell differentiation. A case report.

Spindle-cell differentiation and tumor formation have been observed rarely in cases of malignant histiocytosis. We describe below one case of malignant histiocytosis with spindle-cell differentiation. Touch preparation of autopsy material revealed cytologic features that correlated with the histologic appearance of atypical components of this entity, such as spindle and nonspindle histiocytes and abundant erythrophagocytosis. Cytochemical properties indicated the histiocytic nature of the cells that composed this tumor. A morphologic account of the different types of cells is presented.


Cytopathologic characteristics of permanent cell lines derived from anaplastic human gliomas.

Five permanent cell lines derived from human gliomas were examined at 24-hour intervals to determine optimal phases of their population growth curves for comparative morphologic studies. In early exponential growth phase, individual cytologic criteria were well displayed, while the increased cellular density of late exponential and plateau phase growth was advantageous for evaluating growth pattern, bizarre multinucleate giant cells and abnormal mitoses. These morphologic characteristics of permanent cell lines derived from human gliomas are potentially useful for correlation with their biologic, immunologic, biochemical and cell biologic parameters.


"Reactions" to standard patch test materials.

Twelve compounds tested by closed patch test at recommended concentrations produced numerous "Fallse positive" non-allergenic reactions in a panel of 100 vollunteers. These results indicate the need for further basic studies to determine appropriate non-irritating concentrations of materials used in biagnostic patch testing for contact allergy.


Lupus erythematosus panniculitis(profoundus).

A 39 year-old man developed on trunk, buttock and thighs scaling, atrophic, erythematous lesions which in some places became infiltrated and ulcerated. The clinical, histopathological and immunlogical picture corresponded with the diagnosis of discoid lupus erythematosus. In sites of infiltrations and necrosis, however, histological features of panniculitis with proliferative and inflammatory changes of deep vessels could be seen. The direct immunofluorescence of uninvolved skin showed deposits of IgM and C3 at the dermal-epidermal junction and within the vessel walls. The patient responded promptly to treatment with chloroquine.


Contact allergy without skin disease.

Patch tests with a standard series were performed in 274 non-dermatologic patients undergoing orthopedic surgery. Allergic reactions were observed in 22%, particularly to nickel (7%) and balsam of Peru (5%). Contact allergy in patients without previous or present skin disease was observed in 9%. A certain frequency of contact allergy in the general population should be held in mind when considering the incidence in patients with skin disease.


Intradermal test in contact allergy to metals.

Variations of intradermal test results were studied in a group of patients with clinically evident contact dermatitis and with the history suggestive of contact with metals and with negative patch tests reactions to the latter. The positive reactions obtained in several cases indicate that intradermal tests may reveal specific sensitivities, which patch tests using standard concentrations are not always capable of demonstrating.


Irritation and staining by dithranol (anthralin) and related compounds: I. Estimation with chamber testing and contact thermography.

Irritation and staining by dithranol and some related compounds was studied with the chamber-testing technique in a series of 62 psoriasis patients. Suitable to routine testing of the individual tolerance to dithranol is the use of 0.05 and 0.5 per cent concentrations in petrolatum, exposure of the mid-back skin for 24 hours, and reading of the reactions (erythema, brown staining, edema) on the second day after the application. Contact themography was used when the brown stain hampered the extimation of erythema. Low concentrations of 10 acetyldithranol elicited weaker reactions than dithranol but at the 0.5 per cent level the acetylderivative tended to give stronger reactions than the parent compound. Ten per cent dithranol triacetate caused only occasionally slight erythematous reactions, whereas 10,10'-bis-(formylethyl) dithranol and dithranol anthraquinone elicited no reactions at all. The mechanisms of the staining and inflammatory reactions and possibilities of their reduction are discussed. The use of the chamber-testing technique is recommended to screening of new less irritating and staining hydroxyanthrones for clinical trial.


On erythema annulare centrifugum-type of psoriasis.

A case of EAC type psoriasis is reported. Routine and immunologic investigations were negative. HLA-B8 was found by typing. Some therapeutic benefit was achieved by combination of retinoid (Ro-10-9359) plus PUVA. According to a review of the literature half of the cases are unconnected to classical psoriasis, whereas the other half is connected and mostly of (periodic) pustular character. The necessity of clinical research in this intermediate type between psoriasis vulgaris and pustulosa is emphasized.


Subcorneal pustular dermatosis: a variant of pustular psoriasis.

A patient with clinical lesions typical of subcorneal pustular dermatosis of Sneddon and Wilkinson also had stigmata of psoriasis, namely psoriatic plaques, pitting of nails, and psoriatic arthritis. Histologic studies of the pustular lesions were consonant with pustular psoriasis. Correlating the phenomena of previously reported cases of subcorneal pustular dermatosis with those of our patient, we conclude that subcorneal pustular dermatosis of Sneddon and Wilkinson is but another variant of psoriasis.


Caterpillar dermatitis of the palm associated with osteitis of finger bones.

A 3-year-old boy during a picnic collected caterpillars of Macrothylasia rubi. He developed dermatitis and was generally ill during some days. Edema developed on the affected hand and reduced the mobility. Osteitis developed corresponding to all falangeal bones on his right hand. The changes disappeared following immobilisation of the severely affected hand.


The cause of striae distensae.

Striae are always initiated by stretch whether the stretch is excessive or minimal: spontaneous striae do not occur. Cross-linkage of collagen appears to be more important than amount of collagen in permitting striae in response to stretch. An increase in cross linkage as in age increases the resistance to stretch deformation, but this rigidity leads ultimately to tearing of the skin and not striae. At the other extreme, the absence of crosslinkage leads to "elasticity" and excessive stretching with eventual rupture of the skin if the stretch goes beyond the elastic limit, but again, no striae. Striae appear to occur therefore only in skin in which the rigid cross-linked collagen and "elastic" unlinked collagen thus permitting a limited degree of stretch and a limited intradermal rupture, i.e. striae. (Although rigidity and elasticity are presented here in terms of collagen cross-linkage it seems probable that changes in interfibrillary materials such as glycosaminoglycans will prove important in this respect). This balance of stretch and limited tear is a continuous process and is an adaptation to the needs of growth in adolescence and change in body mass in early adult life and there are many many subclinical "striae" for each gross tear which is recognised clinically. An important factor likewise appears to be rate of stretch since if it is very slow, striae are less likely; there is "give" and new collagen formation. Although this working hypothesis is consonant with the facts only further work will show whether this smooth consonance is that of the fable or the weathered rock of fact.


The presentation of psychiatric illness to the dermatologist.

An account is given of the manner in which patients suffering from psychoneurosis and psychoses present to the Dermatologist. Cases of monosymptomatic hypochondriasis, trichorrhexis nodosa in an obsessional neurotic, acne excoriée, schizophrenia, depression and delusions of infestation are described. The value of modern neuroleptic drugs in the management of monosymptomatic hypochondriasis in cluding delusions of infestation is confirmed.


An outbreak of periporitis staphylogenes of complex origin.

During the summer 1971 an outbreak of periporitis staphylogenes occurred among newborn in Horsens Hospital. 23 babies (16 boys and 7 girls) were infected with Staphylococcus aureus resistant to penicillin. Some of them also developed pemphigus neonatorum and sweat gland abscesses. Phage typing of staphylococci from the infected babies indicated, that some had acquired bacteria from the hand-eczema of a midwife and others from a doctor carrying Staphylococcus aureus, in his nose.


Confluent and reticulated papillomatosis (Gougerot-Carteaud).

Seven cases, one female and six males with confluent and reticulated papillomatosis are presented. Age range was 13-25 years and the skin disease had lasted for 6 months to 3 years. Initially, acanthosis nigricans was suspected in all cases as the skin histology was compatible with that diagnosis. Pityrosporum orbiculare was cultured in 4 cases, but treatment with selenium sulfide and miconazole was unsuccessfull. No endocrinological abnormities were revealed. Only associated feature was a marked xeroderma. The importance of the awareness of the disease is stressed.


Changes in disease pattern in a skin clinic 1947 to 1977.

The changes in disease pattern in a Danish skin clinic during the period 1947 to 1977 is reported. The data rest upon comparisons from patient registrations taken with ten years interval. The study also comprises comparison of frequencies of positive patch tests between 1947 and 1977. The data show, that the disease pattern was far from stable. An increased frequency was registered in atopic dermatitis, allergic contact dermatitis, drug eruptions, urticaria, skin cancer, psoriasis and viral diseases. While reductions were found in all other infectious diseases, seborrheic dermatitis, and so called "non classified eczema". The changes are postulated to be of a multifactorial origine. Environment was supposed to be the main factor in regard to contact dermatitis and some infections and to be of great importance to skin cancer, while better therapeutic posibilities seem to have influenced the frequency of most of the remaining disease groups. Pronounced changes were also registered among the ten most commonly detected contact allergens. It is stated that preventive measures are extremely important within this area. The decrease in contact allergy to balsam of Peru is used as an example of the effects of good preventive medicine.


Human labia majora skin: transepidermal water loss in vivo.

Transepidermal water (TEW) loss of normal vulvar and flexor forearm skin was measured in 12 subjects. A significantly elevated vulvar TEW loss was demonstrated. Depsite subcutaneous administration of atropine in seven subjects to eliminate eccrine sweating, no alteration in the elevated TEW loss was found. A significant anatomic and/or physiologic uniqueness of vulvar skin is demonstrated and warrants further investigation.


Disseminated superficial porokeratosis in patients with pemphigus vulgaris treated with steroids.

In two patients with pemphigus vulgaris a rash identical with that seen in disseminated superficial porokeratosis developed on the trunk and extremities during periods in which they were receiving relatively high doses of steroids. Some time after reduction of the daily dose or discontinuance of treatment this rash disappeared. In one patient, however, this rash subsequently recurred twice, both times after reinstitution of treatment because of the reappearance of pemphigus lesions. It is suggested that disseminated superficial porokeratosis should be added to the list of possible skin eruptions developing as the result of the systemic use of corticosteroids at a high dose for a prolonged period of time, although the mechanism of its appearance in these cases is not yet clear.


Erythroplakic lesions in relation to oral lichen planus.

In a cohort of 740 referred patients with oral lichen planus eight patients were found with a sharply demarcated slightly depressed erythroplakic area. The histological examination of the biopsies from the erythroplakic lesion of the 8 patients showed seven with epithelial dysplasia. In addition, two of the lesions revealed a squamous cell carcinoma. In the erythroplakic lesion without dysplasia the histological picture was found to be characteristic of lichen planus. All eight patients were seen at later follow-up examinations (median observation period: 3.6 years) and in one patient a squamous cell carcinoma arose in the erythroplakic lesion during the control period. It is concluded that the reported erythroplakic lesions in relation to oral lichen planus seem to be premalignant and they should  be followed and/or treated like oral erythroplakias.


Public health aspects of cancer deaths.

In 1976, the toll of cancer in Denmark (5 million inhabitants) was 12,481 deaths, or 23% of deaths from all causes. Seven manifestations accounted for more than half of the cancer deaths, namely lung (19%), breast (9%), stomach (7%), colon (9%), rectum (5%), pancreas (6%) and prostate (5%). The median age of the cancer patients was 70 years, ranging from 65 years for breast cancer patients to 75 years for those with prostate cancer. Cancer caused a reduction in the patients' normal life-span; it totalled 182,486 years for all the dead patients, 37% of which were in productive age. The future caseload was projected from the time trend for the years 1968-76. During the following five years an annual increase by 200 deaths is expected. The trend differs between the seven major manifestations, since some will increase and others will stabilize or decrease. When case reports are combined with mortality data, survival tables can be produced. Follow-up surveys of the patient's health, combined with modern data processing, can produce a detailed description of the impact of cancer on the patient's life. These health tables, which illustrate the natural history of the disease, can also be used to assess new therapeutic regimens.


Eczemas due to plant allergens in manufactured products.

Intolerance to plant allergens in manufactured products is widespread. Results of epidemiological investigations in STRASBOURG are given. The rate of allergy to sesquiterpenic lactones has fallen since 1974, due to the fact that the use of an ointment containing these lactones has decreased. Disguised forms of allergens are reviewed, for instance limonene of Niaouli oil (Biogaze), colophony of "hypoallergenic" tapes or of testing material. Chemical investigations are useful in prevention and in allergological control of medicaments.


Is the stratum corneum of uninvolved psoriatic skin abnormal?

A variety of abnormalities of the uninvolved skin have been reported in psoriasis, but there are few studies in which abnormalities of the stratum corneum (SC) have been investigated. In this study we have examined the intracorneal cohesion and structural detail of corneocytes of the SC from involved and uninvolved sites in 24 patients with psoriasis and 10 controls. We have found that intracorneal cohesion is increased in the involved and uninvolved skin of psoriatic patients compared to controls and that there are abnormalities of stratum corneum and corneocyte structure as determined by scanning electron microscopy. The changes in the uninvolved sites may well be due to the increased rate of epidermal cell production in these areas.


Anti-androgen TSAA-291. VII. On the mechanism of anti-androgenic action of 16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one (TSAA-291).

The mechanism of anti-androgenic action of a steroidal compound, TSAA-291, was summarized and discussed in reference to its drug-designing and structure-activity relationship. The target of the drug-design was to obtain a substance which is inactive in androgenic activity and is capable of antagonistically competing with androgen for the receptor. With this intention, the androgen molecule was rendered with a steric hindrance influencing upon the functional 17 beta-hydroxy group. Introduction of a bulky group at the steroidal position-13 or -16 led to anti-androgenic properties. Intense steric hindrance by introducing an enormously bulky group or complete elimination of the 17 beta-hydroxy group rather decreased the anti-androgenic activity. Of these anti-androgens thus synthesized, TSAA-291 proved to be the most active in the anti-androgen assay and also antagonistic against the uptake of [3H]testosterone by the rat ventral prostate.


Anti-androgen TSAA-291. II. Manifestation of the anti-androgenic action of a steroid ester TSAA-330 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one caproate) and elucidation of its long-lasting mechanism using a simple steroid determination technique.

Using a simple steroid determination technique, in situ steroid absorption from a subcutaneously injected sesame oil solution in rats was pursued following the time-course changes in the steroid concentration. Based on the knowledge thus obtained, the anti-androgenic effect of a steroidal compound, TSAA-330, could be manifested in the subcutaneous route. (1) Anti-androgenic steroid TSAA-291 and its esters in the subcutaneously injected sesame oil solution were selectively absorbed into the general circulation at different rates according to their chemical nature and structures, while the oil itself remained at the injected site for a considerably long period. At the injected site where subcutaneous doses of steroids molar equivalent to 50 mg of TSAA-291 were administered in 5 ml/rat of sesame oil, TSAA-291 decreased to the level of 10% of the initial concentration on the 4th day. TSAA-328 decreased slowly to the 50% and 20% levels on the 7th and 21st day, respectively. TSAA-335 decreased more slowly to the 50% level on the 14th day. TSAA-330 decreased most slowly only to the 70% level on the 49th day. (2) A single subcutaneous administration of 200 mg of TSAA-330 suppressed the weight increase of the accessory sex organs caused by a single subcutaneous injection of testosterone caproate (10 mg) in the immature orchiectomized rat. The suppressive effect was obvious from 2 weeks after the administration, and seemed to last for more than two weeks. The levator ani weight was not affected by the administration of TSAA-330. (3) Dose-dependent inhibitions of the accessory sex organs were obtained three weeks after a single subcutaneous administration of 50 to 400 mg of TSAA-330 in the adult male rat. (4) Daily oral administrations of 50 mg of TSAA-291 or TSAA-330 to the adult male rat for 8 days resulted in depression of the accessory sex organs to almost the same extent obtained with either agent. One week after the last administration, however, the weight of the accessory sex organs of the TSAA-291-administered animals recovered to almost the comparable level with the control, whereas a significant after-effect of the inhibition was still evident in the TSAA-330-administered animals.


Anti-androgen TSAA-291. III. Hormonal spectra of anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives.

For the purpose of obtaining hormonal spectra of anti-androgen TSAA-291 and its derivatives, a variety of endocrine characteristics were studied. (1) Androgenic and anabolic activity : Subcutaneous administration of anti-androgen TSAA-291 and its acetate, TSAA-328, to the immature orchiectomized rat resulted in significant weight increase of the levator ani but in only a nominal response of seminal vesicles and prostates even at a large daily dose of 9.6 mg. The resultant anabolic/androgenic ratio was estimated to be extremely high. (2) Oestrogenic activity : Uterine weight in response to these anti-androgens were sluggishly dose-dependent, and the maximal plateau response remained considerably lower than that induced by oestradiol-17 beta. The oestrogenic activity of these anti-androgens was estimated to be 1/200 000 or less as that of oestradiol-17 beta. A single subcutaneous dose of 100 mg of TSAA-291 or its caproate, TSAA-330, did not induce the vaginal cornification in the adult ovariectomized rat. (3) Anti-oestrogenic activity : Antagonistic effect of these anti-androgenic compounds on the uterine weight response to oestradiol-17 beta was found in the immature ovariectomized rat. A single subcutaneous dose of 100 mg of TSAA-291 or TSAA-330 also induced the antagonism against the cornification caused by daily treatments with 1 microgram oestrone in the adult ovariectomized rat. (4) Progestational activity : These anti-androgenic compounds proved to be less active than progesterone in the McPhail's test. (5) Anti-inflammatory activity : Daily subcutaneous dose of 20 mg of TSAA-291 for 6 days did not significantly depress the weight of granuloma developed around the cotton-pellet implanted in the young male rat. TSAA-291 did not affect the anti-inflammatory action of 1/6 mg of prednisolone phosphate. Combination of both agents seemed to be effective in enhancing the anti-androgenic action of TSAA-291, whereas prednisolone phosphate alone rather increased the weight of the accessory sex organs. (6) Liver glycogen deposition activity : Daily intramuscular doses up to 38.4 mg of TSAA-291 for 5 days did not increase the liver glycogen level in the adrenalectomized rat.


Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins.

Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied. (1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular administrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.


Anti-androgen TSAA-291. V. Effects of the anti-androgen TSAA-291 on the androgen-receptor complex formation from [3H]testosterone in rat ventral prostates.

Intramuscular administration of a new steroidal anti-androgen, TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one), in doses of 0.05, 0.5 and 5 mg/kg body weight reduced the in vivo uptake of [3H]testosterone by the ventral prostate of castrated rats of 78, 59 and 37% of the control level, respectively. Analysis on subcellular fractions of the prostate by gel-filtration and sucrose density-gradient centrifugation followed by thin layer chromatographic identification of testosterone metabolites revealed that 5 alpha-dihydrotestosterone (5 alpha-DHT) which was found to be largely bound to macromolecules in the cytosol and nucleus was the predominant metabolite even in the presence of the anti-androgen, and radioactivities corresponding to the 5 alpha-DHT-macromolecular complexes were decreased by the anti-androgen. TSAA-291 also inhibited the in vitro formation of the 5 alpha-DHT-macromolecular complexes in both cytosol and nucleus from minced prostates incubated with [3H]testosterone. The importance of the findings is discussed in connection with the mode of anti-androgenic action of TSAA-291 in terms of the interaction with the androgen receptor.


Anti-androgen TSAA-291. VI. Effects of the anti-androgen TSAA-291 and its related compounds on the in vitro formation of 5 alpha-DHT-receptor complex in the cytosol of rat ventral prostates.

Inhibitory effect of a synthetic steroidal anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the in vitro formation of 5 alpha-dihydrotestosterone(5 alpha-DHT)-receptor complex was examined. An aliquot of the cytosol from rat ventral prostates was incubated with [3H]5 alpha-DHT in the presence of various amounts of the anti-androgen. By means of dextran-coated charcoal assay and sucrose density-gradient centrifugation analysis, TSAA-291 was demonstrated to inhibit directly, in a competitive manner, the binding of 5 alpha-DHT to a component analogous in its properties to the cytosol androgen receptor. Further, displacing study using a variety of TSAA-291 analogues was undertaken to examine which of the functional groups of TSAA-291 is important for the affinity to the 5 alpha-DHT binding component, and elucidated that 3-hydroxy or 5 alpha-dihydro derivatives of TSAA-291 and others having axial methyl group at C-10 were less potent competitors for [3H]5 alpha-DHT binding than TSAA-291. Furthermore, using other steroids including androgens and anti-androgens, considerable knowledge was obtained about structural requirements for a steroid molecule to displace the bound [3H]5 alpha-DHT, and this displacing activity of the steroids was discussed in terms of their anti-androgenic activity.


Ovulation inhibition with a combined oral contraceptive containing 20 micrograms ethinyl estradiol and 250 micrograms levonorgestrel. Serum levels of the active ingredients and FSH, LH, estradiol 17-beta and progesterone.

In order to investigate the possible ovulation inhibitory effect of a new oral contraceptive containing a combination of 20 micrograms ethinyl estradiol and 250 micrograms levonorgestrel peripheral serum from five healthy women between 17 and 24 years were analysed for FSH, LH, estradiol 17-beta and progesterone. The measurements were carried out during a control cycle before the treatment, during two treatment cycles and during a subsequent control cycle. In addition, serum levels of ethinyl estradiol and norgestrel were determined during the treatment periods. Radioimmunological methods were utilized for all the measurements. In all five women studied there was a complete inhibition of ovulation during treatment as indicated by a lack of mid-cycle LH peaks and by suppression of normal luteal phase levels of progesterone. Four out of the five women showed no biphasic estradiol pattern. During treatment the serum levels of levonorgestrel varied between 1 and 10 nmol/l while the levels of ethinyl estradiol usually were below the limit of detection for the method used (below 85 pmol/l). Post-treatment control cycles revealed a re-establishment of the ovulatory pattern in four of the five subjects.


Plasma levels of active ingredients after single and repeated administration of a new oral contraceptive containing 2 mg of cyproterone acetate and 50 micrograms of ethinyl estradiol (DIANE) to five young women.

Peripheral plasma from five young women was analyzed for cyproterone acetate and ethinyl estradiol during a period of 96 hours duration after single oral intake of a coated tablet of DIANE (2 mg of cyproterone acetate + 50 micrograms of ethinyl estradiol), and during a treatment cycle of 21 days during which the formulation was given daily. Radioimmunoassays were utilized for quantifications. A maximum concentration of 11.0 +/- 3.4 ng of cyproterone acetate/ml plasma was found 1.6 +/- 0.6 hours after a single administration of DIANE. Postmaximal disposition took place in two phases with half-lives of 1.9 +/- 0.6 hours and 2.2 +/- 0.2 days. The maximum level of 0.08 +/- 0.03 ng of ethinyl estradiol/ml plasma was found 1.6 +/- 0.6 hours after such single administration. Following commencement of a daily oral intake of DIANE a steady state was reached by the 5th to 8th days, during which 24 hours after each dose cyproterone acetate concentrations were found to be 2.4 +/- 0.7 times higher than at the corresponding time after a single administration. Accordingly, after the first third of the 21 day treatment cycle an almost constant plasma level was reached indicating an equilibrium of intake and elimination. Except for a change in the mean terminal half life after multiple dosing, there was evidently no change in the kinetics of cyproterone acetate. No pointers to an accumulation of ethinyl estradiol upon daily administration of DIANE could be found.


Adjustments of circulation including blood pressure to orthostatic reaction and physical exercise during application of a low estrogen dose steroid oral contraceptive.

The orthostatic circulatory reaction, the physical working capacity on a bicycle ergometer, the blood pressure reactions at rest both during and after the ergometer test, the total hemoglobin content and the heart volume in the supine position were all determined on four separate occasions in 34 nulligravidae who were taking a low estrogen dose steroid oral contraceptive consisting of 30 micrograms of ethinyl estradiol and 150 micrograms of levonorgestrel (known as Neovletta, Schering AG). These examinations were performed once prior to the commencement of this medication, and 6, 12 and 24 months thereafter. The orthostatic pulse and blood pressure reactions taken on these subjects standing upright for a period of eight minutes were pronounced up to and including the 12 month control, but decreased thereafter. Physical working capacity at a pulse rate of 170 beats per minute on the different test occasions decreased up to and including the 12 month control, but thereafter seemed to increase almost to their initial levels. Blood pressure, heart volume and total amount of hemoglobin increased up to and including the 12 month control but thereafter seemed to return to the pre-treatment level. These circulatory changes during the first year of the application of this contraceptive may be as the result of a marked sympathicotonic reaction induced by the steroids. Possibly because of some form of adaptive mechanism, this reaction seems to decrease (and almost to "normalize") during the second year of use.


Demographic techniques in describing contraceptive use applied on the situation in Sweden.

The authors suggest expressing the amount of use of contraceptives in a female population in the same terms as used to denote the occurrence of births, with one year of contraceptive use regarded as an event in the same sense as a birth. If the prevalence of contraceptives in a population can be expressed in the same terms as other events associated with reproduction, such as births and abortions, it may help to clarify the relationships between these events. Applying the method used to calculate the total fertility and abortion rates on the use of oral contraceptives and intrauterine devices in Sweden in 1975, they noted 1.8 deliveries, 0.6 legal abortions and seven years' use of oral contraceptives and six years' use of intrauterine device per women.


The role of hormones in the etiology of breast and endometrial cancer.

Despite many years of extensive investigation, there has been neither a clear-cut pattern of hormonal production nor milieu found in women with breast cancer. Estrogen replacement therapy for menopause does not significantly increase the risk of breast cancer and one study indicated that estrogen users have a lower incidence of breast cancer than that observed in untreated women. Some studies have shown that the mortality rate from breast cancer is lower in estrogen-treated postmenopausal women. Only one investigator has found any significantly increased risk of breast cancer in oral contraceptive users. In that report, increased duration of birth control pill use decreased the risk of breast carcinoma. Several studies were unable to find an increased risk of breast cancer from oral contraceptives while one investigation observed a lower incidence in birth control pill users than that expected. The mortality from carcinoma of the breast in oral contraceptive users was lower than in non-users, most likely due to earlier detection. Although some retrospective studies have indicated that estrogen use increases the risk of endometrial cancer, a prospective investigation found only an insignificant increase. Progestogens afford some protection from cancer in estrogen-treated postmenopausal women. The incidence of endometrial adenocarcinoma is lower than that observed in untreated postmenopausal women. Combination oral contraceptives are protective against developing adenocarcinoma of the endometrium but sequential birth control pills may afford less protection.


The occurrence of taste buds in the palate of human adults as evidenced by light microscopy.

There is some uncertainty in the literature as to the existence of taste buds in the palate of the human adult. In those histologic studies in which the ages of the individuals have been reported, taste buds have not been found in the palates of adults, but have been found in fetuses or newborn. However, clinical studies have demonstrated taste perception in the palate of the human adult. Thus, the aim of the present study was to attempt to find taste buds in the human palate in subjects of different ages. In serial sections of selected areas of the palatal mucosa from autopsy material from individuals 0--80 years of age no taste buds could be demonstrated. However, in four of seven subjects aged 25--44 years, one or two taste buds were found in biopsies from areas of the soft palate where taste perception had been demonstrated clinically just prior to excision. Thus the present study indicates that scattered taste buds exist also in the soft palate of human adults.


The use of dental services in a population in Northern Norway.

The utilization of dental services was studied by means of records from dentist's files, a method which permits gathering of detailed information with high reliability and validity. 53% of the adult population of 358 persons living in a coastal community in Northern Norway had visited a dentist during a period of two years. In the group of 13% who were considered to be regular treatment attenders, number of teeth, sex and socio-economical status were the most influential predictors of utilization. Among the 182 persons with 10 or more remaining teeth, 59% had made preventive and restorative dental visits, and in this group there was a dominating proportion of women, young people and people with high income and/or social class. In contrast, only six persons out of 61 with one to nine remaining teeth had made such visits. People in social class 3 were overrepresented among the 26% of the population who visited a dentist because of extractions or complete denture services. The treatment profile according to age showed that younger people used most of their treatment time on consultations, preventive measures and conservative treatments, while fixed and removable prosthetics constituted a major part of the treatment time among elderly people.


Oral health status in a population in Northern Norway.

Information concerning oral health status was obtained through a clinical and radiographic examination of 297 persons aged 20--69 years out of a population of 358 persons living in a coastal community in Northern Norway. The oral health was generally poor. 71% had one or more remaining teeth and the dentulous persons had a mean number of 18 remaining teeth. The mean number of DMF teeth was 27,3 while the mean number of decayed teeth was 4,9 and filled teeth 12,0 giving a percent of decayed and filled teeth of 27 and 65 respectively. Only every fourth dentulous person had one or more crowns and/or bridge units and 4% of all teeth had been treated endodontically. 41% of the teeth had visible plaque and 56% of the teeth had one or more gingival margins bleeding after gentle probing. One fourth of all teeth had gingival pockets exceeding 3 mm and 17% of all teeth showed a bone loss of 20% or more. The number of remaining teeth decreased with increasing age and decreasing income and/or social class. In general, women, young people and people with a high socioeconomic status had less caries, better oral hygiene and periodontal condition and had received more restorative dental care than the remaining part of the population.


Methods for evaluation of working and setting times of periodontal dressings.

Three different methods were used to determine working and setting times of periodontal dressings. The Gillmore needle and the rheometer employed were not suitable for recording setting reactions. A penetration test was found applicable for determination of working and setting times for all three dressings although they exhibited different setting characteristics.


Transplantable osteosarcoma in mice. Structural characterization of a transplantable osteosarcoma obtained in an allogenic system.

Light microscopic, histochemical and ultrastructural studies of a transplantable mouse osteosarcoma were carried out. The osteosarcoma grew in CBA mice after injection of cultured cells derived from a Dunn osteosarcoma. The tumour differed from the original Dunn osteosarcoma with respect to metastatic potential and structural features. The transplantable tumour was an anaplastic, richly vascularized fibroblastic osteosarcoma with alkaline phosphatase activity and rather sparse osteoid formation, resulting in death of the animals within 6 to 8 weeks. Virus particles were found intracellularly, mainly localized to cisterns of rough endoplasmic reticulum, and extracellularly often close to plasma membranes and collagen fibres. Sign suggestive of formation of collagen fibres by tumour cells were observed. A possible viral influence upon the tumour was suggested also by its growth behaviour in vitro. The results indicate that this new transplantable tumour, obtained in an allogenic system, represents a clonal derivative of the original Dunn osteosarcoma.


Insulin and glucagon secretion in hepatic glycogenoses.

Insulin and glucagon secretion was investigated in ten patients with hepatic glycogenosis, types I and III, in order to understand the relationship between hypoglycemia and pancreatic function. In all patients, both oral glucose tolerance and intravenous arginine infusion tests revealed hypoinsulinemia. Decreased urinary C-peptide levels with standard food intake also supported hypofunction of pancreatic beta cells. On the contrary, the normal secretion pattern of glucagon in both types indicated in the arginine loading test, intact alpha cells in the pancreas. Persistent hypoinsulinism, which is apparently an adaptation to hypoglycemia, could be an important cause of nutritional dwarfism in both types of glycogenosis. The usefulness of the measurement of urinary C-peptide, which evaluates the pancreatic function and provides management for normal body growth, is discussed.


Renal tubular acidosis associated with type III glycogenosis.

Two children who presented with severe failure to thrive were found to have Type III glycogen storage disease. They both also had defects of tubular acidification, an association not previously described. The nature of the tubular lesion is characterized and the explanation and therapeutic implications are discussed.


Variated serum gastrin concentration: trophic effects on the gastrointestinal tract of the rat.

Gastrin is thought to be a trophic agent for the digestive tract and the pancreas. This concept was studied on rats subjected to various operations designed to create hyper- or hypo-gastrinemia. Elevated serum gastrin concentration resulted from vagal denervation, antrum exclusion and fundectomy. Reduced serum gastrin concentration resulted from antrectomy. Antrum exclusion but not vagotomy increased the weight and height of the oxyntic mucosa; antrectomy had the opposite effects. There were no trophic changes in the small and large bowel or pancreas, attributable to the serum gastrin concentration. In the bypassed duodenum (following antrum exclusion or antrectomy B II) the villus height was greatly lowered suggesting that in this location the passage of food acts as a trophic stimulant. Our results show that endogenous gastrin exerts a trophic effect on the oxyntic mucosa; there was no evidence for a similar effect on the extragastric gut and pancreas.


Effect of prolonged in vivo administration of leukocyte interferon on the mitogen responsiveness of human lymphocytes.

Peripheral lymphocytes from patients with osteosarcoma receiving interferon (IF) as adjuvant therapy were tested in vitro for response to various mitogens. Prolonged parenteral administration of IF preparations caused no major change of the mitogen responses. The ability of IF, when added in vitro, to inhibit lymphocyte response to mitogens was not altered to any major extent by in vivo administration of IF.


Penicillamine in the treatment of pulmonary fibrosis.

On the basis of theoretical considerations and the results of other authors we share the opinion of CEGLA that an early combined therapy of corticoids and D-penicillamine is the preferred therapy for pulmonary fibrosis. After subsidence of the exudative stages of pulmonary fibrosis the glucocorticoids should be, in our opinion, gradually reduced, so that a D-penicillamine therapy of a smaller dosage can also be efficient. However, a measurable therapeutical effect can only be objectively determined after a longer period of administration (approximately one year).


Proliferative lesion of arthritis: a target for therapy?

The term proliferative lesion refers to the increase in the amount of connective tissue and in the number of small blood vessels and mesenchymal cells with both phagocytic and synthetic functions, characterizing the rheumatoid synovium. This type of lesion is probably responsible for most of the joint destruction and synovial tissue fibrosis seen in this disease. In vitro data indicate that not only factors inducing bone resorption, for instance osteoclast activating factor and prostoglandins, but also connective tissue-degrading enzymes, can be produced locally in the joint, which suggests that these factors play a role in the destruction of articular structures. D-Penicillamine suppresses the immuno-inflammatory process of rheumatoid arthritis, which indirectly may lead to a depression of the stimuli perpetuating the proliferative lesion. As yet, there are no unequivocal clinical data indicating that D-Penicillamine has a direct suppressive effect on the proliferative lesion.


Prostaglandins and granuloma formation in vivo.

The formation of granuloma tissue is one of the major characteristics of chronic inflammation. Infiltration of phagocytic cells (a major source of prostaglandins) and in many cases (including rheumatoid arthritis) lymphocytes, is one of the earliest events in granuloma formation. Prostaglandins (PGs) may modulate the infiltration of some or all of these cells, though much in-vivo data is lacking. Additionally, PGs may modulate the release of the products of these inflammatory cells, which contribute to granuloma formation. Once granulomatous tissue becomes established, PGs may also control the growth of the granuloma through actions on proliferating cells and connective tissue constituents. In-vivo data suggest that the anti-granuloma actions may be mediated by cyclic AMP. While prevention of endogenous PG production by anti-inflammatory drugs has little beneficial effect on preexisting granuloma, facilitation or mimickry of the anti-granuloma actions of PGs may be a possible line for future therapy of diseases such as rheumatoid arthritis.


Prostaglandins and the side effects of anti-inflammatory drugs--the kidney.

The most important renal side effect of non-steroidal anti-inflammatory therapy in man is analgesic nephropathy. One possible mechanism for this effect is inhibition of renal prostaglandin synthesis. However, an understanding of the regional biosynthesis of renal prostaglandins, of their pharmacological, physiological and pathological properties in the kidney and an understanding of the consequences of their inhibition by drugs is required in order to assess whether such a mechanism is involved. These aspects are reviewed, using much of the early work of the author as a basis for the discussion. The following conclusions can be drawn form a review of published work. "The consequences of the inhbiition of renal prostaglandin synthesis do not seem to bear much relationship to the renal side effects of anti-inflammatory therapy in man". It is further suggested that impaired renomedullary blood flow arising from decreased renomedullary PGE2 synthesis results in increased accumulation of drug in the renal medulla leading to direct toxic damage. Finally, examples of diseases associated with increased or decreased renal PGE2 synthesis are discussed and some examples of drug interactions are presented.


Plasma levels of immunoreactive 15-keto-13,14-dihydro-thromboxane B2 in guinea pigs during anaphylaxis and after histamine injection.

A sensitive radioimmunoassay for 15-keto13,14-dihydro-thromboxane B2 was developed using a monovalent iodinated tracer. The radioimmunoassay was used to determine levels of 15-keto-13, 14-dihydro-thromboxane B2 in guinea pig plasma after injection of histamine and during anaphylactic shock.


Effects of prostaglandins on peripheral nociceptors in acute inflammation.

The effects of different prostaglandins were determined on (a) the hyperalgesia produced by subplantar injections of yeast given into the hind paws of weanling rats, and (b) the reflex vasopressor responses to bradykinin (BK) injected dose-arterially into the spleen of anaesthetised cats and dogs. In the rat prostaglandins (E1 greater than E2 greater than F2 alpha = F2 beta=A2=D2=I2O) injected into the same paw either with the yeast or 25 min later reduced the latency to the onset of hyperalgesia. In the cat and dog prostaglandins (E1 greater than E2 greater than F2 alpha greater than or equal to F2 beta greater than A1=A2=O) potentiated vasopressor responses to BK and reversed the inhibition of BK responses by indomethacin. It is likely that prostaglandins sensitize peripheral nociceptors through a specific prostaglandin receptor.


[H.R.P.-System 2000: a new universally applicable ventilation system for single or limited multiple use with high bacteriologic-hygienical safety (author's transl)].

A new bacteriologically safe system for artificial respiration, H.R.P.-System 2000, is presented. Only two different SETS for artificial respiration of prematures, newborns and infants (P.N.J.) and adults, children and todlers (A.T.) are necessary. They can be adapted very easily on different types of respirators. Besides the tubing and expiratory valve the H.R.P.-SETS include a highly efficient electronically controlled humidifier working on the principle of gas bubbling through a heated water bath, a special tracheal tube adapter with an automatic water exhaust and flexible gas-reservoir for manual ventilation as well as C.P.A.P. or I.M.V. therapy. The H.R.P.-SETS are available as steril disposables. Resterilisation with gas on several occasions is possible. In a control study on thirty children, mainly premature infants and newborns a conventional SET, similar to the Bennett respiration system with disposable tubing and the H.R.P.-SETS are compared under the conditions of our intensive care unit. Using the criteria of serial bacteriological examinations of the tracheo-bronchial secretions and clinical criteria, H.R.P.-SETS proved superior. Artificial respiration without bacterial contamination by hospital strains for more than 10--14 days seems to be possible as a routine in newborns and children.


Cell ultrastructure during the development and the transformation of a pig--uterine tube cell line.

Observations by electron microscopy disclosed ultrastructural features which were not apparent by light microscopy during the three stages of the development of a pig uterine tube cell line. Ciliated cells without dynein arms were found naturally occurring in the first 100 subcultures (pseudo-diploid stage). They were not observed in the routinely growing cultures after the concomitant detection of the first chromosome marker and expression of a type C virus, unless the cells were treated with estradiol (transformed stage). Gap junctions and increased numbers of lamellar and lysosomic bodies and vacuole-like structures were observed in clusters of tumoral cells in the high subcultures if a new chromosome marker occurred (malignant stage). Type C viruses were found as early as the 106th subculture (transformed stage) in populations of actively dividing cells 3 days after seeding, but not in populations of nondividing cells a week after seeding. Both viruses and viral reverse transcriptase were continuously released in the 300 subsequent subcultures.


[Acute myeloid leukemia with megakaryocytic predominance and malignant megakaryocyte proliferation. Apropos of 3 cases].

Three cases of acute myeloid leukemia with megakaryocyte predominance are reported. In the first case megakaryocytosis was particularly evident in bone marrow, liver and spleen. In the second case high content of megakaryocytes was observed in the bone marrow and spleen, during the preleukemic phase only. Third case exhibited a strong predominance of megakaryocytes exclusively within the bone marrow. The characteristics of such observations and their nosologic position within myeloproliferative disorders group are discussed, with special reference to modern views concerning myeloid leukemia.


Evidence of a mixed population from uterine tube epithelium in a continuous line of pig cells.

The pig uterine tube (PFT) cell line is composed of a mixed population which is undifferentiated. However, specific markers indicating the original tissue of the uterine tube were shown if cells differentiated into epithelial cells forming spheroids in the 254th subculture. Ciliated and secretory cells, and cells with a basal lamina and interstitial collagen were observed in the spheroids. Microlumina found in the spheroids appeared morphologically similar to the lumen of the uterine tube. These observations indicate that undifferentiated cells can multiply in vitro and keep their potentiality of differentiation for future expression. It is proposed that the PFT cell line was partly derived from epithelial cells originally harvested from the PFT.


Long-term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec.

Among a cohort of 544 men with at least 20 years of employment in chrysotile mining and milling at Thetford Mines, Canada, 16% of the deaths were from lung cancer and 15% from asbestosis. The excess over expected deaths from these causes account for 43 of 178 deaths in the group. The risk of death of asbestosis, at equal times fron onset of exposure, is very similar in miners and millers, factory workmen and insulators. The ratio of observed to expected deaths from lung cancer is similar in the miners and millers and factory workers, but higher in insulators. The risk of death of mesothelioma in miners and millers is decidedly less than the other two groups. The exact causes of the reduced risk in this category are not yet completely clarified.


Asbestos exposure: factors associated with excess cancer and respiratory disease mortality.

A cohort of 1075 men who completed their working lifetimes with an asbestos company, worked at a facility in the United States, and retired with a company pension during the period 1941--67 was updated for deaths through 1973. The average length of employment was 25 years, and all had been exposed to asbestos dust. Respiratory cancer and pneumoconiosis-pulmonary fibrosis mortalities were examined in relation to cumulative dust exposure and to other factors after taking into account cumulative dust exposure. Men who worked in the production of asbestos cement pipe exhibited a higher risk of respiratory cancer, as did men with some crocidolite asbestos exposure. Because these two groups overlap, we could not be certain that crocidolite asbestos was responsible for the increased risk. Men working in general plant maintenance displayed a striking lack of deaths due to pneumoconiosis-pulmonary fibrosis, as compared with production workers and with maintenance personnel assigned to specific departments. Five mesothelioma deaths were observed at age 65 and over. Three of these deaths occurred during the period 1970--3.


Asbestos disease in maintenance workers of the chemical industry.

In several large groups of workers employed in chemical plants, chest x-ray abnormalities (small irregular opacities and/or pleural changes) of the type known to be induced by asbestos were found in a proportion of those examined. A cross-sectional study of maintenance workers in a large chemical plant was undertaken to evaluate the prevalence of asbestosis; 185 workers were examined. Radiologic evidence of parenchymal interstitial fibrosis was found in 24% of those examined; in 10% of workers, parenchymal fibrosis was the only abnormality. Pleural fibrosis and/or calcification was found in the absence of parenchymal fibrosis in 14% of cases; in another 14% of workers, both parenchymal and pleural abnormalities were detected. The prevalence was significantly higher in those employed 20 or more years. Pleural abnormalities were more prevalent than were parenchymal changes. The increased risk of lung cancer and mesothelioma remains to be studied.