Error estimate for the diffusion approximation of the Wright--Fisher model. The Wright--Fisher model and its approximating diffusion model are compared in terms of the expected value of a smooth but arbitrary function of nth-generation gene frequency. In the absence of selection, this expectation is shown to differ in the two models by at most a linear combination (with coefficients depending only on the derivatives of the smooth function involved) of the maximum mutation rate and the reciprocal of the population size.


Chloroplast DNA distribution in parasexual hybrids as shown by polypeptide composition of fraction I protein. Sixteen different mature interspecific parasexual hybrids, produced by fusing leaf protoplasts of Nicotiana glauca (G) and N. langsdorffii (L), were analyzed for fraction I protein (ribulose-1,5-bisphosphate carboxylase/oxygenase) which consists of large subunit polypeptides coded by chloroplast DNA and small subunit polypeptides coded by nuclear DNA. All the hybrids showed the combined small subunits of both parents, thus confirming the hybridity of each of the fusion products. Fourteen of the hybrids displayed the large subunit electrofocusing pattern characteristic of only one parent (eight L and six G). From one hybrid callus, two plants were regenerated, of which one had exclusively L-type large subunit and the other had exclusively G. A single plant retained a mixture of L ang G chloroplast DNA's; this later yielded six F2 progeny from one branch, all of which were G type, and three asexual progeny from another branch, all of which had the L-type pattern. In all, 46 F2 progeny and 8 different F3s were analyzed and each of these, with few if any exceptions, showed the same single subunit type as the F1 and F2 parent hybrid plants. Reasons for the rapid sorting out of the chloroplast types are discussed.


Reduction of syngeneic tumor growth by an anti-I-J-alloantiserum. Highly significant suppression of the growth of S1509a and Sa-I syngeneic sarcomas was observed in A/J mice following daily intravenous injections of 2 microliter of anti-I-Jk alloantiserum. This effect persisted as long as the anti-I-Jk serum was administered (day 15), In contrast, a control anti-I-Js serum had no discernible effect on the growth of the S1509a tumor. The inhibitory activity of the anti-I-Jk serum on the growth of the tumor was absorbed specifically by B10-BR spleen cells bearing I-Jk determinants. In other experiments, we established that A/J mice treated with anti-I-Jk serum, according to the protocol described above, are no longer a source of tumor-specific suppressor cells for adoptive transfer into immune tumor-bearing recipient mice. We conclude that anti-I-Jk serum inhibits tumor growth in A/J mice by abolishing tumor-specific suppressor activity.


Idiotypic-anti-idiotypic regulation of antibody synthesis in rabbits. Anti-ribonuclease antibodies (Ab1) of one rabbit were used to prepare in two other rabbits anti-idiotypic antibodies (Ab2) against them. Anti-idiotypic antibodies (Ab3) were prepared against Ab2 of one rabbit in two other rabbits that had the same phenotype as the former three for the allotypic a and b systems. After a rest period of 4 months, the latter two rabbits were immunized against ribonuclease. The antibodies produced (Ab1') crossreacted with the two anti-idiotypic sera (Ab2) against Ab1, showing an idiotypic similarity between anti-ribonuclease Ab1' and anti-ribonuclease Ab1. No such crossreaction was observed between the anti-idiotypic sera (Ab2) against Ab1 and any of the 12 unrelated antisera against ribonuclease that were tested. These results suggest (i) that rabbits, at least with the same allotypes, possess a closely related idiotypic repertoire; and (ii) that the immune system is a network of variable (V)-domains.


Chemical characterization of murine Ia alloantigens determined by the i-E/i-C subregions of the H-2 complex. Alloantisera directed against the alloantigens determined by the I-E and I-C subregions of the murine major histocompatibility complex precipitate two components that have molecular weights of 35,000 and 29,000. These components, when analyzed by partial NH2-terminal sequencing, show no homology to two components of similar size determined by the I-A subregion. However, the large chain determined by the murine I-E and/or I-C subregion is homologous to the large chain of the human HLA-D region alloantigen, although the small chains isolated from these two species do not display any such homology.


Structure of murine Ia antigens: partial NH2-terminal amino acid sequences of products of the I-E or I-C subregion. Partial amino acid sequence of the Ia molecule encoded by the I-E or I-C (I-EC) subregion of the major histocompatibility complex of the mouse are presented. The Ia molecule appears to be comprised of two noncovalently associated polypeptides. The larger subunit, alpha, has an approximate molecular weight of 35,000 and the smaller subunit, beta, an approximate molecular weight of 28,000. Several interesting homology relationships (or the lack thereof) are apparent when the Ia polypeptides from the I-EC subregion are compared both with their counterparts from man and guinea pig and with the molecules encoded in the I-A subregion. Clearly the most impressive homology relationship is that seen between the alpha polypeptide from the I-EC subregion of mouse and its human counterpart. This is in striking contrast to the beta polypeptide, which bears no apparent homology to its human counterpart.


Three-dimensional structure of an intact human immunoglobulin. We have examined the low-resolution structure of a complete human IgG1 using known domain coordinates from crystallographic investigations of immunoglobulin fragment structures. Our results indicate that the Fc portion of this molecule has a structure similar to that of an isolated Fc fragment, with the carbohydrate moiety playing a central role as the principal contact between the CH2 domains. Carbohydrate also forms a large part of the interface between the Fc and Fab regions. The relative orientations of the variable and constant portions of the Fab regions are intermediate between those reported previously, emphasizing the flexibility of the switch region. These data do not support a two-state allosteric model such as has been proposed for antibody effector functions.


The nucleotide sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs. The complete sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs were determined by sequence analysis of full-length cDNAs. The single-stranded cDNAs were digested with the restriction endonuclease Hae III, and the two 3'-terminal fragments of 75 and 132 nucleotides, complementary to the 5' termini of the alpha- and beta-globin mRNAs, respectively, were isolated and sequenced. Including the initiation codon AUG, the untranslated 5' regions of human alpha- and beta-globin mRNAs contain 41 and 54 nucleotides, respectively, and exhibit striking homologies with the corresponding sequences in the rabbit. Human alpha- and beta-globin mRNAs have five bases in the region of the initiation codon that may form base pairs with the 3' terminus of 18S rRNA. Stable secondary structures with hairpin loops can be constructed in the untranslated 5' regions.


Gyrate atrophy of the choroid and retina: deficiency of ornithine aminotransferase in transformed lymphocytes. Gyrate atrophy of the choroid and retina is an inherited form of chorioretinal degeneration associated with hyperornithinemia. We measured the activity of ornithine aminotransferase (L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13) in phytohemagglutinin-stimulated lymphocytes of a patient with gyrate atrophy and her daughter. The patient's cells had no detectable ornithine aminotransferase activity, and the activity in the heterozygote's cells was 44% of normal values. Measurements of [3H]thymidine incorporation and other transformation-affected enzymes verified that the patient's cells were transformed. These results demonstrate an enzyme deficiency in gyrate atrophy.


Regional dissociation of beta-endorphin and enkephalin contents in rat brain and pituitary. beta-Endorphin and enkephalin in extracts of whole brain, various brain regions, adenohypophysis, and combined pars intermedia and neurohypophysis of the rat were measured by radioimmunoassay. In brain extracts, the immunoreactive substances were further separated according to molecular size by gel filtration. beta-Endorphin was found in the diencephalon but not in the hippocampus, cerebral cortex, cerebellum, and striatum. Enkephalin was found predominantly in the striatum and diencephalon. Attention is called to possible artifactual interference by myelin basic protein in the immunoassays for beta-endorphin in some regions of the brain. In the pituitary, enkephalin was mainly restricted to the pars intermedia-neurohypophysis. Neither adrenalectomy nor hypophysectomy significantly altered levels of beta-endorphin in brain extracts. Adrenalectomy increased the levels of beta-endorphin in adenohypophysis and pars intermedia-neurohypophysis; after adrenalectomy, enkephalin was also increased in the adenohypophysis but less so in the pars intermedia-neurohypophysis. These results show that brain endorphin levels are independent of pituitary endorphin levels; they suggest that beta-endorphin-containing neurons and those containing enkephalin constitute two separate groups of brain cells.


Development of electrophysiological and biochemical membrane properties during differentiation of embryonic skeletal muscle in culture. Newly fused chick myotubes undergo simultaneous and rapid changes in cell membrane properties during synchronous differentiation in culture. These changes are coordinately regulated and include increases in acetylcholine receptor, acetylcholinesterase, and resting potential, as well as the appearance of action potentials in discrete membrane areas upon stimulation. Subsequently, the acetylcholine receptor reaches maximal levels, whereas the development of electrical properties is marked by a further increase in resting potential, changes in the characteristics of the elicited action potential, and the recruitment of additional membrane areas for action potential generation. Maturation of electrical excitability, marked by the acquisition of the ability to fire repetitively and to conduct action potentials along the membrane, occurs well after resting potential has reached a maximum. During post-maturational development, myotubes exhibit spontaneous electrical and contractile activity, and levels of acetylcholine receptor accessible to externally applied 125I-labeled alpha-bungarotoxin decrease markedly. It is suggested that electrophysiological membrane maturation is autonomously regulated with no requirement for neuronal intervention and involves the coordinated biosynthesis of discrete membrane components and their subsequent organization in the myotube membrane.


Dissociated ciliary ganglion neurons in vitro: survival and synapse formation. Normally, about half of the ciliary ganglion neurons in 8-day-old chick embryos die before day 14 in ovo. However, when dissociated ciliary ganglion neurons were prepared from either 8- or 14-day-old embryos and grown in cell culture with skeletal myotubes, essentially all of the neurons survived for at least 3 weeks. Many of the neurons formed functional synapses on myotubes under these conditions; some neuromuscular synapses could be detected as early as 20 hr after addition of the ganglion cells to muscle cultures. In contrast, most neurons from 8-day embryos survived for only a few days when grown alone on either polyornithine- or collagen-coated dishes. These results suggest that neurons destined to die in ovo can be rescued when grown in cell culture with myotubes and that under these conditions the neurons develop and express differentiated properties.


How to label nerve cells so that they can interconnect in an ordered fashion. We present a method for setting up topographically ordered mappings between two sheets of nerve cells. A set of chemical markers that express the neighborhood relationships within the presynaptic sheet is induced by the fibers into the postsynaptic sheet. The markers are used to guide the fibers to their terminal sites. A case for which this idea may be relevant is the retinotectal projection; our model exhibits types of plasticity found experimentally. The fact that the postsynaptic markers remain after removal of the projecting fibers suggests an important difference between development and regeneration. This paper concentrates on explaining the basic idea, and in addition presents a set of preliminary computer simulations.


Proposal for the biologically active conformation of opiates and enkephalin. A model for the opiate receptor has been defined by using a computer-based molecular display and x-ray crystallographic input data. The model can explain the stereochemical fashion in which the morphine, morphinan, and oripavine classes of compounds interact with the receptor. The minimal structural unit of the enkephalins demonstrated to be pharmacologically active. Tyr-Gly-Gly-Phe, was also fitted to this model by using a systematic search of conformational space.


Storage and release of acetylcholine by a clonal cell line. The nerve cell line PC12, in its morphologically undifferentiated state, synthesizes, stores, and secretes catecholamines and acetylcholine. At least 60% of the basal level of neurotransmitter release is due to a calcium-dependent mechanism, and the rate of secretion is enhanced by increasing external potassium. A minimum of 80% of the intracellular acetylcholine and catecholamines are stored in particulate structures. The storage site for acetylcholine is dense core vesicles that can be distinguished from those containing catecholamines on the basis of vesicle density on sucrose gradients, vesicle size, and reserpine sensitivity. These results are discussed in relation to what are thought to be the early stages of synapse formation in cell culture.


Generalizing Fisher's "reproductive value": linear differential and difference equations of "dilute" biological systems. R. A. Fisher's 1930 "reproductive value" is defined as the contribution made by a population's initial age elements to its asymptotically dominating exponential growth mode. For the Leslie discrete-time model, it is the characteristic row vector of the Leslie matrix, and for the integral-equation model of Lotka the similar eigenfunction. It generalizes neatly to a 2-sex model of linear differential equations, and to general n-variable linear systems. However, when resource limitations end the "dilute" stage of linearity, reproductive value loses positive definability. The present linear analysis prepares the way for generalizing reproductive value to nonlinear systems involving first-degree-homogeneous relationships.


Behavior-genetic analysis of Phormia regina: conditioning, reliable individual differences, and selection. Using proboscis extension (unconditioned response) to sucrose (unconditioned stimulus), individual blowflies (Phormia regina) were classically conditioned to saline and to water (conditioned stimuli) with sensitization controls, thus providing unique, independently replicated evidence both of learning in Diptera and of reliably measured individual differences. Directional and stabilizing selection have bred high and low performance lines markedly different from an unselected control line as a step in the analysis of behavior-genetic correlates. This replicates and extends previous selection analysis with improved conditioning technique. Also, some unwarranted claims of learning in Diptera are discussed.


[Choice of technic for periapical radiography and determination of exposure time]. The factors which influence the choice of the radiographic technique are discussed. It is concluded that the long cone technique is preferable because of its simplicity, efficiency, the quality of the image and the low radiation dose. A description is given of the penetrometer method ascribed to Wainwright for arranging an exposure table for a certain X-ray machine - timer combination.


[Dentifrices and dental hygiene].

[Dentifrices and dental hygiene]. The best known dentifrices are pastes. The various constituents save to respect integrity of soft and hard tissues. The abrasive must suppress coloration without enamel abrasion. The foaming agent facilitates detachment and elimination of coloration without lesion to the gingiva. Flavours, humectants, binders will not irritate the mucosa. Chlorhexidine and fluoride are among the most studied and interesting therapeutic agents.


[Indications for extraction of the lower third molars]. Lower third molars are often removed, because of complaints such as pain and trismus. A survey of 932 lower third molars reveals that abnormal position, caries or inflammation the direct reason are for removal in 9 out of 10 cases. So prophylactic removal is necessary. The best time is between 15 and 25 years of age.


The electronic and serotonin receptor binding affinity properties of N,N-dimethyltryptamine analogs. The electronic properties of a series of N,N-dimethyltryptamines and related analogs, for which binding affinity data are available, were examined using both a pi-electron and an all-valence electron method. The results suggest that affinity is related to the ability of these compounds to donate electrons in a localized charge transfer manner from the 4-position of the indole nucleus.


[Treatment of essential facial neuralgia by selective thermocoagulation of Gasser's ganglion]. The authors report their experience in the treatment of essential facial neuralgia by differential thermocoagulation of the gasserian ganglion. This method is based upon the fact that small pain fibres (A delta and C) are more sensitive to warmth than large touch fibres. Thus progressive and controlled thermocoagulation of the trigeminal ganglion makes it possible to obtain selective destruction of the small fibres (analgesia without anaesthesia). 76 patients were treated using the method, and in 75 cases the symptoms of neuralgia disappeared immediately. Mortality is nil and morbidity insignificant other than the effects on the trigeminal nerve. The most serious complication (Approximately 10% of cases) was that of marked hypoaesthesia, rather than pure analgesia, in the coagulated area.


[Diagnostic problems posed by acute necrosis of the extremities after electrocoagulation of an epithelioma of the floor of the mouth]. Three weeks after electrocoagulation of an enormous epithelioma of the floor of the mouth, a 62-year-old man presented after a shower-bath with symmetrical cyanosis of the toes and fingers with painful oedema coloured by livedo reticularis of the lower third of the legs and forearms. In the hands this developed into a dry necrosis and necessitated their amputation. In the absence of biological tests and a posteriori the authors discuss the diagnosis of cryoglobulinaemia and intravascular disseminated coagulopathy; but in fact, these two syndromes produce very similar cutaneous symptoms, notably, cryofibrinogenaemias, cryofibrinogen being a degradation product of fibrin liberated in C. I. V. D.


[Extrusion into the inferior dental canal of filling material. Apropos of 18 cases]. The purpose of this article is to draw the reader's attention to a fairly frequent complication in root treatments with suspicious clinical symptoms and in which painful complications are particularly to be feared. This complication appears therefore to be a stomatological emergency, treatment for which is aimed at bringing about regeneration of the traumatised nerve, prognosis being dependent on prompt surgical measures, the site of the complication and the anatomical damage done to the lower dental nerve.


[The mandible in labio-maxillary clefts]. The writers have studied mandibular anomalies in a series of 20 surgically treated clefts. Anomalies of shape occur in one case out of two and are in the form of a mandible which is too long. Anomalies of position most often show a mandible in front of the maxillary and to the rear in comparison to the base of the skull.


[Mesiodens and heredity].

[Mesiodens and heredity]. The authors describe the case of mesiodens in two non-identical twins and in their grandfather. They recall that, although no investigation confirmed the hereditary nature of the mesiodens, it is quite undeniable in view of the frequency of familial cases. They think there is a recessive gene on an autosome and a gene on the inhibiting chromosome X. They discount the theory of mutation.


[Z-plasty technic, applied to hypertrophy of the upper labial frenum]. The authors used the technique of Z-palsty in the surgical treatment of hypertrophy of the superior labial fraenum. They consider that this operation is indicated when there is hypertrophy of the fraenum with a low insertion, associated with an inter-incisor diastema, and that the lateral incisors have appeared without causing the diastema to disappear. This technique eliminates the possibility of a hypertrophic scar, a possible source of failure.


[Superficial structure of dental cement as shown by acid etching and scanning electron microscope]. The superficial layer of the cement is made up of a mineralised structure in which are included organic fibres which would seem to serve as the intracemental anchorage of Sharpey's fibre. The appearance seen on sweep electron microscopy after acid demineralisation confirm those seen using the electron microscope by Selvig. These fibres included in the cement have a variable diameter ranging from a few microns and 45 microns on our pictures (10 microns according to Selvig). They consist of a numerous fibrils with a diameter of the order of 0.3 microns. In the cement these fibers are parallel to the surface of the tooth, this confirming Selvig's finding. Finally, our observations show that, in the superficial part of the cement, these fibres form a markedly flattened three-dimensional network.


Localization of the globin gene in the template active fraction of chromatin of Friend leukemia cells. Friend leukemia cell chromatin has been fractionated into template active and inactive components. The globin gene sequence is associated with the template active component both prior to and after the cells are induced with dimethyl sulfoxide to synthesize hemoglobin and therefore appears to be in an active configuration in uninduced as well as in induced Friend leukemia cells. In cells which have lost the ability to produce hemoglobin, the globin gene sequence is not associated with the template active fraction of chromatin. These results demonstrate the success of the fractionation procedure.


[Histoautoradiographic studies on protein synthesis by odontoblasts]. The protein-producing function of the odontoblasts was studied in 120 Wistar rats with an initial weight ranging from 30 to 40 g determining the rate of the migration of radio-active isotopes (glycine-2-14C, lysine-1-14C) from the odontoblasts to the predentine. The odontoblasts exert a protein-synthetizing function and play an active part in predentine formation. Under the influence of a cariogenic saccharose-casein diet and the simultaneous induction of experimental caries, the intensity of the migration of the labelled amino acids from the odontoblasts to the predentine increases during the first and second stages of caries, which must be interpreted as an increase of the protein-synthetizing function of the odontoblasts associated with an intensification of dentinogenesis. During the third stage of caries, the protein-producing function of the odontoblasts decreases.


[Physico-mechanical and structural changes in the hard dental tissues after physiological abrasion]. The authors studied the specific hardness, micromorphology, electric resistance and penetration by 22Na ions in teeth extracted from juvenile subjects with beginning abrasion of the enamel differentiating between tooth parts affected with attrition and tooth parts not affected. The structural or physicomechanical properties of the enamel and dentine were quantitatively evaluated with regard to their relation to caries disposition.


[Morphological aspects of vascular changes in the gingival tissue in periodontosis]. The authors report the results from detailed morphological, histochemical and electron microscopic studies on the gingivae of patients without diseases other than periodontosis and of patients with periodontosis and underlying hypertension and atherosclerosis. In each group of patients, the authors established a relationship between the clinical particularities of the course of the periodontosis and the characteristics of the microcirculation in the periodontium. It was also evidenced that the changes in the gingival tissues observed in these groups of patients were due to fundamental differences in the impairment of the transcapillary metabolism which depends on the morphofunctional condition of the microcapillaries. These facts should be considered when adopting a treatment method.


[Methods for the preparation of ceramic jacket crowns by means of channel grinders]. Self-designed grooving grinders are used for the controlled reduction of dental hard tissues (fig. 1-4). Thereby the preparation of the smooth surfaces and shoulder becomes more accurate and less time-consuming. This method has been used on 59 teeth without complications.


[Diagnosis and therapy of the distal bite]. Of all the malocclusions, distocclusion is most frequently associated with functional disorders. 60% of the patients suffered from diseases of the upper respiratory tract. A classification into 9 forms is suggested (fig.). Treatment with the Fränkel type I and type II function regulators is performed in the active phase of growth at the end of the period of deciduous dentition and during the early period of mixed dentition. The rectification of the morphological and functional disorders that is simultaneously achieved justifies the recommendation of this treatment for practice.


[Etiology and pathogenesis of neurological symptoms in low bite]. 50 patients were subjected to complex examination. In bite lowering the head of the condyle is displaced backwards and upwards into the depth of the glenoid fossa. The pressure of the displaced mandibular joints upon the arterial cord and the tympanic vein as well as upon the venous network around the mandibular joint capsule may produce disturbed blood supply to the mucosa of the middle ear and of the auditory tube, and finally, obstruction of the auditory tube. Disturbances in the blood supply of the middle ear irritate the tympanic cord and tympanic plexus, which causes burning of the tongue, taste and salivation troubles, and also ear complaints. Since the sympathetic fibres of the tympanic plexus and of the eye are closely interrelated, this leads also to an irritation of the dilator muscle of the pupil. The reflectory irradiations from the tympanic plexus and mandibular joint explain many other neurologic symptoms. In bite lowering these symptoms are not always associated with joint disturbances.


[Clinico-statistical and biometric evaluation of the effectiveness of the Fränkel method for the treatment of distal bite]. 84 patients with distocclusion were treated with type I and type II function regulators for two years. Correlation analyses showed that the dental arch width and length as well as the apical base are positively influenced and the there are significant correlations between treatment expenditure and treatment duration, between treatment duration and the summary changes in measuring data, and between treatment expenditure and the changes in measuring data. Almost recurrence-free, positive therapeutical results were achieved. Fränkel's method is recommended for practice.


[Effective methods for the production of esthetically satisfactory fixed partial dentures]. Metal ceramics and ceramic bridges with aluminum-oxide profile components are optical solutions. The use of silanetreated "Keracetten" (mineral facets) avoids the disadvantages of plastic facing and has stood the test during a 5-year period of observation.


[Indications for and usefulness of all-plastic dentures]. All-plastic bridges are mainly indicated as temporary bridges. As a definitive measure they are indicated only in case of sagittal shoulder, slight overbite and secure support in the posterior region for the replacement of a missing incisor.


[Assessment of the need for treatment of periodontal diseases by means of the Bellini system]. The authors evaluate the usefulness of a new classification system for the need for care of peridodontal diseases. The system in question has been elaborated by Bellini and is to date little known in the People's Republic of Poland. The system was tested in students of the Medical Academy and employees of an enterprise in Poznań. It was stated that Bellini's system is very suited for the examination of great population groups. It permits to appreciate in no time the periodontal condition and to determine the kind and the number of the necessary prophylactic and therapeutic measures and the time required for them.


[The eosinophilic granuloma in the jaw region]. The eosinophilic granuloma is nowadays generally considered as a reticulosis associated with secondary lipoid storage. It occurs very rarely in the jaws. During a period of 10 years, we had but 5 inpatients with a central, monostotic, eosinophilic granuloma. Diagnostic difficulties result from atypical clinical, radiological and paraclinical findings. The diagnosis can be confirmed solely by histologic methods. In agreement with most of the other authors we are of the opinion that the radiological treatment (if necessary, in combination with surgical measures) is optimal.


Xeroradiographic evaluation of murine osteosarcoma. Xeroradiography, a method of X-ray imaging based upon selenium photoconductivity, was used for the study of experimental osteosarcoma induced by MSV-M virus in rats. Due to the peculiar features of xeroradiographic image (enhancement of details and lowering of the overall contrast) good pictures of osseous structures together with soft tissues were obtained even in very young animals. Serially perfomred xeroradiographies gave a permanent representation of tumor evolution with time. Advantages and drawbacks of this method are discussed, particularly with respect to radiation dosage. Xeroradiography is proposed for the study of the response to antiblastic chemotherapy of experimental bone tumors.


Prevention of meningeal CNS involvement as a factor influencing the duration of complete remission and survival in childhood acute lymphoblastic leukemia. The influence on the duration of CR and survival of 2 modalities (MTX + hydrocortisone IT, with and without TCT) for the prevention of meningeal CNS involvement was assessed in 24 children with acute lymphoblastic leukemia. Of the 9 subjects who received MTX and hydrocortisone only, 42% were still in CR 33 months after its attainment, as opposed to 75% of the 15 who also received TCT. Survival at 33 months after diagnosis was 89% and 82% in the 2 groups. The results are compared with those obtained in an earlier series of 14 children who received no prophylactic treatment. Here CR at 45 months was 25% and survival 46%. Eight subjects died, as opposed to 3 (1 in CR) in the present series.


[Changes in amino acid concentrations in plasma after oral ingestion of oligopeptides and analogous amino acid mixtures]. To what extent an oligopeptide mixture differs in equimolar dosage from an equivalent amino acid mixture after oral intake was tested on 11 subjects. The plotted course and absolute order of magnitude of the two mixtures revealed no differentiation in the total amino acid concentration of the peripheral blood plasma. The same was true of the individual free amino acids in the plasma. The only difference was found in the graphic representation of the maximum amino acid concentration of the individual test subjects, which was usually reached at an earlier date with oligopeptides than with free amino acids. The difference is even more obvious in the portal vein, as is shown in a test series not yet completed, where the plasma amino acid concentration increased at a clearly earlier date after oligopeptide substitution than after the supply of the equivalent amino acid mixture.


Natural history of acute hepatitis B in previously healthy patients: A prospective study. A prospective study of the natural history of acute hepatitis B was performed in 38 patients. Fatigue started median 4 weeks, abdominal symptoms median 3 weeks and signs of cholestasis median 2.5 weeks before peak SGPT values were reached. Extrahepatic manifestations occurred throughout the prodromal stage, the presence of arthropathy, urticaria or skin rashes was not related to the biochemical severity of liver disease. The higher the the maximal values of serum bilirubin and/or the older the patient, the longer the period of bilirubin elevation; a maximal bilirubin elevation less than 20 X the upper limit of normal was associated with normalisation of serum bilirubin within 6 weeks. No such correlations were found between the height of serum glutamic pyruvic transaminase, alkaline phosphatase, thymol turbidity and cholesterol levels and the subsequent duration of their abnormality. The elevation of alkaline phosphatase as well as the abdominal complaints might partly be caused by gastro-intestinal involvement. Immobilisation before peak SGPT was attained was associated with normalisation of serum glutamic pyruvic transaminase levels within 8 weeks after peak levels. 37 patients recovered completely. In one HBs-antigenemia and slight SGPT elevation persisted. Long term follow up was possible in 33 patients for 4 to 7 years, median 5 years.


Relation between curability and tumor volume in a murine carcinoma and sarcoma. Tumor control doses (TCD50) using single 60CO doses were determined on C3HBA adenocarcinoma and Dunn osteosaroma ranging in size from microscopic pulmonary colonies (3 X 13(-5) mm3) to palpable subcutaneous tumors (300 mm3) in the hind limb. The power function TCD50 =23.57 TV0.15, with TCD50 in GY and TV (tumor volume) in mm3, fits the data for both tumors over the entire range of tumor volumes used.


Comparison of lithium and haloperidol therapy in Gilles de la Tourette syndrome. Three patients suffering from Gilles de la Tourette Syndrome were initially treated with haloperidol. Depressive side effects and symptom breakthrough necessitated the search for another agent. The efficacy of lithium carbonate in treating stereotyped hyperkinetic behavior (such as is seen in Gilles de la Tourette syndrome) prompted the evaluation of lithium carbonate. An objective behavioral observation technique, clinical ratings and the patient's subjective reports were used to systematically record the response to treatment during the entire course of the study. Initially blood plasma Li+ levels in the 0.5 to 0.6 mEq/L range were obtained and these correlated with reduced frequency, as well as intensity, of involuntary motor acts (tics) and sounds. When the Li+ blood levels had stabilized at 0.8 to 0.9 mEq/L the major tics and involuntary sounds cleared dramatically. The patients experienced no side effects and have been followed for several months without recurrence of the original symptoms.


Allescheria boydii infections in the immunosuppressed host. Allescheria boydii, a true fungus frequently isolated from soil, is best known as a causative agent of maduromycosis of the foot. In our report we describe two patients under treatment for acute leukemia who died from rapidly progressive A. boydii infections. One patient had signs of central nervous system infection and was found at autopsy to have had a large brain abscess. The second patient had a cavitary necrotizing pneumonia with thoracic inlet obstruction (Pancoast's syndrome) and failed to show improvement despite treatment with amphotericin B. The clinical spectrum of allescheriasis is reviewed with particular emphasis on its role as a pathogen in the compromised host. Since A. boydii may resemble other fungi morphologically in tissue sections and may produce infections clinically similar to other mycoses, culture of the organism is required for definitive diagnosis. Based on recently reported in vitro susceptibility studies, miconazole may have a future role in the therapy of A. boydii infections which are resistant to presently available antifungal agents.


The Takaoka respiratory for use during pneumoencephalography. The Takaoka respiratory was used during lumbar pneumoencephalography in 12 patients in a rotatory chair of X-ray apparatus. Anaesthesia and ventilation were maintained with oxygen or 50% nitrous oxide in oxygen supplemented by neuroleptanalgesia. The mean minute volume of ventilation was 84.5+/- 5.4 ml/min/kg and the mean respiratory rate was 8.5 +/- 1.7 breaths/min. Under these ventilatory conditions the blood gas data were acceptable (PaCO2: 35.0 +/- 4.3 torr). The Takaoka respirator can be fixed to the rotatory chair with no risk of accidental disconnection and there is no disturbance of the general monitoring or of the manipulations of the X-ray technicians. I provides adequate ventilation independent of position.


Depression following myocardial infarction: the effects of distance running. A proportion of postcoronary patients seen 16 to 18 months after infarction are seriously depressed (high D score on Minnesota Multiphasic Personality Inventory). A follow-up of 44 such depressed patients showed a significant (p less than 0.001) decrease of standardized D scores, from 80 to 72 units over 4 years of exercise-based rehabilitation. There were associated decreases in scores for hysteria, hypochondriasis, and psychasthenia. A decrease of D score was associated with exercise compliance. An increase of D score was associated with a significant (p less than 0.05) worsening of ST segmental sagging, suggesting that progression of the disease process had contributed to the increase of depression. All of the patients had high (feminine) scores on the masculinity/femininity scale of the MMPI test. This finding was unrelated to the daily running distance or medication; it could represent a "feminine" personality, or be a typical response in a well-educated white collar group. Evidence of successful group interaction may be indicated by reduction in scores for social introversion and schizophrenic traits.


Work-heat tolerance of distance runners. Physical training in a cool environment by subjects not previously trained improves their work-heat tolerance, but can not replace heat acclimatization to the standard heat stress conditions employed by a variety of investigators. This is attributed to the inability of these subjects to sustain prolonged work at high metabolic rates. Thus, they are not maintaining high core body temperatures long enough to bring about an adaptive change to heat. On the other hand, the intense and prolonged (years) training of long distance runners in a temperature environment at high metabolic rates has acclimatized them for at least 4 hours of mild work (MR 160 kcal/m2-hr) in both hot dry (50/27 C db/wb) and hot wet (36.7/33.1 C db/wb) environments, but not for work at high energy expenditures (MR 540 kcal/m2-hr) in a less severe thermal stress (35/21 C db/wb). These highly trained athletes can improve their work-heat tolerance at high metabolic rates in a warm climate by training at competitive speeds in a cool environment dressed in sweat clothing or by training at near competitive speeds in the heat. In either of these situations the athlete is cautioned to consume water at frequent intervals to offset the dehydration associated with excessive sweating under these conditions.


The interplay between peripheral and central factors in the adaptive response to exercise and training. (1) Local adaptation of skeletal muscles (fibers) only occurs in the extremity involved in the training. (2) Work performance and maximal oxygen uptake were significantly increased only in the trained leg, and the "transfer" to the untrained leg was very small. (3) The classical sign of a training effect with a lowered submaximal heart rate response could only be elicited when exercising the trained leg. Lactate concentration and release of lactate were also lower when the trained leg performed the exercise. (4) The present results suggest that the local adaptation of skeletal muscle to training is of primary importance for enhancing work capacity and oxygen uptake. (5) The results also indicate that there may exist a peripheral factor in the regulation of the heart rate response during exercise. Moreover, the data favor the hypothesis of a chemical receptor playing a role in such a peripheral control system.


The hemodynamic and metabolic alterations associated with acute heat stress injury in marathon runners. Studies of clinical, metabolic, and hemodynamic responses to heat stress in eight marathon runners have demonstrated several important differences from those observed in nonconditioned subjects. Three marathoners manifested a nonanhidrotic form of heat stroke, a phenomenon not observed in our Marine recruits. Five patients with heat exhaustion evidenced signs of severe mental confusion despite apparently adequate hemodynamic function. Heart rate was significantly lower in all eight marathoners in comparison to the 15 Marine recruits. This latter observation suggests that either selective regional shunting of blood or increased stroke volume index occurs in marathoners subject to heat stress.


Intramuscular substrate utilization during prolonged exercise. Large stores of intramuscular substrates are found in the different fiber types of human skeletal muscle, and with prolonged exercise both glycogen and triglyceride stores are utilized. The contribution from intramuscular glycogen stores is greatest at higher work intensities while triglyceride stores are utilized at moderate intensities. In man all fiber types have a similar glycogen content whereas the highest lipid content is found in the more oxidative fibers. The muscle metabolism is well adapted to the supply of substrate as well as to the demand for energy. Among several regulatory mechanisms, changes in citrate concentration seems to be an important factor in the interplay between carbohydrate and lipid metabolism.


Submaximal and maximal working capacity of elite distance runners. Part II. Muscle fiber composition and enzyme activities. The present study confirms earlier observations that the musculature of elite distance runners is characterized by a high predominance of ST fibers. Although the percent ST fibers effectively discriminates between good and elite distance runners, fiber composition alone is a poor predictor of distance running success within the group of elite runners. Muscle enzyme measurements suggest that the 11 to 20 miles (17.7 to 32.2 km) of daily training performed by the elite runners produced a significantly greater increase in muscle SDH activity than was observed in the good distance runners, who were running 7 to 11 miles (11.3 to 17.7 km) per day, Although such endurance training enhances the oxidative capacity of the muscle, it apparently has little influence on the enzymes of glycogenolysis.


Limitations of marathon running in the rehabilitation of coronary patients: anatomic and physiologic determinants. Prescribed, supervised exercise training has proved valuable in the rehabilitation of selected coronary patients. However, long distance (marathon) running has limited cardiovascular value in the rehabilitation of patients for a majority of occupations, which involve predominantly upper extremity effort. The age of patients with coronary heart disease and the severity of the lesions preclude the wide application of marathon running to the general coronary heart disease population. Less than 6/1000 subjects with coronary heart disease have been estimated as potentially being able to achieve by high-level training a maximum Vo2 sufficient to complete a marathon race in 5 hours. The hazards of high-level-activity-induced cardiac arrest that is reversible mandates the availability of CPR equipment and personnel in the immediate vicinity of all coronary patients and most coronary-prone patients who are undertaking such heroic activity. Over-publicized marathon running by a few subjects has aroused unrealistic expectations for the majority of coronary heart disease subjects and probably similarly for a considerable number of coronary-prone subjects, many of whom have "silent" coronary disease.


Marathon running and immunity to atherosclerosis. This is an interim report of an on-going study of deaths in 42-km men. The absence of fatal ASCVD in these athletes can not be construed as evidence for the protective role of exercise alone. The ability to run 42 km depends on many factors. Exercise is only one. Avoiding tobacco is another. Dietary factors also play a role. It has not been feasible to remove one of these factors while maintaining the ability to cover the 42 km distance. Some 42-km men claim that megadoses of ascorbic acid protect them from collagen injury. This is supported by animal studies that show increased collagen synthesis proportional to ascorbic acid intake up to dosage levels that would equal 10 grams per day for humans. Their self-selected macrobiotic diet contains a high ratio of peanuts:steak resulting in a high P/S ratio (polyunsaturates/saturates). Dietary manipulation quickly effects their ability to train. Smoking is so rare among these runners that it must be related to specific effects, such as a catalytic agent in tobacco smoke converting linoleic acid into a toxic lipid oxide. Noakes and Opie recently confirmed again (May, 1976) that no cases of "death due to coronary atherosclerosis" have been recorded in marathon finishers. If this holds true for the second 10-year period of this study, then marathon runners will have joined the longshoremen by earning life-long protection against ASCVD. These longshoremen burned 1,876 kcals on the job, equivalent to a 30-km run. Roberts and Straus suggest that many factors can cause atherosclerosis. Only time will tell whether the marathoner is protected from all of them.


Coronary heart disease in marathon runners. Six highly trained marathon runners developed myocardial infarction. One of the two cases of clinically diagnosed myocardial infarction was fatal, and there were four cases of angiographically-proven infarction. Two athletes had significant arterial disease of two major coronary arteries, a third had stenosis of the anterior descending and the fourth of the right coronary artery. All these athletes had warning symptoms. Three of them completed marathon races despite symptoms, one athlete running more than 20 miles after the onset of exertional discomfort to complete the 56 mile Comrades Marathon. In spite of developing chest pain, another athlete who died had continued training for three weeks, including a 40 mile run. Two other athletes also continued to train with chest pain. We conclude that the marathon runners studied were not immune to coronary heart disease, nor to coronary atherosclerosis and that high levels of physical fitness did not guarantee the absence of significant cardiovascular disease. In addition, the relationship of exercise and myocardial infarction was complex because two athletes developed myocardial infarction during marathon running in the absence of complete coronary artery occlusion. We stress that marathon runners, like other sportsmen, should be warned of the serious significance of the development of exertional symptoms. Our conclusions do not reflect on the possible value of exercise in the prevention of coronary heart disease. Rather we refute exaggerated claims that marathon running provides complete immunity from coronary heart disease.


A 4-year prospective study of the relationship of different habitual vocational physical activity to risk and incidence of ischemic heart disease in volunteer male federal employees. A prospective study of coronary heart disease (CHD) was done in 2,635 volunteer male federal employees of postal, health, aerospace, and other agencies, aged 35--59 years at intake. The present analysis is concerned with 2,065 initially well whites, of whom 65 suffered clinical CHD during a 4 years of annual follow-up. The subjects differed markedly in their levels of habitual vocational physical activity, which is classified (1) by division into sedentary, moderate, and heavy activity groups, (2) by blue collar or white collar type of occupation, and (3) by calculated annual caloric expenditure for both vocational and non-vocational physical activities. Intake variables that were studied in relation to physical activity and the CHD incidence include age, serum cholesterol, systolic blood pressure, relative body weight, ECG abnormality, and cigarette smoking. Socioeconomic status (SES) is assessed by levels of education and income and by a combined SES categorization based upon both. Estimated composite CHD risk scores are based upon Framingham equations. The CHD risk factors, singly, as well as in a derived composite risk score, are higher for men with heavy compared to sedentary or moderate habitual physical activity. However, this is a spurious association found to be induced by differences of SES. Thus, when physical activity and SES are studied in a concurrent analysis, a higher CHD risk is significantly associated with lower SES status but not with differences of vocational physical activity. The CHD incidence in this population is studied in relationship both to the risk factors and physical activity by multivariate analysis, using the multiple logistic risk model. The incidence of CHD is significantly associated with age, serum cholesterol, systolic blood pressure, and cigarette smoking. It is not found to be associated with the type of occupation (i.e., blue or white collar), the level of reported habitual vocational physical activity, or the calculated total vocational plus nonvocational caloric expenditure in physical activity.


The important role of fitness determination and stress testing in predicting coronary incidence. The question of whether there is some effect of status of cardiorespiratory fitness and exercise ECG abnormalities on occurrence of CHD other than their effect on the risk factors of serum cholesterol, blood pressure, glucose, and smoking seems to have been answered in the affirmative by this study. The relative prognostic importance of the measures considered here, the role of exercise, and the interrelationships between fitness, exercise, other risk factors, and CHD provide many interesting hypotheses for continued study. A future investigation will involve a large prospective study in which the risk function to be derived would include stress ECG and treadmill performance as predictor variables. The retrospective approach reported in this paper had certain limitations. It did, however, permit demonstration of new results because, essentially for the first time, all of the important risk factors are measured in the study population and can be evaluated simultaneously.


Effects of an endurance training regimen on assessment of work capacity in prepubertal children. The cardiovascular effects of a 12-week endurance training regimen were studied among normally active and healthy prepubertal children. Twenty-six 8- to 12-year-old children (20 boys and 6 girls) volunteered and 10 acted as control subjects. The training regimen consisted of distance running for progressively longer periods (from 10 to 35 min) 2 to 3 times per week, with 2 additional sessions per week devoted to running games. Those who were trained ran a cumulative average distance of 95.6 km (58.9 miles). Intensity of work was assessed from running pace and heart rate. The target workout intensity was 75% to 80% of aerobic capacity (Vo2 max). Growth and development accounted for increases in height, weight, body circumferences, and diameters, and fat-free body weight. Heart rate (HR) during submaximal workloads, both running and walking, decreased in the trained group (p less than 0.01) and (p less than 0.05). HRmax did not change, but Vo2 max increased significantly (average 7%) in the trained group but not in the controls. No significant change attributable to training was found for submaximal cardiac output, stroke volume, or arteriovenous oxygen difference. The Vo2 max value before conditioning was a relatively poor predictor of the magnitude of improvement in functional capacity, but those with higher initial Vo2 max logged more cumulative training mileage. It was concluded that prepubertal children respond to an endurance training regimen by improving their running capacity, which is, to a limited extent, associated with increased aerobic capacity.


A biomechanical approach to running injuries. I have introduced the concept of controlling overuse syndromes by controlling the etiology. The etiology of most overuse syndromes is biomechanical deformity of the lower extremity as well as nonadherence to sound principles of training and conditioning. It is important to realize these factors to provide for many years of injury-free athletic involvement.


Role of infection in the death of children with acute lymphoblastic leukaemia. Twenty-four consecutive deaths from a total of 70 children receiving treatment for acute lymphoblastic leukaemia (ALL) have been reviewed. An attempt has been made to ascribe the cause of death to either infection, haemorrhage, the leukaemia itself, or a combination of these factors. No child was free of infection at death. Infection, with or without haemorrhage, was responsible for the deaths of all 15 children whose leukaemia had not relapsed. Although infection was present at death in all 9 children whose leukaemia had relapsed, the leukaemia process itself was also a major contributing factor. Viruses were associated with death in many of the children and may be emerging as important pathogens in children with ALL. Familiarity with a protocol may be an important factor in the prevention of fatal infections in such children. Centralization of treatment is necessary if this expertise is to be acquired.


The value of a simple medical questionnaire in dentistry. A short specific medical questionnaire was given to 1125 new patients attending for their initial examination at the Perth Dental Hospital. A positive history was given by 398 patients. A wide variety of conditions was revealed and the dental significance is discussed. The extent of the information provided illustrates that the simple questionnaire is valuable in exposing conditions which may affect dental treatment.


An elementary study of deformation of molar teeth during amalgam restorative procedures. A technique using an optical comparator was employed to examine the dimensional changes resulting from cavity preparation, application of the matrix and packing with amalgam in three extracted molar teeth. The changes have been reported and the nature of the change discussed. A modification in the use of the matrix and amalgam packing technique is suggested.


A rapid spectrophotometric assay of amide type dental anaesthetic agents. A spectrophotometric procedure for the determination of lignocaine in ointments was investigated and standardized for general application to local anaesthetic solutions of the amide type commonly used for dental injection, namely, lignocaine, prilocaine, mepivacaine, pyrrocaine and tolycaine. The method is based on the controlled formation of a copper complex and the Beer-Lambert law was found to be obeyed over a useful range. Results indicated that the method would be accurate, convenient and rapid, saving substantial time over wet-way methods conventionally used. For confirmation of the identify of the anaesthetic agent, infrared spectroscopy was shown to be a rewarding technique.


Factors affecting the structure of a fissure sealant at the enamel/sealant interface. Scanning electron microscope study of a fissure sealant on enamel in vitro shows the effect of varying methods of application, viscosity, dryness and time of etching of enamel. The effective attachment of the sealant to enamel required that it be brushed into the dry etched enamel. Viscosity seemed unimportant.


The influence of some manipulative factors on creep. The effects of a number of factors on creep in dental amalgam was investigated. The factors studied were the delayed time between mixing and packing, the packing technique, the alloy system and the annealing or ageing of specimens at 37 degrees C for one and 190 days. The delayed time and the alloy system factors as well as an interaction between them had a significant influence on the one day annealed specimens. The alloy system in the 190 days annealed specimen was the only factor to affect creep.


Immunological abnormalities in coeliac disease and their response to dietary restriction. I. Serum immunoglobulins, antibodies and complement. Twenty-three patients with coeliac disease were studied whilst on a normal diet and again after a mean period of 15 months on a gluten-free diet. Serum levels of IgG, IgA and IgM, total haemolytic complement, C3, serum autoantibodies and precipitins to dietary proteins were compared to those in age and sex matched control subjects. There was considerable individual variation, but as a group, patients on a normal diet had significantly raised IgA and low IgM and an increased prevalence of antibody to reticulin, smooth muscle and dietary protein. These abnormalities disappeared during the period of dietary restriction suggesting that they are disease epiphenomena rather than primary pathogenetic factors.


Immunological abnormalities in coeliac disease and their response to dietary restriction. II. Immunoglobulin containing cells, immunoglobulins and dietary antibodies in the small bowel. The numbers of immunoglobulin (Ig) containing cells in jejunal mucosa were determined in 29 patients with untreated coeliac disease and 28 control subjects. The patients had significantly increased numbers of IgM containing cells. Seven of the patients were studied again after 12 months on a gluten-free diet and showed a significant reduction in the number of IgM containing cells. The increase noted in untreated patients is therefore likely to be a manifestation of the disease rather than a primary abnormality of aetiological significance.


Factors influencing small bowel changes in dermatitis herpetiformis. Factors influencing small bowel morphology in dermatitis herpetiformis (DH) were investigated by comparing patients with DH and normal small bowel biopsies to patients with DH and abnormal small bowel biopsies. The mean age of 18 patients with morphological changes in small bowel (38 years) was significantly lower (P less than 0-001) than the mean age of nine patients with normal bowel mucosa (60 years). HLA typing confirmed the high frequency of HLA-B8 in DH (64%) but HLA-B8 was unrelated to the presence or severity of small bowel lesions. Four patients had diarrhoea with progressive weight loss or abdominal cramps subsequently responsive to gluten withdrawal. In this subgroup serum levels of IgG and IgM were significantly lower than in patients with normal small bowel mucosa. Small bowel involvement appeared to be independent of the duration and severity of skin disease, and the deposition of immunoglobulin and complement (C3) in the dermal papillae of skin adjacent to skin lesions.


Cancer and teratogenesis: infrequent occurrence after medical use of immunosuppressive drugs. This study examines long term "medical" immunosuppression with azathioprine or cyclophosphamide for immunopathic disease in relation to cancer and foetal malformation. The experience represent an aggregate of 241 years of treatment and 508 patient-years of follow-up in 133 non-transplant patients. For azathioprine the mean duration of treatment was 1-9 years and the mean duration of observation was 3-8 years, and for cyclophosphamide, the mean durations of treatment and observation were 0-7 and 4-6 years. A sample of 70 patients was shown by in vivo tests to have significantly suppressed cell-mediated immunity. In the period of review there were observed two cancers, both squamous cell carcinomas of skin, two benign neoplasms and six keratoses; after the period of review, three further cancers were recorded, one being in a subject with a known previous cancer. Nine pregnancies with azathioprine yielded no foetal malformations.


Do Australian Aborigines suffer from renal tract calculi? Analysis of intravenous pyelograms performed in the Darwin Hospital over the five-year period, 1970-1974, showed that 9% of the examinations carried out on non-Aboriginal patients demonstrated calculi in the renal tract. Although considerably fewer pyelograms had been performed on Aboriginal patients, only one showed a calculus. The result has been shown to be highly significant and is discussed in relation to racial and other differences between the Aboriginal and non-Aboriginal people of the Northern Territory.


Adverse reactions to drugs: a 12-month hospital survey. A formalised system of adverse drug reaction (ADR) reporting was instituted at the Royal Adelaide Hospital in August 1975. The present report reviews the results obtained from this system after a 12-month period of operation. A significant number of reports associated with the use of antibiotics and radiographic contrast media were received. The importance of "feed-back" of ADR information to prescribers is emphasised.


Salivary antipyrine kinetics in hepatic and renal disease and in patients on anticonvulsant therapy. The effects in man of liver disease, renal failure and hepatic microsomal enzyme induction on the elimination kinetics of antipyrine in saliva have been examined. Antipyrine (10 mg/kg) was given orally and assayed in saliva by gas-liquid chromatography. The mean antipyrine half-life from saliva in nine epileptic subjects receiving long term anticonvulsant drug therapy (6 hr +/- 0-9 SEM) was significantly shorter than in twenty normal healthy volunteers (10-7 +/- 0-6). Therapy included phenytoin and phenobarbitone, two drugs known to induce hepatic microsomal enzymes. Five subjects with chronic renal failure exhibited no significant difference in salivary anti-pyrine half-life (11-7 +/- 1-9) compared to the control group, whereas six subjects with chronic liver disease and impaired hepatic function had significantly increased half-life values (42-4 +/- 10). The results suggest that differences in the activity of hepatic microsomal enzymes are reflected by changes in salivary antipyrine elimination kinetics. Chronic renal failure appeared to have no effect on the function of these enzymes.


Left main coronary artery obstruction: early surgical experience with forty-two patients. Direct coronary artery surgery was performed on 42 patients with high grade obstruction of the left main coronary artery (LMCA), with a perioperative infarction rate of 7% and a hospital mortality of 9-6%. There was no significant difference in presentation of patients with LMCA lesions and no prediction of this lesion could be made by preangiographic assessment. Significant obstructive lesions in other coronary vessels were noted in most patients, triple vessel disease occurring in 27 patients (64-3%), double vessel in 14 patients (33-3%) and the LMCA lesion was an isolated lesion in only one patient (2-4%). Right coronary lesions occurred in 35 patients (83%), left anterior descending artery artery lesions in 38 patients (90%) and left circumflex system lesions in 34 patients (81%). The surgical procedures are discussed.


Hepatitis B antigen--a survey in a major metropolitan hospital. The prevalence of hepatitis B antigen in blood donors in the Wellington Hospital region is 0-27%. A retrospective survey of 66 persons found by the Wellington Hospital Laboratory to be hepatitis B antigen positive between September, 1971 and August, 1975, showed that over this period there has been a consistent decline in the number of new antigen positive cases found per year. This appears to be due to a decline in the numbers originating in the renal unit. A liver biopsy was taken in only one case and this showed chronic persisting hepatitis. Apart from the renal unit, high risk patients and staff are not tested regularly for hepatitis B antigen. Regular testing of laboratory staff and patients and staff of the cardiothoracic and haematology departments is recommended.


Hepatic venous occlusion from carcinoma of bile duct in ulcerative colitis. The illness is described of a 25-year-old man with an 18-year history of ulcerative colitis, who presented with obstructive jaundice due to a carcinoma of the bile duct. Terminally, he developed acute symptomatic hepatic venous occlusion due to extrinsic compression of the ostia of the hepatic veins. This was caused by a large mass of intrahepatic metastatic tumour.


Herpes simplex encephalitis.

Herpes simplex encephalitis. In this paper seven cases of severe viral encephalitis seen over a four year period at the Princes Alexandria Hospital, Brisbane, are presented. Four of these cases were proven cases of Herpes simplex encephalitis on the basis of viral culture, and three were probable cases of Herpes simplex encephalitis on the basis of rising serum antibody titres. A summary of the clinical aspects and laboratory investigations of the cases is followed by a brief discussion of the diagnostic and therapeutic problems of this condition.


Use of a microprocessor in the control of malignant hypertension with sodium nitroprusside. In a malignant hypertensive, steady control of blood pressure at a pre-determined level has been achieved with the continuous intravenous infusion of sodium nitroprusside. A microprocessor was programmed to assess the patient's blood pressure and adjust the rate of nitroprusside infusion so that a mean pressure of 106 mmHg was achieved. Brief interruption of the nitroprusside infusion allowed the effectiveness of changes in oral therapy to be evaluated. Thiocyanate concentrations were measured throughout as an index of potential nitroprusside toxicity. After six days, blood pressure control was maintained with oral therapy alone and papilloedema had almost resolved.


Bilateral ptosis and proximal myopathy--muscular manifestations of hypothyroidism. The case report of a 28-year-old hypothyroid female is presented. She demonstrated several muscular disorders of hypothyroidism including proximal myopathy and the previously unreported occurrence of severe bilateral ptosis.


Primary hyperparathyroidism presenting as a proximal myopathy. A 46-year-old female presented with a three year history of progressive weakness. Asymptomatic apart from proximal myopathy, multi channel screening and radiological features indicated primary hyperparathyroidism with severe metabolic bone disease. Removal of a parathyroid adenoma led to improvement of muscle strength and regression of bony and metabolic changes.


Recurrent venous thrombosis with a "lupus" coagulation inhibitor in the absence of systemic lupus. A young man presenting with recurrent deep venous thrombosis was found to have a lupus type coagulation inhibitor. He showed neither clinical nor serological evidence of systemic lupus. The value of the Russell viper venom coagulation time in the detection of the inhibitor is demonstrated. Anticoagulant therapy has not caused any bleeding complication despite the presence of the inhibitor.


Primary amyloidosis with cardiac involvement diagnosed by left ventricular endomyocardial biopsy. A case of primary amyloidosis is described. The patient presented with the nephrotic syndrome and later developed heart failure. Left ventricular endomyocardial biopsy was performed and haemodynamic data were recorded. The findings were those of a 'restrictive' cardiomyopathy. Histology of the biopsy was pathognomonic of amyloid involvement of the heart. The patient was started on chemotherapy consisting of prednisone, penicillamine, melphalan and fluoxymesterone. This case demonstrates the ability of endomyocardial biopsy in arriving at a definitive diagnosis in this patient.


[Results of the treatment of nonlymphoblastic acute leukemia in a pediatric population]. On a prospective fashion during approximately two years, 22 pediatric patients with acute non lymphocytic leukemia were evaluated. Of this population the majority had acute mielocytic leukemia, followed by acute myelomonocytic leukemia. Absolutely all patients at the time of diagnosis and subsequently every 4 to 6 weeks had a bone marrow aspiration test. When the patients were first seen, 54% of them presented fever; lymph node enlargement was not a common finding. Only few of this patients presented splenomegaly and/or hepatomegaly. In regards to complete blood counts the most outstanding of its was the presence of leukocyte count above 20000/mm.3 in 8 of this patients. From the 22 patients studied only 21 are evaluable. All 21 patients were treated with a 4 drug combination (modified COAP). Sixteen patients (76%) achieved bone marrow remission, of which only 15 patients (71%) achieved complete remission. The median duration remission was of 9.2 months with a range of 2 to 26 months. At the present time only 7 patients (33%) are alive and on remission. Two more patients are alive but in full relapse. The mortality rate of this study is of 59%. The review of recent chemotherapy reports is presented and the need for further trials is emphasized especially in view of recent papers published in which it appears that better results are being obtained at last in children's acute non lymphocitic leukemia.


Incidence of bone sarcoma in SW England, 1946-74, in relation to age, sex, tumour site and histology. A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours presenting during each hemi-decade did not markedly diverge from the 5-year mean for the period, nor was any significant change found in tumour incidence during the last 20 years of the survey. The age, sex and site distributions correspond with those reported elsewhere. Age-specific incidence rates are compared with those published for Sweden. For osteosarcoma and Ewing's tumour, both commoner in young people, the two series agree closely up to age 55 years, after which the Swedish incidence rates rise and are not exceeded when, for the present cases, Paget's osteosarcomas are included. Whilst Paget's disease may change the age incidence of some types of bone sarcoma, it is uncertain whether it increases the total number which occur. Differences in tumour incidence between males and females, whether for a specific type or for all bone sarcomas, are seldom statistically significant, but the patterns appear to be consistent.


Refractory anaemia with excess of myeloblasts in the bone marrow: a clinical trial of androgens in 90 patients. In a cooperative trial, 90 patients with refractory anaemia with an excess of blast cells in the marrow were evaluated and treated with androgens. The clinical presentation was very similar to previously published observations: features of medullary insufficiency were less marked than in primary aplastic anaemia; bone marrow blastic infiltration varied from case to case, and remained stable until death or until an acute leukaemic change. All the patients were treated with high doses of androgens as for aplastic anaemia. The efficacy of this therapy was poor. The average life expectancy was 13 months, 64% of deaths being associated with a change to acute myeloid leukaemia. A severe bone marrow deficiency foreshadowed early death, but myeloblastic transformation was observed whatever the initial degree of blastic infiltration of the bone marrow. A comparison with the literature suggests that androgen therapy may accelerate the change to acute leukaemia.


Morphanalysis of craniofacial dysharmony. The first stage in the morphanalysis of craniofacial dysharmony involves induction. In this process, individual analytic morphograms are combined to form analytic histograms, which in turn are connected to form analytic histomorphograms, which provide three-dimensional statements about the variation in craniofacial structures in a population. The second stage involves deduction, in which the analytic morphograms of a particular patient are compared with appropriate analytic histomorphograms, so that a diagnosis of the three-dimensional nature of the dysharmony can be made. Craniofacial morphanalysis is performed manually in small scale enquiries but the methods have been converted to computer-graphic technology for large-scale studies. A clinical morphanalysis service is currently conducted and a standard reference atlas is being prepared.


Bilateral mandibular condylysis-a morphanalytic diagnosis. Four cases of bilateral mandibular condylysis are presented. The condition does not appear to be included in current teaching or existing nomenclature and consists of an acquired absence of the mandibular condyles, unassociated with temporomandibular ankylosis or aural/facial anomalies. In the literature of condylar maldevelopment four published cases appear to justify reclassification as bilateral mandibular condylysis, bringing the recorded total to eight. Whereas previous writers have regarded the condition as a prenatal condylar aplasia or hypoplasia, morphanalysis studies of the four current cases have shown that the probable aetiology is postnatal local disturbance in the condylar region. The term condylysis has been chosen to emphasise the locally destructive (or lytic) mechanism which appears to be involved. Mandibular condylysis is distinguished from condylar aplasia by its non-association with aural/facial anomalies and because normal development appears to proceed until the lytic event occurs. It is further distinguished from primary and secondary condylar hypoplasia because the condyle is absent rather than small, because normal development appears to proceed until the lytic event occurs and because of its non-association with aural/facial anomalies or temporomandibular ankylosis.


Jaw lymphoma in Middle East children.

Jaw lymphoma in Middle East children. Six cases of jaw lymphoma occurring in Middle East children between 1971-1976 are reported. While the histological and radiological appearances of the tumours were suggestive of a diagnosis of Burkitt's tumour, the Middle East tumour failed to respond clinically to treatment which is effective against Burkitt's lymphoma. It is believed that these tumours may constitute a separate clinical entity. The identification of the initiating agent should be a matter of urgency, for treatment at present is invariably unsuccessful.


Clinical statistics of odontogenic cysts in West Malaysia. A study was made of the clinical statistics of odontogenic cysts treated at two hospitals in West Malaysia over a 6-year period. The general incidence of the individual cyst-types is similar to that reported in previous studies. A marked difference in the age distribution of radicular cysts emerged and 80% of the residual cysts in the survey occurred amongst the Chinese population. Reasons for the distribution variation are discussed.


Multiple cystic adenomas of labial salivary glands. A case of multiple cystic adenomas is described and their histological characteristics discussed. Review of the literature showed no previous publication of multiple tumours from labial salivary glands.


Current principles of morphanalysis and their implications in oral surgical practice. This survey of morphanalysis in an oral surgical context summarises current conventions concerning the fixed relations theory, the analytic morphograph and craniofacial morphography. The oral surgical implications are then discussed in preparation for subsequent papers on the morphanalysis of craniofacial dysharmony and mandibular condylysis.


Measurements of endosteal surface areas in human long bones: relationship to sites of occurrence of osteosarcoma. Using techniques of bone scanning and ashing, the areas of the endosteal surfaces in cortical and trabecular bone have been determined for the proximal, mid and distal thirds of each of the six long bones of an adult human subject. The relative frequency of occurrence of bone sarcomas, scored as to site, has been analysed in relation to these measured areas. Data on tumour occurrence have been drawn from three sources: radium-case data from Rowland and Keane (33 cases), naturally-occurring cases from series by Sissons (139 cases) and by Dahlin (473 cases). A strong correlation is demonstrated between tumour frequency and trabecular area, but correlation with cortical area is poor. By comparing the tumour frequency in the mid thirds of the bones with the total recorded it has been possible to show that the probability of tumour occurrence per unit area of cortical bone, relative to that of trabecular bone, is 0.16 +/- 0.06. Analysis of the available dose data for the radium cases shows that in this instance dose has not contributed to the observed correlations. The results lend support to the thesis that tumour occurrence depends on surface area, i.e. on the number of cells at risk.


Methotrexate-induced malabsorption in children with acute lymphoblastic leukaemia. A one-hour D-xylose absorption test was performed on 18 children with acute lymphoblastic leukaemia. Xylose absorption was normal in children who had not received methotrexate, but there was a significant degree of malabsorption in those who had taken methotrexate within the previous seven days. There was a progressive and significant increase in malabsorption related to the cumulative dose of methotrexate. These findings provide further evidence that regular methotrexate treatment every seven days is more toxic than if it is more widely spaced. The spacing of treatment is currently under investigation.


Classification of bone tumours.

Classification of bone tumours. Primary tumours of bone can be classified conveniently into distinct groups based on the appearance of the tumour cell, or its product, or both. Almost all the groups have benign and malignant counterparts. However, malignant bone tumours usually do not arise from benign tumours. Although the cell of origin in many tumours is unknown, the classification described in this paper refers to well-defined clinicopathologic entities, so that the behaviour of a given tumour can be anticipated. This classification is accepted the world over and provides a "common language" for those who treat patients with bone tumours.


En bloc resection for osteogenic sarcoma. Preservation of a limb without sacrifice of the principles of cancer surgery is desirable in young people with osteogenic sarcoma. At present amputation is generally regarded as the only well-established curative treatment for this condition. To determine whether en bloc resection with intensive chemotherapy is a realistic alternative to radical amputation and chemotherapy, 43 patients who underwent en bloc resection for osteogenic sarcoma of the distal femur (20 patients), proximal tibia (11 patients), shoulder girdle (11 patients) and fibula (1 patient) were studied. After tumour resection, chemotherapy and pulmonary resection 32 (74%) of the 43 patients are alive and 20 (67%) have no evidence of distant disease. Of the 38 patients without metastatic disease at the time of admission (5 were admitted with pulmonary metastases) 24 (63%) are alive without evidence of disease and without having had postoperative metastases.


Radiation treatment of Ewing's sarcoma and osteogenic sarcoma. At the Princess Margaret Hospital, Toronto, during the period 1960 to 1975, radiation therapy was given to 59 patients with Ewing's sarcoma without overt metastases. Over this period treatment was modified to include, as well as irradiation to the primary tumour, total body irradiation (TBI) and chemotherapy according to various regiments. The 5-year survival rate of 38% in 26% patients who received TBI suggests that this may be of value. In patients with osteogenic sarcoma preoperative irradiation was not found to be of value. Recently the resection of pulmonary metastases combined with chemotherapy has increased the survival rate. When the primary site makes resection impracticable, the response to irradiation and chemotherapy is encouraging. Three cases so treated are described.


Paraparesis following intrathecal cytosine arabinoside: a case report with neuropathologic findings. A 65-year-old white male with acute myelogenous leukemia received whole brain irradiation (2550 rads) and intrathecal cytosine arabinoside for CNS prophylaxis. Bone marrow remission had been previously achieved with systemic chemotherapy (vincristine, Adriamycin, prednisone, and cytosine arabinoside). Two weeks following the last intrathecal cytosine arabinoside treatment, the patient developed a spastic paraparesis requiring the use of a walker. A gas myelogram was normal and CSF examination revealed a protein of 50 mg/100 ml but was otherwise unremarkable. Five months later, the patient had improved in that he could stand on his own. A relapse of his leukemia subsequently occurred and the patient died the following month. Striking degenerative changes were found in the spinal cord at postmortem examination. These included microvacuolization, axonal swellings, and loss of myelin with scattered macrophages laden with fat.


Metastatic osteosarcoma to lung: a clinicopathologic study of surgical biopsies and resections. Metastatic tumor to the lungs is one of the most important factors in the poor prognosis of primary osteosarcoma of bone. Until recently, pulmonary resection alone was the only therapeutic method available to salvage these patients. Previous investigators have reviewed a number of clinical and pathologic parameters which may possibly relate to the prognosis of osteosarcoma and the occurrence of pulmonary metastases. The pathologic features of these latter lesions have received little attention other than to state that they generally are less differentiated than the primary tumor. A review of multiple pulmonary nodules resected from 15 patients has demonstrated that 66% of all lesions were essentially identical to the primary tumor. The 5-year survival from the original amputation was 33% in this series; however, it was not possible to prognosticate a favorable outcome from the metastasis, a similar type of observation which has been made by others in relation to the primary osteosarcoma.


Extraosseous osteogenic sarcoma following an intramuscular injection. A 29-year-old white male with an extraosseous osteogenic sarcoma is reported. He first noted a nodule at the site of eventual tumor development some eight years previously, following an intramuscular penicillin injection. Treatment consisted of wide surgical excision and radiation therapy, and he remains healthy some 8 months later. To our knowledge this represents the first case of extraosseous osteogenic sarcoma occurring at the site of a previous intramuscular injection.


Carcinocythemia (carcinoma cell leukemia) due to metastatic carcinoma of the breast: report of a case. A patient with a 17-year course of metastatic lobular carcinoma of the breast is described who developed large numbers of circulating carcinoma cells which were easily detectable in several routine peripheral blood smears shortly before death. This rare complication of carcinoma has been called "carcinocythemia." Carcinocythemia is probably due to widespread infiltration of many bone marrow sites and may also be related to splenectomy, which may impair reticuloendothelial clearance of circulating tumor cells. The differential diagnosis of carcinocythemia from superimposed acute myelogenous leukemia, which can complicate radiotherapy and chemotherapy for the primary tumor, is discussed. Cytomorphology, histochemistry, and electron microscopy of abnormal circulating cells should aid in the distinction of these two processes.


A factor in human saliva that induces differentiation of mouse myeloid leukemia cells. The differentiated functions of phagocytosis, locomotion, and morphological changes into cells resembling granulocytes and macrophages were induced in cultured mouse myeloid leukemic cells, M1 clone 34, by treatment with human saliva. The rates of induction of these differentiated phenotypes were proportional to the concentration of saliva added and the period of treatment. The factor inducing differentiation was nondialyzable and heat labile. This factor was purified 70-fold by fractionation with Diaflo membranes and DE52 column chromatography. The activities inducing the three differentiated characters examined were purified together, suggesting that they were all due to the same factor.


Transplantable granulocytic leukemia in strain 13 guinea pigs. The occurrence of a granulocytic leukemia in 1 of 40 female strain 13/N guinea pigs given N-nitroso-N-butylurea continuously in their drinking water for 21 weeks is reported here. This leukemia has been successfully transplanted in this guinea pig strain for 13 transplant generations by i.p. inoculation of leukemic blood or marrow cells. Macroscopically and microscopically, this leukemia resembles the chronic myelogenous form in humans. Histochemical studies showed, however, that unlike the human leukemic cells those in the leukemic guinea pigs are alkaline phosphatase positive. Electron microscopic studies of the guinea pig leukemic cells revealed the presence of numerous intracisternal A-type particles that are not found in corresponding normal leukocytes.


Guanosine diphosphate-L-fucose plasma: N-acetylglucosaminide fucosyltransferase as in index of bone marrow hyperplasia after chemotherapy. We have measured the plasma level of a fucosyltransferase in patients with acute myelogenous leukemia and non-Hodgkin's lymphoma at various stages of the disease and in normal controls. This enzyme transfers the sugar fucose from a guanosine diphosphate-L-fucose donor to high-molecular-weight acceptors with a terminal N-acetyl-glucosamine residue. The enzyme levels of fucosyltransferase in individuals free from disease and in patients with untreated leukemia or lymphoma were comparable. A substantial increase in plasma enzyme level was measured during drug-induced remissions, three weeks after drug therapy. The enzyme level fell to the normal range during unmaintained remissions inpatients with lymphomas; comparable information for the leukemia is not available since all remissions were drug maintained. These data, together with microscopic examination of marrow samples, indicate that the level of this fucosyltransferase is correlated with regeneration of a normal marrow population after chemotherapy. The enzyme assay may prove useful in defining normal bone marrow recovery and in timing cyclic combination chemotherapy in patients with neoplastic disease.


Murine myeloid leukemia: I. Pathophysiology and drug sensitivity. The pathophysiology of serially passaged myeloid leukemia of the RFM mouse was studied. The disease was characterized by progressive splenomegaly and infiltration of both marrow and spleen by myeloblasts. The animals became anemic and there was an associated erythroid hyperplasia in the spleen. Leukemic spleen cells obtained from animals early in the course of the leukemia were less malignant than those obtained from preterminal mice. The leukemia is most sensitive to alkylating agents but is also responsive to antimetabolites.


Studies on flies in Korea II. Taxonomical studies on sarcophagid flies (Diptera). Thirty-eight species belonging to 15 genera of the family Sarcophagidae were found so far in Korea. The description, locality in Korea, distribution and bionomics of these species are given in this paper. The fifth sternite, forceps and genitalia of these male flies are illustrated. The key to the species of sarcophagid flies in Korea are also presented.


[Congestive cardiomyopathy after doxorubicin (adriamycin)author's transl)]. Doxorubicin at a dose of 470 mg/m2 body surface, was administered to a 15-year-old boy with metastasising osteosarcoma. The cumulative dose caused severe "secondary congestive cardiomyopathy", which ended fatally, although the cumulative dose was below the recommended limit of 550 mg/m2. No other treatment for the tumour had been given. Postmortem examination revealed obliterative lesions in the intramural coronary vessels and electron-microscopy showed all the features of a cardiomyopathy at cellular level.


Correlation between hypomethylation of DNA and expression of globin genes in Friend erythroleukemia cells. This report identifies L-ethionine as an inducer of differentiation in murine erythroleukemia cells. When Friend erythroleukemia cells are grown in the presence of 4mM L-ethionine, globin mRNA accumulates and in 4-5 days, 25-30% of the cells in the culture contain hemoglobin. Incubation of the cells with bromodeoxyuridine prevents both ethionine-induced accumulation of globin mRNA and erythroide differentiation. At the concentration where L-ethionine acts as an inducer of FL cell differentiation it inhibits methylation of DNA and tRNA in vivo but does not prevent macromolecular synthesis or cell division. To establish whether a link existed between inhibition of a specific methyltransferase and activation of globin synthesis in FL cells, we examined the degree of hypomethylation of DNA and tRNA from FL cells induced to differentiate with dimethylsulfoxide and butyrate. In contrast to the tRNA from ethionine-treated cells, tRNA from cells induced by butyrate or Me2SO cannot be methylated in vitro using homologous enzymes. DNA isolated from cells exposed to any of the three inducers, however, was significantly hypomethylated when compared with DNA from uninduced cells. These data suggest that methylation of DNA may play a role in the regulation of gene expression.


Interactions of partial LSD analogs with behavioral disrupting effects of LSD and DMT in the rat. Adult male Holtzman rats were trained to barpress on a schedule whereby every fourth press earned a reward of 0.01 ml of sugar-sweetened milk (FR4). After an i.p. injection of LSD (0.1 mg/kg) or DMT (3.2 or 10 mg/kg) such barpressing is abolished completely and resumed, usually within an hour, at a rate near the preinjection control rate of pressing. It continues at a steady, uninterrupted pace until the animals are removed from the operant chamber one-half hour later. A series of N,N-diethylnipecotamide derivatives were synthesized and tested for their ability to modify the disruptive effect of these hallucinogens. N,N-diethylbutyramide (DBA) and 1-methyl-1,2,5,6-tetrahydropyridine-3-(N,N-diethylcarboxamide) (THPC) were also tested. Pretreatment with a single i.p. injection of any of these compounds (5--40 mg/kg) either had no effect on or else prolonged the duration of hallucinogen-induced cessation of barpressing.


Patterns of alveolar bone loss in Nigerian Yorubas. Unusual patterns of alveolar bone loss in 33 Nigerian Yorubas with severe periodontal disease are described. The subjects, aged 15-50 yr represented 1.4% of a population of dental patients in Western Nigeria. Periodontal pocketing and alveolar bone loss in the incisor and first molar regions, far in advance of other mouth areas, were the criteria for inclusion in this report. Intra-oral radiographs showed advanced horizontal or crescentic bone resorption in incisor regions, and vertical or arc-like bone defects around first molars. Incisors and first molars were frequently missing as a result of periodontal disease. Surveys of tooth mortality and periodontal pocketing in Western Nigeria, and immunological findings elsewhere, suggest these cases represent a severe form of plaque-induced inflammatory periodontal disease. The role of protein-calorie malnutrition as an aetiological factor is discussed.


Potential for clinical cooperation between dentistry and speech pathology. Clinical management of articulation dysfunctions is one area in which the joint efforts of dentistry and speech pathology are particularly beneficial. Those articulation deviations discussed result from: (1) deformities in the upper lip, teeth, mandible and the hard and soft palates; (2) introduction of dentures; (3) difficulties in adjusting to esophageal speech; and (4) special problems associated with cleft palate/cleft prepalate. Team management of the individual with cleft palate and/or cleft prepalate was also reviewed. While orthodontists and prosthodontists provide the technology for correct speech production, speech pathologists furnish therapy for cultivating speech or modifying defective articulation patterns. Speech pathologists also serve as liaisons with respect to patients and other professionals. The authors believe that, ideally, clinicians from all disciplines should assume a holistic attitude in treating organic and functional human pathologies. Such interdisciplinary clinical cooperation is especially effective between dentistry and speech pathology. The concept of team management of cleft palate/cleft prepalate is an excellent example of how concomitant treatment effects total patient care. However, joint research and educational ventures also contribute to this objective and should continue to be encouraged.


Tumor-associated humoral cytotoxicity in patients with acute myelogenous leukemia before and after chemotherapy. Sera of eight unselected adult patients with acute myelogenous leukemia obtained before and after chemotherapy were repeatedly tested for specific complement-dependent cytotoxicity against autochthonous peripheral white blood cells from the acute leukemia stage and from the remission stage, respectively. Complement-dependent cytotas demonstrated in all of the eight patients, while none of three patients' sera were reactive against white blood cells from the remission stage tested in parallel. The cytotoxicity was increased after chemotherapy, also in those patients in whom remission was not achieved.


Further evidence for a non-random chromosomal abnormality in acute promyelocytic leukemia. We have previously reported on two patients with acute promyelocytic leukemia (APL) who had what appeared to be a deletion of chromosome No. 17. We now describe a third patient with APL. All three patients had a structural rearrangement involving No. 15 and No. 17. Our current interpretation of the chromosomal abnormality is that it is a reciprocal translocation, t (15;17) (q22; q21). Evidence that this is a consistent rearrangement associated with APL comes not only from our three patients, but also from two other published cases of APL, studied with banding, who also had an identical abnormality.


Inhibition of RNA and protein syntheses makes non-differentiating mouse myeloid leukemia cells sensitive to a factor(s) stimulating differentiation. Treatment with ascitic fluid from animals bearing various tumors, can induce mouse myeloid leukemia line cells, M1, to differentiate in vitro into macrophages and granulocytes. Cells were isolated that were resistant to the ascitic fluid factor(s) stimulating differentiation (D-factor). The resistant cells became sensitive to the D-factor and differentiated after treatment with various inhibitors of RNA synthesis (actinomycin D, nogalamycin, chromomycin A3 or cordycepin) or protein synthesis (puromycin or cycloheximide). The cells could not be induced to differentiate by treatment with the inhibitors alone. The effective doses of the inhibitors of protein synthesis were toxic to the cells. Among these inhibitors actinomycin D (5 ng/ml) was the most effective for sensitizing the resistant cells. Inhibitors of DNA synthesis did not sensitize the resistant cells. Added actinomcyin D was mainly recovered in the nuclear fraction of the cells. The sensitizing effect of actinomycin D on the cells was roughly parallel to the extent of its inhibition of RNA synthesis in the cells. The effective concentration of actinomycin D (5 ng/ml) mainly inhibited it also inhibited alpha-amanitin-resistant RNA synthesis to some extent. These results suggest that alpha-amanitin-sensitive RNA synthesis may be involved in sensitization of the resistant cells to the D-factor.


Glucocorticoid binding and mechanism of resistance in some clones of mouse myeloid leukemic cells resistant to induction of differentiation by dexamethasone. Several clones of dexamethasone-resistant cells, which could not differentiate even in a high concentration of dexamethasone, were isolated from glucocorticoid-sensitive myeloid leukemic cells. Some of them were shown to be deficient in steroid binding to specific cytoplasmic receptors, while the others contained glucocorticoid-specific cytoplasmic receptors that might be the same as those in sensitive cells. One of the resistant clones was found to be almost completely deficient in nuclear acceptor sites for cytoplasmic steroid-receptor complexes. The remaining clones were also characterized by significantly reduced amounts of nuclear-bound glucocorticoid. These results suggest that resistibility to glucocorticoids in the resistant clones of myeloid leukemic cells is due mainly to a defect in some steps of intracellular transfer of the steroid. Dexamethasone-sensitive cells, which could differentiate in the presence of dexamethasone, could be also induced to differentiate by protein factor(s) in ascitic fluid. Although all the resistant cells showed a low response to ascitic fluid, some of them showed 10-fold enhancement of phagocytic activity which is a typical character of differentiated cells. These results suggest that response to steroids is not directly correlated with that to protein inducer(s).