[Impedance cardiography (author's transl)].

Determination of cardiac output by impedance cardiography exhibited perfect agreement with determinations performed by the Fick principle (r = 0.905; p less than 0.001); the measurements were carried out on 11 patients without valvular disease, 15 patients with mitral stenosis, 5 patients with aortic stenosis and 4 patients with combined aortic valvular disease. Impedance cardiography tends to give an underestimate of the cardiac output in patients with mitral insufficiency (N = 7) and in cases with combined mitral valvular disease (N = 9); in patients suffering from aortic insufficiency (N = 6), combined valvular disease (N = 5) and left to right shunts (N = 10) the cardiac output is often overestimated. Impedance cardiography is also suitable for determination of the cardiac output under exercise testing conditions up to submaximum ranges. This was demonstrated on 30 well-trained sportsmen, in a comperison and oxygen consumption testing (r = 0.937; p less than 0.001). Zo impedance does not change in healthy persons during exercise testing. Pharmacological investigations can be performed using impedance cardiography; a reduction in pressure values in pulmonary hypertension was demonstrated under the influence of nitroprusside. The stroke volume of a single cardiac revolution was, more over, measured in 12 patients with implanted pacemakers. P-ST intervals were 70--200 msec. The increase in cardiac output by 33% indifies the opinion that in certain cases, especially in young people, atrial synchronous pacemaker systems should be tried, despite the reported pitfalls and lack of success to date.


[Cytoid bodies in human skin (author's transl)].

Cytoid bodies represent ovoid, round or polygonal, approximately cellsized structures. In human skin such bodies may occur under normal as well as under pathological conditions. A number of heterogenous materials contribute to the morphogenesis of cytoid bodies, but in sections of human skin prepared for routine histology, different groups of cytoid bodies can not always be distinguished from each other. However, such a differentiation is necessary, if their presence is to be utilized as a diagnostic parameter or interpreted as a sign of physiological or pathological events in the dermoepidermal junction area. The object of the present studies was to (i) characterize the different groups of cytoid bodies by histological, histochemical, immunological and electron microscopical techniques, (ii) elucidate their nature, origin and morphogenesis and (iii) determine their significance in the histology of the skin. The following results were obtained: (1) Elastic globes can easily be identified by their bright autofluorescence and their affinity for elastin stains. Electron microscopically they exhibit a mixture of amorphous, granular and filamentous material, thus showing simlarities with elastic fibers. They are regularly found in normal skin of the extremities and the face but usually are absent on the trunk. Therefore their demonstration may be of importance in forensic medicine by allowing a better determination of the origin of isolated skin pieces. (2) Russel bodies may show gross variations in their histological, histochemical and ultrastructural properties. They contain different amounts of carbohydrates, lipids, proteins and immunoglobulins. These variable component result in a polymorphous structure. Russel bodies are produced by plasma cells and can frequently be found in skin infiltrates with a predominant admixture of this cell type. Their presence may be correlated with an increased local production of immunoglobulins, but their differentiation from other cytoid bodies and fungal elements is also of importance. (3) Civatte bodies are also eosinophil, PAS-positive and exhibit a typical fibrillar ultrastructure. They may be localised intraepidermally as well as in the upper corium. Although most frequently ecountered in lichen planus they may also be found in numerous other dermatoses and even in clinically normal skin. As indicated by their characteristics, they originate from epidermal keratinocytes and probably represent a morphological substrate of "apoptosis". (4) Amyloid is identified by the green birefringence of Congo red stained sections and by the more irregular arrangement of the individual filaments under the electron microscope. Cytoid aggregates of amyloid in the skin occur mainly in lichen amyloidosus and macular amyloidosis. Their presence should prompt further investigations of the patient for other signs of amyloidosis. (5) Fibrin in the form of cytoid clumps and clusters can frequently and specifically be demonstrated in skin diseases by immunofluorescence...


[Perduodenal Sphincterotomy (author's transl)].

In spite of immaculate surgical technique conventional transduodenal sphincterotomy is attended by a non-lethal complication rate of about 5.8% and a mortality rate of about 4.5%, the most frequent cause being dehiscence of the duodenal suture. The primary and secondary pathogenesis hereof is explained by the particular predisposition duodenal laceration on account of its special anatomy and operative vulnerability. Bearing these facts in mind, the method of so-called perduodenal sphincterotomy (p. sph.) seemed to offer more promising results for the following reasons: 1. Splitting of the sphincter through a minute incision in the duodenum (stab incision with a tenotome). 2. The advantage of primary closure of the cystic duct in the transcystic approach with medium-sized probes for the splitting. Experimental evidence shows the cystic duct to be very resistent towards dilation and rupture, especially in the presence of inflammatory processes. From 1967 to 1973 in 1441 cases of gall-bladder surgery p. sph. was performed 374 times and transduodenal sphincterotomy only 121 times. The statistic evaluation of the outcome of both methods showed significantly better results with p. sph. with regard to the incidence of postoperative non-lethal complications and duration of hospitalization. Assessment of non-lethal postoperative mortality and follow-up studies on 79% of the operated patients over a period from 3 to 9 years showed that the results of both methods were equal. In our experience the p. sph. is not only advisable when sphincterotomy is generally indicated, but also in the following special situations: a) as so-called "emergency papillotomy" in poor-risk patients; b) if the transduodenal approach is impossible awing to technical difficulties (poor accessibility, low site of the papilla); c) if the indication for papilotomy is dubious it can be chosen as the less dangerous method; d) for reoperation on the sphincter. On account of its prevailing advantages this new method for repairing papillary drainage is practicable as a routine method in sphincteric surgery.


Critical closing pressure or yield shear stress as the cause of disturbed peripheral circulation?

Rheological obstruction is possible on the basis of the known physical properties of blood. The angioarchitectonic arrangement of the mammalian microvasculature makes it especially susceptible to rheological obstruction. This is a price to be paid for the high efficacy and minituarisation which ameliorates the function under physiological conditions. Whenever blood looses its unique fluidity and assumes quasi conventional flow properties of a suspension, obstruction of the microvessels occurs: 1) when the blood perfuses vessels of the appropriate design under pressure insufficient to desaggregate, or deform the cells, or 2) when abnormal interaction between blood cells and cell wall occurs. In these respects, organ-specific differences also have to be taken into consideration; organs in which there are many venules are more susceptible than those with long capillaries: this facts will certainly have to be taken into account when discussing differences between skin and muscle perfusion.


Vibration-induced changes in vascular tone.

Longitudinal mechanical vibrations in sonic range (10-100 Hz) and of moderate amplitude (50-500) considerably reduce the contractile force of smooth muscle as well as striated muscle. Experiments elucidating the mechanism behind this effect are described. The inhibition of the contractile force is probably due to a direct interference with the action of the contractile proteins. Vibrations are supposed to increase the rate with which the interfilamentary crosslinks are broken. Thereby the number of established crosslinks is reduced and thus the force. Finally a hypothesis concerning the possible role fo this phenomenon in the pathogenesis of vibration induced Raynaud syndrome is forwarded.


Finger blood flow in healthy subjects of different age and sex and in patients with primary Raynaud's disease.

Finger blood flow measured at rest and after 3 minutes of circulatory arrest by strain gauge venous occlusion plethysmography was significantly higher (p less than 0.001) in a group of 13 healthy young men than in a group of 12 healthy young women. The flow values in 13 women in the meopause reached almost the level found in men. Hormonal factors might explain these differences. Between the group of the healthy young women and the 12 patients with Raynaud's disease there were only gradual differences in finger blood flow. Peak flow after 3 minutes of circulatory arrest was significantly lower in the patients (p less than 0.05). Whereas flow at rest showed only a tendency to lower values (mean room temperature 24 degrees C). The spontaneous and cold induced vasopastic attacks characterized by a decrease in finger volume and by very low or not measurable finger flow.


Fluorescein angiography especially of the upper extremities.

The technique used in sequential fluorescein angiography of the upper extremities is described. The sensitivity and reproducibility of the method are exemplified and discussed in regard to its applicability in diagnosis of organic arterial obliterations, e.g. in Raynaud's phenomenon as well as to its usefulness in evaluation of reconstructive arterial surgery and medical treatment with respectively thrombolytic (Brinase, Astra) and microhaemorheologic agents (Venoruton, Zyma; Arwin, Knoll) or those with an influence on systemic haemodynamic factors as in induced hypertension. The importance of standardized experimental conditions is emphasized, particularly with reference to vasodilatation. The method represents a new possibility of obtaining clinically a functional over-all information on the nutritional blood flow of rather extensive skin areas. Also, it can illustrate the interaction between macro- and microcirculation. Segmental macrovascular occlusions without concomitant damage of the corresponding terminal vascular area mainly cause a prolongation of the fluorescence appearance time. Obstruction of the microvascular blood flow reveals itself as more definite changes in the fluorescence pattern of the affected skin areas.


Effect of nicotine on isolated human blood vessels.

The action of nicotine was studied in isolated human vascular strip preparations using isometric recording of tension. Nicotine per se did not elicit any significant changes of smooth muscle tone. The effect of noradrenaline and direct smooth muscle stimulation, however, was enhanced. This action presumably is not dependent upon an adrenergic nervous mechanism, as in the intact organism but seems to be dependent upon a direct smooth muscle stimulation in itself not sufficiently strong to induce a contraction but leading to facilitated stimulation and propagation of the response.


Stenosing arteritis of the subclavian-axillary arteries (polymyalgia rheumatica sive arteritica).

According to recent investigations a stenosing arteritis of the subclavian-axillary arteries almost always is only one localization and an extreme variant of a systemic vascular disease, affecting aorta and large arteries, by pathologists called giant-cell arteritis or non-syphilitic aortitis and arteritis. The clinical manifestation of this disease process is often limited to a "painful shoulder syndrome".


Treatment of patients with secondary Raynaud's syndrome.

Treatment of secondary Raynaud's disease must be a treatment of the impaired microcirculation in the ischemic tissue. It can be performed in 3 ways: 1) By treating the vasospastic component 2) By reconstruction of occlusions or stenosis in the greater arteries 3) By improvement of the flow properties of blood. While the first two types of treatment often give unsatisfactory results, a new rheological therapy using Ancrod seems to be successful. This drug, a purified fraction from a snake venom lowers the fibrinogen concentration in blood therapy improving the flow properties of blood and plasma. In 5 patients suffering from severe secondary Raynaud's disease Ancrod was injected subcutaneously for a 2-4 week period. Some days after starting the treatment, the ischemic pain was reduced and finally disappeared. The beneficial effect continued even after ending the treatment. The mode of action of this new drug has been discussed.


Fibroxanthosarcoma of the uterine cervix: cytopathologic and histopathologic manifestations.

A case of fibroxanthosarcoma of the uterine cervix is reported with its cytopathologic manifestations. The cellular features of two cell populations characterized by atypical cells of fibroblastic and histiocytic types, suggests the correct diagnosis. The possibility of uterine sarcoma must be considered in the differential diagnosis of bizarre and unusual cytologic findings.


Condylomatous lesions of the cervix and vagina. I. Cytologic patterns.

Condylomatous lesions, although readily diagnosed on the vulva, are often missed in the vagina and on the cervix by clinical examination alone. The lesions are, however, quite common and may be misdiagnosed as mild dysplasia by cytology, colposcopy and even tissue examination. Condylomatous lesions are presently diagnosed on cytologic evidence in nearly two per cent of asymptomatic patients screened in our program and followed-up by colposcopy and tissue examination, when indicated. The cytologic presentation of these lesions is quite characteristic. The main features are seen in squamous cells: enlargement, bi- or multinucleation, hyperchromasia, peri-nuclear clearing, amphophilia and dyskeratotic changes. Our present experience indicates that a large number of lesions previously classed as mild dysplasias actually represent various stages of condylomatous lesions. When these stages of viral changes are removed from the group of dysplasias, the remaining cases become of much greater significance as the early stages of evolution of carcinomata of the cervix.


The role of cytology in the detection of malignant lymphoma of the uterine cervix.

The success of cytologic examination in the diagnosis of malignant lymphoma of the cervix is at present limited. The generally accepted cytologic criteria for the identification of malignant lymphoma may have to be applied with caution when examining material obtained by abrasive technique; the diagnosis should not be entirely excluded, even in the presence of cell aggregates.


Sputum cytology of metastatic carcinoma of the lung.

The cytopathology of 47 cases of metastatic carcinoma of the lung and of 28 cases of recurrent or metastatic bronchogenic carcinoma is reviewed. The diagnostic yield was better for recurrent than for metastatic carcinoma but overall was comparable to that of primary bronchogenic carcinomas. The metastatic tumors were located in all areas of the lung and included single as well as multiple lesions. The positive yield did not differ significantly in relation to any of the pathologic features but was somewhat higher if the metastases were large and centrally located. A definite differentiation of the metastatic tumors, usually adenocarcinomas, from new primary bronchogenic carcinomas is often possible particularly if the cytopathology can be compared with that of the primary lesion. Specific cytologic features include the relative lack of cohesion and the formation of columns in metastatic breast carcinomas, the formation of larger cohesive well circumscribed nodules composed of tall columnar cells in metastatic colon carcinomas, clear cell features in some metastatic adenocarcinomas of the kidney, and the small cell size and uniform, regular nuclear features in the often cytologically well differentiated metastatic carcinomas of the prostate.


Relation between cell composition of pleural effusions in patients with pulmonary carcinomas and their clinical courses.

1) Cancer cells of the effusions were decreased by chemotherapy, but this did not always indicate a good clinical course. 2) When the clinical condition was fairly good, the percentage of lymphocytes predominated in the pleural effusion. 3) When the clinical conditions became rather critical, there was an increase in the number of macrophage. 4) The cytologic findings were observed prior to the time the clinical symptoms became manifest. 5) The percentage of lymphocytes and macrophages in pleural effusions was not related to the percentage of lymphocytes and monocytes in peripheral blood.


Characterization of mononuclear phagocytes in human CSF using membrane markers.

The purpose of this investigation was to demonstrate those membrane receptor sites on mononuclear phagocytes of human CSF which provide additional evidence for their monocytic origin and function. Using a heterologous system, sheep red blood cells were coated with IgG- and IgM-fraction of the anti-Forssman-antiserum of rabbits. In another series of experiments, sheep red blood cells were additionally sensitized with fresh human serum as a source of complement. The possible inhibitory effect of human IgG on the uptake of red cell antibody complexes was tested. Washed and pretreated sheep red cells were added to different fresh CSF specimens from patients, whose CSF exhibited no conspicious biochemical, serologic or cytologic alterations. The percentage of phagocytizing mononuclear phagocytes was evaluated. When the particular IgG EA reagent described was utilized, most of the mononuclear phagocytes consistently exhibited the IgG- and complement-receptor activity which selectively characterizes blood monocytes and related cells.


Morphology and DNA content of endometrial cancer nuclei under progestogen treatment.

Twelve endometrial cancers have been observed before and during progestogen treatment. Eight were well-differentiated and displayed an objective response. It was essentially characterized by a volumetric reduction of the nucleus and the disappearance of tetraploid nuclei. The DNA content remained diploid or near-diploid. Reduction of nuclear non DNA proteins under hormonal treatment is suggested.


The influence of the internal compliance of a respirator on the alveolar gas distribution.

The occurrence of intrapulmonary redistribution "pendelluft" during the plateau phase of a respirator, with and without internal compliance, was studied in a lung-model which simulated an obstructive inhomogeneity. Internal compliance was achieved by adding a flask, with a variable volume, to the patient circuit of a respirator which had a low compressible volume (Engström Care System ECS 2000, Junger Instrument AB, Sweden). The amount of redistributed volume was found to be dependent upon the internal compliance. Without additional compressible volume, the ventilator produced up to 18% redistribution which under all conditions could be brought below the 1% level when an internal compliance was introduced. A highly significant correlation between the amount of redistributed volume (pendelluft) and the discharge time-constant of the plateau (taupl = CI (RI + Rtr) could be established. The results of mathematical consideration gained from an electrical analogue coincided with our experimental findings. From this, some consequences could be derived for the design of an internal compliance for use with a respirator.


Monolayer cell cultures as target cells for the study of lymphocyte cytotoxicity in cancer patients.

Lymphocytotoxicity using S3-Hela target cells has been studied in 20 cancer patients treated with ionizing radiation (head and neck, lung and breast cancers). Monolayer cultures of Hela cells were marked with radioactive 51 Chromium and cultured with non stimulated or phytohemagglutinin (PHA) stimulated lymphocytes. This study shows a spontaneous decrease of lymphocytotoxicity in cancer patients as compared with normal subjects and an immunodepressive effect of radiotherapy. We observe a significant decrease of lymphocytotoxicity for either stimulated or non-stimulated lymphocytes at the end of radiation treatment. Moreover one month after completion of radiotherapy a possible repair of a lymphocytoxicity seems to be related with a short-term (6 months) good prognosis.


[Adrenal function in chronic myeloid leukemia].

Adrenal function was studied in patients with chronic myeloid leukaemia treated in the past or presently with Busulphan. Adrenocortical function was determined by means of 24-hour profile of 11-hydroxysteroids (11-OHCS) in plasma, and urinary 24-hour 17 hydrocorticosteroids (17-OHCS) and 17-ketosteroids (17-KS). The adrenomedullary function was determined measuring VMA level in 24-hour urine. In most patients normal 24-hour 11-OHCS profiles and 24-levels of 17-OHCS, 17-KS and VMA. Only in some cases these levels were raised. This rise was observed more frequently in patients with blastic crisis of myeloid leukaemia which may indicate that the adrenal reserve was maintained in these patients. The investigations failed to show that the disease itself or Busulphan treatment impaired adrenal function. The possibility of a direct effect of Busulphan on melanin metabolism in the organism is discussed.


An autopsy case of type II glycogenosis.

An autopsy case of Type II glycogenosis was reported with detailed description of ultrastructural findings. In addition to two typical patterns of glycogen deposition, membrane-bound lysosomal glycogen and membrane-free cytoplasmic glycogen, we observed numerous vacuolar structures in liver cells and a large deposition of nomogeneous materials between fragmented myocardial fibrils. These findings were briefly discussed in this manuscript.


Long-term cytogenetic studies in acute leukemia of children; the nature of relapse.

Sequential long-term cytogenetic studies in 71 children with acute leukemia were designed to investigate the nature of relapse after prolonged remission. In the overwhelming majority of the cases the findings suggested clonal identity of the leukemic cell population in relapse with that studied at the onset of the disease, notwithstanding considerable karyotypic instability in almost half of the patients. In a small minority an independent origin of the relapse clone could not be excluded on cytogenetic grounds but was considered unlikely, since mechanisms capable of accounting for the changes observed in these patients could be demonstrated in other cases. The persistence of diploid leukemic cells in the presence of an aneuploid subclone was demonstrated in the relapse bone marrow and/or spinal fluid in all active phases of the disease. On this basis the conversion from an aneuploid to a predominantly or exclusively diploid karyotype could be visualized, and a new model of clonal evolution, involving repetitive formation of abnormal karyotypes from a surviving diploid clone could be suggested.


IMFRA (intermittent intrathecal methotrexate and fractional radiation) plus chemotherapy in childhood leukemia.

A protocol for the prophylaxis of CNS leukemia was devised involving intermittent low-dosage radiation of the craniospinal axis combined with single intrathecal injections of MTX. The retionale for this protocol was the timing of first CNS relapses in patients not receiving prophylaxis which suggests that leukemic colonization of the CNS is not restricted to the initial stage of the disease and that periodic measures might be advantageous. The low dosage of radiation was chosen because it is well tolerated and has been found temporaily effective in overt CNS relapse. The two series of patients were comparable as to various parameters. Results after three years of observation were comparable to those obtained by other with a single initial course of high-dose radiation, with an expected 50% uninterrupted complete 5-year remission. On the basis of 30 months follow up in 26 patients, the therapy is well tolerated. An increase in morbidity due to infections in remission was not associated with a higher mortality.


Chemotherapy of acute lymphoblastic leukemia in children.

Between 1969-1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple-drug regimen (L-2). Prophylaxis for meningeal leukemia was limited to the repeated intrathecal injections of methotrexate. Seventy-four patients achieved remission; the duration of remissions could be evaluated only for 70. Relapse terminated complete remission within 1-54 months in 21 children. Four of these relapses were confined to the central nervous system. Forty-nine patients continue in complete remission from 23 to 63 months. Chemotherapy has been discontinued in 29 children, and 25 of these remain without evidence of recurrence for 2-27 months posttreatment.


Bilateral interstitial pneumonia in acute lymphoblastic leukemia.

Of 148 children with acute lymphoblastic leukemia (ALL) 34 had bilateral interstitial pneumonia (BIP). Their records were reviewed retrospectively to evaluate the incidence of this pneumonia and delineate the various etiologic factors involved. All but 1 were in remission; 82% of the episodes occurred within the first 6 months, the majority of these occurring during the first 3 months of diagnosis of ALL; 16 were receiving methotrexate (MTX), and 14 were receiving combination chemotherapy with vincristine, prednisone and 6-mercaptopurine (6-Mp) and 4 were on no systemic therapy. Thirty patients with 35 episodes recovered within an average period of 18 days, including clearance of radiologic findings; 4 died. Four had open lung biopsies without complications. There was a single case of pneumocystis carinii infection diagnosed postmortem. Laboratory data and histopathologic findings (of 4 biopsies and 3 remaining autopsies) were suggestive of a viral etiology. The incidence of BIP in ALL at Children's Hospital of Michigan is 22.9% with a mortality rate of 10.3%. The incidence of pneumocystis carinii infection appeared to be low. Hypersensitivity to MTX was not substantiated.


The human spleen as revealed by scanning electron microscopy.

The three-dimensional world of the spleen was explored by scanning electron microscopy on both arterially perfused and nonperfused specimens, as well as on plastic corrosion casts of splenic vasculatures. Of 25 spleens studied, 18 were examples of hypersplenism. These were contrasted to 7 essentially normal spleens taken from children being staged for treatment of Hodgkin's disease whose spleens proved to be uninvolved in the pathologic process. Splenic sinuses in all 25 spleens were typified by a degree of porosity. RBC were caught in the act of entering sinuses from splenic cords. These sinus windows thus represent one end of an "open" circulation pathway. In casts of microvasculature, direct arteriovenous connections were demonstrated, thus establishing an anatomical basis for an often disputed "closed" circulation pathway. Spleens from 7 patients with hereditary spherocytosis had a super abundance of red pulp. Splenic cords were thickened and crowded with spherocytes, many of which presented slightly wrinkled membranes, as were also noted on the peripheral blood RBC. It is possible that these membrane features are unique for HS and reflect the intrinsic membrane abnormality in protein composition. The 7 spleens from chronic idiopathic thrombocytopenic purpura had white pulp as the predominant region. Germinal centers were frequent. Lymphocytes and plasma cells with well-developed microvilli were suggestive that release of antiplatelet antibody might be occurring in white pulp. Platelets were especially notable in peripheral white pulp and marginal zones. Platelet clumps were observed, generally adjacent to spleenic macrophages.


The reliability of head film measurements. 3. Tracing superimposition.

The superimposition of tracings from lateral skull x-ray films taken at different timepoints is an important method for assessing developmental and treatment changes through time. The usefulness of the data derived is, however, limited by the fact that the physical act of superimposing tracings is performed with some error. The magnitudes of error for superimpositions on different "planes" have not been amenable to quantitation by previously available methods. Using newly developed computer-aided techniques, we have been able to quantitate both the primary errors of tracing superimposition and the associated secondary landmark displacements for four conventionally employed anatomic reference "planes". For each reference "plane," twenty-five independent film pairs were examined independently by each of four judges. Therefore, 100 acts of tracing superimposition were available for each reference "plane." Output data are presented which appear to support the conclusion that measurement errors in tracing superimposition are a consequential factor affecting the confidence which should be placed in head film comparisons, particularly with regard to individual cases. Some consequences of this conclusion with respect to growth prediction and to the evaluation of treatment effects are considered.


The influence of transseptal fibers on incisor position and diastema formation.

Transseptal fibers are a part of the gingival group of fibers of the periodontal membrane, and they are very tough and resistant. They form a chain from tooth to tooth which, provided that it remains intact and is sufficiently strong to resist displacing muscular pressures, will preserve the contacts between the teeth throughout the arch. If the continuity of the chain is interrupted, the balance of the forces acting upon the teeth on either side of the break is upset and considerable displacements can occur. Maxillary median diastemas are classified as "simple" or "persistent" according to their etiology, and an operation to clear the upper midline suture of transeptal fibers is described as an essential part of the treatment of persistent upper median diastema.


Superior repositioning of the maxilla: stability and soft tissue osseous relations.

The skeletal stability and soft-tissue changes associated with superior repositioning of the maxilla by Le Fort I osteotomy or simultaneous anterior and posterior maxillary osteotomies was studied in thirty patients by means of a computerized craniofacial model. Excellent skeletal stability was demonstrated 14 months postoperatively. Postsurgically, the reduction in lower face height and amount of maxillary incisor exposure resulted in improved facial balance. The use of a computerized osseous and soft-tissue craniofacial model has added a new dimension to evaluation of surgical changes associated with correction of dentofacial and craniofacial deformities.


Inherent cellular radiosensitivity of human tumors of varying clinical curability.

It is well known that radiation therapy can be successfully used to cure or control some types of human tumors, while consistently failing in others. This has been ascribed to several factors including differences in the intrinsic sensitivity of the tumor cells and in their ability to recover from radiation damage. In this study, human tumor cells from an osteogenic sarcoma, a glioblastoma, and two medulloblastomas, as well as cells from human skin, were established in tissue culture, and the in vitrox x-ray survival and DNA repair parameters determined. No significant differences in either clonogenic survival or DNA strand rejoining ability could be detected among these human tumors or skin cells, despite the wide variability in their radiocurability in vivo. In addition, skin cell strains derived from patients exhibiting markedly sensitive or resistant skin reactions during fractionated radiotherapy showed no differences in survival characteristics from normal controls. It is therefore suggested that the wide range of radiocurabilities seen among various human tumors cannot be explained on the basis of inherent cellular factors responsible for the survival of tumor cells after x-irradiation.


Advantages of infant ventilators over adapted adult ventilators in pediatrics.

A lung simulator with variable compliance and resistance components was used to evaluate the dynamic compliance of the Bournes, Babybird, and Pediatric Emerson postoperative ventilators. With increase in airway pressure from combined changes in compliance and resistance, the internal compliance of the Bournes was lowest and the internal compliance of the Emerson was highest. With low constant airway resistance (50 cm/L/sec), the Babybird exhibited tidal volume losses similar to those of the Bournes in the face of decreased lung compliance. With constant lung compliance (10 ml/cm H2O) and increasing airway resistance, the Babybird had marked volume losses at higher volumes. Under all simulated conditions, internal compliance of the Emerson, although large, was relatively constant and the Bournes had the smallest internal compliance.


Cancer experience among coke by-product workers.

This paper presents the site-specific cancer mortality, 1953-1966, for men employed in by-product coke plants in Allegheny County, Pa. Approximate relative risks, which take into account race, age, and calendar years of follow-up, have been calculated for various work areas of the coke plant. The major findings are: 1. As indicated previously by Lloyd and Redmond, men with five or more years at the coke ovens have an excess risk of dying from lung cancer and kidney cancer. 2. Cancers of the digestive system are significantly elevated in nonoven workers. Cancers of two sites, the colon and pancreas, account for the total excess in cancers of the digestive system. 3. Cancers of the buccal cavity and pharynx appear high in nonoven workers, although the number of deaths involved is small. These observations clearly indicate the need to consider nonoven as well as oven workers when evaluating cancer hazards in the coke plant.


Cancer mortality among rubber workers: an epidemiologic study.

Several previous epidemiologic studies of the rubber industry--an industry that uses many chemicals--have identified excess mortality from certain specific cancers. In this study, four cohorts of active and retired workers, at four major rubber-tire plants, were identified historically and followed for the ten-year period from 1964 to 1973. The cancer mortality of these four population was compared, separately and combined, with that of the general community. For all cancers combined, there was a slight excess above the expected number of deaths, whereas for some specific cancers (stomach, colon, prostate, and neoplasms of the lymphatic and hematopoietic system) there was a marked excess of deaths. Proportional mortality analysis at other small plants revealed similar excesses for these cancers, and some excess for lung, bladder, and CNS cancers. Analysis of detailed individual work histories reveals an association of certain cancers with specific job exposures; in particular, lymphatic leukemia and solvent exposure, and lung cancer and curing-room exposure. For both bladder cancer and stomach cancer, preliminary analyses indicate an association with groups of jobs in adjacent production stages (handling and mixing raw ingredients, and processing the "green" precured rubber, respectively). Further analytic studies are currently under way to identify groups of rubber workers at increased risk of other specific cancers.


Case study 1: asbestos--the TLV approach.

A review of the control of carcinogenic exposures using the TLV approach presents a prospect of limited effectiveness. With asbestos, as with any carcinogen, no threshold is known below which no health effect may be manifest. At best, we have only limited dose-response information at levels much above those of practical concern. In the case of asbestos, current exposures can only be described crudely at any level of exposure, and health effects are only known for past high, but ill-defined, exposures. Limited information exists on the effects of synergistic interactions with other materials. The current U.S. TLV, based on data concerned with occurrence of asbestosis, has not been evaluated with regard to possible effectiveness in the prevention of asbestos cancer. Yet cancer is the heart of the asbestos-hazard problem. Finally, enforcement of the existing TLV, especially for asbestos has been limited, frequently absent, and often ineffective. Workers are exposed in many situations to levels much above the current standard. As discouraging as this picture may seem, a TLV can be useful for stimulating the development and application of engineering-control procedures. The application of these procedures, however, must be specified and mandated in future standards to lower worker exposures to the minimum commensurate with existing technology. As technology is developed that makes lower exposure levels possible in a large part of the industry, TLVs should be reduced to take advantage of that technology.


Inorganic arsenic--ambient level approach to the control of occupational cancerigenic exposures.

In 1820 the first malignancies ascribed as due to occupational arsenic exposure were reported as scrotal cancers among smelters. A century later the causal relationship between chronic occupational, environmental or medical arsenical exposure and skin carcinogenesis was firmly established. From 1948 to 1975, nine out of eleven epidemiological studies have shown, initially or upon review, significant excess mortality from respiratory cancer among diverse occupations exposed to various inorganic arsenicals. Two of the nine studies have shown concommitant, significant excess mortality from lymphatic cancer, and another, from skin cancer. Additionally, two such studies have revealed a dose-response relationship between arsenical exposure and lung carcinogenesis. In the first, reported in 1969, the relationship was semi-quantitative, with a possible interactive role by sulfur dioxide or other contaminants. The other demonstrated a dose-response which was quantitative for arsenic per se. Upon our reinterpretation, this dose-response also demonstrated an increased lung cancer mortality risk apparently at arsenic concentrations above 1 mug/M3, calculated as the 8-hour TWA daily exposure over a 40-year working life. However, these and related data do not reveal a definite no-effect exposure level. Thus, in the absence of data documenting a cancerigenically safe level of occupational exposure and because of the environmental ubiquity of arsenic, the conclusion is drawn that the arsenic body burden of workers should not be occupationally increased above that produced by the ambient level.


Cancer mortality patterns in the lead industry.

The mortality of 7,032 men employed for one or more years in lead production facilities ("smelters") or battery plants was observed over a 23-year period, 1947-1970. There were 1,267 certified deaths. Lead absorption in many members of the cohort was known to have been greatly in excess of accepted standards. The standardized mortality ratio (SMR) for all causes was 107 for smelter workers and 99 for battery plant workers. Deaths from malignant neoplasms were somewhat elevated in both groups, the SMR being 133 for smelter workers and 111 for battery plants. The excesses arose largely from tumors of the digestive organs and the respiratory system. Only three deaths are attributed to malignant renal tumors and seven to tumors of the central nervous system. The latter findings were of interest in view of the experimental production of renal tumors in rats and mice by the injection or oral administration of very large doses of lead salts, and the report by one group of investigators of gliomas in rats fed lead subacetate. Studies are continuing to characterize more fully the exposure of the above lead workers to substances other than lead. Additional follow-up of the cohort is also contemplated.


Metal-material workers and lung cancer in Japan.

The distribution by occupation of 39,255 lung cancer deaths in eight years, from 1960 to 1967, was analyzed. An age-standardized comparison of actual deaths and expected deaths revealed that cancer of the lung had tendency to occur with a significantly higher frequency in (1) metal material workers (Obs., 232; Exp., 176.5), and (2) workers in mining and quarrying occupations (Obs., 151; Exp., 127.9). By similar analysis, farmers, miners, and metal-material workers were noted as high-risk occupations for stomach cancer and clerical workers, and farmers were noted as such for leukemia. The value of occupational cancer in monitoring by such a simple analysis was stressed (see Figure 1).


Respiratory disease mortality among uranium miners.

A mortality analysis of a group of white and Indian uranium miners was done by a life-table method. A significant excess of respiratory cancer among both whites and Indians was found. Nonmalignant respiratory disease deaths among the whites are approaching cancer in importance as a cause of death, probably as a result of diffuse parenchymal radiation damage. Exposure-response curves for nonsmokers are linear for both respiratory cancer and "other respiratory disease." Cigaret smoking elevates and distorts that curve. Light cigaret smokers appear to be most vulnerable to lung parenchymal damage. The predominant histologic cancer among nonsmokers is small-cell undifferntiated, just as it is among cigaret smokers.


Occupational carcinogenesis. High-risk industrial groups: identification, education, and surveillance. Tyler Asbestos Workers Program.

It is concluded that sputum cytopathology is an excellent, simple, noninvasive, painless, and inexpensive means for early detection of malignant and premalignant lesions of the lung, and that no special techniques are necessary for the identification of ferruginous bodies.


The IARC program on the evaluation of the carcinogenic risk of chemicals to man.

The International Agency for Research on Cancer has initiated a program to evaluate the carcinogenic risk of chemicals to man. This program is centered on the production of monographs on individual chemicals, consisting of data on use and production, carcinogenicity in experimental animals, epidemiological studies and case reports, and other biological data such as metabolism and mutagenicity, and ending with a balanced evaluation of all the data made by an international group of experts. Chemicals to be surveyed for the preparation of monographs have so far been selected among those for which some evidence or suspicion of carcinogenicity in experimental animals and/or man exists and for which human exposure is known to occur. Of the 196 compounds already evaluated, 17 have been found to be associated with cancer in man. Ninety-four compounds were definitely carcinogenic in experimental animals, and 41 were shown to have a limited carcinogenic effect in experimental animals. A number of the chemicals found to be carcinogenic in experimental animals are produced in very large quantities. The type of exposure to the 17 chemicals found carcinogenic to man was occupational for fourteen, medicinal for two, and dietary for one.


Bacillus Calmette-Guérin contact immunotherapy of local and metastatic deposits of rat tumors.

Adjuvant contact therapy with BCG can be used to control tumor deposits at local subcutaneous sites and at other sites, particularly pulmonary metastases and pleural tumor growths. This treatment method is generally quantitatively more effective than general immunostimulation, or active immunotherapy that employs vaccines of adjuvant and tumor cells. Furthermore, this treatment is effective in hosts that lack full immunocompetence, making it still feasible in immunosuppressed patients. The current evidence indicates that local activation of host macrophages is probably the essential effector mechanism of adjuvant contact therapy.


Immunotherapy of cancer patients with Bacillus Calmette-Guérin: summary of four years of experience in Japan.

Active immunotherapy with living BCG was conducted on 98 patients with various types of cancer. The candidates for this therapy were patients with residual or inoperable cancer of the colorectum, liver, breast, biliary tract, lung, and other organs with a follow-up of 4-58 months. Eleven of the 98 (11%) were able to survive for as long as 37-58 months (mean survival time 42.5 months) because of this treatment and are still living. Another 11 patients are also alive more than 24 months after starting treatment. Thirty-seven patients, however, succumbed within 12 months despite BCG immunotherapy. On the other hand, 37 patients in the control group, who shared the same clinical status and did not receive BCG therapy during this period, underwent unhappy courses for 2-12 months (mean survival time 8.7 months). The pretreatment immunoresponsiveness of these 98 patients was suppressed, as measured by the following immunologic parameters: T-cell subpopulation in the peripheral blood, stimulation index of PHA, and skin tests to DNCB, KLH, PPD, and PHA. All of these parameters improved shortly after initiation of BCG injections in 22 patients who survived more than 24 months. In contrast, in patients who died within 12 months, immunoresponsiveness remained suppressed throughout the course. This result has suggested that there was an apparent correlation between the effectiveness of BCG and immunoresponsiveness. In addition, a good correlation was observed between the duration of inflammatory reactions at BCG injection sites and clinical prognoses. Moreover, it was shown that a relatively high amount of BCG (20-80 mg as an initial dosage) and repeated injections of living BCG were necessary to obtain a sufficient enhancing effect on the immunocompetency of these late-stage cancer patients. The most conventional criterion used to determine an optimal time for booster injections of BCG was measurement of the PPD-evoked skin reaction at the BCG injection site, that is, Koch's phenomenon. When a marked flare-up reaction of more than 2.5 X 2.5 cm in size was observed, the effect of BCG was considered to be continuing, and no additional booster injection was needed. The mean interval between the first and second BCG injections was 6.2+/-1.1 months in patients who survived more than 2 years. In contrast, the duration of this reaction was only transient in ineffective cases. The most frequent side effects of this therapy were fever and malaise; these complications occurred in 62% of the cases. No severe side effects, such as dissemination, anaphylactic shock, or granulomatous hepatitis, have been experienced throughout this study, even in patients to whom a total dosage of more than 200 mg of living BCG were injected.


Therapeutic effectiveness of neuraminidase-treated tumor cells as an immunogen in man and experimental animals with leukemia.

The immunogenicity of leukemia L1210 in DBA/2 Ha and 6C3HED lymphosarcoma tumor cells in C3H/f mice was significantly increased after treatment with V. cholerae neuraminidase. DBA/2 Ha and C3H/f mice repeatedly immunized with neuraminidase-treated tumor cells rejected subsequent challenge of 10(7) or 10(6) untreated tumor cells, respectively. Based on the 51Cr microcytotoxicity assay, both strains of mice showed strong complement-dependent antibody titers and cell-mediated immunity. Sera and splenic lymphocytes from immunized C3H/f mice neutralized the tumorigenicity of 6C3HED lymphosarcoma and protected the recipient C3H/f mice against the disease. Immune lymphocytes pretreated with anti-theta sera lost their ability to neutralize the tumorigenicity of lymphosarcoma, and they failed to be stimulated by T-cell mitogens. We studied the effectiveness of chemoimmunotherapy in DBA/2 Ha mice with leukemia L1210. A single near optimal dose of BCNU 2 days after implantation of 10(6) tumor cells increased the survival time. A single immunization with 2 X 10(7) neuraminidase-treated L1210 tumor cells 4 days after cytoreductive therapy increased survival and resulted in cures for 50% of  animals. Immunization of mice with neuraminidase-treated tumor cells and MER produced indefinite survival in a larger percentage of mice than did either treatment alone. AKR mice with spontaneous leukemia treated with combination chemotherapy sustained an 180% increase in life-span. Combination chemotherapy plus immunization with neuraminidase-treated syngeneic or allogeneic (Gross virus-induced) E2G leukemia cells were highly effective in prolonging the life-span of the immunized leukemic AKR mice. The experimental data led to clinical trials in acute myelocytic leukemia with neuraminidase-treated a-logeneic myeloblasts. Patients with acute myelocytic leukemia were randomized into two groups after remission induction. The median remission duration of patients on sustaining chemotherapy alone was 19 weeks (8 patients), whereas six of nine patients who received neuraminidase-treated allogeneic myeloblasts remain in remission 79-132 weeks. Statistical analysis of the remission duration and survival of patients who received chemoimmunotherapy versus the control group shows highly significant differences.


Active specific immunotherapy of human solid tumors.

Active specific immunotherapy of human solid tumors by use of enzyme altered cells appears to be a feasible approach. Our initial results, we believe, warrant continued effort in this area. There seem to be no adverse clinical effects to such treatment. In vitro assay methods, to document enhanced immunity, must be included in any immunotherapy program. Equally importantly, such test methods should be expanded for the earliest detection of adverse effects, such as blocking during the course of immunotherapy. The role of immunotherapy must be that of adjuvant treatment, and its only applicability will be in that role.


Adjuvant immunotherapy in bronchogenic carcinoma.

Ten patients with locally far advanced bronchogenic carcinoma were treated with autologous tumor vaccine after a radical surgical resection. Three of 10 patients treated with tumor vaccine are alive (median survival of 26 months) whereas all nine patients in the control group are dead (median survival of 6.5 months). Active immunotherapy adjunct to radical surgery appeared to improve cellular immunity of the treated patients in the postoperative period, and the migration inhibition test indicated sensitization of treated patients against their tumor.


Immunotherapy of chronic myelocytic leukemia: effects of different vaccination schedules.

In a clinical trial of immunotherapy in chronic myelocytic leukemia, 62 patients received repeated intradermal injections of BCG-cultured cell mixtures, while 16 were vaccinated with BCG alone. The lymphoblastoid cell lines used for vaccination were established from blood of patients with advanced myeloid leukemia and were reactive with "specific" primate antisera against myeloid leukemic cells. Both sensitization to target cell antigens and substantial general increases in delayed hypersensitivity responses were recorded among immunized patients. Major immunologic complications (hypersensitivity and "autoimmune" phenomena) were observed in 10 patients. These complications were attributable to the BCG content of vaccines, and their incidence correlated with intensity of immunologic stimulation. Data from cases in which intermittent busulfan therapy was used provided suggestive evidence that immunotherapy (either with BCG-cell mixtures or with BCG alone) prolonged unmaintained remissions in one-third of the patients. Among 48 "good-risk" patients, there was an inverse correlation between intensity of immunologic stimulation and survival. The survival of 18 patients who received the most intensive vaccination schedule was identical to that of controls. Survival of the other 30 patients was significantly better (p = 0.03), with an increase of 2 years in median survival. Survival of 30 poor-risk patients (24, most intensive vaccination schedule) was identical to that of controls. We conclude that immunologic stimulation may produce worthwhile prolongation of life in CML but that overly aggressive schedules of immunotherapy abrogate this effect. Our experience raises the question whether results in other clinical trials of immunotherapy may have been adversely affected by excessive frequency or dosage of immunologic stimulants.


Immunotherapy of osteosarcoma patients with virus-modified tumor cells.

Twelve patients 11-20 years of age with recurrent osteosarcoma were immunized with either autologous or allogeneic tumor cells infected with influenza virus, strain B/Michigan or A/Port Chalmers. Six patients received only the vaccine, and the remaining six patients continued to receive methotrexate chemotherapy. The main objectives of this study were to determine if immunizations were toxic, if antibodies developed to the influenza virus antigen component of the vaccine, if this vaccine increased tumor-specific cellular and humoral immunity, and if the increase in immune response could be correlated with clinical course and prognosis. In all 12 cases, toxicity was negligible, and immunizations boosted antibody titers to both tumor cell and influenza virus antigens. However, in four of the six patients with advanced disease who received immunotherapy only, the vaccine did not stimulate mixed lymphocytes nor did it increase cell-mediated immunity. By contrast, five of six patients with minimal disease who continued methotrexate therapy developed cellular and humoral immunity in response to both allogeneic and autologous tumor cells. Although no clear-cut relationship between responses to the tumor cell vaccine and clinical course and prognosis could be demonstrated, three of the six patients with minimal disease have survived for 7-8 months after the first vaccination, without progression of disease. This study demonstrates that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.


Preparation and therapeutic potential of rabbit antisera with "directed" specificities for mouse leukemias.

Several immunization regimens for preparation of ALK-NABS were compared. One series of eight intravenous injections spaced over 5 weeks gave an ALK-NABS with potency and specificity that could be bettered only slightly by a second series of four injections spaced over 2 weeks, whereas a third series of injections was deleterious. Use of late immune antisplenocyte NABS for such immunizations produced ALK-NABS reagents with the highest in vitro specificity to leukemia cells relative to splenocytes after absorption, whereas early immune antisplenocyte NABS gave ALK-NABS with the highest antileukemia specificity relative to thymocytes. Therapy experiments with leukemias L1210 and BW-A showed increased survival times for isogeneic mice injected intraperitoneally with 10(3) (L1210 only), 10(4), and 10(5) (higher significance for L1210) cells, when ALK-NABS was given intraperitoneally in high dose on 4 or 5 successive days starting 1 day after inoculation of leukemia cells. In additional experiments with 10(5) cells given intraperitoneally, lower doses of ALK-NABS were progressively more effective with L1210 leukemia, producing some survivors without any apparent toxicity from the antiserum. In contrast, a similar experiment with leukemia BW-A was entirely negative. Addition of guinea pig serum to already excessive amounts of antiserum was not helpful.


Discussion paper: protective immunity in leukemic mice treated with specific "immunogenic" RNA.

Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.


Acute renal failure and gout as presenting features of acute lymphoblastic leukaemia.

A leukaemic child is described who presented with renal failure and gout attributable to hyperuricaemia before the leukaemia could be diagnosed.


Primary intimal sarcoma of pulmonary valve and trunk with osteogenic sarcomatous elements. Report of a case considered to be pulmonary embolus.

A 49-year-old woman had a six-week history of increasing shortness of breath and fatigue. X-ray films and pulmonary scans showed multiple areas of emboli, especially in the right lung. Treatment with heparin was unsuccessful, and although a repeat scan showed only slight changes, the patient's condition deteriorated. Acute pulmonary edema and ventricular tachycardia preceded her death. Autopsy revealed a primary intimal sarcoma with osteogenic elements arising in the posterior leaflet of the pulmonary valve and obstructing the main pulmonary artery and its right branch.


In vitro correlates of clinical response to methotrexate in actue leukaemia and Burkitt's lymphoma.

The response of drug-resistant patients with acute leukaemia and Burkitt's lymphoma to treatment with a 24 h infusion of methotrexate (MTX) followed, in some cases,by cytosine arabinoside was correlated with in vitro measurements of total intracellular MTX, exchangeable intracellular MTX, and suppressibility of deoxyuridine (UdR) incorporation in isolated marrow blast cells at extracellular MTX concentrations of 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M. Total intracellular MTX levels and exchangeable intracellular MTX levels were not significantly different in responding or non-responding patients at any MTX concentration, but increased four-fold for every ten-fold concentration increment studied. Extracellular MTX levels in excess of 10(-7)M appeared necessary to allow accumulation of exchangeable intracellular MTX. UdR incorporation at 10(-6)M and 10(-5)M differed significantly between responding and non-responding patients, with responders having less than 20% of control values and non-responders having greater than 40% of control values. Further, increasing the extracellular MTX concentration from 10(-6)M to 10(-5)M produced no significant decrease in UdR incorporation in either group. The therapeutic implications of this apparent threshold are discussed.


Cell volume measurements in acute leukaemia: method and value for diagnosis and prognosis.

Cell volume was measured using a Coulter counter in 42 cases of adult acute leukaemia, before any therapy. In every patient, the distribution was log-normal. A breakdown of the results with regard to the cell-type gives the following informations: The mean modal volume (M.M.V.) differs significantly from one type of leukaemia to another: the cell size in the myeloblastic type is larger than in the lymphoblastic, and smaller than in the monoblastic and myelomonocytic types. The dispersion of cell volumes, for a single patient, is low in acute lymphoblastic leukaemia, wider in myeloblastic cases and is even larger in myelo-monocytic patients. In 9 of the 10 acute myelo-monocytic leukaemias studied, the existence of two populations was shown by a double peak. Once relapse occurs, the cell volumes seem greater than during the first phase of the disease, at least in acute lymphoblastic leukaemia. No correlation has been found between the mean modal volumes and the labeling index, after incorporation of 3H-TdR.


Specific xenogenous antiserum to cells of chronic myeloid leukemia (CML) in blastic crisis.

The antiserum was obtained from horses immunized with cells from patients with blastic crisis of CML and completely absorbed with normal white blood cells (WBC). The absorbed antiserum remained cytotoxic to blast cells from nearly half of the patients in blastic crisis and did not react with WBC from patients with Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL), Chronic Lymphoid Leukemia (CLL) and Chronic Myeloid Leukemia (CML) in its chronic phase as well as with cells of human normal bone marrow or fetal liver.


Chemo-immunotherapy versus chemotherapy in acute myeloid leukemia. Preliminary results.

Since November 1974, 44 patients with acute myeloid leukemia, in first remission were randomized between chemotherapy alone and chemotherapy plus BCG. There were 8 relapses and 7 deaths with chemotherapy, 7 relapses and 3 deaths with chemotherapy plus BCG. The survival of both groups is not, at the time, significantly different.


A simplified in vitro classification for prognosis in adult acute leukemia: the application of in vitro results in remission-predictive models.

Previous classification in vitro of adult acute leukemia incorporating morphology has been complex and difficult to understand. We have devised a simplified classification based solely on leuekemic proliferation in vitro. Seventy-six patients with adult acute leukemia previously untreated were included in this study and received identical chemotherapy. Three groups were recognized. The complete remission rate was 76% in the 21 patients with no leukemic growth in vitro (Group 1), 75% in 36 patients with leukemic cell growth but aggregates of 20 cells or less (Group 2), and only 21% in the 15 patients with aggregates of greater than 20 (Group 3). There was a highly significant difference in complete remission rates between Group 3 and the other two groups (p less than 0.001). Linear logistic regression analysis demonstrated the independence of the growth in vitro from other prognostic variables. A predictive model utilizing the in vitro result more accurately predicted for remission, both retrospectively and prospectively, than a model constructed with presently known prognostic parameters. The cause of death in failures suggested that this system detects resistance to the chemotherapy.


A case of chronic granulocytic leukemia in a dog.

A case of chronic granulocytic leukemia was diagnosed in a ten year old miniature poodle and was observed for four and one half years. Methods of diagnosis and characteristic features are described. A persistent granulocytosis with a preponderance of mature forms and the absence of a detectable underlying pyogenic process were key diagnostic features which enabled distinction of this neoplastic process from acute granylocytic leukemia and a leukemoid reaction. Other features included dysplastic granulocytes in various developmental stages, marginal anemia and hyperplastic bone marrow (myeloid elements). No blast crisis occurred. This dog was euthanatized in August 1975.


Erythroleukemia-like syndrome due to busulfan toxicity in polycythemia vera.

Over a 19-year period, a patient with polycythemia vera who had undergone a splenectomy received six courses of busulfan for recurrent thrombocytosis. The total dose of busulfan given for the sixth course was greater than that used for the previous ones. Severe pancytopenia followed, which persisted for 4 months. During this period there was marked erythroid hyperplasia in the bone marrow with striking dyserythropoiesis; PAS-positive red cell precursors, as well as moderate numbers of circulating normoblasts and evidence of chronic and acute hemolysis, were present. All of these findings reverted to normal without therapy, and the polycythemic state eventually recurred. These events are interpreted as an unusual marrow reaction following busulfan overdosage rather than a transient erythroleukemia.


Telangiectatic osteogenic sarcoma.

Of approximately 1,999 cases of osteogenic sarcomas at the Mayo Clinic, 25 were diagnosed as telangiectatic osteogenic sarcomas. Of the 25 patients involved, 16 were males and 9 were females, and their ages ranged from 6 to 49 years. Six patients had had pathologic fracture. The lesions were typically located centrally and usually in the distal femur or proximal humerus and roentgenographically were large and purely lytic with destruction of cortex. Grossly, the lesions were cystic and contained clotted blood. Histologically, cystic spaces that contained blood were lined with anaplastic spindle cells and benign giant cells; sometimes, there were so few malignant cells that diagnosis was difficult. Usually, fine, lacelike osteoid was present. Of the 25 patients, 23 have died of metastatic disease, and another has developed pulmonary metastasis 11 months after amputation. Only one patient has survived for more than five years; however, he has developed pneumothorax. Data from this series suggest that the outlook in telangiectatic osteogenic sarcoma is more bleak than in conventional osteosarcoma.


Occurrence of acute leukemia in females in a genetically isolated population.

Acute lymphoblastic leukemia was found in six young females in a genetically isolated Syrian Jewish Community in Brooklyn, N.Y. over a 15-year period. This represents a frequency 30 times greater than the expected rate. In this community the frequency of first cousin marriages is estimated to be seven percent. Three cases were related on their maternal side, the parents of a fourth case were themselves related as were both sets of grandparents of a fifth case. In two families a history of infertility was present. On average, fathers of the cases were 5.5 years older at birth of the cases than a matched sample of community controls and 7.2 years older than a matched sample of non-community controls. The high frequency of consanguinity and the older age of the fathers may increase risk to acute leukemia for young girls in this community.


Simultaneous occurrence of non-Hodgkin's lymphoma and acute myelomonocytic leukemia.

The simultaneous occurrence of nodular poorly differentiated lymphocytic lymphoma (NLPD) and acute myelomonocytic leukemia (AMML) was confirmed by the histologic examination of lymph node section, peripheral blood, and bone marrow. This association in the absence of previous chemotherapy or radiotherapy has not been previously documented. There have been six previous case reports of patients with non-Hodgkin's lymphocytic lymphoma who, during treatment with alkylating agents or radiotherapy, developed acute myeloid leukemia (AML). These methods of therapy may have had a leukemogenic role in such patients. The possible relationship between these two diseases is discussed.


Cytotoxic effects of 1-beta-D-arabinofuranosylcytosine and 6-thioguanine in vitro on granulocytic progenitor cells.

We have utilized an in vitro clonogenic assay of mouse and human marrow granulocytic progenitor cells to determine the cytotoxic effects on granulopoiesis of the chemotherapeutic agents 1-beta-D-arabinofuranosylcytosine (ara-C) and 6-thioguanine. Concentration- and time-dependent decrements to plateau levels of granulocytic colony-forming capacity occurred. The sequence of drug administration was important and synergistic cytotoxicity was noted when certain schedules of ara-C and 6-thioguanine combinations were used. Endotoxin-stimulated colony-forming cells had increased sensitivity to the in vitro ara-C exposure. High or intermittent doses of ara-C demonstrated enhanced cytotoxicity when short exposure times (1 to 8 hr) were utilized, whereas low doses were markedly cytotoxic with prolonged exposure (10 days). Normal and leukemic human colony-forming cells had similar susceptibility to the cytotoxic effects of ara-C. Exposure of granulocytic precursors to these drugs in vitro produced effects similar to those previously reported with in vivo drug administration. These techniques appear applicable for providing improved screening models to evaluate chemotherapeutic regimens for clinical use.


Accumulation of giant heterogeneous RNA molecules in acute myeloid leukemia blast cells.

Time course and "chase" experiments showed that, after incubation of acute myeloid leukemia blast cells with a labeled RNA precursor, a large proportion of radioactivity remained associated with RNA molecules larger than 45 S even after several hr. Double-labeling experiments with [5-3H]uridine and [methyl-14C]methionine indicated that unmethylated giant heterogeneous RNA larger than 45 S is processed much more slowly than the 45 S ribosomal precursor, so that relatively large amounts of fairly stable RNA of the former class accumulate in the cell. The measurement of labeled giant heterogeneous RNA molecules bound to polyuridylate-fiberglass filters showed that molecules carrying polyadenylate segments seemingly turn over faster than those lacking polyadenylate.


Randomized clinical comparison of daunorubicin (NSC-82151) alone with a combination of daunorubicin, cytosine arabinoside (NSC-63878), 6-thioguanine (NSC-752), and pyrimethamine (NSC-3061) for the treatment of acute nonlymphocytic leukemia.

Sixty-six newly diagnosed patients with acute nonlymphocytic leukemia received either daunorubicin alone or a combination of daunorubicin, cytosine arabinoside, 6-thioguanine, and pyrimethamine for remission-induction therapy. The two treatment groups were comparable with respect to the two major prognostic factors in this disease, which were age and presence or absence of infection on admission. The two therapies produced similar results with respect to CR rate and median survival results. Single-agent therapy was associated with less frequent utilization of hospital inpatient facilities and fewer platelet transfusions. The four-drug combination did not decrease the incidence of meningeal leukemia. Patients who achieved CR were treated with two half-dose consolidation courses of the successful remission-induction regimen. Subsequently, all patients received cyclophosphamide and guanazole monthly for maintenance therapy. Median durations of remission for both induction-treatment groups were similar (6.8 and 5.6 mos). The therapeutic results with the single agent in this study were not inferior to those obtained with the drug combination tested, as well as most other previously reported combinations of antileukemic drugs.


Dental insurance and equity of access to dental services.

The first-year consequences of national dental insurance, introduced in Sweden in 1974, are examined here from the point of view of social justice. The concept of equity of access in medical care is discussed. In a local survey, a comparison is made between use of dental services in 1972, 1973, and 1974. The results indicate that the fewer people visited the dentist after the implementation of the insurance than before. Other evidence supports this conclusion. People traditionally considered to be underprivileged as to dental care were compared with other people. One underprivileged group, edentulous persons, received more treatment after the insurance was instituted than before.


Utilization of dental services in the adult Danish population 1975.

Lack of information on the dental behavior of adults in Denmark has become a major problem in the national planning of dental services. The purpose of this study was to establish the pattern of utilization of dental services among adult Danes (aged 15 and above). A three-stage cluster sampling design covering the total adult population of Denmark was used to draw a representative sample comprising 1,600 persons. Household interviews by trained interviewers were carried out. Of the adults interviewed, 58% reported yearly dental visits the last 5 years, 32% had not seen a dentist or only when in pain, and 10% went irregularly. Differences according to place of living, age, sex, occupation and school dental care were found. 63% of those who had seen a dentist reported bad teeth or were edentulous with or without dentures. 10% reported fear, 9% had good teeth and 5% reported economic difficulties. The most frequent treatments at the latest dental visit were cleaning and filling for the regular patients and extractions and dentures for the nonregular patients. A multiple classification analysis revealed that the number of teeth was the strongest predictor for dental services, with the following predictors in descending order: age, occupation, place of living, economy, sex and school dental care. These variables could explain 58% of the variation in utilization.


Testing the internal and external validity of a simplified dental caries index on an adult population.

This analysis of a caries index, proposed in 1966 to WHO as a simplified method of measurement, as tested on a 16- to 45-year-old population who were seeking dental care at the University of Minnesota School of Dentistry revealed several weaknesses associated with the index. An analysis of the external validity of this index, a comparison with subjects' DMFS scores, revealed a correlation coefficient of 0.71. Although the index purports to measure the prevalence and severity of dental caries by dividing the dentition into five zones representing increasing severity of dental caries experience, an analysis of this index's internal validity, i.e. whether these five zones truly represent a rank-order scale of severity, revealed misclassification rates of from 21% for the total population up to 44% for a subgroup. When zones were recombined to reduce the misclassification rates, the descriptive capabilities of the index were greatly reduced as most subjects were then classified in only one or two of the zones.


The effect of various plaque control measures on gingivitis and caries in schoolchildren.

The aims of the present study were (1) to analyze the separate effects on plaque, caries, and gingivitis of several measures (oral hygiene instruction, professional tooth cleaning with mechanical instruments, topical application of sodium monofluorophosphate - MFP) which have been incorporated in a prophylactic treatment program, described by AXELSSON & LINDHE1, and (2) to prevent caries and gingivitis by applying the combined treatment but replacing the professional mechanical tooth cleaning with chemical cleaning using a chlorhexidine-containing gel. 164 children, 13-14 years old, divided into four groups, participated in a 2-year trial. All participants were recalled once every 2nd week for preventive treatment provided by dental nurses. During the 1st year Group 3 and 4 received prophylactic treatment identical to that described by AXELSSON & LINDHE1. During the 2nd year the professional tooth cleaning was omitted but oral hygiene instruction was given every 2nd week. During the 1st year Groups 1 and 2 were treated with 0.5% chlorhexidine but during the 2nd year they were subjected to professional tooth cleaning with mechanical instruments. Throughout the trial Groups 1 and 3 rinsed once every 2nd week with a 2% MFP solution. The results showed that by oral hygiene instruction and frequently repeated professional tooth cleanings it was possible to substantially reduce the frequency of gingivitis and prevent caries. When this treatment was used, mouthrinsings with 2% MFP had no additional effect on caries. The substitution of the mechanical cleaning procedure with topical application of a 0.5% chlorhexidine gel failed to (1) remove supragingival plaque accumulations, (2) reduce the frequency of gingivitis, and (3) retard the rate of caries development. The data also revealed that interdental cleaning with mechanical instruments was of decisive importance in the prevention of approximal surface caries.


Effect on caries experience of lifetime residents after 10 years of fluoridation in Townsville, Australia.

An oral health survey was conducted in the tropical city of Townsville 10 years after its water supply was fluoridated to a level of 0.7 parts/106. The results of the calibration of examiners prior to the survey are presented. Checks on the consistency and comparability of the results obtained by each examiner during the survey show that the results are reliable and reproducible. Dental caries experience of both primary and permanent teeth was found to be significantly lower in Townsville than in 16 non-fluoridated towns. Comparisons are also made between the prevalence of caries in Townsville and four naturally fluoridated towns.


A comparative radiographic investigation of caries prevalence in Danish schoolchildren.

In order to assess the prevalence of untreated caries in two groups of Danish 7th grade (13- to 14-year-old) school children in a blind study, a radiographic investigation was carried out. Only half of the children (394) had received regular school dental care during their years of attendance of primary school; the other children (368) had not. A bitewing radiograph of the right side of the mouth of each child was taken, employing a standardized technique. The radiographs were read without the examiner knowing the group identity of the radiographs. The criteria for discarding poor radiographs, teeth, and tooth surfaces are described. Some of the radiographic results are compared with the clinical caries score of the same group. Most of the radiographs without untreated caries were found among those of the children who received school dental service. Uncertainty of method in connection with radiographic investigation is discussed.


[Radiation exposure and radiation protection in radiodiagnosis of the temporomandibular joint].

There are considerable differences in the various methods of taking x-rays of the temporo-mandibular joint as far as skin exposure to radiation is concerned. Our own measurements revealed doses ranging from 0.2 to 0.8 rem. The values were especially high when using the method of PARMA. Therefore the question is raised whether, considering the provisions of the radiology regulations, there are any cases in which this way to demonstrate the temporomandibular joint is still indicated. As to the measured gonadal doses ranging between 0.02 and 0.18 mrem, no essential differences in the indications of the various methods need to be considered.


[Metric recording of color changes in filling materials].

A new test arrangement for metric recording of color changes is described. Its usability is demonstrated by measurements made in test specimens of composite filling materials. Measurable differences were observed with both the original color and "yellowing" after irradiation. The color changes are visible with the naked eye, but objective comparison is possible by metric determination only.


[Comparative studies on the cytotoxic effect of composite filling materials and silicate cement].

The biologic compatibility of two composite materials (Cosmic, Epstic) based on Bowen's resin and two silicate cements (Frontasil, Silicap) and theirs components were assessed in cell culture. The compounds eluated from the material specimens under physiological conditions affected monolayer cultures of rat fibroblasts and rat epithelial cells (linr RL-19). Silicate cement eluate brings about death of cells due to high concentration of H-ions. Neutralized eluate of freshly prepared Cosmic, Estic and Frontasil caused the same cell damage which was less pronounced following Silicap eluate. The toxicity was markedly reduced following use of an eluate material which had a setting time of 24 hours. After the 2nd and 3rd elution of same specimen the cytoxicity was noticeably weakened, however, it was still demonstrable. The patterns of injury were different following composite material and silicate cement. All tested components soluted in Eagle medium have an irritating effect on the cultivated cells.


[Compression of amalgam specimens under various loads].

To test the behavior of amalgam fillings under masticatory load, 72 cylindrical amalgam specimens (d=5mm, h=10mm) were exposed to alternating loads changing from zero pressure to a pressure of 10 N/mm2. The tests were made in a conventional and four silver amalgams rich in copper, in water baths of 30 degrees, 37 degrees, 50 degrees, and 60 degrees C. Compression of the specimens results, which increases proportionally to the cube root of the number of alternating loads and with rising temperature. The compression lies between 0.3 per cent to 5 per cent of the original length after 10,000 alternating loads, depending on amalgam and temperature. Compressive strength increased under alternating load.


[Therapeutic possibilities in the changing dentition in generalized developmental disorders of the hard substance, ultrastructurally diagnosed I].

Three 5 to 14-year old patients with generalized developmental disturbances of dental hard substance--clinical diagnosis: dentinogenesis imperfecta--are used as examples of age-specific therapy groups in order to demonstrate the various courses of therapy. Early therapy of permanent teeth consists of treating enamel defects with UV hardening resin of the Nuva system. To evaluate adhesion of dental hard substances to resin, it is proposed to use adhesive matrices.


Radiographic features of bone in several strains of laboratory mice and of their tumours induced by bone-seeking radionuclides.

The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours.


[Evolution of the pulp chamber and pseudodentin in the selachians the Brazilian coast (suborder Galeoidea). Morphological study].

The author made a morphological study of Selachii (Suborder Galeoidae) of the Brazil coast using ground sections. Dental structures undergo modifications as one studies species of different evolutionary stages. The lower Selachii have an osteodentine nucleus which suffer alterations until it disappears leaving a pulp chamber in its place. The layer of pseudodentine shows modification too. It consists of pseudodentine in lower Selachii but its modifications are such that in higher Selachii (Sphyrnidae, for instance) one may suppose it is made of orthodentine. Based on these and other published data the author concludes that the degree of evolution of the pulp chamber and pseudodentine allows the establishment, with great probability, of the phylogenitic position of the Selachii within the Galeoidea Suborder.


[Ultrastructure of the alveolodental ligament of the rat].

The ultrastructural study of periodontal ligaments of adult rat molars showed that the predominant cellular element consisted of fibroblasts and fibrocytes. These cells were responsible for the elaboration of the collagen precursors and for their destruction as was demonstrated by the presence of ellipsoidal intracytoplasmic vacuoles containing collagen. The abundance of microfilaments and microtubules as well as the presence of intermediary and tight junctions and nexus between the cell processes seemed to indicate that these cells are contractile and motile. Other cell types were intrequent. The ligament presented a high density of collagen fibrils grouped in bundles. Oxytalan fibrils were also observed. The blood capillaries showed mainly a continuous endothelium. Numerous myelinated and non-myelinated nerve fibrils, as well as nerve endings and mechano-receptors were identified.


[Bacterial accumulation on silicate and composite materials].

It was shown in a previous study that more plaque accumulates on composite filling materials than on silicate cement and amalgam. The purpose of the present investigation was to compare the accumulation of Streptococcus mutans on silicate cement and on composite material by scanning electron microscopy. Whether the adhesion was dependent on the presence of sucrose was also tested. Round disks, 6 mm in diameter, were made from the two materials. The disks were submerged in media with and without sucrose and inoculated with S. mutans OMZ 176. The disks were removed after 1 or 30 minutes, rinsed in saline and prepared for SEM. Along the diameter of each disk pictures were taken at similar intervals. From a total of 48 pictures from each material 18 pictures were selected at random and the number of microorganisms counted. The results indicated that bacteria initially adhered to both silicate and composite in about the same number. The presence of sucrose did not influence the initial adsorption. After 30 minutes bacteria were scarcely found on silicate, whereas large clumps of bacteria were attached to the composite. Sucrose increased bacterial accumulation on composites but did not affect the adherence to silicate cement.


[Topographic distribution of mitosis in the lower incisor and 1st molar in the mouse embryo].

The analysis of serial frontal sections of lower mandibular arches of 14 to 18 days old mice embryos allowed the study of the pattern of mitosis in the incisor and the first molar. A very clear dissociation between the values of the mitotic index of the internal and external dental epithelia was observed. The high mitotic activity of the inner dental epithelium was considered as playing a very important role during the growth of these teeth.


Tongue fissures. A classification and comparative prevalence study among 825 European Caucasian and 605 Xhosa Negro school children.

Six distinct patterns of tongue fissuring have been observed: plication, central longitudinal fissuring, double fissures, transverse fissures arising from a central fissure (type "A"), transverse fissures without a central fissure (type "B") and lateral longitudinal fissures. Some tongues exhibited more than one pattern. There was a significant correlation between double fissures and central longitudinal fissuring (P less than 0.002) but not between other forms of fissuring. No significant relationship was found between the occurrence of atrophic lesions and the prese-ce of fissuring. Significant differences were found between the prevalences in Xhosa and Europeans for central longitudinal fissuring, double fissures and both types of transverse fissures but not for plication. No significant differences were found between males and females and in the age distribution for those with and those without each type of fissuring. It is suggested that most tongue fissuring seen in children should be considered variations in normal anatomy rather than an abnormality.


Influence of amalgam, alloy, and Hg on the in vitro growth of Streptococcus mutans: III. Effect of specimen age and composition.

We will now summarize the conclusions from parts I, II and III of this study. A test procedure has been developed that provides a simple, quick, and nondestructive means of monitoring the in vitro growth of S mutans in the presence of amalgams and alloys. The spectrophotometric readings are related in a simple way to growth expressed as dry weight of bacteria and metabolic products. Results are expressed as growth relative to controls which represent bacteria growing under identical conditions but not in contact with metals. The %RA60 value that represents growth after 60 hours relative to controls is used as a measure of growth in the presence of alloys or amalgams. Spherical, fine cut, and dispersion alloys were studied as well as amalgams prepared from these alloys. The dispersion alloy inhibits growth less than the spherical alloy which in turn inhibits growth less than the fine cut alloy. The results for amalgams prepared from the alloys are reversed. At an aging time of two hours, dispersion alloy amalgams inhibit growth more than spherical alloy amalgams and fine cut alloy amalgams. Aging time of amalgams greatly influences the growth inhibition. Immediately after trituration growth is inhibited, but this inhibition is lost with aging. Different types of amalgams seem to lose growth inhibition at different rates. Hg composition in the range of 48 to 52% seems to have little effect on growth inhibition. It remains for clinical studies, which are concerned with the incidence of secondary caries associated with amalgams, to demonstrate that the age and nature of the amalgam are significant.


Finite element stress analysis of the crowns of normal and restored teeth.

Stress distributions are presented for a normal and a restored mandibular second premolar under masticatory-type forces. These were obtained using the finite element method of stress analysis applied to two-dimensional models. The effect of the relative stiffness of the materials is examined in each instance.


Microprobe analysis of a Au-containing alloy and its amalgam.

Under near-equilibrium conditions, an alloy ingot containing approximately 64% Ag, 26% Sn, and 10% Au was found by X-ray diffraction to consist of large grains demonstrating the gamma (Ag-Sn) structure. Microprobe analysis of these grains showed a 64.2% Ag, 25.3% Sn, and 10.5% Au composition with very small amounts of AuSn2 and AuSn4 segregated at the grain boundaries. When this alloy is manufactured in the form of rapidly colled spherical particles, X-ray diffraction shows both beta (Ag-Sn) and gamma (Ag-Sn) structures with Au substituting for Ag, and microprobe analysis demonstrates a segregation of small high Sn, high Au areas having a AuSn2 composition. When Hg is mixed with these spherical particles, gamma1, some gamma2, and Sn-Au phases (AuSn2 and AuSn4) form. The Au that combines with Sn seems to come from the beta or gamma phases rather than from the Sn-Au segregations in the alloy. The small amount of the gamma2 phase that is initially formed apparently disappears after a short period of time although there is some question as to whether a very small amount may still remain. The Ag-Hg hase (gamma1) is essentially the same as found in conventional amalgams as is the small amount of gamma2 initially formed. Furthermore, a nonequilibrium state seems to be necessary for the early and possibly complete elimination of gamma2. In the as-cast condition, after a period of time at 37 C, A Ag-Hg-Sn phase (beta1) is formed that is similar to that found in conventional amalgams that serve as restorations in the mouth for a period of time. However, in the 135-annealed amalgam, no beta1 appears.


Optical method for articulator comparison and study of occlusal determinants.

A method of articulator comparison and a technique demonstrating the effects of three occlusal determinants were demonstrated and proved successful. The techniques used could be used in dental research circumstances and in dental schools as a means to study the determinants of occlusion.


Erythrocyte velocity in vascular networks of young noninflamed dog gingiva.

Measurements of erythrocyte velocity in vascular networks of noninflamed gingiva of deciduous canines of four young dogs were obtained using vital microscopy and high-speed cinephotomicrography. Mean erythrocyte velocity in small gingival vessels was 1.59 +/- 0.29 mm/sec. Differences in erythrocyte velocity of vessels comprising a gingival microcirculation and of vessels within different gingival samples were not significant.


Surface properties of hydroxyapatite: I. The effect of various inorganic ions on the electrophoretic behavior.

The zeta potential of hydroxyapatite (HA) at a constant pH depends on the type of acid used. Fluoride ions increase the charge density and make the surface less prone to attack by acid or alkali. Sn2+ and Th4+ ionic complexes with fluoride ions and increase the uptake of fluoride by HA.


Effects of dietary fats on the fatty acid composition of enamel and dentinal lipids of rabbit molars.

The effect of dietary fats such as butter, lard, cottonseed oil, and hydrogenated cottonseed oil on the fatty acid composition of enamel and dentin lipids of rabbit molars was studied. The enamel and dentin of molars of all of the rabbits contained a variety of fatty acids, palmitic, stearic, oliec, linoleic, and eicosapentaenoic being the major ones. Enamal lipids were more unsaturated than dentinal lipids in all of the groups. A significant difference was noticed in the fatty acid composition of both the enamel and dentin between these four groups of rabbits. Linoleic acid content was highest in both the enamel and dentin lipids of rabbits fed cottonseed oil. There was no marked difference in the saturated-unsaturated fatty acid ratio in both the enamel and dentin among rabbits fed cottonseed oil, lard, and butter. It is concluded that tooth lipids are responsive to diets and are in direct equilibrium with dietary components.


Magnesium in bone mineral: an in vitro study.

The solubility of magnesium in bone mineral from control and magnesium-dificient rats receiving varying fluoride intakes was assessed. Evidence for the existence of a fluoride-related pool of skeletal magnesium possessing a diminished solubility was obtained.


Calcification of membranes isolated from Bacterionema matruchotii.

Lytic cultures of Bacterionema matruchotii were found to release vesicular membranes into the medium which could be obtained virtually free of other cell structures by differential centrifugation. Suspension of the membrane fraction in a metastable calcium phosphate solution resulted in the formation of both amorphous mineral and hydroxyapatite. Examination by electron microscopy showed that mineralization was associated with the membrane bilayers. The results provide further evidence that calcification of B matruchotii is related to intracytoplasmic membranes.


Enhancement of the antiplaque value of antibacterial agents by enamel conditioning methods: III. Animal results.

A 1:1 water-paste slurry of a placebo and several experimental dentifrices was swabbed daily for six weeks on the teeth of albino rats, and the plaque collected on the teeth was measured in vivo first before the treatments began and one, two, three, and six weeks after. The results indicate that adding a suitable antimicrobial agent to a placebo dentifrice markedly reduced plaque accumulations on the teeth brushed with that product. When an enamel-conditioning vehicle was used instead of the placebo, the antiplaque effectiveness increased severalfold. It was concluded from the two first articles of this series 1,2 that adding antibacterial agents to enamel-conditioning systems resulted in the incorporation of the antimicrobial compound into enamel treated with these systems, and that enamel treated in such a fashion acquired marked antibacterial properties of its own. The data reported in this article support a third conclusion, namely, that the enamel-conditioning-antibacterial systems have a considerable antiplaque effect in laboratory rats.


Cariostatic activity of calcium glycerophosphate in hamsters: topical vs dietary administration.

Two experiments were conducted to determine if calcium glycerophosphate administered continuously in a diet or intermittently as a single daily topical application to teeth had an anticaries potential in young hamsters that were fed a cariogenic diet. The hamsters were inoculated with a caries-conductive streptococcal strain. Within the 60-day experimental period, results of these evaluations indicated calcium glycerophosphate significantly reduces caries when fed in the diet at levels of 1% and higher, and significantly reduces caries when applied topically at levels of 2% and higher. There were no observable differences in plaque formation among treatments.


Identification of the cultivable bacteria in dental plaque from the beagle dog.

Fifteen different genera of microorganisms were isolated from the 27-month-old plaque of two beagle dogs. They were as follows: Pseudomonas, Proteus, Neisseria, Escherichia, Staphylococcus, Streptococcus, Lactobacillus, Nocardia, Actinomyces, Corynebacterium, Micrococcus, Microbacterium, Brevibacterium, Arthrobacter, and Kurthia. The dog plaque was characterized by a low number of streptococci and the presence of several noncarbohydrate-fermenting organisms.


Caries experience in deciduous and permanent dentition of the same individuals.

Caries of the permanent first molars of 5-year-old children was found to be associated with caries of their diciduous teeth. The sample consisted of 220 children whose permanent first molars had erupted. They were selected out of 965 children who were a representative sample of children attending compulsory kindergartens in Jerusalem, 1971.