Biomedical subjects
Publications and source records attributed to S Lange.
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Thorium dioxide (Thorotrast) was used as a contrast medium from 1930 to 1945. It gave excellent contrast and was well tolerated during the application, but due to its radioactivity and its long biological half life it caused various late complications as fibrosis and malignant tumors. The late side effects of the substance are reported on, and the most frequent complication--the induction of hepatomas--is illustrated by two cases.
Using a skull like phantome imaging characteristics of conventional x-ray technique and computerized tomography are compared. The contrast transfer function of x-ray films proofs to be superior, whichis due to overrange artefacts found in computerized tomography. Only 8 out of 50 skull fractures diagnosed by plain film technique were identified on computer-tomograms. Even though CT technique is excellent for the detection of intracranial lesions, fractures are more easily seen on conventional films. This is especially important for analysing size and site of impression fractures.
Median sagittal sections of the cranium of 18 males and 7 females aging from 42 to 74 years were investigated. The distance of brain structures from the skull varied about 11 to 22 mm if the orbitomeatal line is used as reference. A correlation coefficient below 0.5 is found between distances on the outside of the skull and on the median sagittal section as well in horizontal as in the vertical direction. The statistical deviation of the outline of the brain is less extended with an intracerebral reference line than with reference points on the outer surface of the skull. The localization of several telencephalic parts are correlated with the inclination angle of the brain stem. The long axis of the brain stem therefore appears to be the best reference line for localization of brain structures.
The present experiments have been conducted to study the immediate effects of graded immersion on the central circulation. When taking heart volume as an indicator, it was found that immersion to the diaphragm of a standing subject produces the same changes as assumption of the supine posture. Heart volume increases by approximately 130 ml. When the water level is raised to the neck, an extra pressure corresponding to a water column extending from the diaphragm to the surface of the water of approximately 25 cm H2O forces blood into the thorax. The heart becomes distended by an additional 120 ml. Correspondingly the central venous pressure at the height of the right atrium increases from 2.5 to 12.8 mm HG when the water level rises from the diaphragm to the neck. The greater filling of the pulmonary circulation is accompanied by a decrease in vital capacity and visualized by scintigrams. The preferential increase in blood volume of the apical regions is striking. When raising the water level from the symphysis to the xiphoid heart rate falls by about 15%.
13 subjects standing in a narrow upright tank were exposed to rapid water immersion up to the neck. The tank was filled from an elevated reservoir in less than 4 s. In 8 subjects heart size was measured by Roentgen-cinematography combined with video tape recording. Planimetry of the diastolic postero-anterior area of the heart showed an average increase in heart size of 30% within 6 s. In 5 subjects central venous pressure and the height of hydrostatic pressure in the tank were recorded. The two pressures rose and fell simultaneously without delay when the hydrostatic pressure exceeded the level of the diaphragm. Rapid immersion caused a fall in heart rate of approximately 20%. The findings speak in favor of the concept that the right heart does not constitute a resistance and that the pulmonary circulation and the systemic capacitance vessels form a functional unit.
The paper deals with CT followup studies on 73 patients with cerebral tumors who received radiotherapy. The value of CT for the indication of radiotherapy, for followup therapy and for the demonstration of therapeutic success are discussed. Since the cerebral tumors become visualized by means of CT in their entire extent and can be differentiated from perifocal edema, the question arises whether radiotherapy should consist of higher doses in the future. It is also suggested that the "clinical malignancy" may be used to compare the behavior of cerebral tumors when there is no exact histological classification. The possible histopathological effects of radiotherapy (edema, necrosis) and their demonstration by CT are discussed.
In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes.
Among 2,600 patients, examined by computerized tomography, 404 had brain tumours, which were gliomas in 150 cases. There were 73 glioblastomas. Examination was performed according to Ambrose's method using an intravenous injection of 1 ml 60% contrast medium per kg body weight. Thus 98% of all gliomas could be demonstrated. Glioblastomas are shown in three different forms: an annular type (55%), a nodular type (18%), and a combined type (27%). Perifocal oedema is found in 88% of glioblastomas. The oedema most frequently belongs to grade II or III. Differentialdiagnosis of gliomas, abscess, metastases and other tumours with central necrosis are discussed.
The suitability of the E.M.I. mark I computer scanner for carrying out bone densitometry has been tested, using the forearm. Within the region of interest there was an almost linear relationship between CT densities and the concentration of the bone equivalent substance K2HPO4. By means of a special computer programme, the spongiosa and cortex of both forearm bones could be analysed quantitatively. The reproducibility of the results (coefficient of variation 5%) was similar to that of other procedures in current use. The advantage of the method lies in the fact that it is possible to estimate the spongiosa and cortex separately. Investigations on patients with normal bones have shown that senile demineralisation affects the cortex most severely. On the other hand, in renal osteopathies of chronically dialysed patients, demineralisation in the forearm predominantly involves the spongiosa.
An adult mouse model has been elaborated for studies of experimental cholera (Vibrio cholerae enterotoxin-induced intestinal secretion) and protective antitoxic immunity in either ligated small bowel loops or intact small intestine. Mice of different inbred strains varied markedly in intestinal susceptibility to toxin, C57B1 being the most sensitive strain tested. Fluid accumulation started within 1 h after the inoculation of toxin and was maximal after 5 h, whereafter recovery gradually ensued. The dose-response curve was sigmoid, the ED50 of crude toxin being equivalent to about 0.1 microgram purified toxin/cm in the loops and 0.3 microgram/cm in the nonligated intestine. Two peroral (p.o.) immunizations induced significant protective immunity which increased markedly after two further immunizations by the same route. Additional p.o. immunizations did not appreciably enhance the protective immunity any further. Intravenous (i.v.) vaccination had to be repeated more than 5 times before intestinal immunity could be observed. No correlation between serum antitoxin titers and protective immunity was found. Electron microscopic examination revealed that whereas peroxidase-coupled cholera toxin bound tightly to intestinal microvilli from unimmunized or 5-times i.v. immunized mice it did not bind to the microvilli of p.o. immunized animals. The data thus suggest that the protective immunity is mediated exclusively by locally produced antibodies which prevent the binding to toxin to the gut epithelium.
The importance of locally and systemically formed antibodies of various classes for protection against experimental cholera has been studied in mice immunized with cholera toxin. Groups of mice were given various numbers of peroral or intravenous immunizations, or a combination of both. Serum antibodies and antibodies synthesized by spleen and small intestine in vitro during tissue culture were measured by the enzyme-linked immunosorbent assay, and protective immunity against intestinal toxin challenge was determined by means of a small-bowel loop assay. Regression analyses showed a close correlation between the magnitude of intestinal synthesis of specific immunoglobulin A (IgA) antibodies and protection (r = 0.98), whereas neither the local formation of IgG or IgM nor the production of antitoxin antibodies of any immunoglobulin class by spleen showed any significant correlation with protection. The serum titers of IgG and IgM antibodies did not show any such relation, whereas the level of specific IgA in serum, probably mainly derived from the intestine, correlated significantly (r = 0.90).
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The influence of cholera toxin (CT), and thus probably of cyclic AMP, on the capacity of parental lymphoid cells to elicit a graft-versus-host reaction (GVHR) was studied. Toxin-treated DBA/1 mice were used as cell donors and untreated DBA/1xC57B1/6 F1 hybrid mice as recipients, and the GVHR reactivity of the transferred cells was estimated by their ability to induce spleen enlargement or stimulation of antibody formation ('allogenic effect') in the recipients. Spleen cells from donors intravenously injected with 1 microgram CT 1-3 days earlier, gave a significantly stronger GVHR than did spleen cells of untreated mice. Choleragenoid, a toxin analog devoid of the toxin's ability to activate plasma membrane adenylate cyclase even though it binds efficiently to cells, had no effect on the GVHR-inducing capacity of the spleen cells. The enhanced GVHR by spleen cells from toxin-treated DBA/1 animals was reduced to the normal level when the donor cells were transferred along with lymphoid cells from untreated animals of the same strain. Spleen was the most powerful source of the suppressive influence. No evidence for a redistribution of suppressor cells following administration of CT was found. Spleen cells from mice syngeneic with the recipients had no suppressive effect. The results suggest that parenterally administered CT, directly or indirectly, can inhibit a cell population in spleen which normally exerts an antigen-specific suppressive regulatory influence on the development of GVHR.
The CT patterns of 295 glioblastomas examined with pre- and postcontrast scans using an EMI scanner Mark I (Matrix 160/160) have been reviewed and compared with the CT appearances of other brain tumors, metastases and abscesses. There is a great variety of CT patterns with glioblastomas. However, a garland-shaped CT appearance, representing a subgroup of ring-shaped lesions, seems to be most typical for glioblastomas since it was observed in 19% of ring-shaped glioblastomas but in only one out of 172 metastases and in no case of an astrocytoma grade II or an abscess in our series. The initial CT diagnosis, based on the CT finding, the patient's history and the clinical data, was correct in 69.8% of the glioblastomas, 41 recurrent glioblastomas included. In 12% of the cases the presence of a glioblastoma was within differential diagnosis. These results lead to the conclusion that in many cases additional diagnostic methods, such as serial scintigraphy and/or cerebral angiography, are required for a reliable differential diagnosis.
Computed tomography (CT) has given us a new method for examining the orbit and its contents. The technique of examination is described, and the indications for the application of computed tomography in ophthalmology are considered: suspected orbital tumors, unilateral exophthalmos, pareses of the ocular muscles, traumatic lesions and malformations in the region of the orbit. The findings in 210 cases of orbital lesions examined in this study are reported and the differential diagnosis is discussed. Considerable improvement and greater accuracy in diagnosis have been achieved in the field of ophthalmology by using computed tomography. Early tumor visualization is possible without risk or discomfort to the patient.
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2 female patients with malignant melanoma were treated with L-asparaginase immobilized in an extra-corporeal perfusion chamber constructed by Hydén et al. The patients were treated for 80 h during 26 d and for 99 h during 36 d, respectively. L-asparaginase was immobilized by covalent bonds on the surfaces of the chamber. Perfusion resulted in an effective decrease down to less than 7 mmol/1 serum of the asparagine content. The patients withstood the treatments well without any signs of allergic reactions. Antibodies against L-asparaginase were not found. Analyses were continuously performed during the treatment with respect to electrolytes, enzymes and immunoglobulins. No abnormal variations could be found.