[Selective muscle fiber type anomalies in neuromusclar disorders. An analysis of 124 consecutive muscle biopsies (author's transl)]. The following parameters were measured and calculated in 124 consecutive muscle biopsies: mean fiber diameter, standard deviation, percentage of type I and Type II fibers, variability coefficient, hypertrophy and atrophy factor. Twenty percent of the histometrically analyzed biopsies showed a type II atrophy and four percent a type I atrophy. Type II atrophy was found particularly in the following disorders: collagen vascular diseases, steroid myopathies, cachexia and as a result of inactivity. Some neurogenic processes also demonstrated a selective type II atrophy. The combination of a grouped type II atrophy with a type I hypertrophy is characteristic of chronic and usually heredodegenerative disorders of the motoneurons. The presence of a selective type II atrophy argues against a genetically determined muscular dystrophy. A mixed atrophy classified here as strong or very strong primarily suggests a neuropathy. A selective type I hypertrophy has been found exclusively in neurogenic processes, and type II hypertrophy predominantly in the cases of chronic heredodegenerative neurogenic and primarily myopathic diseases. An increase of the variability coefficient of both types of muscle fibers is more frequent and pronounced in neurogenic processes than in myopathic syndromes. Type II fibers show a selective increase in the variability coefficient considerably more often than type I fibers. In contrast to other reports we seldom found a fiber type predominance or a pathological type-grouping. Only two out of five biopsies with pathological fiber type-grouping were definitely neurogenic. In special cases the histometric analysis of muscle fiber types improves the diagnostic efficiency of muscle biopsies.


Electrophoretic and morphologic studies on normal human white matter obtained at surgery with special reference to its basic protein component. Histologically confirmed normal pieces of human white matter removed during surgical approach to underlying pathology were studied by acrylamide disc gel electrophoresis and electron microscopy. A basic electrophoretic pattern of the white matter homogenates from three separate patients is described. Aliquots of white matter from two of these patients were incubated at 4 degrees C and 23 degrees C for intervals up to 18 hours, then homogenized and electrophoresed to detect any degradative changes in the basic protein band. Results of these studies indicated that the basic protein band of freshly obtained normal human white matter was unaffected by incubation at 23 degrees C for as long as 18 hours. Electron microscopic examination of white matter that was incubated for 2 hours at room temperature prior to fixation, showed sporadic areas of lamellar separation, a finding similar to but not as extensive as that described earlier in white matter obtained at autopsy that was performed 8 hours post-mortem. These findings 1) confirm earlier observations made on autopsy material, 2) are compatible with location of basic protein along the cytoplasmic surface of myelin lamellae, and 3) further emphasize the remarkable resistance of basic protein in situ to autolytic degradation.


Electrophysiological findings in the syndrome of acute ocular muscle palsy with ataxia (Fisher syndrome). 4 patients are described with ophthalmoplegia (Figs. 1 and 2) and ataxia with acute onset. Three of them showed only very slight symptoms of generalized polyneuritis. Measurement of sensory nerve conduction velocity (Fig. 4, Table 2) and determination of vibration sense by an electrical vibrator (Fig. 3) proved to be helpful for diagnosis. The ocular EMG revealed signs of peripheral denervation in 3 cases. Pathological changes of the somatosensory evoked potential (Fig. 5) which has been registered in one case, might give some speculation as to whether or not central nervous pathways are affected.


[Demonstration of a factor in cerebrospinal fluid with inhibitory activity for electrophoretic cell mobility in multiple sclerosis (author's transl)]. Inhibition of electrophoretic cell migration using cerebrospinal fluid (CSF) directly was investigated by the modified MEM (macrophage electrophoretic mobility) and TEEM (tanned sheep erythrocyte electrophoretic mobility) tests, respectively. An inhibitory activity of macrophage slowing factor (MSF)--one of in vivo lymphokines--in CSF was established in cases of multiple sclerosis (17.5 +/- 3.8%), and neurolues. The value of this MSF assay turned out to be significantly different from the remaining inflammatory ailments of the nervous system (10.1 +/- 6.8%). Results of other neurological diseases were found to be very much lower (5.1 +/- 4.2%). It seems important, for immunopathogenesis and the diagnosis of neuroimmunological diseases with enhanced cellular immunoreaction, to evaluate MSF activity in CSF. To characterize the active factor in CSF (and serum) these fluids were fractionated by gel filtration chromatography as well as supernatants from lymphocyte-antigen incubation in MS patients. The main activity for inhibition of electrophoretic cell mobility was eluated in the same fraction in these fluids. It could be shown that units have a molecular weight of about 15000 Daltons; this value for MSF lies below those for other inhibitory lymphokines.


Erythrocyte ghosts (Na+ + K+) ATPase activity in Duchenne's dystrophy and myotonia. In Duchenne muscular dystrophy the activity of (Na+ + K+)ATPase in erythrocyte ghosts is reduced and its reaction to ouabain is paradoxical both in low sodium and high sodium systems. No such changes were seen in a case of Becker dystrophy, in limb-girdle dystrophy, and in neurogenic atrophy of muscles. In myotonic dystrophy and congenital myotonia the activity of ATPase and its inhibition by ouabain were depressed.


Muscle enzymatic changes induced by blockage of axoplasmic transport. The activity of malic dehydrogenase, pyruvic kinase, and phosphorylase b was measured in the geniohyoid muscle of the cat after injection of 10 10 mM colchicine into the hypoglossal nerve. Experiments performed 1-60 days after the injection showed that the activity of the three enzymes gradually decreased (day 4-5), reached a maximum fall (day 10-25), and subsequently returned to control values (day 30-60). Concomitantly to these enzymatic alterations, the muscles showed fibrillation and ACh hypersensitivity; however, in contrast to denervation, the drug had no effect on nerve conduction, effective neuromuscular transmission, and ultrastructure of motor end plates. Experiments with [3H]colchicine indicated that the observed changes were brought about by the drug acting directly on the motor axons rather than on the muscle cells. The transsynaptic effects induced by colchicine treatment to the nerve can be ascribed to a temporary interruption of axoplasmic transport. It is suggested that neurotrophic regulation of some muscle-soluble enzymes partly depend on the normal operation of the axoplasmic transport system.


Influence of dimercaprol on the early hepatic uptake of 111In-bleomycin in the BALB/c mouse. Dimercaprol (BAL) administered 1 hr before 111In-bleomycin in the normal BALB/c mouse produced an early preferential hepatic loading of 111In-bleomycin without a loading of the spleen, skin, bone, or muscle. Liver-to-muscle ratios were increased about threefold under the influence of BAL. Liver (c BAL)/liver (s BAL) ratios also increased threefold at 3 hr whereas relative muscle uptake remained at about unity. Indium-111 chloride (colloid, pH 6.5) used as a control did not show a similar increase. The findings suggest that the kinetics and distribution of 111In-bleomycin in the normal BALB/c mouse can be influenced by pretreatment with BAL.


Differential transmission in the superior cervical ganglion of the cat. Mechanisms in the superior cervical ganglion resulting in contraction of the nictitating membrane (NM) and dilation of the parasympathectimized pupil were studies in anesthetized cats. Frequency-response curves were  obtained following pregangionic stimulation with NM and pupillary responses recorded simultaneously in the same preparations.


The instructional effect of verbal/visual feedback in visualized instruction. This study was designed to measure the instructional effect of verbal/visual beedback in facilitating S achievement and to determine whether the amount of realistic detail contained in the visualization influences S achievement. Two hundred sixty-seven university students were randomly assigned to one of three presentation method. Ss received a pretest, participated in their respective instructional presentation, and received four individual criterion measures. Results indicate that all feedback strategies are not equally effective in facilitating student achievement of different educational objectives and that specific feedback techniques may be so elaborate as to interfere with rather than facilitate achievement.


Central terminations of muscle afferents on motoneurones in the cat spinal cord. Intraspinal branches of primary afferent axons in the cat lumbar cord have been revealed by filling then with cobalt, followed by precipitation as cobalt sulphide and silver intensification. 2. Primary afferent collaterals which reached the ventral horn were myelinated and had axon diameters of around 2 mum. Up to four (mean 1) side branches occurred at nodes within the ventral horn. The finest branches were less than 1 mum in diameter. 3. The finest branches formed synaptic boutons on nerve cells. The total observed association between one afferent and a motoneurone (synaptic structure) consisted of up to six boutons (mean 1-85). The boutons constituting a synaptic structure were usually located close together on the soma or dendrites, but sometimes were spread along more than 60 mum of dendrite. It was assumed that these monosynaptic structures on moto-neurones were formed by muscle spindle afferents. 4. There was no correlation between the total contact area of a synaptic structure and its location on a motoneurone. 5. A computer model of the motoneurone was used to investigate the effect of multiple synaptic contact on electrophysiological estimates of synaptic location. It was concluded that the observed spread of boutons making up a synaptic structure would not significantly affect distance allocation of distal synapses but could lead to some proximal dendrite structures being incorrectly classified as somatic.


Rat alpha-fetoprotein in experimental utero-placental ischaemia. Retardation of growth and death of fetal rats were produced after uteroplacental ischaemia was induced by surgical ligation of the uterine arteries. Changes in maternal plasma levels of alpha-fetoprotein (AFP) were measured by radioimmunoassay. In rats in which the uterine blood supply was totally occluded, the resultant increase in maternal plasma AFP was due to resorption of fetal elements, because AFP levels in maternal rat plasma did not increase following hysterectomy in a control group. Maternal plasma AFP levels in rats with a partly occluded blood supply (and therefore some dead and some live fetuses) paralleled those of sham-operated rats, suggesting that increased placental transfer of AFP to maternal plasma may have offset the anticipated decline of AFP due to a decreased number of live fetuses.


Differences in motility of human X- and Y-bearing spermatozoa. Human Y-bearing spermatozoa, as identified by the quinacrine staining technique, were found to be significantly more motile than X-bearing spermatozoa under laboratory conditions. This difference is consistent with current estimates of the difference in mean head DNA content.


Ectopic and eutopic secretion of chorionic gonadotropin and its sub-nits in vitro: comparison of clonal strains from carcinomas of lung and placenta. We compared rates of secretion in vitro of human chorionic gonadotropin (HCG) and its subunits alpha and beta by established clonal cell lines of a bronchogenic carcinoma (ChaGo) and a choriocarcinoma (JEG). Clones showing the highest secretion rates of either HCG or its subunits were studied: ChaGo-K1, a new clonal strain, and ChaGo-C5 and JEG-3, two previously reported clonal lines. Cells were grown under identical conditions in the same laboratory. Hormone and subunit concentrations were measured by radioimmunoassays. ChaGo-K1 and ChaGo-C5 secreted only alpha-subunit whereas JEG-3 secreted only HCG. Average peak secretion rates in picomoles/day/mg protein were: for ChaGo-K1, HCG less than 0.3, alpha=290, and beta less than 0.5; for ChaGo-C5, HCG less than 0.3, alpha=21, and beta less than 0.5; and for JEG-3, HCG=18, alpha less than 0.7, and beta less than 0.5. The ChaGo-K1 secretion rate of alpha was greater than that of any of out previously reported ChaGo clones. Significant quantities of estradiol and progesterone accumulated in the media of all three cell lines; however, only JEG-3 secreted detectable quantities of placental lactogen. Thus under identical culture conditions, a bronchogenic carcinoma clonal line secreted only alpha-subunit, whereas a choriocarcinoma line secreted only HCG; these findings implied major differences in cellular control mechanisms. Moreover, the ectopic secretions of alpha exceeded the eutopic trophoblastic secretion of HCG, which suggested that in certain cases ectopic protein production may be even more efficient than nonectopic production.


Secondary cell-mediated cytotoxic response to challenge of rats with syngeneic Gross virus-induced lymphoma. Secondary cell-mediated cytotoxicity generated in vivo against a syngeneic Gross virus-induced lymphoma [(C58NT)D] in WF rats was detected by the 4-hour 51Cr release assay. At 30 days or more following primary tumor cell inoculation, after the tumors had regressed, lymphoid cells had little or no detectable direct cytotoxic reactivity. At rechallenge with tumor cells, high levels of cytotoxicity were detected in the peritoneal exudate, peripheral blood, mesenteric lymph node, and spleen cells. The secondary cellular immune response after challenge developed earlier, reached higher levels, and lasted longer than the primary immune response. The secondary cytotoxic reactivity was shown to be immunologically specific by the use of various tumor cells both as target and inhibitor cells. Treatment of immune spleen cells with specific antiserum to rat T-cells and complement abolished their cytotoxic reactivity, whereas removal of complement receptor-bearing cells or phagocytic cells did not reduct the cytotoxicity. These data demonstrated that specific-memory T-cells persisted for long periods in the lymphoid organs of immune rats and could rapidly become cytotoxic from rechallenge with the tumor.


Leukemia-associated antigens detected by heterologous antisera. An antiserum was produced by immunization of rabbits with the membrane fraction of a lymphoblastoid cell line, RPMI 4265. This antiserum reacted against leukemia-associated antigens on immature blast cells of 24 patients with acute leukemia (13 myeloblastic, 11 lymphoblastic). No reactivity was observed against morphologically normal blood mononuclear cells from patients in remission, cells from normal control subjects and patients with unrelated disorders, phytohemagglutinin-induced lymphoblasts, or normal bone marrow cells. Reactivity against leukemia cells was not reduced by absorption with fetal tissues. These findings were consistent with the presence of tumor-associated antigens on leukemia cells. The antigens were detectable neither during hematologic remission nor on cells from patients with unrelated diseases.


Characterization of virus-free guinea pig tumors induced by Kirsten sarcoma virus. Tumors were induced by Kirsten sarcoma virus (KiSV) in an inbred guinea pig, strain 13. The tumor cells were established in culture and characterized. The KiSV-induced sarcoma cells were virus-free and nonproducing; however, they contained resuable sarcoma genome. A type B guinea pig retravirus was readily activated from the tumor cells after induction with 5-bromodeoxyuridine (BUDR). BUDR induction of guinea pig retravirus was further enhanced by treatment with dexamethasone, a synthetic glucocorticoid hormone.


Deficits in reticuloendothelial humoral control mechanisms in patients after trauma. Plasma opsonic activity as expressed by an alpha-2-globulin which stimulates hepatic Kupffer cell phagocytosis, and thus modulates RES clearance, was determined in patients at varying intervals following whole-body trauma. Plasma opsonic activity decreased markedly following trauma in both nonsurviving (NS) and surviving (S) trauma patients as compared to an age- and sex-matched group of healthy volunteers. The initial post-traumatic hypoopsonemia (0-72 hr) was more severe (p less than 0.01) in nonsurviving patients than surviving patients. Survivors following trauma manifested restoration of opsonin levels with a definite transient rebound hyperopsonemia during the recovery phase (11-30 days); nonsurviving patients exhibited persistent systemic alpha-2-globulin opsonic deficiency. On the basis of previous animal and human studies, the presently observed humoral deficits following trauma in patients could contribute to impairment of reticuloendothelial Kupffer cell clearance of blood-borne particulate matter such as fibrin, damaged platelets, and other altered autologous tissue. The importance of post-trauma RES dysfunction to survival following severe injury warrants further investigation and clinical consideration.


Induction of GIX antigen and gross cell surface antigen after infection by ecotropic and xenotropic murine leukemia viruses in vitro. A number of ecotropic and xenotropic murine leukemia viruses were examined for their ability to induce the GIX antigen and Gross cell surface antigen (GCSA) in tissue culture fibroblasts. GIX appears to be a constituent of murine leukemia virus gp70; a molecular characterization of GCSA has not yet been reported. Antigen induction was measured by the ability of productively infected cells to absorb cytotoxic activity from the standard GIX- and GCSA-typing antisera. Cells infected by ecotropic viruses displayed four distinct phenotypes GIX:+/GCSA++, GIX-/GCSA++, GIX++/GCSA+, and GIX-/GSCA+; cells infected by xenotropic viruses were either GIX-/GCSA+ or GIX-/GCSA-. GIX induction appeared to be a type-specific property of some but not all Gross-AKR type ecotropic viruses. Differences in the degree of absorption of the GCSA antiserum by ecotropic virus- and xenotropic virus-infected cells indicated that GCSA may comprise multiple antigenic determinants.


Type C particle-positive and type C particle-negative rat cell lines: characterization of the coding capacity of endogenous sarcoma virus-specific RNA. Various rat cell lines have been analyzed for expression of endogenous RNA homologous either to RT21C, a typical rat type C virus, or to Kirsten sarcoma virus. Cells have been found that express either (i) high levels of RNA homologous to RT21C rat type C virus and low levels of RNA homologous to Kirsten sarcoma virus (RT21Chigh,sarclow) or (ii) high levels of RNA homologous to Kirsten sarcoma virus and low levels of RNA homologous to typical rat type C virus (sarchigh, RT21Clow). The properties of these two classes of cell lines have been compared. Each type of cell contains an equal amount of the expressed RNA on polysomes. Cell lines that are RT21Chigh produce abundant rat p30 nad p12 structural proteins and release rat type C particles containing viral RNA and reverse transcriptase into supernatant fluids from these cultures. Cell lines that are sarchigh,RTC21Clow have no detectable rat viral p12 protein and no p30 protein immunoreactive in even broad interspecies radioimmunoassays, and do not release type C particles into the supernatant from the cultures. When the particle-negative cell lines are superinfected with heterologous mouse or wooly type C viruses or are producing typical rat type C virus particles, the endogenous sarcoma virus-specific RNA is secreted from these cells. The sarcoma virus-specific RNA can be transcribed in complementary DNA in the endogenous reverse transcriptase reactions carried out in vitro with such virus preparations. However, exposure of cells that are permissive to the helper virus with the particles containing sarcoma virus-specific RNA has not yet resulted in cell transformation or in the synthesis of these RNA sequences. The results suggest: (i) that the first step in the genesis of sarcoma viruses involves the packaging of this expressed sarcoma virus-specific RNA in helper viral particles; (ii) that efficient transmission of the sarcoma virus-specific RNA requires additional events; and (iii) that the formation of a stable sarcoma virus by recombination between the helper viral genome and part of the rescued sarcoma virus-specific RNA is much less common event than the rescue process itself.


A new combination chemotherapy for resistant Hodgkin disease. A new four-drug combination chemotherapeutic regimen (BVDS) was used in the treatment of advanced Hodgkin disease resistant to MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone). The BVDS regimen, consisting of 12 cycles of bleomycin sulfate, vinblastine sulfate, doxorubicin hydrochloride (Adriamycin), and streptozocin (streptozotocin), was administered to ten patients. Responses were seen in five (50%) of these patients. Complete remissions occurred in three (30%). These results suggest that BVDS is an effective alternative regimen to MOPP, and may be of benefit not only to patients resistant to MOPP, but also to newly-diagnosed patients with advanced hodgkin disease when combined sequentially with MOPP.


Action of bleomycin on proliferating plant cells. Bleomycin (10-(6) M) has been tested in Allium cepa L. meristems which are formed by a proliferating cell population growing under steady state conditions. Chromosome breaks were apparently induced by the antibiotic in cells in G2 period since anaphases with chromatid breaks were formed at a time shorter than G2 + prophase duration. Stimulation of entrance of G2 cells into mitosis is suggested both by an increase in the frequency of early prophases and by the study of waves of prophases in a synchronous subpopulation labelled by caffeine. Progression of other mitotic phases was unaffected. Nucleologenesis rate was increased by the antibiotic in a fashion resembling protein synthesis inhibitors. Protein synthesis is inhibited by 10-(6) M bleomycin to the same extent as 4 X 10(-6) M anisomycin. Both facts suggest that bleomycin has a direct inhibitory effect on protein synthesis in meristems. Given the nucleologenesis sensitivity to nucleolar RNA inhibition it is suggested that the antibiotic activity on nucleolar transcription is mediated through DNA.


Interactions between bleomycins and metals. Gel filtration has shown that there are considerable differences between the metal complexes of bleomycin A2 and B2 with indium, cobalt or copper. Differences in the rates of formation of the complexes have also been found and it is thought that these effects are due to a difference in co-ordination between the metals and the bleomycin. The co-ordination changes are thought to be the cause of the differences in in vivo distribution of metal bleomycin complexes found in the radiodiagnosis of tumours. The ease of formation of the copper or cobalt complexes is suggested as a possible mechanism for the inhibition of the attack of DNA by bleomycins.


Experimental allergic encephalitis (EAE) in mice: histological studies on EAE induced by myelin basic protein, and role of pertussis vaccine. The histological evidence of EAE in mice was presented to show the identity with those of other species of animals. There was a typical perivascular mononuclear cell infiltration. In addition, a hyperacute form was characterized by edema and the infiltration of polymorphs. In vascular lesions, vascular stasis, thrombosis, and hemorrhage were observed. As for the effect of pertussis vaccine used in the induction of mouse EAE, responsiveness to the histamine sensitizing factor was not directly correlated to the incidence of EAE. However, the intravenous administration of pertussis vaccine caused remarkable leukocytosis, which might play a certain role in mouse EAE induction.


Preparation of anti-etiocholenic acid antiserum and anti-cholesterol succinate antiserum and their cross reactivities. Anti-3-hydroxy 5-androstene carbonic acid (etiocholenic acid) antiserum was obtained by immunizing rabbits with anetiocholenic acid-polylysine complex. Anticholesterol succinate antiserum was also prepared by immunizing rabbits with a cholesterol succinate-polylysine complex. The cross reactivities of these antisera were examined by means of radioimmunoassay system, immunolysis of liposome and passive hemagglutination reaction. Anti-etiocholenic acid antiserum was specific against the structure of ring A of cholesterol and the nature of OH group at C3 position and anti-cholesterol succinate antiserum was specific against the side chain similar to that of cholesterol.


Grouping antigens of four Lactobacillus species and their characteristics. Antigenic analyses of Lactobacillus bulgaricus, Lactobacillus lactis, Lactobacillus brevis and Lactobacillus buchneri were carried out by double immunodiffusion in agar. Antigens were extracted from whole cells and cell wall preparations with cold trichloroacetic acid. Most strains of the four species possessed antigen 9 in their cell walls. Another antigen, antigen 10, was found in the cell walls of all the strains of L. brevis and L. buchneri, and in some strains of L. lactis, but not in L. bulgaricus. Fractionation of the antigens was attempted using the cell wall extracts of L. lactis L-10 with only antigen 9 and of L. brevis X-1 with both antigens 9 and 10. The partially purified fractions of antigen 9 and of the complex of antigens 9 and 10 were obtained by zone electrophoresis. However, antigen 10 from the complex could not be separated by the same method or gel filtration on Sephadex G-100 since the two antigens 9 and 10 of the complex always behaved together. The fraction of antigen 9 consisted almost entirely of glycerol and glucose as sugar components, the molar ratio being 2: 1. The complex of antigens 9 and 10 also consisted of the same sugars, and the molar ratio of glycerol: glucose was 4: 1. Inhibition tests indicated that the immunodominant component of antigen 9 was a-methylglucoside (glucose), and most probably the determinant is a glycosylated glycerol teichoic acid. It was considered that the determinant of antigen 10 is a glycerol teichoic acid although glucosamine and galactosamine inhibited effectively the reaction between antigen 10 and its antibody.


Nephritic factor: Description of a new quantitative assay and findings in glomerulonephritis. A sensitive quantitative test for nephritic factor (NF) in human serum is reported. The test is based on the capacity of NF to initiate fluid phase consumption of the third complement (C) component in the presence of magnesium ions (Mg++) and of factors of the alternative pathway of C activation. These factors as well as C3 and C5 were supplied by the incorporation of normal human serum (NHS) into the assay mixture. In order to prevent C3 (and C5) consumption via the Ca++- and Mg++-dependent classical pathway, the test was performed in the presence of the chelating agent Mg-ethylene bis (oxyethylene-nitrilo) tetraacetic acid (Mg EGTA) which interacts preferentially with Ca++. The Mg EGTA concentration was found to be critical, a final concentration of 5 mM in the assay mixture being required for optimal results. By its heat stability (54 degrees to 56 degrees C, 30 min), NF could be distinguished from other, heat-labile NF-like factors. The NF test was applied to five categories of patients with glomerulonephritis (GN). Heat-stable NF activity was found in seven of 17 sera in the membranoproliferative glomerulonephritis (MPGN) group. Two of the 12 acute poststreptococcal GN sera had NF-like activity which disappeared upon heating. Serum C3 and proactivator (PA) concentrations varied widely in all groups but a clear positive relationship was found between the presence of NF and low serum C3 concentrations in MPGN. Renal immunofluorescence in MPGN indicated a lesser amount of lg deposited in glomeruli from patients with NF when compared to the NF-negative patients. Both groups had heavy C3 deposits. The availability of a sensitive, quantitative assay for NF may help to provide further insight into the various pathogenic mechanisms in different forms of MPGN.


The use of glutaraldehyde-conjugated horseradish peroxidase-bovine serum albumin in the visualization of concanavalin A binding to tissue sections of human colonic tumor. A method is reported for the preparation of glutaraldehyde cross-linked horseradish peroxidase conjugates for the visualization of concanavalin A binding to frozen sections. The binding of concanavalin A to tissue sections of human colonic tumor is used to compare staining by horseradish peroxidase conjugates and monomers. Without decreasing specificity, the use of progressively larger molecular weight conjugates provides progressively greater intensity of staining of the epithelial components of colonic carcinomas and normal colons.


Morphologic and biochemical study of pulmonary changes induced by bleomycin in mice. Pulmonary changes induced by bleomycin were investigated in mice by using light and electron microscopy and by phospholipid analysis of the alveolar washings. The damage began in the endothelium of capillaries and was accompanied by interstitial edema and an appearance of enlarged macrophages along with hypertrophy of type II epithelial cells. This condition was followed by degeneration of type I cells. The denuded epithelium appeared to be repaired by two different mechanisms. In areas away from the bronchioles, division of existing type II cells and subsequent transformation into type I cells appeared to be the pattern of epithelial repair. In areas near the bronchiole, downgrowth of bronchiolar undifferentiated cells and subsequent maturation of these cells to type II and type I cells appeared to be prominent. Biochemically, total phospholipids and disaturated lecithin in the alveolar wash increased along with the increase of the alveolar lining layer and the hypertrophy of type II cells. This was considered to be consistent with the view that the hyperactive type II cells secreted more surfactant in the early phase of the experiment.


Variety of determinants in an adrenal antigen common to man and some animals. Precipitating adrenal antibodies are specifically associated with the moniliasis-polyendocrinopathy syndrome. This may include several simultaneous autoimmune disorders such as Addison's disease, hypoparathyroidism, thyroiditis, pernicious anaemia and ovarian failure often combined with moniliasis and alopecia. The antibodies react with two adrenal specific antigens present in man and in different animals. One of these antigens designated S-(soluble) antigen is present in all subcellular fractions and the other designated P-(particulate) antigen was found in precipitable form only in the mitochondrial fractions. Rabbits immunized with bovine adrenal homogenate and different subcellular fractions, produced three to four adrenal specific antibodies, which were qualitatively identical. The corresponding antigens were designed as S1-S4, one of which (S4) was strictly specific for bovine tissue. S1-, S2- and S3-antigens were identical in bovine and ovine adrenals, whereas a partial reaction of identity was found between ruminants and the S1- and S2-antigens of all other species tested. The S1- and S2-antigens seem to contain a variety of determinants, some common to all the species studied and some limited to certain species only. Of the four S-antigens only one (S1) in rabbits, was found to contain autoantigenic determinants. Comparative studies with sera from patients with the moniliasis-polyendocrinopathy syndrome indicate, that this molecule is the one with which human and rabbit antisera react.


Gastric-juice nitrite. A risk factor for cancer in the hypochlorhydric stomach? Nitrite and hydrogen ion concentrations have been measured in the fasting gastric juice of 69 patients undergoing routine gastrointestinal investigations. There was an inverse relationship between nitrite concentration and hydrogen ion concentration, with a highly significant increase in gastric-juice nitrite in hypochlorhydric subjects. Thiocyanate was also found in all specimens in concentrations likely to increase nitrosamine formation, if nitrosation of amines occurs in the fasting stomach. Neutral gastric juice contains metabolically active bacteria capable both of generating nitrite from nitrate and of catalysing nitrosation. In this way an intragastric environment suitable for the formation of carcinogenic nitrosamines exists in the hypochlorhydric and achlorhydric stomach, providing a possible mechanism for the high incidence of gastric cancer in these subjects.


Penicillin-induced coagulation disorder. A coagulation disorder was seen after penicillin-G administration (10 million units/day) in uraemic patients and after high-dose penicillin G (40 million units/day) in patients with a normal glomerular filtration-rate (5 patients after cardiac surgery). This disorder was characterised by: prolongation of bleeding-time, appearing immediately after penicillin-G administration and persisting until 4 days after withdrawal of therapy; disturbance of collagen-induced and ristocetin-induced platelet aggregation; increase of antithrombin-III activity; and inhibition of factor-xa activity. The inhibition of factor-xa activity corresponded to that seen after low-dose-heparin prophylaxis. The clinically latent coagulation disorder, when super-imposed upon pre-existing coagulation abnormalities (uraemia, treatment with anti-coagulants) may cause severe bleeding, as observed in 1 patient with acute renal failure on haemodialysis.


Strong association between B-lymphocyte group-2 specificity and asthma. 30 families in which at least one member has asthma were tested for five new specificities of B lymphocytes as well as for twenty-five HLA antigens. 41 other asthmatic patients were also tested. HLA-B8 was slightly less common than normal in the 71 patients with asthma and there was a trend towards an increased frequency of HLA-A2 in these patients. However, 88% of the 30 asthma patients had B lymphocyte group 2 compared with 24% of the 109 controls. This strong association between asthma and B lymphocyte group 2 was not completely paralleled by linkage with a postulated susceptibility gene of the HLA complex in 9 families whose members were investigated in detail.


Effect of long-term diuretic treatment on body-potassium in heart-disease. Plasma and total body potassium have been measured in 151 patients with chronic heart-disease, 83 of whom were taking diuretics and potassium supplements. After allowance for age and body-size, the deficit in total body-potassium was only 3-5% (100-150 mmol) in the diuretic group. 13 of the 83 patients taking diuretic had hypokalaemia (less than 3-5 mmol/1) but the potassium deficit was no greater than in the patients with normal plasma-potassium. There was no relation between the dose of potassium supplements and either the plasma-potassium or the total body-potasium. It is suggested that potassium depletion is not a major problem in patients with heart-failure treated with diuretics. The dose of potassium supplements should therefore be determined entirely by the plasma-potassium.


Cardiovascular-disease mortality trends and oral-contraceptive use in young women. Analysis of mortality trends in 21 countries indicates that, since oral contraceptives first became available, changes in mortality from non-rheumatic heart-disease and hypertension (I.C.D. 400-429), cerebrovascular disease (I.C.D. 430-439), and all non-rheumatic cardiovascular diseases (I.C.D. 400-469) among women aged 15-44 years have been strongly associated with changes in the prevalence of oral-contraceptive use in each country. This relationship is highly specific for women of reproductive age. The relative risks of death from heart-disease and hypertension, cerebrovascular disease, and all cardiovascular diseases for women using oral contraceptives compared with non-users were estimated to be 5 to 1,2 to 1, and 3 to 1 respectively. These findings suggest that the range of vascular diseases affected by oral-contraceptive use and the size of the associated risks may be greater than previously recognised. Furthermore, the increased risks of cardiovascular disease might exist not only with the pills containing high oestrogen doses, but also with the new "lower dose" pills.


Patterns of blood-pressure during chronic administration of postganglionic sympathetic blocking drugs for hypertension. Continuous recording of intra-arterial blood pressure in 11 ambulant patients taking postganglionic blocking drugs for the treatment of hypertension has shown an alternating pattern of high pressures at rest and very low pressures associated with exertion during normal daily activities. In 4 patients there was evidence of decreased cerebral or myocardial blood-flow during hypotensive episodes. It is suggested that these agents may predispose towards cerebral and myocardial infarction.


Substance P: a naturally occurring transmitter in human spinal cord. Immunoreactive substance P-like material has been found in axonal processes of human spinal cord in a location similar to that in other mammals. Substance P may be a primary sensory transmitter (or modulator) in man.


Indium-111-labelled leucocytes for localisation of abscesses. Leucocytes from eight patients who were thought to have an abscess were labelled with indium-111 and reintroduced into the circulation. The distribution of radioactivity was followed by whole-body scanning and imaging with a gamma camera. Focal accumulation of radioactivity were observed in the lesion in the three patients with abscesses, in the lungs of a boy with bacterial endocarditis, in the knee of a woman with rheumatoid arthritis, and at the site of intramuscular injections in another patient. The use of radiolabelled cells for the detection of focal pathological processes would seem to be an important addition to conventional diagnostic methods.


Target cell in chronic myeloid leukaemia and its relationship to acute lymphoid leukaemia. On the basis of membrane marker analysis with an antiserum made against acute lymphoblastic leukaemia and other immunological markers it is suggested that some chronic myeloid leukaemias (C.M.L.) and some acute lymphoblastic leukaemias (A.L.L.) originate in a common target cell or precursor. This is possibly a pluripotential stem cell or a closely related derivative. These leukaemic cells retain their undifferentiated membrane characteristics C.M.L. patients in blast crisis who are A.L.L.-antigen-positive and have terminal transferase enzyme activity might benefit from therapy usually given in typical Philadelphia-chromosome-negative A.L.L.


Pancreatic islet-cell antibody as a marker for asymptomatic and latent diabetes and prediabetes. Pancreatic islet-cell antibodies (I.C.Ab) were detected in 31 patients with organ-specific autoimmune disorders, 4 first-degree relatives of I.C.Ab-positive diabetics, and 1 apparently normal subject, none of whom had clinical evidence of diabetes. 10 of these 36 subjects were found to have diabetic glucose-tolerance tests (G.T.T.S), 4 had lag storage, and 22 had normal G.T.T.S.2 had latent diabetes, as evidenced by diabetic G.T.T.S during pregnancy and thyrotoxicosis; another 2 subsequently developed insulin-dependent diabetes (I.D.D.) Serum from 26 subjects had been stored for 1-11 yr before the G.T.T.S were done. The titres in some were shown to rise and fall over the years, while in others they remained remarkably constant. There was no correlation between the titre, change in titre or the duration of I.C.Ab or the presence of HLA-B8, BW15, or CW3 and the result of the G.T.T. In addition to acting as a marker for asymptomatic and latent diabetes and prediabetes, it seems that the presence of I.C.Ab in the serum may define a new group of potential diabetics with normal G.T.T.S. Many such subjects have one or more organ-specific autoimmune disorders (irrespective of diabetic family history), but some are first-degree relatives of I.C.Ab-positive subjects (mainly I.D.D.). About 0-5% of the general population also have I.C.Ab in their serum.


Short-course chemotherapy in pulmonary tuberculosis. A controlled trial by the British Thoracic and Tuberculosis Association. A rigimen of rifampicin plus isoniazid, supplemented in the first two months by ethambutol or streptomycin, was given for six, nine, twelve, or eighteen months in a controlled study of 696 patients with culture-positive pulmonary tuberculosis. The results obtained in the thirty-three months since the start of treatment when all the patients in the six-month and nine-month groups had completed at least two years and those in the twelve-month group had completed twenty-one months of post-chemotherapy follow-up revealed no relapses among patients receiving nine months chemotherapy and a 1% relapse-rate in the twelve-month group. The same regimen given for only six months resulted in a relapse-rate of 5% during the subsequent twenty-seven months. There were adverse effects with streptomycin but not with ethambutol. It is concluded that treatment with rifampicin plus isoniazid for nine months, supplemented by ethambutol in a dose of 25 mg/kg for the first two months, is now acceptable as standard chemotherapy for pulmonary tuberculosis in Britain.


Response of protracted neonatal hypocalcaemia to 1alpha,25-dihydroxyvitamin D3. Six infants with protracted hypocalcaemia (5 classed as tetany of the newborn) had a mean plasma-calcium of less than 6-4 mg/dl and raised plasma-inorganic-phosphate. Four had been hypocalcaemic for longer than 2 weeks despite treatment with low phosphate formulae and extra calcium. All the infants were treated with 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), usually in a dose of 0-05 mug/kg body-weight/day, administered intravenously for 5--12 days. The plasma-calcium levels began to rise within 24 h after starting 1alpha,25-(OH)2D3 treatment, increased above 7-5 mg/dl within 3 days, and reached the normal range within 8 days. Four of the infants remained normocalcaemic when 1alpha,25-(OH)2D3 was discontinued, but two infants became hypocalcaemic again and required long-term treatment. 1alpha,25-(OH)2D3 has been found safe and dependable as treatment for protracted neonatal hypocalcaemia.


Urinary infection in boys.A three-year prospective study. 73 boys who presented to their general practitioners over the course of one year with symptoms of urinary-tract infection and were found to have bacteriuria were referred to a three-year prospective study. This included clinical and radiological investigations and monitoring of the preputial flora and midstream-urine culture at monthyl intervals. 22 (30%) of the boys had radiological abnormalities of the urinary tract; 6 had pyelonephritic changes. Only 2 required urinary-tract surgery. Several findings of the study suggest that the natural history of the disease in boys is different from that in girls. Proteus spp.predominated as the infecting organisms. Culture of swabs from the preputial sac, and comparison with matched controls, suggested that the source of infection in boys is the prepuce or urethra rather than the bowel as in girls. Recurrence of infection, in the absence of radiological abnormality, was rare; 51 boys (70%) had no recurrence throughout the follow-up period. There was evidence that recurrence in boys is related to the persistence of gram-negative organisms in the urethra, revealed by low bacterial counts on midstream culture, and it is suggested that in boys urethral infection may be as important as bladder bacteriuria.


Effects of incubator noise on the cochlea of the newborn. The possible effects of incubator noise on the hearing of premature babies have long been debated. The type of hearing loss found in 12 low-birthweight children was examined; and the variable noise level in regularly used incubators was measured. This noise, applied to guinea pigs continuously during their second week after birth, was shown histologically to destroy a proportion of the sensory cells in the cochlea. Adult guinea pigs, however, were not vulnerable in this way. The conclusion is that there is definite circumstantial evidence of the damaging effect of many incubators on the hearing of premature infants.


T-lymphocyte colonies in malignant disease. T-lymphocyte colonies have been cultured in 106 subjects comprising healthy individuals and hospital inpatients as controls and patients with a wide variety of malignancies. Abnormal results were recorded in 89% of patients with malignant disease and in 23 of 24 patients with carcinomas (96%). This test may be valuable in research, and in diagnosis and monitoring of progress in malignant disease.


Chloroquine, quinine, procaine, quinidine, tricyclic antidepressants, and methylxanthines as prostaglandin agonists and antagonists. Chloroquine, quanine, procaine, quinidine, clomipramine, theophylline, and caffeine have been shown to be strong prostaglandin antagonists and weak agonists. The antagonist effect is clearly demonstrable at concentrations reached in human plasma when the drugs are used therapeutically. This suggests that prostaglandins are important in several situations in which their role has hitherto been unsuspected. New approaches to the development of prostaglandin antagonists and new uses for established drugs are indicated. In a preliminary study chloroquine has been successfully used to close patent ductus arteriosus in three infants.


Mask wiggling as a potential cause of wound contamination. Some operating-theatre staff have a habit of wiggling their surgical masks by moving their facial muscles. The field contamination which can result from this practice was studied. A firmly fitting, moulded, synthetic-fibre mask produced significant bacterial contamination of culture plates held beneath the mask, compared with that found on simultaneously exposed control plates placed nearby. Softer fibreglass masks produced less contamination when moved by facial muscles, and are more suitable for mask wigglers.


The incidence, importance, and prophylaxis of acute mountain sickness. Acute mountain sickness (A.M.S.) and its severe complications, high-altitude pulmonary oedema (H.A.P.O.) and cerebral oedema (C.O.), were studied in 278 unacclimatised hikers at 4243 m altitude at Pheriche in the Himalayas of Nepal. The overall incidence of A.M.S. was 53%, the incidence being increased in the young and in those who flew to 2800 m, climbed fast, and spent fewer nights acclimatising en route. It was unrelated to sex, to previous altitude experience, to the load carried, and to recent respiratory infections. The severity of A.M.S. was inversely related to age (independent of rate of ascent) and the highest altitude attained, and was highly ocrrelated with speed of ascent. There were 7 cases of H.A.P.O. and 5 with the more intractable C.O. and, of these 12, 11 had flown in, 9 had spent only one night at Pheriche, and none were on acetazolamide. 11 required evacuation. Acetazolamide, compared in a double-blind study with a placebo and also compared with no tablets at all, reduced both the incidence and the severity of A.M.S. in those who flew to 2800 m but not in those who hiked up to that altitude. Prevention consists in slow ascent, rapid recognition of warning signs, and prompt descent to avoid progression.


Comparative efficacy of chloramphenicol, ampicillin, and co-trimoxazole in the treatment of typhoid fever. Two clinical trials were conducted to compare the efficacy of 3 antimicrobial agents often recommended for the treatment of typhoid fever. Chloramphenicol was more effective than parenteral ampicillin or oral co-trimoxazole (trimethaprim/sulphamethoxazole) in reducing the duration of fever. Oral chloramphenicol was more effective than parenteral chloramphenicol probably because oral doses resulted in higher blood concentrations of the drug. However, parenteral chloramphenicol was given during the initial period of acute illness, without loss of efficacy.


Intrapulmonary heparin. A new procedure for anticoagulant therapy. Heparin was administered by the intrapulmonary route to dogs, mice, and human volunteers. In all species, a single administration of a large quantity of heparin via the lung resulted in a prolonged state of moderate hypocoagulability (3 days in dogs, 14 days in man) due to the production of a sustained low concentration of heparin in plasma. The lengthening of clotting-time and duration of this response increased with dosage. Effective doses are above 8 mg (1300 units) per kg body-weight. Examination of the lungs, body-fluids, and tissues shows that the heparin is cleared rapidly from the lung and enters a body cellular compartment (probably the macrophages) from which it is slowly released to plasma. No evidence was found (symptomatic or on gross or histological postmortem examination) of haemorrhage or any heparin-related pathological change indicating either immediate or long-term toxic effects in the lung or other tissues. Suggestions are made for the clinical use of the unique features of anticoagulant treatment by intrapulmonary heparin.


Plasma-fibrinogen and thromboemboli after myocardial infarction. In 120 patients with myocardial infarction subsequent non-fatal thromboemboli occurred only in patients in whom plasma-fibrinogen had exceeded 750 mg/dl. It is suggested that patients at risk from thromboembolism after infarction can be identified by monitoring plasma-fibrinogen and that appropriate anticoagulation might reduce morbidity.


Treatment of neurogenic orthostatic hypotension with a monoamine oxidase inhibitor and tyramine. Six patients with neurogenic orthostatic hypotension were treated with a chemical preparation of tyramine and tranylcypromine ("Parnate"), a monoamine oxidase inhibitor (M.A.O.I.). Four had autonomic failure with no other neurological deficit (idiopathic orthostatic hypotension), and in two patients other neuronal systems were also involved (Shy-Drager syndrome). Previous therapy with fludrocortisone, ephedrine, elastic garments, postural training, and, in one patient, an anti-G suit was unsatisfactory. Tyramine given orally with tranylcypromine produced a moderate rise in blood-pressure which was sustained for 2-4 hours, enabling patients to walk about without symptoms of orthostatic hypotension. Measurement of circulating adrenaline and noradrenaline during therapy suggested that release of noradrenaline caused the pressor response. In three patients there has been a pronounced improvement for 8, 20 and 30 months. In a further patient, therapy has been successful in treating the orthostatic hypotension, although his mobility has been restricted by cerebellar ataxia. In one patient a confusional state developed during treatment and therapy was stopped. The only patient in whom the drugs did not produce a pressor response had orthostatic hypotension with failure of noradrenaline release. It is suggested that the pressor response to a M.A.O.I. and tyramine should be examined in patients with neurogenic orthostatic hypotension and that this treatment should be tried in those who respond.


Fatal graft-versus-host disease following transfusion of granulocytes from normal donors. A case of fatal graft-versus-host disease was seen in an adult with acute leukaemia, after transfusion of leucocytes from normal donors. This is the first reported case of graft-versus-host disease following transfusion of normal blood-products to a patient with a disease not usually associated with severe immunoincompetence. The number of lymphocytes transfused was no higher than that given when platelet concentrates are prepared from a single donor.


In-vitro monitoring of cell-mediated immunity to dinitrochlorobenzene. A dinitrochlorobenzene (D.N.C.B.)/red-blood-cell conjugate inhibited migration of leucocytes which came from D.N.C.B. sensitised patients. This effect provided the basis for a rapid, sensitive, and quantitative in-vitro measure of D.N.C.B. sensitivity. Frequent serial measurement of cell-mediated immunity was possible with the test, provided D.N.C.B. sensitivity was maintained by occasional skin patch tests.


Evidence for prevention of borderline leprosy reactions by dapsone. 68 patients were included in a prospective study of the treatment of borderline leprosy. 34 were treated with dapsone 5 mg daily, and 34 with 50 mg daily. Reversal reactions developed in 11 of those on 5 mg daily and in 3 of those on 50 mg daily. The statistically significant difference between the two treatment groups indicates that, contrary to previous teaching, dapsone given in higher dosage does not predispose patients to reversal reactions and indeed may prevent them.


Treatment of lamellar ichthyosis and other keratinising dermatoses with an oral synthetic retinoid. Thirteen patients with keratinising dermatoses were treated for 2-17 weeks with oral 13-cis retinoic acid. There was near complete clearing of the skin lesions beginning within 2 weeks of starting treatment in all five patients with lamellar ichthyosis (including two cases of non-bullous congenital ichthyosiform erythroderma), in two of the three patients with Darier's disease, and in one patient with pityriasis rubra pilaris. The patients with psoriasis and naevus comedonicus did not improve. The main form of toxicity was cheilitis. These results indicate that 13-cis retinoic acid may be more effective and is less toxic than naturally occurring retinoic acid (all-trans vitamin A acid), and that the synthetic retinoids may represent a potent new class of drugs in the treatment of cutaneous disease.


Lymphomas and animal-protein consumption. Geographic comparison reveals a positive correlation between consumption of animal protein, particularly bovine protein, and lymphoma mortality. Allied observations suggest that excessive consumption of animal protein may, through antigen absorption and chronic persistent stimulation, impose considerable wear and tear on lymphoid tissue and thereby encourage malignant changes.


Vitamin-D deficiency in the osteomalacia of chronic renal failure. The plasma level of 25-hydroxy-vitamin D (25-OHD) has been measured and the histological appearances of bone examined in 22 patients with stable chronic renal failure. The results show that osteomalacia occurred only in those patients with relatively low levels of 25-OHD. It is concluded that the osteomalacia of chronic renal failure results from a lack of 25-hydroxy-vitamin D3 superimposed on an existing deficiency of 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) rather than from lack of 1,25-(OH)2D3 alone.


Occult osteomalacia amongst healthy and pregnant women in Pakistan. A survey has been carried out on 206 healthy Pakistani women attending with their sick children at the paediatric outpatients department and 252 pregnant Pakistani women near term attending the antenatal clinic of the Karachi Prosgraduate Medical Centre. 12-6% of helathy women and 33% of pregnant women had biochemical abnormalities in serum calcium, phosphorus, and alkaline phosphatase which were corrected with subsequent administration of vitamin D. The absence of clinical disease has been ascribed to the supplementation received through the ultraviolet irradiation of the skin.


Influence of somatostatin on carbohydrate disposal and absorption in diabetes mellitus. Infusion of somatostatin, an inhibitor of glucagon secretion, in insulin-dependent diabetics resulted in a 75-100% reduction in the blood-glucose rise after oral glucose administration, but did not improve intravenous glucose tolerance. Somatostatin reduced blood-xylose levels by 50-90% after ingestion of this pentose and delayed the peak increment in blood-xylose by 1-2 h. Similar effects on blood-xylose levels and a 30% reduction in splanchnic blood-flow were observed in normal subjects during infusion of somatostatin. Glucagon administration (3 ng per kg per min) or intraduodenal administration of xylose did not reverse somatostatin's effect on xylose tolerance. Somatostatin reduces postprandial hyperglycaemia in diabetes primarily by decreasing and/or delaying carbohydrate absorption rather than enhancing carbohydrate disposal. This effect may be mediated, in part, but a reduction in splanchnic blood-flow. These findings indicate that postprandial hyperglycaemia in diabetes is due primarily to insulin deficiency rather than glucagon excess.


The primary enzyme defect in hereditary coproporphyria. The activity of coproporphyrinogen oxidase (E.C. 1.3.3.3) in cultured skin fibroblasts from three patients with hereditary coproporphyria (H.C.) was approximately half that in fibroblasts from normal subjects and patients with other types of porphyria. It is suggested that this is the primary defect in H.C., which is inherited as an autosomal dominant, and that the same abnormality is present in the liver. Consideration of the probable relative activities of the enzymes of haem biosynthesis in the liver in H.C. suggests that the acute attacks of porphyria which are its major clinical manifestation occur when the activity of uroporphyrinogen-I-synthase (E.C. 4.3.1.8) becomes rate-limiting for haem synthesis.


Herpes zoster with dysfunction of bladder and anus. Herpes zoster may give rise to dysfunction of bladder and anus. Mucosal lesions have been reported, and 7 cases are described with retention, loss of sensation, or incontinence. Sacral shingles is associated with sensory loss and flaccid detrusor paralysis. Lumbar shingles may cause retention, and zoster at higher levels can also damage the spinal cord. Recovery is usually complete. The implication for schemes of bladder innervation is discussed.


Blood-cadmium in hypertensives and normotensives. 70 hypertensive patients and 70 controls matched for age and sex were investigated for a possible relationship between blood-cadmium and hypertension. No significant differences between the two groups were detected, although the blood-cadmium level was significantly higher in smokers as compared to non-smokers. These data do not support the hypothesis that cadmium is involved in the development of hypertension in man.


Cyclic nucleotide phosphodiesterase activity of human normal and carcinomatous lung tissue. The activity of the phosphodiesterase enzyme(s) responsible for the degradation of cylic adenosine monophosphate (CA.M.P.) and cyclic guanosine monophosphate (CG.M.P. (in human normal and carcinomatous lung tissue has been investigated. Enzyme activities were 3-5 times greater in normal than in carcinomatous lung. This is compatible with the known higher concentrations of these cyclic nucleotides in normal tissues. It is suggested that cancer chemotherapy designed to block the phosphodiesterase activity, and thus promote accretion of CA.M.P and CG.M.P., may provide a means of normalising cancerous tissue. Both phosphodiesterase activities in both types of tissue were inhibited by methylxanthines at 10(-3) mol/l, but some enzyme potentiation was observed at lower concentration.


Where do all the tablets go?

Where do all the tablets go? Barium sulphate tablets, identical in size and shape to those of aspirin, were given to 98 consecutive patients during routine radiological studies of the upper gastrointestinal tract. In 57 patients the tablets remained in the oesophagus for longer than five minutes. Delay in passage of the tablets was particularly likely to occur in patients with hiatus hernia and reflux and if defects of peristalsis in the oesophagus were observed.


Wastage of pharmaceuticals.

Wastage of pharmaceuticals. Wastage of pharmaceuticals was studied for three months at a 520-bed hospital in Suffolk. Drugs worth 1104 pounds were brought to the pharmacy for destruction. Only 40 pounds worth could be put back into stock. It is suggested that the use of blister-packing together with conservative prescribing, supply, and suitable storage of medicines could lead to important savings of drugs discarded each year in English hospitals, which from this study were estimated to cost in excess of 1 million pounds.


[Blocking surgery for esophageal varices]. If it is not possible to arrest massive hemorrhage from esophageal varices within 48 h by conservative means or by endoscopic phlebosclerosation, surgery should be performed as soon as possible. In most cases a palliative operation is performed, by which irreversible shock and consequent heart failure can be avoided. The method of phlebosclerosation preferred by the authors is transection of the lower esophagus via a thoracic approach.


[Sclerosing therapy of esophageal varicosis (author's transl)]. As long-term results of portosystemic shunt operations for decompression of the portal hypertension are unsatisfactory, the author's therapeutic trials are directed increasingly at local treatment of varicosity. One treatment used is esophagoscopic submucosal sclerosing therapy of the esophageal wall for detachment of the varices from the surface. This method proved to be of great value in 420 patients, as the incidence of fatal recurrences of bleeding was only 12% and primary mortality was 15%. Suggested indications for endoscopic mural sclerosing are discussed. Mural sclerosing associated with transhepatic percutaneous esophageal varix sclerosis (following Lunderquist) might improve the results further in some cases.


[Surgical procedure in acute variceal hemorrhage (author's transl)]. The author recommends various general rules to be observed in the surgical treatment of acute variceal hemorrhage: 1. attempts to arrest the hemorrhage by conservative means are always justified in the case of variceal  bleeding, but should be comprehensive, and both patient and staff should first be prepared for surgery in case it should become necessary: 2. if when the GI tract is free of blood the indications for surgery are found to be present, a shunt should be constructed at once (Crile's stage A); 3. if hemorrhage starts again after carefully monitored release of the ballons of the Sengstaken-Blakemore tube, conservative measures should be carefully applied again at once. If an experienced endoscopist is available, paravariceal sclerosing injections should be given at this point. Otherwise a shunt operation is indicated (Crile's stage B). In patients in whom liver tolerance is poor (Crile's stage C), transhoracic dissection of the esophageal varices is indicated as the only possible, definitive treatment.


[Extirpation of metastases (author's transl)]. Seventy-two lung and 25 liver metastases were excised after radical local removal of the primary tumor. The 5-year survival rate was 41% and the 10-year survival rate 22% for patients in whom lung metastases had been excised. After the removal of liver metastases the 5-year and 10-year survival rates were 36% and 29% respectively. It is concluded that lung or liver metastases should be excised in certain defined cases. Pathologic fractures caused by bone metastases are stabilized by palliative internal fixation. In the cases of bone metastases, cure can only be expected when they are caused by hypernephroid and thyroid carcinomas.


[Multiple-stage treatment of malignant melanoma (author's transl)]. The paper reports on 11 patients with very advanced melanoma, who were treated with a modified version of multiple-stage cancer therapy. No improvement in the course of the illness resulted, but survival may have been slightly prolonged.


[The effect of ear surgery to the immunologic defense system of the middle ear during chronic otitis media (author's transl)]. Alpha-1-antitrypsin and alpha-2-macroglobuline are very important proteinase inhibitors for the healing process in chronic otitis media, because they can inhibit numerous bacterial and leukocytic proteinases: Alpha-2-macroglobuline can block the malignant proteinases of pseudomonas aeruginosa, staphylococcus aureus and proteus vulgaris. In 58 cases in the middle ear secretion was examined and the level of alpha-1-antitrypsin and alpha-2-macroglobulin investigated pre- and postoperatively. By these investigations we could demonstrate that the postoperative level of these two inhibitors is higher than preoperatively. In a couple of cases with cholesteatoma the postoperative concentration of alpha-2-macroglobuline was nearly three times higher than prior to the tympanoplasty. We believe that one of the causes for this high inhibitor level is the liberation of alpha-2-macroglobuline by injuring blood vessels during a tympanoplasty. It is our opinion that the increase of the inhibitor level in the postoperative phase is one of the prerequisites for the healing process in chronic otitis media.


[Compression of the external carotid artery. An anatomical finding to Eagle's syndrome (author's transl)]. An anatomical finding to Eagle's styloid process-carotid artery syndrome is presented. The left external carotid artery of a 64-year-old male is compressed by an anomalous styloid process and by the tendon of the stylohyoid muscle. Symptoms caused by anomality of the styloid process are reported by means of literature. The histological examination of the vessel wall in the level, where it is compressed, reveals typical characteristics of early arteriosclerosis.


Neurologic disease in patients with treated Whipple's disease. Four patients with Whipple's disease which had responded to antibiotic therapy, later developed neurologic disease identical to that seen in patients with Whipple's disease who died without treatment. Dementia, myoclonus, ataxia, and supranuclear ophthalmoplegia were the main neurologic features. Restarting antibiotics has been followed by stabilization of disease in all four. Two have improved. In three, the previously diagnosed and treated Whipple's disease was not considered as a possible cause of the neurologic disease until the symptoms and signs were far advanced. It is advisable to periodically evaluate all patients with Whipple's disease, even after successful treatment. Signs of neurologic disease should be considered a possible recurrence of Whipple's disease and antibiotics restarted.


Effect of inhibitors of sterol biosynthesis on growth and sexuality of Pythium and Zygorhynchus. Seven commercial inhibitors of sterol biosynthesis were tested for their effect upon vegatative growth and sexuality in Pythium acanthicum and Zygorhynchus moelleri. Five compounds (SKF 525, Chlorpropamide, Tolbutamide, Benzmalacene, AY 9944) inhibited both growth and sexuality of both fungi and two (SKF 7732 and SKF 7997) were ineffective. Pythium was more sensitive to the activity of the inhibitors than was Zygorhynchus. None of the compounds tested inhibited sexuality without similarly reducing vegetative growth.


[Changes in plasma values of alpha-fetoprotein in subjects with prior acute hepatitis]. Plasma alpha-FP values were examined in patients with a prior acute hepatitis episode. One group had been examined during the active stage and were then seen 4-5 months after clinical cure. In the second group, the episode had occurred 2-22 yr previously. Liver performance was fully normal in all cases. No subject presented clinical or serological signs of persistence or recurrence. Values were above the normal mean +/- 2 S.D. in 10-13 cases in the first group and were pathological in 31-38 of the second. These differences were statistically significant with respect to a control series. Increased alpha-FP in acute hepatitis can be seen as the result of post-necrotic regeneration. Experimental data have shown that alpha-FP synthesis is peculiar to only a few liver cell clones. It may be deduced, therefore, that these clones are mainly concerned in the repair process and are thus present in greater numbers when it has been completed.


Prediction of fetal outcome by urinary estriol, maternal serum placental lactogen, and alpha-fetoprotein in diabetes and hepatosis of pregnancy. Urinary estriol, serum placental lactogen (hPL), and alphafetoprotein (AFP) levels were investigated in singleton pregnancies of 75 diabetic women and 84 women with obstetric hepatosis. Fetal distress was demonstrated in 19 diabetic patients (25%) and in 18 cases of obstetric hepatosis (21%). Low urinary estriol correctly predicted fetal distress in 26% of the cases of diabetes and in 29% of the cases of hepatosis. False pathologic readings were found in 9% of pregnancies in either group. Diabetes was associated with higher than normal hPL levels with overlap of levels between cases with fetal distress and normal outcome. hPL levels were higher than normal and correctly predicted fetal distress in 2 of 18 cases of hepatosis (11%) with no false pathologic values. In diabetes, AFP predicted fetal distress in 2 of 4 cases in which a subsequent perinatal death occurred, and 1 additional case of fetal distress. False pathologic values were found in 4% of cases. Maternal AFP levels were normal in 2 cases of closed neural tube anomalies. In cases of hepatosis, AFP gave no information. In combination, estriol and AFP determinations gave correct information in 35% of diabetic pregnancies with pernatal morbidity or death. In hepatosis, estriol and hPL pointed out 33% of the cases of fetal distress.


Maternal serum and amniotic fluid alpha-fetoprotein as a marker of acute fetal distress in a midtrimester abortion model. Maternal serum (MS) and amniotic fluid (AF) alpha-fetoprotein (alpha-FP) levels were serially determined in 18 cases of elective midtrimester abortion. Prostaglandin F2alpha (PGF2alpha) and 20% NaCl were used as the abortifacients in 2 groups of 9 patients, respectively. The time from instillation to abortion (IAT) was accurately recorded in all cases. A marked 260-600% increase in MS alpha-FP occurred prior to fetal demise in both groups. Amniotic fluid alpha-FP content remained largely unchanged for the first 6 hours following intraamniotic prostaglandin injection. A 50% INCREASE WAS OBSERVED IN THE AF alpha-FP content in the group with 20% NaCl-induced abortion (after an initial dilutionary drop). The results of this investigation confirm the value of alpha-FP in MS as a marker of impending fetal demise. This rise is not caused by a prior alpha-FP change in the AF. The data suggest a major fetomaternal transplacental route for alpha-FP.


Symptomatic degenerative joint disease. Report of a case. Although degenerative joint disease is a most common type of arthritis in persons past 40 years of age, and associated with an aging process, this case has been presented as an interesting finding because of the early occurrence. Clinical symptoms, radiographic changes, and microscopic alterations were demonstrated. Conservative therapy was unable to relieve the symptoms and slow the progressive degeneration, and resolution of the subjective complaints was achieved by surgical intervention.


[On the radio-surgery of the carcinoma of the tongue (n = 1,000) (author's transl)]. In the period 1931 to 1976 1,116 patients were admitted to our department--1,000 were treatable. The 5 year survival rate is 26.7% out of 975 cases with follow-up. There is a marked difference between the regions of the corpus and the radix linguae which present with different symptoms and--in relation to these--have a very different prognosis. The Ca linguae and sublinguale are without symptoms--after treatment--in 29.15%, the Ca radicis linguae in 10.5% only. The method of choice was in case of circumscribed invasion radio-surgery, in case of Radix Ca or diffusion or involvement of fixated lymphnodes irradiation with external beams: Radium, Cobalt, Betatron. 20 years ago, Wasserburger, the late leader of our departement, published the results of his investigations on data of 628 patients with Ca of the tongue. The good results which are due to a methodical approach and meticulous treatment were not equalled by another method, neither irradiation alone nor surgery. To preserve the unique homogeneity of this material we stuck to this therapy which consists in the coagulation of the tumor, interstitial implants of radium-needles in the layers adjacent to the electrocoagulation and in external radiation of the regional lymphnodes and additional chemotherapy if indicated. On january, 21st., 1976, the thousandst patient with Ca of the tongue was admitted to our departement to be treated and so continues the chain of patients which were extensively documented and are followed up in coordinative work with the ENT departement in our hospital. In summary there were 1,116 cases, 116 were too progredient to be treated.


Rheumatic diseases. 1. Differential diagnosis. In a case of rheumatic disease, the patient's history and a careful physical examination should yield most of the information needed to identify the specific disorder present. A convenient classification is based on four differentiating features: number of joints affected, acuteness or chronicity of disease, absence of joint involvement, and anatomic distribution.


[New strategies in psychiatric diagnosis through the use of audio-visual technics. 2. Importance of verbal and non-verbal information for assessment of depressive patients]. Sections of 150 seconds duration were taken on a random basis out of TV stored interviews of day 0, 10 and 20 of a double-blind antidepressive drug trial. Not identical sections were selected for the isolated audio and video channel and for the combined presentation in such a way that for each of the 20 patients three times three parts were presented for evaluation. It was the two rater's task to rank each patient's tapes in terms of the degree of depression. They were blind regarding the day of recording the interview (day 0, 10 or 20). The best results were reached with the combined presentation of the audio-video-channel while each channel taken seperately rendered less diagnostic information. The raters evaluated the material in two different modifications: a) Video, audio and than audio-video-channel or b) audio, video and audio-video-channel. The first version (a) was evaluated in a better way than the second one with respect to the content of diagnostic information. Furthemore we found that the evaluation of the visual information became less safe if the audio presentation preceded as in version b.


Slide-tape versus lecture demonstration presentation of thermal agents in a physical therapist assistant program. A slide-tape individualized method and a conventional lecture-demonstration method of teaching thermal agents to physical therapist assistant students were compared. Performance measures included clinical procedures, written tests, attitudes toward the method used, and time spent in the learning center and in the classroom laboratory. No significant differences were found between the groups on performance of clinical procedures, written tests, or attitudes. The group using the slide-tape individualized method, however, spent significantly less time in achieving satisfactory performance on written tests and in clinical procedures.


Brain metastases and possibilities of their treatment, with special reference to single-session whole-brain irradiation. A brief review of methods used in the treatment of brain metastases is followed by a discussion of single-session whole-brain irradiation, with special reference to three important practical problems: (a) difficulties in evaluation of the clinical condition, and particularly the quality of survival, after treatment; (b) cerebral oedema induced by single-session whole-brain irradiation and methods to reduce it; (c) selection of patients. The tentative conclusion is that single-session whole-brain irradiation affords a possibility of palliative treatment of brain metastases.


Comparison of I-bleomycin prepared by two methods stability and pharmacokinetics in tumor-bearing mice. Bleomycin, a chemotherapeutic antibiotic agent, was radio-iodinated by the ICI and chloramine-T methods; the radiochemical stabilities and pharmacokinetics of the two I-bleomycins in tumor-bearing mice were compared. The ICI preparation was more stable with respect to deiodination in vitro. Both products were sufficiently stable in vivo that high body background due to free isotope, a disadvantage of 111In- and 99mTc-bleomycin, was not encountered. Tumor uptake of the ICI preparation was constant from 2 to 24 hrs., and the tumor/blood ratio increased with time; with chloramine-T, this ratio decreased, and was less than that for ICI. The two preparations are chemically and biologically different; the ICI product is the superior tumor radiodiagnostic agent.


Abnormal fat collections in the omentum and mesocolon of children. Two cases of abnormal collection of fat in the abdomen are reported. One involved the omentum, the other involved the mesocolon. Both patients had few symptoms with strikingly similar radiological findings of increased radiolucency due to fat surrounding the small bowel.


The occurrence of orcein-positive hepatocellular material in various liver diseases. Liver specimens from 103 patients with various hepatic diseases and from 297 consecutive liver biopsies examined routinely were stained with orcein after oxidation of the tissue sections with potassium permanganate. Orcein-positive dark brown cytoplasmic material could be demonstrated in 27 cases with long-standing cholestasis. These patients had either primary biliary cirrhosis, the cholestatic liver disease of ulcerative colitis or chronic active hepatitis, advanced alcoholic cirrhosis or secondary biliary cirrhosis due to extrahepatic biliary obstruction. Orcein-positive material could not be demonstrated in congenital disorders of bilirubin metabolism or in hemochromatosis. Similarly, it could not be found in acute, toxic, alcoholic or chronic persistent hepatitis.


The cellular origin of motilin in the gastrointestinal tract. The semithin-thin technique applied to serial resin-embedded sections, using sequential immunocytochemistry, conventional electron microscopy and silver staining, indicates that a population of enterochromaffin cells in the intestine contain, and therefore presumably synthesize and secrete, the 22-amino acid residue peptide motilin.


Differential localisation of substance P and motilin. Motilin, and Substance P, have previously been shown to be present in enterochromaffin (EC) cells in the gut mucosa. By comparing a specific immunofluorescence stain for Substance P with an immunoperoxidase reaction for motilin, applied sequentially to the same tissue section, it is possible to demonstrate that the two peptides are present in different cells. It is concluded that a) at least two different types of EC cells must exist and b) these results provide further evidence for the neuroectodermal origin of the gastrointestinal APUD cells. Studies of the degranulation pattern of EC cells could help to elucidate the role of amines in the mechanism of storage and secretion of different peptides under normal and pathological conditions.


Heparin cofactor activity and antithrombin III concentration in plasma related to age and sex. Heparin cofactor activity and antithrombin III (At-III) concentration were measured in plasma from 219 healthy men and 177 women. Narrow ranges for heparin cofactor activity and At-III concentration were found. The standard deviation for heparin cofactor activity in men and women was 8.6 and 10.1, respectively, for At-III concentration 10.4 and 12.5. In men, mean heparin cofactor activity and mean At-III concentration decreased significantly with increasing age. In women, mean heparin cofactor activity and mean At-III concentration tended to be lower in fertile age. Hereditary At-III deficiency was detected in one individual.


Activation of human lymphocyte subpopulations by rabbit anti-human beta2-microglobulin and by lipopolysaccharide. Rabbit anti-human beta2-microglobulin (anti-beta2m) was found to increase DNA synthesis in peripheral blood lymphocytes (PBLs) and in cells from abdominal lymph nodes, spleen, tonsil, adenoid, appendix, and bone marrow. The response to anti-beta2m was highest in cells originating from abdominal lymph node, appendix, and spleen. These organs were shown to contain a high proportion of surface-Ig-positive cells. No response to anti-beta2m was seen in thymus cells or in B-cell-depleted lymphocyte populations. Lipopolysaccharide (LPS) increased DNA synthesis in spleen cells, bone marrow cells, tonsil cells, and, sometimes, in cells from abdominal lymph nodes but weakly or not at all in PBLs. To study whether anti-beta2m and LPS activated the same subpopulation of lymphocytes, cultures were exposed to both mitogens in various concentrations. The effect on DNA synthesis in spleen cells was almost additive. This may indicate that these two polyclonal B-cell activators (PBAs) stimulate mainly distinct subsets of B cells in spleen. On the other hand, these two mitogens have a synergistic effect on DNA synthesis in PBLs. Since anti-beta2m is the first described selective B-cell mitogen activating human PBLs, it might be of clinical importance in the functional characterization of lymphocyte subpopulations.


[Treatment of disseminated oro-pharyngo-laryngeal epidermoid carcinomas with a combination of methotrexate and bleomycine in small doses]. In the previously published series of patients with generalized head and neck epidermoid carcinoma, a high dose combination of methotrexate (MTX) (0.4 mg/kg biw. i.v.) and bleomycin (BLM) (30 mg biw. iv) produced an objective remission rate of 60% with a median duration of 9 weeks. The disappointingly short duration of the remissions was tentatively related to the short period of treatment, which was limited to 5 weeks in order to keep the cumulative dosage of BLM below 300 mg. In the present study, covering 26 patients, a lower weekly dose was adopted (BLM 15 mg, MTX 0.6 mg/kg). 13 partial remissions were obtained with a median duration of 26 weeks; in 7 cases there was no evolution, in 6 cases progression of the tumor was registered, and there was one death from hematological toxicity. The major toxicity was leuko- and thrombopenia with one toxic death. Digestive and cutaneous side effects and fever were minor. There were 2 cases of major pulmonary toxicity, one of which was lethal. In conclusion, a combination of MTX and BLM at a relatively low dosage is active in disseminated head and neck carcinoma and appears to be compatible with longer maintenance of palliation in comparison with results obtained at a high dose level.


[Simultaneous combination of adriamycin, bleomycin, cyclohexyl-chloroethyl nitrosourea with dimethyl-triazeno imidazole carboxamide in the treatment of Hodgkin's lymphoma]. Sixteen patients with Hodgkin's (10) and non-Hodgkin's (6) lymphoma were treated by the "ABCD scheme", which is a combination of adriamycin (25-30 mg/m2 day 1), bleomycin (15 mg day 1-5), CCNU (60 mg/m2 day 1) and DIC (90-100 mg/m2 day 1-5). 15 results are evaluable and included 5 complete remissions, 5 partial remissions, 2 stabilizations, 2 progressions and 1 early death (remission rate: 66%). 45 ABCD courses were given. 8 patients received more than one course (maximum 7 courses). Toxicity was tolerable and consisted mainly of myelodepression, nausea, vomiting and muco-cutaneous alterations. Two patients died following toxicity, one from myelosuppression and the other from interstitial pulmonary fibrosis. The results suggest that this combination can be useful where the usual chemotherapy combination fails.


Centrifugal fibers to the eye in a nonavian vertebrate: source revealed by horseradish peroxidase studies. A source of efferent fibers to the eye of snakes of the genus Thamnophis has been identified by the use of the retrograde transport of horseradish peroxidase. Cell bodies of the contralateral nucleus of the ventral supraoptic decussation accumulate horseradish peroxidase after intraocular but not intraorbital injections. Intraocular injections also result in anterograde transport of horseradish peroxidase to retinofugal axon terminals. Intraorbital injections result in accumulation of horseradish peroxidase in the cell bodies of the cranial nerve nuclei of extraocular muscles.


Prophylactic and therapeutic use of anticoagulants in inherited antithrombin III deficiency. A family with a pronounced history of venous thrombotic disease is described. Several members were found to have reduced antithrombin III levels. Heparin cofactor activity was reduced in the antithrombin III-deficient plasma. The proposita, who presented with bilateral iliofemoral vein thrombosis early in pregnancy, was treated initially with heparin, and after the 12th week of pregnancy was maintained on oral anticoagulants until she was 38 weeks pregnant. Heparin was then given and continued throughout the delivery period and for 10 days postpartum with no evidence of recurrent thrombosis. The effect of infusing 5 units of fresh frozen plasma on the antithrombin III level and the response to heparin were minimal and short-lived. Oral anticoagulatns produced a rise in the antithrombin III level. These results demonstrate the importance of maintaining antithrombin III-deficient subjects on long-term oral anticoagulant therapy.


Immunological aspects of hepatocellular carcinoma in the guinea-pig. Experimental observations were made on hepatic cancer induced with diethylnitrosamine (DEN) in guinea-pigs. Two cancer cell lines have been established in tissue culture and their antigenicity investigated. Tumour antignes were not found on normal liver cells, liver cells damaged wtih carbon tetrachloride and fetal liver cells obtained from fetuses more than 35 days old. The possibility of using immunological techniques to investigate the antigenicity of human cancer is discussed.


Expression of the cystic fibrosis genotype in cultured somatic cells. Observations on the characteristics of the cell with the cystic fibrosis (CF) genotype in culture are reviewed. Although numerous and diverse abnormalities have been described, none were specific for the CF gene. The relevance of each of these abnormalities to the clinical syndrome known as CF is discussed, emphasizing that the value thus far of such cell culture research has been to learn how the CF gene influences cellular function.


Kinetics of microcolonies of cultured mammalian cells after bleomycin treatment. Cultured ascites hepatoma cells of the rat were treated with 400 to 900 R of gamma rays or 25 to 100 mug/ml of bleomycin for 30 min. The cells were followed up for 133 hr and the pedigrees were analyzed. Gamma rays and 2 low doses of bleomycin gave rise to typical reproductive death in generations 1 and 2 but 100 mug of the drug produced frequent interphase death. Natural death and induced death did not follow statistical randomness suggesting an existence of weak and sensitive clones in a population.


Hexachrome modification of Movat's stain. A less than three-hour hexachrome modification of Movat's pentachrome stain is described, its various steps discussed, and its principal uses in histopathology presented. The hexachrome procedure consistently yields good results, with excellent and colorful differentiation of muscle, various connective tissue components, mucinous secretions and intra-cytoplasmic structures in human and animal tissues obtained surgically or at autopsy. Alternative abbreviated procedures for muscle-connective tissue differential staining and for study of nuclear detail are also described.


The nature of mycobacterial acid-fastness. Phenol is not essential to acid-fast staining, for it will occur in the absence of phenol where such lipoid-soluble basic dyes as night blue, Victoria blue B or Victoria R are used; it is essential for acid-fast staining with water soluble basic dyes such as basic fuchsin. When phenol is added to the staining solution, such water soluble basic dyes behave in effect like their lipid-soluble counterparts. The loss of mycobacterial acid-fastness with carbol-fuchsin after bromination or chromation indicates that this phenomenon is related to the presence of unsaturated lipids in the bacterial cells. Within the cells these acid-fast lipids are bound in such a way that they are easily removed from all mycobacteria by hot dilute HCl; from leprosy bacilli alone they are easily removed with hot pyridine. From the results of various blocking reactions it appears that carboxyl and especially hydroxyl groups of these cellular lipids are essential to the acid-fast reaction of mycobacteria.


A Bodian method for mounted frozen sections. For application of the Bodian method to frozen sections, cut frozen peripheral nerve or muscle at 10 mum and mount. Fix for 4 days in 18 parts 80% ethanol, 1 part 10% formalin, and 1 part glacial acetic acid. Fix central nervous tissue in the same mixture prior to freezing and sectioning, and after mounting postfix for 4 days. Impregnate by the Bodian procedure. The results equal Bodian stains of paraffin sections. The technique is simple and reliable. The use of 10 mum frozen sections produces little artifact and allows alternate serial sections to be stained with other techniques.


Absorption of lead through the skin.

Absorption of lead through the skin. Absorption of lead through the skin was studied by comparing the effect produced by lead naphthenate or lead acetate solution, when coated on the skin of rats, with data obtained from subcutaneous injections of these solutions. Body weight and liver size and weight decreased in the case of rats receiving the subcutaneous dose. delta-Aminolevulinic acid dehydratase (ALA-D) in liver was decreased in all rats having been treated with lead compounds. The distribution of absorbed lead has been evaluated by assay of the lead content in brain, liver, kidney, spleen and muscle in the rats. The results of this study seem to verify that absorption of lead through the skin does occur and the findings confirm lead naphthenate to be more toxic than lead acetate.


Immunopathological studies of the ruptured human renal allograft. The immunopathology of five cases of spontaneous allograft rupture has been studied. All kidneys were edematous on exploration and routine histological sections showed interstitial edema and mononuclear cell infiltration characteristic of acute rejection. Immunofluorescence revealed, at most, scattered vascular deposition of IgM and mild mesangial C3 deposition. These findings are compared with findings in normal kidneys and kidneys which had been hyperacutely rejected. The normal kidney showed focal afferent arteriolar and proximal mesangial stalk deposition of C3 without IgM. The kidneys of patients with hyperacute rejection showed brilliant staining for fibrin and IgM in all arterial and arteriolar walls with lesser amounts of C3 and IgG; IgM and C3 were prominent in the glomerulus. These findings suggest that mechanisms other than circulating preformed antibodies are responsible for the pathogenesis of spontaneous allograft rupture.


Absence of a serologically detectable association of murine beta2-microglobulin with the embryonic F9 antigen. The association of murine beta2-microglobulin to the early embryonic F9 antigen has been investigated by indirect immunofluorescence and by radioimmunoassay. Although some cell lines carry both types of molecules, the beta2-microglobulin was not found expressed on primitive teratocarcinoma cells, where F9 antigen was primarily detected. It is concluded that the low m.w. (12,000 daltons) subunit that was reported to be associated to the F9 antigen is not the adult beta2-microglobulin.


Purification of HLA antigens from urine. HLA antigens were purified from urines of kidney transplanted patients, HLA was recovered as a single peak of 45,000 mol wt that was dissociated into beta2-microglobulin and a 33,000 mol wt fraction bearing the allospecificity. The purified fractions contain carbohydrates but no lipids. Electrophoretical mobility and the relative salt concentration of eluting buffers in DEAE-Sephadex chromatography were determined for six antigens of the A locus and seven antigens of the B locus. Isolectric points of antigens A1, A2, A9, and B12 were measured. Physiochemical characteristics of HLA purified from urine appear to be similar to those of papain-solubilized cell membrane HLA. Urinary HLA was shown to originate from serum and not from renal or ureteric tissue.


[Diagnostic laparotomy and palliative surgery in jaundice caused by tumors of the pancreato-duodenal zone]. The remote results of palliative operations for tumors of the pancreatoduodenal zone in 266 patients were analysed. Among palliative procedures cholecysto-jejunoanastomosis was most frequently employed in the clinic. 72 patients died. An acute hepatic insufficiency and cancerous intoxication was the main cause of the mortality. It is concluded that the survival of patients postoperatively depends on tumor localization and the degree of cancerous intoxication. The construction of cholecysto-jejunoanastomosis with the Brown enteroanastomosis seems to be mostly rational.


[Several properties of one of the acid neurospecific antigens]. The identity of one of the acid neurospecific antigens (antigen A) and S-100 protein has been established through agar gel immunoelectrophoresis and Sephadex G-100 gelchromatography. On agar gel electrophoresis antigen A moves as 2 fractions which occupy positions of blood serum prealbumins and alpha2 globulins. Both fractions of the antigen have a molecular weight of 25000. The heterogenic nature of antigen A (protein S-100) during electrophoresis on agar gel is discussed.


[New polymerase gene in pancytopenia (author's transl)]. Increasing evidence has accumulated that the direct assay of reverse transcriptase in human blood cells is of value in the diagnosis of leukaemia. The isolation and characterization of this enzyme has shown that it possesses remarkable similarities to the DNA-polymerase of the RNA-tumour virus of simian sarcoma. Hence, leukaemic cells in humans are thought to possess a virus-related gene, namely, reverse transcriptase. Various clinical reports have established the presence of this enzyme in blood cells, not only in the case of morphologically-proven malignant change, but also in cases classified as non-leukaemic from the morphological picture, such as acute leukaemia in remission and in the pre-leukaemic state. In confirmation and augmentation of earlier views we now report on the presence of reverse transcriptase in a patient with pancytopenia, who subsequently developed acute leukaemia i.e. isolation of the enzyme occurred in the pre-leukaemic state.


[Malignant disease of the paranasal sinuses (author's transl)]. During the period 1931 to 1974 167 men and 97 women with tumours of the maxilla or of the paranasal sinuses were treated at the Department of Radiotherapy and Oncology, Lainz Hospital. The peak incidence is found in the age group 51 to 70 years. The survival rate is determined by the extent of spread of the tumour. Cases in which the malignant process is still localized in the mucosa, without infiltration of the adjacent bony structures, have a good prognosis and so have the early cases of all tumours of the paranasal sinuses (Stage T1 and T2, according to Schwab) with a 5-year survival rate of 59.3%. Of the late cases (stage T3 and T4), however, no more than 20% survive for 5 years. In sarcomas there is no difference in survival rate between early and late cases because of their natural tendency to systemic spread. The 5-year survival rate is 33% in each group. Chemotherapy of these malignant tumours with Bleomycin appears promising, with a reduction of even massive infiltrations of the osseous structures in squamous cell carcinomas. However, there is no evidence as yet of any increase in 5-year survival rate with this type of therapy.


[Cytodiagnosis of the synovial fluid].

[Cytodiagnosis of the synovial fluid]. In a survey in a general part the differential-diagnostic approach in the establishment of cytological findings of the arthrocentesis for the judgment of the normal and pathologically changed synovial fluid are described. Especially the differential-diagnostic possibilities by constellations of the findings from determination of the total number of leucocytes, the differential cell picture and the determination of the individual signs characteristic for a disease are demonstrated. A special part deals with the assessment of the cytologic findings of the arthrocentesis for the diagnosis, the local and general judgment of the activity and the judgment of the therapeutic success of medicamentous and operative measures in rheumatoid arthritis with the help of the cytology of the puncture of a joint.


[Studies on the antigenicity of variously preserved skin]. The authors have investigated a model of second-set-rejection after allo-transplantation of chemically preserved skin by different methods. The relative increase of weight of regional lymph nodes as well as the production of lymphocytotoxic antibodies served as additioned indicators of senzitation. All regimes of preservation used in this model of second-set-rejection have been responsable for a decrease in antigenity. The results are discussed with regard to recent publications.