Avian retrovirus-induced surface antigens and their cross-reactivity with chemically-transformed cells and primary embryonic cells of Japanese quails. By testing spleen cells from avian leukosis (ALV) and avian sarcoma virus (ASV)-injected Japanese quails in a microcytotoxicity assay against various target cells, we have demonstrated the existence of several target antigens. With non-transformed ALV-infected Japanese quail cells used as target cells, an avian retrovirus subgroup-specific destruction was obtained when spleen cells from animals infected with either avaian sarcoma or leukosis virus of the same subgroup were employed. This reaction is probably due to the virus envelope glycoproteins (Ve-gp) expressed on the cell surface. Apart from this subgroup-specific reaction, avian retrovirus group-specific destruction of ASV-transformed cells was demonstrated by means of effector cells immunized with ASV of a different subgroup. This reaction is restricted to transformed cells and not due to the virus envelope glycoprotein because the same effector cells are not cytotoxic to ALV-infected non-transformed cells but cytotoxic to sarcoma-virus-transformed cells which lack Ve-gp. Quail methylcholanthrene-tumor cells which show a transformation phenotype similar to that of ASV-transformed cells but which are free of detectable endogenous and exogenous retrovirus were also destroyed by the spleen cells from ASV tumorbearing animals. The same effector cells also exerted a weak cytotoxic effect on uninfected primary embryo cells but not to embryo cells after several passages.


Feline malignant mammary tumors. III. Presence of C-particles and intracisternal A-particles and their relationship with feline leukemia virus antigens and RD-114 virus antigens. Thirty-six feline mammary tumors were examined by the electron microscope, and by the indirect immunofluorescence (IFA) test with anti-FeLV and anti-RD-114 serum. In 11 (30.6%) tumors intracisternal A-particles (IAP) were found. One of these tumors contained a few particles with an electron-dense nucleoid in the cisternae of the endoplasmic reticulum. In 7 (19.4%) other tumors C-particles were found and in the remaining 18 (50.0%) no particles at all could be detected. In 11 (30.6%) tumors FeLV antigens and in 20 (55.5%) tumors RD-114 virus antigens were present. In 9 (25%) tumors we found a high (greater than 1/64) and in 11 (30.6%) tumors a low (greater than 1/16 less than or equal to 1/64) titer. There was a good correlation between the presence of C-particles and the demonstration of FeLV-antigen but none between IAP and FeLV antigens. No correlation was found between RD-114 virus antigens and any type of particle. Morphologically, the IAP found in feline mammary tumors were indistinguishable from the IAP present in mammary tumors of some inbred mice strains. The IAP in feline mammary tumors possibly represent an endogenous virus, different from RD-114 virus. The role of these viruses in the etiology of feline mammary tumors is discussed.


Quantitative histochemistry of myelin using Luxol Fast Blue MBS. The amount of Luxol Fast Blue MBS in the band of Genarri was measured with two types of scanning microdensitometer and the optical density determined. The amount of stain measured was proportional to the section thickness employed, thus demonstrating that the dye has stoichiometric properties in tissue sections. Blocks of tissue treated with phospholipid solvents showed an increased uptake of stain, suggesting that phospholipids are not a primary substrate for the dye in myelin staining. The dye may, therefore, be used to quantify myelin in tissue sections.


Histochemical and ultrastructural identification of neurotensin cells in the dog ileum. In the dog ileum, neurotensin cells stained with immunofluorescence or immunoperoxidase proved distinct from argentaffin (EC) cells, glucagon immunoreactive (GLI) cells and pancreatic peptide immunoreactive (PP) cells. Neurotensin cells showed various degrees of reactivity with Grimelius' silver. With electron microscopy, besides EC cells, large granule cells with a thin peripheral rim of Grimelius-reactivity (L cells) and large granule cells with variable Grimelius-reactivity of the core (N cells) were found. On distributive grounds, L cells were identified with GLI cells and N cells were interpreted as neurotensin cells.


Media for an integrated nursing curriculum. In conclussion, the media decision-making process for an integrated nursing curriculum is based upon the following steps: - An analysis of the philosophy and unifying strands in the conceptual framework of the curriculum model, - An evaluation of currently owned media in terms of the theoretical framework and educational objectives of the model, - An assessment of commercial media with realistic planning for purchase and/or production, and - The development of a systematic ongoing evaluation process by students, faculty, and nursing service personnel. The focus of this discussion has been clarification of the assessment and planning steps necessary in the media decision-making process for an integrated nursing curriculum. While these steps are applicable to any educational model, they have particular relevance to a curriculum model in which concept learning and interrelationships are stressed.


Immunochemical studies of fragments of bovine serum albumin. Antigenic properties of 14 fragments of bovine albumin were measured using antisera to albumin and to two of its fragments. All seven fragments larger than 21,000 daltons formed immune precipitates. Although immune precipitates were not formed with smaller fragments, inhibition tests indicated the presence of antigenic sites on several of these fragments as well. The results predict the occurrence of six or more antigenic determinants and allow assignment of their positions in the parent molecule. These sites are distributed along the entire protein chain, with the sites of greatest antibody affinity situated in the COOH-terminal region. Evidence is presented that some sites are homologous, reacting with the same populations of antibodies, and that other sites are unique, binding to an exclusive population of antibodies.


The role of three genetically distinct collagen types in endochondral ossification and calcification of cartilage. The role of three genetically distinct collagen types in the formation of endochondral bone and in calcification and resorption of cartilage has been assessed. Using antibodies specific to types I, II and III collagen we have demonstrated in the embryonic chick tibia that endochondral bone formation began with deposition of type III collagen in lacunae of hypertropic chondrocytes by invading bone-marrow-derived cells. This was followed by the deposition of type I collagen, which is the collagenous constituent of endochondral osteoid. At later stages of development endochondral osteoid was found in the epiphysial growth plate in apparently intact lacunae of hypertrophic chondrocytes; this indicated that the latter might contribute to the synthesis of osteoid type I collagen. Immuno-histological staining for collagen types, and von Kossa staining for calcium phosphate on parallel sections, demonstrated that type I and type II collagen matrices were substrates for calcification. Endochondral bone (with type I collagen) was found on scaffolding of both uncalcified and calcified cartilage (with type II collagen), indicating that calcification of endochondral osteoid and of the underlying cartilage occurred independentyl. Spicules of endochondral cancellous bone of a four-week-old chick contained a core of calcified type II collagen.


Enzyme-linked immunosorbent assay for chlamydial antibodies. An enzyme-linked immunosorbent assay (ELISA) detected chlamydial antibodies in human sera. The assay antigen produced in cell cultures infected with Chlamydia psittaci was Formalin-fixed to microplates. Single convalescent-phase sera positive for chlamydial antibodies by a complement-fixation test were positive at even higher dilutions by ELISA. Paired sera with diagnostic rises in complement-fixing antibody showed seroconversion by ELISA also. Control sera from persons with no history of chlamydial infection were negative by both tests. Sera from patients with psittacosis or lymphogranuloma venereum were ELISA positive, indicating that the assay with the antigen used in this study is genus specific rather than species specific.


Preparation of antisera to neurofilament protein from chicken brain and human sciatic nerve. Antigens isolated by hydroxyapatite chromatography from human sciatic nerve (SN1 protein) and from 8 M urea extracts of chicken brain were selectively localized by immunofluorescence to neurofibrils in rat and chicken CNS. Absorption of the antisera with SN1 protein, chicken antigen or GFA protein abolished the staining. Antisera raised against antigen isolated with the same procedure from buffer extracts of chicken brain stained both neurofibrils and glial fibrils by immunofluorescence. Neurofibrillary staining was selectively abolished by absorption of the antisera with SN1 protein. Antisera prepared against axonal preparations isolated from bovine white matter only stained astroglia and were thus undistinguishable from anti-GFA sera in this respect. The data suggested that the protein subunits of neurofilament and glial filaments, although difficult to separate in brain extracts by standard biochemical procedures and by subcellular fractionation in bovine white matter, still retain immunological specificity. In addition, the immunological cross reactivity between human and chicken antigens suggested that neurofilaments, as other constituents of the cytoskeleton such as microtubules and actin microfilaments, show a high degree of evolutionary stability.


The effects of undernutrition on Purkinje cell dendritic growth in the rat. The effects of undernutrition on the developing cerebellum were studied in 30-day-old rats undernourished from birth by restricting access to the lactating mother. These animals showed a significant reduction in cerebellar weight when compared with well-nourished controls. Quantitative studies of the cerebellar vermis revealed a 34.2% reduction in total area, with the density of both granule cells and Purkinje cells increased. Network analysis of Golgi-Cox preparations indicated a significant increase in the density of dendritic fields of Purkinje cells, although there was a 37% decrease in overall network size, due to reduction in the total number of dendritic segments, and a reduction in the length of distal segments. Topological analysis indicated that the network had developed by terminal branching, as in normal animals, but with some deviation from the usual purely random branching pattern. All the observed modifications may be accounted for in terms of alterations in protein synthesis and DNA synthesis occurring in undernourished animals. This leads to alterations in the extent of the interneuronal matrix, a reduction in the number of granule cells and direct effects on Purkinje cell metabolism, all of which influence dendritic development, although the relative importance of each of these factors awaits precise definition.


Root surface caries in the molar teeth of Rice rats. I. A method for quantitative scoring. A new system was devised for scoring root surface caries. The roots were divided circumferentially and apically into areas. Each exposed area and any carious involvement was given a score of 1. Root surface caries was expressed as total areas affected and as a percentage of the exposed root surface.


Remodeling of compact bone studied with lead acetate as an intravital stain. Remodeling of the osteons or Haversian canal system in compact bone was studied in young monkeys that received serial injections of lead acetate as an intravital strain. The successive stages of the formation of an osteon have been demonstrated. The rate of the filling of the lamellar bone decelerated as the lumen of the Haversian canal decreased. The total formation time of individual osteons was estimated.


A plastic tube technique for direct vision of endodontic procedures. A technique for the direct visualization of endodontic procedures utilizing clear plastic tubes machined to simulate root canals is described. The visualization of endodontic procedures allows for their evaluation by the clinician as well as their use as an adjunct to didactic courses in endodontics. During mechanical instrumentation it is evident that a concerted effort must be made to debride all of the walls of a canal. Hydraulic forces are seen to play a major role in irrigation and in applying root canal cement. The technique also reveals voids in the completed root canal filling when verticle condensation is used to obturate the canals.


Distribution of 14C-lindane in Japanese quail using autoradiography of whole body sections. Information on the distribution of lindane in Japanese quails was obtained by autoradiography of whole body sections. The most part of lindane was found in fatty tissues of the animals and the distribution in the other parts of the organism was equal. A single dose of 14C-lindane is found in the organism of Japanese quails mainly in the gastro-intestinal tract and is excreted within 72 hours after the application.


Neurotoxicity of organophosphorus insecticides Leptophos and EPN. Phosfolan, chlorpyrifos, and stirophos when applied to white mice at sublethal doses did not induce any delayed neurotoxic effect. On the other hand, Leptophos and EPN when administered orally at sublethal or lethal levels clearly produced a delayed neurotoxic ataxia in treated mice. The five tested organophosphorus insecticides were compared for their ability to inhibit cholinesterase, neurotoxic esterases and monoamine oxidase. I50 values were estimated for each case. The results revealed that all five compounds were inhibitors of cholinesterase, but only Leptophos and EPN were shown to be potent inhibitors for both neurotoxic esterase and monoamine oxidase in the mouse brain. Additional particular properties of both Leptophos and EPN were found in their ability to cause delayed neurotoxic ataxia in chickens and sheep fed once on sublethal doses of these compounds. It is believed that the phosphonate ester configuration of EPN and Leptophos has a specific mode of toxic action which is mainly located at the central nervous system. It is also postulated that these delayed neurotoxic agents might inhibit postganglionic sympathetic neurons, thus resulting in chronic paralytic effects.


A cytochemical study of the bag cell organs of Aplysia californica. Egg-laying hormone in Aplysia californica is synthesized and secreted by cells that seem to be homogeneous ultrastructurally and electrophysiologically. Several conventional methods have been used to demonstrate histochemical homogeneity and special staining techniques based on the known properties of the hormone show the neuroendocrine organ to be uniform in appearance. Furthermore, since stain specificity for egg-laying hormone is demonstrable using release and biochemical studies, the authors concluded that the organ consists of a population of biochemically homogeneous neurons.


Specific enrichment of the suppressor T cell bearing I-J determinants: parallel functional and serological characterizations. A simple procedure to enrich the antigen (keyhole limpet hemocyanin, KLH)-specific suppressor T cell was described. The suppressor T cell from KLH)-immunized mice specifically bound to the KLH-coated Sephadex G-200 column at 37 degrees C, and was eluted from the column by cold (0-4 degrees C) medium. The helper T cell did not bind to the column under the identical condition. The suppressor T cell thus obtained had 100 times as potent suppressor activity as the original spleen cells in in vivo and in vitro secondary antibody responses against a hapten coupled to KLH. This procedure also enriched the cells bearing I-J determinants and Lyt-2,3 alloantigens, allowing us to study the phenotypic expressions on the suppressor T cell by direct serological procedures as well as by the use of the fluorescence activated cell sorter. Parallel functional and serological analyses indicated that the antigen-specific suppressor T cell belongs to a population of I-J+, Lyt-2+,3+ and Fc R- T cells.


Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance. Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.


Immune response of Lewis rats to peptide C1 (residues 68-88) of guinea pig and rat myelin basic proteins. Peptide C1 (residues 68-88) from GP and rat BP differ by a single amino acid interchange at residue 79. This residue is serine in GP C1 and threonine in rat C1. GP C1 was encephalitogenic in Le rats at doses as low as 15 ng. Rat C1 was encephalitogenic at doses of 1,500 ng or greater. LNC from rats challenged with 25 X 10(-4) micronmol of GP C1 and 250 X 10(-4) micronmol of rat C1 showed a proliferative response in vitro to both peptides, but in each instance the magnitude of the response was greater to the GP peptide. GP C1 also induced higher levels of circulating antibodies at 25 X 10(-4) micronmol, but the specificity of antibodies produced by the two peptides was the same. These results have been interpreted as indicating that the presence of serine at position 79 in GP C1 results in the stimulation of greater numbers of T cells involved in (a) the induction of EAE, (b) the in vitro proliferative response and (c) helper function in antibody production.


Nylon adherent antigen-specific rosette-forming T cells. Shortly after intravenous immunization of mice with heterologous erythrocytes (RBC) antigen-specific Thy 1+ cells which form rosettes with the immunizing RBC (thymic-derived lymphocytes-forming rosettes [T-RFC]) appear in the spleen. These T-RFC are much less stable than Thy 1- RFC (non-thymic-derived [B-RFC]) although most if not all of both classes of RFC adhere to nylon. T-RFC are induced with low doses of antigen (which fail to induce B-RFC) and are inhibited by higher antigen doses which are optimal for induction of B-RFC. Pretreatment of mice with cyclophosphamide prevents the high dose inhibition of T-RFC. Although there are many parallels between the production of T-RFC and delayed-type hypersensitivity (DTH) it is unlikely that the T-RFC are essential for DTH reactions since DTH can be transferred with cells which pass through nylon, and such cells are almost totally depleted of T-RFC. Thus immunization can lead to the production of large numbers of antigen-specific T-RFC whose functional role in the immune response is unknown. However, the characteristics of the T-RFC suggest that they may play an important role in amplification of suppressor cell activity.


Immunochemical evidence for three Ia loci in the I-region of the H-2 complex. Sequential immunoprecipitation analyses of Ia antigens were performed with 125I-labeled B10, B10.A(3R), and B10.A(5R) spleen cell lysates. The results suggest the presence of one I-region associated (Ia) locus (Ia-1) in the I-A subregion. In addition, they indicate that two Ia loci map between the I-J and S regions. One locus, Ia-5, maps in the I-E subregion. The second locus, most likely Ia-3, maps in either the I-E or I-C subregion. Taken together, the data demonstrate that at least three Ia loci in the I-region of the H-2 complex code for molecules detectable by immunoprecipitation.


Complete inhibition of the expression of an idiotype by a mechanism of B-cell dominance. Mice of the C.AL-20 strain, which express genes controlling CH regions of the AL/N strain on a BALB/c background, normally synthesize antibodies to the p-azophenylarsonate group (anti-Ar antibodies) with an idiotype characteristic of the A strain. The synthesis of the idiotype, as quantitated by a sensitive assay, can be completely inhibited by the transfer of leukocytes from BALB/c mice producing anti-Ar antibodies, which lack the idiotype. A number of control experiments show that the inhibition is not attributable to suppressor T cells and that the synergistic action of such cells is not required. The results indicate that B-cell dominance, mediated by secondary cells, can completely prevent the expression of unprimed cells with receptors of the same specificity. It is uncertain whether this effect is due entirely to selective capture of antigen by the secondary cells, or whether some type of active suppression by B cells is involved.


The role of surface IgD in the response to thymic-independent antigens. An alloanti-delta antibody was prepared by immunizing C57BL/Ka mice with BALB/c spleen cells. Its specificity for delta-chain was demonstrated by immunoprecipitation and SDS-PAGE of 125I-labeled membrane proteins from BC8 spleen cells. BC8 mice possess C57BL/Ka "background" genes and BALB/c IgH genes. The anti-delta reagent without complement inhibited the primary in vitro anti-TNP antibody response to TNP-AECM-Ficoll by BC8 spleen cells, although it had no effect of the anti-TNP response of congenic C57BL/Ka spleen cells, which lack the delta-allotype identified by this antibody. On the other hand, the anti-delta antibody had no effect on the anti-TNP response of BC8 spleen cells to TNP-BA, except at limiting antigen concentrations. Both TNP-AECM-Ficoll and TNP-BA are T-I antigens, but they differ in that TNP-AECM-Ficoll fails to stimulate in vitro responses by immunologically defective CBA/N and neonatal spleen cells whereas TNP-BA can cause responses from both these animals. These results suggest that the IgD receptor is critical to T-I antibody responses initiated by TNP-AECM-Ficoll but that it is not required for T-I responses stimulated by TNP-BA.


The control of specificity of cytotoxic T lymphocytes by the major histocompatibility complex (AG-B) in rats and identification of a new alloantigen system showing no AG-B restriction. The regulatory influence of the rat major histocompatibility complex (MHC) (Ag-B complex) on the specificity of cytotoxic T lymphocytes was investigated. It was shown that the effector cells were specific for the original Ag-B phenotype in rat systems in which the responder and stimulator cell populations were unquestionably MHC identical but expressed different minor alloantigens of viral antigens. However, combined in vivo immunization and restimulation in culture of lymphocytes from rat strains previously thought to be MHC compatible resulted in the generation of cytotoxic T lymphocytes which effectively lyse not only target cells from the specific stimulating strains but also, to varying degrees, target cells from third party strains regardless of their Ag-B haplotypes. Genetic analysis indicates that expression of these cytotoxic T-cell-defined ("CT") antigens, found on both T and B lymphocytes, detectable thus far only with cytotoxic lymphocytes, is controlled by a single locus which segregates in backcross populations with the rat MHC. Discrepancies between the nature  of CT antigens of the rat Ag-B and I-region specificities of the mouse H-2 are discussed.


Evidence for multiple cell surface chicken fetal-leukemic antigens (CFA) in the developing chick and other avian species. Chicken fetal antigen (CFA), a membrane antigen present on fetal chicken red blood cells is lost with chicken development, and reappears on the red blood cells of leukemic chickens. Seven avian species were found to possess CFA. A species hierarchy comparing the quantitative expression of CFA has been established. The levels of CFA expression with development are compared in the chicken and Japanese quail. Specific adsorptions of R-anti-CFA with avian red blood cells revealed the existence of multiple CFAs. Four groups of antigenic determinants (CFA a,b,c,d) have been characterized and defined by their expression among avian species. Multiple CFA determinants are discussed with regard to possible membrane alterations and gene function.


Laboratory characteristics of poxviruses isolated from captive elephants in Germany. Proxviruses isolated from captive elephants in Germany have been characterized. Although related to vaccinia and even more closely to cowpox virus, the separate identity of elephantpox virus was established by both biological and serological methods. Elephantpox virus produces A-type inclusions in infected cells, as did cowpox, but had a lower ceiling temperature, was more heat resistant and affected rabbits differently. Cross neutralization tests on absorbed sera indicated that elephantpox, cowpox and vaccinia viruses shared one surface antigen, that elephantopox and vaccinia shared an antigen absent from cowpox, and that vaccinia virus had a surface antigen absent from elephantopox and cowpox viruses.


Ferric ion, ferrocyanide, and inorganic phosphate as cytochemical reactants at peripheral nodes of Ranvier. Ferric ion (Fe3+) and ferrocyanide (Fe(CN)64-) were used under a variety of conditions to stain nodes of Ranvier in mammalian peripheral nerves. Principal findings are: 1. Ferric ion will bind to the extracellular nodal gap substance if nerves are pretreated with a phosphate buffer; or, it will bind to the cytoplasmic surface of the nodal axolemma if pretreatment is with cacodylate or veronal--acetate buffer. 2. Ferrocyanide will bind to the inner surface of the nodal axolemma, where it may react with ferric ion to form a blue stain, or with an osmium compound to form a black stain. 3. Ferric ion and ferrocyanide are bound to nodes as colloidal precipitates, and may migrate away from their sites of formation. 4. Not all nodes in a single piece of tissue, or in a single fibre have identical staining properties. It is concluded that ferric ion, ferrocyanide, and inorganic phosphate are valuable as cytochemical reactants for peripheral nodes of Ranvier, but they must be used in carefully controlled experimental situations in order to avoid spurious results.


Combined application of cytodiagnostic technics to the cerebrospinal fluid. The major purpose of the examination of the cells in the cerebrospinal fluid (CSF) is the diagnosis of malignant growths. However, unequivocal tumor cell diagnosis is often problematical, since cells of local origin can also demonstrate considerable proliferative activity and great morphological variety. In these circumstances, it is advisable to evaluate cells from several points of view. One can demonstrate morphological characteristics with panoptic staining and can gain an impression of the RNA content of a cell with acridine orange (AO) fluorescent stain. Quantitative measurements of DNA synthesis in vitro can be made by labelling with tritiated thymidine. Multidimensional cytodiagnosis gives a comprehensive impression of the quality of the cells in question and provides the clinician with information which can be valuable for subsequent diagnostic and therapeutic efforts.


Vincristine polyneuropathy in man. A clinical and electrophysiological study. A clinical and electrophysiological follow up study of 14 cases of hemopathic patients patients undergoing VCR therapy showed evidence that the drug has a direct action on the motor and sensory axon but not on the propagation velocity. Sensory nerves seem to be affected earlier and more than motor ones. Correlation was good between clinical and electrophysiological findings for both functions. The findings in man correspond with the animal data and therefore lead to the conclusion that VCR polyneuropathy is due to an involvement of the nerve axon.


Increased voltage of the muscle action potential of normal subjects after local cooling. The compound muscle action potential (MAP) and the isometric twitch force of the adductor pollicis of 25 normal subjects were registered after local cooling. Intramuscular temperature ranged from 36.6 to 18.0 degrees C. The amplitude of the MAP increased while the twitch force decreased at lower temperatures. The increase of the MAP could be caused by the effect of cooling directly at the muscle cell membrane. The decreased twitch force probably is due to an affect on the contractile apparatus.


Complement dependen cytotoxic antibody activity against measles virus in multiple sclerosis. The presence of measles cytotoxic (CT) and hemagglutination inhibition (HI) antibodies in 195 multiples sclerosis (MS) patients and 251 controls was tested. The measles virus Lu carrier cells labeled with 51Cr were exposed to serum specimens in the presence of complement in order to test the presence of CT antibody. The analysis of complement dependent CT antibodies against measles virus revealed significantly (P less than 0.01) higher titers in MS patients than in the control group. However, the measles HI test failed to show this difference. Measles CT titers greater than or equal to 1: 32 among MS patients occured in 54.9% and in 35.5% among the controls. In comparison with this the HI method revealed measles titers greater than or equal to 1:128 more often in the control group than in MS cases (27.9 and 17.9%, respectively). The presence of CT antibodies against measles virus in MS proves that these patients have a function defence mechanism to eliminate virus infected cells. The high measles antibody titer among MS patients could be due to recurrent antigenic stimulation caused measles virus persistency. Whether this virus persistency plays a role in MS can not be decided on the available data.


Serological response of multiple sclerosis patients and controls to 6/94-parainfluenza virus. The serological responses of 195 multiple sclerosis (MS) patients and 251 controls were tested against 6/94-parainfluenza virus, which was previously isolated from brain tissue of two patients with MS. The hemagglutination-inhibition titers of greater than or equal to 1: 128 were found more frequently in MS patients (21.5%) than in controls (14.0%). However, the geometric mean titers did not differ between these two groups. The present study concludes that a causal relationship of 6/94-virus to MS, based on a specific immune response, is improbable, although it does not exclude the possibility of a pathogenetic significance of the agent in the cases from which the autopsy material was derived.


A heat stable serum inhibitor of an antigen antibody reaction of subacute sclerosing panencephalitis. A factor which inhibits the antigen antibody reaction was isolated from the sera of patients affected with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS) and also of control subjects. This factor inhibits the immune reaction between SSPE serum IgGs and measles virus. This inhibiting factor was detected in the alpha globulin region after agar gel electrophoresis, and is heat stable at 100 degrees C for ten minutes.


The fatty acid composition of sphingomyelin from adult human cerebral white matter and changes in childhood, senium and unspecific brain damage. A micromethod for the investigation of the fatty acid composition of sphingomyelin in presented. In the cerebral white matter of 17 normal adult brains, analyzed for reference, the predominant fatty acids are C 18:0 and C 24:1. Our results are in agreement with those of other authors. Short chained fatty acids are relatively increased in young children; this shift is typical of "immature" myelin. Similar changes are described here in old persons and cases of non-specific brain damage associated with demyelination (autolysis, chronic uremia, juvenile chorea). Sphingomyelin fatty acid composition can be considered a sensitive measure of both disturbed myelination and demyelination.


Hypokalemia shortens relative refractory period of peripheral sensory nerves in man. Absolute and relative refractory periods and the sensory conduction velocity of the median and ulnar nerves were determined in six patients suffering from hypokalemia of various origins. Nerve impulse conduction and the absolute refractory period remained normal, but the relative refractory period was shortened to 1.7 to 2.6 ms at serum K+ levels from 1.6 to 2.9 mval/l. As compared with normal values this decrease was statistically significant.


[Radiation myelopathy-two cases with unusual development (author transl)]. This is a report of two women who experienced radiation myelopathy 2,5 and 9 months after telecobalt radiation. Tetraplegia and paralysis of the inspiratory muscles developed rapidly in the first case whereas in the second case the paralysis and the initial Brown-Sequard syndrome improved after treatment with corticosteroids and infusion of Rheomacrodex and Sorbit. It should be stressed that in both cases the radiation stress on the spinal cord was under the limit of tolerance of 3300 to 4000 R. The differential diagnosis of radiation myelopathy from spinal metastasis is most important because the treatment is different for each conditions.


Myotonia not aggravated by cooling. Force and relaxation of the adductor pollicis in normal subjects and in myotonia as compared to paramyotonia. The effect of local cooling has been studied in 27 normal subjects, 8 cases of myotonia congenita, 5 of myotonic dystrophy and one of paramyotonia. Using the adductor pollicis we registered the compound muscle action potential, the isometric twitch force and the time to half relaxation, the maximum tetanic force and to time 3/4 relaxation. 1. In normal subjects the twitch force and maximum tetanic force decreased after cooling (Fig. 2). The amplitude of the action potential increased. 2. Myotonia congenita and myotonic dystrophy were not aggravated by cooling. Muscle force was reduced only in the same proportion as in normal subjects (Fig. 2). The myotonic after-contraction was made normal by cooling (Figs. 5 and 6). 3. In paramyotonia initial tonic stiffness with a pronouncedly prolonged twitch relaxation occured directly after cooling (Fig. 1 B). Paradoxical myotonia occured only after exercise and was accompained by increasing paresis (Figs. 3 and 8). The results indicate that exposure to cold has a specific effect on muscle function only in paramyotonia.


Histamine metabolism in cluster headache and migraine. Catabolism of 14C histamine. Various parameters of histamine metabolism were studied in patients with migraine, cluster headache and chronic paroxysmal hemicrania. These included urinary excretion of radioactivity and of 14C histamine and its metabolites, exhaled 14CO2 and fecal radioactivity after oral as well as subcutaneous administration of radioactive histamine. No marked deviation from the normal was found except in one patient with the cluster headache variant, chronic paroxysmal hemicrania, in whom an aberration in 14C histamine degradation seemed to be present. Only minute quantities of the 14C histamine metabolite C14 imidazoleacetic acid riboside seemed to be formed during a period with severe paroxysms. During a symptom-free period no deviation from normal was observed. The most likely explanation for this finding seems to be a defect in the conversion of imidazoleacetic acid to its riboside. This defect may possibly explain the increased urinary excretion of histamine in this particular patient. The relationship of this metabolic aberration to the production of headache still remains dubious for various reasons.


Recurrent Bell's palsy. Etiology, frequency, prognosis. The etiology, frequency and prognosis of recurrent Bell's palsy were studied in patients with peripheral paresis of n.facialis of various etiology. Fourteen (11.9%) of 117 patients with Bell's palsy had a recurrent paresis of n.facialis. Nine of these were of homolateral and five contralateral type. Seven recurrent facial paralyses in idiopathic Bell's palsy (i.e. 10.4% of the patients with idiopathic facial palsy), 3 facial palsies of viral origin (i.e. 8.8% of the patients with viral facial palsy), one in association with diabetes mellitus, one during pregnancy, one combined with positive rheumatic serological tests, and one in a case of Melkersson-Rosenthal syndrome were found. The frequency and heterogenity of etiology of recurrent facial palsies suggest a predisposing factor or immune mechanisms. In eight patients there was within 6 to 8 weeks a good, in two patients a moderate and in four patients a poor recovery of function. The greater reduction of the compound action potential of the m.orbicularis oris in recurrent homolateral facial palsy in relation to patients with single manifestation point out the greater denervation and therefore the poorer prognosis of recurrent palsies. A prophylactic decompression to prevent a third attack of recurrent facial paresis is considered.


A morphological and chemical study of calcification of the choroid plexus. Human choroid plexus was submitted to low temperature ashing (LTA) in order to isolate the calcification. The ashing residue was then subjected to morphological, chemical and structural studies using technics such as scanning electron microscopy, flame and flameless atomic absorption spectrometry, infrared spectrometry and X-ray diffraction. Morphologically, the calcification consisted of wound-up fibers forming granules with a diameter of 0.05 to 0.15 mm. The concretions were identified as cristalline Ca3(PO4)2 and hydroxylapatite. The content of trace elements was high, but within the limits found in other biological apatites. In some cases, however, the Fe content exceeded these limit values.


Anomalous lymphocyte-antigen reaction in relatives of multiple sclerosis patients. A study of a possible genetic factor in the disease. A combined familial study of multiple sclerosis (MS) in England and in the Rostock area of the GDR using the macrophage electrophoretic mobility (MEM)-LAD test embracing 132 relatives has revealed a closely similar pattern of distribution of "anomalous" LAD (Linoleic Acid Depression) values in relatives (77% type of reaction) to that originally reported in the British study. The anomaly in predominantly associated with females--all mothers of MS patients being affected, whilst daughters and sisters are also represented. In addition unusual full MS type of reaction (90% reduction) has been found in some children related to patients. There is clearly a genetic element in the development of MS probably mainfested in the inborn mishandling of unsaturated fatty acids suggested by Thompson; no recognizable pattern of inheritance is noticeable even within the combined material. There is evidence that the metabolic anomaly alone does not inevitably lead to MS, and the full abnormality may be present at an early age. A survey about the examinations and a selection of characteristic family trees of MS are given, illustrating the manner in which the 77% type anomaly is distributed with occasional omission of a generation.


Histochemical study of normal human muscle spindle. Histochemical classification of intrafusal muscle fibers and intrafusal nerve endings. Normal muscle spindles of human skeletal muscle were studied histochemically. 1) Four histochemical types of intrafusal muscle fibers were classified by ATPase stain: Bag I fiber, Bag II fiber, Chain I fiber and Chain II fiber. Moreover, two types of nuclear bag fibers were classified by NADH Tetrazolium Reductase stain and PAS stain: Bag I fiber and Bag II fiber. 2) Three kinds of fusimotor endings were verified by the cholinesterase technic: en plaque, en grappe and diffuse endings. 3) Two kinds of fusisensory endings were verified by NADH TR stain and also electron-microscopically: primary and secondary sensory endings.


Urinary histamine excretion in migraine and cluster headache. Further observations. Urinary excretion of histamine, as well as histaminuria following intravenous L-histidine loading, were studied in patients with so-called vascular headache. It was found that urinary excretion of histamine was increased on one or more occasions in 7 of 22 patients with cluster headache. The excretion was significantly higher on attack days than on attack free days. With migraine, increased excretion was found in 5 of 31 patients on days of an attack, whereas the corresponding figure for headache free days was 7 of 24 patients. Three patients showed increased histamine excretion during, as well as between, attacks. The excretion on attack days was not significantly different from that on attack free days. In cluster headache patients, L-histdine administration on attack days did not indicate that an increased histamine formation took place under such circumstances. The underlying mechanism behind the increased histamine output with cluster headache may be increased formation or liberation or altered catabolism. Histamine is more likely to be a consequence than the cause of an attack of cluster headache.


Residual lesions of cerebral fat embolism. Necropsy findings of a case which survived for three months after massive cerebral fat embolism are presented. The lesions are characterized by numerous patchy necroses and areas of demyelination in the white matter of cerebral and cerebellar hemispheres and brain stem, accompanied by atrophy of white matter and ventricular enlargement. Attention is drawn to the significance of these lesions for posttraumatic coma or dementia.


Quantitative EMG and histological carrier detection of Duchenne muscular dystrophy. Seventy-nine women known as, or suspected to be, carriers of the Duchenne type of muscular dystrophy were examined. The 15 known carriers had an estimation of the CPK serum level and a manual quantitative EMG, which gave the high detection rate of 93%. The 64 suspected carriers had CPK determination and quantitative EMG, or CPK and muscle biopsy, and the value of each technic is discussed. The problem of giving a reassuring answer to women considered to be possible carriers on genetic criteria, but who are not really carriers, is solved if the results of all three tests are negative.


Isoelectric focusing of CSF and serum proteins in neurological disorders combined with benign and malignant proliferations of reticulocytes, lymphocytes and plasmocytes. The clinical data and the CSF and serum findings on isoelectric focusing (IEF) and electrophoresis were studied in nine patients with neurological disorders combined with proliferations of reticulocytes, lymphocytes or plasmocytes. Paraneoplastic neurological manifestations were considered in some of the subjects. CSF findings compatible with intrathecal synthesis of oligoclonal immunoglobulins were observed in two patients with lymphoreticular neoplasms. One of these had an IEF band spectrum differing from those found with multiple sclerosis (MS), while the other had changes indistingusihable from those with MS. On IEF the CSF and serum M components of the patients with plasma cell dyscrasias, as well as the serum M components of nine other patients with myelomatosis, exhibited considerable microheterogeneity with 3-18 abnormal bands. The isoelectric point (pI) of the individual bands was 5.8-9.2, mostly greater than 6.4; the band spectra exhibited pI ranges of 0.4-2.5 pH units, most frequently 0.4-1.2. The CSF findings, possible modified by the blood-CSF barrier, reflected the serum changes of plasma cell dyscrasias. The immunoglobulins produced in such disorders gave IEF band spectra differing from those of intrathecally produced immunoglobulins in MS.


Cerebral coenurosis. Report of a case with arteritis. A case of the unusual clinical condition of cerebral coenurosis, the unique parasitic disease that is localized only in the CNS, is reported. The patient had repeated attacks of transient hemiparesis due to intracranial arteritis which was demonstrated by several angiographic studies. The CSF showed a discreet lymphocytosis and increased immunoglobulins. This inflammatory reaction which preceeded the manifestations of the intracranial mass can be explained by the parasitic foreign bodies, the liberation of somatic and metabolic parasitic toxins and the immunological reaction of the organism. The arteritis of the basal intracranial vessels was probably secondary to the inflammatory reaction of the leptomeninges. In presence of the rare association of meningovascular disease and an expanding intracranial lesion a parasitic condition due to a larval stage of Cestodes (Hydatidosis, Cysticercosis, Coenurosis) should be always considered.


Influence of temperature on neuromuscular transmission in myasthenia gravis. The effect of local cooling was studied in 28 patients with myastenia gravis. We stimulated the ulnar nerve with single stimuli and trains at 3/s for 2s and at 50/s for 1.5 s. The compound muscle action potential (MAP), the muscle twitch and the isometric tetanic force of the adductor pollicis were registered. 1. At 3/s stimulation the pathological decrement of the MAP decreased after slight cooling. 2. The amplitude of the single MAP was higher at lower temperature when compared to normal temperature. The same increase is however to be found in healthy subjects. 3. After slight cooling, the maximum tetanic force was higher. However, the decrement of the force was higher also, therefore ruling out a practicable application of cooling for the patient. 4. After severe cooling (18-22 degrees C) the tetanic force was much lower and in many cases a complete failure of the neuromuscular transmission occured.


The effect of hydrocortisone on the serum creatine kinase activity of muscles diseases. Intravenous administration of a single dose of hydrocortisone to patients with the Duchenne type of progressive muscular dystrophy, carriers of Duchenne dystrophy gene caused a short-lasting rise of the serum creatine kinase activity. Administration of hydrocortisone also raised the serum CPK activity in some carriers with a primarly normal CPK level. This phenomenon was observed, though to a lower degree, in limb-girdle muscular dystrophy. The serum CPK activity was sometimes increased after hydrocortisone administration in patients with polymyositis and Kugelberg-Welander spinal muscular atrophy. This phenomenon was never observed in the control group or in cases of myotonic dystrophy. The mechanism of this effect of hydrocortisone on the CPK level is still unknown.


Correlation of electrophysiological and quantitative histological findings in the sural nerve of man. Studies on alcoholic neuropathy. Electrophysiological results of sural nerve conduction studies were compared with quantitative histological data from the same nerve in 27 patients with alcoholic neuropathy. Diminution of amplitude and/or conduction velocity of the main component was seen in 14 nerves. Minimum nerve conduction velocity, which was studied in 11 nerves, was lowered in eight cases. Histological investigations revealed that nerve fibers of different diameter were involved to a variable extent, so at least four different types of fiber loss could be distingusihed. Relation of nerve conduction velocity to external fiber diameter revealed a conversion factor within normal range in 13 nerves, indicating axonal degeneration. A borderline value was found in four of the nerves, teased fiber studied showed demyelination in three nerves and axonal degeneration in one of the four. It was impossible in 10 nerves to relate external fiber diameter to nerve conduction velocities of the different components of the potential caused by demyelination or extensive remyelination.


Serological studies on the etiological role of measles-like virus in subacute sclerosing panencephalitis. Significantly higher CSF titers of hemagglutination (HI) measles virus antibody were found in 22 patients with subacute sclerosing panencephalitis (SSPE) and more elevated titers of measles virus neutralization (NV) antibody were encountered in 19 patients with SSPE than in 50 children and young adults with other neurological diseases. Similar differences occurred in the sera of patients and controls. The serum: CSF antibody ratio was examined in 15 SSPE cases. All but one patient showed reduced antibody ratio (less than 80) as compared with the normal index. In addition, serological studies in some SSPE patients showed the presence of CSF antimeasles fluorescent (FA) and mixed hemadsorption (HAd) antibodies as well as serum anti-ribonucleoprotein antibody (RNP), HAd and FA had titers from 1:16 to 1:32000. SSPE patients harbored serum antibodies against three components of the measles virus as measles patients did. Most of SSPE patients had increasing CSF and serum titers of measles-like virus antibodies over the course of the disease.


Absorption of lindane (gamma benzene hexachloride) in infants and children. Concentrations of lindane (gamma benzene hexachloride) were measured in blood from children who had received treatment with 1% lindane lotion. Lindane was present in the blood of all patients from two of 48 hours following application. Concentrations were inversely related to weight, surface area, and were independent of the quantity of lindane applied.


Mathematical model for cyclocytidine pharmacokinetics. The pharmacokinetics of the drug cyclocytidine in humans were modeled by using a physiological and anatomical approach. Each pertinent tissue is represented by a single compartment, and these compartments are linked together by the circulatory system. Each compartment is then represented by an ordinary differential equation that represents the rate of change in drug concentration as function of convecting transport, metabolism, and urinary clearance. The models for cyclocytidine and cytarabine are linked together by a hydrolysis term in each equation set. The resulting equation sets are then solved numerically to predict the concentration of both drug species in situ. The models use physiological blood flows, tissue volumes, and clearance parameters. The results of the model show that cyclocytidine can act as a reservoir for cytarabine in vivo over the time studied. This effect is confined to relatively long times and relatively low plasma concentrations.


Urinary excretion of hydromorphone and metabolites in humans, rats, dogs, guinea pigs, and rabbits. Hydromorphone was administered as a single dose to humans, rats, dogs, guinea pigs, and rabbits, and timed urinary collections were made. GLC-mass spectrometric and GLC analyses of the samples revealed the presence of the parent compound and both 6-hydroxy epimers as metabolites in the urine of all species. Free or conjugated parent drug predominated, while levels of free or conjugated 6beta-hydroxy metabolite were higher than or equal to those of the 6alpha-form. The time courses of excretion of drug and metabolites were similar for all species, with the major portion being excreted in the first 24 hr. Generally, free and conjugated drug were undetectable in human urine after 8 and 48 hr, respectively.


Comparative pharmacokinetics of coumarin anticoagulants XXX: Relationship between total clearance and serum protein binding of dicumarol in rats. The effect of serum protein binding on the elimination kinetics of dicumarol was studied. The serum free fraction of dicumarol was essentially independent of concentration over a wide concentration range and ranged from 0.00015 to 0.00079 in 10 adult rats. The total clearance of dicumarol in these animals ranged from 3.93 to 14.5 ml/kg/hr. As in previous studies, there was an excellent linear correlation between the elimination rate constant for dicumarol and the fraction of dicumarol in the liver (i.e., the amount of drug in the liver divided by the amount of drug in the body). Consistent with theoretical considerations, there was a positive and apparently linear relationship between the total clearance and the serum free fraction of dicumarol. The individual serum free fraction and the fraction in liver values for dicumarol were strongly correlated. The pharmacokinetic model based on a proportional relationship between the apparent elimination rate constant and the fraction in the liver applies to dicumarol but not to warfarin and has limited utility. On the other hand, the model relating total clearance to the serum free fraction has been found to apply to dicumarol, warfarin, and other extensively plasma protein-bound drugs and can be utilized under clinical conditions.


Comparative pharmacokinetics of coumarin anticoagulants XXXI: Effect of plasma protein binding on distribution kinetics of dicumarol in rats. The purpose of this investigation was to determine, with respect to dicumarol, the effect of plasma protein binding on the pharmacokinetic parameters used conventionally to describe the distribution kinetics of a drug on the basis of the time course of its plasma concentration. After rapid intravenous injection, plasma dicumarol concentrations in adult male Sprague-Dawley rats declined triexponentially, with the terminal exponential phase starting at about 4 hr. The free fraction f, of dicumarol in the serum of individual animals ranged from 0.000150 to 0.000790. The parameters of the equation Ct = Pe-pit + Ae-alphat + Be-betat for plasma concentration Ct at time t were obtained by nonlinear least-squares computer fitting of the experimental data and varied appreciably between animals. Of these parameters, only beta showed a significant correlation with f. These observations indicate that the distribution kinetics of this very extensively plasma protein-bound drug, as reflected by the time course of its plasma concentration after intravenous injection, are apparently not affected by intersubject differences in plasma protein binding. There is a remarkable similarity in the valves of P, A, B, pi, and alpha for dicumarol and warfarin, even though the serum free fraction of these drugs differs considerably.


15/15 translocation in Prader-Willi syndrome. Two further cases (one previously published as D/D translocation) of 15/15 translocation in Prader-Willi syndrome are reported, which brings the total cases of this specific chromosomal anomaly in connection with this specific syndrome up to three or possibly four. It is suggested that Prader-Willi syndrome might be caused by loss of short arm material of chromosome 15.


Determination of levels of carcinoembryonic antigen and nonspecific cross-reacting antigen in the sera of neonatal infants: brief communication. Seventy-eight sera from neonatal infants, born at full term or prematurely, were studied for their carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen (NCA) concentrations, which were compared to the normal adult concentrations. The levels of CEA in the sera were significantly higher in newborns than in adults: 9.05 ng CEA/ml in newborns as compared to 2.5 ng CEA/ml in adults (P=0.001). The levels of NCA in the sera were also higher in newborns: 164 ng NCA/ml in newborns as compared to 130 ng NCA/ml in adults. This difference in NCA levels was not significant, although 80% of the newborns had increased values (greater than 130 ng/ml). Whether the infant was born at full term or prematurely and whether the infant was a boy or girl had no statistically significant influence on the concentration of the CEA and the NCA in the infant.


Characterization of an antigen from the myelogenous leukemia cell line K-562. A protein was solubilized from the myelogenous leukemia cell line K-562 WITh 3 M KCl that specifically inhibited the antibody-dependent, complement-mediated cytolysis of 51Cr-labeled K-562 cells by a monkey antiserum to K-562. When the crude 3 M KCl extract uas fractionated with ammonium sulfate, an eightfold increase in specific activity (U inhibition/mg protein) resulted. This purified fraction migrated as a single protein band after polyacrylamide gel electrophoresis (PGE) with no detectable carbohydrate or lipid. The molecular weight of the denatured protein determined by sodium dodecyl sulfate-PGE was 77,000, similar to that of the native protein (80,000) determined by Sephadex exclusion chromatography. The protein was stable at pH 6-8, with an apparent isoelectric point between pH 5 and 6. In addition to being irreversibly denatured at pH 5 or less, it was unstable at osmolarities below 0.25 M (NaCl). It was denatured at temperatures of 56 degrees C or above. Normal human peripheral blood leukocytes were extracted similarly with 3 M KCl and fractionated with ammonium sulfate. Neither the crude preparation nor any fraction purified as described for the specific antigen inhibited the cytolytic assay, which indicated at least a quantitative lack of the protein on the surfaces of normal leukocytes.


Inhibition of recovery from bleomycin-induced potentially lethal damage. Mammalian cells are able to recover from bleomycin (Bleo)-induced potentially lethal damage. We examined the influences of inhibitors of DNA, RNA, or protein synthesis on that recovery. Cytosine arabinoside and cycloheximide did not inhibit recovery from Bleo-induced damage; however, actinomycin D (Act D) did inhibit it. At a dose that produced minimal cell killing and inhibited only RNA synthesis, inhibition of recovery by Act D was immediate and complete.


A surface antigen associated with Hodgkin's disease: brief communication. We used an indirect immunofluorescence technique to detect a surface antigen that may be associated with Hodgkin's disease (HD). A heteroantiserum raised in a rabbit given an injection of cells obtained from an HD lymph node (Stage I, classification of Lukes and Butler) allowed us to detect an antigen on the surfaces of HD-derived cells in 25 of 27 instances. Benign and malignant non-HD-type lesions (both lymph node and spleen) did not have this antigen. The nature of this antigen and the type of cells bearing it are unknown.


Stimulation of soluble guanylate cyclase activity and cellular accumulation of cyclic guanosine 3',5'-monophosphate by the carcinogen 4-nitroquinoline 1-oxide: brief communication. 4-Nitroquinoline 1-oxide (4NQO), a compound that induces tumors in various rat organs, rapidly increased the cellular accumulation of cyclic guanosine 3',5'-monophosphate (cGMP) to peak values fourfold to 13-fold over basal levels in the liver, lung, renal cortex, and gastric and colon mucosa of rats. This action of 4NQO was expressed in the presence or absence of extracellular calcium. When added directly to the broken cell preparations, 4NQO also stimulated guanylate cyclase activity threefold to sixfold over basal levels in the 100,000 X g soluble fractions of each of these tissues. Dicumarol, which blocks the reduction of 4NQO, inhibited 4NQO stimulation of guanylate cyclase and cGMP. Conversely, phenythydrazine, which enhances the reduction of 4NQO, potentiated the actions of 4NQO on guanylate cyclase and cGMP. These results suggested that the activation of the guanylate cyclase-cGMP system may be mediated by reduction products of 4NQO. The activation of the guanylate cyclase system by 4NQO or its derivatives could function in the expression of carcinogenicity.


Problems in evaluating chronic toxicity of contraceptive steroids in dogs. The long-term effects of oral contraceptive steroids including a combination of norethindrone and ethynylestradiol, a sequential regimen of dimethisterone and ethynylestradiol, and daily administration of megestrol acetate were studied in female beagle dogs at dose levels of 1, 10, or 25 times the projected human dose levels. The major findings included cystic endometrial hyperplasia and pyometra requiring hysterectomies and alopecia for the norethindrone-ethynylestradiol and dimethisterone-ethynylestradiol treated dogs. These groups did not have accentuated mammary development or treatment-related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethynylestradiol, numerous acne-like lesions occurred in the skin of the mammary areas. Dogs given the higher dose levels of megestrol acetate had marked mammary stimulation, hyperplastic and neoplastic changes in the mammary glands, and clinical and pathologic changes typical of diabetes mellitus. Mammary changes of nodular hyperplasia, benign mixed tumor, and adenocarcinoma appeared as distinct entities although constant and intense mammary stimulation may be a common denominator. Such mammary changes have not been found in long-term studies in monkeys or rats with megestrol acetate, and the relevance of the canine mammary changes to projecting potential tumorigenesis in women is questioned.


Supravital staining of spermatozoa: relationship of eosin concentration to the percentage of cells staining live. Supravital staining of human spermatozoa is a useful technique to assess semen quality. We compared 3 concentrations of eosin (1, 2.5 and 5 per cent) for their effectiveness to differentiate viable and non-viable spermatozoa. The percentage of viable cells determined by each concentration was compared as well as the percentage of cells estimated to be active. The results indicate that the percentage of spermatozoa determined to be viable with the supravital stains can be altered by changing the percentage of eosin in the stains. Use of 1 per cent eosin gave values that were significantly higher than the percentage of cells determined to be viable with 5 per cent eosin and the percentage of cells estimated to be active. Better quality slides were produced with 5 per cent eosin, which provided values that correlated favorably with motility estimations.


The effects of castration on adrenal testosterone secretion in men with prostatic carcinoma. Selective adrenal vein catheterization was done on intact and castrated men with prostatic carcinoma. Adrenal to peripheral venous testosterone gradients were observed in all patients, indicating adrenal production of this hormone. No compensatory adrenal production of testosterone was noted during a 17-month period after orchiectomy. The data suggest that the human adrenal in castrates produces testosterone, which may explain why adrenal ablation can offer palliation in some patients with prostatic carcinoma.


Retrospective study of 95 patients with staghorn calculus disease. Medical records were reviewed for 95 consecutive patients hospitalized with a diagnosis of staghorn calculus disease. Of those patients in whom a conservative, non-operative approach was taken 30 per cent ultimately died of renal failure and/or sepsis. It is concluded that surgical intervention is the treatment of choice for patients with staghorn calculus disease.


Treatment of female stress incontinence with midodrine: preliminary report. For 10 days 21 female patients with clinical stages I to III stress incontinence and 4 continent control female patients were treated with the alpha-sympathomimetic midodrine. Urethrometry revealed that alpha-adrenergic stimulation resulted in an increase in the urethral occlusion pressure of up to 30 per cent and, cystometrically, to an increase in the detrusor pressure of up to 35 per cent without impairment of bladder capacity. In the stage I group 83 per cent and in the stage II group 63 per cent of the patients became continent. Midodrine, the advantage of which over comparable sympathomimetics, such as ephedrine, synephrine and norphenylephrine, lies in the absolutely sure and sustained action in oral use, is recommended as an alternative therapy to traditional surgical procedures in the treatment of stages I and II female stress incontinence.


Analysis of the heart antigens. Homologous and heterologous anti-heart antibodies and analysis of the heart specific antigens. The present study has indicated the presence of 3 heart specific antigens, using homologous and heterologous antibodies produced in immunized rabbits. Two of these antigenic proteins exhibit restricted organ specificity for heart and the other one shares by heart and kidney. One of these 2 heart specific antigens reacts to both homologous and heterologous anti-heart sera absorbed with kidney, while the other reacts to only heterologous anti-heart sera. The former has an electrophoretic mobility corresponding to that of serum beta-globulin, and is found to have a molecular weight of about 175,000. The latter has the same electrophoretic mobility as that of alpha2-globulin and is found to have a molecular weight of about 50,000.


[Continuous automatic analysis of the ECG with the aid of a computer with cardiosignal input directly from the patient. 1. Isolation of the active signal of the ECG, identification and measurement of its elements]. Because when fed to an on-line computer the ECG information carries a good deal of noise, of prime importance is devising a method for representation and filtration of the useful asignal. It is shown that in order to separate the ueful signal with a protracted direct ECG input from the patient to a computer the use of the proposed modified method of coherent accumulation is advisable. This modification envisages a step-wise solution of the following problems: current diagnosis of arrhythmic contractions exclusion of arrhythmic contractions from the accumulation procedure, automatic search of the normal duration of the RR intervals, equalization of the RRh intervals duration, statistical averaging of the obtained quantum values. The devised modification of the coherent accumulation method, while considerably increasing the noise-immunity of the algorhythm, enables it to effect a direct long-term automatic analysis of the ECG at intensive care units. The identification and measurement of the ECG waves and intervals are done through and automatic selection of the curve elements search zones, finding local maxima and also of the commencement and end of waves by using the method of the "moving window" with an adaptive evaluation of the first signal derivative intensity.


[Kallikrein-kinin system of the blood plasma in patients with infectious-allergic myocarditis]. The state of the blood plasma kallikrein-kinin system in infectious-allergic myocarditis was studied for the first time. Biological methods for the determination of kallikrein, kininogen, kininases, and free kinins were used. Changes in the activity of the kinin system were revealed in 92% of 38 individuals examined: activation in the first 2-4 months and exhaustion later (in 6-8 months). It was shown that the generally accepted clinico-laboratory criteria on myocarditis are not always informative. Determination of the components of the plasma kinin system is suggested as an additional diagnostic test. The use of kinin antagonists and inhibitors of the kinin system in the complex of drug therapy in infectious-allergic myocarditis is recommended.


A method for mechanised straining of rat and mouse foetuses for teratological examination. The staining method uses alizarin red S and has been adapted for a 4-5 day cycle on a standard tissue processor. It gives consistently well stained bones and clear soft tissues in both rats and mice.


Lung cancer.

Lung cancer. Only patients with localized lung cancer benefit from curative resection. Curative radiotherapy is recommended in patients with a resectable tumor in whom surgery is precluded for medical reasons. Adjuvant preoperative or postoperative therapy of any type does not improve the results of surgery except in patients with Pancoast tumor. Therapy for nonlocalized tumors does not affect survival. Radiotherapy has a palliative effect in 50 to 75 per cent of patients presenting with symptoms from either a primary lesion or metastases and should therefore be recommended in symptomatic patients. The palliative effect of chemotherapy is limited in lung cancers other than small cell carcinomas. However, chemotherapy alone or in association with radiotherapy produces remarkable tumor regression and some improvement of survival in small cell carcinoma. The use of immunotherapy in the treatment of lung cancer is still under evaluation.


Pulmonary reactions to drugs.

Pulmonary reactions to drugs. Reactions to drugs may take many forms, most commonly skin and gastrointestinal reactions. Often forgotten are the pulmonary toxic effects, which can be devastating. Unfortunately, treatment of many of these iatrogenically produced diseases is unsatisfactory. Supportive pulmonary care and corticosteroids, in some cases, are the major modalities of therapy. The physician must be aware of the serious pulmonary consequences of many commonly used agents. Judicious use of these drugs coupled with careful pulmonary monitoring will prevent serious toxicity.


Blood viscosity and local response to cold in primary Raynaud's phenomenon. Some workers regard whole-blood and plasma viscosity as provoking factors in Raynaud's disease. There was no significant difference, however, in whole-blood and plasma viscosity between ten young women with primary Raynaud's phenomenon and ten age and sex matched controls. Venesection, which reduces plasma viscosity, did not change the ease with which Raynaud's phenomenon was provoked in five patients. Increased viscosity might be a causal factor in secondary forms of Raynaud's disease, but it does not seem to be an important factor in primary Raynaud's disease.


Induction of hair growth in alopecia areata with D.N.C.B. 43 patients with alopecia areata were treated with weekly applications of dinitrochlorobenzene (D.N.C.B.), dissolved in acetone, on one side of the head, with the other side serving as control region. The therapeutic aim was a mild contact dermatitis. A significant difference of hair growth between the treated and untreated sides was observed in 33 patients. 21 patients showed regrowth of hair exclusively on the treated side, and in 12 patients regrowth was considerably faster and more dense on the treated side. In the majority of patients the difference was noted within 3 months.


Severe sensorineural deafness in children due to perforation of the round-window membrane. Perforation of the round-window membrane was found in three children with severe sensorineural deafness. After a simple repair, all three have had a small improvement in hearing.


Modification of antihypertensive effect of beta-adrenoceptor-blocking agents by inhibition of endogenous prostaglandin synthesis. The effect of indomethacin-induced inhibition of endogenous prostaglandin synthesis on the antihypertensive activity of pindolol (15 mg daily) and propranolol (80--160 mg daily) was studied in 7 hypertensive patients. In four test phases of 10 days each, patients received beta-blocker alone, placebo, beta-blocker plus indomethacin (100 mg daily), and beta-blocker alone. Mean supine diastolic blood-pressure rose from 82 +/- 2 mm Hg in the first beta-blocker phase to 98 +/- 3 mm Hg in the placebo phase, remained elevated (96 +/- 3 mm Hg) in the beta-blocker-plus-indomethacin phase, and fell to 83 +/- 3 mm Hg in the last beta-blocker phase. Diastolic blood-pressure values obtained in the beta-blocker-plus-indomethacin phase were not significantly different from those obtained in the placebo phase but were significantly different from the values measured in both beta-blocker phases (P less than 0-01). The changes in systolic blood-pressure and pulse-rate were not significant. These preliminary results suggest that the antihypertensive effect of these two beta-blockers in some hypertensive patients may be related to the endogenous prostaglandin system.


Minimun information for sensible use of self-prescribed medicines. An international consensus. An independent group, mainly clinical pharmacologists and physicians from 16 countries, worked out what they thought was the minimum information needed by the general public for the sensible use of six medicines that are widely self-prescribed (aspirin, paracetamol, ferrous sulphate, aluminium hydroxide, senna, and a multivitamin preparation). For each medicine the information is presented under four headings: nature and purpose of the drug, dosage and administration, unwanted effects, and keeping qualities. The group recommends that this "minimum information" be used as the standard basic information about these drugs for users in all countries. Additional items of information that may be needed in some circumstances are also discussed.


Stability studies on lyophilised reference thromboplastins for standardisation of prothrombin-times. An international framework for anticoagulant control has been developed based on British Comparative Thomboplastin (B.C.T.) and the model provided by the British system for anticoagulant control. An alternative international system has been proposed, based on lymphilised thromboplastins prepared at the National Institute of Biological Standards and Control, London. Since 1969, stability studies on two of the N.I.B.S.& C. reagents, the primary material 67/40 and the secondary thromboplastin 69/223, have been in progress at the National (U.K.) Reference Laboratory for Anticoagulant Reagents and Control, Manchester. Both the proposed N.I.B.S.&C. reference preparations have deteriorated, while two lyophilised reagents prepared at the National (U.K.) Reference Laboratory have revealed no evidence of instability. In national and international standardisation reliance on B.C.T. should continue.


Evidence for two distinct types of penicillinase-producing Neisseria gonorrhoeae. Since their recognition early in 1976, penicillinase (beta-lactamase)-producing Neisseria gonorrhoeae (P.P.N.G.) have been isolated in more than 15 countries. Most strains isolated in or epidemiologically linked with the Far East are relatively resistant to tetracycline in vitro, are phenotypically wild-type or proline-dependent auxotypes, and carry a plasmid with a molecular weight of 5800 000 (5-8 X 10(6)) daltons coding for beta-lactamase production. In contrast, P.P.N.G. epidemiologically linked with West Africa are more susceptible to tetracycline, require arginine for growth, and their gene coding for beta-lactamase synthesis is contained in a smaller 3-2 X 10(6) dalton plasmid. Moreover, 43% of the Far Eastern strains, but none of those from West Africa, have an additional 24-5 X 10(6) dalton conjugative plasmid which transfers the beta-lactamase R factor(s) to other gonococci. The presence of this conjugative plasmid may explain the relatively high prevalence of P.P.N.G. in certain areas of the Far East.


Streptococcus pneumoniae resistant to penicillin and chloramphenicol. Three cases of meningitis and two of septicaemia were caused by pneumococci resistant to the penicillins/cephalosporins and chloramphenicol. No beta-lactamase was demonstrated in any of the organisms. All three patients with meningitis died, but the patients with septicaemia recovered after being given appropriate antibiotic therapy.


Suppression of gonadotrophin release in many by an inhibitory analogue of L.H.-releasing hormone. The ability of an inhibitory analogue of L.H.-releasing hormone (L.H.R.H.) to suppress the release of luteinising hormone (L.H.) and follicle-stimulating hormone (F.S.H.) after administration of a small does of L.H.R.H. was tested in four men. A single intramuscular injection of 90 mg (D-Phe-2,D-Trp-3,D-Phe-6)-L.H.R.H. diminished the gonadotrophin response to 25 micrometer of L.H.R.H. given 1, 4, 8, and 24 hours afterwards. Basal levels of L.H. and F.S.H. were not lowered. The results demonstrate that an inhibitory analogue of L.H.R.H. is active in man and suggest the possibility that inhibitors of L.H.R.H. might eventually form the basis of a new method of birth control.


Association between exaggerated responsiveness to thyrotrophin-releasing hormone and hypercholesterolaemia. Thyroid-function tests were performed on one hundred patients with suspected premyxoedema and the results compared with those in twenty age and sex matched controls. The increase in thyroid-stimulating hormone (T.S.H.) in response to thyrotrophin-releasing hormone (T.R.H.) was exaggerated in eighty-eight of the hundred patients with suspected premyxoedema. These included twenty-five with normal basal T.S.H. and sixty-three with a raised basal T.S.H. Serum-cholesterol concentration was significantly higher in those in whom premyxoedema was suspected than in the controls, even when patients presenting with degenerative arterial disease were excluded.


Prevention of wound infection in abdominal operations by peroperative antibiotics or povidone-iodine. A controlled trial. The wound-infection rate after abdominal operations was compared in 113 patients randomly allocated to an untreated control group, a group receiving preoperative lincomycin and tobramycin, or a group receiving local instillation of povidone-iodine. The wound-infection rate was 8.1% in 37 patients receiving antibiotics, 42.1% in 38 untreated controls, and 39.5% in 38 patients in the povidone-iodine group.


Absence of measles-virus antigen in jejunum of multiple-sclerosis patients. Measles antigen was not demonstrated in the jejunal tissue of four patients with multiple sclerosis. There was non-specific staining in cells of the lamina propria, basement membrane, and epithelial cells of the jejunum from patients with multiple sclerosis, human controls, and normal monkeys. This staining was not observed after proper absorption of reagents nor after application of Evans-blue counterstain.


alpha 1-antitrypsin phenotypes in fibrosing alveolitis and rheumatoid arthritis. alpha 1-antitrypsin (alpha 1-A.T.) phenotypes were determined in 55 patients with rheumatoid arthritis (R.A.), 33 patients with R.A. and either obstructive airways disease or recurrent chest infections, 49 patients with fibrosing alveolitis (F.A.), 22 patients with R.A. and F.A., and 200 healthy controls. A highly significant increase in the frequency of MZ phenotype was found among patients with F.A., both with and without R.A. Patients with R.A. alone had a normal distribution of phenotypes. Inherited modification of immune function may predispose to F.A. Alternatively, lowered levels of alpha 1-A.T. associated with non-M phenotypes may predispose to tissue damage with subsequent fibrosis.


Aluminium hydroxide in bile-salt diarrhoea. The treatment of choleraic diarrhoea remains a problem. Cholestyramine is effective but long-term treatment is often impracticable. In-vitro studies have shown that aluminium hydroxide has bile-acid-binding properties comparable with those of cholestyramine. The bile-acid-binding properties of aluminium hydroxide have now been investigated in vivo and applied to the treatment of patients with choleraic diarrhoea. Aluminium hydroxide increased the faecal bile-salt concentration of patients with a normal bowel habit whereas magnesium hydroxide had no effect. Eight patients with severe choleraic diarrhoea were treated with aluminium-hydroxide suspension: bowel motion became less frequent and daily faecal weight fell.


Abdominal-wall tenderness: A useful sign in the acute abdomen. 120 patients admitted as an emergency with localised abdominal pain were tested for abdominal-wall tenderness. Of the 24 patients with a positive test only 1 had a detectable intra-abdominal cause. In the remaining 23 no reason for the pain could be found.


Discontinuation of maintenance digoxin therapy in general practice. All 24 patients on long-term digoxin in a general practice were reviewed. 17 of the 18 patients in sinus rhythm had their digoxin discontinued without any alteration in their  cardiovascular signs or symptoms. Other therapy was adjusted as necessary. These results suggest that heart-failure can often be managed without long-term digoxin therapy.


Transfer-factor treatment in congenital cytomegalovirus infection. When two doses of transfer factor were given to three infants with congenital cytomegalovirus (C.M.V.) infection, urine cultures for C.M.V. became negative, briefly, after five of the six doses.


Effect of zinc on thymus of recently malnourished children. Zinc-deficient animals and children have thymic atrophy and an increased susceptibility to infections. Children with protein-energy malnutrition similarly have thymic atrophy, zinc deficiency, and increased susceptibility to infections. 8 children, recently malnourished, who were supplemented with zinc, showed an increase in thymic size as judged radiographically. It is suggested that zinc deficiency may play a part in the thymic atrophy and infections associated with malnutrition.


A clinic within a general hospital for the assessment of urgent psychiatric problems. Of 100 consecutive referrals to a clinic for urgent psychiatric assessment only a third (34 patients) were considered to warrant such urgent attention. In 29 of the 34 cases the patient's behaviour--either intent to harm himself or unpredictable behaviour that alarmed the referring agent--was the most important consideration for urgent assessment.


Cystic-fibrosis screening in the newborn. In a new method of testing stool samples from newborn babies for cystic fibrosis (C.F.), a colourless substrate, benzoyl-arginine-p-nitroanilide (B.A.P.N.A.), releases yellow p-nitroaniline when hydrolysed by trypsin. Samples from infants with C.F., who lack trypsin, give negligible colour. 2 infants with C.F. were detected among 2500 consecutive newborn babies tested. The incidence of false-positive results was 1.2% after the first specimen and 0.05% after the second specimen. A further refinement has reduced the positive rate to 0.1% after the first specimen (2000 samples). Tests on samples from 5 other older patients with untreated C.F. have yielded no evidence for false-negative results.


Renal transplantation and B-cell cross-matches with autoantibodies and alloantibodies. Of 51 cadaveric kidneys transplanted between June, 1976, and June, 1977, 18 were transplanted in the presence of a positive cross-match against the donor's B lymphocytes. 11 of these positive cross-matches were due to alloantibodies and 7 due to autoantibodies. Autoantibodies were defined not only on the basis of autoreactivity with B lymphocytes but also by their absent or restricted reactivity with lymphocytes from patients with chronic lymphocytic leukaemia. Transplants in 8 of 11 patients with a positive alloantibody-B-cell cross-match and in 6 of 7 patients with a positive autoantibody-B-cell cross-match were successful at 3 months. These success-rates were no different from those found in patients with a negative B-cell cross-match. Thus, renal allografts may be performed with a reasonable assurance of success in the presence of a positive B-cell cross-match whether due to autoantibodies or to alloantibodies.


Infant feeding and subcutaneous fat at birth and at one year. Skin folds were measured at birth and at 1 year in infants who were obese, normal or thin at birth, infants of obese mothers and infants of diabetic mothers. There was no significant correlation between skinfold thickness at birth and skinfold thickness at 1 year and there was no significant difference in skinfold thickness between any of the groups at 1 year of age. These findings are not consistent with the hypothesis that overnutrition in the last 10 weeks of pregnancy has a permanent effect on the adiposity of the infant. The distributions of triceps and subscapular skinfolds in these 1-year-old infants were considerably lower than in a 1967-68 survey of British 1-year-olds. In this (1976) survey, the breast-feeding rate (40% at 2 months) and the mean age of introduction of solids (15 weeks) were both greater than in previous British surveys. Recent warnings against overfeeding in infancy may be changing feeding practices, resulting in slimmer 1-year-old children.


Outbreak of necrotising enterocolitis caused by Clostridium butyricum. 12 hospital-born babies had necrotising enterocolitis, of varying severity, within six weeks, 5 of them within ten days. The usually described predisposing causes were absent in most, though no baby was exclusively breast -fed. Evidence of the presence of Clostridium butyricum was found in the blood of 9 out of 10 babies examined. Cl. butyricum is probably a primary, not a secondary invader.


Antibiotic-induced colitis implication of a toxin neutralised by Clostridium sordellii antitoxin. A toxin(s) has been demonstrated in the stools of two patients with antibiotic-associated colitis. This toxin(s) was heat-labile, was rapidly lethal for hamsters, increased vascular permeability in rabbit skin, and was cytotoxic for cells in tissue-culture. It was neutralised by Clostridium sordellii antitoxin but not by antitoxins prepared against other clostridia; Escherichia coli, and Vibrio cholerae toxins. These characteristics were identical to those of a toxin implicated in the aetiology of antibiotic-induced colitis in the hamster. One patient improved rapidly after treatment with oral vancomycin, and at the same time the toxin disappeared from the stool.


Clofibrate increases lipoprotein-lipase activity in adipose tissue of hypertriglyceridaemic patients. Clearance of plasma-triglycerides and activity of lipoprotein lipase in adipose tissue were studied in six hypertriglyceridaemic patients before and after a week of clofibrate therapy (2 g/day). Plasma-triglycerides decreased significantly from 6.85 +/- 1.1 to 2.66 +/- 0.29 mmol/l and triglyceride clearance increased significantly from 1.3 +/- 0.2 to 2.4 +/- 0.4%/min. There were concomitant significant increases in heparin-releasable lipoprotein lipase (95 +/- 16 to 181 +/- 34 nmol free fatty acids/10(6) cells/h) and in extractable lipase (88 +/- 14 to 179 +/- 28 nmol free fatty acids/10(6) cells/h). It is concluded that an important effect of clofibrate may be to increase the levels of adipose-tissue lipoprotein lipase and thereby improve the clearance of plasma-triglycerides.


Maintenance of remission in acute myelogenous leukaemia by a mixture of B.C.G. and irradiated leukaemia cells. Thirty patients with acute myelogenous leukaemia (A.M.L.) in full haematological remission were allocated alternately to two groups of fifteen patients each. All patients received immunotherapy, given weekly as intradermal and subcutaneous injections of killed allogeneic A.M.L. cells, plus Glaxo B.C.G. given by Heaf gun at a separate site. One group also received a mixture of A.M.L. cells and B.C.G. on 4 occasions early in remission. Four patients in this group have remained in remission for 92 to 134 weeks, whereas all patients in the other group had relapsed by 68 weeks. The findings suggest that cells mixed with B.C.G. may be effective in prolonging remission.


Effect of piracetam on level of consciousness after neurosurgery. 2-oxopyrollidine acetamide (piracetam) is said to protect the cerebral cortex against hypoxia. Since surgery is believed to aggravate cerebral hypoxia and the consequent neurological dysfunction, patients undergoing surgery for brain tumours or ruptured cerebral aneurysms were studied. A random, non-stratified study of 100 patients showed that a significantly higher percentage of patients receiving piracetam attain or maintain a normal or near-normal level of consciousness postoperatively than those receiving a placebo. No side-effects or interaction of piracetam with other medications were noted.


Changes in hospital antibiotic therapy after a quality-of-use study. During the first quarters of 1976 and 1977, the use of parenteral gentamicin, cloxacillin, ampicillin, and cephalothin was surveyed in 219 (in 1976) and 240 (in 1977) patients admitted to a surgical, a gynaecological, and a medical ward of a teaching hospital. In 1976, therapy was assessed as irrational in 42%, 50%, and 12% of the surgical, gynaecological, and medical patients, respectively; the corresponding figures for 1977 were 24%, 25%, and 22%. The more rational therapy in 1977 was due to a shorter duration of prophylactic therapy; and to fewer patients receiving oral antibiotics just before or after the parenteral antibiotic.


Is jejunal biopsy really necessary in cow's milk protein intolerance? Thirty-nine infants suspected of having cow's milk protein intolerance (C.M.P.I.) were investigated, and jejunal biopsies were performed before and after challenge with cow's milk. Thirty patients had significant jejunal mucosal damage after milk challenge, but symptoms of diarrhoea and vomiting developed in only twenty-two. The patients with symptoms were subsequently managed on a diet free from cow's milk until tolerance developed. However, the eight infants without symptoms (but with jejunal mucosal damage) made satisfactory clinical progress, with adequate weight-gain, on a diet of cow's milk. Repeat jejunal biopsy specimens from two of these patients showed that there had been a definite improvement since the immediate post-challenge biopsy specimens were taken. Most patients with C.M.P.I. who need to be treated with a diet from which cow's milk has been eliminated may be detected by clinical means alone, and the remainder may continue on a cow's milk diet unless or until symptoms develop. There seems to be no clinical justification for routine jejunal biopsy in infants in whom C.M.P.I. is suspected.


Treatment of aplastic anaemia by antilymphocyte globulin with and without allogeneic bone-marrow infusions. 29 patients with severe aplastic anaemia were treated with either antilymphocyte globulin (A.L.G.) alone (15 patients) or A.L.G. followed by infusion of allogeneic bone-marrow (14 patients). The overall response to both forms of treatment in terms of 1-year survival was 55%; 12 of the 29 patients showed a sustained haematological improvement, during a period of observation of up to 4 1/2 years. No potentially fatal complications were observed. None of the bone-marrow infusions led to a permanent "take" or graft-versus-host disease. How A.L.G. acts is unknown, but our findings accord with the hypothesis that, in a substantial proportion of cases of aplastic anaemia, unspecified autoimmune reactions block the development of residual stem cells A.L.G. seems to offer a good chance of survival, especially for those patients who do not have HLA-matched siblings. Its value should be further established.


Rotavirus infections of neonates.

Rotavirus infections of neonates. Faecal specimens from 628 newborn babies in the nurseries of six metropolitan hospitals were examined by electron microscopy for rotaviruses. 304 babies (49%) were found to be excreting virus. All those infected were in five nurseries; viruses were not detected in specimens from the sixth nursery. Two nurseries were studied for 9 mo and another for 11 mo and rotaviruses were found consistently in 40-50% of stools examined. There was no seasonal variation. None of the neonates under the age of one day were infected but by the age of three to four days approximately 50% were excreting virus. Most of those shedding virus were symptom-free but 84 (28%) had diarrhoea. Persisting endemic rotavirus infection is apparently common in hospital nurseries in Sydney. The virus is probably transmitted by environmental spread from neonate to neonate.


Immune complexes in myeloproliferative disorders. A fluorescein-labelled anti-human immunoglobulin was used to demonstrate that peripheral blood from patients with myelofibrosis had a high proportion of phagocytic cells containing fluorescent immune complexes. Cells from patients with other myeloproliferative diseases (either chronic myeloid leukaemia or polycythaemia rubra vera) did not show similar intracellular immune complexes. Serum from patients with myelofibrosis incubated with polymorphs from healthy subjects caused the appearance of inclusions similar to those found when the patients' own cells were used, the healthy phagocytes apparently engulfing complexes from the patients' sera. The presence of platelets or complement did not alter the incidence of intracellular fluorescence. These tests may help in the diagnosis of myelofibrosis and may also be valuable in recognising the onset of this condition in patients with polycythaemia rubra vera.


Treatment of acute viral hepatitis with (+)-cyanidanol-3. A double-blind trial of (+)-cyanidanol-3 (2 g/day) versus placebo tablets was carried out in 100 patients with acute viral hepatitis. 51 received the drug and 49 placebo. (+)-Cyanidanol-3 accelerated the disappearance of HBsAg from the blood, lowered serum-bilirubin, and relieved symptoms such as anorexia, nausea, and pruritus. The drug was well tolerated. None of the patients had a relapse of acute hepatitis. Chronic active hepatitis developed in 1 of the placebo-treated patients. Thus, (+)-cyanidanol-3 seems to be of benefit in acute viral hepatitis.


Glycosylated haemoglobin concentrations and clinitest results in insulin-dependent diabetes. In 11 insulin-dependent diabetic outpatients, haemoglobin AIc (HbAIc) was measured by an electrofocusing method. Diabetic control was evaluated by the semiquantitative urine test for sugar, 'Clinitest', three times a day every day in the 8 weeks before the HbAIc determination. 24-hour glycosuria and fasting and postprandial blood-glucose levels were measured one to five times during this period. The HbAIc concentration correlated highly with the semi-quantitative urinary-sugar-concentration index but not with the other parameters.


Increased brain dopamine and reduced glutamic acid decarboxylase and choline acetyl transferase activity in schizophrenia and related psychoses. Dopamine, glutamic acid decarboxylase (G.A.D.) and choline acetyltransferase (C.A.T.) were measured in four regions of post-mortem brains. 41 patients with the hospital diagnosis of schizophrenia (psychotic group) were compared with a control grout normal in the putamen. G.A.D. activity was significantly reduced in the psychotic group, by about 50% in the nucleus accumbens, amygdala and hippocampus, and by about 30% in the putamen. C.A.T. activity was significantly lower in nucleus accumbens from the psychotic group, but normal in other brain regions. From an assessment of case notes, "schizophrenia" was distinguished from "schizophrenia-like psychosis". The biochemical findings for these subgroups were essentially similar, although C.A.T. activity in nucleus accumbens and hippocampus from the schizophrenic group was significantly lower than in controls. It is of brain are associated with schizophrenia and schizophrenia-like psychoses, although whether such neurochemical abnormalities are related to the illness or are a consequence of prolonged treatment with neuroleptic drugs remains unclear.


Oedema and heart-failure in the tropics. A mechanism is outlined to explain why oedema forms so readily in hot climates. A continual cutaneous vasodilation produces a low total peripheral resistance so that the mean arterial pressure cannot be raised except by increasing cardiac output. This inability to raise the arterial pressure as efficiently as usual will lead to difficulties in dealing with excess sodium and water loads, because the mean arterial pressure is the major determinant of urinary output. Anything which favours the retention of sodium and water in hot climates must therefore make things worse. This mechanism will also explain the post-partum cardiac failure syndrome which occurs in Northern Nigeria, since Hausa women take high-sodium diets and lie on heated beds during the post-partum period. The necessity for a further increase of cardiac output to excrete excess sodium and water in hot climates causes stress in persons with vulnerable myocardia and produces the symptoms and signs of cardiac failure more rapidly.


Early ultrasound examination in antenatal care. Ultrasound examination was done on 442 women early in pregnancy. If there was a discrepancy the date of delivery calculated from ultrasound readings was preferred to that calculated by traditional means. As a result of this policy induction for planned caesarean section was postponed or cancelled in 10.4% of cases. In 9.7% of women the menstrual history was unreliable and the ultrasound measurement was used to estimate the date of delivery. Thus in 21.1% of pregnancies the early ultrasound measurement decided when or whether labour was to be induced. In women induced for postmaturity there was no increase in prolonged labour or need for caesarean section. There were no cases of neonatal respiratory distress and neonatal jaundice was less common than it was when the onset of labour was spontaneous. This evidence suggests that neonatal jaundice is not caused by induction of labour or by the agents used. The low frequency of jaundice in this series is thought to be due to accurate prediction of the expected date of delivery and consequent exclusion of premature babies born to "postmature" women.


[New aspects of therapy and prophylaxis of virus hepatitis (author's transl)]. The etiology of viral hepatitis is well known, since the hepatitis A virus and the hepatitis B virus were detected. There is, however, no specific treatment of the disease. Steroids should not be used, since a therapeutical value in viral hepatitis is not definitely proven and since they may contribute to the development of chronic hepatitis. The application of hepatitis B immunoglobulin (HBIG), interferon or interferon inducers in hepatitis B infections has yielded some interesting results, which, however, do not yet justify general recommendations for therapeutical use. Specific preventive measures against viral hepatitis B have been rendered possible by demonstration of HBS-Ag. In selected cases the application of standard gamma-globulin or HBIG is recommended for prophylaxis of viral hepatitis A or viral hepatitis B, respectively. Active immunization against hepatitis B is still in an experimental stage.