High density lipoprotein (HDL) polymorphisms in rabbit. III. Quantitative determination of HDL and the inherited Hl 1 and R 67 antigens. Immunological quantification of HDL and the inherited antigens Hl 1 and R 67 was performed on serum samples from two rabbit populations (Dutch and Albino) comprising a total of 106 animals. The female animals were found to have a higher concentration of both antigens and of HDL than the male animals. The amounts of antigens and of HDL were not obviously normally distributed, but appeared to be more bimodally distributed. The relationship between the amount of antigens and amount of HDL were tested for each animal. A significant positive correlation was found between the amount of R 67 antigen and HDL both for male and female animals in the Albino rabbit population, and for male animals in the Dutch rabbit population. A significant correlation was also found between amounts of Hl 1 and R 67 antigens in the Dutch rabbit population.


Herpes gestationis. Ultrastructure and ultrastructural localization of in vivo-bound complement. Ultrastructural localization of C3 deposition in the skin of two patients with herpes gestationis was determined by using a peroxidase-antiperoxidase multistep technique. The tissue preparations can be stored for long periods of time and identical sections may be used for light and electron microscopic examination. The reaction products were seen throughout the entire lamina lucida and the basal cell plasma membrane appeared to be accentuated. The most remarkable ultrastructural changes in normal-appearing skin were the destruction of the basal cell membranes on the dermal side, localized cytoplasmic dissolution, and intracellular edema unaccompanied by inflammatory cells. Early, nonvesicular lesions showed basal cell degeneration and dermal inflammatory cells. Necrosis and loss of basal cells occurred in the next stage which resulted in microvesicles in which collagen or a well-preserved basal lamina formed the vesicle base. In the later blister stage, the basal lamina was usually lost. It is suggested that damage of basal cell membranes on their dermal side leads to the destruction of basal cells with the subsequent protrusion of epidermal and junctional substances into the dermis. This may result in inflammatory cell infiltration and blister formation.


Cutaneous innervation.

Cutaneous innervation. This is a review of historical facets of research in cutaneous neurohistology. The silver stains, used for some 150 years, led to the discovery of the neurone theory and to contemporary comparative studies. The cholinesterase methods, used since 1950, are the most convenient for general studies of nerves. The fluorescence technique of Falck (1962) is valuable for the study of adrenergic fibers. The electron microscope techniques used since 1950 have allowed the comprehensive description of myelinated and unmyelinated nerve fibers and of corpuscles. The most important unsettled questions pertain to the physiology of cutaneous nerves and precise definitions of cutaneous sensibility.


IgE-mediated histamine and SRS-A release from respiratory cells and peripheral blood leukocytes of rhesus monkeys. Peripheral blood leukocytes (PBL) and free respiratory cells (RC) of the mast cell-basophil type were obtained from normal rhesus monkeys or rhesus monkeys with defined immediate-type hypersensitivity to ascaris antigen (AA). PBL or RC from the latter were exposed to AA and the former were exposed to anti-IgE. Histamine (H) release and release of a slow reacting substance of anaphylaxis (SRS-A) occurred following exposure of the appropriate cells to AA or anti-IgE. The release of both H and SRS-A from PBL was potentiated by D2O. D2O did not potentiate release of SRS-A or H from RC due to anti-IgE to the same extent. Although potentiation of H release from RC due to AA was observed in the presence of D2O in some individual animals, this could not be demonstrated by statistical analysis of group results. We could not demonstrate potentiation of SRS-A release from RC due to anti-IgE or AA. The results suggest the possibility that there may be differences in antigen reactive cells of the respiratory tree and peripheral blood and biochemical studies may be of use in demonstrating these differences.


alpha2-Macroglobulin on human vascular endothelium. alpha2-Macroglobulin (alpha2M) has been identified on the luminal surface of endothelial cells in sections of normal human arteries, veins, and lymphatics by the indirect immunofluorescent technique. The specificity of the immunofluorescent reaction was confirmed by immunoabsorption studies. Prior absorption of the anti-alpha2M antiserum by purified alpha2M at equivalence completely inhibited endothelial surface as well as hepatic parenchymal cell staining. Endothelial cells in blood vessels were not stained when sections were treated with rabbit antisera toward alpha1-antitrypsin, antithrombin III, IgG, IgA, IgM, C3, or fibrinogen. The location of alpha2M at the surface of the vessel wall suggests that this protease inhibitor may protect the vascular endothelium from potentially injurious intravascular proteases.


Beta 2-microglobulin is selectively associated with H-2 and TL alloantigens on murine lymphoid cells. We have used a rabbit antiserum prepared against purified rat beta2-microglobulin to immunoprecipitate molecules from lysates of radioiodinated murine thymocytes and splenocytes. All the molecules that are reactive with this serum have subunits of 44,000 and 12,000 and can be identified as H-2 and TL antigens. Thus, the anti-beta2mu serum can deplete lysates of the majority of the TL and H-2 atigens which can be subsequently recognized by alloantisera. If TL and H-2 are precipitated from the lysates before the addition of anti-beta2mu, no beta2mu-reactive molecules remain. Our results indicate that Ia antigens cannot be depleted from the lysates with anti-beta2mu. The studies also suggest that TL and H-2 heavy chains can exist as both monomers and dimers. These observations are discussed with regard to previous studies concerning the native structure of H-2 and TL antigens.


Synthesis of basement membrane collagen by cultured human endothelial cells. Studies were performed to determine if cultured human endothelial cells synthesized basement membrane collagen. In culture, endothelial cells were attached to grossly visible membranous structures which on light microscopy were composed of ribbons of dense, amorphous material. On transmission electron microscopy, these membranous structures consisted of amorphous basement membrane, and material morphologically similar to microfibrils and elastic fibers. By immunofluorescence microscopy, these membranous structures stained brightly with antisera to human glomerular basement membrane. Cultured endothelial cells incorporated [3H]proline into protein; 18% of the incorporated [3H]proline was solubilized by purified collagenase. When endothelial cells were cultured with [14C]proline, 7.1% of the incorporated counts were present as [14C]hydroxyproline. Cultured endothelial cells were labeled with [3H]glycine and [3H]proline and digested with pepsin. The resulting fractions on analysis by SDS-polyacrylamide gel electrophoresis contained two radioactive protein peaks of mol wt 94,200 and 120,500. Both these peaks disappeared after digestion with purified collagenase. The peak of mol wt 120,500 corresponds to that of alpha1 (IV) collagen; the peak of the mol wt 94,200 probably corresponds to that of alpha1 (III) collagen. Thus, cultured human endothelial cells synthesize material which is morphologically and immunologically like amorphous basement membrane and biochemically like basement membrane collagen. Cultured endothelial cells probably also synthesize material which is morphologically similar to microfibrils and elastic fibers.


Streptococcal M protein extracted by nonionic detergent. I. Properties of the antiphagocytic and type-specific molecules. Group A streptococcal M protein was extracted with nonionic detergent and subjected to a number of physical, chemical, and immunological tests. M protein thus extracted was composed of multiple protein bands, ranging from 35,000 down to 6,000 daltons, all having type-specific precipitating activity. The anti-phagocytic proteins, however, were limited to three molecular species having mol wt of 28,000, 31,000, and 35,000 daltons, and could be separated from those proteins that had only type specificity. Physical studies indicated that these proteins existed as individual asymmetrical molecules which were not aggregated. By radiolabeling M protein on living streptococci, it was determined that these protein bands were found on the streptococcal cell wall in this multiple form. Also, by pulse chase experiments supported by chemical and immunological data, evidence was obtained strongly suggesting that the smaller, type-specific molecules are used to assemble the larger, antiphagocytic proteins.


Isolation and immunologic characterization of a human. B-lymphocyte-specific, cell surface antigen. In addition to HL-A antigens, another cell surface protein complex has been obtained from membranes of the human B-lymphoblast cell line IM-1. This complex which was solubilized with papain, consisted of polypeptides of 23,000 and 30,000 daltons (p23, 30). Rabbit antisera to this material precipitated from [35S]methionine-labeled detergent-solubilized cells, three proteins of 39,000, 34,000, and 29,000 daltons. These antisera were specifically cytotoxic for B lymphocytes of peripheral blood, for B-lymphoblast cell lines, and for EAC rosette receptor-positive surface Ig-negative (Null) lymphocytes. The p23,30 complex was not present on T lymphocytes, EAC rosette receptor-negative Null lymphocytes, or platelets. In addition, the p23,30 complex from several cell lines inhibited alloantisera from multiparous Amish women which had been shown to recognize non-HL-A, B-lymphocyte antigens. Some other properties of the anti-p23,30 sera antisera were described.


Improvements and simplifications of the ozonolysis-Schiff staining method for plasma lipoproteins on cellulose acetate. Modifications of the ozonolysis and Schiff staining of plasma lipoproteins reduce 11 pre-spectrometric steps to 3. Picrate denaturation of the lipoproteins and absorption spectrometry directly on the wet opaque membrane increase the sensitivity; the volume of sub-specimen needed per length of application site is reduced from 0.7 to 0.1 mul/mm. Reasonably good proportionality between the total lipoprotein concentration and the spectrometric findings are obtained. Two specimens were obtained at an interval of 8-13 days from each of 10 patients; for the arbitrary substance fraction of alpha-, prebeta-, and beta-lipoproteins in plasma the between-series intra-individual standard deviations were 0.021, 0.023 and 0.032 respectively.


Specificity of cytoplasmic and cell-wall antigens from four species of Phytophthora. Cytoplasmic and cell-wall antigens and antisera were prepared from four Phytophthora species, and cell-wall antigens were prepared from two Pythium species. Immunodiffusion of the Pythium and Phytophthora cell-wall antigens showed that the two Pythium species did not cross-react with the Phytophthora cell-wall antisera. Immunodiffusion analysis of both cell-wall and cytoplasmic antigens of Phytophthora revealed some degree of specificity between species but not between A1 and A2 mating types in Phytophthora cinnamomi. Species specificity was improved by using indirect fluorescent antibody techniques and by the use of cross-absorbed sera. Agglutination and quantitative precipitation techniques did not significantly improve specificity. It was possible to distinguish serologically between Phytophthora cinnamomi and Phytophthora cambivora and the Phytophthora cryptogea-Phytophthora drechsleri group. The absence of consistent serological variation between P. cryptogea and P dreschsleri is consistent with the suggestion (Bumbieris, 1974) that P. cryptogea and P. drechsleri should be considered as one species.


Morphological components of herpesvirus. II. Preservation of virus during negative staining procedures. The disruption of envelopes and the fragmentation of capsids of equine herpes-virus type I observed in negatively stained samples were attributed to viral dehydration on carbon films during preparation for electron microscopy. Prior fixation of virus with OSO4 or glutaraldehyde and subsequent application of negative stain before drying minimized envelope disruption and virtually eliminated the occurrence of capsomere sheets and broken capsids. This sample procedure significantly improves electron microscopic evaluation of herpesvirus samples.


Comparison of swine vesicular disease virus and Coxsackie B5 virus by serological and RNA hybridization methods. The relatedness of swine vesicular disease virus (SVDV) and Coxsackie B5 virus has been studied by virus neutralization and immunodiffusion tests and by hybridization of the virus RNAs. Clearly defined differences between the two viruses were found by the three methods. Isolates of SVDV from several countries were very closely related but could be differentiated. Recent isolates of Coxsackie B5 virus also appeared to be similar but clear differences could be detected between these and the prototype (Faulkner) strain of the virus. The SVDV isolates were more closely related to the Faulkner strain than to the recent isolates of Coxsackie B5 virus. Perhaps of more importance, the Faulkner strain was more closely related to SVDV than it was to the recent Coxsackie B5 isolates. The significance of these observations in relation to the recent emergence of swine vesicular disease is discussed.


Electron microscopy of tobacco mosaic virus prepared with the aid of negative staining-carbon film techniques. The negative staining-carbon technique has been applied to suspensions of freshly prepared type strain tobacco mosaic virus particles in high concentrations. Electron microscope images show that paracrystalline arrays of the virus were formed, in which large areas of rods could be viewed along their long axes and in parallel arrays in horizontal positions. High-resolution micrographs showed the protein structure units in rods photographed in both vertical and horizontal orientations.


Differential sensitivity of Rauscher murine leukaemia virus (MuLV-R) to interferons in two interferon-responsive cell lines. The effect of interferon on the replication of vesicular stomatitis virus (VSV) and type-C oncornavirus in two Balb/c mouse cell lines, JLS-V5 and JLS-V9R, infected with MuLV-R was examined. VSV replication was inhibited threefold (0-5 log10) in both cell lines by 10 to 20 units of interferon/ml. In JLS-V5 cells C-type virus yields, as measured by 3H-uridine incorporation and reverse transcriptase activity, were also reduced threefold by 10 to 20 units of interferon/ml. However, in JLS-V9R cells, C-type virus replication was refractory to interferon at concentrations up to 1 x 10(4) units/ml. Infectious C-type virus transmitted from JLS-V9R cells to Balb/3TS cells was as sensitive to interferon as virus transmitted from JLS-V5 cells, indicating that resistance of C-type virus in JLS-V9R cells is a feature of the cells rather than of the virus strain.


An iridovirus from bees.

An iridovirus from bees. An iridovirus, Apis iridescent virus (AIV), isolated from sick adult specimens of Apis cerana (Hymenoptera) from Kashmir, closely resembles iridescent viruses from Tipula and Sericesthis spp. (TIV and SIV). However, AIV is only distantly related serologically to TIV and SIV and is even more remotely related to several other similar viruses that were tested in tube precipitation tests with intact particles. AIV multiplies in Apis mellifera, forming cytoplasmic iridescent crystalline aggregates in several tissues, but unlike all the other iridoviruses tested, it failed to multiply in Galleria mellonella.


[Translocation 46,XY,t(2;5) (q37;q14) and mental retardation. Clinical and cytogenetic study]. A boy, suffering from severe mental and motor retardation, was found to be the carrier of an apparently balanced chromosomal rearrangement studied by autoradiography and fluorescence.


Uptake of bleomycin by human brain tumours. The uptake of bleomycin (BLM) by various types of brain tumours after intravenous or intrathecal administration was investigated by bioassay in 67 patients. The correlation between the BLM distribution and the type and characteristics of brain tumours was studied.


Amyotrophic lateral sclerosis: a population study. A country-wide study of the frequency of amyotrophic lateral sclerosis (ALS) was undertaken in Israel for the period 1960-1970. Israel was chosen for this study because of its excellent medical facilities and detailed demographic information. Moreover, the population includes representative groups from all parts of the world for comparison of frequency. A wide variety of motor system disease was screened in all hospitals, clinics, and chronic care facilities in the country, death certificates were reviewed and physicians with a neurological practice were contacted to derive a tentative list of cases. Only those who fit strict clinical diagnostic criteria or had autopsy confirmation were included in estimates of prevalence and incidence. On January 1, 1965, the mid-point of the study, 62 patients with ALS were living in Israel. The age-adjusted prevalence of ALS on that date was 3 per 100,000 population. The average annual age-adjusted incidence for the period 1960-1970 was 0.78 per 100000 population )0.86 in males, 0.46 in females; ratio 1.9:1). There was no appreciable change in trend of incidence over the study interval. Age-specific incidence rates were similar in native-born inhabitants of Israel, immigrants from Europe and immigrants from Afro-Asian countries. The range in age-adjusted incidence among subgroups of immigrants to Israel from various countries was 0.25 to 1.20 per 100000 population but small numbers precluded testing the statistical significance of these rather narrow differences. Mean age at onset was 55.4 years for males and 52.4 years for females. The mean age at death was 60.2 for males and 58.0 for females. The average annual mortality from ALS was 0.58 per 100000 population. There were no familial aggregates of ALS in Israel and autopsy data showed no neurofibrillary changes, granulovacuolar or inclusion bodies. There are only a few other population studies of ALS in different regions of the world. The average annual incidence in these other studies ranged from 0.4 to 1.4 per 100000 population. Thus, the incidence in Israel falls within this narrow range. The present study lends further support to the impression that ALS has a remarkably uniform geographic distribution with Guam and the Kii peninsula of Japan being the only known areas with significantly high rates. If an environmental factor contributes to the pathogenesis of ALS, the factor must also have a uniform geographic distribution.


[Nonaneurysmal vascular pressure lesions of the cranial nerves (author's transl)]. Four cases of facial spasm and 1 case of oculomotor paresis are described. The source of the disorder in all 5 cases is mostlikely not an aneurysm of the vessels of the base of the brain. The literature is discussed and thereby it is shown that mechanical disturbances of other cranial nerves (II, V, VI, IX, XII) can be caused by similar vascular (nonaneurysmal) abnormalities.


Brain changes in newborns, infants and children with congenital heart disease in association with cardiac surgery. Additional observations. The histopathologic pattern in the Central Nervous System in 12 out of 21 new-borns and young infants, below 2 months of age, operated for various congenital heart defects, is that of recent necroses in the deep and subcortical white matter of the pallium, seen from a few hours to 8 days following completion of surgery. Type and location of these lesions of ischemic coagulative necrosis, resembling findings in the perinatal respiratory distress syndrome, seem to depend on shock-like states, the low output syndrome of the left heart with hypovolemia and hypotension. The cause of death in all these infants was cardio-respiratory failure. The question to what extent glial scars replacing necroses within the mostly non-myelinated fiber systems of the pallium will lead to defective maturation of the brain in later infancy and childhood remains a challenge for neurologic and psychological investigation, even if the heart defect has been successfully repaired by the surgeon. Post-mortem data of the CNS in 24 older infants and children below 9 years of age in association with cardia surgery include thrombembolic infarctions, also, after catheterization alone, diffuse or segmental cortical necroses, and cortical scars, especially in children older than 1 year, confirming data recently reported from this laboratory.


The symptomatology, morphology and biochemistry of glycogenosis type II (Pompe) in the adult. The mild, generalized myopathy (glycogenosis type II) of a 23-year-old male, previously thought to have progressive muscular dystrophy, was studied clinically, electro-myographically, biochemically and with light- and electron microscopes. However, the history and clinical aspects, as well as the registration of high frequency discharges in the electromyogram first made the diagnosis uncertain. This kind of spontaneous activity has been found in nearly all cases reported in the literature. Light microscopic and histochemical examinations show vacular degeneration and glycogen storage in muscle fibres. With the electron microscope we found free dispersed glycogen in the cytoplasm and membrane-bound glycogen, glycogen-filled lysosomes. Biochemical measurements of the muscle enzymes, involved in the glycogen breakdown, were normal except for acid alpha-1,4-glucosidase, which was deficient. The evidence of these findings in this abortive form of glycogenosis type II is discussed and compared with the few cases found in the literature.


The differential diagnosis of scapuloperoneal amyotrophy. This report deals with a scapuloperoneal syndrome which developed simultanously with pain and distal paresthesias. In addition there was a slight sensory disturbance of glove and stocking type distribution. Motor conduction velocity was within normal limits and all distal latencies of response were normal; only the sensory conduction velocity of the left median nerve was found to be decreased (42.1 m/s). Electromyographic investigations revealed only signs of myopathy. Histological findings (m. deltoideus, m. tibialis anterior) favoured a primary myopathic process. Biopsy of the n. suralis revealed no certain pathological changes. The affection appears to have an autosomal dominant mode of inheritance. The sensory disturbance and decreased reflexes indicate an involvement of the nervous system, but the question of relationship to the scapuloperoneal muscular atrophy cannot yet be answered.


[A transferable "myasthenogenic" factor in the serum of patients with myasthenia gravis (author's transl)]. Recent evidence indicates that patients with myasthenia gravis (MG) have a reduced number of acetylcholine receptors (Ach-R) at the neuromuscular junction. It has been shown that this abnormality by itself, when produced experimentally, may induce all electrophysiological signs of MG. Furthermore, autoantibodies against human Ach-R have been detected in the serum of patients with MG. It has been proposed that serum autoantibodies may produce the symptomatology of the disease. The purpose of this study was to evaluate whether prolonged exposure to a MG serum fraction in vivo might serve to bring about the myasthenic disorder. A 33% ammonium sulfate precipitated fraction of serum from 9 patients with MG was injected daily into BDF1 mice for up to 14 days. The amount of IgG in this fraction equaled 10-15 mg per single injection. The mice showed reduced amplitudes of the miniature endplate potentials in the diaphragm (mean reduction by 65%), and a reduced number of Ach-R available for 125I-alpha-bungarotoxin binding (mean reduction by 38% in the extensor digitorum m. and 54% in the soleus m.). In some of the mice a decremental response on repetitive nerve stimulation and clinical signs of muscle weakness could also be demonstrated. None of the animals injected with the immunoglobulin fraction from control sera developed these abnormalities. The results indicate that the immunoglobulin fraction of MG serum contains a transferable "myasthenogenic" factor, presumably an antibody, which is able to bring about many of the characteristic features of MG. These findings provide support for the concept of MG as an autoimmune disease.


A family with amyotrophic lateral sclerosis and Parkinsonism. Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) are known to occur simultaneously among some Chamorro inhabitants of Guam and other Mariana Islands (Stanhope et al., 1972). Outside of the Western Pacific Islands, the concurrence of ALS and PD seems to be rare. However, it has been observed to occur with sufficient frequency to suggest some causal association. The following is a report of a patient suffering from ALS whose family history included PD in several of the immediate relatives.


Protein synthesis in zinc deficient rats during tularemia. The effect of zinc deficiency on protein synthesis in rats during tularemia was studied. Five weeks prior to infection with the live vaccine strain of Francisella tularensis, rats had been assigned to one of three dietary groups: zinc deficient (-Zn), pair-fed (PF) or ad libitum (AL). Within 4 weeks, zinc deficiency manifested itself by diminished growth rate, decreased serum and liver zinc concentrations and alopecia. By 18 hour post infection, rats of all groups were febrile and exhibited an increased hepatic uptake of zinc. Despite initially lower concentrations of seromucoid in the PF and -Zn groups, infection elicited an increase in seromucoid concentration as well as enhanced incorporation of 3H-leucine into this fraction of comparable degree in all dietary groups. The same held true for ceruloplasmin. Alpha 2-macrofetoprotein also increased to the same extent in all dietary groups. Infection was associated with a decrease in extractable albumin in ad libitum and pair fed control groups. Only the -Zn group showed a significant decrease in specific activity suggestive of diminished albumin synthesis. Zinc deficiency of itself did not cause a decrement in radiolabel in muscle protein. Thus, despite documented zinc deficiency, rats subjected to the stress of infection respond by synthesizing increased amounts of acute phase globulins apparently at the expense of serum albumin and muscle protein synthesis.


Immunocytochemical localization of mouse alpha 2-macroglobulinlike antigenic determinants on Schistosoma mansoni adults. Antiserum prepared in rhesus monkeys against purified mouse alpha 2-macroglobulin (alpha2M) was labeled with peroxidase and incubated with both living and formalin-fixed S. mansoni adults (perfused from mice or rhesus monkeys) in order to test for the presence of mouse alpha2M antigenic determinants on their surfaces. Following standard cytochemical processing with the appropriate controls, adult worms of both murine and primate origin were found to have mouse alpha2M-like determinants on their surfaces. Earlier observations by other methods on the presence, approximate distribution, and quantitative difference of alpha2M antigenic determinants on adult worms of mouse or rhesus origin were confirmed.


Effect of phthalate plasticizer on blood compatibility of polyvinyl chloride. The amount of a phthalate plasticizer on the surface of a sheet of polyvinyl chloride used in the fabrication of blood storage bags was quantified using attenuated total reflectance spectroscopy, water contact angle measurement, and weight loss due to methanol extraction. Water wettability increased as the amount of surface phthalate extracted by methanol increased, which indicates that the accumulation of phthalate on the surface increases hydrophobicity. The extraction of phthalate by methanol consists of two steps: (a) methanol first dissolves surface phthalate, and (b) phthalate in the bulk then diffuses through the surface. The adsorption of plasma proteins was investigated to determine the initial events as blood contacts the surface. The composition of adsorbed proteins on the methanol-cleansed surface differs from that on the uncleansed polyvinyl chloride surface. Albumin adsorption onto phthalate-contaminated surfaces is less than on cleansed surfaces while adsorption of gamma-globulin and fibrinogen is greater on phthalate-contaminated surfaces. Protein adsorption can be related to surface thrombus formation. Increases in platelet numbers appeared on phthalate-contaminated surfaces as compared with methanol-treated surfaces. A phthalate may enhance platelet adhesion and aggregation when it exists on a polymer surface.


Immunopharmacologic properties of WY-16, 922, a new orally effective antiallergic agent. In a series of tests designed to illustrate immune reactions similar to those obtained in atopic disease, Wy-16,922 effectively inhibited reaginic-mediated immunologic reactions in the skin, lungs and mast cell. It was found to be devoid of immunosuppressant, antimediator, anti-inflammatory, steroid or bronchodilator properties as well as acute toxicity. Although the mechanism of action of Wy-16,922 is unknown, it appears to limit the release (not the effects) of allergic mediators in a manner similar to that described for disodium cromoglycate.


The relation of agglutinins to antigenic variation of Trypanosoma lewisi. During the course of infection in the rat, Trypanosoma lewisi produces 2 antigenic variants: the 1st represents the initial, reproducing population of cells; and the 2nd the nonreproducing, ablastin-inhibited adult population. The specificities of the agglutinins elicited by the variants were studied by adsorption and agglutination methods and the newer immunoelectroadsorption technic. It was found that the reproducing variant has a surface antigen that reacts with the agglutinin specific for the adult variant, but this antigen does not become immunogenic until transformation to the adult variant occurs. It was also found, with fractions of immune sera obtained by gel filtration, that the agglutinin specific for the reproducing variant is IgG and that specific for the adult variant, IgM. The antigenic variants of pathogenic and nonpathogenic trypanosomes are compared, and the roles of trypanocidal and ablastic antibodies in the induction of antigenic variation are discussed.


Prenatal diagnosis of genetic disorders. Three hundred and fifty pregnancies were monitored by transabdominal amniocentesis in the fourteenth to sixteenth week of gestation followed by karyotyping or biochemica assays of cultured amniotic fluid cells and analysis of alpha-fetoprotein in the amniotic fluid supernatant. The pregnancy was interrupted in 36 cases (10%) either becasue of a fetal abnormality or the presence of a male fetus in pregnancies at risk for an X-linked disease. Four chromosomal aberrations were found in 87 pregnancies tested because of advanced maternal age. In 101 pregnancies with a recurrence risk of Down's syndrome, 2 fetuses with an abnormal karyotype were detected. In 11 cases, in which 1 parent was a carrier of a balanced translocation, 2 unbalanced fetal karyotypes were found. Fetal chromosome studies in 43 pregancies at risk for an X-linked disease indicated  the presence of a male fetus in 21 cases. Prenatal diagnosis of 11 different metabolic diseases was performed in a total of 34 cases. Microchemical techniques were used to allow completion of the diagnosis of seven different enzyme deficiencies within 9 to 22 days after amniocentesis. Alpha-fetoprotein assay in the amniotic fluid supernatant of 47 pregnancies at risk for an open neural tube defect resulted in the detection of 3 anencephalic fetuses during the second half of pregnancy. The safety and reliability of amniocentesis and the possible effects on the outcome of pregnancy are evaluated. Prenatal diagnosis offers a promising alternative for parents who are at risk of having a child with a genetic disease which can be detected in amniotic fluid or in cultured amniotic fluid cells.


The relationship between Neisseria meningitidis of serogroups Z1 and 29E. Meningococci of serogroups Z1 and 29E were examined serologically and shown to be identical. These meningococci should be designated either as group Z1, which has priority, or preferably by a new designation forming a logical sequence with the currently accepted serogroups.


The use of ionophores of rapid loading of human red cells with radioactive cations for cation-pump studies. Techniques are described for the rapid loading of intact human red cells with radioactive isotopes of alkali cations or Ca2+ by using ionophorous compounds (nigericin, gramicidin D and A 23187). Loading was rapid and efficient if the membrane potential of the cells was rendered more negative inside. After cation loading the ionophores could be bound to albumin and removed by repeated washings. The ATP and 2,3-DPG contents of the cells were practically unaltered by this treatment. Passive membrane permeability to Na+ and Ca2+ returned to normal. Loaded erythrocytes pumped out Na+ in a ouabain-sensitive and Ca2+ in a lanthanum-sensitive way. Ca2+ -loaded red cells were microspherocytes and exhibited a rapid K+ -efflux. Parallel with the extrusion of Ca2+ cells regained their biconcave shape and normal passive permeability to K+.


Pigment containing lipid vesicles. I. Preparation and characterization of chlorophyll a-lecithin vesicles. Vesicles obtained by sonication of chlorophyll a-lecithin mixtures dispersed in anaqueous medium closely resemble the well-characterized vesicles similarly prepared from pure lipids. They are bounded by one spherical lipid bilayer which contains the chlorophyll a. Appropriate conditions for sonication prevent substantial degradation of the membrane constituents. Up to one chlorophyll a molecule per 55 lecithins can be incorporated into membranes. The average Stokes' radius of the vesicles determined by analytical sieve chromatography is 102 +/- 5 A and independent of the chloropyll a content. The membrane is visible in the electron-microscope when the vesicles are treated with osmium tetroxide prior to negative staining. The osmium fixation is, however, not strong enough to allow for a preparation of the vesicles for thin sectioning (dehydration, embedding in epoxide).


Thoracotracheostomy.

Thoracotracheostomy. When laryngeal carcinoma extends into the cervical trachea, peritracheal nodes, prelaryngeal tissues and skin, or when it recurs at the tracheal stoma, the prognosis becomes rather dismal. To have a hope of cure, a palliative excision must be radical. Developments in the surgical techniques for exposure, excision, and reconstruction which have evolved during the past quarter century are reviewed, along with a case presentation through which the problems and techniques are illustrated.


Retroperitoneal lymphadenectomy as adjunctive therapy in selected cases of advanced testicular carcinoma. The findings in 10 patients with advanced non-seminomatous testicular malignant disease in whom either complete remission or reduction in clinical stage was achieved with chemotherapy and later retroperitoneal lymphadenectomy are presented. The procedure in these selected instances allowed for a more accurate assessment of the disease status. The operative findings served as an accurate guide to determine the need for further drug therapy.


Hemodynamics of hyperthyroidism. The effects of autonomic nervous blocking and anti-thyroid drug treatment. This work was intended to analyze the sympathetic and parasympathetic factors affecting the hemodynamics of hyperthyroidism. Seven patients with hyperthyroidism, diagnosed based on the determinations of BMR, 131I-uptake, T3-resin sponge uptake (T3-RSU), and serum level of thyroxine (T4) were subjected to the study. The hemo-dynamic estimation was done (1) at rest, (2) after vagus blocking by the injection of 0.04 mg/Kg b.wt. atropine and 0.2 mg/Kg b.wt. propranolol before (hyperthyroid state=H) and after (euthyroid state=E) anti-thyroid drug therapy. Cardiac output was measured by the dye-dilution method, and the valve was calculated according to the standard Hamilton formula. The following results were obtained. (1) The vagal tone is lower in H than in E, on the other hand, sympathetic beta-receptor tone is higher in H than in E. (2) The sympathetic alpha-receptor tone in H may be equivalent to that in E. (3) There might exist inotropic factors which affect the hemo-dynamics, other than autonomic nervous system in H.


Inhibition of hypersensitivity reactions by soluble derivatives of baicalein. Baicalein, a flavonoid, is anti-allergic but only slightly soluble in water. The soluble derivatives of baicalein, disodium baicalein-6-phosphate (BPS) and sodium baicalein-6-sulfate (BSS), were synthesized and examined regarding their effects on hypersensitivity reactions. These derivatives inhibited type I and II reactions as classified by Coombs and Gell. The Arthus reaction belonging to type III reaction, however, was hardly affected with either BPS or BSS. The experimental asthma caused by passive systemic anaphylaxis in guinea pigs was prevented with application of BPS. Thus even by the oral route, BPS appears to be clinically applicable to extensive allergy related diseases.


Characterisation of the enzyme defect in chronic granulomatous disease. Strikingly reduced activity of an enzyme, normally located in the plasma membrane of human neutrophils, has been demonstrated in a male patient with chronic granulomatous disease (C.G.D.). The subcellular distribution of N.A.D.H.-dependent reduction of nitroblue tetrazolium (N.B.T.) was determined in neutrophils because reduction of this dye by these patients is grossly impaired. Assayed at high concentrations of N.A.D.H. (1 mmol/1), N.B.T. is reduced by enzymes in the cytosol and mitochondria in addition to the plasma membrane by both normal and C.G.D. cells--properties which previously obscured the identity and location of this enzyme. At a more physiological concentration of N.A.D.H. (25 mumol/1), reduction of the dye by the plasma membrane, the principal site of N.B.T. reduction by normal neutrophils, was absent in the patient with C.G.D. It is suggested that absence or imperfect function of this reductase enzyme is the primary lesion in this disease.


Histochemical studies on the distribution of acidic glycosaminoglycans in human rib cartilage during the aging process. In human cadavers of different age five zones of basic substances can be distinguished around the cartilage cell by using hyaluronidase digestion and Alcian blue stain combined with various MgC12-concentrations. This treatment produces different reactions in the various zones. The zones are numbered according to their distance from the cell; thus zone 1 (Z1 = pericellular zone) is the nearest to the cell. Z 1 and Z 2 (inner territorial zone) contain hyaluronidase-digestible substance but Z 1 stains at higher electrolyte concentrations than does Z 2. The third zone (Z 3 = outer territorial zone) which first appears in childhood always contains hyaluronidase-resistant material and, besides, hyaluronidase-digestible material in adolescence. Since the distance between the cells increases with the proceeding process of aging, Z 4 (periterritorial zone) and Z 5 (interterritorial zone) appear in the cartilage centre. In adolescence only Z 5 can be found; it is slightly hyaluronidase-sensitive and stains even at high MgC12-concentrations. In adult and old cartilage a weakly basophilic zone 4 appears. The comparison of fixed and unfixed tissues renders the distinction between the zones feasible as the hyalurinodase resistance is increased in fixed tissue and, on the other hand, the structures appear less outlined in unfixed tissue. As far as the distribution of acidic glycosaminoglycans (GAG) is concerned the territories and interterritories are not clearly defined units, for part of the zones mentioned above can be arranged circumcellularly or, in addition, interstitially depending on the various cartilage regions and on the different periods of life. We assume that the pericellular as well as the inner and outer territorial zones belong to the cell itself and that their step by step appearance is due to a process of development whereas the periterritorial and interterritorial zones result from cell degeneration caused by aging, and expand, mainly, without cellular control.


The absence of B-cell antigen B2 from leukaemia cells and lymphoblastoid cell lines. 60 leukaemia patients with acute mylogenous leukaemia, chronic myelocytic leukaemia, acute lymphatic leukaemia, and chronic lymphocytic leukaemia were tested for five specificities of the new B-lymphocyte alloantigenic system. Two specificities of the first B-cell locus were significantly lower in frequency than in B lymphocytes from 105 controls. B-cell group 1 was found in 18% of leukaemia patients vs. 48% of controls (p less than 0.025) and B-cell group 2 was found in 0% of leukaemia patients vs 23% of controls (p less than 0.025). Group 2 was also absent in 37 cultured lymphoblastoid lines. It is suggested that resistance to B-cell leukaemia and to Epstein-Barr virus transformation in vitro may be linked to a B-lymphocyte specificity on the first B-lymphocyte locus.


Immunisation against hepatitis B in man. An inactivated vaccine against hepatitis B was prepared from blood-donor HBs antigen purified on immunoadsorbents. Its safety and efficacy were tested in chimpanzees. Vaccination was then applied in an attempt to protect patients and staff in a haemodialysis unit. The efficacy of the vaccine in man was assessed by observing humoral and cellular immune reactions and by comparing changes in HBs antigenaemia in vaccinated and non-vaccinated subjects. The results indicate that this vaccine protects against hepatitis B in the circumstances in which it was administered.


Plasma-urate measurements in predicting fetal death in hypertensive pregnancy. The relation of perinatal mortality to plasma-urate concentrations and blood-pressure was studied in 332 pregnant patients with hypertension. Perinatal mortality was markedly increased when maternal plasma-urate concentrations were raised, generally in association with severe pre-eclampsia of early onset. Plasma-urate was a better indicator than blood-pressure of prognosis for the fetus. Maternal hypertension, even severe, without hyperuricaemia, was associated with an excellent prognosis for the fetus. Conversely, when maternal hypertension was mild and hyperuricaemia was severe, the prognosis for the fetus was poor. These findings suggest that, in terms of fetal health, changes in renal handling of urate may be a more important feature of pre-eclampsia than the hypertension.


Perinatal mortality and birth-weight in relation to aspirin taken during pregnancy. In a cohort of 41 337 gravidas and their offspring in the U.S.A. there was no evidence that aspirin taken in pregnancy is a cause of stillbirth, neonatal death, or reduced birth-weight. The women were divided into those who were not exposed to aspirin (14 956), those with intermediate exposure (24 866), and those who were heavily exposed (1515). Stillbirth-rates were similar for all three groups. Differences in neonatal death-rates and mean birth-weights were slight and none were statistically significant. Trends were opposite among approximately equal numbers of White and Black children.


Aspirin and congenital malformations.

Aspirin and congenital malformations. In a cohort of 50 282 gravidas and their offspring in the U.S.A., malformation rates were similar in the children of 35 418 women not exposed to aspirin, 9736 with intermediate exposure, and 5128 women heavily exposed during the first four lunar months of pregnancy. After controlling a wide range of potential confounding factors using multi-variate analysis, the observed and expected numbers for a variety of malformation categories were similar in all three comparison groups. The data suggest that aspirin is not teratogenic.


Sensitisation of neuroblastoma patients and related and unrelated contacts to neuroblastoma extracts. Sensitisation to neuroblastoma extracts was tested by the leucocyte migration inhibition technique in 8 neuroblastoma patients, 22 relatives, and 49 unrelated contacts. All three groups showed a high frequency of positive reactions compared with 61 controls having no exposure to neuroblastoma. The frequency of sensitisation could be related to closeness of contact, but the nature of the sensitising material and its mode of transmission are unknown. Virus studies by the sensitive techniques of tumour virology are suggested. The absence of case clustering and the low familial incidence of neuroblastoma indicate that simple exposure to the tumour is not a major oncogenic factor.


Human diploid cell strain rabies vaccine. Rapid prophylactic immunisation of volunteers with small doses. The clinical and antibody responses of volunteers to three intradermal schedules of human diploid cell strain rabies vaccine (0.4 ml on day 0; 0-1 ml on days 0, 1, 2, 3; and 0-1 ml on days 0, 3, 7, and 14) are described. Vaccine was administered to 114 contacts of two rabid patients in order to evoke a rapid antibody response and the antibody titres of 30 of those who were vaccinated and bled were measured. High antibody titres were obtained in all subjects irrespective of their immunisation schedule; there were only minimal local reactions. All volunteers had titres greater than 1/78 (1.7 I.U./ml) by day 14, and 7 of 10 receiving 0.1 ml into each limb on day 0 had detectable antibody by day 7.


Six cases of cerebromedullospinal disconnection after cardiac arrest. Six cases of cerebromedullospinal disconnection after cardiac arrest are reported. The diagnosis was based on mutism, consciousness and/or wakefulness, and global paralysis, except for some very limited motor functions, mostly eye movements. Consciousness was defined as repetitive contact with the patient by way of simple motor response. Despite of the fatal outcome in all cases, the importance of diagnosis and correct handling is stressed.


Dorsal-column stimulation in the rehabilitation of patients with multiple sclerosis. Two patients with chroic neurological deficit due to multiple sclerosis have been treated by percutaneous continuous dorsal-column stimulation. Motor, sensory, and bladder function improved significantly.


An immunological factor in epilepsy.

An immunological factor in epilepsy. It is proposed that epileptic discharges could be the result of an autoimmune response to either an antigen released during tissue destruction or an infective agent. A possible mechanism involves the blocking by antibodies of transmitter receptor sites at synapses, whereby synaptic transmission is reduced.


Is lactase the receptor and uncoating enzyme for infantile enteritis (rota) viruses? Rotaviruses are now regarded as important causes of diarrhoea in man, cattle, pigs, mice, and possibly other animals. Characteristically, disease occurs in newborn and young animals, and infection seems limited to the differentiated gut epithelial cells. The major surface polypeptide of the calf scours rotavirus is glycosylated, and highly purified beta-galactosidase (lactase) interacts with the virus in vitro causing removal of the outer shell of the capsid (uncoating). It is suggested that lactase present in the brush border of the intestinal epithelial cell performs a similar function in vivo by acting as a combined receptor and uncoating enzyme for the rotavirus. This hypothesis is consistent with the observations that rotaviruses seem to infect only gut epithelial cells, and that infant animals, whose lactase concentrations are generally higher than those of adult animals, seem more susceptible to rotavirus infections. Implications of the hypothesis include possible new approaches to laboratory cultivation of rotaviruses, which should be more successful in cells selected for surface lactase activity, and the suggestion that the epidemiology of human rotavirus infections may be influenced by the fact that different ethnic groups have different lactase levels (and hence lactose intolerance) in adulthood.


Blood-lead and hypertension.

Blood-lead and hypertension. Blood and tap-water lead levels were examined in 135 hypertensives and 135 age and sex matched normotensives. Among male hypertensives there was a significant excess of cases with high blood-lead levels and a similar but statistically non-significant trend was found amongst female hypertensives. A positive correlation was found between blood-lead and tap-water lead. It is concluded that in the West of Scotland high blood-pressure is associated with high blood-lead levels, which might explain the high prevalence of cardiovascular disease in the area.


Von Willebrand disease San Diego, a new variant. A reduced level of factor XII has been observed in 9 of 39 patients with von Willebrand's disease. This apparent common variant of von Willebrand's disease has not previously been described, and its significance is not known.


Evidence for hyperoestrogenaemia as a risk factor for myocardial infarction in men. Fifteen men who had had a myocardial infarction between the ages of 32 and 42 years were compared with fifteen age-matched healthy men. Seven of the patients had a strikingly slow rate of beard growth, three had evidence of gynaecomastia, and three had a loss of libido. The slow beard growth and decreased libido, and possibly the gynaecomastia, preceded the myocardial infarction. Mean serum oestradiol and oestrone concentrations were significantly increased in the patients, 43.5 +/- 8.8 (standard deviation) and 50.7 +/- 9.5, respectively, compared wth 33.5 +/- 5.5 and 37.5 +/- 5.8 pg/ml in the controls (p less than 0.001). Mean serum testosterone and dihydrotestosterone concentrations were not significantly different in the two groups. Serum oestradiol and oestrone concentrations were directly proportional to each other as were those of testosterone and dihydrotestosterone. These results suggest that the hyperoestrogenaemia preceded the myocardial infarction and that hyperoestrogenaemia may be an important risk factor for myocardial infarction in men.


Glucagon resistance as a case of hypertriglyceridaemia. The hypothesis that glucagon resistance is a cause of hypertriglyceridaemia has been tested by studying the effects of exogenous glucagon in patients with hypertriglyceridaemia and controls. Glucagon and a greater triglyceride-lowering-effect in hypertriglyceridaemic patients than in controls. The other metabolic response to glucagon were similar in both groups. No evidence of glucagon resistance was found.


"Normal" elimination of aberrant autoimmune clones. Tetraparental mouse chimaeras formed by aggregation of early embryos have been utilised in the study of immunological mechanisms. Tolerance in chimaeras has proven somewhat controversial, but recent evidence has suggested the existence of "classic" tolerance and furthermore that this is achieved by elimination of cells potentially capable of fatal self in equilibrium self reactivity. Clonal elimination was also considered to be responsible for the "correction" of the autoimmune disease of NZB mice made chimaeric with a normal strain. It is now suggested that a similar mechanism may be responsible for the "normal" elimination of any aberrant autoimmune clone in both mouse and man.


Virulence for man of a human influenza-A virus antigenically similar to "classical" swine viruses. The newly isolated human influenza-A strain containing swine antigens isolated in New Jersey, U.S.A., was inoculated into six volunteers. Clinical reactions were mild although all volunteers were infected. The longest period for which the virus was excreted was 8 days and the shortest 3 days. In its virulence for man the New Jersey strain was intermediate between a human and animal virus, and was quite clearly more virulent than known swine viruses. It seems possible that the outbreak in the U.S.A. was an isolated event and that the virus will not become established in man.


Intensive care in rabies therapy. Clinical observations. Seven patients in India with dog-bite rabies were treated by intensive therapy. Hypoxia was prevented by intermittent positive-pressure ventilation facilitated by muscle relaxants and sedatives. Other measures, included maintenance of nutrition, correction of fluid/electrolyte and acid/base balances, antiviral agents, immunological stimulation, and intensive nursing care by immunised volunteer staff. The patients survived for from 1 to 17 days after the onset of clinical disease. When survival was prolonged (i.e., more than 2-4 days) by intensive care, the disease had diverse and serious effects, including fluctuations in temperature and blood-pressure, cardiac arrhythmia, and diabetes insipidus. Although none of the patients survived, advances in the use of this technique raised hopes that it may eventually be possible to save some patients.


Rauwolfia derivatives and breast cancer in hypertensive women. Three groups of women were selected from a sample of death certificates that had been coded by the Office of Population Censuses and Surveys for all conditions mentioned on them: (1) all women with reference to both breast cancer and hypertension; (2) all women with reference to hypertension and other cancers; (3) a group of women with reference to hypertension without cancer, selected to match the breast-cancer patients with respect to five features. When the women with breast cancer were compared with both the women with other cancers and the women without cancer, there was a positive association between breast cancer and the use of rauwolfia derivatives, although neither the differences in the frequency nor duration observed were statistically significant. The association appeared to be strongest for use near the time of diagnosis of the cancer. This agrees with nearly all other data and would be expected if rauwolfia derivatives promoted the development of breast cancer from previously initiated cells.


Percutaneous transhepatic obliteration of gastro-oesophageal varices. Percutaneous transhepatic portal-vein catheterisation was attempted to obliterate the major variceal venous supply in 13 decompensated cirrhotic patients, who continued to bleed after conservative therapy. Obliteration was achieved and bleeding stopped in 7 patients. In 5 patients obliteration was technically unsuccessful. The remaining patient had an unsuspected portal-vein block diagnosed by the transhepatic technique. 1 patient with successfully obliterated varices died after a haemothorax and haemorperitoneum developed. Follow-up splenic venography at three to six months in the 6 successfully thrombosed patients showed that 4 had persistent obliteration and had not re-bled. 2 patients re-bled from incompletely obliterated varices. It is concluded that selective obliteration of the major variceal supply is effective in stopping acute gastro-oesophageal variceal bleeding, but that greater experience is necessary before the long-term effectiveness of the procedure can be determined.


Successful renal allografts across a positive cross-match for donor B-lymphocyte alloantigens. Seven patients received a renal allograft with negative standard and T-lymphocyte microlymphocytotoxicity cross-matches, but a positive B-lymphocyte cross-match using donor lymphocytes. In spite of this presensitisation, none underwent hyperacute rejection and all are functioning from one and a half to six months after transplantation. This procedure may help in the detection of false-positive cross-matches and possibly in detection of enhancing antibodies against a specific donor.


Effect of a single dose of dexamethasone on serum concentrations of thyroid hormones. In ten euthyroid subjects, in whom endogenous thyroid-stimulating hormone (T.S.H.) production was suppressed by oral thyroxine (T4), a single dose of dexamethasone resulted in reduced serum-3,3'5-triidothyronine (T3) concentration and raised serum-3,3',5'-triiodothyronine (reverse T3 or rT3) concentration after 24 h. These changes were not related to changes in free hormones or binding proteins. Adrenal glucocorticoids may have a pathophysiological role in modulating the peripheral metabolism of thyroid hormones in stress.


Quantitative throat-swab culture in the diagnosis of streptococcal pharyngitis in children. A striking difference in the detection of a heavy growth of Streptococcus pyogenes in throat swabs taken from 1054 children with pharyngitis compared with those from 462 normal children was demonstrated when a standardised technique of quantitative culture was used. In patients with pharyngitis 71% of the isolates were heavy whereas a heavy culture was obtained in only 1-7% of healthy children. Also, a significant correlation between the clinical observations suggestive of streptococcal pharyngitis and the results of culture was confined to those patients whose throat swabs yielded a heavy growth of streptococci. It is concluded that bacteriological examination is of value as a diagnostic test only when the results of culture are quantitatively assessed.


Induced tolerance in cold urticaria caused by cold-evoked histamine release. The interrelations between cold sensitivity and release of histamine and other mediators in five patients with cold urticaria undergoing cold tolerance treatment were studied. Tolerance to cold was produced in all patients by repeated cold exposure. In four patients tolerance was maintained by once daily exposures. In the fifth patient 4-hourly exposures were necessary. Cold sensitivity was associated with histamine release in venous blood draining urticated skin. No prostaglandin activity was detected, and low concentrations of kinin activity were found in blood draining the normal and exposed skin of healthy subjects as well as in patients with cold urticaria. After induction of tolerance, no histamine release occurred on challenge by cold. Relapse of sensitivity was associated with reappearance of histamine release on challenge. The conclusion that tolerance is due to depletion of histamine stores in skin after repeated cold exposure was supported by diminished wealing in response to injection of a histamine liberator (compound 48/80) in cold-tolerant skin.


Prevention of muscle cramps in haemodialysis patients by quinine sulphate. Nine patients on maintenance haemodialysis with frequent muscle cramps were given 320 mg quinine sulphate or placebo (in an identical gelatin capsule) at the beginning of each dialysis for a period of 12 weeks. The frequency of cramps was significantly reduced during dialysis in patients receiving quinine sulphate. None of the haematological, auditory, or visual disturbances ascribed to quinine sulphate were noted.


Effect of beta-adrenergic blockade on plasma-renin activity and intractable hypertension in patients receiving regular dialysis treatment. The effect of propranolol has been studied in two patients with chronic renal failure and hypertension which remained refractory despite the removal of excess sodium and water by dialysis. Measurements of plasma-renin, exchangeable sodium, and blood-volume demonstrated that in both patients hypertension was due to excess renin. The administration of propranolol was followed by a rapid fall in blood-pressure to normal, thereby obviating the need for bilateral nephrectomy. In both patients the fall in blood-pressure was accompanied by a striking fall in plasma-renin, and in one there was a highly significant association between plasma-renin activity and mean arterial pressure.


Bacteroides: an unusual cause of breast abscess. Three cases of breast abscess from which the non-sporing anaerobe Bacteroides was isolated are described. This organism has apparently not previously been reported as a cause of abscess in a breast without underlying malignancy.


Peptide transmitters: a unifying hypothesis for euphoria, respiration, sleep, and the action of lithium. Actions of morphine include analgesia, sleep, euphoria, and depression of respiration. Transmitter or modulator substances in the brain that have actions similar to morphine may control these functions in man. This hypothesis proposes that enkephalin is a controlling neurotransmitter and its binding to opiate receptors determines mood state as well as influencing respiratory and sleep patterns. Lithium may act through modification of the opiate receptor affinity for an endogenous morphine-like substance. The theory predicts blocking action of naloxone in mania and in most drug-induced euphorias. It implies a new chemical pathophysiological basis for the phenomenology of mental illness.


Two mechanisms for hypothyroidism after 131I therapy. It is proposed that the incidence of hypothyroidism after radioiodine therapy of thyrotoxicosis has two distinct mechanism. One operates in the first two years after therapy and depends on radiation dose. The other operates in later years, and is not, to any significant extent, dose dependent. Possible canidates for each mechanism are explored.


Cholera transmission near a cholera hospital. A review of the incidence of cholera from 1964 through 1974 in Matlab, Bangladesh, revealed that among the villages several had very high incidence-rates. Investigation indicated that high cholera-rates in two of these villages were probably related to water contamination from a nearby cholera hospital established in 1963. The data imply that heavy contamination can overcome any immunity resulting from repeated exposure.


Failure of sanitary wells to protect against cholera and other diarrhoeas in Bangladesh. Within an area of Bangladesh in which the incidence of cholera was high, use of sanitary pipe wells did not protect against cholera or related non-cholera diarrhoeas because well users also used contaminated water sources regularly enough to maintain high infection-rates. Protection was found to correlate with education and wealth.


Cysteamine, methionine, and penicillamine in the treatment of paracetamol poisoning. 60 patients with paracetamol poisoning have been treated with intravenous cysteamine, L-methionine, or D-penicillamine and the incidence and severity of hepatic necrosis compared with those observed in 70 patients receiving supportive therapy only. Of 31 patients with 4-hour plasma-paracetamol concentrations greater than 250 mug/ml given supportive therapy 22 sustained severe liver damage, 3 died in hepatic failure, and 4 developed acute renal failure. None of 23 similarly poisoned patients given cysteamine within 10 hours of ingestion suffered severe liver damage or renal failure and none died. Cysteamine was partially effective at 10-12 hours, but ineffective 12 hours or more after ingestion. Liver damage was absent or mild in 17 patients given L-methionine within 10-12 hours of ingestion but severe in 3 treated within 10 hours. Of 5 patients treated with D-penicillamine, 1 developed severe liver damage with acute renal failure. It is concluded that cysteamine prevents severe liver damage after paracetamol poisoning if given within 10 hours in adequate dosage.


Death from ischaemic heart-disease and malignancy in adult patients with coeliac disease. The cause of death was obtained for 77 members of the Coeliac Society resident in England and Wales. Proportional mortality analysis revealed a significant deficiency in deaths from ischaemic heart-disease in males and a non-significant deficiency in females. It is suggested that this apparent protective effect of coeliac disease might result from malabsorption of dietary lipids. The study also confirmed findings of an excess of deaths from lymphoma and upper gastrointestinal neoplasms.


Suppression of sympathetic nervous function in low-renin essential hypertension. Study of general haemodynamics in 15 patients with low-renin essential hypertension showed haemodynamic and pathophysiological heterogeneity. However, there was suppression of sympathetic nervous system function in all low-renin patients, regardless of haemodynamic pattern. Subnormal sympathetic nervous activity was manifested by a low normal mean plasma-noradrenaline concentration at rest, diminished noradrenaline responsiveness to postural stimulation, and a reduced blood-pressure response to the indirectly acting sympathomimetic amine tyramine. It is proposed that the syndrome of low-renin essential hypertension is of diverse aetiology, but with secondary sympathetic nervous system underactivity as a feature common to the various forms. The low plasma-renin activity is probably an expression of defective sympathetic nervous system stimulation of renin release.


Cirrhosis in South London.

Cirrhosis in South London. Alcoholism was the major aetiological factor in 65% of 78 patients presenting with cirrhosis to a hospital in Central London during 1968-74. It is suggested that in the U.K. the importance of alcoholism in patients with cirrhosis has been underestimated.


Effectiveness of Zagreb antivenom against envenoming by the adder, Vipera berus. Rhesus monkeys injected subcutaneously with 2, 3, or 4 mg Vipera berus venom per kg body-weight all died in shock. With 1 mg/kg the monkey had severe systemic and local effects taking 12 days to resolve. Five monkeys each recieved 4 mg/kg (a triple-lethal dose) and Zagreb antivenom was injected intravenously 1-4 hours after venom injection. The contents of 2 ampoules (10-8 ml) up to 3 hours later saved the monkeys; at 4 hours later the monkey died. But when the antivenom dose was raised to 16-2 ml 4 hours after venom, it saved the monkey. In addition to saving life, the antivenom greatly reduced the local venom effects. It is suggested that the results justify giving Zagreb antivenom to patients with severe adder-bite poisoning; and it should also be considered in adults to minimise morbidity from local effects.


Congenital nephrotic syndrome: prenatal diagnosis and genetic counselling by estimation of aminotic-fluid and maternal serum alpha-fetoprotein. Nine families in which a previous child had had congenital nephrotic syndrome (C.N.) sought genetic counselling and possible antenatal diagnosis of fetal disease. Maternal serum and amniotic-fluid alpha-fetoprotein (A.F.P.) assays were carried out between the 15th and 20th weeks of subsequent pregnancies. Seven women in whom A.F.P. concentrations were normal chose to continue pregnancy, and they were all delivered of a healthy child. Markedly raised amniotic A.F.P. concentrations were found in two cases; in one of these cases maternal serum-A.F.P. was also raised. These pregnancies were terminated, and electron microscopy of the fetal kidneys showed evidence of C.N. in the fetus--i.e., loss of foot processes and an increase in the mesangial matrix of the glomeruli. The outcomes of these at-risk pregnancies indicate that prenatal diagnosis and genetic counselling are possible in families with a history of C.N. The results also stress the importance of carefully examining fetal kidneys whenever amniotic-fluid A.F.P. concentration is raised in the absence of apparent malformations.


Dietary antibodies and myocardial infarction. Serum milk, egg, and gluten antibody titres were measured in ninety men with acute myocardial infarction and compared with those of thirty-six age-matched male controls. None of the antibody titres was higher in the patients with myocardial infarction, nor was there a significant correlation between antibody titres and the Norris prognostic index or death before hospital discharge. The results do not support the suggestion that immunological mechanisms are involved in the pathogenesis of coronary heart-disease and atherosclerosis.


Behaviour of e antigen and antibody during chronic active liver disease. Relation to HB antigen-antibody system and prognosis. Serial determinations of e antigen and e antibody were made in 20 patients with chronic active liver disease and hepatitis-B surface antigen (HBsAg) or antibody (anti-HBs). The presence of e antigen was associated with failure to clear HBsAg, produce anti-HBs, or respond to treatment with steroids. It is proposed that the presence of the e antigen is associated with impaired host immune responses to hepatitis-B virus infection and a poor prognosis.


Topical therapy of ulcerative herpetic keratitis with human interferon. 55 patients with dendritic ulcer have been treated in a double-blind randomised manner by minimal wiping debridement of their ulcers followed by daily application of either partially purified human interferon (P.I.N.F.) or placebo. There were 6 recurrences of epithelial herpetic disease in 30 patients who received P.I.N.F. and 13 in 25 who received placebo. This provides the long-awaited data proving the antiviral effect of exogenous interferon in treatment of naturally occurring viral disease in man, and furnishes a sighting shot on the lower edge of the target of effective therapy.


Cultivation of viral agents from Crohn's disease. A new sensitive system. The isolation and animal transmission of a viral agent from Crohn's disease patients stimulated studies aimed at the development of improved tissue culture techniques. The need for an effective tissue-culture system led to a comparison of African green monkey tissue-culture cells (A.G.M.K.), human diploid lung cells (WI-38), and a new tissue-culture line--continuous rabbit ileum (C.R.I.). Homogenates prepared from ileal specimens from four Crohn's disease patients and from four control patients without inflammatory bowel disease were filtered through a 0-2mu 'Millipore' filter. After confluence, groups of six tissue-culture flasks were inoculated with 0-3 ml of Crohn's disease or control filtrates. No cytopathic agents were isolated from A.G.M.K. tissue-culture. Cytopathic agents were isolated in WI-38 and C.R.I. tissue-cultures from each of the four Crohn's disease specimens but from none of the control specimens. A comparison of C.R.I. and WI-38 demonstrated that cytopathogenic change (C.P.E.) developed in C.R.I. earlier than in WI-38. C.P.E. was complete in a shorter period of time in C.R.I. but was irregular in WI-38. The sensitivity of WI-38 varied with the passage level and age of the monolayer. C.R.I. was found to be free of cytopathic adventitial agents upon inoculation of standard tissue-culture systems and weanling mice. Therefore C.R.I. is a sensitive and superior tissue-culture system for the cultivation of viral agents from Crohn's disease filtrates. The reproducible isolation of a viral agent from the ileum of patient's with Crohn's disease is confirmed by these studies.


Electron microscopic studies of viral agents in Crohn's disease. Viral agents isolated from ileal filtrates of patients with Crohn's disease have been successfully cultivated in continuous rabbit ileum tissue-culture and grown to titres sufficient to allow electron microscopic characterisation. Electron microscopic studies showed clusters of viral particles only in tissue-cultures inoculated with cultivated viruses originally obtained from tissues from patients with Crohn's disease. Control cultures showed no evidence of viral agents. The mean virus-particle diameter was 30 nm. An electron-dense central core was present and a spiculated coat was demonstrated. The physical chemical properties of this agent, as previously described, together with the electron microscopic appearance are consistent with the appearance of a picornavirus.


Neutrophil dysfunction in Crohn's disease. The migration of neutrophils into skin windows has been examined in patients with Crohn's disease and rheumatoid arthritis and compared with normal. Leucocyte migration was significantly lower in patients with Crohn's disease than in others. This abnormality of neutrophil function in Crohn's disease appears to be secondary to a defective acute inflammatory response as the neutrophils themselves were found to behave normally on in-vitro testing. A weak acute inflammatory response to particulate or antigenic material in the bowel wall could result in the chronic inflammation observed in this condition.


The risk of pelvic inflammatory disease in women using intrauterine contraceptive devices as compared to non-users. The frequency of women using an intrauterine contraceptive device (I.U.D.) among 515 patients presenting with acute, laparoscopically verified salpingitis, has been compared with the corresponding frequency in 741 sexually active women who were matched to the patients by date of birth, domicile, and socioeconomic status. The frequency of I.U.D. use was significantly (P less than 0-001) higher in the patients than in the controls. It was estimated that the relative risk of acute salpingitis for any woman using an I.U.D. was 3-fold as compared to non-users. For women using I.U.D.s who had not been pregnant at any time, the corresponding risk was found to be 7-fold.


Chronic mastitis and carcinoma of the breast. 733 women in whom chronic mastitis had been diagnosed were followed for an average of 30-3 years. 49 died from breast cancer compared with an expected number of 18-8. The excess risk of dying from breast cancer persisted for at least 30 years after chronic mastitis was diagnosed.


Inheritance in protoporphyria. Comparison of haem synthetase activity in skin fibroblasts with clinical features. The activity of haem synthetase, the enzyme which chelates iron to protoporphyrin to form haem, was measured in cultured skin fibroblasts of children with protoporphyria and their parents from three families. In each family, one parent had deficient haem synthetase activity (3-0-11-1 pmol protohaem formed/mg protein/h) when compared to values in eight non-porphyric controls (means 24-9, range 13-7-51-5). The level of activity in the three parents was similar to that in their affected children. In two families the parent with deficient activity was also thought to be the carrier of the abnormal gene, as judged from a history of photosensitivity and analysis of erythrocyte protoporphyrin concentrations, but in the third family the pattern of inheritance could not be determined from these criteria. The activity of delta-aminolaevulinic acid synthetase was normal in cultured fibroblasts from the protoporphyric children and their parents, excluding a generalised defect in haem-pathway enzymes. These results support the premise that deficient haem synthetase activity, inherited in an autosomal dominant patter, is the primary defect in protoporphyria.


IgA deficiency, epilepsy, and hydantoin medication. Serum-immunoglobulin concentrations were measured in 364 patients with epilepsy. On dividing the patients into those treated with or without hydantoins, and according to possible aetiological factors, a characteristic pattern emerged. Irrespective of the treatment given, the mean values of IgA were significantly reduced in patients in whom constitutional factors were apparent, including those with familial prevalence of seizures. While IgA was rarely found below 0-6 mg/ml, a limit chosen to define IgA deficiency in patients not treated with hydantoins, the IgA level was subnormal in 20-25% of the patients treated with such drugs. In contrast, the mean concentration of IgA was normal and no individual subnormal values were observed in epileptic patients treated with or without hydantoins whose disease was thought to be secondary to traumatic or infectious events or to metabolic disturbances. The data suggest that epilepsy with constitutional characteristics might predispose to low IgA, but that IgA deficiency only occurs when hydantoins are given. Whether this postulated predisposition is relevant to the aetiology or pathogenesis of epilepsy remained unresolved.


Ventricular arrhythmias and hypokalaemia. Two cases of life-threatening ventricular arrhythmia (torsade de pointes) due to chronic mild hypokalaemia, caused by hyperaldosteronism and familial periodic paralysis are described. Correction of the hypokalaemia, supplemented by mexiletine, controlled the arrhythmias.


Computerised axial tomography for diagnosis of pancreatic cancer. Computerised axial tomography demonstrated the presence of a mass lesion in the pancreas in 9 (64%) of 14 patients with histologically confirmed pancreatic cancer. Since this was a retrospective analysis, the percentage of false positive and negative results using this technique is not as yet known. The technique appears accurate in detecting abnormal pancreatic masses of 10 cm in diameter or more, however, for masses less than 10 cm in diameter the yield at present is only 33%. With further technical refinement to increase resolution, the automatic computerised transverse axial scan should prove to be an invaluable procedure for the detection of pancreatic carcinoma, in designing radiation therapy ports, and in providing objective information regarding response of therapy and progression of disease.


Atmospheric derivatives of anaesthetic gases as a possible hazard to operating-room personnel. During surgical procedures in which nitrous oxide (N2O) anaesthesia was administered there was an increased concentration of both nitric oxide (NO) and nitrogen dioxide (NO2) in operating-room air. Preliminary studies suggest that the use of certain devices (e.g., electric cauteries, X-ray machines) capable of releasing energy in the operating-room produce the oxidation of nitrous oxide. Further evaluation of gas phase reactions of anaesthetic agents within the operating-room appear warranted, particularly in relation to the occupational risks of operating-room personnel.


Swine influenza virus and the recycling of influenza-A viruses in man. Sera collected in 1967 and 1972 from people in the 0-100 age-group showed haemagglutination-inhibition (H.I.) antibody to swine virus A/Iowa/15/30 (Hsw1N1) in greatest number and with highest titre in people born before 1918. A slight decrease was observed from 1967 to 1972 in the number of sera with antibody to swine virus and in the height of the titres. The recently isolated A/New Jersey/10/76 (Hsw1N1) virus showed a result comparable to that of the Swine/1930 virus in sera of 1972. On the analogy of the findings in 1968, when the Hong Kong virus became epidemic in human populations and antibody to this virus was found in sera of people over 70 years, the suggestion is made that the recurrence of swine virus as an epidemic agent of human influenza may be expected around 1986. Fourfold or greater increase of antibody to Swine/1930 virus was observed in about 4--5% of people infected by or immunised with H3N2 viruses. This response occurred in people who had been in touch with the epidemic influenza-A viruses Hsw1N1, H0N1, and H1N1 during the swine era of 1918 to 1956. Following immunisation with H3N2 viruses of persons showing no response to H3N2 viruses in their serum 5% did show a fourfold or greater heterotypic H.I. antibody rise to swine virus. This finding is of consequence for the diagnostic serology of influenza.


[Clinical and morphological features during the course of Whipple's disease(author's transl)]. Clinical and histological characteristics of Whipple's disease have been described extensively by various authors, but there are only few reports about repeated documentation of clinical and especially of micromorphological features during the course of the disease. We therefore report a case who was followed closely over a period of 3 years; small bowel biopsy was performed on 6 occasions during this time. Antibiotic therapy brought complete recovery from the disease and was followed by the disappearance of bacillary bodies in the lamina propria of intestinal mucosa. Despite this, many macrophages containing the typical PAS-positive material could still be demonstrated. The development of macrophages as well as etiologic aspects of the disease are discussed.


[Active immunization against tetanus and its evaluation]. The introduction of 5 ml. tetanus toxoid into guinea pigs stimulates the production of antibodies. The new specific substance can be measured invivo and invitro. In our tests 30 guinea pigs of 300-350 gr. were used. Before and after toxoid injections blood samples were taken and the sera were separated. In electrophoretic studies of the sera 5 fractions; albumin, alpha 1, alpha 2, beta and gamma globulins were noticed. The value of fractions and the statistical estimation are shown in tables 1-2. The experimental data have shown significant statistical values between them.


Oncornaviruslike particles in human malignancies. Mesenchymal and epithelial human malignancies were examined in the simultaneous detection test for the presence of particles with 70 S RNA and reverse transcriptase. Out of the 23 tumors tested 14 were found to be positive (61%). The finding that 2 uterine cancers contained 70 S RNA and reverse transcriptase indicates that uterine cancers may belong to the list of malignancies where the involvement of oncornaviruses is suspected. Out of the 10 human sarcomas examined in this study 4 were shown to contain particles with properties of oncornaviruses.


CCNU and bleomycin in the treatment of cancer: a Southwest Oncology Group Study. CCNU and Bleomycin, alone or in combination, were used to treat 397 evaluable cases of advanced cancer. Responses defined as 50% or greater reduction in all tumor masses occurred in 13/35 lymphomas, 8/50 brain cancers, and 28/312 other solid tumors. Hematologic toxicity of a life-threatening degree occurred in 33/298 patients evaluable for CCNU toxicity; in an additional 50 it was considered severe. Pulmonary toxicity was severe in 4 patients. Drug-associated deaths (4) included one each due to leukopenia and thrombocytopenia after CCNU; one due to pulmonary toxicity after Bleomycin; and one due to shock after the 20th dose of Bleomycin. There was no suggestion of synergism or additive activity with the two drugs.


[The chromosome bands. Significance for clinical and cytogenetic research (author's transl)]. The methods of performing chromosomal investigations have been fundamentally changed in the last few years through the discovery of differential staining methods. While only a rough classification of the chromosomes into single groups could be carried out earlier, it is now possible to identify every individual pair of chromosomes on the basis of a typical pattern of bands. By means of these banding techniques smaller chromosomal variations can be recognized which were overlooked earlier and which have led to the delineation of new chromosomal malformation syndromes. In the present work, the modern methods of chromosome analysis are reviewed. Examples from clinical diagnosis show the necessity of using these techniques.


[Liver metabolism of drugs (author's transl)]. Even if all problems of liver metabolism have not yet been clarified, it is nevertheless established that medicaments induces enzymes in the hepatic cells which influence the metabolism of drugs. Because their effect is unspecific, these enzymes can catabolize many drugs with different structures. About 200 substances are known which induce such enzymes. Among them, for example, is phenobarbital. It is therefore used in the treatment of some forms of icterus with freee bilirubin and for Cushing's syndrome. But enzyme induction can also lead to acute intermittent porphyrias and distrubances of the phosphorus-calcium metabolism. Extreme catabolism of a drug can be caused by overinduction of enzymes due to the administration of several incompatible medicaments.


Alpha-fetoprotein in the serum of patients with neoplasms of the gastrointestinal tract. Serum alpha-fetoprotein was estimated in 61 patients with neoplasms of the gastrointestinal tract, 29 healthy controls and 10 pregnant women. Almost half ot the patients had increased values of alpha-fetoprotein and no parellelism between alpha-fetoprotein and liver metastasis was found. Decreasing of the alpha-fetoprotein during the postoperative period could be considered a sign for a total removal of the tumor, and, on the contrary -- increasing of alpha-fetoprotein -- for a recurrence.


Protein histochemistry methods for colloid identification to metastases of thyroid carcinoma. Evidence for a thyroid origin of tumorous metastases may be facilitated by a histochemical determination of colloid. It is supported by the presence of proteins, demonstrable especially by the reaction for tyrosine, and a simultaneous absence, or only traces of acid mucosubstances. Contrary to existing literary reports, an intraplasmatic formation of mucin has been detected in certain thyroid carcinomas and their metastases. The most difficult to diferentiate histochemically from thyroid colloid is the secrete of certain adenocarcinomas of the prostate.


Serum glycoprotein: glycosyl transferase activity in patients with renal disease. Glycoprotein: galactosyl and glycoprotein: sialic acid transferase activities were measured in the serum of patients with minimal lesion nephrotic syndrome, acute renal failure, and chronic renal insufficiency of varying severity. The activity of galactosyl transferase was elevated in all patients but one. Sialic acid transferase activity was increased in the patient group as a whole, but the magnitude of the increase was smaller and less predictable compared to the galactosyl transferase enzyme. The physiologic consequence of increased glycosyl transferase activity in serum is discussed.


[Distribution of HB s Ag subtypes in a sample of acute viral hepatitis of type B in Northern Italy]. 82 HBsAg from acute hepatitis B patients living in Northern Italy were subtyped. HBsAg has been detected by immunodiffusion (ID), electrosyneresis (ES), complement fixation (CF) and radioimmunoassay (RIA, Kit Ausria I and II, Abbott). Subtyping was performed by ES in 50 and by ID in 30 of the 82 assayed sera. An higher frequency of ayw subtype (83,1%) in comparison with adw subtype (16,9%) has been observed. No difference was found between adw and ayw subtypes analyzed as far as geographic-ethnic characters, incubation time, course and prognosis of the disease or the biohumoral indices. No patient was found to have both y and d specificities and so r determinant was never found.


[Mechanism of action of drugs currently used in the prevention of migraine]. The mode of action of some classical and newer drugs used in the preventive interval treatment of migraine is discussed in the light of a modern theory of the pathogenesis of migraine headache. This headache is produced when two elements--a passive distension of the extracranial arteries and a lowering of the pain threshold of the receptors situated in the walls of the affected vessels--are present simultaneously. The main humoral factors involved in this phenomenon are plasma-kinins, serotonin and--to a lesser degree--histamine. The role played by serotonin which is released by the blood platelets at the onset of the attack is twofold: on the one hand, free serotonin increases the permeability of the capillaries, favouring transudation of plasmakinins, and lowers the pain threshold, while on the other hand, its increased excretion causes a secondary reduction in its plasma concentration, promoting hypotonicity of the extracranial vessels. Among the substances used for prophylactic interval treatment, some, such as dihydroergotamine, clonidine and the beta-blocking agents have a purely vascular site of action, maintaining--by various mechanisms--the tone of the extracranial arteries and thus reducing their lability. Methysergide and pizotifene have a chiefly indirect effect on the vessels, by potentiating the effect of catecholamines or helping to maintain free serotonin at a certain level. They act primarily against the humoral elements responsible for lowering the pain threshold: methysergide by inhibiting the release and blocking the effects of serotonin, by countering the potentiating effect of serotonin on the pain induced by plasmakinins and by inhibiting histamine release; pizotifene by inhibiting the release and blocking the effects of histamine, by blocking the effects of serotonin and by slightly inhibiting the peripheral effects of plasmakinins. Thus, the multifactorial pathogenesis of migraine helps to explain the effectiveness against migraine of substances possessing the most varied pharmacodynamic profiles.


Origin of amniotic fluid alpha-fetoprotein in normal and defective pregnancies. Alpha-fetoprotein was determined by electroimmunodiffusion and radioimmunoassay in 109 neonatal urine samples and 94 amniotic fluid samples. The samples were obtained from newborns and from pregnancies ranging in gestational age from 20 to 40 weeks. When alpha-fetoprotein values of neonatal urine and amniotic fluid were correspondingly correlated with gestational age, almost identical declining curves could be drawn. Twenty-one cerebrospinal fluid samples from newborns ranging from 25 to 40 weeks of gestation were similarly determined. No correlation between cerebrospinal fluid alpha-fetoprotein and gestational age could be demonstrated. It is concluded that fetal urine is the major source of alpha-fetoprotein in the amniotic fluid of normal pregnancy. In pregnancies associated with neural tube defects, alpha-fetoprotein elevation is probably not due to the leakage of cerebrospinal fluid into the amniotic cavity.


Prenatal diagnosis of neural tube defects. I. Problems and pitfalls: analysis of 2495 cases using the alpha-fetoprotein assay. The alpha-fetoprotein (AFP) assay is now an established tool for the prenatal diagnosis of neural tube defects (NTDs). About 90% of these defects are diagnosable prenatally early in the second trimester, the other 10% consisting of closed lesions that are not amenable to this approach. From the analysis of our 2495 consecutive cases, 49 NTDs were diagnosed with AFP levels 3 SD above the mean. One closed NTD sample, as expected, did not have an elevated AFP level. Various other fetal disorders or conditions were also associated with elevated AFP levels. AFP assays on amniotic fluids from 1858 patients without a family history of NTD and studied primarily for fetal karyotyping yielded a frequency of 1 NTD in 310 cases. Any amniotic fluid study in the second trimester of pregnancy should include an assay for AFP.


Prenatal diagnosis of neural tube defects. II. Analysis of false positive and false negative alpha-fetoprotein results. Certain problems and pitfalls attend the use of the alpha-fetoprotein (AFP) assay for the prenatal diagnosis of neural tube defects (NTDs). Analysis of 2495 consecutive cases revealed 57 (2.3%) with amniotic fluid AFP levels greater than 3 SD above the mean. Fetal deaths (9), various fetal abnormalities, (7) and spontaneous abortions (4) occurred among this group. In addition, there were 30 cases with AFP levels greater than + 3 SD above the mean in which a normal child was delivered--a true false positive rate of 1.2%. To determine if the false positive rate could be diminished, 40 amniotic fluid samples with AFP greater than + 2 SD were subjected to further detailed analysis for fetal hemoglobin, total protein, and IgM concentrations. Even with this battery of tests, we estimate that between 1 and 2% of normal amniotic fluids have elevated AFP levels and either fall as expected outside the + 3 SD range, or have elevated AFP levels due to unknown causes.


Combination chemothereapy with cis-diamminedichloroplatinum (II) and bleomycin in tumors of the head and neck. 28 patients with head and neck tumors not suitable for definitive treatment with radiation or surgery were treated with cis-diamminedichloroplatinum (II) and bleomycin in combination. Of 24 adequately treated patients, there were 3 partial remissions lasting for 3,3 and 6 months, respectively. Toxicity of the regimen as given was substantial; 13 patients showed some evidence of nephrotoxicity and there were 2 drug deaths related to progressive renal failure. 1 patient developed bleomycin pulmonary toxicity.


Recurrent haemolytic uraemic syndrome.

Recurrent haemolytic uraemic syndrome. Two children are described with frequent relapsing haemolytic uraemic syndrome. In the first child, the disease reoccurred twice and in the second three times. In both, relapses could be related to a viral infection, as well as to a preceding inoculation for diphtheria--pertussis--tetanus--poliomyelitis in the second patient. Recurrent haemolytic-uraemic syndrome (H.U.S.) may constitute a discrete clinical form of H.U.S.


[Immunochemical aspects of antigenicity (author's transl)]. A number of chemically definable parameters related to antigenicity are discussed. These include determinant size and density, antigen shape as well as eliciting, inhibiting and tolerogenic capacities of model antigens, notably those of the penicillin allergy model. A kinitic argument for a restricted antibody diversity is presented.


Reappearance of alpha-fetoprotein in spontaneous hepatitis in the rat. Reappearance of AFP was demonstrated in a single rat out of a large control population. At autopsy, this DOCA-hypertensive rat was found to have a form of hepatitis associated with proliferative activity, i.e., cellular unrest, mitotic figures and oval cell hyperplasia. It is submitted that increased AFP synthesis in this animal with spontaneous hepatitis is causally related to hepatocellular regeneration.


[Preventive and therapeutic effect convalescent zona and varicella sera in high risk children (659 cases)]. Study of 659 cases treated with serum from patients convalescent after herpes zoster and chickenpox over a period of two and a half years in French hospital departments, showed the obvious effectiveness of this type of therapy which seems to be better than that of zoster specific gamma globulin used by other workers since we obtained protection against chickenpox in 90 p. cent of cases, and attenuation of chickenpox in 82 p. cent. It would seem that these results could be improved by increasing the doses used.


Serum electrophoretic pattern of chickens vaccinated with R2B (Mukteswar) and F strain of Newcastle disease virus. Sera from NDV (Mukteswar and F strain) vaccinated chickens of various age groups were subjected to paper, starch-gel and immunoelectrophoresis. An increase in total serum protein, gamma globulin, alpha globulin, and a decrease in beta globulin and albumin concentrations was observed in adult birds. The concentration of the various serum proteins varied widely depending upon the age of the other test birds. IgM and IgG band characteristics did not differ in sera from vaccinated and unvaccinated birds. The one transferrin band observed in the sera from unvaccinated chickens was not observed when chickens were vaccinated with the R2B vaccine. However, this transferrin band was again observed in the sera of chickens revaccinated with the R2B. No such changes were evident in the sera of chickens vaccinated with F strain only or followed by an R2B vaccination.


Antithyroid activity of goitrin in chicks. Antithyroid activity of orally administered goitrin was assessed by parallel-line assay in chicks using four indices. The relative potency of goitrin in chicks was estimated to be approximately 0.31 times the potency of PTU in causing enlargement of thyroid gland, 0.06 times in effect on depression in plasma thyroid hormone, and 0.08 times in inhibitory effects on biosynthesis of thyroid hormone in the gland. It might be concluded that thyroid hormone synthesis is not so much suppressed to the degree expected from the enlargement of thyroid gland when goitrin is administered orally to the chick.


Gastrointestinal changes in patients with hypogammaglobulinemia. Three cases of hypogammaglobulinemia are described. In all cases the first symptoms of disease manifesting as pneumonia were preceded by diarrhea. In gastric biopsy there was atrophic gastritis with lack of plasmocytes. All patients demonstrated gastric achylia and symptoms of malabsorption syndrome. The causes of gastrointestinal changes, most probably infections, with simultaneous defective mucosal barrier are discussed.


[The effect of thyroid hormones and thyrostatic preparations on blood glycoprotein metabolism]. The author presents materials of parallel studies carried out in 322 male rats; the effect of various thyroid hormones and thyrostatics on the change in the concentration of glycoproteid fractions and of their individual carbohydrate-containing components in the blood serum was investigated. The dynamics of the changes of these tests and also their normalization depending on the applied type of the hormone or of the thyrostatic factor, the dose, the duration of administration and the emotional condition of the animals was established. On the basis of the data, obtained and literature data an attempt is made to explain the ways of the changes in the content of individual blood glycoproteins and also their relationships and the nature of appearance.


[The character of functional connections in the endocrine system of female white rats and their transformation with age]. The authors studied the functional interrelations between the adrenal glands and the thyroid gland of female albino rats of various age groups. Blood content of 11-oxycorticosteroids and protein-bound iodine was determined. Analogous determinations were carried out in partial exclusion of the adrenal gland function (metapyron block) and of the thyroid gland function (6-methyluracil block). It is supposed that in the young sexually-mature female albino rats the functions of the adrenal glands and the thyroid gland were in direct relationship irrespective of the cyclic variations in the sex steroid secretion; with the advance of age this association became deranged.