[Retrospective consideration of the incidence of anaphylactoid reactions following administration of Plasmasteril and Longasteril]. The frequency of anaphylacotid reactions following the infusion of colloidal volume substitutes has become more transparent in the recent years due to retrospective reports of several hospitals and especially by a prospective multi-clinical study carried out in the Bavarian area. As a contribution towards medicament safety by the manufacturers of infusion solutions, a quantitation of the incidents should be tried. For the period January 1974-June 1977 Dr. E. Fresenius KG has compared the units sold of HES (Plasmasteril) and Dextran 75 (Longasteril 75) with the reported incidents. The frequency of severe anaphylactoid reactions (type III + IV) amounted to 19/458 924 = 0.0041% for Dextran 75 and to 2/550 350 = 0.0004% for hydroxyethyl starch. The frequency of life-threatening incidents with HES proved to be lower than for Dextran 75 by the factor 10.


[Varied circulatory effects after rapid infusion of hydroxyethyl starch, dextran 60 and blood in the postoperative patient]. The acute hemodynamic effects which occur after a quick infusion (500 ml per 10 minutes) of hydroxyethyl starch, dextran 60 or autologous blood with identical hematocrit were studied in three groups of 10 patients each on the first day after laparotomy. If blood is infused there is only a moderate increase of the total perfusion (+18%) observed, however hydroxyethyl starch or dextran 60 infusions result in a striking increase of the cardiac output (+34%, +44%, respectively). There is no significant difference among the latter two groups. Thus, hydroxyethyl starch as well as dextran 60 can be considered as a potent volume substitute, if an acute effectiveness is wanted.


Cross-reaction between the mycelial galactomannas of three Hormodendrum strains and the mannans of two Candida albicans strains of different serotypes, A and B. Cross-reactivity between galactomannans of three representative Hormodendrum strains, H. pedrosoi IFO 6071, H. compactum IFO 6726, and H. dermatitidis IFO 6421, and the mannans of two Candida strains, C. albicans NIH A-207 (serotype A) and C. albicans NIH B-792 (serotype B), were investigated by means of agar-gel double diffusion, quantitative preciptin reaction, and passive cutaneous anaphylaxis. The following results were obtained. (i) Antisera to whole cells of three Hormodendrum strains were completely inactive in all in vitro antigen-antibody reactions to mannans of C. albicans NIH A-207 and C. albicans NIH B-792, whereas antisera to both C. albicans strains were found to be cross-reactive against the three Hormodendrum galactomannans. (ii) The results of cross-passive cutaneous anaphylaxis tests using guinea pigs sensitized with antiserum of three Hormodendrum and two Candida seemed to be consistent with those of the vitro assay. (iii) The reactivities of the corresponding acid-resistant core moieties of the three Hormodendrum galactomannas against two anti-C. albicans sera were nearly identical to those of the parent galactomannans in both in vitro and in vivo tests.


Antigenic properties of human lymphoblastoid interferons. Most virus-induced human lymphoblastoid interferons examined contained variable proportions of the Le and F antigenic species described for human leukocyte interferon. The F species was not detectable in interferons liberated spontaneously from human lymphoblastoid cells in culture. Lymphoblastoid interferons differed considerably in their interaction with the same anti-interferon serum. Spontaneous interferons required approximately ten times less antibody for neutralization than interferon induced by virus in the same cultures or in Namalva cells. The findings suggest that either spontaneous interferons contain fewer inactive antibody-binding molecules than virus-induced lymphoblastoid interferons or the number and distribution of antibody-combining sites, and possibly other surface properties of the interferon molecule, may be influenced by the manner in which spontaneous and induced interferons egress from the cells.


Persistence of e antigen as prognostic marker in acute hepatitis B. Serial determinations of HBeAg and anti-HBe were made in sera of 155 selected patients with acute hepatitis B who were followed up for one to four years. In the early phase of hepatitis, HBeAg was present in 43 cases (27.7%) and anti-HBe in 12 cases (7.7%). Evaluation of the outcome of hepatitis showed that development of chronic hepatitis occurred in 11 out of 43 HBeAg positive patients, in 10 out of 100 HBeAg negative patients (P = less than 0.05) and in 2 out of 12 patients carrying anti-HBe. Nine out of 11 HBeAg positive chronic subjects showed persistent HBe antigenemia over two months, while the remaining 32 patients, who recovered completely, lost HBeAg within two to three weeks from the onset of the disease. These data suggest that the prognostic value of HBeAg in acute hepatitis patients may be taken into account when HBeAg persists in the serum and that anti-HBe does not invariably protect from the development of chronic hepatitis.


Immunochemistry of Salmonella O-antigens. Specificity and cross-reactivity of factor O9 serum and of antibodies against tyvelose (Formula: see text) mannose coupled to bovine serum albumin. The octasaccharide Galp (Formula: see text) Rhap, the synthesized disaccharides methyl 3-O-a-tyvelopyranosyl-a-D-mannopyranoside, methyl 3-O-a-tyvelopyranosyl-beta-D-mannopyranoside and methyl alpha-tyveloside, in order of decreasing effectiveness, inhibited the precipitation of S. typhi T2 alkali-treated lipopolysaccharide by O-factor 9 serum. On a molar basis the relative inhibiting activities of the glycosides were by O-factor 9 serum. On a molar basis the relative inhibiting activities of the glycosides were 100:22:8:2. With rabbit aniserum raised against 3-O-a-tyvelopyranosyl-D-mannopyranosyl covalently linked to bovine serum albumin the relative inhibitory activities of the four glycosides were 11:100:26:3. These data establish that the 3-O-a-tyvelopyranosyl-a-D-mannopyranosyl structure is immunodominant in the Salmonella O-antigen 9. The specificity of the antigen-antibody interaction was high: glycosides in which the tyvelose (3,6-dideoxy-D-arabino-hexose) residue had been replaced by abequose (3,6-dideoxy-D-xylo-hexose) or paratose (3,6-dideoxy-K-ribo-hexose), had less than one fiftieth of the activity of the most active inhibitor in either of the two precipitation systems used. Moreover, the results show that 3-O-a-tyvelopyranosyl-D-mannopyranosyl coupled to bovine serum albumin elicits O-antibodies of higher specificity than those obtained by absorption of antibacterial immune serum.


Immunoregulatory function of specific IgG. II. Clinical evaluation of combined active and passive immunotherapy. Based upon previous clinical data suggesting that the potential therapeutic benefits of hyperimmune specific IgG could involve neutralization and regulatory effects, this cooperative study evaluated the efficacy and safety of combined active and passive immunotherapy in previously untreated ragweed-sensitive patients. Symptom scores and indices of patients receiving ragweed-specific globulin plus rush desensitization with ragweed extract were significantly reduced (p less than 0.05), as compared to control patients treated with albumin and active rush immunotherapy. Postseasonal RAST levels were either unchanged or decreased in 28 of 33 patients receiving hyperimmune gamma-globulin. These data were significantly different from those in albumin-treated patients (p less than 0.002). The usual anamnestic rise of ragweed-specific IgE was modified without affecting the ongoing synthesis of ragweed specific IgG. Mild constitutional symptoms were observed in patients undergoing rush immunization, but the overall procedure was relatively well tolerated and no serious or treatment-refractory constitutional problems were encountered. This clinical trial suggests that ragweed immune gamma-globulin might be a useful therapeutic adjunct when administered in close association with optimal amounts of allergen.


Effect of quantity and quality of IgG antibodies on blocking of allergenic histamine release in vitro. In a study of the protective role of IgG antibodies in allergen injection therapy, serum antibodies to timothy grass allergens were raised in rabbits and tested for inhibition of histamine release from basophils of grass pollen-sensitive human subjects. Rabbit sera were not inhibitory until late in the immune response when large amounts of relatively low affinity IgG antibodies were detected by primary binding. Inhibition of histamine release by late sera required preincubation of allergen and antibody prior to addition of sensitive basophils, and could not be demonstrated when basophils and IgG antibodies had simultaneous access to allergen. Hence intravascular inhibition of mediator release in allergen-treated patients may require high affinity IgG antibodies. The predominantly low affinity of antibodies raised in the rabbits precluded testing of this possibility.


Characterization and quantitation of murine-delayed hypersensitivity responses elicted with particle-associated human gamma-globulin. Parameters delineating the utilization of particle-associated human gamma-globulin to quantitate murine-delayed hypersensitivity (DHS) responses include: (1) the conditions used to prepare HGG-coated polystyrene latex particles; (2) the marked increase in sensitivity of detection of delayed immune responsiveness using particle-bound HGG; (3) a histologic analysis of the lesions induced by HGG-latex in DHS mice, and (4) the increased retention of particle-associated as opposed to soluble HGG at the site of challenge. The potential utilization of particle-bound antigens as a sensitive method of assessing the role of delayed-type responsiveness in tumor and transplantation immunity is discussed.


Delayed type hypersensitivity to allogeneic cells in mice. I. Requirements for optimal sensitization and definition of the response. Mice were sensitized to allogeneic cells under defined conditions, and their response to antigen deposition in the ear was measured by the influx of radioisotope-labeled cells. The delayed onset, T cell dependency and histology of the ear reaction were characteristic of delayed type hypersensitivity (DTH). Positive responses were obtained in a strain combination unable to elicit a mixed lymphocyte reaction (MLR), in B-Ly mice incapable of cytotoxic T lymphocyte (CTL) generation and in allogeneic combinations challenged with noncellular material. This suggests that MLR and CTL cannot, on their own, account for the response. Hence the ear reaction can best be explained in terms of DTH.


In vitro histamine and serotonin release studies in atopic dermatitis. 6 patients suffering from severe atopic dermatitis with high serum IgE were investigated. 3 of the patients had elevated plasma histamine levels (1.5-2.0 ng/ml). Compared to 9 nonatopic normal volunteers, the patient showed increased in vitro histamine release from peripheral leukocytes after stimulation with iothalamate and methacholine: while there was no significant histamine release at a methacholine concentration of 10(-4) M in normals, 4 of the patients with atopic dermatitis showed measurable histamine release under these conditions in vitro. The uptake of radiolabeled serotonin by platelets in vitro was decreased in 2 of the patients. There was no significant difference in serotonin release induced in vitro by different concentrations of thrombin, epinephrine and methacholine; 2 patients showed an increased platelet release reaction after iodipamide stimulation. It is concluded that a general tendency to release vasoactive mediators, even after 'nonimmunologic' stimulation, might play a role in the pathogenesis of atopic dermatitis.


Attempts to modulate the immune response to a hapten-carrier complex with various hapten-containing compounds. The immune response to a hapten-carrier conjugate appears to be a complex phenomenon where reactions of the T-cell population are not restricted to the carrier and where the reactions of the B-cell population are not limited to the hapten determinant of the antigen molecule. To get a better understanding of the different cell interactions during the immune response to a hapten-carrier complex, the effects of immunogenic or tolerogenic injections of various hapten-containing compounds on the responses induced by immunization with the same hapten coupled to protein carriers were studied. The results indicate that T cells involved in delayed hypersensitivity and T cells involved in contact dermatitis could belong to distinct subclasses and confirm that hapten and carrier moieties of the antigen molecule could compete, probably at the macrophage level, for both delayed hypersensitivity to the carrier and antibody synthesis to the hapten.


The allergenic structure of allergen M from cod. III. Studies on the antigenicity of long-sequence peptides. Fragments TM 1 (75 amino acid residues) and TM 2 (38 amino acid residues), and 3 other polypeptides (range 16-25 amino acid residues) of Allergen M from cod were shown to be active in rabbit IgG-mediated reactions. The same peptides were previously found to possess reactivity in IgE-mediated reactions, thus suggesting a structural relationship between their antigenic and allergenic determinants.


Evaluation of mycobacteriology laboratories: the acid-fast smear. In a proficiency testing program, slides bearing acid-fast bacilli were sent to laboratories in New York State. The most reliable results were obtained in laboratories using the Ziehl-Neelsen method. Cold staining procedures were less reliable. The auramine-rhodamine fluorescent stain, which produced many false positives, should be confirmed by the Ziehl-Neelsen procedure. The testing program described can be used to determine whether laboratories perform the acid-fast stain effectively.


Energetic coupling in the primary processes of photosynthesis in Chromatium. pH dependence of delayed fluorescence, electron transfer and degree of coupling. The effects of pH on the thermodynamic properties of the proton-translocating cyclic electron transfer system in a purple photosynthetic bacterium Chromatium vinosum were studied. Two thermodynamic parameters, the flux (Je) and force (deltamue) of the electron transfer process, were analyzed. The rate of electron transfer in the re-reduction of photooxidized reaction-center bacteriochlorophyll was used as Je. deltamue was determined from the intensity of the delayed fluorescence from bacteriochlorophyll. deltamue is composed of the redox potential difference and the electrical potential difference between two electron transfer components. In the steady state under illumination, the flux-to-force ratio is determined by the following relationship: Je = (1--q2)Lee deltamue where q is the "degree of coupling" of electron transfer to proton translocation and Lee is the value of Je/delta-approximately similar e when there is no back pressure by formation of delta approximately muH+ (electrochemical potential difference of H+). The value of (1--q2) Lee increased with increasing pH in the neutral pH range. Uncouplers and ionophores that dissipate delta-approximately muH+ increased Je and decreased deltamue. The effects were more prominent in the lower pH range. Therefore, q must be smaller at higher pH. The coupling is probably tight when redox components are saturated with protons. The experimental results agreed with the theoretical predictions for a system where a hydrogen-translocating component functions as an electron-proton symport carrier.


tRNATrp as primer for RNA-directed DNA polymerase: structural determinants of function. The specific interactions between the RNA-directed DNA polymerase of avian oncornavirus and the tRNATrp primer required for initiation of viral DNA synthesis in vitro were examined. Two distinct interactions, stable binding of the tRNATrp to the enzyme and initiation of viral DNA synthesis by the enzyme with tRNATrp as primer, were characterized as to the structure of tRNATrp required. Different structural features of the tRNATrp were shown to be necessary for each type of interaction. The entire primary structure and native conformation of tRNATrp are both required for binding to reverse transcriptase. Fragments of tRNATrp and intact tRNATrp in an altered conformation cannot be bound by the enzyme using an assay which detects high affinity binding between reverse transcriptase and native tRNATrp. In contrast, fragments of the tRNATrp molecule can serve as primers for viral DNA synthesis with normal efficiency as compared to intact tRNATrp. The fragments which initiate transcription must contain a minimum specific nucleotide sequence which extends from the 3' terminus of the tRNATrp through 27 residues of the molecule. This portion of the tRNATrp may be a major structural determinant of specificity in initiation.


Ribonucleoprotein staining of centrioles and kinetochores in newt lung cell spindles. The distribution of ribonucleoprotein (RNP) within the mitotic spindle of newt lung epithelial cells was studied with the high voltage electron microscope (HVEM) using Bernhard's uranyl-EDTA-lead staining of thick sections in conjunction with the ribonuclease digestion of fixed cells. The results indicate that aside from ribosomes, the major RNP-containing components of the spindle are the kinetochores and centrioles, both of which stain electron-opaque after EDTA treatment. In both cases, the electron-opaque material associated with these microtubule organizing centers (MTOC's) can be removed by RNAse digestion and cold perchloric acid (PCA) extraction under conditions which leave the spindle microtubules (Mts) centrioles, and kinetochores intact. The staining reaction is not abolished by cold PCA extraction alone or by substituting other positively charged proteins (i.e., cytochrome c or lysozyme) for RNAse. The RNP component of the kinetochore is closely associated with the bases of the kinetochore microtubules. The RNP component of the centriole can be seen to surround the microtubules of the triplet blades. No evidence was found to indicate the presence of RNP in the pericentriolar material. The possible function of both kinetochore and centriolar RNP is discussed.


The role of algal antigenic determinants in the recognition of potential algal symbionts by cells of Chlorohydra. Algal cells grown in the green hydra Chlorohydra viridissima were shown to possess characteristic antigenic determinants not found in algae cultured in vitro. These antigenic determinants, including those localized on the algal cell surface, were shown to be responsible for the phagocytic recognition of potential algal symbionts by digestive cells of Chlorohydra. The results of this study indicate the existence of two systems governing phagocytosis in Chlorohydra, one specific for algal cells grown in hydra, another governing the uptake of other particles by the hydra digestive cells.


[Palliative methods permitting oral feeding in patients with carcinoma of the esophagus (author's transl)]. 405 patient with carcinoma of the esophagus were operated on the unit from 1st January 1972 to 15th February 1977. Among these 405 patients, 55 underwent prolonged esophageal intubation and 24 a palliative operation. We considered successively the various methods of prolonged intubation and the various types of palliative operation possible. At the end of this study, it appears that palliative surgery for carcinoma of the esophagus owing to the severity of the operation and the high post-operative mortality and the doubtful functional results, should be reserved for eso-respiratory fistulas, per-operative loss of esophageal blood supply, and the contra-indications to prolonged intubation. On the other hand, it seems that the indications for prolonged intubation should be enlarged at the expense of those for gastrectomy, excluding however stenosing or too extensive carcinomas and carcinoma of the upper.


Measurement of beta-endorphin in human plasma. beta-endorphin has been identified in human plasma by means of gel filtration and a sensitive radioimmunoassay for human beta-endorphin (beta h-endorphin). Mean baseline plasma beta h-endorphin concentration in 5 individuals was 21 +/- 7.3 (SD) pg/ml (6.2 +/- 2.2 (SD) fmole/ml). Following metyrapone stimulation mean plasma concentration increased to 55.4 +/- 10.1 (SD) pg/ml (16.3 +/- 3.1 (SD) fmole/ml). The molar ratio of human beta-lipotropin (beta h-LPH) to beta h-endorphin was 2.2 in baseline plasma and 2.4 after metyrapone stimulation.


Location of type-specific antigens in calf rotaviruses. Rotavirus antisera with and without neutralizing activity to calf rotavirus were compared for their ability to agglutinate calf rotavirus particles with and without an outer capsid layer. Particles without the outer capsid layer were agglutinated by antisera with immunofluorescent antibody activity and by antisera with immunofluorescent antibody and neutralizing activity. Particles with the outer capsid layer were agglutinated only by antisera with neutralizing activity. The neutralization test appears to be type specific, and it was concluded that type-specific antigens are associated with the outer capsid layer of rotaviruses. Since particles with the outer capsid layer were not agglutinated by antisera lacking neutralizing activity but possessing immunofluorescent antibody activity, it was concluded that in intact particles the group-specific antigen is masked by the outer capsid layer.


Electron microscopic studies of serially sectioned cat spinal alpha-motoneurons. I. Effects of microelectrode impalement and intracellular staining with the fluorescent dye "Procion Yellow". Cat spinal alpha-motoneurons were studied in the light and electron microscope after intracellular recording and staining with the fluorescent dye Procion Yellow. Generally, the ultrastructural preservation of the stained neurons improved when the amount of dye delivered was decreased, and when the duration of the microelectrode impalement of the neuron as well as the time between the intracellular staining and the tissue fixation was kept as short as possible. Utilizing the optimal experimental procedure finally arrived at, about one-third of the stained neurons could be used for further quantitative morphometric analysis. With respect to synaptology and gross architecture these cells appeared to differ from control motoneurons mainly with regard to a focal disarrangement of the cell body periphery, probably a result of the microelectrode injury, and a certain degree of damage to some large boutons.


Electron microscopic studies of serially sectioned cat spinal alpha-motoneurons. III. Motoneurons innervating fast-twitch (type FR) units of the gastrocnemius muscle. Two intracellularly stained cat gastrocnemius alpha-motoneurons of the FR-type (Burke et al., '73) were studied ultrastructurally. The architecture and synaptology of the cell body and proximal parts of the dendrites were analyzed from a long series of consecutive sections, according to a method presented in a preceding paper (Conradi et al., '79a). Several of the dendrites had a base diameter exceeding 10 micrometer. The proportion of the surface covered by boutons was 40-50% for the cell body and about 80% for the proximal dendrites. In both regions, about 20% of the boutons were of the S-type and 70% of the F-type. The large C-boutons were clustered around the dendritic roots and were also present on the axon hillock. M-boutons of dorsal root origin were located on the proximal parts of the majority of the dendrites.


Serum proteins and secretory component in human carious dentin. By the use of the peroxidase-labeled antibody method, significant localization of IgG, IgA, albumin and transferrin was demonstrated in the deep lesion of 20 carious teeth, where the secretory component was absent. These serum proteins formed a distinct zone, surrounding the overlying, shallow lesion infected with bacteria.


Evaluation of the prophylactic effect of gamma globulin in meningococcal infection. Results of two controlled epidemiological tests evaluating the prophylactic effect of gamma globulin of Monogolian and Soviet production against meningococcal infection are presented. Observations were carried out on children aged 3 months to 4 years, not attending children's establishments. The results of the observation revealed the following prophylactic effect of gamma globulin of Mongolian production in the first two months after administration: index of efficiency--5.0, coefficient of efficiency--80%, P greater than 0.01. The efficiency of the prophylactic effect of Soviet gamma globulin was limited to one month: the index of efficiency amounted to 5.3, the coefficient of efficiency  to 82.2%, P greater than 0.01. The course of meningococcal infection in the children who had received gamma globulin was less severe than in the children of the control group. Lethal outcome was recorded only in the group of children who had not received gamma globulin. The duration of the prophylactic effect of gamma globulin was found to depend on the height of the titres of specific antibodies in the preparation. The preparations are recommended as prophylactic means for children aged from 3 months to 4 years in doses of 1.5 ml (one dose) in the foci of meningococcal infection.


Coupling of gamma-globulin to microcrytstalline cellulose by periodate oxidation. Anti-rabbit IgG sheep gamma-globulins were covalently coupled to periodate oxidized microcrystalline cellulose using the Schiff reaction. Optimal conditions (sodium m-periodate concentration and gamma-globulin amount) were studied measuring the ability of this solid-phase antibody to bind glucose oxidase-labeled rabbit IgG.


Reduction of the non-specific binding of DNA to gamma-globulin in Farr radioimmunoassay by addition of dextran sulfate and calcium chloride. The effect of non-specific binding caused by the interaction between gamma-globulin and denatured DNA was markedly reduced by addition of dextran sulfate or CaCl2 at alkaline pH. This method was shown to be applicable in the detection of anti-DNA antibodies in sera from cases of human systemic lupus erythematosus.


A simple reliable system for studying antigen-specific murine T cell proliferation. Antigen-specific T cell proliferation can be readily elicited from the popliteal lymph node cells of mice which have received immunizations of antigen in the hind footpads. The advantages of our system over other published methods are (i) simplicity in method and materials, (ii) much improved reproducibility, (iii) negligible concomitant B cell proliferation, (iv) large degrees of antigen specific proliferation with very low background, and (v) complete dependence of the response on accessory cells or macrophages. These results were brought about by proper immunization procedures for mice and judicious choice of culture conditions. Our data show that the system is very suitable for the study of macrophage-T cell interaction in the induction of T cell proliferation as well as the genetic basis of responsiveness or non-responsiveness to protein and polypeptide antigens.


[Hydramnios and fetal malformations. Use of estimating the level of alpha-fetoprotein and of bilirubin in the amniotic fluid during the last trimester of pregnancy (author's transl)]. Alpha-fetoprotein (AFP) levels in amniotic fluid have been measured by electro-immunodiffusion methods in the last trimester of pregnancy. 122 samples have been taken by abdominal amniocentesis during 58 pregnancies without hydramnios and 51 pregnancies with hydramnios. The level of AFP was always less than 1.2 mcg/ml when the children were normal in the latter group. On the other hand levels were higher than 1.2 mcg/ml in 17 out of 19 abnormal children. These had 5 neural tube abnormalities, 1 hydrocephalus, 3 duodenal atresias, 1 oesophageal atresia, 1 hare lip, 1 omphalocoele and 5 different malformations. The two abnormal children who had levels of AFP within normal limits were hydrocephalic. The diagnostic value of measuring bilirubinaemia which was also measured in 22 cases has been demonstrated.


Differential sensitivities of normal human and chronic lymphocytic leukemia lymphocytes to 1-methyl,3-isobutylxanthine and N6-2'-o-dibutyryl adenosine-3',5'-cyclic monophosphate. Lymphocytes from patients with chronic lymphocytic leukemia (CLL) and from normal donors were cultured with 1-methyl,3-isobutyl xanthine (MIX) and N6-2'-o-dibutyryl adenosine-3',5'cyclic monophosphate (dbcAMP). MIX decreased the survival of CLL and normal lymphocytes during one day in culture; the magnitude of the MIX-sensitivity of the populations was similar to their colchicine-sensitivity, i.e. high for CLL and low for normal. dbcAMP increased cell death in one day cultures of lymphocytes from seven of fifteen CLL donors but inhibited the death of lymphocytes from the other eight donors. The protective effect of dbcAMP was not mimicked by adenosine monophosphate or adenosine diphosphate. The difference in sensitivity to dbcAMP provided a method for subdividing CLL lymphocyte populations which was examined for possible clinical significance.


Initial vector rates in differentiation between supraventricular extrasystoles with aberration and ventricular extrasystoles. A computer method was constructed for analysing vector rates. Initial vector rates of QRS of ventricular extrasystoles (VES) and of aberrant supraventricular extrasystoles were compared. Bundle branch block (BBB) was used as a model for aberration. Spontaneous VES during heart catheterization and VES found by His-bundle recording represented the VES group. The VES were found to contain a longer average "activation time," i.e. the duration from the onset to the spatial amplitude maximum, than the BBB. The maximum amplitudes were similar. A method for calculating initial vector rate distribution was also developed. This showed a significantly higher proportion of fast rate components in BBB than in VES. The calculation of vector rate distribution gave advantages over the calculation of the mean initial vector rate, when considering electrocardiographic abnormalities such as preexcitation QRS or post-infarction Q waves. With a simple discriminatory analysis using initial vector rate distribution values, a 95% precision was obtained in differentiating between VES and BBB. It is concluded that a QRS from a supraventricular impulse focus with aberration has faster initial vector rates than a QRS from a ventricular focus and that this difference is useful in distinguishing between them.


Effect of trypsin and chymotrypsin on the polypeptides of large and small plaque variants of foot-and-mouth disease virus: relationship to specific antigenicity and infectivity. Large and small plaque variants of A12 foot-and-mouth disease virus were shown to have specific antigenic determinants. Large plaque virus antigenic specificity was destroyed by trypsin treatment, but the small plaque antigen was resistant despite cleavage of the trypsin-sensitive polypeptide. The cleavage of polypeptide VP3 by trypsin resulted in the formation of a new antigen not present on untreated virus. The effects of chymotrypsin and trypsin on the polypeptides of the plaque variants have been examined and related to changes in antigenicity, infectivity, and exposure of the polypeptides at the surface of the capsid. The results are discussed in relation to the orientation of the trypsin-sensitive polypeptide in the virus capsid.


Solid phase indirect radioimmunoassays for the rapid diagnosis of Sindbis virus antigen. Indirect radioimmunoassays have been developed for the rapid detection of Sindbis virus. Dilutions of Sindbis virus from tissue culture fluids have been immobilized and allowed to react with rabbit anti-Sindbis virus antibodies. The bound antibodies were assayed either by 125I-labelled anti-rabbit IgG-antibodies or alternatively by addition of human complement and 125I-labelled anti-human C1q antibodies or 125I-labelled protein A.


Bioisomerization of lindane in rats.

Bioisomerization of lindane in rats. The major environmental problem associated with the use of gamma-hexachlorocyclohexane (gamma-HCH, lindane) has been the appearance of the more oncogenic alpha- and beta- isomers as terminal residues in nature. To account for these residues it was suggested that gamma-hexachlorocyclohexane had been bioisomerized to the more stable alpha- and beta- isomers. In this study the effect of dose and duration of treatment on the proposed bioisomerization of gamma-hexachlorocyclohexane in the rat was investigated. Weanling female Sprague-Dawley rats were randomly assigned to one of four groups receiving Purina Lab Chow fortified with 0, 130, 215, or 350 ppm gamma-HCH. Six animals from each group were sacrificed after 1, 2, 4, 8, 16, and 24 weeks of treatment. Twenty-four hours prior to sacrifice all rats received a single oral dose of gamma-HCH in peanut oil. There were no significant differences in food consumption or body weights, and no deaths occurred throughout the study. The in vitro dechlorinase activity of the treated rats was significantly higher after 1, 4, and 24 weeks of treatment. Except at 4 weeks after treatment began, the liver/body weight ratios of the rats fed diets containing 350 ppm and 215 ppm lindane were significantly greater than the controls; while those receiving 130 ppm lindane were significantly greater than the controls after 1 and 2 weeks of treatment. No beta-HCH was detected in any of the samples analyzed throughout the study. The levels of alpha-HCH found in the adipose tissue after 24 weeks of treatment could be accounted for by trace contamination of the lindane used in this study. There was a negative correlation between the hepatic content of alpha-, gamma-, and sigma-HCH  and duration of treatment. It was concluded that bioisomerization does not play a significant role in the metabolism of lindane by rats.


Demonstration by electron microscopy of intracellular virus in Acholeplasma laidlawii infected with either MV-L3 or a similar but serologically distinct virus (BN1 virus). Cultures of Acholeplasma laidlawii strain M1305/68 were inoculated with Mycoplasmatales virus-laidlawii 3 (MV-L3) and examined by electron microscopy. Particles resembling MV-L3 were observed both intra- and extracellularly in thin sections prepared from MV-L3 infected cultures, but not from uninfected cultures. Similar particles were occasionally observed in uninoculated cultures of A. laidlawii strain BN1 cells, from which a virus (BN1 virus) was subsequently isolated. This virus was morphologically similar but not identical to MV-L3. It also differed serologically from, and in its resistance to, MV-L3 and the other mycoplasma viruses.


The carcinogenicity kepone.

The carcinogenicity kepone. Kepone is unmistakably carcinogenic in rats and mice. Kepone induced malignant tumors in the liver of rats and mice in the NCI studies and in the liver in rats in the Medical College of Virginia study. Malignant tumors were also found in organs other than the liver in rats in both studies, including the lowest dose administered. Female rats given Kepone were more susceptible to the development of malignant tumors than were male rats. There also were toxic changes, particularly in male rats, ingesting Kepone. These lesions include interstitial fibrisos of the kidney, polyarteritis of the mesenteric, pancreatic and other arteries; and atrophy of the testes. Such lesions generally interfere with the health of the rats and with the development of tumors. Atrophy of the testes would also prevent reproduction.


Cross-neutralization study of seven California group (Bunyaviridae) strains in homoiothermous (PS) and poikilothermous (XTC-2) vertebrate cells. Antigenic relationships among seven California group strains were studied by a plaque-reduction neutralization test (PRNT). Cross-reactions occurred in most cases but three subgroups were noted: (1) the major serogroup contained the viruses of California encephalitis, LaCrosse, Snowshoe Hare and Trahyna (including the Lumbo strain) whereas (2) Jamestown Canyon and (3) Trivittatus viruses were distinct. There was no significant difference between the PRNT results in mammalian (PS) cells incubated at 37 degrees C and amphibian (XTC-2) cells incubated at 28 degrees C. Trivittatus virus failed to produce plaques in XTC-2 cells.


Clinical and theoretical aspects of head movement dependent oscillopsia (HMDO). A review. Head movement-dependent oscillopsia (HMDO) with peripheral vestibular, brainstem and cerebellar lesions is reviewed. The differentiation of this kind of oscillopsia is based mainly on clinical grounds. HMDO with bilateral abolition of caloric responses, and in the absence of disease of the central nervous system, is due to bilateral vestibular disease. HMDO in patients with internuclear ophthalmoplegia and other brainstem signs is probably due to a lesion of VOR pathways in or near the medial longitudinal fasciculus. The occurrence of HMDO with ataxia of gait and cerebellar eye movement disorders (rebound nystagmus, flutter-like oscillations), in the absence of brainstem lesions (medial longitudinal fasciculus), is clinical evidence for HMDO due to a cerebellar lesion. An attempt is made to associate the different kinds of oscillopsia with current knowledge of the vestibulo-ocular reflexes.


Experimental studies on hydrocarbon neuropathies induced by methyl-ethyl-ketone (MEK). An outbreak of neuropathies among Berlin solvent sniffers was closely related to the denaturation by methyl-ethyl-ketone (MEK) of the mixture used. The solvent was composed of n-hexane, toluene and ethyl-acetate. Nervous system responses to chronic repeated exposure to 10,000 ppm pure n-hexane, 10,000 ppm MEK/n-hexane (ratio 1:9) and 6000 ppm pure MEK were investigated in rats. Motor neuropathy of the dying back type with giant swelling of axons in the peripheral and central nervous system developed in animals exposed to MEK/n-hexane and n-hexane. Severe potentiation of n-hexane neurotoxicity and shortened onset of morphological and clinical signs were demonstrated in animals exposed to MEK/n-hexane. MEK alone did not produce neuropathy under these conditions. The findings suggest that commercial solvent mixtures containing MEK/n-hexane should be avoided.


Early degeneration of the cerebellar cortex, particularly the granular cells. An 8 month old infant, who died of severe gastroenteritis, presented a degeneration of the cerebellar cortex involving cells arising from the outer granular layer as well as Purkinje and Golgi II cells. Residual Purkinje cells showed vacuolar change of the cell body and dendritic abnormalities. Related lesions were atrophy of the inferior olives and degeneration of the mossy fibers.


T and B lymphocytes in the cerebrospinal fluid of various neurological diseases. Cerebrospinal fluids (CSF) from 66 patients with a variety of neurological disorders were studied for total protein content, absolute amount of albumin, IgA, IgG and IgM, as well as their quotients (fraction to total protein ratio), cell numbers and B cell and T cell levels. In addition, the percentage of B cells and T cells in the blood was determined in 34 patients and serum immunoglobulin levels were estimated in 51 patients. In noninflammatory diseases of the CNS, the percentage of B cells was slightly higher and T cell levels were lower in the CSF in comparison to corresponding blood values. The B cell to T cell ratio in viral meningitis was altered in the CSF. An apparent increase in the T cell level led to a decrease of B cell values. Similar changes were also found in optic neuritis. The percentage of T cells was higher in relapsing multiple sclerosis than in the chronic progressive form. There were less striking changes in the B cell to T cell ratios in the CSF of other inflammatory diseases of the CNS.


Cochleovestibular involvement as the first sign of syphilis. Three cases of syphilis with cochleovestibular symptoms are reported. There was either cochlear or vestibular involvement in two cases and, in the trird, cochlear and vestibular involvement together. The disorder was unilateral in all three. In one case there was a concurrent lesion of the oculomotor nerve which was the motive for consultation. There was no other symptom suggesting the diagnosis of syphilis in any case. The important features of diagnosis are discussed.


Frequency of minor nervous dysfunction in school children. A study was made on 88 third grade school children to determine the frequency of minor nervous dysfunction (MND) Touwen and Prechtl). The study consisted of a neurological and an motoscopic examination as well as a visuomotor performance test (Gleiss). The following results were obtained: 1. Suspected MND was found in 15.9% of the population. 2. Only two children had optimal performance according to Prechtl's optimality concept. 3. If the diagnosis MBD is made excluding the behavioral description as a diagnostic criterion, no significant statistical correlation was found with school marks or social class. 4. The specific character of Lempp's "frühkindliches exogenes Psychosyndrom" and the behavioral disturbances described seems to us to be questionable. We found such disturbances with our methods as frequently in children with disturbed organic brain function as in children from a low social class.


Abducens palsy after lumbar myelography with watersoluble contrast media. Five patients who developed abducens palsy after myelography with watersoluble contrast media are reported. These palsies can be compared to abducens palsies after spinal anesthesia and diagnostic lumbar puncture. They are most likely due to the lumbar puncture. The arguments for this explanation are discussed. The experience with these five patients suggests a greater incidence of postpuncture abducens palsy after myelography with watersoluble contrast media than after spinal anesthesia or lumbar puncture. If this first impression is verified, it could point to an additional toxic action.


Transsphenoidal hypophysectomy for disseminated carcinoma of the prostate gland. Results in 53 patients. Transsphenoidal microsurgical hypophysectomy was performed in 53 men with disseminated carcinoma (Stage IV) of the prostate gland. The mean age was 64.8 years. Forty-three of the 53 men had severe pain due to their disease. Significant pain relief was obtained following hypophysectomy, usually within 24 hours, in 39 (91%) of these 43 patients. Objective remission occurred in 16 (36%) of 45 patients in whom the follow-up review was adequate to make this decision. Although dramatic, pain relief was not permanent in every patient. Four patients died in the early postoperative period, and in one, death was directly related to the operative procedure. Significant complications included partial diabetes insipidus in 40 cases (75.5%), and cerebrospinal fluid leaks in six (11.3%). The authors conclude that hypophysectomy is an appropriate operation in patients with disseminated carcinoma of the prostate gland, particularly when pain is a significant feature of the illness. Further, the transsphenoidal microsurgical approach appears to be the operative procedure of choice for performing hypophysectomy.


Rapid high-performance liquid chromatographic determination of bleomycin A2 in plasma. A rapid and specific method for the determination of bleomycin A2 is described. A 50-microliter aliquot of 20% trichloroacetic acid was added to 200 microliter of plasma. The sample was vortexed and centrifuged, and 50 microliter of the clear supernate was injected into a liquid chromatograph equipped with a microparticulate reversed-phase column and a fixed wavelength detector. Elution was carried out using methanol-acetonitrile-0.0085 M heptanesulfonic acid-acetic acid. A linear calibration curve was found in the 0.05-5 microgram/ml range with an estimated precision of +/-6% (CV). Preliminary pharmacokinetic data in the rabbit also are reported.


Rapid orthograde and retrograde axonal transport of acetylcholinesterase as characterized by the stop-flow technique. 1. In rabbit peroneal nerves incubated in vitro at 37 degrees C, acetylcholinesterase (AChE) activity accumulated at both borders of a short region cooled to 5 degrees C. Accumulation was unaffected by concentrations of cycloheximide that inhibited 86% of local protein synthesis, as measured by the incorporation of [3H]leucine. It is probable that the local changes in enzyme activity during incubation reflected redistribution of the enzyme by axonal transport. 2. AChE activity accumulated almost three times faster at the proximal than at the distal border of cooled regions. This suggests that three times more enzyme is normally exported from nerve cell bodies than is returned to them, as though most of the transported AChE were degraded or secreted from distal parts of the neurones. The rates of accumulation of enzyme activity were consistent with average velocities of transport of 24 mm/day in the distal (orthograde) direction and 8.6 mm/day in the proximal (retrograde) direction. 3. When nerves that had been locally cooled for 3 hr were rewarmed to 37 degrees C, the accumulated AChE activity moved rapidly away from the cooled region. More than half of the activity appeared in a wave moving distally with a maximum velocity of 400 +/- 35 mm/day. A smaller wave moved proximally with a maximum velocity of 288 mm/day. 4. The observed behaviour of AChE is direct evidence that a small amount of this enzyme, probably less than 10% of the axonal content, is normally transported away from cell bodies as rapidly as any substance known. A still smaller amount of the enzyme is subject to an almost equally rapid retrograde transport. However, 85% of the AChE in peripheral nerve appears to be stationary, which probably explains why the average velocity of transport of this enzyme is so low.


On the origin and fate of external acetylcholinesterase in peripheral nerve. 1. Rabbit peroneal nerves were exposed to echothiophate, a quaternary ammonium inhibitor of acetylcholinesterase (AChE), and 217-AO, its tertiary analogue, in an attempt to characterize the localization of the enzyme. Although 217-AO readily inhibited AChE throughout the nerves, echothiophate spared significant amounts unless the tissues had first been homogenized. Notably, doses of echothiophate inhibiting 84% of the total AChE inhibited only 30% of the rapidly transported enzyme, suggesting that AChE was distributed between compartments differing greatly in their accessibility to this drug. 2. Since charged molecules penetrate cells poorly, it seemed likely that the more accessible compartment of AChE was external, perhaps consisting mainly of enzyme incorporated into the outer surface of the axolemma. If one assumes that the inhibition of the transported enzyme accurately reflected the inhibition throughout the inaccessible compartment, it can be calculated that external AChE comprised about 80% of the total. 3. The quasi-irreversible inhibition of AChE by echothiophate was used to probe the dynamics of the external enzyme. Locally exposing nerves to this drug in vivo markedly inhibited the AChE in a short region, which subsequently recovered with a half-time of about 5 days. Recovery appeared to reflect delivery of new enzyme into the inhibited region rather than spontaneous reactivation or local synthesis of AChE. Surprisingly, the zone of inhibition neither broadened nor moved noticeably for at least 8 days. This implies that external AChE is largely fixed in place and must be renewed locally, presumably by incorporation of rapidly transported enzyme from the internal compartment.


Aryloxyalkyloxy- and aralkyloxy-4-hydroxy-3-nitrocoumarins which inhibit histamine release in the rat and also antagonize the effects of a slow reacting substance of anaphylaxis. The syntheses and structure--activity relationships of a number of 4-hydroxy-3-nitrocoumarins, which are both antagonists of a slow reacting substance of anaphylaxis and potent inhibitors of antigen-induced histamine release in the rat, are described. Most active among these are 7-[3-(4-acetyl-3-hydroxy-2-n-propylphenoxy(-2-hydroxypropoxy] derivatives having hydrogen or lower alkyl substituents at the C-8 position of the coumarin ring, 168, 171, 173, and 174.


A method for marking and relocating identified cells in whole tissue for electron microscopy. Deposits of silver chloride made on the surface of animal tissue are visible by reflected light after osmication. When the tissue is flat embedded, the deposits permit precise relocation and thin sectioning of specific identified cells.


Prostatography.

Prostatography. The direct intraprostatic injection of ethiodol was done in 10 cases to visualize the prostate gland. Immediately after the injection the contrast material was distributed uniformly throughout the prostatic lobe, opacifying it with a fine reticular pattern (prostatogram). The size, shape and intravesical projection of the prostate could be studied accurately in all patients and the findings were confirmed at operation. All patients tolerated the procedure well without any local or systemic complications. Direct intraprostatic injection of the contrast material did not alter the gross nor the microscopic anatomy of the gland. Prostatography is a safe adjuvant radiologic procedure to obtain a 3-dimensional image of prostatic hypertrophy. This information would be useful in the proper planning of operative or radiation treatment of prostatic diseases. It also might be helpful in delineating the deep-seated suspicious prostatic nodules that are inaccessible for clinical examination.


Prostatic lymphography.

Prostatic lymphography. Direct intraprostatic injection of ethiodol was done in 12 patients with benign prostatic hypertrophy to visualize lymphatic drainage of the prostate gland. In all 12 patients lymphatics of the prostate could be visualized well. The findings of our study indicate that the prostate mainly drains through 3 sets of lymphatics: 1) the main and important set of lymphatics starts from the superolateral angle of the prostate and courses along the lateral pelvic wall to drain into the internal iliac lymph nodes, 2) some lymphatics drain into the lymph nodes in the presacral area and 3) in 45% of the patients lymphatics from the apex of the prostate travel along the course of the internal pudendal vessels to the internal iliac lymph nodes. From the internal iliac lymph nodes the drainage is to the common iliac lymph nodes and, finally, to the lumbar lymph nodes. Each lateral lobe of the prostate drains mainly into the ipsilateral group of lymph nodes with little crossover of lymphatics to the opposite side. All patients tolerated the procedure well and there were no complication during or after the procedure. We believe that this procedure is a safe, simple and direct method to visualize lymphatic drainage of the human prostate gland.


[Clinical application of NK 631 to head-and-neck cancers (author's transl)]. NK 631, a new antibiotic of bleomycin analogue, was applied to the treatment of 15 patients with head-and-neck cancers. The results obtained were slightly better than bleomycin-treated cases. For the side effect of NK 631, there were no lung disorders in all patients.


[Clinical effects of NK 631, a new bleomycin derivative, in treatment of oral cancer (author's transl)]. We used only NK 631, a new bleomycin derivative, for 10 cases of primary oral cancer, and obtained following results. (1) Anti-cancer effects were immediate and as follow: remarkably good in 1 case, efficacious in 8 cases, and none in 1 case. (2) In clinical examination, peripheral blood, function of kidney, liver, etc. were normal. But attention must be payed to blood gas. (3) Loss of hair, stomatitis and exanthema were noticed as side effects more clearly than regular bleomycin, but no fever. As the result of the above, NK 631 is better than regular bleomycin in anti-cancer effect and activity, but more attention should be payed to the side effect.


Immunocytochemical localization of human choriogonadotropin in human malignant trophoblast. Model for human choriogonadotropin secretion. Human choriogonadotropin (HCG) and its subunits have been studied immunocytochemically using a recently developed unlabeled antibody method. Factors influencing the antigenicity of HCG and its subunits were explored, and optimum conditions were determined. HCG has been successfully localized at the cellular level using paraffin-embedded tissues. Several antibodies to HCG or its subunits were evaluated for specificity using rigorous immunologic controls. This methodology was applied to placental tissue, in vitro choriocarcinoma, and in vitro breast carcinoma. HCGbeta and HCGalpha were localized in the syncytial trophoblast of first trimester placenta with cytotrophoblast cell islands and Langhans' cells being negative. Conditions of stimulated and unstimulated HCG production have been explored in the BeWo line of malignant trophoblast. Stimulation was accomplished by treatment with dibutyryl cyclic AMP and theophylline for varying periods of time. Only 6 per cent of the cells could be shown to be producing HCGbeta and HCGalpha in the unstimulated condition. Stimulation increased this percentage to 70 and 18 per cent, respectively, after 24 hours of treatment. Ultrastructural localization has shown that the mechanism of synthesis and secretion of HCG follows a pathway that is not as extensively developed as that of the pituitary hormones.


Paracortical post-capillary venules of human lymph nodes with special reference to the distribution of their endothelial IgG. The distribution of IgG in the endothelium of the paracortical post-capillary venules (PCV) of human lymph nodes was studied in frozen sections by using an indirect immunoperoxidase technique. Three different patterns of distribution could be differentiated (luminal site, intraendothelial and basement membrane site). Each of these patterns was characteristically encoutered in association with one of three grades of PCV (graded on the basis of the height of their endothelial cells). The significance of this close relationship between the IgG distribution and the changes in PCV endothelium was discussed in regard to the T-lymphocyte recirculation. A hypothesis was introduced describing the possible sequence of events involved in the traversing of T-lymphocyte through the PCV endothelium.


Prevention of necrotising enteritis in Papua New Guinea by active immunisation. Necrotising enteritis (pig-bel) caused by Clostridium welchii type C is a major cause of illness and death in the Highlands of Papua New Guinea. In a controlled trial of active immunisation with a clostridial toxoid prepared from type-C cultures the incidence of pig-bel in over 2500 immunised children within 24 months of immunisation was less than an eighth of that in a control group. Necrotising enteritis in Papua New Guinea is now a preventable disease.


Recommended site and depth of newborn heel skin punctures based on anatomical measurements and histopathology. The heels of 40 children (0.56--13.15 kg), 35 of whom were newborn infants and 28 of whom had 2--20 visible skin punctures, were examined at necropsy, and the thickness of the tissue layers was measured with a metric vernier caliper. Histological examination showed that uncomplicated skin-puncture wounds heal with minimum scarring and no neuroma formation. 1 infant had an infected puncture track extending into the calcaneus and resulting in cellulitis and focal calcaneal necrotising chondritis. The skin's primary blood-supply is located at the junction of the dermis and subcutaneous tissue, and the distance from the surface of the heel to this junction was quite constant (0.35--1.6 mm). However, the distance from the skin surface to the calcaneus increased with infant weight (in the smallest infant it was 2.4 mm), and at the posterior curvature of the heel it was half that from the plantar surface to the calcaneus. The calcaneus rarely extended lateral to a line drawn posteriorly from a point midway between the 4th and 5th toes and running parallel to the lateral aspect of the heel or medial to a line extending posteriorly from the middle of the great toe and running parallel to the medial surface of the heel. Therefore, in order to avoid calcaneal puncture and the risk of osteochondritis, heel puncture in the newborn should be done: (1) on the most medial or lateral portions of the plantar surface of the heel; (2) no deeper than 2.4 mm; (3) not on the posterior curvature of the heel; and (4) not through previous puncture sites that may be infected.


Predictors of reinfarction and sudden death in a high-risk group of acute myocardial infarction survivors. 75 patients aged under 70 years who had survived acute myocardial infarction complicated by both significant arrhythmias and cardiac failure were followed-up for 1 year in an attempt to identify features which suggest the likelihood of late death or reinfarction. Patients were carefully instructed in the identification and importance of possible prodromal symptoms and the availability of a mobile intensivecare ambulance service and a 24 h hospital control centre. Horizontal ST-segment depression or anginal pain on an exercise test done within 6 weeks of infarction was a useful predictor of late death. Routine twice weekly E.C.G. recordings taken by telephone transmitter at rest and after mild exertion resulted in the identification of significant arrhythmias in only 7 patients. 13 patients (17%) died, 5 of them instantaneously. 4 of the 13 patients and 22 of the 62 survivors reported "prodromal symptoms". Unreported prodromal symptoms were elicited retrospectively in 14 of the 62 survivors and from the relatives of 4 of the 13 patients who died. Thus, 35% of prodromal symptoms were not reported despite intensive patient education and counselling. The incidence of "prodromal symptoms" was no higher in patients who died than in those who did not die.


Gamma-aminobutyric-acid deficiency in brain of schizophrenic patients. Gamma-aminobutyric acid (G.A.B.A.) was measured in the nucleus accumbens and thalamus of brains from patients who had died with schizophrenia or Huntington's chorea (H.C.) and from control subjects. Mean G.A.B.A. content was significantly reduced in both brain areas in schizophrenia and in H.C. Extraneous factors, such as age, interval from death to necropsy, cause of death, and drug use, did not readily explain the observed reduction in brain G.A.B.A. G.A.B.A. deficiency may be a biochemical characteristic of some forms of schizophrenia.


Rapid diagnosis of Bacteroides infections by indirect immunofluorescence assay of clinical specimens. 43 specimens from a variety of sites were directly examined by indirect immunofluorescence assay (I.F.A.) with specific antisera against the capsular polysaccharide of Bacteroides fragilis and pooled antisera against a number of serotypes of Bacteroides sp. (all of the former B. fragilis subspecies). The findings were compared with those of routine anaerobic bacteriology and gas liquid chromatography for short chain fatty acids. Examination by I.F.A. was a sensitive (100%) and specific (90.3%) means of identifying B. fragilis. Use of the pooled serum was sensitive (100%) but less specific (64.3%) than the capsular antiserum (90.3%) although it had the advantage of detecting Bacteroides species other than B. fragilis. The capsular serum I.F.A. gave 9.7% false positives and no false negatives. The predictive value of a positive identification of B. fragilis in a clinical specimen using this anticapsular serum I.F.A. test was 80%; with the pooled Bacteroides group-serum it was 60%. The predictive value of a negative test was 100% for both sera, indicating that a negative I.F.A. test is a reliable index of the absence of Bacteroides from the culture I.F.A. of clinical material provides a rapid (less than 2 h) specific and sensitive means for the diagnosis of B. fragilis infections and would be of use in a clinical laboratory.


Efficacy of acycloguanosine (Wellcome 248U) against herpes-simplex corneal ulcers. Acycloguanosine (9-[-hydroxyethoxymethyl]guanine) (Wellcome 248U) has a highly specific and potent antiviral action against herpes-simplex virus (H.S.V.) types I and II in cell-culture systems and in animal models of H.S.V. infection in the brain, skin, and eye. Its efficacy in man was tested in twenty-four patients with dendritic corneal epithelial ulcers treated by minimal wiping debridement. Patients were randomly allocated to treatment with 3% acycloguanosine eye ointment or placebo. There were seven recurrences or recrudescences of typical corneal epithelial herpetic lesions within 1 week of debridement in the twelve patients who received placebo, and no recurrences in the twelve who received acycloguanosine. Four further patients with dendritic ulcers have been electively treated with topical acycloguanosine alone. Their ulcers all healed briskly. No adverse effects were seen with the acycloguanosine therapy. These results establish that acycloguanosine is a clinically effective antiviral drug against H.S.V. infection in man.


Interferon therapy in myelomatosis.

Interferon therapy in myelomatosis. Four patients with myelomatosis (one IgG-chi-type, two IgA-chi, and one Bence Jones-x) were given human leucocyte interferon as the only treatment for from 3 to 19 months. Remission was complete in two patients and partial in the other two. Normal bone-marrow haematopoiesis was slightly inhibited. The disease has not so far progressed in any of the patients.


A reappraisal of American psychiatry.

A reappraisal of American psychiatry. Remarkable changes have taken place in American psychiatry over the past twenty years. The era of psychoanalytical supremacy has passed, and realism is replacing the exaggerated claims which were made of psychiatry's ability to produce personal, social, and even political change. The importance of phenomenology and accurate diagnosis is increasingly recognised, and American researchers have made many impressive contributions to psychiatric genetics and to psychopharmacology. Despite these advances, office practice generally continues to function on an outmoded model and psychiatric resources remain inequitably distributed.


Congenital rubella deafness: a preventable disease. Over a 4-year period (1972-75) an unselected sample of 568 children aged under 4 years attending the Nuffield Hearing and Speech Centre were tested for rubella antibody. Sensorineural deafness was subsequently diagnosed in 349 of these children, and 83 (24%) of this group had rubella antibody. In contrast, only 19 (9%) of the remaining 219 children in whom sensorineural deafness was excluded had rubella antibody. The seropositive and seronegative children with sensorineural deafness showed striking differences in family history, history of maternal rubella, adverse perinatal events, and presence of other defects. Congenital rubella is an important cause of deafness, and the rubella vaccination programme must be pursued more vigorously if this serious defect is to be prevented in the future.


Cyclical combination chemotherapy and gonadal function. Retrospective study in males. The effect of cyclical chemotherapy on fertility and gonadal function was investigated in seventy-four male patients who had been treated for advanced Hodgkin's disease. All patients were azoospermic after therapy, and, with a median follow-up period of 27 months (range 1--62 months), only four patients have regained spermatogenesis. Testicular biopsy showed an absence of germinal epithelium without other gross architectural changes. Despite this high degree of infertility, 60% of patients were practising contraception. A decline in libido and sexual performance with frequent long periods of sexual inactivity was noted by most men during therapy. Although some recovery was apparent once therapy was stopped, this was incomplete in approximately half of the patients. Follicle-stimulating-hormone levels were consistently raised after therapy at all periods of study. Median luteinising-hormone levels were at, or just above, the upper limit of normal, and median testosterone levels were normal. Increased prolactin levels were noted in 42% of patients, of whom about a half had an identifiable cause for hyperprolactinaemia. Return of spermatogenesis could not be predicted by serial hormone assessment. Because of the guaranteed infertility and the low frequency and unpredictability of recovery of spermatogenesis, sperm storage should be available for male patients undergoing cytotoxic therapy, since most of these patients may enjoy prolonged survival. Hormone-replacement therapy will usually be unnecessary. However, the probability of major changes in libido and sexual performance should be discussed with patients so that additional stress can be avoided. Contraceptive advice should be available to those who require it.


Changing phage typing patterns of epidemic gentamicin-resistant Staphylococcus aureus. Evidence for transmission of gentamicin resistance. In a 10-week period, infection with gentamicin resistant Staphylococcus aureus appeared in 24 adults and infants in one hospital. Medical staff were affected first, and subsequently 16 infants in the neonatal intensive-care unit. The gentamicin-resistant staphyloccal isolates showed three distinct phage susceptibility patterns in two distinct phage groups during the early, middle, and late phases of the outbreak. Although not confirmed with in-vitro or in-vivo laboratory data, this outbreak suggests that gentamicin resistance may be transferred between different strains of Staph. aureus in vivo.


Cardiovascular disease in patients with retinal arterial occlusion. 103 patients with retinal-artery occlusion causing permanent visual-field defect were examined clinically and angiographically to assess the extent of cardiovascular disease. The 68 patients with branch-artery occlusion had a higher prevalence of previous transient episodes, ischaemic and valvular heart-disease, and more often had an operable lesion in the carotid artery than had the 35 patients with central-artery occlusion who were more often hypertensive, had fewer warning attacks, a greater prevalence of complete carotid occlusion, and fewer operable carotid lesions. The two types of retinal vascular occlusion show aetiological differences; branch occlusion is more often embolic and should be fully investigated for carotid and cardiac disease. These measures are less often of practical importance in patients with central-artery occlusion.


Regional lung clearance of excessive bronchial secretions during chest physiotherapy in patients with stable chronic airways obstruction. Clearance of excessive bronchial secretions labelled with inhaled radioactive polystyrene particles has been directly measured with a gamma-camera linked to a computer. Chest physiotherapy significantly increased clearance from central, intermediate, and peripheral lung regions and sputum yield. These findings confirm the value of this form of treatment, which has hitherto been in doubt, in removing excessive bronchial secretions from all lung regions and in aiding their expectoration.


Activity of aryl hydrocarbon hydroxylase in psoriatic skin. The activity of aryl hydrocarbon hydroxylase (A.H.H.), a microsomal mono-oxygenase, was reduced in epidermis from both the psoriatic lesions and clinically normal lesion-free skin from psoriatic patients. Induction of epidermal A.H.H. activity by benzanthracene was also significantly less than normal in both psoriatic lesions and in clinically normal skin from patients with psoriasis. The enzyme defect may be related to the primary genetic abnormality of the disease.


Preventing malignant-cell transfer during endoscopic brush cytology. Transfer of malignant cells on cytology brushes was responsible for false positive cytology reports in 4 patients. In 24 examinations of cytology brushes after patients with gastric carcinoma had been previously endoscoped, malignant cells were identified on 7 occasions. Satisfactory irradication of malignant cells was achieved by autoclaving the brushes for 15 min, not by cleaning with chlorhexidine or pancreatin. Although these observations may argue against the use of non-disposable brushes, non-disposable brushes provide a higher yield of cells and are cheaper than disposable brushes.


Fatal adenovirus infection with misleading positive serology for infectious mononucleosis. Symptoms and serological tests in a 19-year-old man with pneumonia indicated that he had infectious mononucleosis. Adenovirus type 7 was demonstrated in the lung by electron microscopy and was cultured from the liver, lung, lymph-nodes, and kidney.


Prophylaxis of neonatal jaundice with maternal antipyrine treatment. A randomised controlled trial of antipyrine (phenazone) in the prophylaxis of neonatal jaundice was completed in 48 women. Treatment of mothers from the 38th week of pregnancy reduced neonatal plasma-bilirubin concentrations on the 4th day after birth by an average of 44%. Prophylaxis of neonatal jaundice merits a wider trial.


Delay in diagnosis and treatment of symptomatic colorectal cancer. Mean delay between the onset of symptoms and treatment was 30.5 weeks in a hundred patients with colonic carcinoma and 38 weeks in a hundred patients with rectal carcinoma. Most of this delay occurred outside hospital and delays attributable to the patient and family doctor were almost equal in duration. Patient delay is largely the result of not knowing the importance of bowel symptoms, while delay with the family doctor was the result of not examining patients with possible rectal carcinomas and not recognising symptoms suggestive of colonic carcinoma. 42% of patients with colonic carcinoma were admitted for emergency treatment, 76% having already consulted their doctor about symptoms on one or more occasions. Hospital delay consisted mainly in waiting for investigations, poor quality barium enemas, and inadequate sigmoidoscopy. There was no relation between the duration of symptoms and the Dukes stage of the tumour.


Modes of transmission of cholera in a newly infected population on an atoll: implications for control measures. To determine the modes of transmission in a cholera epidemic in a newly infected population on an atoll, two studies were conducted, in which persons with cholera were individually matched, by age and sex, with neighbourhood controls. Among the first recognised cases, cholera was associated with frequent (daily or weekly) consumption of raw lagoon fish that had been salted and partially dried. Vibrio cholerae was isolated from the lagoon, which was contaminated by human wastes. During the declining phase of the epidemic, cholera was associated with consumption of raw clams, salt-fish, sardines, and other fish from the lagoon. When seafood from enclosed bodies of faecally contaminated water is frequently eaten raw, imported V. cholerae can become established and can be extremely difficult to eradicate.


Sensitivity to enkephalin as a cause of non-insulin dependent diabetes. Non-insulin-dependent diabetes is associated with facial flushing after alcohol in patients on chlorpropamide (chlorpropamide alcohol flushing, C.P.A.F.) especially when there is a family history of diabetes. C.P.A.F. in three subjects (two diabetics, one non-diabetic) was blocked by the specific opiate antagonist naloxone. In nine subjects (six diabetics) C.P.A.F. was reproduced by the enkephalin analogue with opiate-like activity [D-Ala2, MePhe4, Met (O)-ol] enkephalin (DAMME). C.P.A.F. thus may be due to increased sensitivity to endogenous opiates. DAMME and other substances with opiate-like activity, such as morphine and beta-endorphin, affect carbohydrate metabolism and insulin secretion. Increased sensitivity to endogenous opiates such as enkephalin may thus give rise to non-insulin-dependent diabetes associated with C.P.A.F.


Selectivity as a clue to diagnosis of postural proteinuria. In 14 patients with fixed and reproducible postural proteinuria and 14 patients with histologically proven glomerulonephritis, the selectivity of proteinuria was measured separately in the day and night urine collections. The selectivity of proteinuria in the urine collected in recumbency was lower in patients with glomerulonephritis than in patients with postural proteinuria. All patients with postural proteinuria showed an increment of the selectivity from day to night of at least 13 degrees, whereas the maximum increment in patients with glomerulonephritis was 5 degrees. The changes in selectivity from day to night in patients with postural proteinuria and patients with glomerulonephritis were significantly different and seem to be a useful discriminatory test.


Rapid emergence of El Tor Vibrio cholerae resistant to antimicrobial agents during first six months of fourth cholera epidemic in Tanzania. 110 El Tor Vibrio cholerae isolates from 102 patients with cholera between November, 1977, and March, 1978, during the early stages of the fourth epidemic of cholera in Tanzania had minimum inhibitory concentrations to tetracycline, chloramphenicol, nitrofurantoin, neomycin, ampicillin, and sulphadimidine determined. All isolates during the first month after the disease was recognised were fully sensitive to tetracycline, but 76% of isolates were resistant to the drug after five months of extensive use of tetracycline therapeutically and prophylactically in the country. Resistance to the five other antibacterial agents developed more slowly. Isolates from patients who failed to clear the organism from their stools or who had cholera soon after tetracycline prophylaxis had increased minimum inhibitory concentrations of the drug. Resistance did not develop in vivo. Although resistance to tetracycline readily developed following extensive use of the drug, such a resistance was not the only reason for failure of tetracycline treatment and prophylaxis. Mass chemoprophylaxis in the control of cholera should be discouraged unless evidence to the contrary becomes available.


Diagnostic value of rectal mucosal acetylcholinesterase levels in Hirschsprung's disease. Acetylcholinesterase (AChE) activity was measured in rectal biopsy specimens obtained from 68 children aged between 2 days and 14 1/2 years in whom Hirschsprung's disease was suspected. The diagnosis was subsequently established in 12; in these, the mean AChE activity was found to be 30.5 X 10(-7) units/g tissue (range 16.9 to 63.0). The 56 non-Hirschsprung cases had a mean of 5.0 X 10(-7) units/g tissue (S.D. 2.2), the highest value in this group being 10.9. The results were unaffected by age, sex, nature of biopsy procedure, or the presence of blood. It is suggested that the assay of AChE activity in rectal biopsy material is a simple and quick procedure that is useful in the diagnosis of Hirschsprung's disease.


A new test showing abnormal net Na+ and K+ fluxes in erythrocytes of essential hypertensive patients. A new and simple laboratory test for measuring net Na+ and K+ fluxes in Na+-loaded/K+-depleted human erythrocytes was developed and applied to hypertension. Moderate essential hypertension (10 patients) was characterised by a constant increase in net K+ influx, possibly related to higher Na+, K+-pump activity. In more severe cases (8 patients) net Na+ efflux from erythrocytes dropped. The ratio of Na+/K+ net fluxes was therefore reduced in all essential hypertensive patients. Conversely, Na+ and K+ erythrocyte fluxes were normal in hypertension of renal origin (5 patients). Erythrocyte K+ influx was normal in young normotensive people born of normotensive parents (17 cases), but was increased in 5 of 8 young normotensive people born of essential hypertensive parents, in families where blood-pressure has been recorded for three generations. This result, which seems to indicate genetic transmission, suggests that measurement of Na+ and K+ erythrocyte fluxes may help to detect subjects liable to high blood-pressure.


Fulminant psittacosis.

Fulminant psittacosis. Two patients died of psittacosis after presenting with generalised toxaemia, acute renal failure, and evidence of pancreatitis. Death was attributed to the virulence of the chlamydial strain and the delay in antemortem diagnosis. In one case Chlamydia psittaci was isolated from necropsy lung tissue. A third case of psittacosis suggested person-to-person or fomite spread, which is rarely reported. Infection was acquired from an apparently healthy, imported and quarantined cockatiel. Import restrictions on psittacines should thus be tightened and psittacosis should be made a notifiable disease.


Two unexpected deaths from pneumothorax. Two patients with primary spontaneous pneumothorax died despite intensive treatment. In the first the pneumothorax had been present for 10 days, and, after insertion of a chest drain, pulmonary oedema developed unilaterally, followed by cardiac arrest. She was resuscitated, but later died of a tension pneumothorax on the other side, probably due to cardiac massage and artificial ventilation. In the second patient, after insertion of a chest drain, mediastinal emphysema spread to the head and neck, causing fatal obstruction of the hypopharynx.


Chemotherapy of localised histiocytic lymphoma. 22 patients with localised (stage I or II) diffuse lymphoma were treated with chemotherapy at the time of diagnosis. 14 patients received chemotherapy as the only treatment, and 8 received chemotherapy plus local irradiation. Doxorubicin-containing drug regimens were used in 20 patients. All 22 patients achieved a complete remission and remain alive with a median survival from the time of diagnosis of 27+ months. 21 patients (95%) have remained continuously free of disease with a median disease-free survival from the completion of chemotherapy of 23+ months. These findings provide a strong rationale for further clinical trials of chemotherapy alone or chemotherapy followed by regional radiotherapy for localised stages of diffuse lymphoma.


Were you knocked out?

Were you knocked out? In the period 1970-75 inclusive 5152 patients were admitted to an accident hospital after an uncomplicated injury to their head. This group was compared with the 116 patients who needed craniotomy in the same period. It is suggested that precautionary admission of patients with minor head injuries is excessive.


Is chloroquine obsolete in treatment of rheumatic disease? Retinal changes associated with chloroquine occurred in 22 out of 222 patients on long-term therapy for rheumatic diseases and were related to patient age, total dose, and duration of treatment. Ophthalmic review showed progression of the retinopathy with deterioration of visual acuity in only 1 case while the remainder retained normal vision. The results suggest that the risks of ocular toxicity related to chloroquine therapy are acceptably low.


Comparison of photochemotherapy and dithranol in the treatment of chronic plaque psoriasis. A two-centre trial has been carried out on 224 patients with chronic plaque psoriasis randomly allocated to treatment with a standard dithranol regimen of 8-methoxypsoralen and long-wave ultraviolet light (P.U.V.A.). Lesions in 91% of the 113 in the P.U.V.A. group cleared satisfactorily compared with 82% of 111 in the dithranol group, but clearing took longer (34.4 +/- 1.8 S.E. days) with P.U.V.A. than with dithranol (20.4 +/- 0.9 S.E. days). P.U.V.A. treatment took less patient-time and nurse-time and was more convenient and acceptable to the patients. Patients in whom lesions had failed to clear with dithranol, and some who had needed methotrexate for control, responded satisfactorily to P.U.V.A. A few patients who had failed on P.U.V.A. were treated with dithranol and responded to it. There is a case for the use of P.U.V.A. for patients who would otherwise require methotrexate and those who cannot be managed successfully with dithranol. There is also no reason to withhold P.U.V.A. in patients of 60 years or above with chronic plaque psoriasis. However, despite its superiority in terms of cost and patient acceptability, P.U.V.A. cannot be recommended as the first line of treatment for patients with uncomplicated, dithranol-responsive plaque psoriasis until there is more information on relapse-rate and toxicity.


Effect of cardioselective and non-selective beta-blockade on the hypoglycaemic response in insulin-dependent diabetics. The response to intravenous insulin was studied in seven diabetics after a dose of placebo, propranolol (40 mg), or metoprolol (50 mg). Two of the seven subjects also had a week's course of each of the same agents taken three times daily. Neither of the beta-blockers potentiated the effect of insulin as judged by the rate of reduction in blood-glucose. However, blood-glucose recovery was reduced significantly by propranolol, but not significantly by metoprolol. Propranolol caused severe bradycardia and raised diastolic blood-pressure during hypoglycaemia; these effects were milder with metoprolol. Propranolol inhibited the free-fatty-acid levels after hypoglycaemia to a greater extent than did metoprolol. The results strongly suggest that propranolol (and presumably other non-selective beta-blockers) is hazardous in subjects prone to hypoglycaemia. When diabetics require beta-blockade a cardioselective beta 1-blocker should be used.


Prednisone in treatment of allergen-associated angio-immunoblastic lymphadenopathy. Angio-immunoblastic lymphadenopathy with dysproteinaemia (A.I.L.D.) is a lymphoproliferative disorder associated in one third of the patients with exposure to an allergen. In four patients with allergen-associated A.I.L.D. single cytotoxic drugs were ineffective but maintenance low-dose prednisone for 6--12 months induced complete remission for up to 13 years. In contrast, three patients with non-allergen-associated A.I.L.D. did not respond to prednisone but achieved remission with combination chemotherapy.


Long-term effects of repeated plasma exchange in myasthenia gravis. Plasma exchange produces a short-term clinical improvement in myasthenia gravis (M.G.) which may be attributable to removal of acetylcholine receptor (AChR) antibody. The possibility that repeated plasma exchanges might confer cumulative long-term benefits was investigated. Serum-AChR-antibody and clinical response were followed for 4--12 months (mean 8 months) in six M.G. patients receiving 4--25 plasma exchanges of 2--4 1 together with immunosuppressive drugs (azathioprine [2.5 mg/kg] with or without alternate-day prednisone therapy), and in seven M.G. patients on immunosuppressive drugs alone. Percentage decrease in AChR antibody was not significantly different in the two treatment groups. Decline in antibody titre was associated with clinical improvement. Eight patients with previous thymoma showed significantly greater decline in antibody than the remaining five patients, irrespective of plasma exchange. Since repeated plasma exchange had no cumulative long-term benefit, the value of this treatment as used here lies only in short-term control of severe M.G. symptoms.


Clinical characteristics of imipramine-induced orthostatic hypotension. The effects of imipramine hydrochloride on blood-pressure were examined in a prospective and a retrospective study. In a prospective study of 44 depressed patients given imipramine in doses to achieve antidepressant plasma-concentrations there was no effect of the drug on lying blood-pressure. When patients then stood up, the drug produced an average fall in systolic pressure of 26 mm Hg (t = 13.6, P less than 0.001) that was consistent over the four weeks of observation. Contrary to expectation, this fall was independent of patients' age, pre-existing heart-disease, or plasma-level of the drug. The best predictor of orthostatic hypotension during treatment was the degree of orthostatic drop in pressure before treatment (r = 0.695, P less than 0.001). In order to establish the clinical significance of this orthostatic drop in pressure, a retrospective study of 148 depressed patients treated with imipramine was conducted. These 148 patients, average age 59 years, received an average dose of 225 mg of imipramine. Almost 20% of them had symptoms usually associated with orthostatic hypotension that were severe enough to interfere with their treatment: over 4% sustained physical injuries. In our experience orthostatic hypotension is the commonest serious cardiovascular side-effect of imipramine.


Dried-blood spot screening for cystic fibrosis in the newborn. Serum-immunoreactive-trypsin (I.R.T.) was measured in children with cystic fibrosis (C.F.) and a variety of controls. In the first few months of life all C.F. children had a raised serum-I.R.T. A dried blood-spot assay for I.R.T. was established and has potential as a screening test for C.F. in the newborn.


Uptake of taurine by platelets in retinitis pigmentosa. Uptake of 3H-taurine by platelets from twelve patients with retinitis pigmentosa (R.P.) and from healthy controls was measured. Platelets were incubated in autologous plasma with 3H-taurine for different times and at different substrate concentrations. The uptake of taurine by R.P. platelets at each incubation time was about two-thirds of the control value, the difference being statistically significant. Km was about the same, but Vmax was lower in R.P. platelets. The results suggest that R.P. is a disease affecting not only the eye but also taurine transport and/or storage in general.


Severe hypertension in primary aldosteronism and good response to surgery. 11 patients with primary aldosteronism have been encountered over 11 years and submitted to surgery in a provincial teaching hospital serving a population of 3 million. Contrary to classical teaching, the hypertension has usually been very severe. Precise identification of the site of the lesion preoperatively has been possible by the measurement of adrenal-vein aldosterone levels, and results of surgery have been excellent. The iodocholesterol adrenal scan also correctly identified the site of the adenoma in 5 out of 7 patients in which it was used. Adrenal venography was of little value except in siting catheters.


Increase in deaths from ischaemic heart-disease after blizzards. Death certificates in eastern Massachusetts after six blizzards in 1974--78, including the record blizzard of Feb. 6, 1978, were examined to identify the effect on mortality of these storms. The total number of deaths was significantly higher (8%) in a "blizzard week" than in the preceding and subsequent (control) weeks (114.1 vs. 105.3 deaths per day). Deaths from ischaemic heart-disease (I.H.D.), which rose significantly by 22% in the blizzard week from 36.7 to 44.6 deaths per day, accounted for 90% of the excess total deaths. The increase was greater in males than in females (30% vs. 12%), and in both sexes there was no difference in the distribution of deaths by age between the blizzard and control weeks. I.H.D. deaths were increased for 8 days after a snowstorm, suggesting that the effect was related to activities such as snow shovelling rather than the storm itself. The identification of those at increased risk of I.H.D. death after major snowstorms and of the circumstances surrounding such deaths could lead to public-health measures to reduce these weather-related premature deaths.


Symptomless diverticular disease and intake of dietary fibre. A study is reported in which the prevalence of symptomless diverticular disease of the colon is related to the consumption of dietary fibre in vegetarians and non-vegetarians. Vegetarians had a significantly higher mean fibre intake (41.5 g/day) than non-vegetarians (21.4 g/day). Diverticular disease was commoner in non-vegetarians (33%) than in vegetarians (12%). Comparison of subjects with and without diverticular disease in the vegetarian and non-vegetarian groups provided some further evidence that a low intake of cereal fibre is associated with the presence of diverticular disease.


Autologous bone-marrow transplantation in relapsed adult acute leukaemia. 24 cases of adult acute leukaemia, of which 21 were evaluable, were treated in irreversible relapse with high-dose piperazinedione and supralethal total-body irradiation (T.B.I.) in conjunction with autologous marrow transplantation (A.B.M.T.). The grafted marrow cells had been collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated on discontinuous albumin gradients in an attempt to separate normal cells from residual leukaemic cells. 11 patients achieved complete remission (C.R.); 7 other patients had signs of engraftment but died before C.R. The median remission duration was 4 months (2-14). 6 of 9 acute myeloblastic leukaemia patients, in whom bone-marrow transplantation was the first treatment of relapse, achieved C.R. 4 of 5 patients with acute lymphoblastic leukaemia, whose bone-marrow cells were collected during first remission, reached C.R. Autologous bone-marrow transplantation is a valuable first treatment for acute myeloblastic leukaemia in relapse and acute lymphoblastic leukaemia in second relapse.


Stimulation of prostacyclin release from vessel wall by Bay g 6575, an antithrombotic compound. Ingestion of 1.2 g Bay g 6575 daily for 1 week by six healthy volunteers had no effect on blood-coagulation, fibrinolysis, or platelet aggregation in vitro, but it seemed to inhibit platelet aggregation in vivo (shown by a smaller reduction in the platelet aggregate ratio after venous occlusion). Plasma drawn from five volunteers after ingestion of a single dose of 1.2 g of the drug stimulated prostacyclin release from slices of rat aorta which had been washed until they stopped releasing anti-aggregating substances, whereas plasma from the same individuals before ingestion of the substance did not. Administration of either Bay g 6575 or dipyridamole alone had no effect on platelet aggregation in vitro, but combined administration resulted in a striking and prolonged inhibition of A.D.P.-induced platelet aggregation. It is proposed that the previously described antithrombotic properties of Bay g 6575 in animals are due to stimulation of prostacyclin release from the vessel wall, and that this effect is also demonstrable in man.


Transmission of non-A non-B hepatitis to chimpanzees by factor-IX concentrates after fatal complications in patients with chronic liver disease. 6 cases of non-A non-B hepatitis which followed administration of four different batches of concentrates of coagulation factor IX from commercial and non-commercial sources are described. Of 17 patients who received the concentrate on account of chronic liver disease, 4 developed hepatitis, and in 3 of these the illness proved fatal. The incubation periods ranged from 42 to 103 days (mean 65 days). 3 chimpanzees were inoculated with concentrate from the same batch used on the above patients, a further commercial batch upon which no adverse reactions had been reported, and plasma from a known non-A non-B carrier. All developed hepatitis after 10 weeks' incubation. Liver biopsy when serum-aminotransferase was at its highest level showed features consistent with acute hepatitis. As in the patients, viral markers for hepatitis A and B, cytomegalovirus, and Epstein-Barr virus were unchanged.


Severe malaria and glucose-6-phosphate-dehydrogenase deficiency: a reappraisal of the malaria/G-6-P.D. hypothesis. Nigerian children with convulsions and Plasmodium falciparium parasitaemia above 100,000/microliter did not show a decreased frequency of glucose-6-phosphate-dehydrogenase (G.-6-P.D.) deficiency. A re-evaluation of earlier studies has led to the conclusion that clinical evidence of protection against falciparum malaria in G.-6-P.D.-deficient individuals is lacking. Evidence for the possible role of malaria in selecting for G.-6-P.D.-deficient genes consists solely of the geographical association of high frequencies of G.-6-P.D. deficiency with endemic malaria.


Epidural morphine in treatment of pain.

Epidural morphine in treatment of pain. Epidural injections of a 2 mg morphine were given to 10 patients with severe acute or chronic pain. All cases had considerable amelioration of pain, which commenced within 2-3 min, reached a peak in 10-15 min, and was effective for 6-24 h. It is suggested that the morphine reached the subarachnoid space and produced its effect by direct action on the specific opiate receptors in the substantia gelatinosa of the posterior-horn cells of the spinal cord.


Schizophrenia: Reconciliation of the dopamine, prostaglandin, and opioid concepts and the role of the pineal. In recent years it has been suggested that the biological defect in schizophrenia may be related to excess dopamine activity, to production of an abnormal opioid or a normal opioid in excess, to a prostaglandin deficiency, to a hypersensitivity to wheat proteins, to an allergic phenomenon, to a defect in zinc metabolism, or to a pineal deficiency. The present hypothesis proposes that the various concepts are not mutually exclusive but represent different aspects of the same problem. The final common path in schizophrenia may be a failure of formation and action of prostaglandins of the 1 series.


Decline of the hospital Staphylococcus? Incidence of multiresistant Staph. aureus in three Birmingham hospitals. The prevalance of antibiotic-resistant strains of Staphylococcus aureus was studied in three Birmingham hospitals. In a general hospital periodic surveys showed a progressive decline in the proportions of patients with Staph. aureus in their noses which were resistant to tetracycline, erythromycin, and kanamycin. This change was associated with a progressive reduction in the use of tetracycline without an overall reduction in the use of antibiotics. There was no similar decline in resistance of staphylococci isolated in a hospital for skin diseases. In a burns unit there was a sudden large reduction during September, 1978, in the proportions of Staph, aureus from burns which were resistant to tetracycline, methicillin, cephaloridine, erythromycin, lincomycin, novobiocin, gentamicin, and kanamycin, and in the proportions of multiresistant strains (resistant to penicillin, tetracycline, erythromycin, kanamycin, methicillin, novobiocin, cephaloridine, and lincomycin). This change was associated with a reduction in the number of patients and in the use of antibiotics; tetracycline was not in use except during one month of the study. Strains of Staph. aureus resistant to these antibiotics became common again in the burns unit when a larger number of patients were admitted and more antibiotics were used in the wards.


Is maintenance digoxin necessary in patients with sinus rhythm? Discontinuation of digoxin in 56 patients with sinus rhythm who had been taking it for a long time did not produce clinical deterioration in 33 of 34 patients whose pre-withdrawal steady-state plasma-digoxin concentration was less than 0.8 ng/ml; fast atrial fibrillation developed in the other patient. 22 patients had plasma-digoxin levels between 0.8 and 2.0 ng/ml before withdrawal--of these, 7 deteriorated without digoxin (5 had atrial fibrillation, which was associated with congestive heart-failure, measurement of the pre-injection period/left-ventricular ejection time (P.E.P./L.V.E.T.) ratio suggested that digoxin did exert a sustained positive inotropic effect. Thus, successful discontinuation of digoxin was possible in 86% of the total group and was more likely when the plasma-digoxin concentration was below 0.8 ng/ml. Unexpected atrial fibrillation was the commonest development inthe 8 patients in whom digoxin withdrawal was unsuccessful.


Bromocriptine associated with a peripheral dopamine blocking agent in treatment of Parkinson's disease. A peripheral dopaminergic blocking agent, domperidone (60 mg daily), or placebo was given, double-blind, to 17 parkinsonian patients who also received increasing doses of bromocriptine. Combined treatment with domperidone reduced total disability by 76% in 8 patients receiving a mean dose of 148 mg of bromocriptine daily. There was no vomiting and involuntary movements and psychic disturbances were similar to those in patients on levodopa and a peripheral decarboxylase inhibitor. In 9 patients taking placebo instead of domperidone, the average daily dose of bromocriptine could not be raised beyond 92 mg. The mean total disability score in this group was reduced by only 48%. Thus, peripheral blockade of dopamine receptors is a promising means of limiting the adverse side-effects of the treatment of parkinsonism with central dopaminergic receptor stimulating agents such as bromocriptine.


Prostaglandin E, pessaries for induction of labour. Vaginal pessaries containing 3 mg of prostaglandin E2 were used to induce labour in 200 patients with variable induction features. Prostaglandin-induced labour was augmented where necessary by synthetic oxytocin. There was on failed induction. Only 23% of patients with favourable induction features and 53% of patients with unfavourable features needed oxytocin. There were no adverse fetal or maternal effects. The prostaglandin E2 pessary was as effective in inducing labour as 350 microgram extra-amniotic prostaglandin E2 in tylose in a comparable group of 200 patients in which there were 4 failed inductions.


Heredopathia atactica polyneuritiformis (refsum's disease) treated by diet and plasma-exchange. A patient with severe heredopathia atactica polyneuritiformis (Refsum's disease) has responded well to treatment by large-volume plasma-exchange. The dietary control of the disease has been shown to depend not only on a diet low in phytanic acid, but also on one high in calories, which prevents mobilisation of phytanic acid from fat stores.


Evidence that Alzheimer neurofibrillary tangles originate from neurotubules. Antiserum against normal human neurotubules purified by in-vitro assembly precipitated both neurotubules and a polypeptide isolated from Alzheimer neurofibrillary tangles in Ouchterlony double-diffusion tests. The antiserum specifically labelled neurofibrillary tangles, in isolated neurons by immunofluorescence and in tissue sections by the peroxidase-antiperoxidase technique. These results indicate that neurofibrillary tangles in Alzheimer's disease probably originate from neurotubules.