[Use of a titrated extract of Centella asiatica in chronic hepatic disorders (author's transl)]. The authors report their preliminary results of a study of the possible therapeutic activity of a titrated extract of Centella asiatica in chronic hepatic disorders. Early results are encouraging, especially from a histological point of view, where improvement in the criteria evaluated was noted in 5 of the 12 patients treated for the longest time. These results have to be assessed in a critical manner until confirmation is obtained by complementary studies.


[About the different steps leading to the quality of medical information (importance of medical computing) (author's transl)]. To draw the best conclusions from a set of medical data, one must first choose correct, valid, representative and well-expressed information. So it's not sufficient to collect data, but we have to valid them before including them in the records. After having put out the general characteristics of any validation and defined the fields where they can be applied we recommend a method over three steps. First, the physician alone, then the physician with an informatician and again the physician seem concerned by the steps of control. It is particularly important to develop the validation of chronology and generally speaking of evolutive data. Of course, the costs of validation with respect to the large groups of data must be taken into account.


[Headaches and cervicarthrosis : arthrosis, vascular or psychic origin? (author's transl)]. Cervicarthrosis is an extremely frequent disease yet often appears as asymptomatic. It can however give birth to varied clinical manifestations, for which it can be held responsible together with other factors : inflammatory as in cervico-brachial neuralgia, vascular as in cervicarthrosis medullopathy, psychological as in posterior cervicalgia and headaches belonging to the classical Barré-Liéou syndrom. We must stress the therapeutic interest of tiapride, which acts on the algic element as well as on the element of psychological tension in the last case.


Objective evaluation and prediction of client improvement in mental health aftercare. External funding sources and review boards appropriately are mandating more objective, clear-cut demonstrations of mental health program effectiveness. Mental health adult aftercare programs, traditionally characterized by globally-defined, imprecise goal and outcome measurement, can be objectively, empirically evaluated. The current paper illustrates how structured ratings and observations can be used feasibly to yield quantified "hard data" on client improvement and program effectiveness. The paper also presents the results of a program evaluation research study which indicate that while psychosocial history variables predict initial client appearance in aftercare, program participation-involvement behavior (and not psychosocial history) predict client improvement. Implications of these finds and the need for objective approaches to aftercare program evaluation are discussed.


Family care for the mentally ill: a new perspective. Family care has been a subject of controversy since large numbers of discharged psychiatric patients have been placed in these homes. The debate has centered on whether such community facilities offer a meaningful alternative in caring for the mentally ill. Findings of a study dealing with the quality of care in the homes and factors deemed responsible for these conditions provide a new perspective on the dilemma.


Right-to-left atrial shunt in cardiac dislocation following extensive pneumonectomy. Previous reports dealing with cardiac herniation following intrapericardial pneumonectomy illustrate the critical and often lethal hemodynamic sequelae of this complication. In the case presented here, the first and nearly exclusive sign of cardiac herniation after left-sided pneumonectomy with extensive resection of the pericardium was systemic arterial hypoxemia. Subsequent investigations suggested inter-atrial right-to-left shunt in the presence of a patent foramen ovale, caused by slight right-ventricular outflow obstruction with consecutively reversed pressure relationships at atrial level. This explanation was supported by the operative findings, and reversibility was achieved by pericardial reconstruction with parietal pleura. When the patient died 8 months later due to general progression of a mucoepidermoid carcinoma, autopsy confirmed a large patent foramen ovale.


HLA-D typing with lymphoblastoid cell lines. VI. Rationale and goals of data reduction. This report documents various characteristics of HLA-D typing by mixed leukocyte culture reactions when lymphoblastoid cell lines (LCLs) are substituted for peripheral blood lymphocytes as the stimulator cells. It also provides the rationale for designing the computer program described in the subsequent report. In such experiments, each donor to be HLA-D typed is stimulated with a panel of 30-50 HLA-D homozygous LCLs, each defined HLA-D allele being represented by several different human homogygous typing cells (LCT-HTCs). Variability in the strength of eahc donor's general response and in the strength of stimulation by each LCL-HTC makes it necessary to normalize raw data before the responses of various combinations can be compared and typing responses distinguished from non-typing responses. The autologous response and its equivalent effect among allogenetic combinations, the so-called "autologous-stimulation" effect, must also be distinguished from true allogeneic responses. The latter has been accomplished by "modelling," as described in the subsequent report. EBV-negative donors can also be HLA-D typed by this method despite the EBV-positivity of the LCL-HTCs. Preliminary analyses suggest that the HLA-D alleles defined by this method appear to segregate with appropriate haplotypes in family studies.


Regional specialization in the Malpighian tubules of the New Zealand glow-worm Arachnocampa luminosa (Diptera: mycetophilidae). The structure and function of type I and II cells. The Malpighian tubules of the glow-worm Arachnocampa luminosa are divided into four morphologically distinct regions (Parts 1--4) each comprised of a different cell type (Types I--IV). The ultrastructure of Type II cells is indicative of a transport function. The basal cell surface is highly invaginated and at the apical surface the lumen is lined with microvilli about 80% of which contain mitochondria. Spherites contained in these cells are formed from small vesicles produced by the Golgi apparatus. They have a central uric acid core enclosed by laminations of phosphates of calcium and magnesium. Cells of Part 2 of the tubule secrete a fluid high in potassium (173 mM) and low in sodium (18 mM). The cell is 30 mV negative and the lumen 44 mV positive to the bathing solution. This is consistent with the proposal of an apical cation pump. The secretion produced by Part 2 of the tubules is modified by the Type I cells by the reabsorption of potassium (162 mM) and the addition of sodium (24 mM) to the primary excretory fluid. Type I cells are 20 mV negative and the lumen 22 mV positive with respect to the bathing medium. From ultrastructural observations, Type I cells exhibit features characteristic of transporting cells thought to have an absorptive function. The basal and apical cell surfaces are extensively folded, and mitochondria are found in bands above the basal infoldings and below the microvilli. Mitochondria do not penetrate the microvilli. On comparative grounds, the fine structure of Type I cells suggest that they reabsorb ions from the tubule lumen. Energy for these processes may come from the breakdown of lipids by microperoxisomes contained within these cells. Alternatively, the fluid produced by Part 2 of the tubule may be modified passively by diffusional processes across Type I cells.


Ultrastructural observations on the erythrocytes and thrombocytes of the tuatara, Sphenodon punctatus (Gray). The erythrocytes of Sphenodon punctatus (Gray) are nucleated, ellipsoidal and flattened, and contain 55--65 microtubules in their marginal band. The thrombocytes are also flattened, ellipsoidal, nucleated cells and in electron-microscopic preparations occurred in aggregrates. The thrombocytes appeared to be 'activated' and possessed many pseudopodia which were devoid of organelles. The latter were concentrated in the perinuclear region and were encircled by a ring of microtubules. The organelles included ribosomes, mitochondria, membrane--bound dense material and numerous actin-like microfilaments. Cytoplasmic vacuoles contained a moderately dense, filamentous material and/or spheroidal electron-dense inclusions, beta-glycogen particles were scattered in the general cytoplasm and were most concentrated in the pseudopodia. The erythrocytes and thrombocytes of S. punctatus are compared with those in other vertebrates.


A scanning electron microscopic study on hepatic changes induced by mouse hepatitis virus-2. No significant changes in the structure of the liver were seen until 9 hr after the inoculation of mouse hepatitis virus-2 (MHV-2) into mice. At the 24 hr stage, distinct swelling of hepatocytes and narrowing of sinusoidal lumina were observed from the middle to the central area of the hepatic lobules. Most of the Kupffer cells were swollen. Their villous projections were decreased in number, and the remaining projections became like blebs. Virus particles appeared from this stage in the hepatocytes, the Kupffer cells and the space of Disse. At the 48 hr stage, parenchymal necrotic foci were present in the central and the middle area of the lobules. The necrotic change was increased from 72 hr after inoculation, and was followed by submassive or massive necrosis. It is suggested that hepatic necrosis in both the central and the middle area, or in either area, of the lobules was advanced by aggravation of the sinusoidal microcirculation, as a result of the swelling of the hepatocytes and the Kupffer cells in addition to the direct affection by virus. Fine granulation was observed on the surface of most of the central flagella of the bile duct. Some flagella were degenerated, and came in part to be a fibrillar net.


Studies on the tissue-disposition and fate of N-[14C]ethyl-N-nitrosourea in mice. The tissue-disposition and fate of N-[14C]ethyl-N-nitrosourea has been studied in mice. A large part of the injected N-[14C]ethyl-N-nitrosourea radioactivity was found to be exhaled as 14CO2. Whole-body autoradiography showed evenly distributed radioactivity in most tissues shortly after the administration of N-[14C]ethyl-N-nitrosourea which probably is due to the homogeneously distributed substance and the non-enzymatically formed ethyl-carbonium ions which have reacted with the tissues. The blood-brain barrier seemed to have a capacity to partially prevent the uptake of the substance in the central nervous system. A high radioactivity was observed in the liver, which may imply that N-[14C]ethyl-N-nitrosourea is enzymatically decomposed in this tissue. An observed labelling of kidneys may be connected with urinary excretion of radioactivity. The radioactivity in the liver and kidney decreased at later survival intervals and a distribution pattern appeared, which was characterized by a labelling of tissues with a high protein or steroid synthesis and of fat containing tissues. The distribution pattern corresponded to the one seen after the administration of [14C]acetaldehyde and is probably due to normal biosynthetic incorporation of radioactivity in the 2-carbon pool. Pretreatments with pyrazole, nialamide and diethyldithiocarbamate caused a marked inhibition of the exhalation of 14CO2 and of the incorporation of radioactivity in the liver. This effect may be directed towards the decomposition of N-[14C]ethyl-N-nitrosourea itself, but an effect on the metabolism of formed 2-carbon fragments is also possible. The incorporation of radioactivity in other tissues was not influenced by the pretreatments.


Effect of phenobarbital on cerebral energy state and metabolism. Enzymatic activities. The changes induced by phenobarbital in cerebral enzymatic activities of the Krebs' cycle (citrate synthase, malate dehydrogenase) and electron transfer chain (total NADH-cytochrome c reductase and cytochrome oxidase) were studied. In addition, the activity of lactate dehydrogenase of acetylcholine esterase and of glutamate dehydrogenase was also studied. These enzymatic activities were evaluated in the homogenate in toto and in a crude mitochondrial fraction from rat brain. The modifications in some of these activities indicate that several new metabolic situations occur in brain tissue after phenobarbital treatment.


Local versus regional procurement and distribution of granulocytes. Granulocyte concentrates obtained by discontinuous flow centrifugation (DFC) and continuous flow centrifugation (CFC) were studied. The DFC granulocytes were obtained from a regional center and stored for 24 hours prior to transfusion. The CFC granulocytes were obtained locally and transfused within a few hours. Even at 24 hours, DFC granulocytes had significantly reduced bactericidal capacity, chemiluminescence, nitroblue tetrazolium reduction, chemotaxis and random mobility. Granulocyte kinetics utilizing DF32P and skin windows demonstrated the ability of DFC granulocytes to circulate and migrate into the tissues despite the in vitro abnormalities. Until effective storage techniques for granulocyte preservation became available, rapid transportation and processing from regional centers or local procurement of granulocytes is necessary to transfuse functional granulocytes.


Single-tissue modeling of decompression schedules. This paper deals with the development of a single-tissue model that simulates the uptake and elimination of inert gases by the body of a diver. The model utilizes an effective single tissue with different uptake and elimination time constants to account for the asymmetrical behavior of multiple-tissue human body models. The parameters of this effective tissue are selected according to an optimal strategy that minimizes safe deviation from the decompression requirements recommended by safe practice. The developed strategy is general in nature and can be readily applied to select the optimal parameters for a single-tissue model suitable for any dive regimen on air or mixed gas. As an illustration, the procedure is used to select the optimal tissue that best fits the Standard Air Decompression Tables recommended by the U.S. Navy. The results obtained are in close and safe agreement with the requirements of the U.S. Navy, and consistently fall in the range between the U.S. Navy and the Royal Navy tables.


Studies of donors who transmit posttransfusion hepatitis. Sera and questionnaires were evaluated retrospectively from 128 volunteer blood donors whose blood had been implicated in cases of clinically recognized post-transfusion hepatitis in recipients of one- or two-unit blood transfusion between 1971 and 1977. Serologic markers of hepatitis B virus (HBV) infection were found in 23 percent, compared to 9.7 percent of 3,230 prospective blood donors. The prevalence of antibody to hepatitis A virus was similar among implicated donors (44%), prospective donors (58%), and among those implicated donors with (41%) and without (44%) HBV markers. Among implicated donors, none had a history at the time of donation of having had clinically recognizable hepatitis, 93 percent had no history of prior blood transfusion, and 80 percent had normal hepatic enzymes. Data from this study confirm that non-A, non-B hepatitis has been a common form of posttransfusion hepatitis in recent years, since 77 percent of these implicated donors had no HBV serologic markers. In addition, these donors could not be distinguished by age, race, sex, history of clinical hepatitis or of prior blood transfusion, or in most cases by hepatic enzyme levels.


Clinical results on the use of human ceruloplasmin in aplastic anemia. Frequent blood transfusions are necessary in aplastic anemia because of decreased hematopoietic function. In order to maintain the hemoglobin level and to decrease the need for blood transfusion, human ceruloplasmin was used for the treatment of 73 patients with aplastic anemia. A marked beneficial effect was obtained in 16 cases. The treatment was moderately effective in 17 cases, slightly effective in eight cases, and ineffective in 32 cases. The usual dose of ceruloplasmin was 15 mg/day, but it was varied according to symptoms. Side effects were minimal when ceruloplasmin was administered by slow intravenous injection.


[Electrophoretic determination of lipoproteins in the blood of dogs after the administration of beta,beta'-dichlorodiethylsulfide]. The effect of a single administration of beta,beta'-dichlorodiethylsulphide at a dose of 35 mg per kg b. w. was studied, as exerted on the level of serum lipoproteins. The blood of experimental dogs showed a significant rise of alpha 3 lipoproteins, reaching its maximum 24 hours after the administration of the substance. During the studied period, the alpha-fraction lipoprotein gradually shifted to the beta-fraction terminating before the exitus.


Detection of hepatitis B surface antigen in fixed tissues of patients with cirrhosis and hepatoma. HBsAg has been sought by light microscopy in liver specimens from patients with cirrhosis (79 cases) and hepatoma (99 cases). The study was carried out on fixed material using orcein staining, immunoperoxidase technique and indirect immunofluorescence. HBsAg was detected in the serum by radio-immunoassay (RIA) using Ausria II-125 in 38 patients with cirrhosis and in 36 with hepatoma. In the 38 seropositive cases of cirrhosis HBsAg-positive cells were observed in 31 (81.6%) by the orcein staining and in 32 (84.2%) by the peroxidase and immunofluorescence staining. Among the 36 seropositive patients with hepatoma, HBsAg was detected in the surrounding non-neoplastic part of the liver, cirrhotic or not, in 30 (83.3%) by orcein staining and in 34 (94.4%) by the immunoperoxidase method and immunofluorescence. Positive solitary-cells were seen occasionally in the tumor tissue in 16 cases using orcein, in 9 using peroxidase and in 7 by fluorescence, out of the 36 seropositive patients with hepatoma. The results of this study do not support the hypothesis of a direct oncogenic effect of HBsAg on the liver cells, since this antigen was detected mainly in the non-neoplastic part of the liver tissue and only occasionally in the tumor cells. Of the 63 cases of seronegative hepatoma, 3 showed some round orcein-positive inclusion bodies in the cytoplasm of the neoplastic and the non-neoplastic cells; these bodies were not stained by the two immunological methods.


Epstein-Barr virus infection in polytransfused patients with homozygous beta-thalassaemia. The frequency of Epstein-Barr virus (EBV) and hepatitis B virus (HBV) infection has been studied in 149 polytransfused thalassaemic patients and in healthy controls. Evidence for EBV infection was based on the detection of antibodies to viral capsid antigen (anti-VCA) and for HBV infection on the detection of either hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs). The frequency of anti-VCA was not significantly higher in the patients (16.4%) compared to the controls (69.8%) whereas HBV infection was more frequently observed in the patients (91.3%) than in the controls (17.3%). There was also no evidence of repeated infection or recent infection with EBV in the polytransfused patients. These data suggest that transfusion of stored blood does not represent a significant factor of spread for EBV.


Some results obtained in the "Stefan S. Nicolau" Institute of Virology by the study of herpes simplex virus. The results obtained in the "Stefan S. Nicolau" Institute of Virology by the study of herpes simplex virus (HSV) are reviewed. The investigations were mainly focused on HSV biology, genetic markers, experimental HSV infection, correlation between HSV and some diseases, action of some chemical and biological preparations on HSV, in vitro and in vivo HSV oncogenicity, HSV-induced surface antigens, a.o.


Results in the study of virus--tumor relationships obtained in the "Stefan S. Nicolau" Institute of Virology. The results of over 200 scientific papers in the field of in vivo and in vitro virus--tumor relationships, worked out in the "Stefan S. Nicolau" Institute of Virology during a period of over 25 years, are very briefly reviewed. Stress is laid on the original theoretical and practical contributions of the institute to the knowledge of viral carcinogenesis in animals and humans. Some personal viewpoints in the interpretation of results are presented and new research prospects in this field--which represents a traditional concern of the institute--are lutlined.


[Physicochemical properties of the Teschen disease virus]. The physical stability of Teschen disease virus (TDV) was tested. It was found that 8 M urea at 37 degrees C and 0.5% Tween-20 for 1-2 hours destroyed TDV with formation of morphologically distinct subunits. The morphology of TDV virions and its subunits formed under the effect of urea and Tween-20 was studied. Sedimentation constant (120 S) and the polypeptide composition of TDV were determined. In TDV, major polypeptides (VP1 less than or equal to 4) and minor polypeptides (VP1m and VP2m) were found their molecular weights being 82,000, 67,000, 35,000, 30,000, 77,000, and 46,000 daltons respectively.


[Etiological role of the herpes simplex virus in causing cervical cancer]. The results of the composite virological and immunological examinations of 46 patients with cervical carcinoma (CC) attest to the association of herpes simplex virus (HSV) with neoplastic processes. HSV strains were isolated from the tumour tissue as well as from the cervical canal secretions and blood of 4 patients. A higher level of virus-neutralizing and complement-fixing antibodies to HSV was found in sera from CC patients as compared with the control group of normal women. Antibody to HSV type 2 was found in 38.8% of sera from the patients and 12.6% in the control group. Lymphocytes from CC patients induced blasttransformation reaction to HSV twice as frequently as those from healthy subjects. The virus-specific antigen was found in tumour cells of 36% CC patients in immunofluorescent examinations of smears from the cervix. The presented results are related to the determination of the etiological role of HSV in cervical carcinoma.


[Scintigraphic study of the sacroiliac joints]. Scintigraphic and radiometric investigation with 99mTc-pyrophosphate was carried out on the sacro-iliac joints of 79 patients: 48 with positive form of Behterev disease, 26 -- with probable form of the disease, 2 -- with Reiter syndrome and 2 -- with rheumatoid arthritis. Scintigraphy was combined with radiometric investigation (determination of sacro-iliac -- sacral index) with a view to obtaining quantitative information about the degree of accumulation of pyrophosphate in sacro-iliac joints. The data from the scintigraphic and radiometric investigations were juxaposed to clinical laboratory and X-ray investigations. Forty of the patients examined were HLA-B27 positive and 38 of them-HLA-B27 negative. Sacro-iliac index, determined in 13 healthy subjects (26 sacro-iliac joints) was within the limits of 1.18 +/- 0.094. The average value of the index of the 78 patients examined was 1.41 +/- 0.20. The index, during the first and second X-ray stage was 1.43 +/- 0.13 and 1.45 +/- 0.19 resp. The values decreased to 1.39 +/- 0.18 during the third X-ray stage, whereas in the fourth stage with completely ankylosis of the joints, the index was 1.20 +/- 0.07, being close to that of the control group of healthy subjects.


REM sleep, stress and search activity. A short critical review and a new conception. Basing themselves on an analysis of data cited by other researchers and the results of their own investigation, conducted on man and animals, the authors disclose that sleep changes are determined by the type of behavioural reaction to emotional stress: the behaviour that includes components of search activity directed at changing the situation is accompanied by a reduction of REM sleep time; renunciation of search, as in the cases of passive avoidance, neurotic anxiety and depression, is attended by an increase in REM sleep requirement. Presumably, the function of REM sleep is to compensate for renunciation of search in the waking period. The authors suggest a method of appraising the character of reaction to stress by sleep changes--calculation of the time ratio of REM sleep to delta-sleep in the first two cycles.


Maturation of REM-patterns from childhood to maturity. The operational value of measuring paradoxical sleep (PS) as a percentage of total sleeping time has been questioned. The purpose of this study was to determine the interactions between the variations in hormonal secretions and paradoxical sleep in women of different age-groups. Three parameters were utilized: REM-percent, REM-density and the eye movement frequencies. The distribution of the time-intervals between the oculomotor signals as indicated by the ratio of the higher to the lower eye movement frequencies gives a clue as to the significance of the spatio-temporal organization of the brain-signals during paradoxical sleep. This notion introduces an internal temporal and dynamic dimension in the concept of REM or Paradoxical Sleep. From our results it appears that the changes in the ratio between the different types of oculomotor discharges are a function not only of hormonal fluctuations but also of age. This point of view opens a new possibility of interpreting the results.


[Design of inactivated polyvalent antiherpes vaccines]. The variants of inactivated vaccine against herpes simplex virus have been developed: 1, 2 and 1 + 2. The first two variants consist of 5 different strains of herpes virus of the appropriate type, and the third variant of their mixture. The strains differ in their antigenic and biological characteristics. Complete inactivation of the virus suspension was achieved by treatment of the vaccine with formalin. Herpes vaccines were used for immunization of 477 patients with frequently relapsing forms of herpes of different localizations. The therapeutic-prophylactic effect of these vaccines indicates their relatively high efficacy: by the end of 9 months favourable results exceeded 95%. Better results were obtained with HSV-1 vaccine. A second cycle of immunization given to some patients resulted in markedly positive effect.


[Viral interaction with stimulated and nonstimulated human tonsil cells]. Interferon induction and the course of infection with paramyxovirus (Newcastle disease virus) and alphaviruses (Venezuelan equine encephalomyelitis, Sindbis, Semliki forest viruses) in human tonsillar cell cultures were studied in comparison with continuous Burkitt lymphoma, Raji, and Nawalva cells. The virus inducers stimulated production of dozens and hundreds IU50/ml of interferon in tonsillar cell cultures. No virus replication could be detected either in intact or phytohemagglutinin-stimulated tonsillar cells. Phytohemagglutinin treatment may lead to blocking of interferon production induced by Newcastle disease virus.


Influence of arginine vasotocin administration on nocturnal sleep of human subjects. Arginine vasotocin (AVT) or placebo were subcutaneously administered to 4 men at 22.00 and 01.00 h, along four nights, and polygraphic recordings were performed between 22.00 and 02.00 h during sleep. AVT significantly increased only the amount of rapid eye movement (REM) sleep (p less than 0.05), but did not influence the latency of the first REM sleep period. This effect of AVT was not dose dependent in the range between 2 and 12 microgram AVT. AVT or placebo were also intravenously injected or perfused to 10 normal adult subjects, at different times of the day, under clinical control. Doses between 2 microgram perfused 4 h and 12 microgram perfused 30 min, did not produce clinical signs of sleep. It is suggested that AVT is not a blood factor for inducing of slow waves sleep (SWS) or REM sleep in humans.


[Study of sensitivity using sinusoidally modulated currents]. A quantitative examination of sensitivity with using modulated sinosoidal currents was carried out in 10 healthy individuals and 44 patients with various disorders of the central and peripheral nervous system. In the healthy probands the magnitudes of the current force causing the specific sensation under the electrodes in various body regions were determined. A substantial, statistically significant rise of the current perception threshold was revealed in patients with superficial sensitivity disturbances. In patients with deep sensitivity disturbances both quantitative and qualitative distinctions were discovered.


[Zinc activated tartrate resistent phosphatases in the brains of different animal species and their characterization]. A zinc activated tartrate resistent phosphatase (ZnTP) of the brain of different animal species was separated by electrofocusing in polyacrylamide gels. It is demonstrable selectively in the presence of 20 mM zinc acetate and 10 mM D,L-sodium tartrate or of 100 mM zinc acetate only. The ZnTP hydrolyzes 1-naphthyl phosphate and 4-nitrophenyl phosphate, respectively. High activity of ZnTP is evident in the brains of rats and rabbits. The activity is moderate or absent in the brains of mice, syrian-hamsters, sheeps, cats, rhesus monkeys, and of human beings. The isoelectric points of the enzyme from the various species are different, but the molecular weight is identical (65 000 estimated by gelfiltration on Sephadex G 100 in the brain of rat, rabbit, syrian-hamster, and man). A method of quantitative evaluation of ZnTP activity is described.


Further characterization of the polyoma virus Y8e from a Rauscher leukaemia virus producing mouse cell line and detection of partial sequence homology between polyoma virus Y8eDNA and hamster papovavirus DNA. A DNA virus of the papovavirus group spontaneously appeared in RLV-infected spleen and thymus cells of mice in vitro was further characterized as polyoma virus Y8e by haemagglutination test, banding in density gradients, sedimentation coefficients of DNA and molecular hybridization of its DNA. The latter technique showed nearly complete sequence homology to polyoma virus strain SE DNA, partial sequence homology to hamster papovavirus DNA and mouse host DNA and little or no sequence homology to SV 40 DNA. The relationship between rodent papovaviruses and primate papovaviruses is discussed.


Synthesis of spontaneous interferon by mouse peritoneal cells in vitro. I. Attempts to elucidate the origin of spontaneous interferon. Interferon-like substance has been obtained in the media of mice 129/AoBoy peritoneal cell cultures after incubation at 26 degrees C. The substance showed characteristics that permitted it to be accepted as an interferon. Looking for the presence (in the media or in the sera) of infectious agents responsible for this event experiments were performed that excluded this possibility. Peritoneal cells cultures in media without calf sera (MEM, PBS) produced spontaneous interferon, too. In the same medium the peritoneal cells from various mouse strains differed in the capacity to spontaneous interferon formation. Finally it was found that the level of this interferon was raised with the age of mice.


[Extension of pituitary adenomas into the cavernous sinuses (clinico-anatomic study)]. The article deals with the study of 288 verified cases with adenomas of the pituitary gland. Growth of the tumor into the cavernous sinus was revealed in 102 cases (35.4%). The possible routes of penetration of pituitary tumours into the cavernous sinus and the relationship of the new growths with the intracavernous structures are described in detail. The findings of purposeful radio-diagnostic examination revealing the characteristic combinations of the symptoms of intracavernous expansion of the tumor are of paramount importance in recognizing growth of pituitary adenomas into the cavernous sinuses. It is emphasized that the possibility of such growth must be borne in mind when the operation is planned.


Production of antiviral and migration inhibitory activities in the peritoneum of mice after inoculation with allogenic Ehrlich ascites tumor cells. Peritoneal inoculation of Ehrlich ascites cells into mice stimulates the appearance of migration inhibitory factor (MIF) not only in the peritoneum but also in the circulation of mice. Whereas the MIF-activity in the peritoneum reached maximum at 6 days and disappeared within 17 days, the MIF-activity of sera reached maximum levels at about 11 days after intraperitoneal inoculation of tumor cells (10(6) of EAC per mouse). In addition, an antiviral activity of peritoneal exudates was observed in the early stage (24--72 h) of tumor challenge. The time-course of appearance of both MIF and AV-inhibitor are presented. A significant decrease of MIF-activity was noted when the tumor-inoculated mice were treated with ds-RNA, antithymocyte serum and cyclophosphamide, respectively. The appearance of antiviral activity in the peritoneum of tumor-inoculated mice seems to be macrophage-dependent. Although the antiviral factor meets several criteria of interferons, further studies are required for its characterization.


Production of human leukocyte interferon for clinical use under immunoelectrophoretic control. Human leukocyte interferon (HLIF) can be contaminated by several antigens which may include also potentially pathogenic agents. For this reason, gel filtration as a separation method was included into the routine procedure of preparation and purification of HLIF for clinical use. Since production of HLIF requires the cultivation of leukocytes in the presence of serum (or albumin), serum proteins represent then the majority of proteins contaminating IF preparations. Measuring the total protein content, as a control of various antigens present in HLIF preparations during purification, becomes ineffective because, essentially, it indicates only the decrease of the amount of proteins derived from cultivation medium. For a better visualization of dissociation of different antigens from molecules with IF activity during the purification procedure, the method of quantitative immunoelectrophoresis was applied utilizing a sheep antiinterferon serum in assay. Our results indicate that this method represents a valuable control test.


Antiviral and anticellular effects of interferon on the mouse embryonic cells transformed by viruses and/or chemical carcinogen. The antiviral and anticellular activity of partially purified mouse interferon has been tested in cell lines transformed with Simian Virus 40 (MEB-SV 40), mouse sarcoma virus (Harvey strain) (MEB-MSV), and 20-methylcholanthrene (MEB-MCH), respectively. The transformed lines were derived from C3H mouse embryonic primary cells. It has been shown that the MEB-MSV cells were 10 to 50 times less sensitive to the antiviral effect of interferon than the MEB-SV 40 or MEB-MCH cells. A 30% reduction of the number of treated cells as compared with untreated control cells was taken as basis for comparison of anticellular activity of interferon in transformed lines. While the MEB-MCH cells required 1000 units of interferon for a 30% growth inhibition, about 3000 units were necessary for a comparable suppression of MEB-SV 40 cells and/or MEB-MSV cells.


The effect of interferon induction on complement level in rat. Relatively high levels of interferon were achieved in rat sera by intracardial inoculation with Sindbis virus followed 15 min later by intraperitoneal application of dimethylsulfoxide. At intervals when interferon titres reached the maximum, the levels of complement were decreased as compared with the control group of rats. Single administration of dimethylsulfoxide did neither induce interferon nor influence the complement levels in sera of rats of the Dobrá Voda breed tested. Similar results were obtained with concentrated Newcastle disease virus inoculated intraperitoneally. Of interest is the finding that properdin levels seem to increase at the same time as interferon.


Secondary malignant tumors accompanied by primary hepatocellular carcinoma. The occurrence of liver cirrhosis and PHC cases were analyzed from the autopsy material of three hospitals. In the course of this work 13,369 autopsy reports were examined. In 339 cases liver cirrhosis was established, the frequency of association with PHC was 19.4% (66 cases). Out of 66 PHC cases 17 (25.6%) were associated with a secondary malignant tumor. This number is 10 times greater than that of other tumors of epithelial origin. It also exceeds the enlarged number of linked secondary tumors as shown in the case of certain lymphoproliferative diseases.


Cytodiagnosis of viral infections in body cavity fluids. Pleural and pericardial fluid specimens have been studied in seven patients with diagnosis of viral infection. Intranuclear inclusions, multinucleated giant cells with gelatinous nuclear changes and atypical mesothelial cells were observed. These observations suggest that viral involvement of the mesothelium produces cellular changes which can be detected cytologically in routine Papanicolaou-stained body cavity fluid specimens.


Acid secretion and mucosal cyclic nucleotide content of the guinea pig isolated stomach during bethanechol stimulation. Acid secretion and mucosal cyclic AMP and cyclic GMP content of guinea pig isolated stomach preparations were measured at various times after stimulation with bethanechol (1.7 X 10(-5) M). Significant increases in acid secretion were observed without changes in cyclic nucleotides. Pre-incubation of the tissues with theophylline (10(-3) M) increased acid secretion and nucleotide content. An additional increase in acid secretion was then obtained with bethanechol in these tissues but without further change in nucleotides. Carbachol (30 micrograms/kg) administered by interperitoneal injection to conscious guinea pigs also failed to change gastric mucosal cyclic nucleotides when the animals were sacrificed 15 min later. These results are discussed in relation to the mechanisms of cholinergic stimulation of gastric acid secretion.


Cytomorphology of carcinoid tumors.

Cytomorphology of carcinoid tumors. This report is based on a review and study of carcinoid tumors as seen in smears prepared from exfoliative or aspiration smears. During a period of eight years (1970 to 1978), 236 cytologic specimens were examined from 64 patients treated for carcinoid tumors at Memorial Hospital. Thirty-eight cytologic specimens from 18 patients were interpreted as either suspicious or positive for malignant cells. Tumor cells were identified most often in tracheobronchial specimens, effusions and percutaneous aspirates. A striking similarity in cell morphology was found between exfoliated and aspirated tumor cells. Certain specific or suggestive cytologic features were recognized. The histogenesis of carcinoids and the role of intracytoplasmic neurosecretory granules in the differential diagnosis is discussed together with the clinicopathologic implication of positive cytologic findings.


The energy systems of gastric tissues, their neural, hormonal and pharmacological regulations in order to gastric H+ secretion and ulcerogenesis. (A review of animal experiments and clinical biochemical studies). In studies conducted over the last 10 years, the ATP, ADP, AMP concentrations, the adenylate pool (ATP + ADP + AMP), the "energy charge" and the cAMP levels were determined:(1) in gastric tissues of pylorus-ligated rats, (2) in gastric and duodenal mucosa and muscular layer (musculature) of human subjects qualified as "hypacid", "normacid" and "hyperacid" on the basis of basal (BAO) and maximal acid output (MAO), (3) in ulcer-bearing and non-ulcerous antral, duodenal and jejunal mucosa and muscular layer of patients with peptic ulcer, including chronic (essential) antral, duodenal ulcer and jejunal ulcer following gastric resection of Billroth II-type. Close analysis of the results centres on: (1) the biochemical background of gastric hypersecretion and of ulcerogenesis in pylorus-ligated rats;(2) the extra- and intracellular feedback system operating between the gastric membrane ATPase and adenylate cyclase systems, under normal and abnormal conditions of the effector organ; (3) questions related to the regulatory mechanisms of functional activity of the effector organ under drug effect; (4) the energy structure of the mucosa and muscular layer of corpus ventriculi, antrum and duodenum in patients considered "hypacid", "normacid" and "hyperacid" on the grounds of the BAO and MAO values; (5) the interrelationships between human gastric H+--K+-dependent ATPase system of gastric corpus mucosa; (6) pharmacological regulation of the ATP--ADcer-free mucosa and musculature of patients with antral, duodenal and jejunal ulcers.


Optic neuritis: local synthesis in the central nervous system of oligoclonal antibodies to measles, mumps, rubella, and herpes simplex viruses. Antibodies to measles, mumps, rubella and herpes simplex type 1 viruses in serum and CSF of 10 patients with acute monosymptomatic optic neuritis were characterized by imprint electro-immunofixation (IEIF). Comparisons of the IEIF antibody patterns in serum and CSF indicated that a local synthesis in the central nervous system of oligoclonal virus antibodies took place in five of the 10 patients. Three of the five patients had a local synthesis of antibody to more than one type of virus. Oligoclonal IgG was detected by agarose electrophoresis of the CSF in four of the five patients with a local synthesis of virus antibodies. There was, however, no association between the locally synthesized antibodies and the oligoclonal CSF IgG, indicating that they account for only a minor fraction of the locally synthesized IgG in these patients. In the fifth patient, distinct fractions of locally synthesized virus-specific oligoclonal Ig were detected by the IEIF method, although the agarose electrophoresis showed a normal pattern of CSF IgG.


Electron microscopy of fine needle aspiration biopsy from a malignant fibrous histiocytoma. Report of a case. A case is reported in which electron microscopy was utilized to make a preoperative differential diagnosis of a soft tissue sarcoma on material obtained by fine-needle aspiration biopsy. The value of electron microscopy as an adjunct to cytologic study of such material is pointed out, as is the suitability of aspirated material for electron microscopic examination.


Selective immunodeficiency and malignant lymphoma of the central nervous system. Possible relationship to the Epstein-Barr virus. This report presents the findings of a study of a 17-year-old male with a selective immunodeficiency to the Epstein-Barr virus, who died of a malignant lymphoma following clinical infectious mononucleosis. Autopsy findings and immunohistochemical techniques demonstrated a malignant lymphoma with B-lymphocyte characteristics which primarily involved the central nervous system (CNS). The relationship of the Epstein-Barr virus to lymphoproliferation is discussed.


Tumorigenic clones of hamster brain cells transformed in vitro by polyoma virus. Ultrastructural and immunohistochemical study. The morphological characteristics of three clones of hamster brain cells transformed in vitro by polyoma virus and of the tumors obtained after subcutaneous grafting of these cells in syngenic animals are reported. These clones appeared to be glial in nature by light and electron microscopy. The initial tumors induced by the three clones presented astrocytic features both by electron microscopy and immunohistochemistry. Analysis of the subsequent in vivo passages showed a decrease in cell differentiation, which was accompanied by a decrease in the latency period; after 2 years of serial transplantation, the tumors seemed poorly differentiated gliomas. A control cell line of hamster cerebellar cells evolved similarly.


Ultrastructural study of medullomyoblastoma. A case of cerebellar medullomyoblastoma in a young boy was investigated by electron microscopy. The neuroectodermal component shows the characteristics of a desmoplastic medulloblastoma. The mesodermal component consists of more or less differentiated cross-striated muscle cells. Undifferentiated muscle cells are very similar to proliferated endothelial cells of blood vessels within the muscular component, so that an origin of this component from pluripotential endothelial cells of the vessel wall is suggested. This tumor is considered a malignant teratoid because of the derivation from two blastodermic layers and because of the midline localization in children suggesting a malformative origin.


Myelin lesions in the rabbit eye model as a bystander effect of herpes simplex and visna virus sensitization. Rabbits were immunized with herpes simplex and visna virus in complete Freund's adjuvant. Uv-inactivated herpes virus and the purified visna virus protein p25 injected intraocularly into these rabbits elicited a moderate inflammatory cell infiltration in the epiretinal myelinated nerve fiber bundles accompanied by signs of demyelination. It is therefore apparent that also viral antigen can induce myelin lesions as a so-called "bystander effect" of a cell-mediated immune response (bystander demyelination).


The ultrastructural variability of non-specific lipopigments. Abnormally structured lipofuscin granules found in various cell types of different conditions not related to the neuronal lipofuscinoses (NCL), emphasize the ultrastructural diversity of non-specific lipofuscin morphologically marked by paracristalline inclusions, pseudo-fingerprint enclosures, and stacks of parallel filaments, all of them embedded in the granular matrix of the lipopigments. Though lipofuscin consisting of the regular granulo-vacuolar ultrastructure was also present in many cells of the same tissues, our findings suggest differences, though of unknown biochemical nature, in lysosomal catabolism resulting in varying lipopigment structures within similar cellular compartments.


Effects of three different combinations of ethinyl estradiol and levonorgestrel on plasma lipids and high density lipoproteins. Seventy-five menstruating women seeking contraceptive advice were randomly allocated to treatment with combined oral contraceptives containing either ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (30/150), ethinyl estradiol 50 micrograms + levonorgestrel 125 micrograms (50/125) or ethinyl estradiol 50 micrograms + levonorgestrel 250 micrograms (50/250). The concentrations of cholesterol, phospholipids, high density lipoprotein (HDL)-cholesterol, HDL-phospholipids and triglycerides were determined prior to treatment and after one, three and six months of medication. Triglycerides increased by 18--42 per cent after one to six months of treatment with 50/125. The HDL-cholesterol and HDL-phospholipids were reduced by 10 per cent during 50/250 medication. No other parameters showed any consistent alteration in any of the treatment groups. Raised triglyceride concentration and/or decreased HDL concentration may increase the risk for cardiovascular disease. It is therefore suggested that in order not to alter the HDL concentration a combined oral contraceptive agent should probably not contain more 19-nortestosterone type of progestogen than corresponding to 125--150 micrograms of levonorgestrel. To avoid a rise of the triglyceride level the weight relation between levonorgestrel and ethinyl estradiol should be about 5:1.


Treatment of post-menopausal hypercholesterolaemia with estradiol. Replacement therapy with estradiol valerate in 29 post-menopausal women reduced low-density lipoprotein (LDL) cholesterol concentrations by 22% and increased high-density lipoprotein (HDL) cholesterol by 21% after 12 months. Apart from a 67% increase of HDL-triglyceride estradiol had only a slight effect on the levels of lipoprotein triglycerides. Post-heparin plasma lipoprotein lipase (LPL) activity was significantly decreased in subjects with normal pre-treatment very-low-density lipoprotein (VLDL) triglyceride levels, and hepatic lipase (HL) activity was significantly decreased in the group as a whole. It is suggested that estradiol replacement therapy should be considered in climacteric women with high LDL-cholesterol or low HDL-cholesterol levels, or both.


Lipid metabolic studies in oophorectomized women. Effects of three different progestogens. Ten oophorectomized women (ranging in age from 27 to 45 years, having a mean age of 34.5 years with a standard deviation of 5.3) were given three different progestogens (norgestrel, norethisterone and medroxyprogesterone) in treatment periods of 3 weeks' duration immediately preceded by 3 weeks "wash out" periods. Venous blood samples were drawn before and after each treatment period. Free and total cholesterol, triglycerides and phospholipids were determined in the three lipoprotein fractions: Very low density lipoproteins (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Individual phosphatides were determined after thin layer chromatography. In addition, the relative fatty acid composition of serum lecithin and cholesterol esters were assessed by gas-liquid-chromatography. Both norethisterone and norgestrel caused a decrease in alpha-lipoprotein cholesterol. The relative fatty acid composition of serum lecithin revealed an increase of biochemical pathway 1 for liver lecithin synthesis on norgestrel and norethisterone but no major changes on medroxyprogesterone. With norgestrel an increase in serum-lysolecithin concomitant with a decrease in lecithin was observed, while the two other progestogens did not induce any significant changes. From the present data it is suggested that the 19-norethisterone derivatives, norethisterone and especially norgestrel, have androgen-like influences on lipid metabolism. Medroxyprogesterone, being a 17-alpha-hydroxyprogesterone, caused less changes and consequently less disturbance of lipid metabolism.


Neutralizing antibodies against herpes simplex virus in maternal and umbilical cord serum. Thirteen Japanese with a full term pregnancy were studied to determine maternal and neonatal serum neutralizing antibodies against herpes simplex virus (HSV). The study included 10 healthy persons, 2 with herpes genitalis and one with herpes oralis. We found that the serum neutralizing antibody titers in neonates were almost identical or slightly higher as compared to those in the mother and such findings suggest, that in the neonate, the lack of certain immunological responses may be responsible for generalized herpes simplex virus infection.


Arteriography and chemotherapy in localized trophoblastic disease, by means of local- (pelvic-) intraarterial infusion. In spite of considerable progress in systemic chemotherapy in malignant throphoblastic disease, there remains a small group of patients who fail to respond to this type of therapy. Here the trophoblastic process may be localized by means of an arteriography, and treated by a local, intraarterial infusion of cytotoxic compounds in high concentration. The latter makes possible the treatment of processes localized in essential organs which are hard to remove, as well as in young women wishing to preserve their reproductive capacity. Our experiences is limited to one case of a young woman with chorioadenoma destruens in the uterus, resistant to systemic chemotherapy, yet successfully treated with pelvic, intraarterial infusion of cytotoxics.


Hyperlipoproteinemia in newborn infants. A study of 1025 families. As part of a screening study for the detection of hyperlipoproteinemia in 10,000 newborns, cord serum lipids and lipoproteins were measured in detail in 1025 infants. Elevated cord serum VLDL-LDL-cholesterol could easily be identified by a rapid turbidimetric estimation of cord serum VLDL-LDL. Cord serum VLDL-LDL-cholesterol was found to be significantly higher than normal in premature, asphyxiated and beta-methasone-phenobarbital-ritodrine treated infants. Other obstetric complications, however, were not associated with hyperlipoproteinemia. Furthermore all 2050 parents had their serum cholesterol determined. 3 parents had familial hypercholesterolemia (FH). One child also had FH, though her cord serum total cholesterol and VLDL-LDL-cholesterol were normal. The 2 other children of the 3 FH parents, had normal lipids and lipoproteins both at birth and follow-up.


Local articular amyloid deposition in pyrophosphate arthritis. Histological aspects. A material of 15 cases of histologically examined pyrophosphate arthritis (hip-joint: 7 cases, knee joint: 8 cases) is presented. Amyloid deposits were found in 14 cases and chondromatosis in the subsynovial connective tissue of all the cases. The significance of this high, not previously reported, coincidence is discussed, together with various pathogenetic possibilities, as related to the theories of the genesis of amyloid substance.


Extreme duct papillomatosis of the juvenile breast. Three cases of peculiar and very severe ductal papillomatosis of the breast are reported. This ductal papillomatosis was unusual, both in its histological architecture and in occurring in juveniles, viz. girls aged 11, 14, and 17 years. In two of the patients breast cancer was diagnosed 27 and 11 years later. In one of them the ductal papillomatosis must be presumed to have been precancerosis, while in the other patient there was possibly from the outset an unusually papilliferous, intraductal carcinoma of low malignancy.


The effect of transmural field stimulation on the serotonin content in rat duodenal enterochromaffin cells--in vitro. The effect of transmural field stimulation (TFS)--in vitro--on the sertonin (5-HT) content in enterochromafffin cells (EC) in rat duodenum was studied with a cytofluorimetric method. TFS caused a significant 25% decrease of 5-HT in EC. The presence of tetrodotoxin or d,1-propranolol in the stimulation bath antagonized the effect of TFS. In biopsies from rats pretreated with 6-OH-dopamine TFS had no effect of the 5-HT content in EC. The results of the present study strongly suggest, that the TFS induced decrease in 5-HT content is due to a direct neural, probably beta-adrenoceptor mediated, influence on the EC.


Transcatheter arterial embolisation in nasopharyngeal angiofibroma. Transcatheter arterial embolisation using gelfoam particles has been used in 4 young male patients with nasopharyngeal angiofibroma. The procedure proved to be extremely useful preoperatively in controlling and limiting profuse bleeding during surgery, allowing total excision of the tumor.


Contrast enhancement with time in gliomas. Stereotactic computer tomography following contrast medium infusion. Dynamic enhancement of astrocytomas has been investigated with CT following infusion of contrast medium. The areas of measurement corresponded with obtained stereotactic biopsies. The resulting types of enhancement are discussed in terms of a 3-compartment model. Great differences exist in the degree of enhancement of astrocytomas of grade I to II and those of grade III to IV. In the latter tumours a dynamic response appears to occur, distinctly different from that in infarctions.


Primary brain tumour presenting as spontaneous intracerebral haemorrhage. In an autopsy series of 430 spontaneous intracerebral haematomas 44 cases, or 10.2 percent, were caused by a proved neoplasm, including 21 anaplastic gliomas, 17 metastases, 2 oligodendrogliomas, 2 malignant lymphomas, and one meningioma. These instances of massive bleeding into brain tumour represented 2.4 percent of about 1,800 primary and secondary cerebral neoplasms proved by necropsy. In only four of the patients with primary brain tumours (two glioblastomas, one oligodendroglioma invading the leptomeninges, and one primary malignant lymphoma), three of them with a history of arterial hypertension, were the presenting symptoms these of a spontaneous intracerebral haemorrhage, and the tumour itself was not diagnosed until surgery or necropsy. One patient with acute haemorrhage into a glioblastoma of the basal ganglia showed a rapidly lethal course, while the others demonstrated one or more episodes before the onset of the acute fatal illness and a prolonged period from the time of the bleed until death. The clinical features and the pathogenesis of spontaneous haemorrhage into cerebral neoplasms are briefly reviewed.


Prostaglandins and fibroblast functions in vitro. Secondary embryonic mouse fibroblasts synthesise mainly E-type PG. The formation of PGF2 alpha is about 10 times lower. No PGI2 formation was observed. Secondary embryonic mouse fibroblasts possess an adenylate cyclase which is stimulated by E-type PGs, but little by PGF2 alpha or PGI2. PGE1-induced stimulation of cAMP levels is dose-dependently linked to an increase in biosynthetic activity of the cells, visible in increased GAG biosynthesis and PG formation. cAMP-dependent enhancement of GAG biosynthesis does not alter the carbohydrate spectrum of the secreted GAG, indicating that only the amount, but not the quality of the secreted GAG is affected by PGE1 or cAMP. Steroidal as well as non-steroidal antirheumatic agents can affect either basal or PGE1 stimulated cAMP levels or other components of the adenylate cyclase system independent of their inhibitory action on PG formation. These effects are always reflected in a decrease or increase of GAG biosynthesis. PGE1-induced stimulation of cAMP levels is related to an inhibition of fibroblast proliferation. Reduction of endogenous PG formation for prolonged periods does not result in a prolonged decrease of intracellular cAMP followed by a decrease in GAG biosynthesis or an increase in proliferation. The initial effect of reduced endogenous PG formation is compensated for by an increased sensitivity of the cells to PG's, resulting in maintenance of basal cAMP levels and an increased sensitivity to exogenous PGE1. These effects on cAMP levels are also reflected in GAG biosynthesis and proliferative activity of the cells.


Distribution and further studies on the activity of prostaglandin E in chronic granulomatous inflammation. Pre-formed granulomata, induced by cannulated, carrageenin-soaked, subdermal sponge implants, were used to further analyse the effects of exogenous PGE and the involvement of endogenous PGE in this model of chronic inflammatory tissue changes in rats. Experiments with 14C-PGE2 indicated that administration of PGE into the sponge creates a kinetic situation likely to imitate, but superimposed upon, the continuous discharge of endogenous PGE in the granuloma. The granuloma-reducing, anti-flammatory effect of PGE can be mimicked by dibutyryl cyclic-AMP, phosphodiesterase inhibitors and indomethacin. Most probably these compounds, in common with PGE, exert their anti-granuloma action through elevation of intracellular cyclic-AMP (in macrophages and/or fibroblasts). The anti-granuloma action is not necessarily associated with a reduction in the endogenous PGE-level and vice versa. The involvement of endogenous PGE in the tissue events of granulomatous inflammation is conjectural as yet.


A new method for the generation of standard atmospheres of organo isocyanates. A new and versatile method for the generation of standard atmospheres of several organo isocyanates based on permeation technique has been developed. Several membranes were screened for integrity, compatibility and permeability of these isocyanates. Silicone membrane was found to be the best membrane for the construction of permeation devices. Two types of permeation are described: liquid phase and gas phase. The liquid phase permeation tubes are recommended for generation of high concentrations (ppm) and gas phase permeation is preferred for generation of atmospheres with low concentrations (ppb). Several simple designs for construction of permeation devices are described. The permeation of isocynates were evaluated gravimetrically and were shown to be constant, provided the temperature and the flow rate of air over the permeation tube are maintained constant.


Age-related neurocytotropism of mouse cytomegalovirus in explanted trigeminal ganglions. Human cytomegalovirus (CMV) causes severe congenital neurologic disease; adult neural infection is associated with transient cranial nerve palsies. In our experimental model, mouse CMV (MCMV) infects neurons and Schwann and satellite cells of cranial nerve ganglions. To study the fate of MCMV in nerve tissue, we explanted trigeminal ganglions from newborn, suckling, and weanling mice, 3 to 36 days after intracranial inoculation. Negative explants were co-cultivated with mouse embryo tissue culture (METC) to test for latency. MCMV, identified by electron microscopy, replicated in fibroblasts, Schwann cells, and/or satellite cells and neurons of trigeminal explants from newborn and suckling, but not weanling, mice. No latent virus was detected by our methods. The age differences in viral replication may be due to the age-dependent intrinsic cellular mechanisms and host inflammatory and immunologic response. Though neurons are infected, they remain relatively resistant to CMV replication.


Recovery of pituitary-adrenal axis after withdrawal or reduction of systemic corticosteroids in patients with bronchial asthma. In 36 patients with bronchial asthma a new inhalable corticosteroid (Fluocortin-butyl-ester) was administered to reduce systemic steroids and especially to study the recovery of pituitary-adrenal function. On the basis of the present results, it can be said that patients with the least degree of emphysema and obstruction and with good coughing dynamics and productive expectoration are most suitable for therapy with inhalable corticosteroids. If the systemic steroid reduction is adequate, the recovery phase of the pituitary-adrenocortical system begins after about 5 months and the response to ACTH appraoches normal values after about 8-9 months. About 4 mg prednisolone-equivalent per day can be assumed to be the systemically effective limiting dose. The reducibility as a percentage of the initial dose-regardless of its absolute value- and the maintenance dose achieved also appear to be of equal importance for the recovery of the functional reserve of the pituitary-adrenocortical system. No relationship to the duration of the disease and the initial steroid dose could be demonstrated. The clinical picture of the corticosteroid withdrawal syndrome is dependent on endogenous cortisol synthesis. The symptoms disappear spontaneously with increasing synthesis.


Humoral inhibitors of the immune response in uremia. II. Further characterization of an immunosuppressive factor in uremic serum. The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes.


Stimulation of cyclic AMP phosphodiesterase activity by the heated supernatant fraction of canine tracheal smooth muscle. The cAMP-hydrolyzing activity (phosphodiesterase) in the supernatant fraction of canine tracheal smooth muscle was approximately doubled by addition of more concentrated, heat-treated tissue extract. The activation was eliminated by EDTA, but addition of calcium produced no greater activation than addition of heated extract alone. It appears that canine tracheal smooth muscle phosphodiesterase can be activated by a heat-stable, calcium-dependent factor.


The effects of ACTH on lung maturation in fetal lambs. The ability of adrenocorticotrophic hormone (ACTH) to induce lung maturation was evaluated in fetal lambs. One member of 14 twin pairs between 114 and 138 days of gestation was infused intravenously with 0.5 mg ACTH over 5 days. The lungs of treated versus control lambs were judged more mature by morphologic criteria by the use of light and electron microscopy and by biochemical criteria by the use of lamellar-body-rich cell fractions. None of 5 premature lambs treated with ACTH and allowed to breathe showed evidence of hyaline membrane disease, while 3 untreated control lambs showed typical hyaline membranes.


Maxillofacial synovial sarcoma. Light- and electron-microscopic study of two cases. The light microscopy and ultrastructural features of two maxillofacial synovial sarcomas are presented. By light microscopy, one of the tumors revealed the typical biphasic pattern while the other was predominantly fibrosarcomatous. Ultrastructurally, both cases revealed a biphasic pattern. Epithelial-like cells displayed abundant mitochondria, Golgi profiles, electron-dense bodies, cytolysosomes, and thin filaments. Stromal cells were spindle-shaped and provided with smaller cytoplasm and scant organelles, mainly consisting of profiles of rough endoplasmic retuculum, mitochondria, and free ribosomes. Pseudoglandular spaces lined by cuboidal to flattened epithelial-like cells with apical microvilli were numerous. Basal lamina and intercellular junctions were prominent in one case, but sparse in the other. The most undifferentiated tumor revealed many intercellular clefts containing filopodia among the epithelial-like cells; occasional intracyltoplasmic lumina were also present. These findings are somewhat similar to those reported in normal and nonneoplastic diseases of the synovium. However, the location of the tumors in areas normally devoid of synovium suggests one more that they might arise from nonspecialized primitive mesenchyme.


Benign histiocytic tumor of lung. A light- and electron-microscopic study. We describe an unusual benign pulmonary neoplasm which was composed entirely of histiocytes and a few chronic inflammatory cells and which posed difficult diagnostic problems. The differential diagnosis is discussed, and the usefulness of electron microscopy in interpreting unusual pulmonary tumors is emphasized.


Toxicologic assessments of a commercial polybrominated biphenyl mixture in the rat. A polybrominated biphenyl fire retardant (Firemaster FF-1) was responsible for the widespread environmental contamination and animal losses in Michigan during 1973 and 1974. In Fischer 344/N rats orally given 30,100,300, and 1,000 mg/kg (5 days/week, 22 total doses) for 4.5 weeks and observed for 90 days after the start of treatment, the LD50 was determined to be 65 mg/kg/day (total 1.43 g/kg) for the female rat and 149 mg/kg/day (total 3.28 g/kg) for the male. All female rats given the dosage of 100 mg/kg/day (22 doses, total 2.20 g/kg) died between 41 and 53 days after the start of treatment, whereas 38% of the males died between 50 and 73 days. Pathologic changes in treated rats were large liver, accentuation of the hepatic lobular markings, and atrophy of thymus and spleen. Microscopically, hepatic changes were characterized by congestion, fatty metamorphosis, and multifocal liquefactive necrosis. Male rats given 100 mg/kg/day and dying after 90 days had subacute to chronic hepatitis with marked focal proliferation of bile ducts. Exposure to Firemaster FF-1 may produce atypical liver nodules in the rat as early as 6 months after they were first given the preparation. Marked hepatotoxic effect persisted in surviving rats when examined after 6 months.


Coronaviral enteritis of young calves: virologic and pathologic findings in naturally occurring infections. Coronavirus was detected in 113 (16.4%) of 689 calf enteric disease accessions received at the South Dakota Animal Disease Research and Diagnostic Laboratory from Mar 1, 1975 to Oct 31, 1976. During this period, modified live coronaviral vaccine was not in common use in this area. The virus was detected by negative stain electron microscopy of feces and intestinal contents and by fluorescent antibody examination of intestine and colon sections. Calves with coronaviral enteritis ranged in age from 1 day to 3 months, with most cases occurring between 1 and 7 days. At necropsy, a green, mucoid fecal cast was commonly seen in the colon. Histopathologic examination revealed necrotizing enterocolitis.


Feline infectious peritonitis: a worldwide serosurvey. Feline sera from 13 countries were assayed for coronavirus antibody, using a heterologous indirect immunofluorescence test. Significantly higher percentages of antibody carriers were obtained during testing randomly collected sera from mature males (greater than 1 year old) than in testing females of the same age. Antibodies were infrequently found in immature cats (less than 6 months old); at 1 year of age or older, a plateau was reached and little change in the percentage of seroconverted animals was observed. Differences were not detected between purebred cats vs mixed-breed cats or household vs stray cats. In animals showing clinical signs of feline infection peritonitis (FIP), antibodies were encountered with higher frequency than in clinically healthy cats. Significant differences in antibody incidence were found between countries, with a range between less than 10% and greater than 50% of seropositive individuals. Antibodies were detected in sera from an isolated cat population (Marion Island) and from wild-caught cheetahs (Acinonyx jubatus). The antibody specificity for FIP virus was confirmed by neutralization tests. The antibody pattern in randomly collected solitary cats, in catteries, and cats with clinical FIP showed characteristic differences in titer and incidence. The implications of these results for the epizootiology of FIP are discussed.


Rotavirus antibody assays on monkey sera: a comparison of enzyme immunoassay with neutralization and complement-fixation tests. An enzyme immunoassay (EIA) for the detection of rotaviral antibodies was developed, using a purified, cell culture-grown SA 11 viral antigen and alkaline phosphatase as an enzyme label. This technique was evaluated by comparative testing with tube neutralization and complement-fixation assays on a collection of simian sera. There was close correlation between positive and negative results obtained by EIA and by neutralization. The EIA was as easy to perform as complement fixation testing, but showed greater sensitivity and fewer nonspecific reactions. Thus, EIA was shown to be a very suitable test for routine detection of rotaviral antibodies in serum. Results of neutralization tests suggested that the monkeys (mostly rhesus macaques) in the present study were infected with viruses varying in their antigenic relatedness to SA 11 virus and to a British isolate of calf rotavirus.


Egg transmission of avian adenovirus-associated virus and CELO virus during a naturally occurring infection. Both avian adenovirus-associated virus (A-AV) and CELO virus were isolated from the embryonating eggs of 25-week-old black sex-linked hens during a naturally occurring infection. In the first 7 days of egg collection, A-AV was isolated from 10 of 43 (23.2%) embryonating eggs, and CELO virus was isolated from 8 of 43 (18.6%) embryonating eggs. Both viruses were isolated from six eggs. In the next 16 days of egg collection, A-AV and CELO virus were coisolated from 1 of 127 (0.8%) eggs; all other samples were negative for both viruses. All six hens transmitting A-AV to eggs and 5 of 6 hens transmitting CELO virus showed seroconversions (fourfold increase in antibody concentrations). Viruses were not isolated from eggs after the hens showed a fourfold increase in antibody concentrations.


A seroepizootiologic study of five viruses in a swine-evaluation station. This serologic study was done to gain information on the spread, maintenance, and effect upon performance of five porcine viruses. Blood samples were taken from two groups of 8- to 11-week-old pigs from a large number of Indiana swine herds in a performance-testing station 1 week after entry, 7 weeks after entry (one group only), and at slaughter. The sera were tested by indirect fluorescent antibody tests for antibodies to transmissible gastroenteritis virus (TGEV), swine influenza virus (SIV), hemagglutinating encephalomyelitis virus (HEV), porcine adenovirus (PAV), and pseudorabies virus (PRV). Seroconversions to TGEV, HEV, and PAV occurred in a group of pigs entered in May and slaughtered in August (group 1). In the group that was entered in October and slaughtered in January (group 2), pigs developed antibodies to SIV, HEV, and PAV, but not to TGEV. Only 1 of the 434 pigs tested had antibodies to PRV, and there were no seroconversions to this virus. The only statistically valid effect of infection on performance was found in group 1 pigs, which had seroconverted to TGEV during the first 7 weeks of their stay. These pigs gained 0.077 kg less per day than pigs that did not develop antibodies to TGEV during that period. The pattern of serologic reactions was indicative of a relatively slow spread of these viruses in the groups. We interpret this as supporting the concept that a relatively slow spread of these viruses through large groups of pigs kept under conditions that are less than optimum for virus spread may be an important means of their interepizootic survival.


Temporal appearance, geographic distribution, and species of origin of bluetongue virus serotypes in the United States. Beginning in 1973, all available laboratory and field strains of bluetongue virus (BTV) from the United States were serotyped. Of the viral strains serotyped, 27 were collected from 1953 through 1972; 173 were collected from 1973 through 1977. Although 20 BTV serotypes have been found worldwide, only BTV serotypes 10, 11, 13, and 17 have been found in the United States. Since 1973, serotypes 11 and 17 have been the prevalent serotypes. Samples were collected over a 24-year period in the United States and represent a wide geographic area and diverse host sources (sheep, cattle, wild ruminants, and insect vectors). The collection was not a statistical sampling.


In vitro cultivation of Anaplasma marginale: growth pattern and morphologic appearance. Anaplasma marginale propagated in vitro showed an increasing rate of replication in a sequence of three experiments. The changes in the percentage of parasitized erythrocytes and identification of the organism in culture were monitored by the Giemsa-staining and the direct fluorescent antibody techniques. The ultrastructure of the organism in culture also was determined. The percentage of parasitized erythrocytes increased more than three times in the first experiment during a period of 8 days, and about ten times in the second experiment during a period of 14 days. After 8 days of observation of the primary culture in the third experiment, the trend of growth was more rapid than in the first and second experiment. The viability of the organism was verified by inoculation of susceptible calves, using 13- and 33-day cultures of the first and the second experiments, respectively. The primary cultures were subcultured twice by dilution with normal bovine erythrocytes.


Safety and efficacy studies of live- and killed-feline leukemia virus vaccines. The safety and the efficacy of several feline leukemia virus (FeLV) vaccines for 16-week-old kittens were determined. Vaccines were derived from an FL74 lymphoblastoid cell line that has been in continuous tissue culture passage for about 4 years. The vaccines were made from living virus, formaldehyde-inactivated whole FL74 cells, and formaldehyde-inactivated whole virus. The efficacy of each produced vaccine was determined by challenge exposure of vaccinated cats with virulent FeLV. The two formaldehyde-inactivated vaccines were found to be safe for use in kittens. Neither vaccine produce a significant feline oncornavirus-associated cell membrane antigen or virus-neutralizing antibody response, nor did they prevent infection with virulent FeLV. The inactivated whole-virus vaccine, however, did substantially decrease the proportion of kittens infected with virulent FeLV that became persistently viremic. In contrast, the whole FL74 cell vaccine did not reduce the number of infected kittens that became persistently viremic. The live-virus vaccine was found to be both safe and efficacious. About a half of the kittens vaccinated with live virus had transient bone marrow infection that lasted from 2 to 4 weeks. Viral antigen was not detected in peripheral blood, and infective virus was not shed in saliva, urine, or feces during the period that the vaccinal virus could be recovered from the bone marrow. In addition, there was no horizontal spread of vaccinal virus from vaccinated to non-vaccinated cagemates. Within several weeks, vaccinated kittens demonstrated no clinical or hematologic abnormalities and had high serum levels of feline oncornavirus-associated cell membrane antigen and virus-neutralizing antibody. Kittens vaccinated with living FeLV were resistant to infection with virulent virus.


Morphologic changes in the bursa of fabricius of chickens after inoculation with infectious bursal disease virus. Sequential morphologic changes in the bursa of Fabricius were studied after oral inoculation of 1-day-old chicks with infectious bursal disease virus (IBDV). The epithelial surface morphology was studied by scanning electron microscopy, whereas the IBDV replication was sequentially followed by immunofluorescence and transmission electron microscopy. The earliest detectable changes in the bursal epithelium were evident at postinoculation hour (PIH) 48. They were characterized by reduction in numbers and size of microvilli on the epithelial cells accompanied by gradual involution of the button-like bursal follicles. At PIH 96 some specimens showed localized surface erosions due to loss of epithelial cells. As the damage progressed, the infolding of the buttomlike follicles became more pronounced and the surface erosions became more extensive. Loss of surface epithelium exposed the underlying damaged bursal follicles which appeared to be bounded by columnar epithelium. Some follicles had lost almost all the lymphocytes and macrophages and appeared as empty craters. Intrafollicular replication of IBDV was detectable as early as PIH 24 by immunofluorescence technique. Viral replication primarily took place in the lymphoid follicles. Regeneration of the follicles was not seen up to postinoculation day 12, suggesting that the IBDV-induced bursal damage could be permanent.


Antigenic variation among strains of the New Jersey serotype of vesicular stomatitis virus. Four strains of vesicular stomatitis virus--New Jersey (Hazelhurst, Guatemala, Panama, and Concan) were compared by cross-neutralization and complement-fixation tests. They were indistinguishable by complement-fixation test; however, by plaque-reduction neutralization method, slight antigenic differences were observed between the Hazelhurst and the three other strains. It is concluded that these antigenic differences are insufficient to warrant reclassification of vesicular stomatitis virus--New Jersey into two distinct subtypes, as has been recently proposed.


An immunodiffusion test for detection of bovine viral diarrhea virus antibodies in bovine serum. An immunodiffusion test (IDT) was developed for detecting bovine viral diarrhea virus antibodies in bovine serum. The antigen utilized in the IDT was prepared from bovine viral diarrhea virus-infected monolayer cultures. Results of the IDT were obtained within 48 hours and correlated with the virus-neutralization test.


Pathology of the placenta and newborn pups with suspected intrauterine infection of canine herpesvirus. Pathologic and virologic investigations were done on the fetal placenta and on pup runts which were obtained from a bitch with a medical history of canine herpesvirus (CHV) infection. Macroscopically, the placenta was poorly developed. Small grayish white foci were observed in the placental labyrinth. Characteristic lesions of CHV infection were not prominent in the pups examined. Microscopically, however, focal degenerative and necrotizing lesions were observed in the placental labyrinth. Rarely, eosinophilic or basophilic intranuclear inclusion bodies were in the trophoblastic cells in the necrotizing lesions. In the adrenal gland of one stillborn pup, focal necrosis and hemorrhages could be seen; these irregularities were essentially the same as those seen in the newborn pups with CHV infection. Focal interstitial pneumonia was also observed in some of the pups. The CHV organism was isolated from the kidney of one pup that survived for 22 days.


Experimental infection of eastern cottontail rabbits Sylvilagus floridanus) with infectious bovine rhinotracheitis virus. Experimental infection of eastern cottontail rabbits (Sylvilagus floridanus) with infectious bovine rhinotracheitis virus caused acute keratoconjunctivitis and a fatal systemic infection. The clinical syndrome was characterized initially by blepharospasm and ocular discharge. The rabbits were markedly depressed on post-exposure day (PED) 5 and were dead or moribund on PED 6. The virus was readily recovered from liver and adrenal gland tissue on PED 6 and from conjunctival swabs on PED 1 to 6. Histopathologic studies revealed a few necrotic foci in the liver and multiple focal to diffuse necrosis of the adrenal glands. Viral isolation and immunofluorescence tests were used to demonstrate a direct association between infectious bovine rhinotracheitis viral antigens and the lesions.


Mortality among shipyard workers in Genoa, Italy. The dockyards of Genoa are exposed to many known or suspect carcinogenic agents, namely, asbestos, silica, polycyclic aromatic hydrocarbons, and halogenated hydrocarbons; other possibly harmful substances are trace amounts of aromatic amines, welding smokes, paints, and lipid-removing solvents. A cohort study of causes of death of 2190 dockyard workers in Genoa was conducted between January 1, 1960 and December 31, 1975. Mortality rates were calculated for 20 different occupational categories, for which there exist different levels of exposure to noxious substances. Two control groups were selected: the general male population of Genoa and all male employees (462) of San Martino Hospital, Genoa for the same period of time. Causes of death that demonstrated significant excesses for both control groups were: cancer of the colon, excluding the rectum; cancer of the larynx; cancer of the lung, bronchus, and trachea; cancer of the kidney, urinary bladder, and other urinary organs; respiratory diseases; and cirrhosis of the liver. The data obtained from these 20 job categories revealed different types and levels of risk for various carcinogenic agents.


[Surgical treatment of chemodectomas of the neck (author's transl)]. About 16 cases of chemodectomas of the neck, with surgical management during the five past years, the authors present an actualisation about surgery of these tumors of the paraganglionnary system at the level of the neck. After recording the different means of the diagnosis, particulary carotid arteriography, they insist about the necessity of a complete excision of these tumors because of local risks due to the neurovascular compression and infiltration, and because of general risks due to malignant metastasis. Three major risks run with surgery in these cases: hemorrhagic, neurologic, and vascular risks (because of the possible extension to the carotidian axis). 14 total excisions and 1 incomplete excision were performed; 1 no-operated tumor was noted because of the death of the patient before surgery due to a metastatis paraplegia. 4 resections of the carotidian axis with 1 repair by end to end anastomosis and 3 by a vein graft were necessary. No mortality after surgery in these patients was encountered. No recurence, no metastatic phenomen in our patients after the total excision of the primary chemodectoma of the neck even for one histologically maligant tumor, three years ago.


Affinity electrophoresis of human alcohol dehydrogenase (ADH) isozymes. 1. The effects of coenzyme NAD and related compounds on the electrophoretic properties of the human ADH isozymes have been examined by the technique of affinity electrophoresis. 2. Incorporation of NAD, NADH or AMP into a starch-gel matrix leads to retardation in the cathodal mobilities of the gamma 2 gamma 2 and alpha alpha isozymes, but not the beta 1 beta 1 and gamma 1 gamma 1 isozymes. The heterodimeric isozymes show intermediate effects, and the genetic polymorphism at the ADH3 locus is only discernible if electrophoresis is carried out in the presence of coenzyme. 3. The behaviour of the ioszymes can be attributed to slight differences between the products (alpha, beta 1 and gamma 1) of the common alleles at the three ADH loci and a pronounced difference between the products (gamma 1 and gamma 2) of the alternative alleles at the ADH3 locus in their affinities for the cofactor NAD.


The Scianna blood group lies distal to uridine monophosphate kinase on chromosome 1p. Linkage between the Scianna blood group and the Rhesus blood group has been confirmed. Families demonstrating recombinants between U M P K and Sc suggest that U M P K lies between Sc and PGM1.


[The endaural approach and surgery of glomus jugulare tumors (5 cases)]. The endaural approach has its in excision surgery of certain forms of jugular glomus tumor. --In the pure, tympanic form, a minimal or extended endaural approach is perfectly suitable. -- In tympano-mastoid forms, without involvement or with minimal involvement of the jugular foramen, a prolonged endaural approach may be used for wider operations involving the whole middle ear and mastoid around a bony aqueduct or an exposed VII. --Nevertheless, in the presence of tympano-jugular or tympano-masto-jugular forms, with marked involvement of jugular foramen, the greatest caution is necessary. It would appear that the endaural route may still be suggested but only for certain tumors, with the express reserve that angiographic studies defining its site and extent are favourable. By virtue of more and more highly developed techniques of exploration (scanner with contrast, films in subtraction) which may be used for measurement and precise localization of the tumor, indications for the type of approach may now be defined with even more precision. --It should be noted that if there is the slightest doubt, the slightest reserve, or the slightest fear that an endaural approach might be inadequate to deal with the situation, it should be definitely avoided with preference for a cervico-retro-auricular or cervicopre and retro-auricular approach, or radiotherapy only, or even abstenstion from operation, with observation. It is only if such rules of good sense and caution are respected that minimal, extended, prolonged endaural approaches will retain a worthy place in the surgical treatment of jugular glomus tumors.


Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh syndrome). A family--mother and 2 sons--with a heredodegenerative neurological disease is described. The disease started with bilateral optic atrophy, central scotoma, and color blindness during the second decade. This was followed by a quiescent period until additional neurological symptoms appeared, around the age of 50 years in the case of the mother and 40 and 30 years, respectively, in the sons. The additional symptoms were ataxia, spastic paresis, clonic jerks, grand mal seizures, psychia lability, and slight dementia. The disease was progressive, resulting in permanent hospitalization within a few years. The mother died at the age of 63 years and the sons at 46 and 43 years of age. Neuropathological examination revealed lesions histopathologically characteristic of subacute necrotizing encephalomyelopathy (SNE, Leigh disease), and their distribution in the brain and brainstem also conformed to this disease. On the basis of the clinical course and neuropathological findings, we consider that these 3 patients represent the first reported familial cases of the adult form of SNE.


[Rare tumors of the septum. 8 reported cases (author's transl)]. The authors present 8 cases of rare tumors of the nasal septum and define a number of characteristic points on the basis of each of them. The following are presented: --a malignant nevus, the rarety of E.N.T. sites of such tumors is emphasized, as well as important role of immunotherapy in their treatment, alongside surgery and radio-therapy. --a keratoacanthoma, difficult in terms of differential diagnosis from a basal cell carcinoma. -- a cavernous hemangioma, excision of which must be wide if recurrence is to be avoided. --one very hemorrhagic mixed tumor. --one case of pseudo tumoral tuberculosis in a woman with no known past history of tuberculous disease. --one very painful glomus tumor, radical treatment of which is surgical, in preference to radiotherapy. --two cylindromas of the septum, one taking the form of a large, angiomatous polyp, which puts in question the name of cystic adenoid carcinoma, suggested for these non-cutaneous tumors.


Disturbances of rapid-eye-movement sleep in 3 brothers with Pelizaeus-Merzbacher disease. The electrophysiological features of 3 brothers with the classic form of Pelizaeus-Merzbacher disease (PMD) were studied. Two consecutive overnight polygraphic sleep recordings indicated a gross distortion of rapid-eye-movement (REM) sleep for all patients. A lower than normal percentage of REM sleep in these patients was consistent with their retarded intellectual development, which supports current thinking that REM sleep may be a sensitive index of brain function integrity. Non-rapid-eye-movement (NREM) sleep, in contrast to reported findings in 1 patient with PMD, was uniformly characterized by distinct stages in which the electroencephalograms contained frequent vertex waves and spindles. Tests of peripheral nerve conduction velocity, acoustic brainstem reflexes, and visual and auditory evoked potentials did not indicate any abnormalities, nor did electroencephalograms obtained during wakefulness. One patient did have epileptiform spikes and spike waves recorded during an all-night EEG, an unusual finding in a child with cerebral white matter disease.


Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID(50)) of 0.15 +/- 0.09 muM. The mean ID(50) for 10 isolates of HSV-2 was 1.62 +/- 0.76 muM, and for four isolates of varicella-zoster virus it was 3.75 +/- 1.30 muM. The ID(50)'s for two cytomegalovirus isolates were 100 and 160 muM, and for four additional isolates of cytomegalovirus no end point (ID(50)) was reached at 200 muM. ACG at a concentration of 200 muM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 muM.


Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals.


Structural and compositional changes associated with chlorine inactivation of polioviruses. Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation.


Survival of enteric viruses under natural conditions in a subarctic river. The survival of enteric viruses was studied in the vicinity of Fairbanks, Alaska at selected stations along a 317-km section of the Tanana River. This section was located downstream from all known domestic wastewater sources and was effectively sealed by a total ice cover. The mean flow time through the region was 7.1 days, during which initial viral population showed a relative survival rate of 34%. The tracing of native viruses at such great distances in the complete absence of other point and nonpoint viral sources has not been previously reported. Of the two methods of virus concentration used, viral recoveries from the disk adsorption virus elution procedure were far greater than those achieved with the Aquella system employed at that time. The fact the ratio of enteric viruses to fecal indicator bacteria was not constant clearly inferred that these bacteria were not an effectual measure of virus concentration. The persistence of fecal coliforms and fecal streptococci, however, attested to the microbiological health risk involved.


Microbiology of bruised tissue.

Microbiology of bruised tissue. No significant differences could be found in the microbial quality of bruised and unbruised tissue provided that the two types of tissue were treated identically. This suggests that there is no good reason for the condemnation of bruised tissue, which could well be used in manufactured products.


[Influence of cyclic adenosine monophosphate on the migration of primordial germ cells of the anuran Amphibians (author's transl)]. After the treatment in toto of the embryos from various species of Anura by cAMP, the number of primordial germ cells (PGC) in genital ridges is strongly reduced; the most part of the PGC are found in the endoderm. A ventral implant of agar impregnated with a solution of cAMP attracts numerous PGC in the same way as grafted chordomesoderm. The chordomesoderm itself, incubated with 3'-5' cyclic nucleotide phosphodiesterase, then grafted on to the ventral area of normal embryos attracts very few PBC compared with the non-incubated chordomesoderm. The results are analyzed and discussed along the following hypothesis: the migration of the PGC of the Anura is guided by cAMP which, diffusing from the chordomesoderm, is distributed along a concentration gradient increasing in a ventrodorsal direction. The PGC go up the gradient by a chemiotactic mechanism and reach the dorsal parts of the embryo.


Hepatitis A and Indian childhood cirrhosis. Antibody to hepatitis A virus (anti-HAV) was found in 50% of patients with Indian childhood cirrhosis; this was not significantly different from the prevalence of anti-HAV in age- and sex-matched controls.


A specific ultrastructural marker for disseminated lipogranulomatosis (Faber). An ultrastructural investigation of two cutaneous lesions in a two-year-old Turkish boy with disseminated lipogranulomatosis (Farber) revealed curvilinear bodies in fibroblasts, histiocytes, and endothelial cells; "elongated membranes" in fibroblasts and endothelial cells; "zebra bodies" in endothelial cells; and spindle-shaped bodies in Schwann cells. In peripheral lymphocytes only alterations of mitochondria (swelling and ruptured cristae) but no inclusion bodies were found. Curvilinear bodies were numerous and easily identifiable; they appear to be characteristic of Farber's disease, and naming them "Farber bodies" is proposed. The diagnosis of this ceramide storage disease, in which the histological examination is relatively unspecific, can therefore be confirmed ultrastructurally.