[Possibilities of cobalt therapy in bronchopulmonary cancer]. Cobaltotherapy was applied in 194 cases of bronchopulmonary cancer in the Oncologic Institute of Cluj-Napoca, during the 1967--1974 period. The mean survial was of 15 months, the results being influenced by the histologic type and locoregional extent apraised on the basis of the TNM classification proposed by the American Joint Committe for Cancer Staging and End Result Reporting. The mean survival after irradiation was of 9.7% and 5.1% at 3 and 5 years respectively. Standardization of the cases according to the TNM criteria showed the advanced stage of the patients referred for radiotherapy, proving a useful tool for establishing the prognosis and therapeutical indications. Next to the histological type and TNM category, the efficiency of radiotherapy is also influenced by the size and shape of the tumor, which conditions the irradiation technique. The central tumours or those of the upper lobes may be irradiated by small 150 cm2 beams and are the only ones that benefit by radical radiotherapy, the survival rate at 2 and 5 years being 12.3% and 7.6% respectively. In all the other cases the prognosis is more reserved, suggesting the necessity of associating chemotherapy or immunotherapy for improving the results.


[Emergency pneumonectomy for severe hemoptysis in pulmonary tuberculosis]. The authors present two cases of severe tuberculous hemopthysis cured by pneumectomy. The patients had repeatedly presented severe hemopthysis meanacing their life and necessitated intensive resbuscitation, with intubation and mechanical respiratory prostheses. The authors also discuss the mechanism of death in severe hemopthysis, demonstrating that death is especially due to bronchial obstruction by clots of blood.


[Non-culturable Koch bacilli during antitubercular chemotherapy]. The authors have performed 58435 microscopic examinations, of which 3813 were positive, and found 209 (5,48%) cases of non-cultivable Koch bacilli. The major bacteriological, clinico-evolutive and therapeutical aspects are examined. Most of the cases showing a syndrome of positive homogenate with a negative culture were rather recent ones (an evolution of less than 2 years in 73,68% of the total) and the highest frequency was found in those in which the treatment was in its first year. No direct relationship could be demonstrated between the number of germs (the Gaffky scale) and the frequency of the syndrome. The factors influencing the occurrence and the development of the syndrome are: the structure of the lesions, the method of bacteriologic examination, the therapy applied, and a certain immunologic reactivity. According to the authors the significance of this syndrome is positive in most of the cases, indicating a regression that has not been completed. The most reasonable attitude is a differentiated one, depending on each case, integrating the data obtained by the bacteriological examination in the therapeutic and evolutive clinico-radiologic context.


[Aspects of pulmonary function in states of hyperhydration]. The authors have investigated in 10 young and healthy men the changes occurring in the cardio-respiratory apparatus following the perfusion with non-colloid isotonie volemic solutions. Exploration of volumetry and of pulmonary mechanics have been performed, hemodynamic tests and pulmonary angiograms. The results indicate the development of slight interstitial oedema, without intra-alveolar transsudation or obstructive phenomena in the aerial pathways. The cardio-vascular apparatus shows satisfactory adaptability through central and peripheral mechanisms in conditions of hyperhydration.


[An experimental study of autotopagnosia (author's transl)]. One hundred and twenty patients with unilateral cerebral hemisphere damage (54 aphasics, 21 non-aphasic left and 45 right brain-damaged patients and 57 control subjects without cerebral lesions were given a battery of verbal and non-verbal tests of autotopagnosia, with the aim of studying the relationships between disorders of body schema and the side of the hemispheric lesion. A second aspect of our research consisted in understanding whether impairment in naming and pointing to body parts following verbal commands was really a specific symptom or if the same difficulty was found when patients were asked to name or to point to parts of objects other than the human body. Our results have shown that: 1) the aphasic patients are significantly more impaired than the non-aphasic patients on all the tests, non-verbal as well as verbal; 2) when results obtained on tests of naming and of pointing to parts of the human body were matched with results obtained on tests of naming and of pointing to parts of objects other than the human body, no difference could be demonstrated. These findings suggest that autotopagnosia is a nonspecific symptom, and that it does not find a satisfactory explanation in terms of "disorders of the body schema".


[Inappropriate secretion of ACTH in cases of bronchial carcinoma]. In the light of seven cases of adrenal hypercorticalism associated with tumoral secretion of ACTH, the syndrome of inappropriate ACTH secretion is reviewed. This entity, which is related primarily to anaplastic bronchial carcinoma is characterized by paucity of clinical signs of hypercorticalism, rapidity of evolution and typical biological modifications. Other important criteria are hypokalemic alkalosis, high plasma levels of ACTH and 17-OHCS and failure of dexamethasome to suppress endogenous steroid secretion. However, the diagnosis can be proven only by extraction of a significant quantity of tumoral ACTH.


Efflux of cyclic nucleotides from rat pineal: release of guanosine 3',5'-monophosphate from sympathetic nerve endings. Potassium and norepinephrine stimulate the efflux of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) from intact pineal glands. The postsynaptic beta-adrenergic receptor mediates the efflux of cyclic AMP. In contrast, the efflux of cyclic GMP requires calcium and intact nerve endings. It appears that sympathetic nerve endings may release cyclic GMP into the synaptic space.


Dibutyryl cyclic AMP mimics ovariectomy: nuclear protein phosphorylation in mammary tumor regression. Growth of mammary carcinoma induced by 7,12-dimethyl-benz(a) anthracene is arrested by either ovariectomy or treatment with N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP). When this occurs, a new nonhistone protein species becomes the predominant endogenous substrate of cyclic AMP-dependent protein kinase in the tumor nuclei. Phosphorylation of this regression-associated protein ceases when resumption of tumor growth is induced by either the injection of 17 beta-estradiol or cessation of dibutyryl cyclic AMP treatment. Thus phosphorylation of regression-associated protein may play a role in the regression of hormone-dependent mammary tumors.


Modulation of macrophage tumoricidal capability by components of normal serum: a central role for lipid. The tumoricidal capabilities of macrophages can be reversibly inhibited by a lipoprotein of high molecular weight, and the inhibition appears to be reproduced by enrichment of macrophage plasma membranes with cholesterol. A second serum component of lower molecular weight enhances macrophage cytotoxicity. The presence of these components in normal serums suggests a physiological role for such factors in the regulation of macrophage function.


Antigenic shift of visna virus in persistently infected sheep. Visna viruses isolated from persistently infected sheep were antigenically distinct from the plaque-purified virus used for inoculation. The selection of antigenic variants under antibody pressure, thought to occur in vivo, was reproduced in sheep cell cultures inoculated with plaque-purified visna virus and maintained in antibody. Antigenic shift may be a mechanism for persistence of virus in slow or recurrent viral infections.


Human chorionic gonadotropin-like substance in nonendocrine tissues of normal subjects. By means of two assay systems, a beta chain human chorionic gonadotropin radioimmunoassay and a radioreceptor gonadotropin assay, a chorionic gonadotropin-like substance was demonstrated in extracts of liver and colon obtained at autopsy from three patients who died of nonneoplastic disease. In contrast to placental chorionic gonadotropin, colon and liver chorionic gonadotropin was not bound to concanavalin A-Sepharose columns, indicating that this substance possessed little or no carbohydrate. Previous workers demonstrated that desialylated human chorionic gonadotropin possesses little or no bioactivity in vivo but retains full radioreceptor and radioimmunoassay activity in vitro. Our data suggest that the genome responsible for the human chorionic gonadotropin production is not completely suppressed in adult nonendocrine tissues, and that the chorionic gonadotropin produced by colon and liver has little or no bioactivity in vivo because of its low carbohydrate content. Since many normal tissues produce chorionic gonadotropin, bioactivity may be modulated by regulation of carbohydrate content.


Three hypolipidemic drugs increase hepatic palmitoyl-coenzyme A oxidation in the rat. Male rats treated with clofibrate, tibric acid, or Wy-14,643 show an 11- to 18-fold increase in the capacity of their livers to oxidize palmitoyl-coenzyme A. This provides a plausible biochemical mechanism for the action of these hypolipidemic drugs in reducing lipid concentrations in the serum.


1,25-dihydroxycholecalciferol and parathormone: effects on isolated osteoclast-like and osteoblast-like cells. The actions of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and parathormone, both effective bone-resorptive agents in vivo and in vitro, were tested on CT (osteoclast-like) and PT (osteoblast-like) bone cells maintained in culture. Both agents stimulated acid phosphatase activity and hyaluronate synthesis in the CT cells and decreased alkaline phosphatase, citrate decarboxylation, and collagen synthesis in the PT cells. Calcitonin inhibited the changes induced in the CT but not in the PT cells. The activity of 1,25-(OH)2D3 differed from that of parathormone in one key respect: it did not increase cellular cyclic adenosine monophosphate, whereas parathormone did. Prior incubation of the bone cells with 1,25-(OH)2D3 for 6 to 24 hours made the cells refractory to the effect of parathormone on cyclic adenosine monophosphate formation. These data suggest that 1,25-(OH)2D3 and parathormone induce bone resorption by affecting the same cell types (osteoblasts and osteoclasts) although at different cellular sites.


Rare occurrence of Addison's disease and diabetes mellitus in children. We report on two children with both Addison's disease and diabetes mellitus, a rare occurrence in children. One of the children first developed Addison's disease and later developed diabetes mellitus, while the other had the onset of diabetes mellitus first and later Addison's disease. In the latter patient a direct relationship was shown between the insulin dose and adrenal cortical hormone. Organ-specific antibody studies are reported and the diagnosis and management of these combined endocrinopathies are discussed.


Endodermal sinus tumor of the anterior mediastinum. An endodermal sinus tumor presenting as a lobulated anterior mediastinal mass in a 20-year-old white man is reported. The clinical implications, histology, and origin of this rare germ cell tumor are discussed. The invasive nature of this highly malignant neoplasm prevented complete surgical resection.


Small cell carcinoma of the lung presenting as bilateral hilar adenopathy. A patient in whom a presumptive diagnosis of sarcoidosis was made on the basis of nonspecific symptoms and BHA on chest roentgenogram is described. At necropsy the BHA was found to be due to a metastatic small cell undifferentiated carcinoma of the lung. This tumor is a previously unrecognized cause of BHA.


Association of breast cancer with myeloproliferative disorders. Three cases of myeloproliferative disorders in patients with breast cancer are described. The first patient developed acute myeloblastic leukemia 26 years after her initial breast cancer; the second patient developed chronic myelogenous leukemia three years after the diagnosis of breast cancer; the third patient had polycythemia vera for nine years before cancer of the breast was noted. The literature dealing with the association of cancer and myeloproliferative disorders is reviewed. Possible explanations for this association are considered.


Pseudomonas endocarditis: cure with carbenicillin and polymyxin B. A case of Pseudomonas endocarditis cured with carbenicillin and polymyxin B is described. Initially, this patient was considered a medical treatment failure when a full course of carbenicillin and gentamicin failed to effect a cure. The importance of monitoring therapy with appropriate laboratory tests is stressed.


Linkage relationship between the genes for thymidine kinase and galactokinase in different primates. In this study we investigated the expression of primate galactokinase in somatic cell hybrids between a thymidine kinase-deficient mouse cell line and two different primate cell lines, one of which was derived from African green monkey kidney cells and the other from chimpanzee fibroblasts. All the African green monkey-mouse hybrid clones, selected in HAT medium, expressed monkey galactokinase activity and contained a monkey chromosome similar to a human E-group chromosome. When these clones were backselected in medium containing 5-bromodeoxyuridine, both this chromosome and the monkey galactokinase activity were lost. All the hybrid clones between mouse and chimpanzee cells, which were selected in HAT medium, contained the chimpanzee chromosome 17 and expressed chimpanzee galactokinase activity. These results indicate that the linkage relationship between galactokinase and thymidine kinase has been maintained in 3 divergent primate species--man, chimpanzee, and Old World monkey.


Chilling of somatic cells unnecessary for Sendai virus-induced heterokaryon formation. Incubation of cell suspensions or monolayers at 4 degrees C for 20 min after addition of beta-propiolactone-inactivated Sendai virus did not enhance heterokaryon formation as compared to parallel cell cultures incubated at 37 degrees C immediately after the addition of Sendai virus. These findings show that the routine chilling of somatic cells in fusion experiments can be omitted.


Genetic homology between man and the chimpanzee: syntenic relationships of genes for galactokinase and thymidine kinase and adenovirus-12-induced gaps using chimpanzee-mouse somatic cell hybrids. The induction by adenovirus-12 of a site-specific gap and assignment of the chimpanzee genes for thymidine kinase and galactokinase were studied by utilizing chimpanzee-mouse hybrid cells. It has been shown that adenovirus-12 induces a specific gap in the long arm of human chromosome 17 (HS 17); with chimpanzee-mouse hybrid cells the specific gap appears on the short arm of the chimpanzee homolog [PTR 19 (HS 17)] of HS 17. This result supports the proposed relationship of HS 17 to PTR 19 (HS 17) by means of a pericentric inversion. The chimpanzee thymidine kinase and galactokinase genes were assigned to PTR 19 (HS 17), further confirming the homology to HS 17. Other syntenic relationships and gene assignments were consistent with proposed homologies between chimpanzee and human chromosomes.


Drug-induced acute pancreatitis.

Drug-induced acute pancreatitis. A review of the literature reflects numerous instances of acute pancreatitis developing in patients while being treated with drugs. The causative relation is not yet definitively established but, in several instances, there appears to be a probable relation. The literature records at least 112 patients with drug-induced acute pancreatitis. Fifty-one instances were caused by steroids or adrenocorticotropic hormone, six by estrogen, two by azathioprine, 16 by diurectics, two by hypercalcemia, 24 by chemotherapy, three by clonidine and phenformin, two by warfarin and one each by salicylate, 1-asparaginase and d-propoxyphene. In addition, many patients have experienced acute pancreatitis while receiving immunosuppressive therapy after renal transplantation.


Minilaparotomy as an aid to diagnosing liver disease. A series of 168 patients who underwent minilaparotomy was analyzed. Twenty of these patients underwent omentoportography only and 148, open transhepatic cholangiogram. Diagnosis was obtained in 92 per cent of those undergoing evaluation of jaundice, and cholangiography was successful in 99 per cent of those with dilated ducts and in 91 per cent of the over-all group. tthe complications of the procedure have been infrequent and have included sepsis, wound infection and renal failure and, early in the series, bile leak and bleeding. The relative merits of this procedure compared with those percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography were evaluated.


Autotransplantation of pancreatic islets without separation of exocrine and endocrine tissue in totally pancreatectomized dogs. The aims of this study were to determine whether diabetes could be ameliorated in dogs by autotransplantation of pancreatic fragments to the spleen and to determine the optimal time of collagenase digestion for pancreatic tissue dispersal. Forty-eight dogs were made diabetic by total pancreatectomy. Fifteen dogs not further treated survived 7.0+/-1.1 (SE) days with a mean plasma glucose of 401+/-5 (SE) mg/100 ml 2 days after pancreatectomy. The pancreases of 33 dogs were distended with Hanks' solution, minced, digested with collagenase (600 microns/ml of tissue), for 0 to 25 minutes, and autotransplanted to the splenic pulp. The incidence of permanent normoglycemia (fasting plasma glucose less than 150 mg/100 ml) and the K value of glucose tolerance tests (GTT) performed 2 and 10 weeks after transplant were determined in experimental groups divided according to the length of collagenase digestion. All five dogs receiving undigested tissue remained hyperglycemic. One of seven dogs receiving tissue digested for 10 minutes became normoglycemic. In contrast, seven of eight, seven of seven, and six of six dogs receiving tissue digested for 15, 20, and 25 minutes, respectively, became normoglycemic (followed for 6 months). K values at 2 weeks were 1.20+/-1.19 (SE)% 1.60+/-0.25 (SE)%, and 0.78+/-0.08 (SE)% in the normolgycemic dogs of the 15, 20, and 25 minute digestion groups, respectively. The K value of normal dogs was 3.30+/-0.27 (SE)%. The glucose tolerance curves of the 20 minute group at 2 and 10 weeks most nearly approximated the curves of normal dogs. K values improved in all recipient dogs. Diabetes recurred immediately and death occurred at a mean of 4.8+/-1.5 days in 12 recipient dogs following splenectomy. We conclude that pancreatic fragments can be successfully autotransplanted to the spleen without separation of endocrine and exocrine tissue and that 20 minutes is the optimal period of collagenase digestion for tissue preparation.


End-to-side anastomosis of the mesenteric vein to the inferior vena cava in the treatment of glycogen storage disease: case report. A 2-year-old boy with Type I glycogen storage disease received an end-to-side anastomosis of the mesenteric vein to the inferior vena cava with marked improvement in his biochemical factors and nutritional status and with shrinkage of the liver. The efficacy and simplicity of this technique and its lack of complications, as evidenced by follow-up studies over a 4 year period, suggest that its further use is warranted.


Binding of collagen by canine blood platelets. The binding of 125I-collagen (tropocollagen) by canine blood platelets occurred in a concentration-dependent manner but no saturation effect could be observed. The binding of collagen was not entirely specific for platelets since various eucaryotic and procaryotic cells quantitatively bound collagen as well or better. The temporal response to added collagen appeared to be binding, 3H-serotonin release, and finally platelet aggregation. Non-polymerizing salt-soluble tropocollagen was bound as well as acid-soluble tropocollagen, however neither 3H-serotonin release nor platelet aggregation occurred. Furthermore, the binding activity was not destroyed by treatment with collagenase, galactose oxidase and glucose oxidase, nor by periodate oxidation. Platelet aggregation closely paralleled acid soluble collagen polymerization and both events were equally inhibited by arginine; however, arginine did not interfere with collagen binding. Scanning electron microscopy revealed an unusual morphological platelet response to collagen and platelets appeared to be nucleation sites for collagen polymerization.


Enhancement of platelet sensitivity to ADP-aggregation by isometric exercise in arteriosclerosis patients and its prevention. A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points: 1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment. 2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positve significant correlations between the values obtained by these three methods. 3. It was proved to be highly reproducible and is thought to be useful clinically. By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.


Radioactive nucleic acids-precursors: their potential value as tumor-localizing agents. The distribution of 125I-uracil and 125I-deoxyuridine in tumor-bearing animals has been studied. 125I-deoxyuridine shows the characteristics of a tumor-scanning agent. The metabolic incorporation by tumors of this DNA-precursor indicates a potential value of this radiocompound for their detection, differentiation and follow-up of their evolution after therapy.


Seroepidemiology of the poliovirus in Monrovia (Liberia). Neutralizing antibodies against poliovirus have been studied in 265 persons in Monrovia (Liberia). 34% of the individuals studied possessed antibodies against the three polioviruses, 23% against two, 26% against one; the remaining 17% showed none. The three poliovirus antibodies were evenly distributed amongst the population, although there was an indication that antibodies to polio 2 occurred more commonly in females than in males. The distribution of the antibodies did not seem to be influenced by place of residence, source of drinking water or social class. Significant variations in the immunological state according to age were noted. The study of concordance and discordance of antibody titre in the blood of neonates and their mothers revealed that the lower percentage of titre concordance for polio 3 has no statistical value. The low titre in the neonates (an average for each poliovirus scarcely above 1:16) is a sign of insufficient titre in the adults. The need for a massive antipoliomyelitis campaign among infants and adult women is stressed.


A method for producing hollow cone illumination electronically in the conventional transmission microscope. An electronic device manipulates the primary beam in the conventional transmission microscope to produce a hollow cone of illumination with its apex located at the specimen. The device uses the existing tilt coils of the microscope, and modulates the D.C. signals to both x and y tilt directions simultaneously with various waveforms to produce Lissajous figures in the back-focal plane of the objective lens. Electron diffraction patterns can be recorded which reflect the manner in which the direct beam is tilted during exposure of a micrograph. In the bright-field imaging mode the device provides a microscope transfer function without zeros in all spatial directions and has been used to obtain high resolution images which are also free from the effect of chromatic aberration. A standard second condenser aperture is employed and the width of the cone annulus is readily controlled by defocusing the second condenser lens. The cone azimuthal angle is also controlled electronically; hence the device can also be used in the dark-field imaging mode. This device has been applied to imaging both amorphous and crystalline materials including biomolecular specimens.


Neuromuscular transmission in the frog at 31 ATA helium pressure. Synaptic potentials were recorded extracellularly in in vitro frog cutaneous pectoris nerve muscle preparation in air at 1 ATA and in a hyperbaric gas environment of 1 ATA air plus 30 ATA helium. Sufficient curare was always used in the bathing solution to prevent propagated muscle action potentials upon maximal stimulation of the nerve. Shape of the synaptic potential and poststimulus facilitation and depression were compared in these two environments. No significant differences were found.


Canine urinary bladder epithelial cells: preparation for cell culture by enzyme dispersion. In a qualitative and quantitative study of enzymic dispersion of cells from the mucosal layer stripped from canine urinary bladder, trypsin was found to be equal or superior to the other enzymes tested for dispersal of urothelial cells specifically. Collagenase or collagenase plus trypsin served to disperse the whole tissue. A procedure for recovering the urothelial cells as a single-cell suspension and establishing them in culture is presented. The morphology, culture behaviour, and chromosome complement of these cells is described.


Reduction of postperfusion cytomegalovirus-infections following the use of leukocyte depleted blood. After extracorporeal perfusion some patients develop evidence of cytomegalovirus (CMV) infection. It is proposed that antigenically stimulated donor and recipient leukocytes may divide and activate latent CMV associated with leukocytes. To test this hypothesis, alternate patients were perfused with leukocyte-depleted or whole blood (controls). Four of six controls who were CMV antibody negative preoperatively seroconverted after perfusion. Virus was recovered from the blood of three and from the urine of two of these patients. One of four controls who were seropositive preoperatively developed a significant titer rise. Only one of eight patients perfused with leukocyte poor blond who were seronegative prior to surgery developed a viremia and became antibody positive; another manifested a viruria but remained antibody negative. These findings are consistent with the proposed hypothesis and suggest a means for reducing transfusion-associated CMV infections.


Electron microscopic search for endogenous type C virus production in organs of dexamethasone-treated C57BL/He and C57BL/6J mice. Several organs of newborn or adult C57BL/He and C57BL/6J mice and of infant AKR mice were examined for type-C viral particles after treatment with dexamethasone, a corticosteroid hormone that stimulates C virus replication. In both C57BL strains C particles were consistently found in the exocrine pancreas of the newborns but in smaller number than that previously observed in the adults. No C particles were observed in the submaxillary salivary glands, bones or other organs examined in adult C57BL/He and C57BL/6J mice. In infant AKR mice, few C particles were observed in the exocrine pancreas or submaxillary salivary glands whereas they were found to be produced in large number by bone cells. The results suggest that in C57BL/He and C57BL/6J mice endogenous C particle production is continuous throughout life in the exocrine pancreas and is restricted to this tissue.


Keratoplasty in infants and children.

Keratoplasty in infants and children. The most common causes of acquired corneal scarring before age 6 are herpes simplex keratitis, penetrating injuries, and congenital dystrophies. We performed 18 keratoplasties in 16 eyes of 15 patients under the age of 12 years, achieving clear grafts in 14 eyes (87%). We also performed 11 grafts in nine eyes of eight patients with congenital, central corneal opacities, achieving only one clear graft and four instances of phthisis bulbi or enucleation for buphthalmos. We do not recommend penetrating keratoplasty in patients with unilateral, congenital corneal opacities. However, those with bilateral cloudy corneas should have an attempt at kertoplasty as early in life as possible. The social and psychologic condition of the family often makes the difference between success and failure.


Pathomorphology of humoral, cellular and combined primary immunodeficiencies. Histologic, immunohistologic and electron microscopic findings in three children with primary immunodeficiencies are reported. Classical X-linked infantile agammaglobulinemia Bruton was present in case 1 (male, aged 16 years), selective cellular immunodeficiency with thrombopenia in case 2 (male, aged 2 1/2 years) and non-lymphopenic severe combined immunodeficiency in case 3 (male, aged 1 3/4 years). At autopsy, all three cases exhibited unusual types of pneumonia. In case 2 a generalized cytomegalovirus infection was present. Case 3 disclosed panmyelopathia and chronic liver lesions due to severe GvH-reaction subsequent to bone marrow transplantation. A detailed morphologic study of the immune system revealed distinct alterations in the thymus, spleen, and lymph nodes and the lymphatic tissues of the gastrointestinal tract characteristic of an immunodeficiency state, either humoral (case 1), cellular (case 2) or combined (case 3).


[Radioimmunological determination of ACTH and its clinical use]. Since radioimmunological methods have been introduced, it has become possible to measure the concentration of ACTH in human plasma directly. We report on first experiences with commercial testing sets. We proved the clinical usefulness of the determination of ACTH in the cases of 13 healthy adult subjects and 8 healthy children. Furthermore patients with evidence of primary adrenal insufficiency and with disturbances in the hypothalamicpituitary system were included in our investigations. The obtained values are in agreement with the known conception of the hypothalamic-pituitary-adrenal system.


[Therapy with synthetic ACTH].

[Therapy with synthetic ACTH]. With the development of the fully-synthetic preparation (tetracosactide) the therapy with ACTH has again obtained importance. The application in internal medicine above all takes place in rheumatoid arthritis and in bronchial asthma. Advantages and disadvantages are described and the possibility of withdrawal of cortisone is especially emphasized.


[Specific and unspecific immune stimulation in recurrent herpes simplex]. According to the present state of our knowledge the clinical picture of the recurrent herpes simplex and the recurrent stomatitis aphthosa is due to a weakness of the immune defense. It cannot be decided yet if it is but a quantitative weakness or if it is a special form of disturbance in the permeation, which allows the virus to remain alive and to reactivate after a short period of time. Injection of a specific herpes simplex vaccine (HVH-1 or HVH-2 strain) or administration of Levamisol are at present the most promising ways of treatment. Both kinds of treatment are well tolerated, they give the same results in herpes simplex recidivans labialis, and whilst in herpes simplex recidivans genitalis the vaccine should be preferred, Levamisol should be given preference in stomatitis aphthosa on account of its broad (less specific) range of action.


[Herpetic eye diseases].

[Herpetic eye diseases]. The ophthalmologist differs between three forms of manifestation of the herpetic infection: 1. The superficial keratitis with involvement of the epithelium, known as keratitis punctata, stellata or dendritica. 2. The deep for: the keratitis disciformis. This is a delaged hypersensitivity against the herpes virus or its products of metabolism. 3. The metaherpetic keratopathy develops on the basis of a disturbed metabolism after relapsing, mainly deep herpetic keratitis. Therapy differs according to the forms of manifestation. The prevention of relapses is a problem. The frequency of relapses of the corneal herpes is considerably less and the intervals between the relapses are in general considerably longer than in dermatological herpes affections. Therefore, the influence on the recidivity by the drug Lupidon can be appreciated by a long-term study over several years only.


Infectious mononucleosis and mononucleosis syndromes. Infectious mononucleosis (IM) and cytomegalovirus (CMV) mononucleosis are caused by a primary infection with related viruses, Epstein-Barr virus (EBV) and CMV. Despite the similarity of clinical manifestations, basic differences exist: (1) The heterophil antibody (HA) response is absent in CMV mononucleosis, whereas it is present in IM. (2) In IM atypical lymphocytosis reflects proliferation of B cells early and of T cells later in the disease course; in CMV mononucleosis the situation appears complex. (3) In blood, EBV is restricted to B lymphocytes, whereas CMV is found in polymorphonuclear and mononuclear leukocytes. (4) Complications of CMV mononucleosis such as hepatitis and pneumonitis may be due to virus cytopathic effect in target organs. Prominent tonsillopharyngitis with adenopathy, and visceral complications of IM are related to lymphoproliferation which is self-limited except in males with a rare familial defect in defense against EBV. Immune complex-mediated pathology may occur in both diseases. (5) CMV is frequently transmitted to a fetus in utero or to an infant during or after birth, and this occasionally leads to severe cytomegalic inclusion disease; vertical transmission of EBV appears to be exceptional. (6) Secondary EBV infections are associated with certain malignancies whereas such an association has not been recognized in the case of CMV. Toxoplasma gondii is another cause of HA-negative mononucleosis. Its complications in the heart, in skeletal muscle and in the central nervous system are related to direct invasion by the parasite. Cellular immunity plays an important role in defense against all three agents.


Cytostatic efficacy of DNA-complexes of adriamycin, daunomycin and actinomycin D. I. Comparative studies in Novikoff hepatoma, human mammary carcinoma cells and human leukemic leukocytes. Inhibitory effects of adriamycin, daunomycin, actinomycin D and of the related DNA-complexes on DNA and RNA synthesis were compared by precursor uptake studies in Novikoff hepatoma cells, human mammary carcinoma cells and human leukemia cells. In addition, nuclear RNA labelling profiles were analyzed in human acute leukemia blast cells and nucleolar RNA synthesis was studied in Novikoff hepatoma cells in vitro after incubations of the tumor cells with adriamycin and DNA-adriamycin. The studies revealed that compared to the free drugs a) the DNA complexes were generally less active with respect to inhibition of overall DNA and RNA synthesis in these divergent tumor cell types, b) characteristic differences between adriamycin and daunomycin which are related to a more rapid cellular uptake of daunomycin were still present after complexing of both drugs to calf thymus DNA, and c) the intracellular mode of action of the free antibiotics was not changed by complex formation with DNA. These results indicate that a preferential incorporation of the macromolecular complexes into the tumor cells by pinocytosis--as originally postulated by Trouet et al. (1972)--is not likely for Novikoff hepatoma cells, human mammary carcinoma cells and human acute leukemia blast cells. In contrast, it may be concluded from this study that the DNA complexes dissociate already at the outer cell membrane resulting in a generally decreased but kinetically drug-specific cellular uptake. In a second communication it will be demonstrated that these in-vitro effects do not correlate with the therapeutic efficacy efficacy of the complexed drugs in vivo.


The combined modality approach in the treatment of inoperable small-cell anaplastic carcinoma of the lung. The combined modality approach with combination chemotherapy ("Comb" or "BACO") and radiotherapy was used in a pilot study comprising 35 evaluable patients with inoperable small-cell anaplastic carcinoma of the lung. Treatment strategy was based on prior assessment of prognostic factors such as histology, performance status and extent of disease. Median survival time was 39.8 weeks for "COMB" treated patients and 21.2 weeks for "BACO" treated patients. Although the combined modality approach has been very helpful against a variety of human cancers it should be used with caution since not all combination chemotherapy regimens are compatible with radiotherapy. Mechanisms of interactions between cytostatic agents and X-rays are discussed with regard to enhanced tumor cell kill and possible toxic side effects.


[The preparation of three dehydrogenases and two kinases from pig heart by a single procedure (author's transl)]. A single procedure for the preparation of lactate dehydrogenase (EC 1.1.1.27), the mitochondrial and cytoplasmic forms of malate dehydrogenase (EC 1.1.1.37), adenylate kinase (EC 2.7.4.3) and pyruvate kinase (EC 2.7.1.40) from pig heart is described. The five enzymes are obtained in preparative amounts in homogenous form with specific activities equal to or higher than those previously reported. Some molecular properties of pig heart pyruvate kinase are determined.


Inhibition of human prolyl hydroxylase as common biochemical denominator of the non-sedative effects of thalidomide in man. The two main non-sedative effects of thalidomide (2-phtalimido-glutarimide) in man are the embryopathy, which finally forced termination of its use as a sedative, and the excellent efficacy in leprosy reactions, alone for whose prevention and treatment the drug is still available. Both effects can be explained on the molecular level by assuming that a non-sedative metabolite of thalidomide mediates inhibition of human prolyl hydroxylase, as suggested by steric considerations and correlation to known data. This metabolite may well be a suitable model compound for drugs designed for selective fibrosuppression and selective immunosuppression.


Liver disease in Papua New Guinea.

Liver disease in Papua New Guinea. This paper gives, in detail, the causes of either liver disease or hepatomegaly in 100 patients, mostly adults, admitted to the medical wards of Angau Memorial Hospital, Lae, during 1968 and 1969. The major findings included liver cell carcinoma, cirrhosis (often with chronic active hepatitis), tropical splenomegaly, pericholangitis and hepatitis. There were 27 with miscellaneous findings including ten with normal, or almost normal, livers despite the definite enlargement. Patients with liver cell carcinoma presented late in the course of their illness and had a poor prognosis. Others, with pericholangitis, had clinical features of portal hypertension indistinguishable from that complicated cirrhosis. There was an unexpected number with chronic active hepatitis and a liver biopsy is essential for such a diagnosis. Hepatic sinusoidal lymphocytosis is almost invariably found in patients with TS but may occasionally be found in those with a non-palpable spleen. Patients with right heart failure of chronic respiratory disease, and jaundice of acute pneumonia were excluded from the study.


Purification of a glycoprotein from bovine leukemia virus (BLV). A precipitating antigen of bovine leukemia virus was isolated by isoelectric focusing and Sephadex gel filtration. In SDS-polyacrylamide gel electrophoresis it was found to be a homogeneous protein with a relative molecular weight of 69000 daltons. Because of its relative molecular weight and staining characteristics it was designated as BLV gp69. A protein with the same molecular weight could also be demonstrated in BLV particles. In 34 out of 35 sera from cattle affected by enzootic bovine leukosis antibodies against gp69 were detected, whereas the sera from 197 animals, free of bovine leukosis, did not react in immunodiffusion test.


African green monkey fibroblast actin morphology during SV40 infection. Monkey skin fibroblasts were infected with simian virus 40. Cells that exhibited the viral tumor antigen were found to retain the normal morphology of actin filaments up to six days after infection. However when cells were transformed in terms of focus formation they had lost the normal actin morphology.


[Isolation and characterization of a membrane-bound pyruvate dehydrogenase complex from the phototrophic bacterium Rhodospirillum rubrum (author's transl)]. The pyruvate dehydrogenase complex from the photosynthetic bacterium Rhodospirillum rubrum was associated with the membrane fraction both in heterotrophically and photosynthetically grown cells. The complex was separated from the membranes and partially purified by precipitation with MgSO4 and gelfiltration through Sepharose 4B. The purified complex had a specific activity of 1.5-2mumol/min-mg protein and contained the following partial activities: pyruvate dehydrogenase (EC 1.2.4.1), dihydrolipoamide transacetylase (EC 2.3.1.12) and dihydrolipoamide dehydrogenase (EC 1.6.4.3). Contrary to other bacterial pyruvate dehydrogenase complexes, the enzyme  complex from R. rubrum revealed no cooperatively between pyruvate binding sites. The kinetic constants (Km) for the overall reaction were (in mM): 0.14 (pyruvate), 0.07 (NAD) and 0.025 (coenzyme A). The Km for thiamine pyrophosphate was dependent on the nature and the concentration of the divalent metal ion (Mn or Mg) present in the reaction mixture, the values ranging from 0.5 to 3 micrometer. NADH was a potent inhibitor (Ki=5 micrometer) of the enzyme complex and the dihydrolipo amide dehydrogenase. The inhibition was competitive with respect to NAD. In addition to its rapid inhibitory effect, NADH also inactivated the enzyme. Cysteine partially protected the enzyme complex against NADH-inactivation. Acetyl-coenzyme A also inhibited the overall reaction (Ki=40 micrometer). The inhibition was dependent on the concentration of coenzyme A, but independent of the concentration of pyruvate. Sugar phosphates, phosphoenolpyruvate, citric acid cycle intermediates and nucleosidephosphates (1 mM) had no pronounced effect on the overall reaction.


Activity of chromatin-bound protease from rat liver and Morris hepatomas. 1. The activity of serine protease was studied in chromatin and in histone preparations from rat liver and Morris hepatomas, lines 5123 D and 7777. 2. Electrophoretic patterns of histones and the amounts of acid-soluble peptides released during incubation of chromatin and histones showed that there was no significant correlation between protease activity and tumour differentiation and its growth rate.


The plant aminoacyl-tRNA synthetases. Effect of sodium chloride on tRNA aminoacylation and aminoacyl-tRNA decomposition catalysed by aminoacyl-tRNA synthetases from yellow lupin seeds. The initial velocity and the extent of aminoacylation are affected by sodium chloride in the lupin aminoacylation systems involving serine, isoleucine, lysine, leucine, phenylalanine and valine. Pyrophosphorolysis and enzymatic hydrolysis of [14C]Val-tRNA catalysed by lupin valyl-tRNA synthetase are inhibited by sodium chloride nearly to the same extent. Evidence is presented that when a limiting amount of synthetase is used, the equilibrium of the aminoacylation reaction in the lupin valine system is determined only by the rate of aminoacylation and non-enzymatic deacylation of aminoacyl-tRNA, the former but not the latter reaction being dependent on concentration of the enzyme and monovalent salt.


[Proof of adenylate cyclase activity in the coronary artery of cattle]. In two fractions obtained from the bovine A. coronaria adenylate cyclase activity was identified and characterized. The adenylate cyclase activity of the 75,000 X g sediment shows a pH optimum at 7.4. The temperature dependence of this adenylate cyclase activity is linear when represented in the Arrhenius plot, and an Arrhenius activation energy of 13.2 kcal Mol-1 can be calculated for the enzyme reaction. The Km-value of the enzyme to ATP is 6 +/- 0.6 - 10(-4) M. The adenylate cyclase activity of the 75,000 X g sediment can be stimulated by NaF. 5'AMP and adenosine inhibit the adenylate cyclase activity of the 75,000 X g sediment. With regard to the enzyme activity, Mn++ and Co++ replace Mg++, but not Ca++. The monovalentcations Na+ and K+ do not influence the adenylate cyclase activity. In a particulate fraction containing plasma membranes, adenylate cyclase activity was also identified. This adenylate cyclase activity can be stimulated by catecholamines, noradrenaline, and isoproterenol. This stimulation can, however, only be proved for the enzyme in the coronaries of 9-week-old and 2-year-old animals. The adenylate cyclase activity from the coronaries of adult animals is not affected by catecholamines. These findings are discussed with regard to hypertension frequently found in adult animals.


5-Formyl-2'-deoxyuridine: cytostatic and antiviral properties and possible modes of action. 5-Formyl-2'-deoxyuridine (fdUrd) was prepared by a new method starting from thymidine and investigated for its influence both on proliferation of cultured mammalian cells and virus replication in vitro. The compound was found to have strong cytostatic and antiviral properties: 50% inhibition of proliferation of BHK 21/C13 cells or Ehrlich ascites tumour cells (EAT) was obtained at 4 - 10(-6) and 6 - 10(-6) M, respectively, while the treatment of pseudorabies virus with the same concentration resulted in about 1.5 log reduction of virus yield. A concentration of 1 - 10(-4) M inhibited cell proliferation by 80 to 100% while the virus yield was reduced by more than 3 orders of magnitude. All inhibitions can be prevented by thymidine.--DNA synthesis of EAT cells in vitro, as estimated by incorporation of [32P]-phosphate or low concentrations of [3H]-thymidine, was inhibited. Further biochemical experiments have provided indirect evidence that the compound is phosphorylated by thymidine and thymidylate phosphorylating enzymes. An inhibition of cell free DNA synthesis was found to be depending on a given period of preincubation with the compound (supposed to be needed for the formation of fdUrd 5'-triphosphate). This suggests that the 5'-triphosphate of fdUrd is an inhibitor of DNA polymerases and--by analogy with experiments with 5-formyluridine-5'-triphosphate and RNA polymerases [14]--may be used as an affinity label for this group of enzymes. It is concluded that the described cytostatic and antiviral effects of fdUrd are due to an intracellular "lethal" synthesis of the relevant phosphates which inhibit thymidylate synthetase (as had been found earlier to occur with the chemically prepared nucleotide in cell free extracts [1, 2]) and DNA synthesizing enzymes.


Maternal plasma triglycerides as a source of fetal fatty acids. The transfer of plasma triglyceride fatty acids from mother to fetus was studied in rats. Following i.v. injection of labelled chylomicron and very low density lipoprotein (VLDL) triglycerides into the mother, the time courses of the plasma triglycerides, free fatty acids, and fetal radioactivity were determined. The data were analysed using a mathematical model. From the results the following conclusions were drawn: To cover the need of fetal fatty acids, the placenta utilizes only VLDL triglycerides but not chylomicron triglycerides. Comparison of the amount of VLDL triglyceride fatty acids (0.04 micromoles/min/litter) and of maternal plasma free fatty acids (0.08 micronmoles/min/litter) transferred into the fetus indicates that the maternal plasma triglycerides are a source of fetal fatty acids, that cannot be neglected.


Principle and application of a multicuvette for determination of enzyme activities and substrate concentrations in microsamples. A method of photometric analysis is described that allows to determine enzyme activities or substrate concentrations of 50 samples simultaneously in a multicuvette. Test volume is in the range of 30-85 micronl, light path between 0.5 and 2.0 mm. The testing principle can be used for colorimetric measurements and for NADH dependent reactions as well. The procedure is particularly suited for kinetic determinations. Variation coefficients for determinations of substrate concentrations and enzyme activities are in the range of conventional enzymatic tests.


[Chacterization of human reticulocytes: respiration, Pasteur effect, and electron microscopic findings on mitochondria]. On 5 blood samples of newborns, whose reticulocytes had been enriched by density gradient centrifugation, and on 25 blood samples of different reticulocytoses of man were determined: the extent of intra- and extramitochondrial respiration, coupling of the electron transfer with the oxidative phosphorylation and the electronmicroscopic appearance, and the number of mitochondria. The reticulocytes occurring in the flowing human blood are in general relatively stiff and are characterized by the following properties:--low respiration--low capacity of the respiratory chain enzymes--weakened Pasteur effect --varying proportion of intramitochondrial respiration and total respiration--decoupling of a major part of the intramitochondrial respiration--low number of mitochondria--qualitative changes of mitochondria. However, there are situations of erythropoiesis where immature reticulocytes are discharged in man (similar to the socalled "stress reticulocytes" of rabbits). On the other hand, it could be shown that the reticulocytes of rabbits are mature in the normal state.


[Inoperable carcinoma of the stomach in exploratory laparotomy]. For the last few years we made 52 exploratory laparotomies. All the patients were treated clinically, through laboratories, with X-rays, and for a while ago by means of gastroscopy. A radical surgical operation was planned for each of them we made radical operation in 12 cases only, and 14 GEA. For all others we made pure exploratory laparotomy with probatory excision. Considering such inauspicious results, it is necessary to give maximum consideration to early detected gastric cancer. In a matter of critical age persons after 40, the attention must be referred to anamnestically suspect cases. For this purpose, the early detailed treatment by the latest diagnostic methods must be done. If in such treated cases there is even the smallest doubt of a malignant process, it is needful not to abstain from diagnostic exploratory laparotomy.


[The gastric syndrome in total gastrectomy using Longmire's technic and its surgical treatment]. Evaluating total gastrectomy Longmire's method in 78 cases, authors analyze appearance of symptomatology and pathological processes of agastrical syndrome. On basis of own 15-years experience, authors believe reconstruction sec. Longmire as most physiological and with minimum negative consequences successful controlled by substitutional vitamin -- enzymatic therapy.


Ganglioside content and pattern in human gliomas in culture. Correlation of morphological changes with altered gangliosides. The ganglioside level and pattern of human gliomas in monolayer cultures were examined. These gliomas revealed morphological variations that correlated with several features of ganglioside analysis. Glioblastoma lines TC 178 and TC 501 that morphologically had changed during extended subculture revealed reduced amounts and a simplified pattern of gangliosides with almost total loss of the characteristic brain complex gangliosides. In contrast, two glioblastoma lines TC 526 and TC 593, as well as the oligodendroglioma line TC 620 showed brain-like gangliosides and the cells in these cultures had maintained their characteristic morphology observed during early subcultures. The possibility that altered ganglioside levels occur in conjunction with morphological changes after propagation in vitro is discussed.


Ultrastructural study of the vacuoles in the peripheral lymphocytes in juvenile amaurotic idiocy. Juvenile form of generalized ceroid lipofuscinosis. Lymphocytes of the peripheral blood of 31 patients with juvenile amaurotic idiocy (juvenile form of ceroid lipofuscinosis) were examined with the electron microscope. In all cases, intracytoplasmic clear vacuoles were present, containing round hollow, fingerprint and highly electron dense structures. The combination of these structures, not necessarily in one and the same vacuole, was considered to be highly indicative for the diagnosis of juvenile amaurotic idiocy. In addition to these three structures, parallel tubular inclusion bodies, rectilinear profiles and rod-shaped structures were found but in a number of the cases. The parallel tubular inclusion bodies were not regarded as having any diagnostic significance.


Atypical subacute sclerosing panencephalitis. An unusual case of panencephalitis in a 4-year-old Japanese boy, with onset at three months after measles infection and rapid progression to a comatose state in approximately one month, is described. A rapid rise in serum measles antibody titre after the onset of the symptoms, and the appearance of various abnormal antibodies in the serum, were noted. Pathologically, the brain showed sclerosing polio- and leucoencephalitis with diffuse gliosis and sporadic intranuclear inclusions. The process is suggested to be intermediate or transitional between acute measles encephalitis and SSPE.


Hematogenous metastases of carcinoma to dorsal root ganglia. Hematogenous metastases of carcinoma to dorsal root ganglia was found in 2 of approximately 500 consecutive autopsies in which a lumbar dorsal root ganglion was routinely examined microscopically. The primary tumors were poorly differentiated colonic adenocarcinoma and oat cell carcinoma of the lung, both with widespread hematogenous metastases which spared the central nervous system. No symptoms were detected clinically. In the same series of patients the sural nerve as well as the lumbar plexus were histologically sampled but no examples of distant endoneurial metastases were found. The vascular endothelium of dorsal root ganglia is fenestrated and, presumably as a consequence, provides no blood-ganglion barrier. This microvascular difference may account for the susceptibility of the ganglia to metastases when compared to nerve trunks which posses unfenestrated endothelium and blood-nerve barrier.


Statistical analysis of factors affecting survival after glioblastoma multiforme. Statistical evaluation of 71 cases (adults) of histologically confirmed supratentorial surgically treated glioblastoma multiforme seen during the period 1958 to 1973 revealed that the state of calcification as determined by roentgenography and the histological appearance of the neoplasm appeared to have a relationship with the postoperative period of survival. Postoperative adjuvant treatment, location of the neoplasm, duration of preoperative symptoms, patient's age at onset, preoperative condition, and cystic formation in the neoplasm also appeared to have a relationship, although it was slight.


Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with astrocytomas. We report 137 recurrent supratentorial astrocytomas. The primary tumours diagnosed on the basis of a grading system with three stages were 72 astrocytomas I and 65 astrocytomas II. In the first group 14% of the recurrences were not changed, 55.5% became astrocytomas II, and 30.5% became glioblastomas. In the second group 55.4% were unchanged, and 44.6% became glioblastomas. The postoperative intervals untile reintervention or death were statistically examined. It seems that the recurrence time chielfy depends on the nature of the primary tumour. The transformation of an astrocytoma I to a glioblastoma takes longer than the transformation of an astrocytoma II into a glioblastoma. In about two thirds of all astrocytomas an increase of malignancy is to be expected. From the histological picture it is not possible in an individual case to predict the likelihood or speed of malignant change. With regard to the effect of irradiation the authors conclude that radiotherapy most probably does not produce malignancy.


Technetium-99m pyrophosphate myocardial uptake in patients with stable angina pectoris. 99m-technetium (Tc) pyrophosphate myocardial scintigrams of 55 patients with stable angina pectoris were compared with those of 13 normal subjects. The mean scintigraphic score, obtained by averaging the blinded interpretations of four readers scoring on an integral scale from 0 to 4, was significantly higher for the patients with angina than for the control subjects (1.36 compared with 0.48, P less than 0.001). Among the patients with angina, those who had a prior myocardial infarction had a higher mean scintigraphic grade than those without a previous infarction (1.73 versus 1.15, P less than 0.005), and the mean grade in both groups was higher than that of control subjects (P less than 0.001). Radionuclide uptake was predominantly diffuse in the patients with angina pectoris (70%), although in those with greater uptake accumulation tended to be localized. Three of the 68 subjects had high levels of radionuclide uptake but no clinical evidence of acute myocardial injury. This study demonstrates that excess myocardial accumulation of 99m-Tc pyrophosphate can occur in patients with stable angina pectoris.


Primary prevention of coronary heart disease: a critique. The question is whether alteration of risk factors will aid primary and secondary prevention of coronary heart disease. Critical review of available evidence indicates that inferences have been made about the beneficial effects of risk factor modification without an adequate test of the hypothesis. Trial interventions to assess the efficacy of serum cholesterol-lowering measures have had negative or equivocal results. It remains to be seen whether the findings of clinical trials on hypertension can be applied toward primary prevention of coronary heart disease in the community. The cigarette smoking habit seems to be unique among coronary heart disease risk factors. The evidence appears sufficient to justify serious consideration of a strategy of preventing the smoking habit now, persuading patients to stop and encouraging teenagers not to start.


Collaborative US-USSR study on the prevalence of dyslipoproteinemias and ischemic heart disease in American and Soviet populations. Prepared by the US-USSR Steering Committee for Problem Area 1: the pathogenesis of atherosclerosis. The ongoing collaborative US-USSR study of the prevalence of dyslipoproteinemias, based on the Lipid Research Clinics Study protocol, is described. The purpose of this multidisciplinary, multiclinic program is to investigate the relation of plasma lipids and lipoproteins and other risk factors to atherosclerotic disease in selected populations. The research design, sampling strategy and general hypotheses of the study are detailed. Common quality control methods and standardized screening procedures used in data collection are reviewed. Components of the study include measurement of plasma lipids and lipoproteins, the collection of demographic and physiologic information, a 24-hour dietary recall, administration of the Rose questionnaire and resting and exercise electrocardiograms. Preliminary comparative data for total plasma cholesterol, triglycerides and high density lipoprotein cholesterol are presented for men aged 40 to 59 years.


Components of 25-hydroxyvitamin D in serum of young children in upper midwestern United States. The relative importance of cholecalciferof (vitamin D3) and ergocalciferol (vitamin D2) in maintaining the vitamin D level in children (1/2 to 6 years old) living in the upper midwestern United States was determined by measurement of total 25-hydroxyvitamin D (25-OH-D), its components, and other indices of calcium homeostasis in serum. In 38 normal children, mean (range) serum total 25-OH-D was 32.8 (less than 5 to 53) ng/ml; in 25 of the 28 sera partitioned, the major component was 25-OH-D3. Significant seasonal variation in serum 25-OH-D3 (mean, range: 35.2, 17 to 51 ng/ml in summer and 15.9, less than 5 to 32 ng/ml in winter) was not accompanied by changes in mean serum 25-OH-D2, calcium, phosphorus, or alkaline phosphatase values. However, individual serum total 25-OH-D values correlated with serum phosphorus values (r = 0.37; P less than 0.05). The proportion of the total represented by 25-OH-D3 varied widely, with a a mean of 83% in summer and 67% in winter. Sources of D3, which include both dermal synthesis and intestinal absorption of D3 added to milk, appear to be more important than sources of D2 in maintaining vitamin D nutrition of young children throughout the year. However, sources of D2 offset the decrease in total 25-OH-D in winter months.


Intranasal mixed tumors (pleomorphic adenomas): a clinicopathologic study of 40 cases. The clinical, gross, and microscopic features of 40 cases of intranasal mixed tumor (pleomorphic adenoma) are reviewed and studied. The majority of these neoplasms originate from the mucosa of the bony or cartilaginous septum; they also occur on the lateral nasal wall. They may be found at any age, but the majority of our cases occurred in persons in the third through sixth decades of life. There was no significant sex predilection. All patients whose race was recorded (35) were Caucasian. The patients commonly had symptoms of nasal obstruction or the presence of a mass in the nasal cavity, or both. Clinically, the lesions were not unique, frequently being described only as polypoid, broad-based swellings. Microscopically, although similar to mixed tumors of major salivary glands, these tumors differed by being highly cellular (epithelial), with little or no stromal component, and thus simulated more aggressive epithelial neoplasms. Follow-up data (mean 7.5 years) in 34 of the 40 cases showed no evidence to suggest aggressive behavior. Thirty-one of the 34 cases followed showed no recurrence, regardless of the type of excisional procedure used. Those that did recur were either persistent from inadequate primary excisions (2 cases) or recurred locally (1) and were removed without sequelae. Local but adequate excision appears to be the treatment of choice.


Sensitive fluorimetric assay for serum angiotensin-converting enzyme with the natural substrate angiotensin I. A simple, rapid, highly sensitive and reproducible fluorimetric assay for angiotensin-converting enzyme in untreated serum using the natural substrate based on a similar assay with hippuryl-L-histidine-L-leucine is described. Angiotensin I (0.2 mM in 0.1 M potassium phosphate-30 mM NaCl, pH 7.5; 37 C) is converted to angiotensin II and L-histidyl-L-leucine, which is quantified fluorimetrically (excitation = 360 nm; fluorescence, 500 nm) by formation of a fluorescent adduct with O-phthaldialdehyde. L-Histidyl-L-leucine peptidase was also monitored in order to correct for significant activity, which was observed only once, in less than 1% sera. The mean value of serum angiotensin-converting enzyme in sera from 45 normal subjects was 4.69+/-0.194 (SEM)+/-1.30 (SD) nmol/min/ml serum, compared with 31.7+/-1.53 (SEM)+/-10.3(SD) with the substrate analog hippuryl-L-histidine-L-leucine. There was a high degree of correlation between the velocity of cleavage of angiotensin I and hippuryl-L-histidyl-L-leucine (r - 0.903 to 0.993). The assay of serum angiotensin-converting enzyme is of use in the diagnosis and possible management of sarcoidosis and Gaucher's disease, and may have other applications.


Comparison of primary rhesus and cynomolgus monkey kidney cell cultures for viral isolation from clinical specimens. Rhesus monkey kidney and cynomolgus monkey kidney cell cultures were compared for viral isolation by using clinical specimens that yielded 203 viral isolates. Cynomolgus and rhesus monkey kidney cells were comparable for the isolation of 22 adenoviruses, 12 coxsackieviruses, and one poliovirus. Four of 50 echoviruses and seven of ten herpesviruses were detected only in cynomolgus monkey kidney cells. Influenza virus was isolated in 84 instances, of which eight were detected only in rhesus and four only in cynomolgus monkey kidney cells. Rhesus monkey kidney cells yielded six more parainfluenza virus isolates. Except possibly for parainfluenza virus, cynomolgus monkey kidney cells appear to be as sensitive as rhesus monkey kidney cells for viral isolation from clinical specimens.


Viruses associated with acute gastroenteritis in young children. Conventional virologic investigations generally failed to implicate viruses as a cause of acute gastroenteritis in young children. When negative-contrast stain electron microscopy was used for the examination of stool samples from affected patients, several candidate etiologic agents were discovered. Rotavirus (otherwise known as orbivirus, reo-like agent, and infantile gastroenteritis virus) emerged as an important causative agent. In a considerable number of patients, however, no causative agent was identified. Several other candidate etiologic viruses now "stand in the wings" awaiting additional evidence as to their role in the pathogenesis of acute gastroenteritis. In a study period of 12 months, 669 patients were found to be shedding virus in association with symptoms of diarrhea, vomiting, and temperature elevation. Approximately one third of these patients acquired their infection in hospital.


Clinical manifestations of renal allograft derived primary cytomegalovirus infection. Seventy seven patients, thirteen younger than 20 years of age, were followed up prospectively for the first three months after renal transplant for evidence of infection and illness due to cytomegalovirus (CMV). Thirty-two developed reactivation of latent CMV and 29 did not develop any CMV infection and wn, five had pneumonia, and four underwent nephrectomy. Of these, 16, eleven received a kidney from a parent, whereas of the other 61 patients, five received parental kidneys (P less than .001). Hence, CMV seronegative individuals who received a kidney from a CMV seropositive parent developed clinical illness and sometimes lost the allograft.


Plasma 25-hydroxyvitamin D and urinary cyclic AMP in German patients with subtotal gastrectomy (Billroth II). In an attempt to clarify the pathogenesis of the disturbed calcium metabolism which sometimes follows partial gastrectomy, we determined plasma 25-hydroxyvitamin D (25-OH-D) concentrations and urinary cyclic 3',5'-adenosine monophosphate (cAMP) excretion in patients who had previously undergone Billroth II gastrectomy and who were without clinical evidence of bone disease. In 17 Billroth II patients plasma 25-OH-D concentrations were reduced (12.6 +/- 4.6 ng/ml, mean +/- SD) compared to values in 17 control patients with diseases not affecting calcium metabolism (31.6 +/- 12.9 ng/ml, P less than 0.001). Urinary cAMP excretion, in part reflecting parathyroid function, was higher in 17 Billroth II patients (5.0 +/- 2.5 micronmol/day) than in the control patients (2.6 +/- 1.3 micronmol/day, P less than 0.001). These results suggest impaired nutrition of vitamin D and secondary hyperparathyroidism in Billroth II patients. While the cause of this phenomenon is unclear, it may contribute to the disturbance of calcium metabolism in patients who have had subtotal gastrectomy.


Cyclic adenosine monophosphate and human gastric acid secretion. This report concerns gastric juice, plasma, and urinary levels of adenosine 3',5'-monophosphate (cAMP) in 27 subjects undergoing routine gastric analysis under maximum stimulation with betazole or pentagastrin. Cyclic AMP was measured by sensitive and specific radioimmunoassay. No increase in concentration of cAMP was noted in gastric juice, plasma, or urine following either betazole or pentagastrin stimulation. Betazole-stimulated human gastric acid secretion was associated with an increased cAMP output into the gastric juice (P less than 0.05). There was no change in cAMP output following pentagastrin stimulation. The peak acid output produced by pentagastrin and betazole was similar. The lack of increase in cAMP concentration lends support to the concept that cyclic AMP is not a primary mediator in the stimulation of gastric acid secretion by betazole or pentagastrin in the human. The physiologic significance of the increase in cAMP output following betazole stimulation remains unresolved.


Genetic complementation of propionyl-CoA carboxylase deficiency in cultured human fibroblasts. Propionyl-CoA carboxylase (PCC) deficiency is an inherited metabolic disorder showing considerable variability of expression. We have investigated the possibility that there is a genetic basis for the clinical heterogeneity in this disorder by examining complementation in Sendai virus mediated heterokaryons of mutant fibroblast strains. Restoration of PCC activity was monitored in individual multinucleate cells in situ using a radioautographic procedure which detects the incorporation of 14C-propionate into trichloracetic acid precipitable material. Each mutant strain incorporated negligible amounts of radioactivity compared to control strains. Activity was not restored when different mutants were mixed without virus or when homokaryons were produced by self-fusion. Seven mutant strains were fused in all pairwise combinations and examined for increased 14C-propionate incorporation in heterokaryons. Two main complementation groups were revealed. One group was composed of three mutants. The other was a complex group composed of four mutants in which intragroup complementation was demonstrated. Two mutants showing excellent complementation by radioautography were examined for complementation by the direct assay of PCC ACTIVITY. The enzyme activity of virus-treated preparations with 23% multinucleate cells was 183 U (pmol/min/mg protein) compared to 16 U for the untreated mixture (normal range 450-850 u). We conclude that PCC deficiency resulted from mutations of heterogeneous origin, although the classification of mutants into complementation groups did not correlate with patterns of clinical heterogeneity.


Human red cell 2,3-diphosphoglycerate mutase and monophosphoglycerate mutase: genetic evidence for two separate loci. Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis. The isozyme patterns showed that genetic variation of the enzymes were independent from each other, thus DPGM and MPGM must be controlled by two separate loci.


Pathogenesis of the slow disease of the central nervous system associated with WM 1504 E virus. I. Relationship of strain susceptibility and replication to disease. Inbred mouse strains vary considerably in their susceptibility to the chronic neurologic disease caused by WM 1504 E virus. Although all strains inoculated with the virus showed evidence of viral replication, those strains destined to develop chronic disease showed consistently higher titers of viral antigen in their sera and also in their tissues, particularly in the central nervous system, than did resistant strains. Studies of hybrids made by mating susceptible C57BR/cdJ and resistant C57BL/6J strains indicated that resistance is dominant and not sex linked. The major areas of injury included neurons in the anterior horn of the spinal cord, the dentate nucleus of the cerebellum, and other nuclei in the brain stem. Involvement of oligodendrocytes with associated primary demyelination was also noted. Tissue damage accompanied intense gliosis but was without leukocyte infiltration. Immunopathologic studies and parabiotic experiments suggested that tissue injury was likely due to primary direct viral effects. Further, thymus-insufficient nude mice developed this chronic neurologic disease.


Surface morphology of normal and neoplastic rat cells. Nontumorigenic rat cells and their tumorigenic counterparts were studied with scanning electron microscopy under controlled conditions in vitro and with transmission electron microscopy after replantation in vivo to discern if external morphology reflected the cell's neoplastic state or the etiology of transformation. Interphase cells in six of seven nontumorigenic lines were flat and monolayered under confluent conditions and exhibited smooth, nonactive cell surfaces. A nontumorigenic cell line morphologically transformed with human adenovirus-2 consisted of spherical cells with blebbed surfaces. Cells from six tumorigenic lines transformed with avian sarcoma virus had highly active surfaces with many surface projections. Cells from two chemical carcinogen-transformed rat embryo lines were flat with no surface projections in subconfluent culture and rounded with only a few microvilli at high densities, but cells from a sarcoma chemically induced in an adult rat were villous. When villous cells were syngeneically replanted in vivo, they lost most microvilli. The external morphology of cells was influenced by a number of factors simultaneously, with no universal pattern associated with tumorigenic capacity or transforming agent.


Early lesions of pancreatic ductal carcinoma in the hamster model. Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system.


Somatostatin-immunoreactive cells in medullary carcinoma of the thyroid. Ten medullary carcinomas of the thyroid were examined by immunohistochemistry using antisera against calcitonin, somatostatin, and ACTH. In addition to calcitonin cells, eight of the tumors contained somatostatin-immunoreactive cells in varying numbers. No ACTH-immunoreactive cells were found. The results indicate that thyroid medullary carcinomas often are multihormonal, and that somatostatin is common in such tumors. In contrast to calcitonin cells, somatostatin cells are not found in normal human thyroid tissue.


Calcium dependence of neuromuscular events in esophageal smooth muscle of the opossum. Intramural nerves in smooth muscle strips from opossum esophagus were stimulated electrically to cause contractions of longitudinal body muscle, off responses of transverse body muscle and relaxations of sphincter muscle. Krebs solution was modified by calcium removal by strontium substitution for calcium, by adding magnesium, and by adding nitroprusside. Longitudinal muscle contractions were abolished by calcium removal and by excess magnesium; they were unaffected by nitroprusside; strontium could not replace calcium. Off responses were abolished by calcium removal and by excess magnesium; they were depressed by nitroprusside; strontium effectively replaced calcium. Resting active tension in sphincter strips was partly reduced by calcium removal and by excess magnesium; it was abolished by nitroprusside; strontium could not replace calcium. Relaxations in sphincter strips were unaffected by all experimental conditions. Longitudinal contractions, off responses, and resting active tension of the sphincter represent different kinds of calcium activation of muscle. The excitatory nerves (which are cholinergic) in longitudinal muscle are calcium dependent, the nerves that produce off responses may not be, and the nerves that relax the sphincter are not.


Fibrinogen synthesis stimulation by prostaglandin E1 and some other vasodilators. Three-hour constant-rate intravenous infusion into rabbits of 1-3 mg prostaglandin E1 (PGE1) per kilogram markedly increased plasma fibrinogen 24 h later. 131I-labeled fibrinogen and model studies showed increased synthesis underlay this. Similar PGE1 doses lowered systolic blood pressure. Maintaining systolic blood pressure by infusing noradrenaline with the PGE1 did not alter plasma fibrinogen response to PGE1; plasma fibrinogen was unchanged by noradrenaline infusion. Regression equations relating plasma fibrinogen increment to PGE1 dose, plasma fibrinogen increment to dose and systolic blood pressure change, and systolic blood pressure change to dose are given as well as the constants relating plasma fibrinogen increment to dose using the Michaelis-Menten equation. Infusions of cyclic AMP, dibutyryl cyclic AMP, and cyclic GMP intravenously led to only small plasma fibrinogen increases. Daily intravenous infusions of PGE1 led to loss of both plasma fibrinogen and systolic blood pressure responses in two animals; a third animal showed only loss of the former and a fourth only loss of the latter response. PGE1 slightly enhanced the small plasma fibrinogen increase following intravenous bradykinin. Approximate arterial blood PGE1 concentrations resulting from the intravenous infusion of 1 mg mg PGE1 kg-1 3 h-1 are calculated. These are compared with measured values.


Action of adenosine and adenine nucleotides on dogs' isolated veins. Adenosine depressed norepinephrine contractions of dogs' saphenous vein strips in both the presence and the absence of Ca2+ and after inhibition of calcium influx by verapamil. It antagonized noncompetitively contractions induced by Ca2+ in depolarized strips after alpha-adrenergic blockade. Contractions obtained with acetylcholine were also depressed by adenosine. This depression was not accompanied by an increase in cAMP or a decrease in the elevated cGMP level. Thus the depression of the smooth muscle cell reactivity still occurs in the absence of calcium influx and is not mediated by the cyclic 3',5'-nucleotide system. Adenosine diphosphate and triphosphate, but not adenosine (10(-6) to 10(-4) M), increased the basal tension of resting saphenous strips. This was prevented by removal of calcium from the bath. In contracted strips, lower concentrations of both nucleotides (10(-6) to 10(-5) M) caused relaxation whereas with high concentrations (10(-4) to 10(-3) M) further contraction occurred. Thus, unlike adenosine, the adenine nucleotides facilitate calcium influx.


Renin-angiotensin-aldosterone system of the normothermic marmot. Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species.


In defense of community mental health.

In defense of community mental health. Initial enthusiasm for community mental health has given way to a barrage of criticism, musch of it deserved. Originated to deal with abysmal conditions in state hospitals, community mental health focused instead on primary prevention, political activism, and the mildly mentally ill. The authors propose a return to the original fundamentals, stressing that the highest priority be given to community treatment and rehabilitation of the severely mentally ill.


Carcinoma of the parotid gland.

Carcinoma of the parotid gland. Sixty-nine patients with parotid gland cancer were studied at the Cancer Control Agency of British Columbia; half were treated successfully. Localized cancers should be treated by total parotidectomy with facial nerve preservation. Facial nerve sacrifice and radical neck dissection for metastatic lymph nodes may be required. If adequate surgery has been done, the histologic type of the tumor significantly determines the outcome. Postoperative radiation to the parotid bed in the more malignant types of tumor is advocated and appears to improve the results of treatment.


Bacterial flora of stored human donor corneas after antibiotic treatment. In 100 out of 122 eyes obtained at autopsy, bacteria could be cultured in swabs taken from the conjunctivae. After individual storage of the excised corneas at +4 degrees C in a modified tissue culture medium containing 100 microgram/ml Gentalmicin, in 18 culture specimens there was still some growth of microorganisms. In comparison to nine other antibiotics, Gentamicin was the most effective against cultivated bacteria in a sensitivity test. However, in 25% of the specimens Ps.aeruginosa was resistant to Gentamicin. Polymyxin, to which Ps.aeruginosa was not resistant in the same test, should be used in combination with Gentamicin for antibiotic treatment of stored human donor corneas.


Cutaneous bullae in coma due to poisoning. An association with deep seated ischaemic lesions of muscle. A deeply unconscious patient may develop ischaemia in those soft tissues subjected to pressure. Pressure on the skin may give rise to blistering which is reversible. Pressure on the limbs may precipitate irreversible ischaemia of the muscles and nerves unless a fasciotomy is performed.


Scanning electron, light, and immunofluorescent microscopy of intestine of gnotobiotic calf infected with reovirus-like agent. Intestinal lesions caused by a calf diarrheal reovirus-like agent were studied by scanning electron microscopy, light microscopy, and immunofluorescent microscopy in 2 gnotobiotic calves inoculated per orum. The calves were euthanatized 6 hours after the onset of diarrhea. Villi in the cranial and middle parts of the small intestine appeared shortened. In these areas, the epithelium was composed of low columnar and cuboidal cells. Villi in the caudal part of the small intestine were short. By scanning electron microscopy, the villous epithelium in the caudal part of the small intestine of both calves and the ridge epithelium in the ansa spiralis coli of 1 calf were composed of various sized cells which gave the surfaces an irregular appearance. The amount of mucopolysaccharide in the colonic epithelial cells of both calves was greatly reduced. The combined use of scanning electron and light microscopic techniques enabled obtaining a more accurate description of the intestinal lesions than either technique alone.


Specific suppression of the bursa-dependent immune system of chicks with infectious bursal disease virus. Chicks which had been inoculated with infectious bursal disease virus (IBDV) at 1 day of age had a severe depression of bursa-dependent humoral immune functions by day 42. Antibody responses against rabbit red blood cells or to immunization with bovine serum albumin were significantly suppressed. In contrast, chicks inoculated with IBDV at 21 days of age produced near normal antibody responses as compared with the responses in noninfected control chicks. The IBDV had no significant effect on the thymus-dependent cellular responses as measured by skin graft rejection or delayed type hypersensitivity reactions to tuberculin.


Immunoglobulin G subclass [IgG and IgG(T)] interaction with the P26 group specific antigen of equine infectious anemia virus: immunodiffusion and complement-fixation reactions. Isolated equine immunoglobulin (Ig)G(T) antibodies to equine infectious anemia virus P26 antigen did not precipitate with antigen when the ratio of antibody to antigen was high. However, at lower ratios of antibody to antigen precipitation occurred. In addition, complement-fixation by IgG and P26 antigen was inhibited by high concentrations of IgG(T). The unusual reaction pattern noted with IgG(T) antibodies was still detectable by the immunodiffusion test for equine infectious anemia virus. In situations of nonprecipitability by IgG(T), the adjacent positive control line was inhibited, and this was interpreted as a positive reaction.


Equine herpesvirus 1 infection of horses: studies on the experimentally induced neurologic disease. Experimental infection with equine herpesvirus 1 (rhinopneumonitis) resulted in neurologic disease in 8 of 15 inoculated horses. Nonpregnant animals did not develop clinical disease, and microscopic examination of tissues revealed no changes. In all mares between 3 and 9 months of gestation, a neurologic syndrome appeared 6 to 8 days after inoculation. Mares inoculated when 10 months pregnant did not develop neurologic disorders, but several aborted. The histopathologic change common to both sequelae was vasculitis, involving smaller arteries and veins. Although blood vessel changes were detected in endometrium of all pregnant mares, vascular changes were present in the central nervous  system only in mares having neurologic disease. Concomitant degeneration of nervous tissue occurred within the central nervous system and, in many sites, anatomic and temporal relationships of vasculitis and nervous tissue degeneration suggested a cause-effect relationship. This theory was strengthened by the lack of usual histopathologic indications of encephalomyelitis. In cerebrospinal fluid from affected mares, there was an increase in protein but not pleocytosis.


Clinical, serologic, and cross-challenge response and virus isolation in cattle infected with three bovine dermatotropic herpesviruses. The relationship of 3 dermatotropic bovine herpes-viruses (bovine mamillitis herpesvirus, dermatotropic bovine herpesvirus, and Allerton virus) was investigated; special emphasis was on the clinical response and the development of complement-fixation and precipitating antibodies in cattle. The immune respnse in steers was determined throughout the disease and after challenge exposure of the steers with 1 of the other 2 herpesviruses. Blood samples and sections of skin were collected intermittently from infected animals and examined for presence of virus.


Immunoglobulin response to bluetongue virus soluble antigen in subcutaneous chambers. Group-specific antibodies were produced by inoculation of bluetongue virus soluble antigen into polyethylene chambers implanted subcutaneously in 8 rabbits and 2 sheep. For comparison, 5 rabbits and 1 sheep were inoculated intramuscularly with the soluble antigen in Freund's complete adjuvant. Antibodies present in the serum and chamber fluids were detected by the agar gel precipitin or serum-neutralization tests, qualitatively examined by immunoelectrophoresis and immunofluorescence, and quantitated by electroimmunodiffusion.


Reproduction and treatment of necrotic enteritis in broilers. A change in ration from one containing 50% fish meal to a standard chick starter containing 10(8) Clostridium perfringens/g of feed resulted in the production of necrotic enteritis in 2-week-old broiler chicks. Lincomycin added to the inoculated ration at a concentration of 20 g/907.2 kg significantly reduced mortality in the chicks. Inoculation of broth cultures of C perfringens directly into the duodenum, using a surgically inserted tetrafluoroethylene resin tube, indicated a relationship existed between the number of C perfringens inoculated and the gross lesions. The disease could be consistently produced by this technique.


Effects on interferon of heavy metal excess and zinc deficiency. Near toxic concentrations of cadmium sulfate, mercuric chloride, and nickel sulfate reduced interferon action in tissue cultures, but increased intake by the intact mouse of lead acetate and mercuric chloride did not reduce interferon action. Lead and nickel given orally inhibited the protective activity of Newcastle disease virus against encephalomyocarditis virus-induced mortality, whereas cadmium, mercury, cobalt sulfate, and sodium arsenite given orally and deficiency of zinc did not influence this action. Excess lead and cobalt and deficiency of zinc, but not excess cadmium, mercury, or nickel, inhibited the protective activity of poly I/poly C against encephalomyocarditis virus-induced mortality. These results illustrate the various actions of increased concentrations of certain metals or a deficiency of zinc on interferon action or on actions of interferon inducers.


Effects of heavy metals and of deficiency of zinc on mortality rates in mice infected with encephalomyocarditis virus. Salts of cadmium, lead, mercury, and nickel given orally to mice increased encephalomyocarditis virus-induced mortality rates. Although lead was the least toxic of the 4 metals, it enhanced the mortality the most. Concentrations of mercuric chloride as low as 0.01 ppm intensified the mortality; a minimal concentration that resulted in no effect was not ascertained. Zinc deficiency caused pronounced retardation of growth in young mice, but it did not influence mortality due to encephalomyocarditis virus.


Evidence for the replication of bovine leukemia virus in the B lymphocytes. Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells.


Current management of carcinoma of the anus and perianus. Malignant lesions of the anus and perianus account for 2.4% of malignant cancers of the colon, rectum, and anus. Based on our experience with 56 patients as well as a review of the recent literature, the following recommendations are made: Bowen's disease, Paget's extramammary disease, basal cell, and perianal epidermoid carcinomas arise in the perianus, rarely metastasize, and may be managed by wide local excision. Cloacogenic transitional cell (basaloid squamous carcinoma) and the more common epidermoid anal canal tumors require abdominoperineal resection with wide perineal excision. Therapeutic groin dissection is indicated if the inguinal nodes are or become the site of metastases, but prophylactic groin dissection is not indicated. The five-year survival for epidermoid carcinoma of anus treated by abdominoperineal resection ranges from 40 to 58%. Improvement in survival rate will require early recognition by the patient and early diagnosis and treatment by the physician. Delay in diagnosis occurs because cancer is not considered frequently enough as a possible cause for the patient's symptoms.


Transmission of non-A, non-B hepatitis.

Transmission of non-A, non-B hepatitis. In studies conducted in the early 1950s, sera from six asymptomatic blood donors, implicated in the transmission of viral hepatitis, were inoculated into 10 to 20 volunteers each. Five of these "implicated" donor sera transmitted clinically apparent hepatitis to the recipients. The stored serum samples from these studies have been reanalyzed using serologic markers for hepatitis B virus and hepatitis A virus infection. Two of the donor sera were hepatitis B surface antigen (HBsAg)-positive, and both transmitted hepatitis B virus infection to all susceptible recipients, half of whom showing clinical symptoms. The remaining three infectious donors were HBs-Ag-negative, yet were icterogenic to 10% to 47% of recipients. Testing of serum samples from these recipients with hepatitis showed no evidence of hepatitis B virus or hepatitis A virus infection. This study and other recent evidence suggest that there is a third type of human viral hepatitis--non-A, non-B hepatitis--which is due to a transmissible agent and may well be associated with a chronic carrier state.


Parenterally transmitted non-A, non-B hepatitis: an epidemic reassessed. In 1972 a nonsocomial outbreak of parenterally transmitted hepatitis affected both marrow transplant patients and normal platelet donors in an oncology unit. Because of the characteristics of the clinical illness, the incubation period of 27 days, and the effect of immune serum globulin on the clinical illness, the outbreak was attributed to hepatitis A; there was no serologic evidence of either hepatitis B virus or cytomegalovirus infection. Stored serums from this outbreak were re-examined by more recently developed serologic techniques for evidence of hepatitis A (HA) virus infection. Ten patients and donors had undetectable anti-HA titers before illness and none seroconverted; five persons had pre-existent anti-HA titers and showed no further rise in convalescent serums. The serum of one patient was inevaluable. With the availability of serologic techniques for the diagnosis of both hepatitis A and hepatitis B virus infections, it is clear that most cases of post-transfusion hepatitis are not due to either of these agents, and short-incubation-period hepatitis can not be assumed to be hepatitis A without further investigation.


Pathophysiology of myocardial infarction. Primary prevention of death from ischemic heart disease requires further understanding of the pathogenesis of this disorder. Cellular defects of cholesterol metabolism may be more significant markers that serum lipid levels for the identification and treatment of atherosclerotic risk. Coronary spasm has been shown to be an important cause of ischemia in the presence and absence of atherosclerotic lesions. Careful manipulation of physiologic variables with vasodilator agents during cardiopulmonary bypass can substantially alter the myocardial oxygen supply-demand relation, thereby minimizing ischemic injury. The cellular basis for loss of mechanical function during ischemia and the factors that determine irreversible injury are yet unknown.


[Epitheliomas of the retro-molar trigone and of the inside surface of the cheeks (author's transl)]. The authors have made a study of 53 cases of tumours of the retro-molar trigone and of the internal surface of the cheeks which were treated between 1959 and 1972; these were malphigian epitheliomas except for one case of cylindroma. The research is concerned with the choice of methods and the therapeutic indications. Retro-molar trigones call for combined telecobaltherapy-electrontherapy;--curie-therapy is too difficult in this area. Electrontherapy may be used on alternate days with telecobaltherapy or as a booster dose after external irradiation by cobaltherapy. In cases of epitheliomas of the cheek, curietherapy or electrontherapy may be used after external irradiation or in isolation for tumours which are small in size. Therapeutic results are satisfactory in lesions at the outset (7/8 and 7/9), for T1-T2. For advanced lesions T3 of the trigone (6/16) and especially for those of the internal surface of the cheeks (2/9), the success rate is considerably lower; in lesions of the T4 type, a palliative effect was obtained but without any definite improvement.


[Molecular mechanism of the action of lucanthone on tumor and normal cells]. The standard analytical and preparative electrophoresis in polyacrylamide gel did not reveal qualitative differences in the fraction composition of c-RNA of the ascitic tumour cells (Zaidel hepatoma, Ehrlich carcinoma, NK/ly lymphoma) and normal liver cells. In vitro the tumour and normal cells efficiently incorporated the labeled uridine into the all main classes of c-RNA (4S, 18S, 28S, fractions above 28S), the process being more intensive in the tumour cells. The presence of tumours in the animal organism had a significant effect on RNA biosynthesis in the liver, the effect being dependent on the tumor nature. Lucantone (miracyl D) had practically no effect in vitro on the quantitative content of the summation c-RNA and its fractions in all cells studied. However, it markedly inhibited the metabolism of the main fractions of c-RNA in the cells of Zaidel hepatoma and Ehrlich carcinoma. The effect of lucatone in the cells of NK/ly lymphoma was contrary.