The coexistence of nodular and diffuse patterns in nodular non-Hodgkin's lymphomas: significance and clinicopathologic correlation. One hundred and twenty-six cases of nodular lymphoma have been classified cytologically by the criteria of Rappaport, and have been divided into three architectural groups, based on the degree of nodularity. Eighty-five percent of the patients have been followed for at least 5 years after initial therapy. Analysis of actuarial survival curves reveals that patients in the poorly differentiated lymphocytic and mixed histiocytic-lymphocytic categories with the three architectural patterns ("nodular only," "nodular with focal diffuse," and "nodular with diffuse") have similar long-term and disease-free survivals. Nevertheless, any degree of nodularity imparts a more favorable prognosis than diffuse lymphoma of coreresponding cell type. In the small number of patients with a nodular lye than in the other two histiocytic type, associated with diffuse areas, the prognosis is less favorable than in the other two histologic groups. Thus, a nodular lymphoma of so-called histiocytic type with diffuse areas may behave more like a diffuse than nodular lymphoma, and warrants appropriate therapy.


Chromosomes and causation of human cancer and leukemia. XXV. Significance of the Ph1 (including unusual translocations) in various acute leukemias. The following rare Ph1-positive chromosome constitutions, based on the cytogenetic findings in three cases with acute leukemia, are presented. 1) A hypodiploid karyotype, primarily 43, -X, -7, -8,9p+ and a Ph1, in a patient with acute lymphoblastic leukemia (ALL) in relapse, followed by a complete remission and a normal chromosomal picture and then by the appearance of cells with a 46,XX,Ph1 karyotype. The Ph1 was due to a standard translocation between chromosomes no. 9 and no. 22. 2) The first demonstration of an unusual Ph1-translocation between chromosomes no. 19 and no. 22 in a condition other than chronic myelocytic leukemia (CML), i.e., acute myeloblastic leukemia (AML). 3) The presence of a Ph1 in acute erythroleukemia (EL) due to a translocation between chromosomes no. 4 and no. 22, this apparently being the first description of such a translocation in any disease. The cytogenetic findings, particularly those in the Ph1-positive case of ALL, were evaluated in relation to the cytologic and immunologic features, clinical courses and implications, and the interrelationship between the three conditions (AML, blastic phase of CML and ALL), which have to be considered in cases of Ph1-positive acute leukemia.


The epidemiology of bladder cancer: a second look. A case-control study among 574 male and 158 female bladder cancer patients and equal numbers of matched controls was conducted between 1969 and 1974 in 17 hospitals in six United States cities. We determined that cigarette smokers of both sexes were at higher relative risk than nonsmokers. Cigarette smoking was responsible for about one-half of male and one-third of female bladder cancer. There was an excess of bladder cancer patients with some previous occupational exposure, such as rubber, chemicals, and textiles. A weak association with coffee drinking, which appeared to be independent of smoking, was found for males. Users of artificial sweeteners were not over-represented among the cases. The authors conclude that the epidemiologic pattern of bladder cancer cannot be fully accounted for by cigarette smoking and occupational exposure and suggest a series of metabolic studies to assess the role of additional factors, such as nutrition.


Consequences of acute myelogenous leukemia in early pregnancy. Cytarabine and thioguanine therapy for acute myelomonocytic leukemia initiated in the tenth week of pregnancy (with the addition of vincristine and rubidomycin at 17 weeks) led to a short complete remission of the leukemia in a 24-year-old primigravida. This is the first case to be reported in which cytarabine was administered in the first trimester and a prostaglandin termination of pregnancy performed at 20 weeks produced an apparently normal fetus. A review of the literature suggests a slightly less than 50% chance of producing a live healthy baby if acute myelogenous leukemia is diagnosed in the first half of pregnancy, with materna mortality approaching 100% by six months postpartum. Current therapy may improve these figures.


Characterization of urothelial carcinoma with respect to the content of carcinoembryonic antigen in exfoliated cells. A sutstance immunologically similar to carcinoembryonic antigen (CEA) was demonstrated in urothelial bladder carcinoma cells. When indirect immunofluorescence with specific anti-CEA antisera was used, CEA-containing cells were seen in 18 out of 40 cases in 5% to 30% of the cells. Among patients with tumor cells of well differentiated morphology, 61% had CEA-containing cells, compared with only 24% of patients with a poorly differentiated tumor. Microfluorometry of single cells was performed in six cases to estimate the range of CEA content. The mean fluorescence intensity with anti-CEA antiserum was three to six times that of the same tumor cell population stained with non-immune rabbit sera. This fluorescence was decreased when the anti-CEA anti-sera were incubated with CEA but not with nonspecific cross-reactive antigen. The results show a wide range of CEA antigen content in exofoliated bladder tumor cells. In addition to proliferative status and differentiation, quantitative CEA measurements give further possibilities to study characteristics of tumor cell populations.


Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma. A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All aptients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care.


Basal cell carcinoma of the nipple: case report and review of the literature. An unusual case of basal cell carcinoma of the nipple from a 66-year-old women is presented. It is important to differentiate this lesion from other nipple-areolar tumors, especially Paget's disease. This report reviews the literature and adds a case that represents the third reported instance of this tumor of the female nipple.


Tobacco and alcohol consumption in relation to the development of multiple primary cancers. The relationship between tobacco and alcohol consumption and the development of additional primary cancers of the upper alimentary tract is reviewed. The chance of developing a second primary is dependent principally on the intensity (i.e., quantity and duration) of the smoking and drinking habit prior to the onset of the first neoplasm. However, results conflict regarding the effect exerted by the continuation of these habits after the first diagnosis. While tobacco smoking is considered the primary risk factor associated with cancers in this area, its interaction with alcohol creates a powerful carcinogenic effect. It is agreed that multiple primaries are selective on a site-specific basis and that risk varies with anatomic location of the first primary.


Role of diet in cancer etiology.

Role of diet in cancer etiology. Current evidence for the involvement of diet in cancer etiology is based on indirect relationships between the consumption of selected food constituents and incidence, dietary studies, and laboratory data. The indirect evidence most often referred to is the suggested correlation between the complex of fats-meat-egg-animal protein and the risk for cancer of the colon. Such observations are, however, hampered by the fact that human diet does not consist of isolated food components. Case control studies implicate a higher intake of starchy foods in gastric cancer, a lower intake of fiber in colon cancer, and possibly coffee in renal cancer. Carcinogenic agents identified include food additives, plant toxicants, aflatoxins, polycyclic hydrocarbons, nitrosamines, and certain normal major food constituents. The experimental evidence is augmented by studies indicating an inter-relationship between dietary constituents, intestinal flora, and bile acid metabolism. A synergistic action of ingested or metabolized carcinogens and a co-carcinogenic function of certain dietary components are suggested.


Carcinogenic action of anticancer drugs with special reference to immunosuppression. Some anticancer drugs, especially alkylating agents, have under certain conditions shown a carcinogenic effect in animals, as well as in man. This carcinogenic effect is not due to the immunosuppressive properties of these substances but is directly related to their physicochemical properties. In extensive experimental studies with rats, a connection between the immune status of the host organism and the chemical carcinogenesis could not be proved.


BCNU with and without cyclophosphamide, vincristine, and prednisone (COP) and cycle-active therapy in non-Hodgkin's lymphoma. Two hundred and ninety-eight evaluable patients with non-Hodgkin's lymphoma were stratified according to histology, treated with either BCNU, cyclophosphamide, Oncovin (vincristine), and prednisone (BCOP) or cyclophosphamide, Oncovin (vincristine), and prednisone (COP), and evaluated at 3 months. Those with a good partial (PR) or complete response (CR) were then separated and randomized to be treated with either cycle-active therapy (methotrexate, cytosine arabinoside, and 6-thioguanine) or more induction therapy with COP or BCOP. Patients not achieving a good PR at 3 months received cycle-active therapy. The results indicate (a) that there is a significant advantage for good over poor histologies with regard to good PRs at 3 months; (b) that the addition of cycle-active therapy (as administered in this study) is of advantage when the tumor has been significantly reduced only for patients receiving COP induction; and (c) that BCOP has an advantage over COP in diffuse histiocytic lymphoma where the percentage of CRs, their durability, and subsequent survival are superior for patients treated with BCOP. Since this lymphoma accounts for about 25% of all non-Hodgkin's lymphoma patients, this regimen represents a useful tool for the chemotherapist.


Combination therapy for diffuse histiocytic lymphoma that includes antimetabolites. Thirty patients with diffuse histiocytic lymphoma (DHL) were treated with one of three regimens that included cyclophosphamide, vincristine, methotrexate with citrovorum factor rescue, and cytosine arabinoside. Twelve patients had a complete response with a predicted 50% survival of at least 76 months. The medium survival of the 11 partial responders and seven nonresponders was 18 and 6 months, respectively. The addition of methotrexate and cytosine arabinoside may have a beneficial effect in therapy for DHL. From analysis of these results, there is reason to believe that efficacy may be partially dependent on the scheduling and dose of these two drugs.


Total-body irradiation in the treatment of lymphocytic lymphoma. Seventy-eight patients with advanced lymphocytic lymphoma have been treated by total-body irradiation (TBI) since 1969. Fifty-one of these patients received TBI as their initial and only primary therapy, and of these, 36 had a nodular histology and 15 had a diffuse histology according to the Rappaport classification. Treatment consisted of 15 rads twice weekly to 150 rads total dose. Persistent local tumors were given local boost irradiation. None of these 78 patients experenced significant morbidity; toxicity was confined to thrombocytopenia, and in 40% of the patients treatment was administered over a prolonged course to allow platelet recovery. Of the 51 patients who received TBI as primary treatment, 80% achieved a complete response for a median relapse-free survival of 24 months and an actuarial 5-year survival of 68%. TBI is an effective therapy in advanced lymphocytic lymphoma and produces long remissions without maintenance in many patients. It should be considered a systemic agent, and its use in combination with chemotherapeutic agents deserves further investigation.


Advanced lymphocytic lymphoma: randomized comparisons of chemotherapy and radiotherapy, alone or in combination. Ninety-nine previously untreated patients with stage III and IV malignant lymphoma were randomized to receive either cyclic combination chemotherapy (50 patients) or extensive "systemic" radiotherapy (49 patients). Histologic classification included nodular poorly differentiated lymphoma (54 patients), nodular mixed lymphoma (21 patients), and diffuse poorly differentiated lymphoma (24 patients). High overall response rates were seen with either approach (90% for radiotherpy; 86% for chemotherapy) and complete remission were relatively common (60%--80%). Overall median survival of all patients in this trial will exceed 5 years regardless of the induction therapy used; however, disease-free survival is not commonly achieved with either regimen. Relapse-free survival rates at 4-year followup, regardless of induction regimen, are 13% for diffuse lymphomas and 24% for nodular lymphomas. The second prospective trial attempts to use a combined approach and compares cyclic combination chemotherapy with total-body irradiation and combination chemotherapy. Initial results on 34 patients indicate high overall response rates (100%) and similar complete remission rates (64%--67%). With 14 months' median followup no patients in either arm of the trial have died but relatively equal numbers have relapsed.


Curability of non-Hodgkin's lymphomas.

Curability of non-Hodgkin's lymphomas. The relapse rates of patients with malignant lymphoma have been analyzed in relation to the number of patients in complete remission (CR) at yearly intervals after the onset of therapy. Several different patterns of relapse have been identified. Patients in CR from nodular poorly differentiated lymphocytic lymphoma have a low rate of recurrent disease (14%) during the first year of treatment but rates of relapse in succeeding years have not decreased. Patients with diffuse poorly differentiated lymphocytic lymphoma have a significantly higher relapse rate during the first year of treatment (33%). However, remission duration curves suggest that the risk of relapse is decreasing with time. Patients with diffuse histiocytic lymphoma, who initially have the greatest risk of disease recurrence (42%), subsequently showed a significant fall in their rate of relapse. As many as 50% of these patients who attain a CR may have been cured of their disease. An analysis of CR duration curves may be used to determine the effective doubling time of various malignant diseases and to estimate cure rates within a few years after the onset of therapy.


Current cooperative clinical trials in the non-Hodgkin's lymphomas. Current cooperative group trails in non-Hodgkin's lymphoma have been analyzed for their overall methods and strategies. There has been more frequent application of staging procedures and individualization of protocols for favorable and unfavorable histologies according to the Rappaport classification. Early-stage protocols are evaluating the extent of radiotherapy and the need for chemotherapy as maintenance. In later stages the incorporation of new agents in induction regimens, use of cycle-active agents, development of non-cross-resistant combinations, and use of radiation in bulk disease are being examined. In childhood lymphoma, strategies using both leukemia- or lymphoma-type approaches are being tested. Cooperative group trials should also serve as an extensive repository of data on late effects of treatment and on alterations of the course of the disease for future analysis.


Combined modality therapy in malignant lymphomas. The treatment of patients with non-Hodgkin's lymphomas remains controversial. The Rappaport classification system has established its clinical value in distinguishing relatively favorable disease (ie, nodular or follicular lymphoma) from relatively unfavorable disease (ie, diffuse lymphoma). Despite the problems of multiple histologies in a given patient posed by the existence of composite lymphomas and by a spectrum of nodularity in a given node, no newer classification has yet proved superior to the Rappaport system. The relative roles of radiotherapy and chemotherapy are reviewed. The primary role of radiation appears to be the control of detectable disease, when adequate doses and volumes are employed. The primary role of chemotherapy appears to be the eradication of microfoci of tumor. Randomized studies of combined modality approaches have produced no definitive evidence of benefit from adjuvant chemotherapy in stage I and II disease of unfavorable histology. The addition of adjuvant radiotherapy in stage III and IV disease of unfavorable histologic types appears to produce some improvement. Aggressive treatment regimes have yet to show any significant advantage over more conservative treatment in patients with favorable histologic types of stage IV extent. This paper emphasizes the need for expert hematopathologic interpretation in every study of non-Hodgkin's lymphoma.


Rappaport classification of non-Hodgkin's lymphoma: histologic features and clinical significance. The architectural arrangement of the neoplastic cells and their cytologic identification form the histologic basis of the Rappaport classification of non-Hodgkin's lymphomas clinical studies have shown the favorable prognosis of the nodular lymphomas while the diffuse lymphomas irrespective of cell type have a poor prognosis. Several recent studies have shown that pathologists can identify the nodular and diffuse patterns with a high degree of reproducibility. The cytologic subclassification has, however, not achieved a similar high degree of reproducibility. The Southwest Oncology Group study has shown the most reproducible subgroups to be the nodular poorly differentiated lymphocytic malignant lymphoma (ML) and the diffuse histiocytic ML. The clinical significance of the Rappaport classification when applied to childhood lymphomas is not as clear as in adult lymphomas. In view of the recent description of a new clinicopathologic entity primarily in children and adolescents (ie, lymphoblastic ML), IT IS APPARENT THAT THE CHILDHOOD LYMPHOMAS Will have to be examined more critically in order to determine the clinical significance of this classification. Although some have proposed new classifications of these lymphomas based upon immunologic identification of cell origin, none have been shown to be of clinical significance. Based on recent immunologic and clinical studies, a modified classification of the non-Hodgkin's lymphoma is proposed which does not alter its clinical usefulness.


Pathology of the non-Hodgkin's lymphomas: new classifications. This paper briefly reviews the various classifications proposed as alternatives to that of Rappaport. Rappaport's classification is valuable because it is applicable to clinicopathologic studies, but there are areas of contention. Following the Airlie Conference, which failed to resolve the current controversy about classification, the National Cancer Institute proposed to support a retrospective study of 1000 cases of non-Hodgkin's lymphoma, during which the various classifications will be applied to the biopsy slides by a selected panel of pathologists. It is hoped that this study will meet the urgent need for a classification which will eliminate controversial terminology and will employ terms acceptable to pathologists in their daily diagnostic work and to hematologists and oncologists burdened with the choice of therapy for patients affected by the non-Hodgkin's lymphomas.


Prognostic significance of lymphocytic surface markers and histology in adult non-Hodgkin's lymphoma. Neoplastic tissues from 75 adults with non-Hodgkin's malignant lymphoma, histologically classified according to the Rappaport schema, were studied for B- and T-lymphocyte surface markers. All nodular poorly differentiated lymphocytic lymphomas and diffuse well-differentiated lymphocytic lymphomas were B cell. Of 30 diffuse poorly differentiated lymphocytic lymphomas 16 were B, five were T, and nine were "null"; of ten diffuse histiocytic lymphomas, seven were B and three were null. In patients with diffuse lymphoma, those whose malignant cells demonstrated B markers survived significantly longer than those whose malignant cells demonstrated no markers. The prognostic capabilities of the Rappaport histologic classification and surface marker studies were compared. For patients with diffuse lymphomas, classification as B or null more accurately predicted survival than did identification as lymphocytic or histiocytic. However, survival was best predicted by a classification combining the Rappaport histologic scheme with surface marker studies.


Isolation of poly-alpha-L-guluronate lyase from Klebsiella aerogenes. The bacterium Klebsiella aerogenes type 25 produces an extracellular alginolyase which has been partly purified. The enzyme is specific for the alpha-L-guluronosyl linkages in whole alginate and fractions therefrom. The end products of its action on polyguluronic acid blocks are mainly the unsaturated di- and tri-saccharides, with a smaller proportion of the homologous tetrasaccharide. Some general properties of the enzyme are reported.


Morphologic observations in biologic conduits between aorta and coronary artery. This report describes morphologic observations in autogenous saphenous veins, autogenous internal mammary arteries, radial arteries and arterial heterografts used as aortocoronary bypass conduits. The normal or expected changes and the abnormal or unexpected changes observed in each type of bypass conduit is discussed. The three major changes seen in saphenous vein grafts in the aortocoronary position are: (1) medial fibrous replacement; (2) adventitial fibrous proliferation; and (3) intimal fibrous proliferation. Medial fibrous replacement is the result of vein wall ischemia and necrosis and ultimately replacement of smooth muscle cells; adventitial fibrosis is the result of organization of fibrin and red cell clot and repair of ischemic damage. The cause of intimal fibrous proliferation is unclear but appears to be the result of chronic repair of injured intima and endothelium. That the severity of the changes varies along the length of one graft or among grafts in the same patient suggests that other factors contribute to the development of the changes observed. Although some structural changes have been observed, internal mammary arteries are relatively resistant to the changes seen in saphenous veins. Radial arterial grafts have shown severe structural changes with time, to a degree greater than that seen in the saphenous vein grafts. Heterograft conduits so far have been unsuccessful in the aortocoronary position in humans. The severe changes seen in radial artery and heterograft conduits indicate that they are inadequate for use as substitutes for saphenous vein and mammary artery as bypass conduits from aorta to coronary artery.


Medical vs. urgent surgical therapy for acute coronary insufficiency: a randomized study. Forty-two patients with acute coronary insufficiency (high risk subgroup) were randomly assigned to urgent coronary bypass surgery or to initial medical therapy followed by elective coronary bypass at four months if indicated at that time for relief of incapacitation angina pectoris. Coronary bypass performed on an urgent basis offered no advantage in preventing early myocardial infarction or death. The acute illness was resolved without permanent complications in most patients by either urgent bypass surgery or intensive medical therapy. The functional capacity at four months as assessed by objective testing was much greater in the urgent surgical group. Elective bypass surgery was carried out at that point in about half of the medical patients due to persistent incapacitating angina. Later serious complications have continued to occur in the medical patients but have not occurred up to the present time in the urgent surgical patients.


Expected course of patients with coronary artery disease. It is apparent that coronary artery disease is extremely common. As many as 15 percent of young men have significant disease of at least one major coronary artery. Each year approximately 1 percent of middle aged men will develop symptoms of coronary disease. The standard risk factors identify people with a greater risk of developing symptoms. The overall mortality rate of symptomatic patients is about 4 to 5 percent per year in patients with all types of angina pectoris and in survivors of acute myocardial infarction. In symptomatic patients it is possible to identify groups with a risk a dying as low as 1 percent per year and other groups with a risk of dying of 25 to 50 percent per year by simple, noninvasive techniques. However the most powerful predictors of survival in asymptomatic or symptomatic patients are the severity of the coronary artery disease and damage to the left ventricle.


Detection of myocardial ischemia.

Detection of myocardial ischemia. Myocardial ischemia causes a series of anatomic and physiologic abnormalities that can be detected and quantified by assessment of myocardial perfusion, mechanical function, electrophysiology, and metabolism. These methods of assessment vary widely in sensitivity, specificity, relevance, cost, and ease of application. Although occasionally the appropriate choice of diagnostic procedures is clinically difficult, the demonstrated potential of coronary artery bypass surgery to reverse both acute and chronic myocardial ischemia makes the detection of ischemia an important effort in the care of patients with coronary artery disease.


Adrenergic control of hypothalamic function during osmotic stress in the mallard duck (Anas platyrhynchos). The role of the paraventricular nucleus (PVN) and biogenic amines (BA) in regulating the level of corticoids in the serum of osmotically stressed mallard ducks (Anas platyrhynchos) was analyzed employing three experimental approaches: 1) pharmacologic alteration of central BA levels, 2) microscopic evaluation of BA distribution, and 3) placement of electrolytic lesions into the PVN. Reserpine and alpha-methyl-p-tyrosine (alphampt), agents that decrease the amount of BA's in the central nervous system, produced a fivefold increase in the concentration of serum corticoids. Conversely, pargyline and amphetamine, agents that increase the functional pool of BA's, prevented the rise in serum corticoid concentration normally observed in birds challenged with an intraperitoneal injection of hypertonic saline. When the topographic distribution of BA's was analyzed in the brains of osmotically stressed and nonstressed ducks distinct changes in the intensity of catecholamine (CA) fluorescence were observed in only bone location, the PVN of the hypothalamus. Additionally, electrolytic lesions stereotaxically placed in the PVN blocked the osmotic stress-induced rise in serum corticoid concentration. These data therefore indicate that the PVN in the mallard duck plays some role in regulating the observed stress-induced rise in serum corticoid concentration, and that this regulatory function is probably inhibited by catecholamines.


Cytoplasmic microtubules in transformed mouse x nontransformed human cell hybrids: correlation with in vitro growth. Patterns of cytoplasmic microtubules in somatic cell hybrids between transformed mouse cells and nontransformed human skin fibroblasts were examined using antitubulin antibodies as an immunofluorescent probe. Nontransformed cells have been shown to exhibit an extensive cytoplasmic microtubule complex (CMTC), while in transformed cells, this complex is greatly diminished. The hybrid populations contained both types of cells. In addition, they contained cells with previously undescribed intermediate CMTC phenotypes. The percentage of each phenotype present in hybrid populations was determined for sixteen hybrid clones. Seven clones were found which appeared transformed on the basis of their CMTC pattern. The others were comprised of various proportions of all the cell types described. Repeated quantitation of the proportions of these types in the hybrid populations showed them to be stable with time in culture. Growth in vitro of the hybrid clones was assayed by determining their saturation densities, their plating efficiencies on plastic and their colony-forming abilities in soft agar. In vitro growth of a cell population was found to be directly proportional to the percentage of cells in the population which showed the greatly diminished CMTC pattern which has been described for transformed cells. This is strong evidence that a greatly reduced CMTC is associated with transformed behavior, especially the increased capacity of transformed cells for in vitro growth.


Effects of muscle contraction and of adenosine on capillary transport and microvascular flow in dog skeletal muscle. The postarteriolar response of capillary transport and microvascular flow distribution to muscle contraction and to adenosine was measured by the indicator dilution technique in isolated dog gracilis muscles perfused with blood at controlled flows. A model of dual circulation was used to analyze the partition of microvascular flow. The extraction (E) of 125I-iodoantipyrine (IAp) served as an indicator of capillary flow whereas the capillary transport capacity coefficient (PSc) of 22Na was used to assess the changes in capillary surface area available for exchange. Muslce contraction produced by electrical stimulation of the motor nerve increased mean E-IAp from 0.94 +/- 0.03 (sd) to 0.95 +/- 0.01 and produced a 2.0- to 2.9-fold increase in PSc-Na. Intra-arterial adenosine produced results similar to those caused by muscle contraction. We conclude that (1) in resting muscle, most of the flow circulates through exchanging blood vessels and (2) in addition to the primary mechanisms of arteriolar vasodilatation, a substantial increase in the number of capillaries available for exchange of materials plays an important role in the adaptive response to increased metabolic demand.


Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta. Apoliporotein B (apoB) was measured in buffer-extracted homogenates of grossly normal and artherosclerotic human aortic intima by means of an electroimmunoassay procedure. The apoB values which were expressed as microgram per mg tissue dry weight, varied widely, ranging from 0.34 to 18.45 in normal intima and from 0.8 to 12.5 in fatty fibrous plaques. No consistent differences in apoB content were found between normal intimas from thoracic and abdominal aortic regions. There was a statistically significant positive correlation between the quantity of buffer-extractable apoB in normal regions and the plasma cholesterol and triglyceride concentration. Buffer-extractable apoB values were significantly higher in fatty fibrous plaques than in ulcerated lesions from the same vessel. However, fatty fibrous plaque apoB values were significantly lower than those from grossly normal regions from the same aorta, although the topographical distribution of apoB was more widespread in plaques than in normal regions, as shown by immunofluorescence studies. This apparent discrepancy reflected the incomplete extraction of apoB from plaques as contrasted to normal regions. The relatively loosely bound apoB, extractable by standard buffers, may represent intact low density lipoprotein (LDL) and/or very low density lipoprotein (VLDL), while the tightly bound fraction may represent insoluble complexes of intact lipoproteins within the plaque or delipidated apoB.


Noninvasive detection and quantification of left-to-right shunts in children using oxygen-15 labeled carbon dioxide. A method for the detection and quantification of left-to-right intracardiac shunts is described which utilizes a single breath inhalation of oxygen-15 labeled carbon dioxide (C15O2). The inhaled gas rapidly crosses the alveolar membrane and the oxygen-15 label is exchanged through the carbonate cycle to form oxygen-15 labeled water within the pulmonary capillary blood. Pulmonary indicator clearance curves are measured by external scintillation probes. A simplified method of shunt flow quantification was developed from indicator dilution principles and used for the analysis of the clearance curves. Inhalation studies were performed with 62 children on the day prior to cardiac catheterization. The presence or absence of left-to-right shunt was confirmed by contrast angiography in all cases. Twenty-six children were found to have no shunts by C15O2 inhalation, oximetry or angiography. Of the 36 with shunts, 34 were detected by C15O2. Two of these were designated as equivocal because they were considered to be less than the threshold of definitive detection by C15O2 (having Qp/Qs less than 1.2); 32 were positive and there were two false negatives with small ventricular septal defects. There were no false positives by C15O2. The correlation coefficient between C15O2 and oximetry values of shunt flow for those patients with proven shunts was 0.82.


Cutaneous eosinophil accumulation in atopic and non-atopic individuals: the effect of an ECF-A tetrapeptide and histamine. The numbers of eosinophils recruited locally to abraded human skin were measured in eight atopic and eight non-atopic volunteers, at time intervals over 24 hr, following the application of an ECF-A tetrapeptide (Val-Gly-Ser-Glu) or histamine. In all subjects the higher doses of the peptide (10(-4) and 10(-6) mol/l) or histamine (10(-3) and 10(-5) mol/l) produced significantly greater counts than the Tyrode's diluent alone. The counts produced with the lowest dose of peptide (10(-8) mol/l) or histamine (10(-7) mol/l) were not significantly different from the control. The peptide or histamine evoked a greater local eosinophilia in the atopics than the non-atopics. This effect was probably independent of the peripheral blood eosinophil counts since at the time of study the numbers of circulating eosinophils between the two groups were not significantly different. In the atopics, histamine in doses of 10(-3) and 10(-5) mol/l were required to give the same eosinophil response as that obtained with 10(-4) and 10(-6) mol/l of the peptide, respectively. It is suggested that the relative paucity of eosinophils recruited by locally applied ECF-A peptide or histamine, when compared to antigen-induced eosinophilia, is due either to an inability to mimic the events associated with the release of these mediators from mast-cells or the involvement of other pharmacological agents.


Alterations of serum enzymes during therapy directed at human malignant sarcomas: a radiological follow-up study of tumor transformation. 1. When a malignant growth is developing in a patient, one often observes in the serum an increased activity of serum enzymes due to necrosis and increased membrane permeability caused by the altered  metabolism of malignant cells. Conversely, I considered it interesting to check the enzymes of the malate-aspartate shuttle in addition to LDH enzyme when a neoplastic growth is regressing due to radiation therapy. The patients who were selected for this study had histologically proved sarcomas (reticulosarcoma, liposarcoma, and post-nosal sarcoma). 2. The data obtained indicated that tumor regression is heralded by progressive decline (to the normal level) of LDH, GOT and MDH activities in serum. Normalization of these systems suggested that reticulosarcoma, liposarcoma, and post-nosal sarcoma are sensitive to the therapeutic agent used. 3. In viewing the data herein reported a definitive conclusion regarding the diagnostic usefulness of these assays is apparent. It seems possible that the measurement of these enzymes in serum of patients with proved sarcomas, may prove to be useful laboratory adjunct to diagnostic radiology and in the management of patients whose diagnosis has already been established.


Immunological dissection of rat pregnancy: study of the mode of action of antisera to luteinizing hormone. The sensitivity of rat pregnancy to luteinizing hormone (LH) depletion on days 7--12 (day 1 = day of insemination) was investigated by intraperitoneal administration of a single injection of various doses of an anti-bovine LH rabbit serum on the day in question. Day 11 was found to be the most susceptible time for this kind of intervention. The fate of the anti-LH antibodies in the recipients was followed in the serum and in various organs of the treated animals. Serological analysis revealed persistence of free antibodies to LH in the serum as late as 48 hr after injection. Immunofluorescence studies showed immune complex deposition in the kidney glomerula.


A mild method for decomplementation of human sera. A mild method for decomplementation of human serum using mercaptoethanol is described. The effect of the treatment on IgM antibody was slight.


Unconjugated hyperbilirubinemia in very low birth weight infants. In very low birth weight infants, the occurrence of bilirubin-related brain damage has been repeatedly observed at low serum bilirubin concentrations in close association with altered pathophysiologic status (hypoxia, acidosis, hypothermia, and so on). This increased susceptibility is accompanied by increased severity and duration of unconjugated hyperbilirubinemia as compared with more mature infants. Clinical manifestations of kernicterus in very low birth weight infants are almost always nonspecific. No single biochemical or physiologic measurement is sufficient to predict the risk for development of the bilirubin-related brain damage in this group. Prevention of bilirubin-related brain damage in very low birth weight infants requires not only the maintenance of physiologic and biochemical milieu within normal limits, but also specific therapy to alleviate unconjugated hyperbilirubinemia. Although exchange transfusion has been the mainstay of therapy for unconjugated hyperbilirubinemia, the increased morbidity and mortality associated with exchange transfusion in these immature infants and the need to maintain very low serum bilirubin concentrations suggest that prophylactic phototherapy may be more beneficial for this group.


Perinatal glucose homeostasis: the unique character of hyperglycemia and hypoglycemia in infants of very low birth weight. Tiny babies have the potential problem of hypoglycemia due to diminished hepatic glycogen stores, which can be potentiated by conditions frequently present in this birth weight group: asphyxia, cold stress, hypoxia, polycythemia. Despite the early administration of fluid and feeding, tiny babies are still at risk for developing hypoglycemia. Their immaturity, expressed by their limited ability to tolerate parenteral glucose infusions, puts them at risk for becoming hyperglycemic as well. Hence careful glucose administration and frequent monitoring of blood glucose are essential during the first several days after birth, in anticipation of hypoglycemia as well as hyperglycemia.


Comparison of trimazosin and methyldopa in hypertension. Eighteen patients with hypertension participated in a double-blind, randomized study to evaluate the effect of trimazosin, methyldopa, and placebo on supine and standing blood pressure and heart rate. Of 6 patients on methyldopa, one developed drug fever (and was dropped from the study) and one developed impotence. None of 6 patients on trimazosin and none of 6 patients on placebo developed any adverse effects. The mean supine blood pressure on 900 mg trimazosin daily was 17.0/12.8 mm Hg lower than that on the first placebo trial (p less than 0.01) and 17.0/12.1 mm Hg lower than that on the second placebo trial (p less than 0.01). The mean supine blood pressure on 2,250 mg methyldopa daily was 17.8/12.4 mm Hg lower than that on the first placebo trial (p less than 0.01) and 16.8/13.0 mm Hg lower than that on the second placebo trial (p less than 0.01). The mean supine blood pressure was not significantly affected by placebo. Trimazosin, 900 mg daily, and methyldopa, 2,250 mg daily, were equally effective in lowering supine and standing systolic and diastolic blood pressure and did not affect supine or standing heart rate.


Trials with an adenosine analogue as antianginal medication. The potential antianginal effects of orally administered ethyl-adenosine-5-carboxylate hydrochloride (EACH) were assessed in 9 patients with stable angina pectoris who underwent two standardized exercise tests for 3 consecutive days. The first daily exercise performed after placebo revealed no daily variation. The second test was preceded by placebo, 26 mg EACH or 33 mg EACH administered in a double-blind fashion with the use of crossover design. After the completion of the study in the first 6 patients, the 33-mg dose of EACH had to be discontinued because 3 patients had severe angina and another one had nausea and diffuse numbness after this dose. In the remaining 3 patients a 6-mg dose of EACH was used instead of 33 mg, after which the study was terminated because no difference could be determined. EACH, 26-mg and 6-mg, had no significant effect on resting and exercise heart rate, on blood pressure, on onset or duration of angina and positive-exercise electrocardiogram, or on exercise duration. Our study revealed that EACH had no potential antianginal effect and that at a dosage of 33 mg it may induce angina.


Muscle blood flow in children, measured by 133Xe clearance method. Resting and maximal values of blood flow through limb muscles are higher in children than in adults; on the contrary, the time necessary for reaching maximal blood flow and the latter's duration are shorter. Simultaneous measurements in both upper or in both lower limbs, and in the right upper and right lower limbs, revealed no statistically significant differences among the values.


An assessment of cardiac output by thermodilution in infants and children following cardiac surgery. A 4 F thermodilution catheter for measuring cardiac output was evaluated for accuracy and linearity in the laboratory and by comparison with the dye dilution method in infants and children following cardiac surgery. When 2 ml of 0 degrees C injectate were used, the correlation of computer determined flows to calibrated pump flows, over a range encountered clinically, was r = 0.998. The means of triplicate determinations by both the thermal and dye methods were compared in 8 of 25 patients and the comparison found to be favorable (r = 0.976). The complications of thermodilution catheter placement are described and related to the need for post-surgical chest x-ray and thermodilution recordings. The simplicity of the thermodilution technique and other advantages over the dye method in children, such as repeatability, and ease of calibration are discussed in relation to the increased flexibility in management which accrues.


The PaO2 response to changes in end expiratory pressure in the newborn respiratory distress syndrome. To quantitate the effect of changes in end-expiratory pressure (EEP) upon PaO2 in infants with the respiratory distress syndrome, arterial blood gas (ABG) data was reviewed in 28 neonates. A total of 94 ABG specimen pairs were analyzed (specimen I taken before EEP adjustment; specimen II taken after EEP change). An overall change in PaO2 of 15 torr was noted per cm H2O change in EEP. Patients in whom the level of EEP was low (0-3 cm H2O) at the time of Sample I had a greater change in PaO2 (p less than 0.01) than infants whose Sample I ABG was taken at mid-range of EEP (4-6 cm H2O) or at high ranges (7-12 cm H2O). At the high ranges of EEP a minimal and variable PaO2 response was observed. The PaO2 response was not statistically different between neonates on controlled ventilation and those breathing spontaneously. Survivors had a greater PaO2 response than did nonsurvivors, but because of the variables affecting respiratory distress syndrome (RDS) patients, it could not be determined if this PaO2 response had a prognostic value. From this data, the clinician is provided with a guide to the expected PaO2 response when a change in EEP is made.


Terbutaline in the treatment of status asthmaticus. The effect of administration of terbutaline on the pulmonary and cardiovascular systems was studied in ten children with status asthmaticus. Terbutaline (0.01 to 0.04 mg/kg of body weight) was given subcutaneously in multiple doses. A significant decrease in respiratory rate and in arterial blood pressure, with no significant change in cardiac rate, was seen only after the first dose of terbutaline. There was a decrease in mean arterial carbon dioxide tension and an increase in mean arterial oxygen pressure. There was gross clinical improvement following administration of terbutaline in nine of the ten patients. One patient who failed to respond to administration of terbutaline also failed to respond to intravenously administered isoproterenol. We conclude that terbutaline is effective in the treatment of status asthmaticus, with only modest effects on the cardiovascular system.


Intermittent positive pressure inflation during fiberoptic bronchoscopy. We describe a new technique for diagnostic fiberoptic bronchoscopic procedures under general anesthesia. The technique of inflation via nasotracheal catheter, which consists of using intermittent high inflating pressure for ventilation by passing a double catheter through the nose to the glottis and into the trachea, gave very satisfactory ventilaton, with high levels of oxygen in the blood. Intratracheal pressure was monitored continuously to guarantee safety, and pulmonary function was assessed before and after the procedure. Continuous electrocardiographic monitoring was used, and blood gas levels were determined at very frequent intervals. The use of infusions of methohexitone and succinylcholine (suxamethonium) provided adequate safe anesthesia and prompt recovery, with absence of recall of the procedure.


Missile migration from lung to heart with delayed systemic embolization. A bullet migrated from the heart to the left femoral artery in a youth ten days after he sustained a gunshot wound to the right chest. The bullet apparently traversed the pulmonary venous system at the time of the injury and lodged in the interior of the left ventricle. The production of an embolism in the systemic circulation was a delayed and unanticipated event.


Studies on the in vitro development of drug resistance of Proteeae to sulfonamides, trimethoprim and combinations of a sulfonamide and trimethoprim. A strain of Proteus mirabilis repeatedly subcultured in the presence of a combination of sulfisoxazole and 0.4 microgram/ml of trimethoprim and a strain of P. vulgaris subcultured in the presence of sulfamethoxazole and trimethoprim combined in a 5:1 ratio gradually developed resistance to the combinations. However, the level of resistance developed by the organisms exposed to the combination was always appreciably lower than the level of resistance developed by the same strains exposed to either the sulfonamide or trimethoprim alone.


Cyclacillin-induced potentiation of Escherichia coli immunogenicity in vivo and in vitro. The efficacy of cyclacillin as an antimicrobial agent against Escherichia coli was assessed in vivo in mice infected with low numbers of bacteria and compared to the relative effectiveness of the antibiotic against the same organisms in vitro. Treatment of mice with cyclacillin resulted in a rapid clearance of E. coli from the blood and their greater killing in the spleen and liver. Furthermore, a significantly higher antibody plaque response against E. coli developed in  cyclacillin-treated mice than in untreated mice or in those given ampicillin. The increased immunogenicity of the E. coli in the antibiotic-treated mice appeared to be due to high levels of cyclacillin in the animals and rapid killing of the bacteria in vivo. In vitro experiments showed that injection of normal mouse peritoneal exudate macrophages which had been incubated with E. coli together with cyclacillin resulted in a greater immunogenicity of the bacteria than when the injection mixture was composed of E. coli which had been incubated alone or only with macrophages. These results suggest that the in vivo effectiveness of an antibiotic such as cyclacillin against a gram-negative organism such as E. coli may be due in part to an effect on the immunogenicity of the bacteria.


Sulfadiazine-trimethoprim combination in the treatment of urinary tract infections. In a clinical double-blind study on 198 patients with a urinary tract infection, no differences were found between comparable groups treated with either sulfadiazine (SD) 1,000 MG/trimethoprim (TM) 320 mg or sulfamethoxazole (SM) 1,600 mg/trimethoprim 320 g daily for 2 weeks. The favorable results were obtained according to the bacteriological control in 85 and 79%, respectively. Also the incidence of side effects was the same (22 and 24%, resp.). The number of cases within which the treatment had to be discontinued did not differ percentually, either (6.6 and 8.4%, resp.). Based on the bacteriological sensitivity tests and the clinical trial, the authors conclude that TM can be combined with SD as well as with SM. Pharmacokinetic advantages, like a lower protein-binding and a lesser metabolism, may even make SD more preferable.


Identification and treatment with a long-acting sulphonamide of 15 carriers of Vibrio cholerae El Tor serotype Ogawa, during the 1973 cholera epidemic in Naples. During the cholera epidemic in 1973, nine contact carriers of Vibrio cholerae El Tor serotype Ogawa were identified in a family from Naples as well as six others coming from different parts of the city or its surroundings. All the subjects were admitted to the quarantine ward of the 'Cotugno Hospital' (Naples) in which they remained continuously for 14 or 16 days. During this time these bacteriologically confirmed carriers were treated orally with a long-acting sulphonamide (sulphamethoxypyrazine, Kelfizine). Coprocultural examinations carried out on each patient on average 7 times after the treatment over a period of 6 months, proved the absence of V. cholerae. Serological tests also showed high levels of agglutinating and vibriocidal anticholera Ogawa antibodies in two unvaccinated carriers.


[Anorectal incontinence. Results of surgical treatment]. Anal incontinence was investigated in 125 patients. Sphincter suture war suitable for only 52. Opening the anal canal was avoided. Perineal female and male anatomy is very different. Reconstruction of continence by sphincter suture is only to be recommended after traumatic lesions.


The effect of lithium on luteinizing hormone and testosterone in man. Serum luteinizing hormone and testosterone were determined weekly during the course of a comparison of the effects of lithium versus placebo on impulsive aggressive behavior in 16-24 year-old male prisoners. The duration of drug treatment for each individual was up to 3 months. A significant reduction of serious agressive behavioral incidents occurred in the third month on lithium and was accompanied by a significant rise in serum luteinizing hormone, with no change in serum testosterone.


Which tricyclic for depressed outpatients, imipramine pamoate or amitriptyline? Fifty-seven neurotically depressed outpatients with sleep disturbance were randomly assigned to treatment with either imipramine pamoate or amitriptyline given in a single dose at bedtime in a double-blind study for four weeks. The results indicate that both imipramine pamoate and amitriptyline are equally effective in treating neurotic depression. The clinical lore that imipramine is more effective for retarded depression and amitriptyline for anxious, agitated depression was not supported by this study. Of special interest is the fact that the imipramine pamoate group had significantly earlier rising times, and a trend toward better quality of sleep. The side effect profiles of the two drugs were also remarkably similar in this population though more patients complained of side effects on amitriptyline than on imipramine.


A script for deep muscle relaxation.

A script for deep muscle relaxation. Deep muscle relaxation has been used as an adjunct to many somatic and psycho-therapies since its introduction by Jacobsen in 1929. It is a therapeutic technique which is taught as a motor skill through the use of instruction, practice, and feedback about progress. The material in this paper provides a script for preparing a relaxation tape for clients to use between or in addition to regular therapy sessions.


Primary brain stem reticulum cell sarcoma causing dementia. Primary reticulum cell sarcoma-microgliomas of the brain stem are extremely rare. Described here is an unusual case with profound episodic dementia as the predominant clinical manifestation.


[Clinical features of malignant follicular non-Hodgkin's lymphoma (author's transl)]. 75 cases treated between 1970 and 1976 for malignant follicular non-Hodgkin's lymphoma were analysed for their cardinal signs. Contrary to non-Hodgkin's lymphoma of "higher malignancy degree", the average age of patients with malignant follicular non-Hodgkin's lymphoma is generally over 50 years, being more common in females. By the time the diagnosis is made a generalised stage has usually been reached. In the described group of patients the five-year survival rate was 65%, but compared with the malignant lymphoma of higher malignancy the prognosis is often complicated by secondary diseases resulting from the higher age. The findings confirm the need for histological sub-classification of malignant non-Hodgkin's lymphoma.


[An epidemic caused by serratia marcescens in an intensive-care unit for premature and other newborns (author's transl)]. An epidemic caused by Serratia marcescens occurred in intensive care unit of the Children's clinic in Essen, with three deaths. Although there was good sensitivity of the strain to gentamicin in vitro, there was no noticeable clinical improvement when it was administered. But cotrimoxazole, given systemically and locally, and colistin locally cured the disease.


[The behavior of pin-stump constructions with and without circular stump rings in a loading experiment]. On 60 identical resin roots comparative loading experiments with two pin-stump constructions were carried out. One half of the roots was supplied with pin constructions with and the other half with pin constructions without a circular ring cap. With both constructions the secondary crowns were inserted separately. The teeth were loaded up to breaking at their palatinal crown surfaces. There were two types of fractures. In both groups a small number of total fractures was located in the region of the tip of the pin. There were no longitudinal fractures. The most frequent fractures were oblique ones in the gingival region and a marked difference between both groups was noted. Pin constructions with a circular ring cap broke with a load of 10 kp less on the average than those without a circular ring cap.


[A new impression method for partial dentures with special reference to the varying resiliency of the jaw mucosa and the abutment teeth]. By use of two different materials, the combination impression facilitates the preparation of models representing the oral situation without compression of the mucosa or tension at the abutment teeth. In addition, the original impression tray can be ground down without much additional effort and used for the determination of jaw relations. The otherwise necessary and additional preparation of bite blocks is no longer required.


[Electromyographic studies on the masticatory muscles after the preparation of terminal molars as denture abutments]. When the occlusal surfaces of terminal molars are ground off during bridge preparation, the occlusal support for the condyle of the affected side disappears and thus the intermaxillary distance declines. The effect of this process on the masticatory muscles was examined electromyographically in nine patients. It was found that the muscle activity especially in the m. temporalis is immediately reduced by 30 to 40%.


[The effect of amyloglucosidase and glucoseoxydase containing toothpastes on plaque formation and gingivitis]. Earlier studies showed that an antibacterial lactoperoxydase system in the saliva is activated by the application of a hydrogen paroxide-generating combination of enzymes: amyloglucosidase and glucose oxydase. The object of the present study was to investigate the effect of these enzymes in a test and control group of 29 subjects. The results showed the plaque-inhibiting effect of the enzyme paste. An influence on the gingiva could not be demonstrated.


Immunoreactive somatostatin and luteinizing hormone releasing hormone in median eminence synaptosomes of the rat: detection by immunohistochemistry and quantification by radioimmunoassay. Somatostatin and LHRH were detected by radioimmunoassay in the synaptosome fraction obtained by homogenization and differential centrifugation of the rat median eminence. Both somatostatin and LHRH were demonstrated by electron microscopic immunocytochemistry in secretory granules within synaptosomes.


Specific glucose protection of pancreatic beta-cell function during culture in chemically defined medium. Microdissected pancreatic islets from non-inbred ob/ob-mice were cultured for 7 days in modified tissue culture medium 199 lacking serum. When 3 mM glucose was present during culture little or no insulin response to glucose stimulation was observed during the following incubation. Culture with 18 mM glucose on the other hand resulted in good preservation of glucose-stimulated insulin release, especially if release into the culture medium had been inhibited by lack of Ca++. High concentrations of leucine or its non-metabolizable analogue, 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), stimulated insulin release into the culture medium but did not preserve glucose-stimulated insulin release. When compared to previously published fresh-islet levels, culture with 3 mM glucose alone or in combination with high concentrations of leucine or BCH resulted in a substantial loss of beta-cell insulin. This loss was less marked after culture with 18 mM glucose, and completely abolished if no Ca++ was included in the high glucose medium. The data indicate that glucose has a specific effect in protecting some glucoreceptor mechanism of the beta-cells during culture.


Regulation of the second (estrous) release of follicle-stimulating hormone in hamsters by the medial basal hypothalamus1,2. In femal proestrous hamsters (1800 h), bilateral electrocoagulative lesions in the arcuate-median eminence (Arc-ME) region blocked the pituitary FSH release that normally would have begun in late proestrus and continued until the afternoon of estrus. This second (estrous) FSH elevation, which is not accompanied by LH release, was unaffected by neural disconnection of the medial preoptic area (MPOA) from the medial basal hypothalamus (MBH) or by production of MBH-pituitary islands. After gonadotropin-releasing hormone was injected into Arc-ME-lesioned hamsters, LH was released. These results suggest that the Arc-ME does not require the MPOA for initiation of the estrous release of FSH.


Metabolic interrelationships between arsenic and selenium. In 1938, Moxon discovered that arsenic protected against selenium toxicity. Since that time it has been shown that this protective effect of arsenic against selenium poisoning can be demonstrated in many different animal species under a wide variety of conditions. Antagonistic effects between arsenic and selenium have also been noted in teratologic experiments. Early metabolic studies showed that arsenic inhibited the expiration of volatile selenium compounds by rats injected with acutely toxic doses of both elements. This was puzzling since pulmonary excretion had long been regarded as a means by which animals could rid themselves of excess selenium. However, later work demonstrated that arsenic increased the biliary excretion of selenium. Not only did arsenic stimulate the excretion of selenium in the bile, but selenium also stimulated the excretion of arsenic in the bile. This increased biliary excretion of selenium caused by arsenic provides a reasonable rationale for the ability of arsenic to counteract the toxicity of selenium, although the chemical mechanism by which arsenic does this is not certain. The most satisfactory explanation is that these two elements react in the liver to form a detoxication conjugate which is then excreted into the bile. This is consistent with the fact that both arsenic and selenium each increase the biliary excretion of the other. Several other metabolic interactions between arsenic and selenium have been demonstrated in vitro, but their physiological significance is not clear. Although arsenic decreased selenium toxicity under most conditions, there is a pronounced synergistic toxicity between arsenic and two methylated selenium metabolites, trimethylselenonium ion or dimethyl selenide. The ecological consequences of these synergisms are largely unexplored, although it is likely that selenium methylation occurs in the environment. All attempts to promote or prevent selenium deficiency diseases in animals by feeding arsenic have been unsuccessful. Over 30 years ago it was suggested that industrial hygienists use arsenic as a tonic to prevent or cure selenium poisoning in workers exposed to this hazard. Organic arsenical feed additives were tried as partial antidotes against selenium poisoning in livestock raised in seleniferous agricultural areas but were not found to be practical.


Effects of arsenite on DNA repair in Escherichia coli. Since environmental exposure to arsenicals has been correlated with a high skin cancer risk among populations exposed to sunlight, it is possible that arsenicals might interfere with the repair of damage to DNA (mostly thymine dimers) resulting from the ultraviolet rays in sunlight. To test this hypothesis, strains of E. coli, differing from each other only in one or more repair functions, were exposed to UV light and then plated in the presence or absence of sodium arsenite. Survival after irradiation of wild type E. coli (WP(2)) was significantly decreased by 0.5mM arsenite. This effect was also seen in strains which are unable to carry out excision repair, suggesting that arsenite inhibits one or more steps in the post-replication repair pathways. This is confirmed by the finding that arsenite has no effect on the post-irradiation survival of a recA mutant, which does not carry out post-replication repair. Mutagenesis after ultraviolet irradiation depends on the rec(+) and lex(+) genes. Arsenite decreases mutagenesis in strains containing these genes. In order to determine its mechanism of action, dose-response relationships of arsenite on a number of cellular functions were carried out. The most sensitive cellular functions found were the induction of beta-galactosidase and the synthesis of RNA. Since error-prone repair in E. coli is an inducible process, the inhibition of mutagenesis after UV irradiation may be the result of inhibition of messenger RNA synthesis.


Indices of potential lead hazard.

Indices of potential lead hazard. This review is concerned with the concentrations of lead in human whole blood, erythrocytes, plasma, serum, soft tissues, bone, and urine. The extent to which redistribution of some of the bound lead occurs is outlines. The effects of lead on enzyme activities and on the accumulation of metabolic intermediates in the blood and urine are described. A brief section deals with the range of signs and symptoms that can occur and differences seen between symptomatic children and adults.


The involvement of a complex between formylmethionyl-tRNA and initiation factor IF-2 in prokaryotic initiation. A complex between initiation factor IF-2 and fMet-tRNA can be formed under ionic conditions, which are optimal for initiation complex formation. The complex can be retained on cellulose nitrate filters after fixing with glutaraldehyde. The IF-2 - FMet-tRNA complex formation is not influenced by GTP and GDP. Other nucleoside di of triphosphates also have no effect. Evidence is presented that this complex acts as an intermediate in polypeptide chain initiation. The IF-2 - fMet-tRNA complex formation is not influenced by initiation factors IF-1 and IF-3. The binary complex can be bound to the 30-S subunit in the absence of GTP, which indicates that there is no concomittant binding of the IF-2 - fMet-tRNA complex and the nucleotide moiety to the 30-S subunit. The binding of the binary complex is stimulated by GTP. The influence of some inhibitors of initiation on the IF-2 - fMet-tRNA complex formation has been tested. Aurin tricarboxylic acid appeared to be a strong inhibitor, whereas the sulfhydryl reagents N-ethylmaleimide and p-chloromercuribenzoate had no effect.


The role of the digital computer in pediatric cardiology. A digital computer system is described which allows the real-time processing of all physiological signals obtained during a heart catheterization procedure and which makes all relevant results and informations available immediately during the investigation. In addition, special electronic units and programs have been developed in our institution for the automated extraction of morphological criteria from biplane angiocardiograms. Thereby right and left ventricular volume, shape and contraction pattern can be quantitated and used to characterize the performance of the heart as muscle and pump in physical terms. Recently, complete digital processing of videoangiocardiograms has been achieved in a stroboscopic mode, each videofield in real time. Application of image enhancement, subtraction, integration and restoration techniques leads to a fundamentally improved angiocardiographic image quality for a given amount of injected contrast material. Based on eight years of experience with digital computer application in pediatric cardiology, computer technologies are considered likely to become the method of choice in the future.


The effect of renal failure on the disposition and neuromuscular blocking action of pancuronium bromide. Plasma concentrations of pancuronium following single dose administration in six patients, and following multiple dose administration in four patients, all undergoing renal transplantation surgery, were measured using a fluorimetric method. A two-compartment open model was used in the pharmacokinetic analysis of the data. Comparison of the pharmacokinetic findings with data previously obtained for patients undergoing elective surgery but having normal renal function indicated that the clearance of the drug was reduced significantly in the patients with renal failure, and that in these individuals the half-life was increased significantly. Measurement of the evoked mechanical twitch response concurrently with plasma concentration monitoring of pancuronium confirmed that the prolongation of half-life in the patients with renal failure was often but not always associated with an extended duration of neuromuscular blockade and furthermore that the rate of recovery from block might also be prolonged. The clinical implications of these findings are discussed.


Bioavailability of metronidazole in fasting and non-fasting healthy subjects and in patients with Crohn's disease. The possible influence of food intake on the bioavailability of metronidazole was examined in ten health volunteers by administration of a single dose of metronidazole on an empty stomach, and with a standardized breakfast. Food intake did not significantly alter the bioavailability of metronidazole. The interindividual variation in bioavailability appeared to be slight. In nine patients with Crohn's disease, the absorption of metronidazole appeared to be reduced and to be more variable than in healthy subjects. In both groups there was a clear relationship between the amount absorbed and dose/kg body weight. Thus, from the pharmacokinetic point of view, metronidazole can safely be given either with or between meals. The dose should be related to body weight.


An investigation of "absolute plasma level effect relationships" and "absolute cardioselectivity" with respect to beta-adrenoceptor blockade. In a group of 6 healthy (but physically unfit) volunteers an investigation was made of whether there was a true plasma level effect relationship and absolute "cardioselectivity" with respect to beta-adrenoceptor blockade due to practolol. To this end three treatments were given orally, namely placebo, practolol 100 mg and practolol 400 mg. Cardiac beta-adrenoceptor blockade was assessed by measuring the inhibition of exercise heart rate and pulmonary beta-adrenoceptor blockade was assessed by measuring the reduction in exercise peak flow rate, up to 24 h after each dose. Plasma practolol levels were determined spectrophotometrically. From the results obtained there was no reason to doubt the existence of a valid relationship between cardiac beta-adrenoceptor blocking activity and the plasma concentration of practolol. It was also concluded that even in non-asthmatics, practolol does not possess absolute "cardioselectivity" since significant reductions in peak flow rate were discernible during vigorous exercise, particularly when the large dose had been given.


Antipyretic therapy. Comparison of rectal and oral paracetamol. The absorption of paracetamol from syrup, tablet and two different suppository bases was compared in six adult volunteers using urinary excretion measurements. The total amount of paracetamol and its metabolites excreted and the peak excretion rates were lower from the suppository bases than from the oral dosage forms. Absorption was a little better from a polyethylene glycol suppository base than from a triglyceride base. The antipyretic efficacy of a paracetamol syrup and suppository at a dose of 10 mg/kg was compared in 30 children between the age of 4 months and 12 years, who had infections and a rectal temperature above 38.5 degrees C. Both dosage forms produced a significant decrease in temperature, the greatest fall being about 2 hours earlier with the oral dosage form. The syrup also seemed to be significantly (p less than 0.05) more effective (maximum fall of temperature 1.58 degrees C) in reducing fever than the suppository, which produced its greatest fall of temperature (1.24 degrees C) six hours after insertion of the suppository. From the practical point of view both forms can be regarded as safe and effective antipyretics.


Molecular structure of human histocompatibility antigens: the HLA-C series. The HLA-CW2 antigen of the B lymphoblastoid cell line BRI 8 is structurally homologous to the HLA-A and B antigens as judged by various criteria. Each antigen comprised a glycosylated polypeptide of 43 000 molecular weight that is noncovalently associated with beta2-microglobulin (beta2m). Some small differences in molecular parameters were, however, revealed. Thus, the deoxycholate-solubilized HLA-CW2 antigen sedimented at the same rate as the HLA-A antigens but at a slightly faster rate than the HLA-B antigens. This variation is apparently is apparently due to different amounts of bound deoxycholate. Also, whereas essentially all of the HLA-A and B antigens and about half of the HLA-CW2 antigen were adsorbed strongly by Lens culinaris lectin-Sepharose, the remaining HLA-CW2 antigen was bound much more weakly and did not require sugar for elution. This difference reflects some structural heterogeneity in the carbohydrate moiety of the HLA-CW2 antigen. The results of various studies suggest that the HLA-CW2 antigen is expressed to a lower extent than the HLA-A or B antigens and that essentially all of the beta2m of the BRI 8 plasma membrane is associated with the HLA-A, B and C alloantigenic polypeptides.


Mouse bone marrow-cultured macrophage as indicator cells for mouse and human migration inhibitory factor (MIF). Macrophages cultured from mouse bone marrow served as excellent indicator cells for mouse as well as for human migration inhibitory factor (MIF) preparations. The tests were performed in the capillary system and showed high reproducibility. Using mouse or human MIF-containing supernatants, we found an inhibition of 53% compared with the controls. Similar results were obtained if concanavalin A-stimulated human peripheral blood lymphocytes were mixed with mouse test macrophages in a ratio of 1:5 or 1:10.


Haemopoietic recovery in spleen and marrow after transplantation of bone marrow from either normal or hydroxyurea treated mice. Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DNA in spleen and femoral bone marrow and the erythroid, granulocytic and mononuclear cell populations were not significantly different between normal (NBM) and hydroxyurea-treated (HUBM) marrow. The response of hypertransfused x-irradiated mice to erythropoietin (EPO) administration was also not significantly different in spleens of mice receiving normal or hydroxyurea-treated marrow.


Identification of erythropoietin producing cells in fetal mouse liver cultures. Fetal mouse liver explants were cultured and the culture media shown to possess an erythropoietically active substance neutralizable by antiserum to sheep plasma erythropoietin, suggesting that the media contain erythropoietin. Immunofluorescent and carbon particle ingestion techniques suggest that the erythropoietin was elaborated by macrophages or Kupffer cells of the hepatic reticuloendothelial system.


Temporal transition in the site of rat erythropoietin production. Plasma erythropoietin levels have been determined in nephrectomized, hepatectomized, nephrectomized and hepatectomized, and intact hypoxic rats--1, 2, 3 and 8 weeks of age. The liver appears to be the primary site of erythropoietin production during the first 2 weeks of life. By the third week, the kidneys began producing erythropoietin and by 8 weeks, they were the major organs of erythropoietin production. Indirect immunofluorescent staining for erythropoietin of renal and hepatic tissue correlated with the results of the erythropoietin bioassay. Fluorescent staining of glomerular cells in the kidney and macrophages or Kupffer cells in the liver implicate these areas as possible specific sites of erythropoietin production.


Luteinizing hormone-releasing hormone in the human fetal brain. Hypothalamic and other brain tissues were obtained after death from human fetuses aborted by hysterectomy at various conceptional ages. Immunoreactive luteinizing hormone-releasing hormone (LHRH) activity in tissue extracts was determined by a double-antibody radioimmunoassay method. Fetal hypothalamic and cortical tissue at 5 weeks after conception showed no assayable LHRH activity. At 6 weeks, immunoreactive LHRH was detectable in extracts of both the hypothalamus and the cortex, and levels appeared to fluctuate with a trend to increase until the 20th week. Two of four fetuses at 13 and 14 weeks' conceptional age had significantly higher LHRH activity in the thalamus than in the rest of the central nervous system. After 16 weeks, LHRH activity was detected in the hypothalamus, thalamus, cerebrum, and cerebellum in decreasing concentrations, respectively. As the age of the fetus progressed from 16 to 20 weeks, the LHRH concentration in the hypothalamus increased significantly, from 1.2 pg/mg to 29.3 pg/mg of wet tissue. LHRH concentrations in specimens of comparable conceptional age that could not be promptly dissected were lower than in those dissected within 30 minutes after the ligation of uterine arteries.


Glucose and 3-O-methylglucose protection against alloxan poisoning of pancreatic alpha and beta cells. Alloxan infused into the isolated perfused rat pancreas caused transient insulin secretion release. Alloxan poisoning also prevented subsequent induction of glucose-mediated unsulin release and also prevented the inhibition of glucagon release by glucose. Glucose or 3-O-methylglucose infused simultaneously with alloxan protected the alpha- and beta-cell, allowing subsequent glucose inhibition of glucagon secretion and stimulation of insulin release. The above alloxan effects were dose-related, the alpha-cell being one fourth as sensitive to alloxan as the beta-cell. The data indicate that (1) alloxan and glucose suppression of amino-acid-stimulated glucagon secretion is independent of concomitant insulin secretion; (2) alloxan, like glucose, affects alpha-and beta-cells directly, stimulating the beta-cell and inhibiting the alpha-cell; and (3) alloxan acts on a glucoreceptor system with comparable physicochemical characteristics common to both cell types.


Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies. Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the CIA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.


Phosphoenolpyruvate in rat pancreatic islets: a possible intracellular trigger of insulin release? The content of phosphoenolpyruvate (PEP) has been measured in isolated rat islets of Langerhans incubated in vitro. Islet PEP was higher in islets incubated with 16.7 mmol/1 glucose than in islets incubated with zero or 2.8 mmol/1 glucose. Islet PEP content was also increased in islet incubated with 5 mmol/1 D-glyceraldehyde. Mannoheptulose abolished the glucose-induced rise in PEP content but not that elicited by D-glyceraldehyde. These results are consistent with a role for PEP as an intracellular mediator or glucose- and glyceraldehyde-induced insulin release. The kinetics of pyruvate kinase in extracts of rat islets were studied. The maximal extractable activity was considerably  higher than known rates of glycolytic flux. The Km values were found to be 0.16 mmol/1 for PEP and 0.5 mmol/1 for ADP. The control of islet PEP content and the possible role of PEP in insulin release are discussed.


Detection of bacterial infection of the pancreatic ducts in patients with pancreatitis and pancreatic cancer during endoscopic cannulation of the pancreatic duct. Bacterial infections of the pancreas and bacteremia may occur during episodes of pancreatitis. Detection of bacterial infections of the pancreas in the past has required laparotomy. The present study was undertaken to determine whether bacterial infection of the pancreas occurred during nonsuppurative pancreatitis. During endoscopic cannulation of the main pancreatic duct, secretin was administered intravenously and pancreatic juice aspirated from within the duct was cultured. Bacterial infections were detected in 11 of 35 patients with pancreatitis and 3 of 5 with pancreatic cancer. The pancreatic juice was sterile in 25 controls. Cultures from the common bile duct in 9 controls were also sterile whereas 4 of 6 with pancreatitis showed infected bile. The infecting organisms were principally gram-negative and the infections were usually polymicrobial. Antibiotics, where used, successfully eradicated the infecting organisms but did not appear to affect the patient's clinical course.


Study of gastric emptying using a ferromagnetic tracer. A new ferromagnetic method for the measurement of gastric emptying is described. An inert tracer, magnesium ferrite, is added to a test meal. Its amount in the stomach is then measured at regular intervals by an external transducer using its ferromagnetic properties. The method is noninvasive and devoid of radiation exposure. The magnetic fields used are harmless. The feasibility, reliability, and reproducibility of the method are described. Gastric emptying was studied in 61 subjects. The shape of the gastric emptying curve conformed best to an exponential function. The mean half-time of gastric emptying was 49 +/- 17.4 min. In this limited series age and sex did not affect gastric emptying.


Immune response to hepatitis B virus in children with papular acrodermatitis. Papular acrodermatitis of childhood (PAC) is characterized by papular eruption of skin, lymphadenopathy, and acute hepatitis B surface antigen (HBsAg)-positive anicteric hepatitis. To study the course of hepatitis B virus infection we followed 16 patients with PAC, 2 to 7 years of age, for periods ranging from 6 to 46 months. All patients tested developed hepatitis B surface antigenemia subtype ay, and produced antibody to hepatitis B core antigen with the highest incidence after 3 to 5 months. Half of the children investigated developed antibody to hepatitis B surface antigen 4 to 18 months (mean, 6.5) after the onset of PAC. At the end of the investigation, 31% of the children were still HBsAg-positive, 50% were antibody to hepatitis B core antigen-positive, and in 43% the activity of serum aminotransferases was abnormal. Liver biopsy repeated in 2 children showed chronic aggressive hepatitis. The pattern of antibody response to hepatitis B virus is similar in both HBsAg-positive hepatitis and PAC. The frequent development of HBSAg carrier state and the high proportion of children with liver abnormalities at the end of the investigation suggest an impaired clearance of hepatitis B virus and a tendency to chronicity.


Hepatic vasculature: a conceptual review. The hepatic circulation is reviewed with emphasis on the role of hepatic blood vessels in hepatic and homeostatic functions. Contrasts are made with resistance, capacitance, and fluid exchange functions in other better known vascular beds. Hemodynamic changes that produce shifts in fluid exchange in other tissues are without effect in the liver. Elevations of hepatic venous pressure are transferred quantitatively to the sinusoids and result in prolonged, massive fluid filtration into the abdominal cavity. Other factors that are involved with control of fluid exchange are discussed. The liver contains a large volume of blood which can be rapidly mobilized during hemorrhage. The hepatic circulation is highly sensitive to changes in circulating blood volume and serves as a major buffer for expanded or contracted blood volume. Control of hepatic blood flow and the reciprocal relationship between portal and hepatic arterial flow is discussed. Changes in hepatic blood flow produce marked changes in hepatic clearance rates of a wide variety of compounds. It is concluded that the hepatic artery is not controlled by local tissue metabolism but rather is controlled by an, as yet unknown, mechanism that tends to maintain hepatic blood flow (and therefore clearance rates) constant.


Evidence for phasic sequences in nuclear HBcAg formation and cell membrane-directed flow of core particles in chronic hepatitis B. Seven liver biopsies (6 chronic aggressive hepatitis B, 1 kidney transplant recipient with chronic persistent hepatitis B) are described showing differential distribution patterns of HBcAg in liver cells (with gradual transitions): pure nuclear, mixed nuclear/cytoplasmic, and pure cytoplasmic (diffuse and/or submembraneous). This was combined with spotty expression of HBsAg (cytoplasm and liver cell membrane) and with Dane particles (DP) in blood. A phasic nuclear formation and release of cores from the nucleus and of DP from the cell, respectively, is suggested. Electron microscopy (EM) of one biopsy indicates a secretory disturbance as a possible cause for HBcAg accumulation in liver cells the tolerance of which is attributed to immunosuppression therapeutically induced in 4 patients and suspected in 3 (2 dialysis patients, 1 spontaneous chronic aggressive hepatitis B).


Gastric secretion and emptying after ordinary meals in duodenal ulcer. We have studied the gastric response to an ordinary solid-liquid meal in 12 patients with active duodenal ulcer and 8 healthy volunteers. Our method employs gastric and duodenal markers to quantify acid, pepsin, and volume outputs in response to the meal, without manipulating intragastric pH. Intragastric volume, rate of gastric emptying, delivery of acid into the duodenum, and serum gastrin response were also measured simultaneously. On a separate day, peak acid output in response to betazole (1.5 mg per kg subcutaneously) was determined. Our results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels. Further, the stomach in duodenal ulcer disease did not "retain" the additional acid secreted in the later postprandial period, and abnormally high rates of acid delivery into the duodenum occurred. Our data are consistent with a dual defect in the duodenal mechanisms regulating both acid secretion and acid delivery into the duodenum.


[Discovery of a new type of restriction and modification in a group of intestinal bacteria]. The adsorption of 23 new lambdoid bacteriophages to 547 strains which isolated from natural population of Enterobacteriaceae was studied. The frequency of positive combinations of phage-bacterium with adsorption is not more than 2%. A study of possible causes of limited growth of lambdoid phages in the bacterial strains revealed that neither homoimmune prophage nor prophage P2 are single factors of the growth limitation. It is found that in natural populations a selection of bacterial strains with the least limitation of phage takes place. Three cases of killing bacteria after infection with high multiplicity are found. The reason of the killing effect is manifestation of some functions by infecting phages. A new restriction-modification system is found which differs from restriction-modification system A, B, K, 15, P1, EcoRI, EcoRII. The most of strains, which adsorb phages but do not support their growth, are supposed to possess several mechanisms of restriction. Thus, the search of new restriction system in Escherichia coli is worthwhile.


[Salmonella typhimurium as a test system for detecting the mutagenic activity of environmental pollutants. I. The mutagenic action of heavy metal salts in in vivo and in vitro systems without metabolic activation]. The work presents the data on mutagenic effects of heavy metal salts (Zn and Cd) on Salmonella typhimurium test strains using mutagenicity test in vitro without metabolic activation and host-mediated assay. The techniques used enabled to determine also the types of mutations arising from the exposure to ZnCl2 and CdCl2.


[Reparation of UV-damaged bacteriophage ed]. A repair of UV-damaged phage DNA in the "phage-host" system in accordance with the excision reparative mechanism is demonstrated by means of centrifugation in alkaline sucrose gradient of virulent 3H-thymidine labelled phage sd. The increase of the transfectants quantity of UV-irradiated DNA on uvr+ bacteria compatibly to uvr- bacteria evidences that the bacterial host participates in phage reparation. Caffeine inhibition of UV-irradiated phage sd survival confirms the participation of cell-host in reparation of UV-damaged phage.


[Induction of the synthesis of various colicins by the action of N-methyl-N'-nitro-N-nitrosoguanidine and chloramphenicol]. The effect of N-methyl-N'-nitro-N-nitrosoguanidine on colicinogenic cells is shown to result in the induction of the synthesis of colicins B1, B4, K, Ia-CA53, Ib-P9 and V3. Chloramphenicol induces the synthesis of colicins B1, B4, K, V3 and, possibly, Ib-P9. The data obtained indicate, that there is a similarity between derepression mechanisms of different colicinogenic factors.


[Treatment of hyperuricemia using daily doses of 50 and 25mg of benzbromarone]. By treating 16 hyperuricemic patients each with 25 and 50 mg of Benzbromarone a significant decrease of the uric acid concentration in the serum into the normal range is achieved. On the 5th and 6th day after beginning the treatment the dosage of 25 mg of Benzbromarone renders a morning value of 5,3 +/- 1,0 and an evening value of 5,0 +/- 0,9 mg/100 ml. After administration of 50 mg of Benzbromarone there is also prevailing a steady-state behaviour on the 5th and 6th day for the uric acid concentration in the serum. Thereby the morning value is 3,7 +/- 0,8 mg/100 ml and th evening value 3,4 +/- 0,9 mg/100 ml. After both dosages an increased urate elimination occurs initially during the 1st, 2nd and 3rd day after beginning of the therapy. However, after having achieved therapeutically reduced uric acid levels, the uric acid elimination from the 4th, 5th and 6th day partially ranges below those values existing before beginning of the therapy. During a chronic treatment no hyperuraturia can be observed on account of the therapeutically reduced serum concentrations. Consequently an increased risk towards a formation of urate calculi is not given under the long-term treatment.


[Peptone-stimulated gastric secretion and antacids. Effect of antacids with various content of calcium, magnesium and aluminiumions on the peptone-induced secretion of gastric juice, double-blind study]. A double-blind-trial was performed to prove the effect of antacids containing Mg (OH)2, Al (OH)3 and CaCO3 on peptone-stimulated gastric secretion (intragastric titration). A high efficacy of antacids given after meals was demonstrated. After application of antacids no significant rise in serum gastrin levels during intragastric titration was found. Serum calcium and magnesium levels remained unchanged. Peptone-stimulated gastric secretion was not influenced by application of different antacids within a period of 2 hours.


Immunofluorescence studies with a specific antiserum to the microfibrillar protein of elastic fibres. Location in elastic and non-elastic connective tissues. The microfibrillar protein (MFP) of foetal bovine ligamentum nuchae elastic fibres was prepared and used to produce a monospecific antiserum. Indirect immunofluorescence studies employing the specific antiserum demonstrated its selectivity for MFP associated with elastic fibres. The antiserum was demonstrated to react with vascular elastic tissue, perivascular connective tissue and reticular basement membranes in a variety of tissues. This evidence suggests that the MFP (or an immunologically related protein) is not confined to elastic fibres but is widely distributed in connective tissue being associated with both elastin and collagen fibres.


A re-evaluation of the role of macrophages in carrageenan-induced immunosuppression. Administration of a single dose of 1 mg carrageenan to mice cause a temporary blockade of hepatic phagocytosis of 51Cr-labelled sheep erythrocytes (SRBC) and a prolonged reduction in the number of splenic plaque-forming cells (PFC) against SRBC. The in vitro responses to phytohaemagglutinin (PHA) and SRBC were also suppressed, whereas the response to the T cell-independent antigen DNP-Ficoll was not affected. Other in vitro experiments have shown that responses of normal cells can be actively suppressed by macrophages from carrageenan-treated mice and the possible mechanisms of this suppression are discussed.


Production of colicin V in vitro and in vivo and observations on its effects in experimental animals. In recent years, a possible relationship between pathogenicity and colicinogeny in some Escherichia coli strains responsible for gastrointestinal infection and bacteremia in man and animals has been inferred. Using enterotoxigen-negative, colicin V-producing E. coli strains, we have (i) elaborated a simple in vitro method for producing greater yields of colicin V free of bacterial cells and large, non-dialyzable molecules; (ii) detected the presence of the bacteriocin in peritoneal fluids of moribund mice injected intraperitoneally 18 h previously with colicin V-producing strains (in these mice, Col V+ exconjugants survived and multiplied more extensively than the Col V- recipient strains from which they were derived; and (iii) observed an increased vascular permeability and inflammatory response in rabbits and guinea pigs when a culture supernatant demonstrating colicin activity was injected intradermally. The vascular response obtained after the injection of either a colicin V-containing dialysate alone or that of a trypsinized colicin-containing supernatant was always smaller than when the colicin V-active supernatant was injected. An enterotoxin-free dialysate containing colicin V also increased markedly in rabbits and guinea pigs the mild inflammatory reaction that occurred in the skin when purified endotoxin was injected subcutaneously in microgram doses. Our results are consistent with the hypothesis that colicin V may act as a virulence factor in some E. coli strains.


Growth of Mycobacterium lepraemurium in cultures of macrophages obtained from various sources. Studies were made on the growth of Mycobacterium lepraemurium in cultures of macrophages obtained from various sources, such as bone marrow, spleen, and blood of mice. Macrophages were maintained in good condition for more than 12 weeks. Marked intracellular multiplication of M. lepraemurium was observed in cultures from all three sources. Whereas M. lepraemurium freshly prepared from the animals showed good growth in the cultures, those that were kept at 4 degrees C for 10 or 14 days showed no growth.


Microtiter solid-phase radioimmunoassay for detection of Escherichia coli heat-labile enterotoxin. The development of a microtiter solid-phase radioimmunoassay for the detection of Vibrio cholerae enterotoxin and heat-labile Escherichia coli enterotoxin is described. The test is based on the immunological similarity between V. cholerae toxin and E. coli heat-labile toxin. The assay is easy to perform, quantitative, and at least as sensitive and specific as the Y-1 adrenal cell system.


Assessment of typhoid vaccines by using the intraperitoneal route of challenge. Present laboratory tests for human typhoid vaccines use an intraperitoneal route of challenge given 7 days after injection of increasing doses of standard and test vaccines by the same route. In studies reported here, groups of B6D2 mice were vaccinated intraperitoneally with 2 x 10(8) acetone-killed Salmonella typhi Ty2, with the Vi antigen-free variant O-901, or with Yersinia enterocolitica and Serratia marcescens suspensions. Other groups of mice received 200 mug of purified S. typhi or S. marcescens endotoxin, or their corresponding purified lipid A components. All of the vaccinated mice (except for saline- or thioglycolate-injected controls) exhibited increased protection against the lethal intraperitoneal challenge with S. typhi Ty2. Serial quantitative bacterial counts carried out on peritoneal washouts and on homogenates of the draining mediastinal lymph nodes indicated the development of an antibacterial response by the vaccinated host which was not observed in the control animals. Mice receiving purified endotoxin (lipopolysaccharide) exhibited varying degrees of protection, both in terms of increased host survival and the amount of inactivation of the challenge population in vivo. The response seen when the antigenically unrelated S. marcescens lipopolysaccharide was injected was little different from that seen when the acetone-killed S. typhi Ty2 whole-cell vaccine was used. This suggests that nonspecific inactivation of the intraperitoneal challenge contributes substantially to the immune response seen in mice vaccinated intraperitoneally with specific typhoid antigens.


Significance of T cells in resistance to experimental murine coccidioidomycosis. The resistance of mice to coccidioidomycosis was found to be dependent on lymphoid cells. Thus, spleen cells from mice immunized with killed spherules of Coccidioides immitis, when transferred to irradiated (500 R) recipients, conferred upon the recipient mice resistance to infection with C. immitis. Prior incubation of these spleen cells with anti-theta serum in the presence of complement abrogated their capacity to protect the recipients from infection with C. immitis. Adult thymectomized mice, which had been irradiated (800 R) and reconstituted with bone marrow from normal mice, were more susceptible to infection with arthrospores than were nonthymectomized, irradiated bone marrow-reconstituted controls. Genetically homozygous athymic ("nude") mice died after infection with a dose of arthrospores that was sublethal for their heterozygote counterparts possessing a thymus, or for normal mice. The results indicate that a functioning T-cell population is an essential component for effective immunity to C. immitis.