Humoral and cellular immune responses in Aspergillus fumigatus pulmonary disease. This study was designed to evaluate immunologic differences between aspergilloma (A) and allergic bronchopulmonary aspergillosis (ABPA), comparing the results to atopic and nonatopic control subjects. Humoral studies included skin tests with common inhalant antigens and Aspergillus fumigatus. Total and specific IgE and other immunologlobulin levels and serum precipitins were evaluated against A. fumigatus. Cellular immunity was studied with routine skin testing and phytohemaqglutinin-induced lymphocyte blast transformation. Antigen-induced blast transformation was also carried out with the use of serial dilutions of A. fumigatus. All patients with ABPA were atopic and had marked elevations of IgE. None of the patients were atopic and they had normal IgE levels. Immediate and late skin reactivity to A. fumigatus was low in control and A groups but high in 2 patients with ABPA. IgG antibody against A. fumigatus was generally greater in the ABPA group. Both ABPA and A had serum precipitating antibody against A. fumigatus. The atopic controls had elevated IgE levels and immediate skin test reactivity to A. fumigatus, and one also had weak serum precipitins against A. fumigatus. IgE antibody against A. fumigatus was generally higher in ABPA than A. ABPA and A patients had elevated stimulation indices (SI) to A. fumigatus. No stimulation could be detected with cells from control subjects. This study indicates that both T and B cell sensitization may play a role in the development of or as a response to aspergillus-related pulmonary disease.


Antibody-dependent cellular cytotoxicity of mononuclear cells from asthmatics tested in three in vitro assays. Using the chicken red blood cell assay, the human Chang liver cell assay, and a lymphoblastoid cell assay, mononuclear cells from asthmatics and normals were tested for antibody-dependent cellular cytotoxicity (ADCC) capacity. Mononuclear cell preparations from perennial nonallergic asthmatics with a history of asthma associated with viral infections had a reduced ADCC capacity in the chicken red blood cell assay, an increased ADCC capacity in the Chang liver cell assay, and normal ADCC capacity in the lymphoblastoid cell assay. The data also suggested that perennial nonallergic asthmatics had increased percentages of surface IgG-negative lymphocytes in the peripheral blood when compared to normals.


Stress management training for the elderly: a psychoeducational approach. A procedure is described for teaching elderly persons the use of relaxation as a coping skill. The procedure, called Stress Management Training, seeks to provide the client with: 1) a cognitive understanding of stress and relaxation, 2) the ability to relax by controlling muscle tension and sympathetic-nervous-system activity, and 3) the ability to extend the relaxation skill to real-life stress situations. A case report demonstrates the process, which is an educational model rather than a medical model. The role of the psychotherapist as an educator and the potential usefulness of the social learning theory as a basis for conceptualizing mental health problems are discussed.


Convergence insufficiency: incidence, diagnosis, and treatment. Convergence insufficiency is one of the most common ocular problems. The paper carefully reviews the existing literature paying particular attention to etiology, diagnosis, sensory findings, treatment, and treatment results.


[A study of two proteins associated with pregnancy. HPL and SPI glycoprotein, in the serum of 692 pregnant women (author's transl)]. The authors study the evolution of the levels of two proteins found in pregnancy (HPL and SP1 glycoprotein) in the serum of 692 pregnant women. They establish normal and pathological zones. They study particular cases (twins, hydramnios and kidney pathologies). The relationships between fetal distress, maturity, and the fetal weight at birth are analysed.


Osteoblastoma of the metacarpal: A case report. Osteoblastoma is a rare tumor, but the small bones of the hands and feet are the second most common location. Despite this, the diagnosis of osteoblastoma is rarely considered in the differential diagnosis of bone tumors of the hand. This is a case similar to Jaffe and Mayer's original report.


Multiple volar carpometacarpal joint dislocation. Case report of traumatic volar dislocation of the medial four carpometacarpal joint in a child and review of the literature. Traumatic dislocation of the medial four carpometacarpal joints in a child is an unusual injury. Descriptions of this injury in the literature have been reviewed and a case is presented to illustrate the pertinent anatomy, biomechanical aspects, and details of management. Specifically, the importance of collateral circulation to the hand and an effective technique of pin fixation are described.


Peanut agglutinin. I. A new tool for studying T lymphocyte subpopulations. Fluorescein-coupled peanut agglutinin (PNA) has been used at the single-cell level to study mouse lymphocyte subpopulations. PNA not only binds to most thymocytes, as has already been shown by other authors, but also binds to a small fraction of peripheral lymphocytes that are all T cells (theta+Ig-) or null cells (theta-Ig-). Most PNA-positive thymocytes are sensitive to in vivo corticosteroids and irradiation (450 rads) treatments. Conversely, the positive spleen cells (5% of total spleen lymphocytes) are essentially resistant to corticosteroids and irradiation. Study of PNA binding during ontogenesis shows the occurrence of PNA-positive cells in the fetal liver before thymus constitution and in the very beginning of embryonic thymus and spleen development. These data indicate that PNA is a marker of early T cell subpopulations but that there are probably several distinct subsets of PNA-positive T cells.


Expression of two differentiation antigens on normal and cultured human T cells. An antiserum specific for human T lymphocytes (AMT) was used to examine patterns of T cell surface antigen expression and to isolate their reactive membrane antigens. By a quantitative adsorption assay, different plateaus of AMT reactivity with blood T cells were observed after serial adsorptions with individual T cell lines. MOLT-3 cells removed 95% of AMT activity to blood T cells whereas MOLT-4 removed 70% and HSB-2 removed only 30%. A cross-adsorption analysis demonstrated that each of the three cell lines differed in their adsorbing efficiency to remove AMT antibodies reactive with the reciprocal cell lines. Radiolabeled membrane proteins were solubilized with either sodium deoxycholate (DOC) or NP-40 detergents, precipitated with AMT, and Staphylococcus aureus Cowan strain I, and analyzed by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis (SDS-PAGE). Two distinct T lymphocyte antigens of approximately 25,000 daltons (p25) and 16,000 (p16) were identified on MOLT-3 cells. Similar relative quantities of p25 and p16 were detected on human peripheral T cells and thymocytes. MOLT-4 cells contained less of the p25 peak than did MOLT-3. HSB-2 cells gave a small peak in the same general location as the MOLT-3 p25 peak, and a relatively large p16 peak. Adsorption of AMT with HSB-2 removed the capacity of the antiserum to precipitate p16 from MOLT-3, but did not eliminate reactivity with p25.


Suppression of humoral and delayed hypersensitivity responses by distinct T cell subpopulations. Immunization of mice with a supraoptimal dose of sheep red blood cells (SRBC) results in splenic T cell populations capable of specifically suppressing recipients' plaque forming cell (PFC) and delayed-type hypersensitivity (DTH) responses to SRBC when tested in an adoptive transfer system. By localization on discontinuous bovine serum albumin (BSA) gradients and relative sensitivity to Cytoxan, two distinct T cell subpopulations suppressing DTH reactivity were identified. One population could not be distinguished from T cells capable of inhibiting direct and indirect PFC responses. However, another population appeared quite distinct and capable of inhibiting DTH, but not PFC responses.


Serum from LPS nonresponder C3H/HeJ mice does not support the formation of functional EAC reagents. Serum from C3H/HeJ mice in contrast to serum from other mouse strains does not convert EA into EAC. A factor in supportive serum permits nonsupportive C3H/HeJ serum to produce a functional EAC-rosetting reagent. This factor is heat stable. Its concentration in serum parallels the sensitivity of mice to LPS. It is absent or inoperative when sensitivity is reduced on a genetic basis and increased when sensitivity is increased by treatment with BCG.


Activation of distinct helper and suppressor T cells in experimental trypanosomiasis. Spleen cells taken from mice soon after infection with Trypanosoma brucei S 42 enhance the primary in vitro antibody response of normal spleen cells to sheep red blood cells (SRBC), but do not affect their response to DNP-Ficoll. Spleen cells harvested later in the infection (day 6 onwards) suppress the antibody response of normal spleen cells to both SRBC and DNP-Ficoll. The enhancing and suppressive effects of "infected" spleen cells are sensitive to treatment with anti-Thy 1.2 anti-serum and complement, and can be mediated by nylon wool-purified populations of T cells. The enhancing T cell is sensitive to ALS, not lost within 4 weeks of adult thymectomy, and bears the Ly-1+, 23- phenotype. The suppressor T cell is insensitive to ALS, lost within 20 weeks of adult thymectomy, and bears the Ly-1+, 23+ phenotype. The significance of the activation of distinct helper and suppressor T cells is discussed in relation to the pathogenesis of trypanosomiasis.


A model for the autosensitization autoantibody production associated with xenogeneic thymic RNA. Normal C57BL/6 bone marrow cells cultured for 3 weeks with xenogeneic thymic RNA and syngeneic C57BL/6 antigens (immunoglobulin G or red blood cells) produced anti-immunoglobulin antibody or anti-mouse red blood cell antibody (hemolysin). Addition of both xenogeneic thymic RNA and autoantigens to bone marrow cultures was necessary to elicit autosensitization. Syngeneic thymic RNA would not substitute for xenogeneic RNA. Normal recipients inoculated with syngeneic kidney or spinal cord homogenates and xenogeneic thymic RNA developed albuminuria or motor neuropathies within 10 days. Histologic examination of tissues from these animals revealed immunoglobulin deposits on glomerular or tubular basement membranes or on myelin sheaths. These changes were not observed in tissues from control animals inoculated with only the organ homogenates. Normal mice injected with syngeneic bone marrow cells, which had been autosensitized in vitro against kidney or spinal cord homogenates, also developed albuminuria or motor neuropathies, respectively. These abnormalities were observed only if bone marrow cells had been cultured with both xenogeneic thymic RNA and autoantigens. Histologic examination of tissues from these mice also revealed immunoglobulin deposits in kidney or spinal cord tissues. These results demonstrate that xenogeneic thymic RNA can play important roles in the formation of autoantibodies.


A microassay for the determination of hemolytic complement activity in mouse serum. A 51Cr release microhemolytic complement assay is described to detect hemolytic complement activity in mouse serum, 51Cr-labeled sheep erythrocytes (SRBC) which have been sensitized with a subagglutinating amount of the 7S IgG fraction of rabbit anti-SRBC serum are placed in microtiter plates and further antibody added to each well prior to the addition of the complement (C) source. The IgG antibody was found to be more efficient in the lytic assay than the 19S IgM antibody. The assay is simple to perform, reproducible, and requires small volumes of mouse serum. Comparative hemolytic values were established for serum from a variety of murine strains using pooled BALB/c serum as the C reference. No apparent relationship was noted between the H-2 type of inbred mouse strains and the presence or absence of hemolytic complement.


A miniaturized in vitro diffusion culture system. A miniaturized diffusion culture apparatus holding 24 individual cultures and utilizing 1/10 the cells and volume of standard Marbrook-type cultures is described. This system was evaluated by studying the anti-sheep erythrocyte response of spleen cells from unprimed or primed and boosted mice. Compared to parallel Mishell--Dutton plate cultures memory responses in mini-diffusion cultures rise more slowly, peak 1--2 days later and thereafter decline less rapidly. Moreover, the diffusion cultures give a pronounced IgG response peaking at 6 days, while the abortive IgG response evident in plate cultures at 4 days rapidly disappears. While viability in the two systems is equivalent, cell recovery on days 7 and 8 is markedly higher in the diffusion cultures. Of 4 cell concentrations tested, 2 million cells are found to produce the optimum anti-sheep erythrocyte plaque-forming cell response. A 0.2 micron nucleopore membrane is preferable to a dialysis membrane and yields up to a 2-fold higher response. Replacement of the reservoir medium on day 4 impairs rather than improves the response. The culture system was also found to support an excellent primary response. This response is dependent on the presence of 2-mercaptoethanol and does not require rocking.


Passive hemagglutination and hemolysis tests for the detection of anti-DNA antibody. Passive hemagglutination (PHA) and hemolysis (PHL) tests using chromium chloride-treated sheep red blood cells were developed to detect and measure the anti-DNA antibodies. Sonication of native DNA was found to prevent the incidence of non-specific agglutination. Sheep red cells were coated with double-stranded DNA (dsDNA) which had been sonicated and treated with nuclease S1 to digest the single-stranded regions in the DNA. The specificities for dsDNA-coated cells were checked by inhibition studies in PHA test and plaque assay. In clinical studies fairly close correlations were found between the antibodies to DNA and the activity of the disease in patients with systemic lupus erythematosus (SLE). Complement-fixing antibodies were detected in most of SLE patients with active lupus nephritis, but rarely in those in remission. Anticomplementary activity seemed to be negligible in PHL test. These tests are simple and may be useful to the diagnosis and the management of SLE.


Use of yeasts in affinity chromatography. The use of the yeast Candida lipolytica as a support in affinity chromatography for the purification of lectins of Ricinus communis seeds has been studied. A comparison was made with columns of erythrocyte stromas and Sepharose 4B with respect to protein yields, the agglutinating activity yield, and the electrophoretic characteristics of the eluted substances. Even though the yield is less than with other supports, it does appear that the yeast columns represent an effective method for the purification of ricin lectins.


A method for preparing leucocyte depleted erythrocytes from rat blood. By centrifuging heparinised rat blood 2 or 3 times through double discontinuous Ficoll--Hypaque density density gradients it is possible to achieve over 99.8% depletion of leucocytes and to retrieve nearly all the erythrocytes and leucocytes in the original specimen.


Eosinophil function related to cutaneous disorders. A concise review of the ultrastructural features and physiological properties of eosinophils is presented with the aim of delineating those properties of eosinophils that set them apart from other granulocytes. It has become clear that eosinophols are subject to chemotaxis by attractants that do not affect other cells (e.g., histamine, ECF-A, ESP) and that they contain antiflogistic agents (arylsulfatase IIB, peroxidase) that neutralize specific substances known to elicit the inflammatory response. The mechanisms underlying eosinophilia in a variety of cutaneous disorders are analyzed in the light of this information.


Stimulation of fibroblast biosynthetic activity by serum of patients with pretibial myxedema. Skin fibroblasts from the shoulder and lower extremities of normal individuals, as well as from patients with pretibial myxedema (PTM) were grown in culture. When cells reached the monolayer stage, they were labeled with 3H-glucosamine and tested for hyaluronic acid synthesis in the presence of either serum from PTM patients or normal human serum. All the fibroblasts from the pretibial area synthesized 2 to 3 times more hyaluronic acid when incubated with PTM sera than when incubated in normal human serum. Fibroblasts cultured from skin of the back or prepuce did not respond to PTM sera. This heat-stable, protease-sensitive, and dialyzable, fibroblast-stimulating factor is not a 7S gamma-globulin. The enhanced sensitivity to PTM sera exhibited by fibroblasts from the lower extremities may explain why the lesions in this disease are restricted primarily to that area.


Regulation of growth of fibroblasts.

Regulation of growth of fibroblasts. Present knowledge on regulation of fibroblast growth is based on in vitro culture of fibroblasts from different sources. The research has focused on 2 problems: identification of the signal that reaches the fibroblast from outside and tells it to grow and identification of metabolic reactions inside the cell that commit it to initiate DNA synthesis after the signal arrives. Although the signal and the metabolic reactions have not yet been clearly identified, and the relationship between in vivo conditions and the result of these in vitro studies still has to be determined, the large body of data collected so far and the steadily growing information concerning these problems suggest a complex interrelation between cellular environment and metabolic processes involved in growth regulation.


Development and differentiation of dermal cells in man. Development and differentiation of the single free cells of mesenchyme and dermis of human embryos and fetuses from week 6 to term is described. From week 6 to week 14, three cell types are present: stellate general mesenchymal cells with long processes, phagocytic macrophages of probable yolk-sac origin, and a granule-secretory type of cell, which could be either a melanoblast or a mast stem cell. From week 14 to week 21, fibroblasts are numerous and active, and perineurial cells, pericytes, melanoblasts, mast cells, and Merkel cells can be individually identified. There is also present another cell type, possible of bone marrow origin, that may be ancestral to the Langerhans cell and that may be carried over into postanal dermis as the "histiocyte" or fixed dermal macrophage. From week 24 to term there is little change apart from the development of fat cells in the deeper dermis. Neither lymphocyte nor plasma cell was observed at any stage of development. These observations were used in the specification and identification of cells of fully developed postnatal dermis.


Monocytes, macrophages, and their diseases in man. Mononuclear phagocytes are a widely distributed system of cells involved in host defense functions, immunologic reactions, disposal of unwanted organic and inorganic materials, and synthesis of biologically active compounds such as complement components and prostaglandins. The system includes early precursor cells in the bone marrow, blood monocytes, alveolar and peritoneal macrophages, sinusoidal lining cells in the spleen, and Kupffer cells in the liver. We have recently come to understand the biology of these interesting cells and the diseases they produce.


Analogous functions of macrophages and Langerhans cells in the initiation in the immune response. Langerhans cells constitute a minor cell population within the mammalian epidermis. This paper defines these cells immunologically and functionally and supports the concept that Langerhans cells are closely related to cells from the monocyte-macrophage-histiocyte series. Both cell types bear surface receptors for Fc-IgG and C3 and express surface glycoproteins, termed Ia antigens, encoded for by immune-response genes (Ir genes) of the major histocompatibility complex of the species. The expression of Ia antigens by Langerhans cells and macrophages is intimately associated with important functions of both cell types, including the capacity to present immunologically relevant antigen to the T lymphocyte and to cause proliferation to allogeneic T lymphocytes in mixed leukocyte reactions.


Recruitment of basophils in delayed hypersensitivity reactions. Basophilic leukocytes constitute a significant proportion of the cellular infiltrates in many forms of delayed-in-onset hypersensitivity reactions in human beings, guinea pigs, and other animals. In this paper, I review current information on the role of basophils in the reactions, and present similarities and differences between Jones-Mote and classic delayed hypersensitivities.


Mast cell secretion: membrane events.

Mast cell secretion: membrane events. Stimulation of secretion with A23187 circumvents the usual mechanism of stimulation of secretion by direct mediation of an increase in cytoplasmic Ca++ and thereby permits study of the terminal components of the secretory process in which granules are externalized by membrane fusion events. Two alterations in the plasma membrane precede fusion: the formation of bulges and the aggregation of intramembranous particles. These changes require a permissive level of ATP and are sensitive to reagents that bind to intracellular protein sulfhydryl groups. They seem not to be attributable to a direct effect of Ca++ on membrane phospholipids. The cell components responsive to Ca++ and responsible for the alterations in the membrane are not known; neither microtubules nor actin filaments seem to qualify.


Connective tissue structure: cell binding to collagen. Established lines of fibroblasts have been shown to adhere to collagen substrates via a serum-derived glycoprotein. The attachment of various other cells to collagen types I-IV is examined here. Cells such as human skin fibroblasts, periosteum, hepatocytes, connective tissue cells, and monocytes required the serum glycoprotein and adhered equally well to all collagens, but attachment of chondrocytes, epidermal cells, and neutrophils was inhibited by the serum glycoprotein. Attachment of 2 tumorigenic cells, an osteosarcoma and a fibrosarcoma, was found to be unaffected by the serum glycoprotein. In addition, the fibrosarcoma and epidermal cells attached preferentially to type IV (basement membrane) collagen.


The correlation between the antibody titers in sera of patients with Pemphigus vulgaris and their clinical state. Immunofluorescent antibodies against the intercellular material of the malpighian layer were detected in the sera of 22 of 24 patients suffering from pemphigus vulgaris. A clear-cut agreement between pretreatment antibody titers and the severity of the clinical manifestations was established only with the extreme values, i.e., patients without antibodies were among the mildest cases while the highest titers were found exclusively among the most severe cases. There was a considerable overlapping of all 3 states of the disease--mild, moderate and severe--in the range of the intermediate titers. On the individual level, 20 of the 24 patients showed a positive correlation between steroid-induced clinical improvement and a fall in the antibody titer. Conversely, in some cases, an exacerbation of the clinical state was associated with a rise in antibody titer. The results of this investigation indicate a positive correlation between the immunological findings and the clinical activity of the disease.


Prognosis in tetanus: Use of data from therapeutic trials. There is a need in clinical tetanus for a simple prognostic classification for all patients at time of admission to the hospital. Data from three randomized clinical trials performed in India in the 1960s, which contained information on several prognostic variables for 1,385 patients, have been used to study different methods of prognosis. A logistic regression performed on the combined data from the trials suggested that the probability of death is related separately to the period of onset (the time from the first symptom to generalized reflex spasms), to the time from first symptom to admission to the hospital, and to the clinical assessment of severity of tetanus on admission; the effects of these variables have been studied by tabulation. A new system is proposed for assigning patients to three prognostic groups, defined by time from first symptom to admission and whether or not reflex spasms were present on admission to the hospital. The range of fatality rates is 10%--63%. Neonates are assigned to a separate group with a fatality rate of 72%. Other prognostic groupings are also explored in case it is felt that the above method relies too heavily on local arrangements for medical care.


The immunologic response to infection with respiratory syncytial virus in infants. Fifty infants younger than six months, hospitalized for infection with respiratory syncytial virus (RSV), were studied by examination of serial samples of nasal secretion. Secretory neutralizing activity was measured by plaque reduction and secretory antibody by indirect fluorescence using conjugated antiserum to human IgA, IgG, or IgM. Secretory neutralizing activity during infection rose or fell fourfold with approximately equal frequency (20% and 26%, respectively). In contrast, levels of IgA antibody to RSV in secretions rose fourfold in 56%--65% of the infants and fell in none. The frequency of such rises in titer of antibody was directly related to age. In individual secretions the correlation between neutralizing activity and IgA antibody to RSV was poor: neutralizing activity was often found in the absence of detectable antibody, and IgA antibody to RSV was often nonneutralizing. Nevertheless, the development of IgA antibody to RSV correlated in time with the disappearance of virus from the respiratory tract. The timing of this secretory response is consistent with the hypothesis that antibody contributes significantly to cure of infection.


Escherichia coli in bacteremia: K and O antigens and serum sensitivity of strains from adults and neonates. Comparisons of O- and K-antigenic types and serum sensitivity were carried out with 149 strains of Escherichia coli isolated from adults with bacteremia and 46 strains from neonates with bacteremia. O-antigenic types O6, O4, O2, O16, O18, and O7 were observed most frequently, but their relative prevalence did not differ materially between adult and neonatal bacteremias. A greater proportion of strains from neonatal bacteremia contained K1 antigen and were autoagglutinable compared with strains from adult bacteremia, although K1 was the most frequent K antigen found in strains from adults. K-antigen-containing strains did not appear to be associated with enhanced severity of bacteremia, but nontypable strains, auto-agglutinable strains, and strains of O-antigenic types O4, O6, and O8 were associated with a greater frequency of shock and fatal outcome in adults. No differences could be detected between the serum sensitivities of E. coli isolated from adult bacteremia and those from neonatal bacteremia. K antigen did not affect serum sensitivity, but E. coli strains of O types O18, O2, O4, and O7 were more serum-resistant than other E. coli. Bacteremia caused by serum-sensitive E. coli was less often associated with shock and death than bacteremia caused by serum-resistant E. coli.


Host defenses in the aged: evaluation of components of the inflammatory and immune responses. Host defenses were evaluated in 70 healthy aged volunteers. Individuals who had diseases or who were taking medication known to affect the inflammatory and immune responses were excluded from the study. Volunteers were followed for 24 months to correlate their state of health with the evaluation of host defenses. Polymorphonuclear leukocyte function and the serum opsonic capacity for Escherichia coli and Staphylococcus aureus were normal. Assays of complement components and activity revealed unexplained elevations in native C3 and properdin, normal concentrations of factor B, normal conversion of C3 by inulin, and normal levels of hemolytic complement. The levels of IgG and IgA did not differ from levels noted in younger controls, but the concentration of IgM was decreased and that of IgE increased. The prevalence of autoantibodies was low. None of the volunteers were anergic, but lymphocyte responses to mitogens were depressed in three-day cultures. The number and percentages of E-rosette-forming cells and cells bearing surface IgD or IgM were normal. No lymphopenia was noted.


Search for heat-labile enterotoxigenic Escherichia coli in humans, livestock, food, and water in a community in the Philippines. Environmental sources of heat-labile enterotoxigenic Escherichia coli are unknown. The feces of 1,086 inhabitants (approximately 5%) of a small town in the Philippines, 28 pigs, and 10 water buffalo were cultured for enteric bacterial pathogens. Twenty-seven persons harbored pathogenic bacteria: five individuals had enterotoxigenic E. coli, 11 Salmonella species, nine Vibrio parahaemolyticus, one Shigella boydii, and one nonagglutinable Vibrio. Enterotoxigenic E. coli were isolated from two of 28 pigs and from one of 10 water buffalo. Cultures of 26 pieces of beef, 25 pieces of pork, and 52 leafy vegetables obtained from a community market failed to grow enterotoxigenic E. coli. None of 47 samples of contaminated surface water contained this pathogen. Serotypes of human and animal strains of enterotoxigenic E. coli were different, although E. coli O78:H12 isolated from a pig has previously been incriminated in human diarrheal disease. In this limited survey of a Philippine community, enterotoxigenic E. coli were isolated from humans and livestock. The possibility that enterotoxigenic E. coli infections are zoonotic warrants further investigation.


Role of complement in host defense against experimental disseminated candidiasis. The role of complement in experimental disseminated candidiasis was studied in normal guinea pigs, animals congenitally deficient in the fourth component of complement (C4), and animals depleted of alternative pathway activity by cobra venom factor (CVF). Animals pretreated with CVF and challenged with Candida albicans had a high rate of mortality. Results of quantitative organ cultures corroborated prior reports that the kidney was the major target organ of infection. Infection of the kidney was markedly enhanced by CVF-induced depletion of the alternative pathway but not by classical pathway deficiency (deficiency in C4). There were differences among organs (kidney, liver, and spleen) in their requirement for complement to mount an effective host defense response. Ultimately, the integrity of the alternative pathway and late components of complement appears necessary for the limitation of and survival from sepsis due to C. albicans in nonimmune animals.


Type distribution of beta-hemolytic streptococci in Israel: a 10-year study. A survey was carried out over 10 years on the distribution of beta-hemolytic streptococci, their identification, and the clinical implications. Curtures were typed by the conventional agglutination and precipitation methods and by enzyme production. The present survey indicates the changes in streptococcal ecology of the various serotypes. Epidemics of acute pharyngitis with complete absence of rheumatic fever provided suggestive evidence that not all group A types are associated with rheumatic fever. The survey also emphasizes the occurence of non-group A streptococci in human infection.


Initial clinical evaluation of a new Rocky Mountain spotted fever vaccine of tissue culture origin. Currently available Rocky Mountain spotted fever (RMSF) vaccines are relatively ineffective in preventing infections in humans and contain considerable amounts of contaminating egg protein. A new formalin-inactivated vaccine was prepared by sucrose density gradient centrifugation of the Sheila Smith strain of Rickettsia rickettsii grown in chick embryo cell tissue culture. The new product has greater protective immunogenicity in rheusus monkeys and guinea pigs than commercial vaccines. Six volunteers without immunologic evidence of prior exposure to RMSF received from one to three inoculations of the vaccine diluted 1:10, and there were two benign local reactions. Titers of antibody (determined by microagglutination and indirect fluorescence techniques) increased in all recipients as did lymphocyte tranformation responses to specific rickettsial antigen. Ten volunteers were immunized twice with vaccine diluted 1:3; there were no local reactions, and immunologic responses were similar to those in the six volunteers in the first group. The proper dosage and immunization schedule for the vaccine must be determined in further studies.


Detection by direct immunofluorescence of antibodies to Treponema pallidum in the cutaneous infiltrates of rabbit syphilomas. By direct immunofluorescence, with use of fluorescein-labeled sonified Treponema pallidum, specific antibodies were detected in the tissue infiltrates of cutaneous syphilomas in rabbits. Specimens from cutaneous and mucosal inflammatory lesions induced by intradermal injection of a keratinous substance from an epidermal cyst served as controls. Granular fluorescence was detected in the dermis of 11 of the 12 syphiloma specimens and corresponded to areas of heavy plasma cell infiltrates, and some fluorescence was found directly on plasma cells identified by subsequent staining with hematoxylin and eosin. This fluorescence could be blocked by preabsorption. Control slides did not show any fluorescence. Immunopathologic techniques using labeled antigens may be of diagnostic value in syphilis and other infectious disorders which feature specific infiltrates.


Sources of gram-negative bacilli colonizing the tracheae of intubated patients. Twenty acutely ill patients requiring prolonged orotracheal intubation were studied to determine the source and progression of gram-negative bacilli colonizing the trachea. Organisms recovered from daily tracheal, hypopharyngeal, and rectal cultures were typed and speciated to identify identical strains at the three sites. All patients acquired gram-negative bacilli in the trachea by day 3 after intubation. Thirty organisms that were not recovered from the tracheal aspirate immediately following intubation were isolated for at least two days some time thereafter. Nine of the 30 colonizing bacteria were Enterobacteriaceae, and all were found in another culture site, usually the hypopharynx, before isolation from the trachea. In contrast, only four of the 21 non-Enterobacteriaceae that colonized the trachea were recovered previously from either the hypopharynx or rectum, a finding which represents a significant difference (P = 0.0002). Quantitation of isolates from the hypopharynx was of no value in predicting subsequent acquisition in the trachea, and the numbers of bacteria recovered from the first positive tracheal specimen were not predictive of subsequent persistence in the trachea.


Legionnaires' disease: antigenic peculiarities, strain differences, and antibiotic sensitivities of the agent. Paired sera from victims of Legionnaires' disease showed, in many cases, significant rises in immunoglobulin G antibodies to both the causative agent (LA) of Legionnaires' disease and Chlamydia psittaci, but concurrent rises in immunoglobulin M antibodies only against LA. Guinea pigs experimentally infected with LA likewise responded with antibodies to both C. psittaci and LA. Guinea pigs infected with LA also reflected significant differences in antigenic makeup and in pathogenicity among four strains of LA examined. In antibiotic studies, rifampin was 200 times more effective than erythromycin and 17,000 times more effective than tetracycline in plaque reduction tests of LA in monolayer cultures of primary chick embryo cells. An isolate of LA recovered from a healthy person was compared with three isolates from persons with fatal infections.


Effects of progesterone on chemosensitivity in normal men. Progesterone administration increase VE in man, but its effects on ventilatory response to hypercapnia and hypoxia have not been well documented. Accordingly, VE, HVR, and HCVR were measured during placebo and MPA administration in 11 normal men. The effect of MPA (20 mg orally q 8 hr for 32 hr) on T degrees, metabolic rate (VO2 and VCO2) was also determined. With MPA, T degrees, rose 0.4 degrees C +/- 0.0008 (S.E.M.) p less than 0.0001), VE increased 0.46 +/- 0.16 L/min (p less than 0.01), and VO2 and VCO2 did not change significantly. HCVR (measured under hyperoxic conditions during rebreathing) increased significantly (P less than 0.01) from 2.9 +/- 0.33 L/min/mm Hg (placebo) to 4.0 +/- 0.29 (MPA). HVR was measured as the shape parameter A, so that when A increased, HVR was augmented. During MPA, HVR increased from A = 132 +/- 19.1 to 179 +/- 20.5 (P less than 0.02). We conclude that 60 mg of MPA daily in normal men increases VE and chemosensitivity as measured by the ventilatory response to hypercapnia and hypoxia.


Radical neck dissection: considerations in flat design. A wide choice of skin incisions and skin flaps is available to the surgeon contemplating radical neck dissection. The choice of incisions, however, may often be influenced by a number of existing or pre-existing conditions. Each situation has to be treated on its own merit depending on the prevailing cicumstances if all objectives are to be achieved.


Active immunization of ewes against luteinizing hormone releasing hormone, and its effects on ovulation and gonadotrophin, prolactin and ovarian steroid secretion. Three Scottish Blackface ewes were immunized against luteinizing hormone releasing hormone (LH-RH) conjugated to bovine serum albumin (BSA) and three control ewes were immunized against BSA alone. When the antibody titre to LH-RH became raised the treated animals failed to show oestrus or ovulate; they had significantly lower levels of plasma luteinizing hormone (LH) and higher levels of prolactin than the controls, whereas the levels of follicle-stimulating hormone (FSH) were unaltered. The integrity of the hypothalamus-pituitary-gonadal system of these animals was then challenged by the injection of a highly active analogue of LH-RH and by ovariectomy. An i.v. injection of 5 microgram D-serine-t-butyl 6 des-glycine-NH2 10 LH-RH ethylamide raised plasma LH and FSH. Ovariectomy caused an eight- and ninefold rise in plasma levels of LH and FSH respectively in controls, but failed to increase plasma levels of LH and FSH in the LH-RH-immunized ewes. Plasma prolactin concentrations in the LH-RH-immunized ewes were significantly reduced by ovariectomy.


Streptococcal M protein extracted by nonionic detergent. III. Correlation between immunological cross-reactions and structural similarities with implications for antiphagocytosis. Three immunologically cross-reactive and non-cross-reactive streptococcal M proteins were analyzed by a chromatographic tryptic peptide mapping system. The results indicate that cross-reactions correlate with the extent of structural similarity among the M protein molecules analyzed. The data also reveal that free lysine is released by the action of trypsin from these three M proteins, suggesting a common lys-lys or arg-lys sequence. In addition, only one peptide has been found to be common within all three M types. This limited structural relatedness among the three M proteins examined indicates that sequence variation plays a major role in the immunological specificity of the M antigens. However, despite sequence variation, all M protein molecules have a common antiphagocytic activity. The fact that no common opsonic antibody has yet been found, even against limited M types, argues against this biological activity being solely the result of a common sequence. Based on these data, it is suggested that the antiphagocytic effect of M protein may be due to a conformationally created environment on the surface of the molecule which is selected by both immunological and biological pressure.


Synthesis of fibronectin by cultured human endothelial cells. Plasma fibronectin is probably the major nonimmune particulate opsonin in blood and is cross-linked to fibrin during the final stage of blood coagulation. Fibronectin also occurs in an insoluble form in basement membranes especially those underlying endothelial cells and in loose connective tissue. Fibronectin was demonstrated in cultured human endothelial cells and in the surrounding extracellular matrix by immunofluorescence microscopy by using antibody to human plasma fibronectin. Cultured human endothelial cells released fibronectin into the culture medium which was immunologically identical to the fibronectin in human plasma. Cultured human endothelial cells were labeled with [3H] leucine. The radioactive fibronectin present in the endothelial postculture medium and in urea extracts of cellular monolayers was isolated with either anti-fibronectin coupled to Protein A-Sepharose or double antibody immunoprecipitation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When reduced, the [3H] fibronectin synthesized by cultured endothelial cells had the same mol wt (approximately 200,000) as plasma fibronectin. Unreduced, the [3H] fibronectin synthesized by endothelial cells migrated as a dimer, as did plasma fibronectin. Fibronectin accounted for approximately 15% of the protein synthesized and released by endothelial cells into the culture medium. Thus, cultured endothelial cells synthesize fibronectin, secrete it into the culture medium, and incorporate it into extracellular matrix. The results suggest that the endothelial cell is potentially a major site of synthesis of circulating plasma fibronectin. In addition, fibronectin derived from endothelial cells may be an important structural component of the subendothelium.


The family as the unit of medical care.

The family as the unit of medical care. This review of the literature on the family and medical care involves an expedition into the sister disciplines of epidemiology, sociology, and psychology. There is a considerable volume of evidence that documents how important to the individual's health is his family. This material has been organized into four categories: (1) the family's contribution to the "cause" of disease, (2) the family's contribution to the "cure" of disease, (3) the family's response to serious or chronic disease, and (4) the family's desire and/or need for family-oriented care. In the conclusion, some implications for the future of the discipline of family medicine are discussed in relation to the material presented.


Role of divalent cations in the resumption of meiosis of rat oocytes. Resumption of meiotic maturation was induced in follicle-enclosed rat-oocytes by treatment with the divalent cationophore A23187 (10(-5)M). However, the same effect was attained by incubation in Ca++-deficient medium, even in the presence of EDTA or EGTA (1mM). The stability of the first polar body was increased under Ca++-deficient conditions. Neither the ionophore nor Ca++-deficient medium interfered with the spontaneous maturation of isolated oocytes of the rat. The experiments with cultured follicles suggest that redistribution of divalent cations may participate in the physiological control of meiosis in mammalian oocytes.


Childhood depression: an overview.

Childhood depression: an overview. A review of the psychiatric literature on childhood depression indicates confusion in the basic concept of depressive illness in childhood. There is no general agreement on criteria for childhood depression. The diagnosis of depression in childhood is being based on clinical impression, arbitrarily selected criteria, or on a favorable response to treatment with antidepressants. There is no distinction between primary and secondary depression. The diagnosis of "masked depression" is given to children with a wide range of different problems, bassed on the hypothesis that depression in childhood can be manifested by clinical symptomatology quite distinct from that found in adults. However, recent studies do not support this hypothesis. Most studies on childhood depression include a wide range of children in spite of the fact that from the data available in current literature it seems justified to distinguish between the different age groups of children, mainly the prepubertal and the adolescent groups.


Sodium valproate in the treatment of levodopa-induced dyskinesia. The effect of sodium valproate 1200 mg daily on the disability of Parkinsonism and on levodopa-induced dyskinesia was assessed in a double-blind crossover trial with matched placebo in 12 patients with Parkinson's disease. No objective change in the severity of Parkinsonism or dyskinesias was noted. However, six out of nine patients who completed the trial noted a slight to moderate improvement in their dyskinesias with no change in their Parkinsonism. Excess salivation improved in four subjects on sodium valproate.


Baclofen in Parkinson's disease.

Baclofen in Parkinson's disease. In a controlled trial, baclofen (mean dose 45 mg daily) signficantly increased disability from Parkinsonism in 12 patients with the long-term levodopa syndrome. Peak dose choreoathetosis was not improved but benefit was observed in all four patients with "off period dystonia." Adverse side effects were common and severe, and included visual hallucinations, vomiting, and dizziness.


Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.


Luteinizing hormone-releasing hormone in human pituitary blood. Luteinizing hormone (LH) and LH-releasing hormone (LHRH) were measured by radioimmunoassay in blood samples collected from the pituitary gland during transsphenoidal surgery in 19 patients. Detectable levels of LHRH were present in 12 patients. Wide fluctuations of LHRH were seen in sequential samples collected at 10-minute intervals, suggesting a pulsatile mode of release. This technique may yield useful data on hypothalamic control of pituitary secretion.


Homogenous bone grafts to the mandible.

Homogenous bone grafts to the mandible. Homogenous bone grafts were used in 20 cases including cysts, nonunions, an open bite, an ameloblastoma, fibrous dysplasia, and cherubism. There was a 75% success rate. This type of graft can solve a number of operative problems in mandibular surgery.


Failure of silastin chin implant four years postoperatively. Failure of a preformed Silastic chin implant nearly four years after insertion is reported. It is the obligation of all clinicians to report failures as well as successes to provide data for comprehensive evaluation of various techniques and materials.


Correction of the atrophic alveolar ridge by interpositional bone grafting: a progress report. A retrospective study of postoperative stability and osseous changes was made on nine patients with maxillary or mandibular atrophy who were treated with interpositional bone grafting techniques. There was minimal discernible positional change or resorption of the portion of the maxilla or mandible that was moved by interpositional grafting procedures. Sequential radiographs and cephalometric tracings showed early consolidation of the grafted bone, minimal resorption of the respositioned osseous segments, and a small decrease of alveolar ridge height during an average potsoperative follow-up period of seven months.


The lipswitch: a modification of Kazanjian's labial vestibuloplasty. A variation of the labial vestibuloplasty can provide an improved base for dentures. Complications with this procedure have been fewer; the pain and edema have been less than or equal to the amounts encountered with other procedures. This modification can be performed on an outpatient basis and requires no free grafts or splints.


Sutures and suturing--current concepts.

Sutures and suturing--current concepts. Currently available suture materials can be classified as nonabsorbable and absorbable types. Too often the surgeon selects the material on the basis of handling properties alone. The "perfect" suture material does not exist. Physical properties such as tensile strength, reactivity, size, and absorbability must be considered in light of current knowledge of wound healing. Placement of sutures is obviously as important as selection of material.


Anemia, splenomegaly, and glomerulonephritis associated with autoantibody in Trypanosoma lewisi infections. Anemia with splenomegaly and signs of glomerulonephritis were found associated with the acute and post-acute phase of Trypanosoma lewisi infections of laboratory rats. The onset of the anemia was associated with the peak of parasitemia and the development of cold-active hemagglutinin (HA) for trypsinized rat erythrocytes. It persisted with gradual recovery for as long as the trypanosomes and HA were detected in the blood. Signs of glomerulonephritis consisted of hypercellularity of the glomerular tuft, swelling of vascular endothelium and tubular epithelium, thickening of Bowman's membrane and tubular basement membrane, and abnormal numbers of hyaline casts in the distal convoluted tubules. Residual damage to the kidneys was not evaluated.


Disaccharidase activity in the intestinal tissue of broilers infected with coccidia. Maltase and sucrase activities were measured in the intestine of broilers inoculated with sporulated coccidial oocysts. Infection with Eimeria acervulina, E. maxima, E. necatrix, and E. brunetti decreased disaccharidase activity in the intestinal region in which maximum infection was found compared with the activity in uninoculated controls. The maximum reduction occurred on the first or second day of patency followed by a rapid recovery in activity. Disaccharidase activity was inversely proportional to the inoculum dose.


A method of decontamination of ultrasonic scalers and high speed handpieces. The use of contaminated water in high speed handpieces and ultrasonic handpieces presents potential hazards to both dentist and patient. This study has shown that after waterline sterilization, the use of a sterile, disposable membrane filter can eliminate the microflora from the water of an ultrasonic scaler for up to 48 hours. Similarly, the water from a high speed handpiece can remain bacteria free for up to 72 hours when a 0.45 micrometer pore size membrane filter is installed into the waterline. This system of decontamination by filtration may present a workable approach to the problem of contaminated water and merits further research and development. Commercial materials and equipment are identified in this report to specify the investigative procedures. Such identification does not simply recommendation or endorsement or that the materials and equipment are necessarily the best available for the purpose. Furthermore, the opinions expressed herein are those of the authors and are not to be construed as those of the Army Medical Department.


T-pins in a direct pattern technique for posts and cores. A practical direct technique for making post and core impressions with a T-pin and self-curing acrylic resin was described. Emphasis was placed on the function of the T-shaped plastic pin in fabricating the pattern. Clinical procedures for each step were described in detail. The unique characteristic of the T-pin of softening and becoming very sticky when exposed to direct contact with acrylic resin monomer allows soft acrylic resin to adhere to it, resulting in an accurate direct impression of the canal.


Effects of occlusal therapy on pantographic reproducibility of mandibular border movements. A clinical experiment was undertaken to study the relationship between occlusal therapy and pantographic reproducibility. Twenty-six subjects were categorized according to their ability to reproduce pantographic border movements and were put into either a control nonreproducible, control reproducible, or experimental nonreproducible group. From each subject a sequence of five pantographic surveys consisting of two morning and two afternoon pantographic recordings was taken. Each survey period lasted a minimum of 30 days. The experimental subjects alone were given occlusal splint therapy and occlusal adjustment therapy during the sequence of recall periods. The relationship between the effect caused by occlusal therapy and pantographic reproducibility was analyzed. For the purpose of analysis, the pantographic recordings were assessed a numerical score using a pantographic reproducibility index. A double-blind technique was used until all data were collected.


Differentiation of Serratia marcescens and Serratia liquefaciens by tests for lipase and phospholipase production. The production of lipase and phospolipase by certain members of the Enterobacteriaceae was examined by thin-layer chromatography of resting-cell suspensions incubated with triolein or lecithin. Most strains of Serratia marcescens produced both enzymes while most strains of Serratia liquefaciens exhibited strong lipase but only a minor phospholipase activity. Enterobacter spp. (25 strains), Klebsiella pneumoniae (20 strains), Escherichia coli (15 strains), Citrobacter freundii (7 strains) and Proteus spp. (20 strains) lacked both types of enzymic activity except for the following: three strains of Enterobacter cloacae, two of Proteus mirabilis and three of Proteus vulgaris possessed slight lipase activity; about one-half of the Enterobacter aerogenes and Enterobacter hafniae strains examined produced slight phospholipase activity. It is suggested that tests for lipase and phospholipase should be used in conjunction with those for DNAase production and sugar fermentation for the differentiation of S. marcescens and S. liquefaciens.


Assay of staphylococcal delta-haemolysin with fish erythrocytes. Suspensions of erythroctes from certain marine fish (cod, saithe, haddock and mackerel) were 4--16 times more sensitive than human or horse erythrocytes to staphylococcal delta-haemolysin. Cod erythrocytes were lysed rapidly by delta-haemolysin and the titres of haemolysin were independent of the temperatures at which the tests were incubated, over the range 0--37 degrees C. Fish erythrocytes were not lysed by purified alpha- and beta-haemolysins and no synergistic action was found between beta- and delta-haemolysins. In blood agar-overlay plates, the zones of lysis that developed in cod blood agar were larger and clearer than those that developed in human or horse blood agar.


The use of fluorescein-labelled lectins in the detection and identification of fungi pathogenic for man: a preliminary study. Fluorescein-labelled lectins of known specificities for different sugars were used in an attempt to identify fungi in paraffin sections of surgical and post-mortem material. Aspergillus fumigatus, Blastomyces dermatitidis, Candida albicans, Cryptococcus neoformans, Paracoccidioides brasiliensis and Rhizopus oryzae have been studied with five fluorescein-labelled lectins and with basis of differences in their reactions with these stains. The results accord well with what is known of the chemistry of the organisms and the method offers promise to practising histopathologists.


Radiation damage in the high resolution electron microscopy of biological materials: a review. Radiation damage to a biological specimen arises from a variety of interactions between the illuminating electrons and the atoms in it. The relative probabilities of these events, and the amout of energy transferred, can be calculated from basic physical theory. The microscopic damage caused in a particular specimen in given operating conditions is more difficult to predict, but it can be measured by a number of macroscopic indicators, the chief of which are loss of mass and changes in the energy loss spectrum (or electron diffraction, pattern, if any). For most biological material the observed rate of damage is such as to set a limit to the intensity of illumination, the maximum magnification and the minimum size of detail that can be made visible. Several techniques have been devised and tested for reducing the radiation sensitivity of a specimen, of which cooling to a very low temperature and encasing it in an inert medium are the most effective. If the various protective measures act cooperatively, they could increase the effective resolution of sensitive material by an order of magnitude, making possible electron microscopy of the atomic structure of, for instance, the nucleic acid bases and other macromolecules. The prospects for observing living cells at a resolution better than that of the best optical microscopes would remain very small.


Acute effects of orally administered levamisole on random monocyte motility and chemotaxis in man. Cellular immune functions were studied in patients with early bladder cancer 2 hours after ingestion of either levamisole or a placebo. Random monocyte motility was significantly increased (P less than 0.025) in 13 of 17 patients receiving levamisole. Monocyte chemotaxis was significantly increased (P less than 0.025) in 16 of the 17 patients. Random monocyte motility and monocyte chemotaxis did not change in either 8 patients on the placebo or in 15 normal controls. Monocytes from normal donors showed increased random motility and chemotaxis after incubation with levamisole in vitro. These results indicated that increases in peripheral blood monocyte motility followed oral administration of levamisole. Kinetic studies indicated that these effects were rapid in onset and short lived.


Detection of mutagenicity of the colon carcinogen 1,2-dimethylhydrazine by the host-mediated assay and its correlation to carcinogenicity. Mutagenic potential of 1,2-dimethylhydrazine (DMH) was investigated in the host-mediated assay with mice used as hosts. This assay revealed potent mutagenicity of this colon carcinogen for Salmonella typhimurium G46. The mutagenicity of DMH was inhibited by pretreatment of mice with disulfiram. In addition, mouse strain and sex differences influenced the mutation induction by DMH: Mutation induction was significantly lower in C57BL/6 mice than in outbred ICR mice of either sex and was generally higher in male than in females of either C57BL/6 or ICR mice.


The respiratory epithelium. I. Human bronchus. Six morphologic cell types comprise the human bronchial epithelium: basal cells that do not reach the bronchial lumen, neurosecretory cells (Kulchitsky's cells, K-cells, or small granule cells) that rarely reach the lumen, and indifferent cells, mucous cells [small mucous granule cells (SMGC) and mucous goblet cells], ciliated cells, and ciliated-mucous cells that do reach the lumen. Ciliated-mucous cells bearing fully developed cilia and containing mucous granules are seen only occasionally. Three of the cell types that reach the lumen are microvillus covered and do not bear cilia. The microvillus-covered nonciliated cells are: 1) neurosecretory cells, 2) indifferent cells, and 3) mucous cells. Neurosecretory cells contain characteristic dense core granules. Such cells rarely reach the lumen. Indifferent cells are rarely seen. They have a pale cytoplasm and show no evidence of either ciliary or mucous differentiation. Similar cells are observed showing early signs of either ciliary or mucous differentiation or even both types of differentiation in the same cell. Mucous cells comprise the vast majority of microvillus-covered cells. They present either as SMGC with a few small mucous granules or as goblet cells, filled with mucus. These columnar cells are characterized ultrastructurally by dense cytoplasm and a well-developed endoplasmic reticulum and Golgi apparatus. The microvilli are coated with a glycocalyx that binds colloidal iron more avidly than that of either cilia or microvilli of ciliated cells. Possible interrelationships between the different cell types in normal epithelium are discussed.


The respiratory epithelium. II. Hamster trachea, bronchus, and bronchioles. The normal female hamster respiratory epithelium at five airway levels was characterized with the use of coordinated morphologic and histochemical techniques. Five morphologic cell types were recognized in the trachea, stem bronchi, and primary bronchl: basal cells and neurosecretory cells that were basally located and did not reach the lumen and mucous cells [mucous goblet cells and small mucous granule cells (SMGC)], indifferent cells showing mucous-ciliary differentiation, and ciliated cells that reached the lumen. Two epithelial cell types were observed in the bronchioles, ciliated cells and nonciliated Clara cells, both of which reached the lumen. Mucous cells presented as either SMGC with a few small periodic acid-Schiff-positive granules (diastase-resistant neutral mucosubstances) or as goblet cells, filled with the same material. Mucous cells were columnar, and the cytoplasm was electron-dense and contained a well-developed endoplasmic reticulum and Golgi complex. The microvilli of the mucous cells were coated more thickly with colloidal iron than either the cilia or microvilli of ciliated cells. Approximately one-half the cells in the trachea, bronchi, and bronchioles were ciliated. Ciliated cells containing intracellular ciliated cysts with normal cilia projecting into a closed space or ciliated cells bearing compound cilia were observed infrequently. Neurosecretory cells were rarely observed. These cells contained characteristic dense-core granules.


The respiratory epithelium. III. Histogenesis of epidermoid metaplasia and carcinoma in situ in the human. The histogenesis of epidermoid metaplasia and carcinoma in situ was analyzed in human bronchial epithelium. The conclusion is that epidermoid metaplasia and carcinoma in situ can result from conversion of mucous cells. This implies the direct transformation of one type of fully differentiated cell to another. The study therefore emphasizes the differentiation potentialities of the mucous cells that can divide and undergo goblet cell hyperplasia and epidermoid metaplasia. Epidermoid metaplasia is a common reaction to injury in the bronchus. In our series of cases it was especially frequent in patients without neoplastic disease who had undergone intratracheal intubation or tracheostomy and who had been maintained on a respirator in the Shock Trauma Unit, University of Maryland. Future studies will be required to distinguish the difference, if any, between epidermoid metaplasia destined to become malignant carcinoma and that which is not. One difference noted in this study was the absence of overt cornification in epidermoid metaplasia in patients without neoplastic disease.


The respiratory epithelium. VI. Histogenesis of lung tumors induced by benzo[a]pyrene-ferric oxide in the hamster. Lung tumors were induced in female Syrian golden hamsters by intratracheal instillation of benzo[a]pyrene-Fe2O3. The tumors were characterized with the use of coordinated morphologic and histochemical techniques including electron microscopy. The lung carcinomas were classified according to their presumed cell of origin. Most were derived from mucous cells and/or basal cells, and they were classified as either epidermoid carcinomas or as combined epidermoid and adenocarcinomas. The tumors in the second group (57% of the total number of carcinomas) presented a wide spectrum of epidermoid and adeno components. The epidermoid component was characterized in well-differentiated tumors by the presence of intercellular bridges and/or keratinization. Well-developed desmosomes and numerous bundles of tonofilaments were observed ultrastructurally. In diagnosing adenocarcinoma, one no longer needs to depend on the presence of tubules or gross glandular structures as criteria for diagnosis. The presence of intracellular and/or extracellular alveoli, well-developed Golgi complex, and endoplasmic reticulum and/or evidence of mucous secretion provide more definitive criteria. A tumor composed of neurosecretory cells that morphologically resembled a bronchial carcinoid of man was observed. Nests of uniform, small, polygonal cells with round-to-oval nuclei were seen at the light microscopic level. Dense-core secretory granules 1,100-2,200 A were present in the cytoplasm of the tumor cells. Several fibrosarcomas were observed. The tumors showed a very cellular structure, composed of either densely packed ovoid or spindle-shaped cells. Ultrastructurally, the cells resembled fibroblasts. The results obtained in this study give strong support for a histogenetic classification, i.e., a classification based on the cell of origin.


The burned hand: a planned treatment program. A planned treatment program for burned hands has been developed and was used in 72 burns of the dorsum of the hands. Treatment was individualized on the basis of whether hand burns were superficial or deep. In the former, there was evidence of spontaneous reepithelialization within 14 to 21 days. In the latter, immediate or delayed excision, followed by resurfacing with autografts was done. Both groups received topical antibiotic creaming, elevation, an exercise program as soon as they were able, and splinting of the burned hand in the antideformity position. Hypertrophic scars and unacceptable epithelium were excised when they interfered with function. Initially, this program allowed us to avoid unnecessary surgical procedures in 94% of the second-degree burns of the dorsum of the hand. The third-degree burned hand needed excision and autografting in 100% of the burned hands. This treatment program has as its goals: prevention of deformity by early motion and protection of the unburned and regenerating epithelium by creaming with topical antibiotic ointment.


The roll-bar hand.

The roll-bar hand. This report describes a new hand injury seen in passengers in dune buggies having rollover accidents. Since these vehicles are usually driven off the road and far from treatment centers the treatment of these injuries is often delayed. As the rollover takes place, the reflex action--usually of the passenger--is to grasp the roll bar. A crush-avulsion injury occurs at the level of the metacarpals, with the thumb frequently spared. Wound contamination, delay in treatment, and the frequency of other serious injuries add to the seriousness of this injury. Redesign of the roll bar, provision of better passenger protection, and an internal grasp support are suggested to reduce its incidence.


Conservative surgical management of urological complications after cadaveric renal transplantation. Review of a consecutive series of 85 cadaveric renal transplants revealed urinary fistulas in 7 cases. Bladder fistulas originated from the anterior cystostomy suture line in 3 patients and required secondary closure in every case. Ureteral fistulas from the donor ureter often required a multistaged operation. In every case the end result has been satisfactory, with closure of the fistula and preservation of renal function.


Studies of introital colonization in women with recurrent urinary infections. X. Adhesive properties of Escherichia coli and Proteus mirabilis: lack of correlation with urinary pathogenicity. The ability of a bacterial strain to adhere to the vaginal mucosa and the mucosa of the urinary conduits seems to be important in the pathogenesis of urinary infection. Bacterial adherence to vaginal epithelial cells was measured in vitro for 37 strains of Escherichia coli and 18 strains of Proteus mirabilis isolated from the anus, bladder and renal pelvis. No correlation could be demonstrated between the adhesive properties of a bacterial strain and its clinical pathogenicity, suggesting that host factors determining bacterial adherence are more important than bacterial adhesive factors in determining susceptibility to urinary infections.


The effect of oral bethanechol chloride on the cystometrogram of the normal male adult. A double-blind study of the effects of placebo and oral bethanechol chloride (25, 50 and 100 mg.) on the carbon dioxide cystometrogram of the normal male adult was done. Statistical analysis of the data showed no significant dose-response relationship for any of the parameters measured.


Urinary tract infection localization in women. The site of urinary infection in 51 adult women was determined by the bladder-washout technique (BW). Of the 37 patients with proved upper-tract infection shown by BW, 16 had upper-tract symptoms, three had lower-tract symptoms, and 18 were asymptomatic; 31 had antibody-coated bacteria (ACB), and six had no ACB. Of 14 patients with proved lower-tract infection shown by BW, three had upper-tract symptoms, five had lower-tract symptoms, and six were asymptomatic; none had ACB. All 31 women whose infecting bacteria were coated with antibody proved to have an upper-tract infection shown by BW. A subset of the population of adult women with upper-tract infection have organisms emanating from their ureters at BW localization, which are not coated with antibody. Physicians must be cautious in interpreting results that are negative for ACB.


Cyclobenzaprine in intractable pain syndromes with muscle spasm. The effectiveness of cyclobenzaprine hydrochloride, a new tricyclic skeletal muscle relaxant, was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness. The investigation was double-blind and randomized, comparing cyclobenzaprine hydrochloride (10 mg three times a day) with diazepam (5 mg three times a day) and with placebo. After two weeks of treatment, the 16 patients in the cyclobenzaprine group showed an overall improvement in pain variables as did the 16 patients in the diazepam group. No serious adverse reactions to cyclobenzaprine were observed in the study. However, dry mouth due to cyclobenzaprine's anticholinergic action and mild degrees of drowsiness were encountered more often than with diazepam or placebo.


Specific muscle protein-sparing postoperative dextrose-free amino acid infusions. The protein-sparing and ketogenic effect of postoperative infusion of maintenance solutions containing either 3.5% amino acids or 5% dextrose in 0.33 normal (N) saline was compared by nitrogen balance and urinary acetone determination in 31 patients. A specific muscle protein sparing effect was determined by quantitation of excretion of 3-methylhistidine in seven patients of the amino acid group and eight patients in the dextrose group. In addition, an extensive hormone and substrate profile was determined. It was found that amino acid infusions not only produce a less negative nitrogen balance but also significantly reduce excretion of 3-methylhistidine indicating specific preservation of the muscle compartment.


[Laboratory and clinical studies on cefoxitin in the field of obstetrics and gynecology (author's transl)]. 1) Serum concentrations of cefoxitin (CFX) was lower than that of cefazolin (CEZ), but the tissue concentrations of CFX were higher in ovary, oviduct and uterus compared with CEZ. 2) CFX was administered to 15 patients with moderate intrapelvic or urinary tract infections at a dose of 4 g per day for 5 to 7 days. The overall results obtained were as follows; excellent in 6 cases, good in 6 cases. The CFX treatment was effective in all patients, 8 cases, with intrapelvic infections. 3) The majority of organisms detected were E. coli (12 strains), and the antimicrobial activity of CFX against them was superior to those of CEZ and CET. 4) No side effects and abnormal laboratory findings were observed. 5) It is considered that CFX will be a useful drug in the field of obstetrics and gynecology.


Successful treatment of Nocardia asteroides infection with minocycline in kidney transplant patients. Two cases of Noca dia asteroides infection were encountered out of 55 kidney transplant patients at Chiba University Hospital. One patient developed an extrapleural abscess and the other had a pulmonary infiltration with chest wall abscess. The patients were successfully treated by surgical drainage of the chest wall abscesses and by oral administration of minocycline. No adverse effects caused by minocycline were observed during the therapy. From 1900, when the first case of Nocardia infection was reported in Japan, there have been 60 cases reported in Japanese literature through 1973, including those we observed. This is the first report on nocardiosis in kidney transplant patients and on successful treatment of nocardiosis with minocycline in Japan.


Congenital fistula of the right coronary artery-left ventricle--a case report. While the incidence of right coronary artery-left ventricle fistulae is low, cardiac catheterization, ascending aortogram and selective coronary angiogram led us to suspect the presence of such a fistula in a 10-year old female patient. Arteriorrhaphy with additional ligation was performed and the patient is in good health more than one year after surgery.


Surgical treatment of juxtarenal aortic occlusion. From 1974 to 1976, four patients with juxtarenal aortic occlusion were operated upon with no surgical mortality. Thromboendarterectomy (TEA) of the aorta with renal revascularization was performed in one patient, and TEA with grafting in three. Intraoperative renal protection was particularly important, since suprarenal aortic clamping was often required in these cases. Possible renal embolism developed in one patient postoperatively. In order to prevent renal embolism and to minimize ischemic insult to the kidney, the value of the following procedures was stressed; (a) irrigation of aortic lumen with saline after TEA under suprarenal aortic clamping with renal arteries kept occluded, and (b) re-application of aortic clamp below the renal arteries after irrigation. Since the most distal level of occlusive process was the common femoral artery in our series, the patient with this disease entity should be treated more actively.


A cellular approach to neurological disease. This presentation is necessarily an overview of the work in our laboratories. We have chosen to study oligodendroglia and myelin first, because we have specific markers we can use, and we can focus on specific disease entities. However, the same strategy can be applied to neurons and neuronal diseases. Despite major advances in the neurosciences, many questions remain unanswered. In general there has been a predictable sequence in our progress in understanding the nature of neurological disorders. Early studies focused on a clinical description of the disease. Next the pathology was described, and attempts were made to correlate these findings with the clinical symptoms. Now that we are able to isolate some of the cells involved in specific diseases (see Table I) we can begin to investigate the normal metabolism of these cells, study their components, and follow any changes that take place under different pathological conditions. Thus, we have shown that it is possible to study and perphaps eventually provide therapy for certain disorders, such as multiple sclerosis, without knowning that delineation of events in the normal cell is an essential step in unraveling the mysteries of neurological disease.


[State of intracardiac hemodynamics in normothermic heart perfusion]. The state of intracardiac hemodynamics during normothermal perfusion was studied on an isolated heart-lung preparation obtained by the Robicsek I method (30 experiments). In appraisal of the hemodynamic and myocardial indices characterizing the functional condition of the right and left ventricles in 2 to 3 hours, definite changes were revealed which allowed prognostication of the duration and effectiveness of preservation. If the functional condition of the transplant (changes predominantly in the right ventricle) diminished in this period, heart arrest occurred within the next 30--60 minutes. If after these 2--3 hours the work of the heart-lung preparation was characterized by stationary parameters of intracardiac hemodynamics, such a transplant was capable of maintaining autoperfusion for 7 to 8 hours; the optimum term of preservation, however, was 6 hours. Irreparable diminution of the transplant viability occurred sharply in the next one or two hours.


[Effect of strophanthin and atropine on atrioventricular conduction in acute myocardial infarct]. The effect of single therapeutic doses of strophanthin (0.25--0.4 mg) and atropine (0.75--1,0 mg) on cardiac contraction was studied in 39 patients with acute myocardial infarction and in 12 subjects with no signs of organic heart affection by recording the electrical potentials of the heart conduction system. The indicated dose of strophanthin caused changes in the intervals of the electrogram neither in individuals who did not have myocardial infarction nor in patients with acute myocardial infarction, including those with myocardial infarction complicated by atrioventricular and intraventricular block. Atropine improved atrioventricular conduction by shortening the PH interval in patients with myocardial infarction complicated by I--II grade atrioventricular block and had no marked effect on the spread of excitation impulses along the atrioventricular node in higher grades of atrioventricular block. Atropin shortened the PH interval slightly in individuals without myocardial infarction and in patients with uncomplicated myocardial infarction, but did not have an effect on intraventricular conduction.


[Interventricular septal defects in combination with aortic valve insufficiency and the problems of their surgical correction]. Twenty-one operative interventions were performed on patients with interventricular septal defects and aortic insufficiency in the period between 1964 and 1976. The authors believe that the main component of the operative tactics is correction of aortic insufficiency, which in most cases may be achieved by plastic surgery of the abnormal cusps. Since mild aortic insufficiency remaining in some of the patients after the operation causes no marked disorders of hemodynamics, the authors assume that at the current stage prosthetics of the valve is justified only if plastic correction of the abnormality is absolutely impossible.


Intrarenal hemodynamics in the transplanted rat kidney. Regional and single glomerular blood flow conditions in the transplanted rat kidney after various periods of cold ischemia were investigated with use of the microsphere method. Intravascular injection of a silicon rubber compound (Microfil) allowed identification and sampling of single glomeruli. The periods of ischemia were two hours (minor damage), 12 hr (intermediate damage), and 16 hr (severe damage). After two hours of cold ischemia, the regional and total renal blood flows were fairly normal. After 12 hr and 16 hr of cold ischemia, the total and regional blood flows were reduced five minutes after recirculation, the reduction being pronounced in the deep cortex and juxtamedullary glomeruli. In the 12-hr group, the blood flow showed complete restitution after 65 min, whereas in the 16-hr group, the blood flow in the inner cortex and juxtamedullary glomeruli remained decreased. An impairment of medullary circulation would seem to be an important component in the pathophysiology of acute renal failure in this model.


Nephron function of the transplanted rat kidney. Tubular function in the early phase (one to three hours) after transplantation of rat kidneys was analyzed with respect to glomerular filtration, vascular and tubular pressures, and excretory variables. Kidneys exposed to a short period of cold ischemia (two hours) functioned almost normally, except for a polyuria. After 12 and 16 hr of cold ischemia, nephron heterogeneity appeared with 1) "normal" tubules, 2) dilated tubules, and 3) collapsed tubules. In the "normal" tubules, the pressure was increased to 20 mm Hg, and the filtration was reduced in proportion to the mean net driving force. The dilated tubules had no filtration due to a more or less complete tubular obstruction, probably located in the thin loop of Henle and in the collecting ducts. The collapsed tubules had no filtration due to glomerular ischemia, which in turn might be the consequence of afferent arteriolar constriction. The total GFR was greatly reduced since only the "normal" tubules contributed to the total filtration. Concentrating ability and potassium secretion were also impaired. We interpreted this impairment as being due to medullary dysfunction, which would explain the isosthenuria and the impaired potassium transport.


[Chromosomal abnormalities in human neoplasia (author's transl)]. Multiple connections exist between chromosomal aberrations and malignant tumors. It is the aim of the present article to summarize the data known so far in view of i) cancer-prone chromosome abnormalities, ii) chromosome abnormalities related to tumors and iii) chromosome abnormalities related to carcinogens. In some instances it seemed useful to discuss the findings in man in connection with the results of in vitro experimental data.


[Cytostatica and small intestine (author's transl)]. Cytostatica not only suppress proliferation in tumor cells but it also checks proliferation in small intestinal epithelium. The consequence is cell reduction and damage resulting in a diminished function. Because of the high reserve capacity of the small intestinal epithelium, clinical signs of diminished function are mostly seen after repeated high doses or one extremely high doses of Cytostatica. Although there is abundant information on the effect of Cytostatica on the small intestinal epithelium (cell turnover, morphology, digestive enzymes and absorption) there are other areas that are as urgent for the interested clinician to work on: 1. Would it be possible to coincide the dose and dosage rate with the cell cycles to reduce the chance of damage to small intestinal epithelium? 2. Which role has the luminal content when there is damage from Cytostatica? Is it possible to concentrate on changing the luminal contents (antibiotics, "elemental diet", cultivate desirable microflora, etc.) Therefore diminishing the damage from Cytostatica? 3. How would Cytostatica influence the barrier function on the intestinal wall? Should the patient on Cytostatica therapy receive special protection against intestinal infection? 4. Does Cytostatica affect the biotransformation in the small intestinal epithelium, especially when taken orally? How important is this biotransformation in small intestinal epithelium damaged by Cytostatica therapy? 5. What factors determine the regeneration of the small intestinal epithelium after Cytostatica damage?


Immunofluorescence studies of skeletal muscle extracellular membranes in diabetes mellitus. Skeletal muscle from 34 insulin-dependent diabetic patients and 20 age-matched controls was examined by immunofluorescent microscopy. Significantly increased staining of capillary and muscle basement membranes of diabetics was seen for IgG, albumin, and fibrin. The immunofluorescent pattern was identical with that observed using heterologous antibasement membrane antiserum, indicating that these proteins were present within these basement membranes. No differences were detected between males and females or between kidney-transplanted and nontransplanted diabetics. No correlation was noted between intensity of staining and duration of diabetes. The presence of certain serum proteins within vascular and nonvascular basement membranes in diabetics is not restricted to the kidney and may reflect widespread alterations in extracellular membranes that permit entrapment of these proteins.


Mesangial proliferative glomerulonephritis. Eleven cases of mesangial proliferative glomerulonephritis whose kidney biopsies were studied with light, immunofluorescent, and electron microscopy are described. Nine patients presented with nephrotic syndrome, one with proteinuria and hematuria, and one with proteinuria alone. Morphologically mesangial proliferative glomerulonephritis was characterized by diffuse mesangial cell proliferation and some increase in mesangial matrix. On immunofluorescence, mesangial IgM deposition was observed in all cases and was considered a distinct feature of mesangial proliferative glomerulonephritis. Electron microscopy showed electron-dense granular deposits within the mesangial matrix in four cases. The clinical course was variable. Of the eight cases with nephrotic syndrome, four treated with steroids alone and four treated with steroids and cytotoxic drugs, one in each group achieved remission while the remaining patients continued to have steroid dependency or resistance. Two of these latter patients manifested steroid responsiveness, steroid resistance, and spontaneous remission at different times in their courses. Renal function remained normal in all. These cases demonstrate that mesangial proliferative glomerulonephritis is an entity characterized by increased mesangial cellularity, deposition of IgM in a mesangial distribution, a relatively benign course, and variable response to treatment.


A morphologic and permeability study of luminal smooth muscle cells after arterial injury in the rat. In the carotid air drying model of arterial endothelial injury in the stressed rat, endothelium does not always regenerate over the zone of intimal thickening; instead, a layer of modified smooth muscle cells appears to form a temporary luminal surface. We examined the properties of these luminal smooth muscle cells in injured right carotid arteries from stressed rats at intervals up to 2 months by light, scanning electron, and transmission electron microscopy. Before perfusion fixation, selected animals were given injections of Evans blue dye, ferritin, or horseradish peroxidase. Unlike adjacent endothelium, the luminal smooth muscle cells most closely resembled neighboring intimal smooth muscle cells, lacked morphologic characteristics of normal endothelium, and did not stain with rabbit antibody to rat factor viii. Unlike normal mature endothelium, this layer did not exclude horseradish peroxidase, Evans blue, or ferritin. These data demonstrate that a nonthrombogenic layer composed of modified smooth muscle cells can appear at the luminal surface of a zone of injury-induced myointimal thickening; however, this layer does not form a permeability barrier to large molecules.


Asymptomatic primary biliary cirrhosis. Presentation, histology, and results with D-penicillamine. Of 103 patients with the syndrome of primary biliary cirrhosis (chronic, nonsuppurative destructive cholangitis) who entered a double-blind, randomized, controlled treatment trial with either D-penicillamine or placebo, 21 (20%) were asymptomatic with respect to their liver disease. Study of these 21 patients revealed that (1) 43% of patients with asymptomatic primary biliary cirrhosis had advanced histologic lesions (fibrosis or cirrhosis); (2) asymptomatic patients with advanced histologic lesions likely have had their disease for 10 years or more; (3) stage of primary biliary cirrhosis may remain unchanged for years; and (4) most asymptomatic patients receiving D-penicillamine, when compared with patients given placebo, had improved liver function tests at 1-year follow-up. However, the incidence of major toxicity with D-penicillamine for primary biliary cirrhosis in a maintenance dose of 1 g approximates 20%. Furthermore, one of our patients who was asymptomatic but who had advanced histologic changes died recently from D-penicillamine-associated bone marrow suppression. It remains to be determined whether the benefit-to-risk ratio of D-penicillamine in primary biliary cirrhosis justifies its use.


Glucagon and diabetes.

Glucagon and diabetes. We have considered the evidence, first, that the presence of glucagon is essential in the pathogenesis of the full syndrome that results from complete insulin deficiency; second, that in the diabetic in whom insulin levels are relatively fixed, a rise in glucagon concentration contributes to endogenous hyperglycemia; and, third, that conventional methods of treatment of diabetes do not fully correct either the abnormal glucagon levels or the hyperglycemia, but when insulin therapy is supplemented with somatostatin, an agent which suppresses both glucagon and growth hormone, both hyperglycemia and hyperglucagonemia are corrected. These facts may one day provide a rationale for therapeutic efforts to suppress excess glucagon secretion in the management of diabetes in man.


Somatostatin and diabetes.

Somatostatin and diabetes. Somatostatin may act as a local regulator of endocrine and exocrine secretion and as a peptidergic neurotransmitter rather than as a classical circulating hormone. The possible physiologic role of its secretion in the regulation of islet A and B cell function, and particularly its significance in nutrient homeostasis and diabetes, are discussed.


Why control diabetes?

Why control diabetes? The concept that appropriate therapy for diabetes should achieve levels of fasting and postprandial blood, serum, or plasma glucose values as close to those of the nondiabetic as possible may be philosophically correct, but in practice is most difficult to obtain.


Diabetic retinopathy.

Diabetic retinopathy. The only methods of treatment for severe diabetic retinopathy that have been proved effective by controlled clinical trials are photocoagulation and pituitary ablation. It must be noted that photocoagulation and pituitary ablation impede but do not cure diabetic retinopathy. Pars plana vitrectomy can be highly effective for removing blood from the vitreous of the eye, allowing better vision, particularly if the retina has been shown to be functional by electrophysiologic testing and ultrasonography. In addition, vitrectomy allows the ophthalmologist to visualize, evaluate, and treat the diabetic retina by photocoagulation or other methods. Attempts at better regulation of blood sugar have reduced the development of microangiopathy in experimental animals and recently in man. The benefits of rigorous regulation of the blood sugar has been noted in a policy statement by the American Diabetes Association. The development of a practical, beneficial pancreas has been undertaken, and may be required in order to reap the full benefits of rigorous blood sugar control. It has been recommended that all patients be evaluated by an ophthalmologist as soon as they have been found to have diabetes, that all diabetics be examined ophthalmologically on an annual basis, and that patients with significant retinopathy be seen at 6 month or shorter intervals by their ophthalmologist. The evaluation and treatment of diabetic retinopathy has progressed enormously during the past decade. It is hoped that the cause of diabetic microangiopathy and retinopathy will be discovered in the near future so that treatment will ultimately cure rather than control the process of diabetic retinopathy.


Hyperosmolar nonketotic coma in the elderly diabetic. The gravity of this syndrome of severe diabetic stupor without ketosis may not be recognized because patients are usually middle-aged or elderly with mild diabetes. A lack of urgency in treating these patients is probably the cause of the widely reported mortality of 40 to 70 per cent.


[The history of plastic surgery (author's transl)]. The plastic surgery begins with rhinoplastic methods in the early medieval India and was unknown to Western medicine until 1400. The first European surgeon, who restored a lost nose, was Branca de'Branca in Sicily. He took the flap from the cheek, but his son Antonio Branca took the reparative flap from the upper arm, and this "Italian method" was first described by the knight of Teutonic Order Heinrich von Pfalzpaint in 1460. Antonio Branca repaired also mutilated lips and ears, and the methods employed by him and by the Vianeo family in Calabria are described by various authors, most extensively by Gaspare Tagliacozzi in his "Chirurgia Curtorum" (1597). -Soon after Tagliacozzi's death, plastic surgery fell into disuse, until in 1794 the description of  a rhinoplastic operation in India brought the methods again to the attention of European surgeons and initiated the revival of the practice. German surgeons as Carl Ferdinand Graefe, Johann Friedrich Dieffenbach and Bernhard Langenbeck leaded it to its full modern development.


[Adam Politzer (1835-1920) (author's transl)]. Politzer's method of tubal inflation was published in 1873. Together with J. Gruber, he was entrusted with the direction of the newly-founded Ohrenklinik of the University of Vienna, the first of its kind in the world. He determined the otic capsule as the cause of otosclerosis for the first time in 1893. After J. Gruber's retirement 1897, he became chief of the Ohrenklinik of Vienna. Politzer published 103 scientific papers dealing with almost all fields of otology, including his well-known textbook of Otology and his History of Otology in 2 volumes. During his 46 years of teaching, Politzer turned otology from a "sterile, hopeless discipline" into an academically recognized field in Austria.


Intra and extracranial meningiomas involving the temporal bone. Meningiomas involving the temporal bone are very rare. Until 1964, only 39 cases had been reported in the world literature. Most series reported are very small and a physician is unable, based on his own experience, to acquire a sufficient knowledge about this entity and may raise serious doubts regarding the diagnosis and management of these tumors. In the past nine years the author has encountered five cases of meningiomas involving the temporal bone. This became a stimulus for a thorough research of the world literature of meningiomas in general, with emphasis on temporal bone involvement. Nine more cases were collected from cooperative physicians with whom the author has been associated. These 14 cases are the clinical material analysed in this study. This thesis is divided into three sections: 1. Exhaustive review of the world literature on meningiomas with emphasis on involvement of the temporal bone. 2. A detailed presentation and discussion of the clinical material stressing the importance of the newer diagnostic methods available and the most modern microsurgical techniques used in otological and neurological surgery procedures, applied to the treatment of those lesions. A light microscopic histopathological study of all cases reported is presented. Electronmicroscopy demonstrates the true intracellular nature of an atypical, recurrent meningioma occurring in a child. 3. A critical evaluation of the cases presented and the value of the diagnostic and therapeutic methods applied in this series of patients are here analysed. Conclusions are then drawn based on the experience and knowledge accumulated in this study. The histopathological diagnosis of meningiomas sometimes is difficult. Probably those tumors involve the temporal bone more commonly than has been reported in the literature. Some of these lesions probably are being misdiagnosed as chemodectomas or other neoplasias. Computerized axial tomography, particularly applied to the diagnosis of brain lesions, is the major break-through of recent modern medicine. A noninvasive technique, when used with contrast enhancement, offers great diagnostic possibilities. Early diagnosis of meningiomas and their complete surgical excision are the key factors necessary for a successful result with a good prognosis and a low recurrence rate. Although these tumors are classically considered radioresistant, radiotherapy may play a role in the treatment of incompletely excised lesions or in patients of a poor surgical risk. Further experiences and time will probably lead to more definite conclusions regarding the role of radiation therapy or the combined surgical and postoperative radiation treatment. Of all brain tumors, meningiomas offer the best prognosis.