Spectrum of gonococcal arthritis: evidence for sequential stages and clinical subgroups. In a series of 84 patients with gonococcal (GC) arthritis, 41 were documented as follows: 17 had positive blood culture or typical skin rash (Hematogenous Group); four had positive joint culture plus hematogenous manifestations (Transition Group); and 20 had positive joint culture without positive blood culture or skin rash (Joint Localization Group). The hematogenous group, especially patients with proved gonococcemia, presented significantly earlier after onset of symptoms than patients with joint localization alone, suggesting sequential stages of disease. Patients with verified bacteremia were significantly more toxic than those with rash or culture-proved joint infection alone. Nine of the joint localization patients had a monoarthritis with minimal systemic manifestations. The remaining 11 had a polyarthritis and were significantly more toxic. A concept of sequential stages and clinical subgroups of GC arthritis is proposed which may improve patient classification and differential diagnosis.


Destructive arthropathy in generalized osteoarthritis with articular chondrocalcinosis. A destructive arthropathy is much more common when generalized osteoarthritis (GOA) and articular chondrocalcinosis (ACC) coexist than in GOA alone. Fifty-two patients with GOA and ACC were compared to a matched control group with GOA alone. A marked increase in the frequency of a destructive arthropathy was found in the group with both GOA and ACC. Nonweight-bearing joints were often involved in the group with GOA and ACC, whereas they were seldom involved in the group with GOA alone.


Sacro-iliac joint in renal osteodystrophy: roentgenographic-Pathologic correlation. A detailed roentgenographic and pathologic study of the sacro-iliac joint in a cadaver with renal osteodystrophy revealed subchondral abnormalities, particularly in the ilium, which consisted of resorption of bone, substitutive fibrosis, and thickening of remaining trabeculae. Overlying articular cartilage degeneration was also apparent. The "pseudo-widening" of the joint space noted in ante and post-mortem radiographs in this patient simulated the findings in early ankylosing spondylitis.


Inflammatory involvement of vertebrae in ankylosing spondylitis. Unusual destructive lesions of the cervical and lumbar vertebrae are described in two patients with ankylosing spondylitis. Biopsy of a lesion from one of the patients showed it to be inflammatory in nature. Possible mechanisms for vertebral centrum involvement in ankylosing spondylitis, centering on the role of enthesopathies are discussed.


Serum complement and immunoglobulin levels in sporadic and familial ankylosing spondylitis. Serum levels of C4, C3, IgG, IgM and IgA were measured by immunodiffusion in age matched groups of 48 sporadically encountered patients with ankylosing spondylitis, 56 with rheumatoid arthritis and 52 normal controls. Mean levels of C4 and IgA were significantly elevated in the sera of patients with sporadic ankylosing spondylitis, in comparison to normal controls. Mean IgA levels were also significantly elevated in 11 HL-A 27 positive patients with familial spondylitis but no such elevation was found in the sera of their healthy first-degree relatives with and without HL-A 27. The results of these studies suggest that humoral immune mechanisms may be involved in the pathophysiology of ankylosing spondylitis.


HL-A27 and ankylosing spondylitis in B.C. Indians. HL-A antigens were determined in Haida and Bella Coola native Indians, two communities known to have a high prevalence of ankylosing spondylitis. Tests were conducted on those with x-ray evidence of sacro-iliitis and on a sample of the community at large. Sacro-iliitis was found to prevail in approximately 10 per cent of adult Haida males and in over two per cent of Bella Coola adult males. Of 20 Haidas with sacro-iliitis, 17 were HL-A 27 positive. Fifty per cent of the Haida community at large were HL-A 27 positive. Three Bella Coolas known to have sacro-iliitis were all HL-A 27 positive, while 25 per cent of the community sampled at large were HL-A 27 positive. About one in five adult Haida males who were HL-A 27 positive showed evidence of sacro-iliitis, a proportion close to that ascertained in Caucasian communities. It would appear, therefore that the risk of disease in HL-A 27 positive Bella Coola males is considerably lower.


HL-A antigens in Europeans and Maoris with rheumatic fever and rheumatic heart disease. Using a standard microtoxicity technique of tissue typing, the distribution of tissue antigens in 75 Maoris and 514 European disease-free blood donors was determined. Fifty Maori and 50 Europeans with rheumatic fever or rheumatic heart disease were compared with each control group. Normal Maoris had HL-A3 less frequently than Europeans (P less than .0005). HL-A28 was reduced (P less than .005) and HL-A17 increased in European patients (P less than .0005). In Maori patients there were minor differences in the frequency of HL-A3 and 8, which were increased, and HL-A10, which was diminished.


Azathioprine hypersensitivity mimicking an acute exacerbation of dermatomyositis. We describe an unusual hypersensitivity reaction to azathioprine occurring in a patient with dermatomyositis, in which the acute manifestations suggested an exacerbation of the patient's underlying disorder. However, laboratory studies were not consistent with an acute exacerbation of dermatomyositis, and the subsequent clinical course confirmed the impression that the patient's symptoms were due to hypersensitivity to azathioprine. Physicians should be aware that a hypersensitivity reaction to azathioprine may mimic a flare of dermatomyositis.


Biochemical studies on the aqueous humour of rhesus monkeys (Macaca mulatta). Aqueous humour of rhesus monkey eye contains lower concentration of glucose and excess of sodium and chloride irons in comparison to constituents of serum of the same animals.


The formation and cytochemical characterization of cortical granules in ovarian oocytes of the golden hamster (Mesocricetus auratus). The formation and cytochemical characterization of cortical granules in the ovarian oocytes of the golden hamster have been investigated by use of light and electron microscopical techniques. Particular emphasis is given to the changing population of organelles associated with cortical granule formation. Our observations indicate that cortical granules are produced by the participation of both the Golgi complex and the rough endoplasmic reticulum. Ultrastructural cytochemistry reveals that the cortical granules are composed of glycoprotein. The cortical granules are released at fertilization by a merocrine-type of secretory process.


Techniques for estimating allometric equations. Morphologists have long been aware that differential size relationships of variables can be fo great value when studying shape. Allometric patterns have been the basis of many interpretations of adaptations, biomechanisms, and taxonomies. It is of importance that the parameters of the allometric equation be as accurate estimates as possible since they are so commonly used in such interpretations. Since the error term may come into the allometric relation either exponentially or additively, there are at least two methods of estimating the parameters of the allometric equation. That most commonly used assumes exponentiality of the error term, and operates by forming a linear function by a logarithmic transformation and then solving by the method of ordinary least squares. On the other hand, if the rrror term comes into the equation in an additive way, a nonlinear method may be used, searching the parameter space for those parameters which minimize the sum of squared residuals. Study of data on body weight and metabolism in birds explores the issues involved in discriminating between the two models by working through a specific example and shows that these two methods of estimation can yield highly different results. Not only minimizing the sum of squared residuals, but also the distribution and randomness of the residuals must be considered in determing which model more precisely estimates the parameters. In general there is no a priori way to tell which model will be best. Given the importance often attached to the parameter estimates, it may be well worth considerable effort to find which method of solution is appropriate for a given set of data.


A gross and microscopic study of the respiratory anatomy of the Antarctic Weddell seal, Leptonychotes weddelli. Four species of Phocidae, or true seals, inhabit the waters surrounding the Antarctic continent. These animals are thought to have different diving capabilities. The Weddell seal, Leptonychotes weddelli, is known to be capable of attaining depths up to 600 meters. The respiratiory system of the Weddell seal shows the usual adaptations to an aquatic environment characteristic of other marine. These include lungs that undergo compression acollapse at depths greater than 70 meters; hyaline cartilage in the tracheo-bronchial tree as far as the terminal bronchioles; and large amounts of smooth muscle surrounding the distal-most bronchioles. The collapsible lungs provide a mechanism by which air is forced from the alveoli adjacent to the pulmonary capillary beds thereby preventing the absorption of nitrogen gas into the bloodsteam. The presence of hyaline cartilage throughout most of the tracheo-bronchial tree increases the effective dead air space that accommodates most of the air forced from the collapsed lungs. The smooth muscle surrounding the respiratory bronchioles prevents their collapse while under the pressures of a deep dive. Collapse of the respiratory bronchioles not supported by cartilage would trap air in the lung alveoli during a dive. In addition, large- sac-like "diverticulae" are found in the submucosa throughout the tracheo-bronchial tree. These diverticulae, which open directly into the lumen of the tree, appear to be modified glands whose cells, in most cases, do not appear to be specialized for secretory function. They are most numerous in the more distal bronchi and terminal bronchioles where they are situated on both the luminal and adventitial sides of the hyaline cartilage supporting the walls of the air passages. Diverticulae are not found in the respiratory bronchioles or in the respiratory portion of the lungs.


Compositional nonrandomness: a quantitatively conserved evolutionary invariant. The a priori probability that the amino acid composition of a protein will exhibit a given overall deviation from the genetic code table frequencies is the same for all protein families independent of protein length, biological function, or origin.


A genetic model for the evolution of the glycosphingolipids. The glycosphingolipids have been found in many animal tissues, but the complexity of their molecular structure varies considerably among the different phyla. Relatively simple structures have been found in invertebrate species, while the most complex have been demonstrated in brain tissue of modern fishes and amphibians. The data on the phylogenetic distribution of the glycosphingolipids has been interpreted to indicate that a significant number of gene duplications, involving many different structural genes, may have occurred during a few specific periods of vertebrate evolution. The transition from invertebrate to jawless vertebrate, the divergence of rays and skates from true sharks, the advent of modern bony fishes and the transition from aquatic to terrestrial vertebrates, each could have veen accompained by duplications of genes involved in the synthesis and degradation of glycosphingolipids. The evolutionary study of such a multi-enzyme system may be one means to detect alterations in the genome as a whole. The apparent correspondence in time of these gene duplications involved in glycosphingolipid metabolism and periods of rapid vertebrate evolution which may have been accompanied by significant increases in the amount of cellular DNA suggests that such changes may have occurred via the mechanism of tetraploidization.


Nature genetic basis and evolution of the haemoblobin polymorphism in Chironomus. Chironomus larvae exhibit considerable haemoblobin polymorphism. Chironomus tnetans has 10 and C. pallidivittatus has 8 electrophoretically different Hb-chains. With the exception of one Hb-chain, all are species-specific. The hybrid which is fertile, shows the Hb-pattern of both parents. In the F2 and subsequent generations, considerable chromosome rearrangements occurs. Since the chromosomes of the parent species can be distinguished in the polytene state, Hb-patterns can be correlated with specific chromosomal constitutions. All the species-specific Hb-genes are located on one chromosome. This finding suggests that the Hb-genes have evolved through multiple gene duplications. Different mechanisms for gene duplication are discussed.


Argyrophil cell microneoplasia in the Mastomys' stomach--an observation on early carcinoid formation. To analyze the early stages of argyrophil cell carcinoid growth, complete serial sections were cut from the glandular portion of the stomachs of 22 Mastomys and submitted to Sevier-Munger's reaction. The 154 grossly invisible foci of argyrophil cell microproliferation thus detected were classified into three stages of microproliferations (I, II, and III), and the last stage was definitely a microcarcinoid. There was a gradual transition in cell proliferation among these three stages; the first stage (microproliferation I), in which the cells were morphologically indistinguishable from those of hyperplastic proliferation by general morphologic criteria, was where the initial change of argyrophil cell carcinoid formation was detectable by a light microscope. Whereas multiple occurrences of microcarcinoids accounted for the multiplicity of well-developed tumors in the stomachs of Mastomys, a well-developed carcinoid in this species was formed by the confluence of several microcarcinoids.


The architecture of 5S rRNA and its relation to function. An extensive comparative analysis of the available primary sequence data  on 5S rRNA has been made. A universal secondary structure is presented for procaryotic 5S rRNA which contains four helical regions. Eucaryotic 5S rRNAs are found to have only three of these helices and thus have a somewhat different architecture. In addition, a highly conserved segment of more than thirty nucleotides is identified in the 5' half of the procaryotic molecule. This segment includes the oligonucleotide -CGAAC- which presumably binds to the t-RNA "common" sequence -GTpsiCG-. Among the eucaryotes, the plants display a procaryotic nature in this region, but no eucaryote has the sequence -CGAAC- in this segment. A functional role for the procaryotic 5S rRNA molecule is discussed in which it is envisioned to undergo conformational change, i.e., coiling and uncoiling of one of the helices, which can result in a cyclic interaction of the 5S rRNA molecule with two t-RNA molecules. A general principle also emerges: the natural rotational motion inherent in coiling and uncoiling of nucleic acid helices can be converted quite simply to linear mechanical motion.


G- and C-banding patterns in the T2 murine leukemia. The bone marrow cells of BALB/c mice with T2 murine leukemia were analyzed cytogenetically. Of 98 leukemia metaphases, 16.3% were hypodiploid, 4.1% hyperdiploid, and 79.5% diploid. The distribution of G bands in diploid metaphases indicated that almost half of them were pseudodiploid, with chromosome abnormalities such as trisomies, monosomies, nullisomies, unidentified chromosomes, translocations, deletions, or duplications. Since all mouse chromosomes are acrocentric and can be identified only tentatively most of the anomalies detected with G-banding procedures would have passed unnoticed with conventional cytogenetic techniques. The C-banding pattern of leukemia cells did not differ from that of normal controls. However, a considerable number of leukemia cell metaphases had bridges connecting the centromeric C bands of two or more chromosomes. This phenomenon probably indicates an increased stickiness of the heterochromatin, which may produce mitotic nondisjunction and the appearance of monosomies and trisomies.


Oral contraceptives as related to cancer and benign lesions of the breast. We conducted a case-control study to search for any relationship between use of oral contraceptives and development of breast cancer or benign breast disease. Women less than 50 years old with these diseases were matched with 2 controls by age, race, religion, and hospital. Home interviews elicited information on oral contraceptive use and other host and environmental factors. The study population comprised 1,770 women, including 452 with breast cancer and 446 with benign breast disease. The relative risk of developing cancer or benign disease was measured by matched set and summary chi-square analyses. Although the relative risk of developing breast cancer among "ever-users" of oral contraceptives was 1.1, the risk among women using oral contraceptives for 2-4 years was 1.9 (significantly increased). This risk estimate reached 2.5 for the 2- to 4-year users if they were still taking oral contraceptives when entered into study. Moreover, prior biopsy for benign breast disease increased the cancer risk among long-term users by as much as 11-fold. The relative risk of breast cancer did not vary by age, interval since first use, earliest year of use, or interval since last use. These results could be interpreted to indicate that oral contraceptives did not induce breast cancer but may have accelerated the growth rate of preexisting breast cancer. The relative risk of developing benign breast disease among ever-users of oral contraceptives was 0.8 (significantly reduced); it decreased with longer duration of use until it reached 0.2 for women who took these hormones 8 years or more. The relative risk of benign breast was not affected by earliest year of use or interval since last use. We concluded that oral contraceptives reduced the incidence of benign breast disease, but that use of steroid hormones is ill-advised for women with already established benign breast disease.


Reactivity of smooth-muscle antibodies, surface ultrastructure, and mobility in cells of human hematopoietic cell lines. Seventeen human hematopoietic cell lines were tested by indirect immunofluorescence (IF) for reactivity with human serum containing smooth-muscle antibodies (SMA). The correlation of the IF pattern to the cell surface ultrastructure was revealed by scanning electron microscopy (SEM). Lymphoma cells, viewed by SEM, had short villi over the entire cell surface, but, by IF, showed a type of membrane fluorescence. Cells of lymphoblastoid lines had thin, long surface villi, sometimes asymmetric but most often distributed over the whole cell surface. Myeloma and leukemia cells, which had few membrane villi but a surface covered by "blebs" as revealed by SEM, demonstrated, by IF, only a few stub-like projections extending from the surface. Time-lapse cinematography revealed that the intensity and pattern of SMA staining were also correlated to the degree of motility. Indirect IF with human SMA-positive serum might be used in the classification of cell lines derived from human hematopoietic tissue.


Measurement of serum ferritin by radioimmunoassay: results in normal individuals and patients with breast cancer. Ferritins are iron-containing proteins found in normal tissues; they increase in concentration in many tumors and the blood of tumor-bearing individuals. We utilized a double-antibody radioimmunoassay for measurement of serum ferritin and defined the upper limit of normal as 146 ng/ml for women (mean 34 ng/ml) and 193 ng/ml for men (mean 93 ng/ml). Serum ferritin levels exceeded these limits in preoperative sera of 41% of women with mammary carcinoma (mean 199 ng/ml) and in 67% of women with locally recurrent or metastatic mammary carcinoma (mean 671 ng/ml). Individuals with hepatic inflammatory states are known to have high serum ferritin, and ferritin was increased in 43% of patients with hepatitis or cirrhosis (mean 364 ng/ml) and in 13% of patients with ulcerative colitis or gastroduodenal ulcers (mean 106 ng/ml). Measurement of serum ferritin may be useful in evaluation of patients with breast cancer and in monitoring their response to therapy.


Location by immunoelectron microscopy of carcinoembryonic antigen on cultured adenocarcinoma cells. The tissue-culture cell line HT-29, derived from a primary colon adenocarcinoma and previously shown to secrete carcinoembryonic antigen (CEA), was examined by immunoelectron microscopy for the location of CEA in relation to the cells. CEA was closely adjacent to the plasma membrane, a location indistinguishable from that of alloantigens and other tumor-associated antigens.


Nonspecific inhibition of DNA repair by promoting and nonpromoting phorbol esters. The effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and its nonpromoting structural analogue, 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate (Me-TPA), on N-acetoxy-2-acetylaminofluorene-elicited DNA repair and replicative DNA synthesis was measured in normal human fibroblasts. Both esters inhibited DNA repair synthesis, and Me-TPA was nearly as effective as TPA. In addition, TPA inhibited replicative DNA synthesis. These findings showed that inhibition of DNA repair synthesis may not be a major factor in the mechanisms of action of tumor promoters.


Dynamic alterations in some surface properties of freshly explanted Moloney lymphoma cells. When Moloney lymphoma (YAC) cells were freshly explanted from the tumor-bearing host into culture, two events occurred in the first 120 minutes: The cells lost their natural IgG coat, and their sensitivity to complement-dependent lysis (CdL) mediated by antibodies to Moloney lymphoma cells decreased or increased. An increasing sensitivity to CdL as a function of incubation time at 37 degrees C was likely to occur when the sensitivity to CdL was low at explantation. A decreasing sensitivity to CdL was probable in instances of a high sensitivity to CdL at explantation. Artifical coating of YAC cells with antibodies to Moloney lymphoma immediately after explantation moderated the alterations in their sensitivity to CdL. This occurred even though a functional antibody did not remain on the cells as evidenced from the gradual decreased sensitivity of these artifically coated cells to the addition of complement. Spent culture media in which freshly explanted cells grew for 60 or 120 minutes sometimes blocked CdL of YAC cells mediated by antibodies to Moloney lymphoma.


Establishment and characteristics of a hamster lung adenocarcinoma in vivo and in vitro. Several cell lines designated HLAC were derived from primary lung carcinomas induced in Syrian hamsters by polonium-210 or benzo[a]pyrene. Primary tumor nodules were initially transplanted into cheek pouches, and the tumors that grew were passed into tissue culture and into the cheek pouches of other hamsters for continued in vivo passage. By serial passage and cloning, cell lines were isolated with plating efficiencies of 20-50% in vitro and 10-25% when cultured directly from solid tumors. These cells formed adenocarcinomas in vivo. The radiosensitivities in vitro of HLAC-4 and HLAC-14 varied; observed D0 (the inverse of the slope of the exponential portion of the survival curve) values were 80 and 155 rads, respectively; n (the dose at which the exponential portion of the survival curve extrapolates to 100% survival) values were approximately 1.8. Survival curves obtained following in situ irradiation of 4- to 5-mm3 HLAC-4 tumors showed a D0 of 80 rads and an n of 7. Morphology and growth characteristics of two HLAC cell lines in vivo and in vitro were described.


Regenerative response of the rat tracheal epithelium after acute exposure to tobacco smoke: a quantitative study. The regenerative response of the rat tracheobronchial epithelium after acute exposure to tobacco smoke was studied. Cigarettes were smoked automatically, and the smoke was diluted with air before being inhaled by the animals. Twenty-four hours after the animals were subjected to tobacco smoke, and with vinblastine as a metaphase-arrest agent, a wave of cell proliferation occurred. The intensity of the response was related to the type of smoke (it was more severe for cigarette than cigar tobacco) and depended on the concentration of smoke, but the timing of the response after moderate exposure was constant. The wave of proliferation would appear to be a local response to cell loss or damage, though morphologically the observed changes were slight. With repeated daily exposure, some adaptation of the tissue was apparent, in that the wave of rapid cell reproduction did not recur, but this did not imply that there was no progression of effect with respect to other pathologic processes. The responses to tobacco smoke and sulfur dioxide were compared. Cell proliferation provided a useful and rapid test of certain irritant effects of different types of tobacco smoke, but it was essential that animals free of chronic respiratory disease be used.


Changes in pepsinogen isozymes in stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine. Changes in the isozymes of pepsinogen (Pg) separated from the glandular stomachs of rats were studied by polyacrylamide gel electrophoresis during carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), from the beginning of MNNG administration to 3 months after the end of its 7-month regimen. In 13 of 25 rats killed successively, one (Pg 1) of the three pepsinogen isozymes (Pg 1, 3, 4) normally present in the pyloric mucosa had decreased or disappeared. It decreas was observed from 1 week after the beginning of MNNG treatment to at least 3 months after the end of the 7-month MNNG administration. Remarkable histopathologic changes were found from 8 months after MNNG was given, and rats showing such unusual histopathologic alterations also had changes in their pepsinogen isozyme pattern. In 4 of 27 rats, two (Pg 1, 2) of the four isozymes of pepsinogen (Pg 1-4) in the fundic mucosa decreased or disappeared from 3 months after the beginning of MNNG treatment to at least 2 months after the end of its 7-month administration. Histopathologic changes induced by MNNG were not as remarkable in the fundic mucosa as in the pyloric mucosa.


Canine thyroid neoplasms: epidemiologic features. A retrospective study of medical records from twelve veterinary university hospitals-clinics yielded 144 dogs with a confirmed diagnosis of a thyroid neoplasm (25 adenomas and 119 carcinomas). Forty-five of these dogs had additional primary neoplasms. As in man, associated tumors suggested the inherited multiple endocrine adenomatosis, type 1, and a possible syndrome of thyroid and chemoreceptor lesions. Although the female preponderance of human thyroid cancer was not seen in dogs, females showed a much sharper increase in risk with advancing age than did males. Three breeds (beagle, boxer, and golden retriever) had a significantly greater risk for thyroid carcinoma than did all dogs combined, whereas miniature and toy poodles had a low risk. The function of thyroiditis in the origin of thyroid cancer, as suggested by reports of thyroid carcinoma in people with Hashimoto's disease, may be clarified by follow-up studies of beagles which are prone to Hashimoto-type thyroiditis.


Immune mechanisms in leukemia: suppression of cellular immunity by starvation. The effects of starvation on the cellular immune response of C58/Wm mice to syngeneic malignant lymphoid cells (1b cells) were studied. Mice were starved 1-3 days before or after immunization. The capacity of starved animals to survive immunization was used to quantify immunosuppression. When starvation bracketed immunization by -1 to +1 days, only 2 of 23 mice survived primary immunization, compared with 100% survival for nonstarved controls. A 2-day period of starvation +1 to +7 days after primary immunization reduced survival about 30%. For a test of the effect of starvation on the secondary immune response, mice were immunized, starved 2 days, and then challenged with viable lb cells. When mice were starved from -3 to +1 days before or after challenge, there was a 25-45% decrease in survival. Starvation caused a disproportionate depletion of lymphoid tissue elements. The proportional loss in the weight of the spleen and thymus was essentially twice as great as the loss in total body weight. The peripheral blood leukocyte count was reduced by about 20% when mice were starved 1 day and by approximately 50% when they were starved 2 days. When mice were starved 1-2 days, the differential leukocyte count did not shift and there was no significant change in the number of blood erythrocytes or in the hematocrit. Starvation for 2 days caused a 65-70% reduction in the number of viable mononuclear spleen cells. Starvation for 3 days caused about 90% reduction. Adoptive cell transfer experiments showed that the immunocompetence of individual spleen immunocytes was not reduced by starvation.


Acetic acid, a potent stimulator of mouse epidermal macromolecular synthesis and hyperplasia but with weak tumor-promoting ability. The effects of a single application of various dose levels of acetic acid or the weak tumor promoter, phorbol-12,13-ditetradecanoate, on the incorporation of tritiated thymidine (3H-TDR), 3H-cytidine, and 3H-leucine into DNA, RNA, and protein of mouse epidermis, respectively, were determined and compared with histologic changes in the skin. Treatment with either 500 or 833 mumoles acetic acid induced a sequential and sustained stimulation of RNA, protein, and DNA synthesis, which was followed by extensive epidermal hyperplasia similar to that reported for the strong promoter and irritant, 12-O-tetradecanoyl-phorbol-13-acetate. A dose-response relationship between the amount of acetic acid and the rate of DNA synthesis was found between the dose levels of 33 to 833 mumoles of acetic acid per application. The latter dose induced the maximum activation of 3H-TDR into DNA at 723% of control at 2 days, whereas 33 mumoles stimulated DNA synthesis earlier and peaked at 210% of control at 3 hours. Phorbol-12,13-ditetradecanoate also stimulated macromolecular synthesis in a similar sequence, though to a lesser degree. No observable inflammation and only a slight hyperplastic response were noted with phorbol-12,13-ditetradecanoate. Weekly applications of 667 mumoles of acetic acid produced a maximal tumor response of 0.73 papilloma/mouse after 32 weeks of promotion. However, a weekly dose of 677 mumoles of acetic acid was essentially inactive when given in two divided doses. When croton oil was administered twice weekly at a 0.25%-dose level, 10.2 papillomas/mouse were induced after 32 weeks of promotion. The results showed that the previously considered nonpromoting inflammatory agent, acetic acid, must be a weak promoter. However, there was no correlation between stimulated macromolecular synthesis or hyperplasia and tumor promotion when phorbol esters were compared with acetic acid.


Trichoplusia ni granulosis virus granulin: a phenol-soluble, phosphorylated protein. Trichoplusia ni granulosis virus granulin consists of one major polypeptide component with an estimated molecular weight of 28,000. The protein is phenol soluble, phosphorylated, and acidic. A protease activated by alkaline conditions is also associated with solubilized granulin preparations. If not properly inactivated, the protease will introduce extensive artifact into the protein giving rise to ambiguous and incorrect results as analyzed by SDS-polyacrylamide gel electrophoresis and peptide mapping. Procedures are documented for enzyme inactivation and the preparation of granulin in highly purified form for characterization.


Molecular structure of human fibroblast and leukocyte interferons: probe by lectin and hydrophobic chromatography. Structural differences between human leukocyte virus-induced interferon and human fibroblast polyinosinic-polycytidylic acid (rIn-rCn)-induced interferon have been noted in previous studies. This study reports the behavior of human leukocyte and fibroblast interferon, induced by virus and by rIn-rCn, in several lectin and hydrophobic chromatographic systems. Differences in both glycosylation and in hydrophobicity of human leukocyte and fibroblast interferons are documented. Human fibroblast interferon is a glycoprotein, whereas our evidence suggests that human leukocyte interferon probably is not. Also, fibroblast interferon is more hydrophobic than leukocyte interferon, as probed on several hydrophobic adsorbents. The possible relationships of these differences to each other and to antigenic variations are discussed. Generally, the differences appear to be attributable to the cell type in which the interferon was induced. However, our results suggest that at least subtle differences in the processing of the induction signal (virus or rIn-rCn) within the same cell type may occur, slightly altering some structural features.


Infective and noninfective hemagglutinating particles of Newcastle disease virus: biological and chemical characterization. Newcastle disease virus (Herts strain), grown in embryonated eggs or in a line of bovine kidney cells, was purified and then separated by sucrose density gradient centrifugation into infectious (IH) and noninfectious hemagglutinating (NIH) particles. These particles were morphologically similar, although the average size of IH was twice that of NIH particles. The activity of hemagglutinin per milligram of virus protein was two- to threefold higher in NIH particles than in IH particles, whereas the specific activity of neuraminidase did not differ in the two particle types. This was consistent with the observed particle size difference. The distribution of the major proteins in IH and NIH particles from egg-grown virus, determined by polyacrylamide gel electrophoresis (PAGE), was significantly different. In IH particles the molar ratio of protein 1 (74,000 daltons) to proteins 2 and 3 (56,000 daltons): protein 6 (41,000 daltons) was 1.0:2.5:2.5; in NIH particles the ratio was 1.0:0.6:1.0. When Newcastle disease virus was grown in bovine kidney cells, the molar ratio of proteins in IH particles resembled that of of egg-grown virus. However, in NIH particles from bovine kidney cells, only protein bands corresponding to protein 1 and proteins 2-3 were present and their molar ratio was 1.0:0.6. Protein 6 was marginally detectable in these particles. Analysis of the proteins in [3H]isoleucine- and [14C]glucosamine-labeled virus showed proteins 1 and 2 (glycoproteins) present in the ratio of 1.0:0.5; protein 3, the nucleoprotein, was not detected. These results are compatible with previous findings by others that NIH particles are deficient in RNA and nucleoprotein antigen, and suggest that formation of discrete particles of Newcastle disease virus by budding requires at most minimal amounts of proteins 3 or 6. The fatty acid composition of egg-grown IH and NIH particles was not significantly different and resembled that of normal allantoic fluid.


Structural aberrations in T-even bacteriophage. VII. In vitro analysis of the canavanine-mediated inhibition of proteolytic cleavage. Canavanine arrests a critical function in head morphogenesis and the potential for forming giant T-even phage particles termed lollipops is induced. Formation of the particles requires the addition of arginine and the restoration of normal functions. We now report on an investigation into the effects of canavanine on both the T4-induced proteolytic activity and on the substrate proteins. Using an in vitro cleavage assay we have shown that the gene 21-dependent proteolytic activity from canavanine-treated extracts is markedly inhibited, whereas the substrate proteins retain a high susceptibility for cleavage. The proteolytic activity in extracts treated with canavanine followed by arginine is readily detectable, and proteins previously synthesized in the presence of canavanine can be cleaved. Protein synthesis is apparently required for the appearance of the proteolytic activity after the canavanine-arginine treatment. Mixing experiments suggest the requirement for a component of the gene 21-dependent proteolytic activity that is not coded for by gene 21.


Polyamines in vaccinia virions and polypeptides released from viral cores by acid extraction. Vaccinia virions propagated in the presence of [3H]ornithine were found to contain two labeled polyamines, spermine and spermidine. In complete virions the ratio of radioactively labeled spermine to spermidine was about 1:10, whereas in viral cores the ratio was 2:5. This suggests that some spermidine was preferentially lost during the conversion of virions to cores or that spermidine was present in the virions both inside and outside the core structure. Addition of [3H]ornithine to vaccinia virus-infected cells as late as 6 h postinfection demonstrated that, although the conversion of this precursor to polyamines was reduced by 50% or more as compared to mock-infected cells, complete inhibition of polyamine synthesis did not occur. Two percent or less of the total radioactivity associated with virions grown in the presence of [3H]ornithine was found to be acid soluble. Polyacrylamide gel electrophoretic analysis showed that all the structural polypeptides were labeled when virions were propagated in the presence of [3H]ornithine. When cores labeled with a mixture of 14C-labeled amino acids were extracted with 0.25 N H2SO4, 12 to 15% of the labeled core polypeptides were released and could be precipitated with acetone. About 40% of [3H]arginine-labeled polypeptides associated with cores were extracted with acid. Four polypeptides or groups of polypeptides were resolved after polyacrylamide gel electrophoresis analysis of the acid-soluble fraction of cores with molecular weights of about 58,000, 34,000, 24,000 and 10,000 to 12,000. About 40% of the [3H]arginine radioactivity extracted from cores coelectrophoresed with the 10,000 to 12,000-molecular weight polypeptide, indicating that this may represent an arginine-rich, histone-like structural polypeptide of the virion.


Multiplication of Coxsackie B1 virus in synchronized HeLa cells. A higher yield of Coxsackie B(1) virus was obtained when HeLa cells were infected late during S phase as compared to the amount produced by random cultures.


das Mutation in bacteriophage T4D does not suppress an amber mutation in T4 gene 59. Mutations termed das were isolated originally (Hercules and Wiberg, 1971) as partial suppressors of mutants in phage T4 genes 46 and 47. Since mutants in genes 46, 47, and 59 exhibit both an early arrest of phage DNA synthesis and the loss of this arrest in the presence of chloramphenicol or of mutations of T4 genes 33 and 55, we asked whether a das mutation can also suppress a gene 59 mutant. We find that it cannot--either at the level of phage production or DNA synthesis.


The supracostal approach to the kidney and adrenal. Our experience with 67 supracostal approaches to the kidney or adrenal gland demonstrates that 1) the exposure was uniformly superb,2) diaphragm reapproximation was unnecessary, 3) a single pericostal suture soundly closed the intercostal space, 4) no complications could be attributed to inadequate exposure and 5) pleural entry was the most common complication. We have found the supracostal approach to the kidney and adrenal to be staisfactory and recommend it to others.


Selective suppression of cellular protein synthesis in BHK-21 cells infected with rabies virus. Under hypertonic conditions, cellular protein synthesis is selectively suppressed in rabies virus-infected cells. The resistance of viral polypeptide synthesis to hypertonic conditions provides a means to study intracellular viral protein synthesis and may represent a property common to translation of many viruses.


Nalidixic acid: intrarenal distribution and its effect upon para-aminohippurate excretion. Studies performed on the intrarenal distribution of nalidixic acid in dogs show that this weak organic acid is indeed accumulated in the kidney, the highest concentration being attained in the cortex and followed in order by the outer medulla, papillae, and inner cortex. Our results also show that nalidixic acid produces significant changes in the para-aminohippuric concentration and on the filtered load, secretion and clearance of para-aminohippuric acid. Stop-flow experiments confirmed the inhibitory effect of nalidixic acid upon para-aminohippuric acid secretion. It is plausible that nalidixic acid may inhibit the secreted moiety of creatinine. This inhibitory effect is localized in the proximal tubule, where para-aminohippuric acid is known to be secreted. Based on our data it is suggested that nalidixic acid competes with para-aminohippuric acid for the same transport system or that the decreased secretory para-aminohippuric acid activity after nalidixic acid may be caused by a direct inhibition produced by the latter.


Effect of intracystic pantopaque on renal cysts. Intracystic pantopaque can alter the natural history of renal cysts. More than two-thirds of all renal cysts treated with percutaneous intracystic instillation of pantopaque decreased to at least half the original volume when followed for up to 4 years. A similar control group without intracystic pantopaque instillation  did not show this dramatic change.


The value of radioisotope renography in the followup of patients operated upon for hydronephrosis. Isotope renography and excretory urography were perfored routinely before and 3 months after an operation on 21 patients with hydronephrosis. A year postoperatively all patients again underwent renography. Renography is a valuable and reliable method to estimate the results of an operation. By 3 months postoperatively the renograms revealed improved renal function and drainage in 75 per cent of the cases.


Hormones in the treatment of metastatic renal cancer. Metastatic renal adenocarcinoma has been highly resistant to most therapeutic approaches. However, hormonal treatment has been reported to induce significant subjective or objective improvement. Two groups of patients receiving either androgens or progestogens were evaluated. The number of responses was disappointing. Furthermore, neither of the 2 regimens appeared to increase the mean surival between detection of metastases and fatal outcome.


An analysis of factors affecting survival in 150 patients with renal carcinoma. A review of 150 patients with renal carcinoma revealed that 45 per cent were hospitalized with distant metastases or tumors that were unresectable. Although the behavior of the neoplasm in the 55 per cent who were theoretically curable was generally unpredictable, longevity and survival were markedly increased in patients with tumors less than 8 cm. in size and concomitantly with other acknowledged features of low stages of the disease. Since patients can survive with tumor for long periods and metastases may occur many years after the operation prognosis must be guarded and long followup is needed to assess the results of therapy at any stage of the disease.


Diagnosis of the occult ectopic ureter in a duplex kidney. Three cases of ureteral ectopia producing non-specific symptoms  are described and the importance of the standard excretory urogram in the detection of such cases is emphasized.


Medical therapy in idiopathic retroperitoneal fibrosis. Except for its linkage with the ergot derivatives retroperitoneal fibrosis is a disease of unknown etiology. Two cases in which the traditional surgical approach was used but with the subsequent use of steroids are presented. The third patient was treated with steroids alone. The use of steroids alone is suggested for a limited number of poor risk patients when certain criteria are met.


Ureteroneocystostomy by means of a modified triangular flap method. A modified triangular flap method of ureteroneocystostomy is described. This method was used in 19 cases (21 ureters) requiring ureteroneocystostomy owing to various diseases. The patients have been followed postoperatively for 1 to 9 years. Our method is more simple than the original method described by Girgis and provides good results. Postoperative complications could be reduced or prevented by gentle manipulation of the ureter and bladder wall and by careful placement of the intravesical ureter into the incised ditch of the bladder floor, loosely anastomosed with interrupted surfaces 5 mm. apart. Dilated hydroureters without peristalsis and/or severe degenerative changes of the bladder wall involving the muscle layer are poor indications for the application of this method.


Cutaneous ureteroileostomy in the spinal cord injured patient: a 15-year experience. A review is presented of 39 patients with spinal cord injury who were diverted by ureteroileostomy. Because of a significant complication rate and the fact that some normal renal units may deteriorate, the procedure is reserved for the patient with irreversible upper tract changes that fail to respond to more conservative management.


Evaluation of lymphangiography for clinical staging of bladder tumors. Preoperative lymphangiography was done on 18 patients with bladder cancer and the results were correlated with the surgicopathological findings at the time of radical cystectomy and pelvic lymph node dissection. Correlation between radiological and pathological findings showed no falsely negative results. One patient had a falsely positive interpretation of lymphangiography. The accuracy of the study was 94 per cent. Accurate interpretation of lymphography is related to the experience of the reader. Routine use of lymphangiography in clinical staging of bladder cancer is recommended.


Bladder carcinoma involving the lower abdominal wall. Our experience in treating 13 patients with bladder tumors involving the abdominal wall is presented. A technique is described wherein part of the suprapubic abdominal wall is excised and the resultant defect is closed with ox fascia. Of the 9 patients treated surgically 8 have had no local recurrence but distant metastases have developed. Presently 2 patients are clinically free of disease, 18 and 22 months after abdominal wall excision. One of these 2 patients required a subsequent groin dissection and was then lost to followup.


Metastases to the eye from transitional cell carcinoma of the bladder. Two patients with eye metastases from widely disseminated transitional cell carcinoma of the bladder are described. Factors relating to patient survival and the rate of metastases of transitional cell malignancies are discussed.


The external shunt in the treatment of idiopathic priapism. A new surgical procedure for idiopathic priapism has been used successfully in patients. In 2 of these patients the procedure was done after 5 days of persistent or recurrent erections. The method consists of a combination of external polyethylene shunts between the corpora cavernosa and the venous systems of the underarms drip infusion of a heparin-saline solution into the corpora and prompt systematic anticoagulant therapy. All 3 patients were cured of the priapism and recovered normal sexual powers.


Cysts of the tunica albuginea. Report of 4 cases and review of the literature. Four cases of benign testicular cysts arising from the tunica albuginea are reported. A review of the literature yielded only 4 more instances of such lesions. Clinically, these cysts may be manifested as a tumor or painful swelling, or are discovered incidentally. In 3 cases a diagnosis of testicular carcinoma was entertained and high inguinal orchiectomies were done. The possibility of a conservative surgical approach, as followed in 1 case, is discussed. These cysts appear in the anterior and lateral aspects of the testis, show ample connection to the albuginea and are lined by a cuboidal epithelium. Gland-like inclusion were found in the fibrous cystic walls and in the albuginea. The histogenesis of these lesions is discussed and evidence for a possible origin in mesothelial rests trapped during development is presented. The differential diagnosis of cystic lesion of the tests is reviewd briefly.


Perineal neoplasms.

Perineal neoplasms. Experience with 2 cases of neurally-derived perineal masses is described. A relevant review of the literature spanning 50 years revealed 36 cases of perineal neoplasm of diverse nature, disclosing that such lesions typically present as otherwise asymptomatic enlarging masses and may comprise a broad spectrum of neoplasia with diagnosis and prognosis often relating to the age of the patient. Management naturally relates to tissue type and degree of local involvement.


The persistent nephrogram: A sentinel sign of contrast reaction. Two cases are presented in which a serious contrast reaction was accompanied by a dense persistent nephrogram. This radiologic sign results from the patient's systemic hypotension and provides the physician with an opportunity for earlier, more effective therapy.


Vascular distal ureteral obstruction.

Vascular distal ureteral obstruction. The diagnosis, treatment and results of 6 patients with 7 obstructed distal ureters secondary to vascular compression are presented. Three ureters were treated by transection of the offending vessels and the  remaining 4 required additional ureteroneocystostomy.


Distal hypospadias, chordee and torsion: The Allen-Spence procedure and new modifications. Hypospadias with chordee and associated torsion can be corrected by a simple 1-step procedure. The repair is based on the procedure described by Allen and Spence but is modified to correct more severe degrees of hypospadias and chordee below skin level. The procedure is simple, involves minimal complications and justifies the repair of marginal defects.


Embryogenesis of chordee.

Embryogenesis of chordee. Gross and microscopic examination of 46 consecutive male therapeutic abortion specimens, ranging in size from 60 to 180 mm. crown-rump, demonstrated that 89 per cent of the fetuses had some ventral curvature of the penis. Athough presumably all penises are ventrally curved through the tenth week of gestation, in our study this curvature was most prominent in the sixteenth through twentieth weeks of gestation and in 44 per cent of the fetuses it persisted through the sixth lunar month. Examination of premature infants revealed a 31 per cent incidence of chordee and serial examinations of a 27-week gestational age infant demonstrated gradual complete correction of the chordee during the ensuing 6 weeks. We propose that ventral curvature of the penis is a normal stage of embryogenesis and chordee without hypospadias may represent an arrest of development at this earlier stage.


Arteriovenous fistula of the renal vessels: Surgical management. The fifth case of arteriovenous fistula following nephrectomy for tuberculosis is presented. It is important to consider an arteriovenous communication in cases of unexplained congestive heart failure, particularly when blood pressure findings suggest arteriovenous shunting. The importance of the history of nephrectomy and findings of a loud bruit upon auscultation of the abdomen is evident. Diagnosis is established by selective renal angiography. The preferred treatment is complete excision of the fistulous communication.


Regression of renal carcinoma following radiation therapy. A case of regression of a renal carcinoma involving the inferior vena carva is presented. After 6 weeks of radiation therapy there was considerable diminution in the size of the tumor, rendering its surgical excision amenable. The tumor thrombus in the inferior vena cava also was markedly diminished after 5,000 rads. Radiation therapy is a valuable tool in the primary or adjunctive treatment of renal cell carcinoma. Preoperative treatment should be considered with large tumors and vena cava involvement.


A case of primary duodenal cancer metastasized to the right kidney. A 40-year-old man with pain and a mass in the right hypochondrium had histological evidence of metastatic tubular adenocarcinoma of the right kidney, originating in the mucosa of pars descendens duodeni. This patient was suspected of having 2 primary cancers: one in the duodenum and the other in the cecum.


Primary amyloidosis of the bladder.

Primary amyloidosis of the bladder. A lesion of the bladder that looks like carcinoma is most likely carcinoma but benign conditions, such as amyloidosis, should be borne in mind in the differential diagnosis. Transurethral resection was adequate treatment for our patient as well as those reported previously. We agree with others that followup is mandatory.


Lipoplastic lymphadenopathy simulating malignant lymphoma and pelvic lipomatosis: Report of a case and review of the literature. The second known cases of pelvic lipoplastic lymphadenopathy is presented. Roentgenographic studies including lymphangiography were instrumental in the diagnostic evaluation but a histopathologic diagnosis was essential to exclude a neoplastic process. The etiology and natural history of this disease are indeterminant but seemed to pursue a benign 17-year course in our patient. A retroperitoneal lymph node dissection is not indicated unless encroachment on adjacent pelvic viscera causes mechanical obstruction.


Ureteral catheter shavings: A potential threat. A combination of a worn panendoscope sheath and a soft, disposable ureteral catheter can evoke a potentially troublesome situation. Shavings or fragements from such a catheter can produce a nidus for stone formation. An illustrative case is presented with a plea for caution in this regard.


Correlation between pulmonary vascular resistance and pulmonary arterial diastolic pressure in congenital heart diseases with left to right shunt. Our studies recently conducted on the correlation between pulmonary vascular resistance and pulmonary arterial diastolic pressure in 467 cases, identified an extremely high correlation between the two. The correlation coefficient between pulmonary arterial diastolic pressure (PAdp) and pulmonary to systemic resistance ratio (Rp/Rs) was 0.799 and that between pulmonary vascular resistance index (RP-index) and PAdp was found to be 0.791. And a still higher correlation was observed between pulmonary vascular resistance and pressure gradient between PAdp and left atrial mean pressure (LAmp), where the correlation coefficient between Rp/Rs and (PAdp-LAmp) was 0.851 and that between Rp-index and (PAdp-LAmp) was 0.813. Those correlations are found to be higher in degree than the correlations between pulmonary arterial mean pressure or pulmonary arterial systolic pressure and pulmonary vascular resistance, leading to the conclusion that the pulmonary arterial diastolic pressure is of extremely high clinical importance as an index for increase in pulmonary vascular resistance.


Persistent atrial standstill due to atrial inexcitability. An electrophysiological and histological study. Electrophysiological and histopathological examinations were carried out in 2 patients with persistent atrial standstill. Intracardiac studies revealed that atrial standstill was due to atrial inexcitability. It was demonstrated in both patients that prolongation of the H-V interval and the duration of H deflection was associated with complete right bundle branch block and that the escape rhythm was an A-V junctional origin. Histologically, marked fibrosis of the right atrium and fibrous strands in the right ventricle were demonstrated in a 69-year-old man with idiopathic cardiomyopathy. In another female patient with peripartum heart disease aged 40 years, there was moderate degeneration of the myocardium in the right ventricle. The results of electron microscopic observations are also presented. The importance of the examination of His bundle electrography in persistent atrial standstill and the diagnostic criteria and treatment of this lesion are discussed.


Brain circulation in cerebral transient ischemic attacks. Cranial blood flow, mean cranial transit time and cranial blood volume were measured by the intravenous RISA technique in 10 patients with cerebral transient ischemic attacks (TIA) at the various time intervals from the onset of last attack. Cranial blood flow was subnormal in 5 out of 11 determinations and mean transit time trended to be prolonged in the diseased hemisphere in cases suggestive of the unilateral hemispheric lesion. A decrease in cranial blood flow was observed in TIA with lowering of heart rate below 60/min, or with atrial fibrillation, whereas no obvious correlation was present between heart rate and cranial blood flow either in 94 patients with, or with 62 patients without cerebrovascular diseases. Cardiac dysrhythmias including bradycardia, leading to reduce perfusion to the brain was discussed as a possible factor for producing TIA.


Glucose tolerance, serum insulin and lipid abnormalities in patients with coronary heart disease. Blood glucose, free fatty acid and insulin responses to oral glucose and the fasting serum lipids were measured in 3 groups: 32 non-obese (mean age: 47.5 years) and 9 obese (mean age: 84.5 years), male patients with coronary heart disease and 12 non-obese male controls (mean age: 46.5 years). The oral glucose tolerance tests were repeated after 3 years in 16 of the non-obese patients with coronary heart disease. The results were as follows: 1) Glucose tolerance was impaired in 19 of 32 non-obese patients (59.4%). There was a significant correlation between impaired glucose tolerance and hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia). 2) In obese patients FFA levels at 30, 60, and 120 min after oral glucose administration were significantly elevated and FFA decrease was delayed with a drop to minimum levels at 180 min. 3) The insulin response after oral glucose administration in the group of non-obese patients with normal glucose tolerance was similar to that of non-obese controls. In the group of non-obese patients with impaired glucose tolerance, serum insulin levels went up to normal levels, but the peak was delayed. The serum insulin levels in obese patients were significantly higher than those of controls of 0, 60, 120, and 180 min. After 3 years the change in insulin response to oral glucose was not related to anginal symptoms or ECG findings, but was related to body weight change in patients with minor changes in glucose tolerance. 4) The metabolic pattern in the non-obese group with impaired glucose tolerance resembled that of "mild diabetes" in delayed response of insulin and FFA, and mild hyperlipidemia. These findings suggest that obesity may contribute to hyperinsulinemia in patients with coronary heart disease and that impaired glucose tolerance observed in patients with coronary heart disease is in part due to "latent diabetes".


Study of posterior left atrial wall motion by echocardiography and its clinical application. Echocardiographic tracings of posterior left atrial wall motion were examined in 30 normal subjects, 17 patients of mitral stenosis with sinus rhythm and 31 coronary patients with elevated left ventricular end-diastolic pressure. Because of the plane of the posterior left atrial wall motion and the angle of the sound beam, usually the postero-inferior portion of the left atrial wall was recorded. In normal subjects, there were 3 positive waves (A,C,V waves) and 2 negative waves (X and Y waves). The A wave during atrial contraction period occurred in the closing motion of the mitral valve and was initiated by a slight negative wave. The fourth heart sound was consistent with the ascending limb of the A wave. The C wave coincided with the first heart sound followed by the pronounced negative depression (X wave). The X trough coincided with the beginning of the mitral valve opening in early diastole and was the deepest point in the motion curve. The V wave was a peaked anterior motion during rapid filling period and followed by the third heart sound. The Y wave was a slight negative depression following the V wave, and its trough occurred when the both leaflets of the mitral valve assumed a semiclosed position. In both mitral stenosis and coronary artery disease, significant increase (p less than 0.01) of the A wave excursion and significant decrease (p less than 0.01) of the V wave excursion were observed, resulting in marked increase (p less than 0.01) of the A/V ratio. The slope of the ascending limb of the V wave was also decreased apparently in both conditions. These findings might reflect increased resistance to left atrial emptying in mitral stenosis and decreased left ventricular filling rate in coronary artery disease. This study shows that echocardiographic examination of the posterior left atrial wall motion is feasible and useful in estimating the presence of either mitral stenosis or decreased left ventricular filling rate.


Effects of verapamil on the blood-perfused, isolated atrium preparation of the dog heart. Thirteen isolated canine right atria were perfused with blood conducted from a support dog. The selective injection of verapamil into the cannulated sinus node artery at a dose level above 1 mug usually induced dose-dependent negative chronotropic and negative inotropic effects. At a dose of 30 mug, verapamil caused sinus arrest in 4 cases out of 7 with marked suppression of the isometric tension development. At 100 mug, in all cases it caused sinus arrest which continued about 1 hour. When calcium chloride was injected into the sinus node artery, a positive inotropic effect was dose-relatedly produced above a dose level of 100 mug, but the threshold dose for inducing a positive chronotropic effect of calcium chloride was approximately 1 mg. On the other hand, norepinephrine when injected into the sinus node artery simultaneously induced a positive chronotropic and inotropic effect at the same threshold dose. A dose level of 10-30 mug of verapamil did not significantly inhibit positive chronotropic and inotropic responses to norepinephrine and a positive inotropic response to calcium chloride in per cent. The negative inotropic response as well as the positive chronotropic and inotropic responses to electric stimulation of the epicardium were not blocked by verapamil which caused marked suppression of the tension development.


Correlation of the electrophysiological and mechanical changes in the dog heart during digitalis administration, and the effect of potassium on it. The present investigation was designed to study the relationship between mechanical and electrophysiological actions on the heart of digitalis and the effects on it of K administration. Nineteen anesthetized dogs were given acetylstrophanthidin (AS) (30 gamma/Kg, followed by 1 gamma/Kg/min. When ectopic tachycardia occurred, sinus rhythm was restored with an infusion of K (5 mEq/Kg/hour, for 5 min). As the dose of AS was increased beyond 30 approximately 40 gamma/Kg, ventricular rate during electrically induced atrial fibrillation was reduced and PQ interval prolonged, while PP interval, QT interval and QRS duration showed little changes. Ectopic tachycardia occurred at an average dose of 56.9 gamma/Kg of AS. The indices of mechanical properties, dp/dt/IIT, max dp/dt and dp/dt (50), began to increase as soon as AS infusion was started and continued to increase during the administration of AS. The dp/dt (50) and PP interval or ventricular rate during atrial fibrillation did not change in parallel. Inotropic activity was not depressed even during ectopic tachycardia. The administration of K eliminated ectopic tachycardia, but caused no changes in the other electrophysiological and mechanical properties of the digitalized heart. The following conclusions were derived from the experiment. 1) The 2 actions of digitalis, mechanical and electrophysiological ones, are not necessarily related to each other. 2) Digitalis intoxication, represented by ectopic tachycardia, does not mean the depression of the inotropic activity. 3) The administration of K does not affect the inotropic activity of digitalis.


Pheochromocytoma with renal artery stenosis and high plasma renin activity. An unusual case of pheochromocytoma is described in this communication. Besides a chain of typical clinical pictures and laboratory findings which suggested a catecholamine-producing tumor, the left renal artery stenosis was demonstrated by an aortography and the plasma renin activity was consistently elevated. Surgery revealed the left renal artery was embedded in the tumor mass, originated from the left adrenal gland, resulting in a high degree of constricture of the vessel. Following the removal of the tumor, blood pressure immediately returned to normal, however, plasma renin activity remained elevated as long as 9 months of the follow-up study. The second aortography performed 14 months after the operation failed to demonstrate the left renal artery stenosis and subsequent studies revealed that plasma renin activity was gradually declining to upper normal levels. It is suggested that an excess of catecholamines secreted by the tumor was responsible for hypertension in this case, and that another factor, probably renal artery stenosis, was involved in the elevation of plasma renin activity, although this high renin activity was maintained for more than 9 months following the tumor extirpation.


Rheumatic valvulitis and constrictive pericarditis. Report of case. A 13-year-old girl was admitted with congestive heart failure, edema, ascites, and jaundice. There was an apical pansystolic murmur of mitral insufficiency and marked cardiomegaly. Her venous pressure was elevated. Despite medical treatment her condition deteriorated, hepatic and renal failure as well as disseminated intravascular coagulation ensued, leading to her death. At post mortem she was found to have rheumatic mitral valvulitis and constrictive pericarditis. The pathologic picture of pericarditis was nonspecific, but in presence of a positive skin test for tuberculosis the latter is considered to be the most likely cause of the pericarditis, nevertheless, rheumatic etiology of pericarditis in this case cannot be excluded. The presence of rheumatic heart disease and cardiomegaly may have led to the exacerbation of symptoms and signs of constrictive pericarditis and severe right heart failure.


A quantitative sampling method for Oncomelania quadrasi by filter paper. Filter paper was found to attract Oncomelania quadrasi in waters the same way as fallen dried banana leaves, although less number of other species of snails was collected on the former than on the latter. Snails were collected in limited areas using a tube (85 cm2 area at cross-section) and a filter paper (20 X 20 CM) samplers. The sheet of filter paper was placed close to the spot where a tube sample was taken, and recovered after 24 hours. At each sampling, 30 samples were taken by each method in an area and sampling was made four times. The correlation of the number of snails collected by the tube and that by filter paper was studied. The ratio of the snail counts by the tube sampler to those by the filter paper was 1.18. A loose correlation was observed between snail counts of both methods as shown by the correlation coefficient r = 0.6502. The formulas for the regression line were Y = 0.77 X + 1.6 and X = 0.55 Y + 1.35 for 3 experiments where Y is the number of snails collected by tube sampling and X is the number of snails collected in the sheet of filter paper. The type of snail distribution was studied in the 30 samples taken by each method and this was observed to be nearly the same in both sampling methods. All sampling data were found to fit the negative binomial distribution with the values of the constant k varying very much from 0.5775 to 5.9186 in (q -- p)-k. In each experiment, the constant k was always larger in tube sampling than in filter paper sampling. This indicates that the uneven distribution of snails on the soil surface becomes more conspicuous by the filter paper sampling.


Enzymatic hydrolysis of allergens extracted from the house dust mite, Dermatophagoides farinae. The crude extract of the house dust mite, Dermatophagoides farinae, was subjected to enzymatic hydrolysis by the use of trypsin and pronase. The hydrolysate was fractionated by gel-filtration and ion-exchange chromatographies. Allergenic activities of the fractions were measured by Prausnitz-Küstner type skin test on guinea pig skin with homocytotropic antibodies. Major allergenic component passed through anion and cation Dowex resins but its yield was not large. On gel-filtration, the mite digest showed two major peaks of absorbance and the allergenic activity was found in the first one. This active peak was resolved into two active fractions when it was chromatographed on DEAE-Sephadex.


Changes of tissue acetylcholine in the distended intestine. The effects of distension of the intestinal wall on the liberation and the synthesis of acetylcholine (ACh) were studied in the isolated guinea-pig ileum measuring the changes in the amount of free and bound ACh. In the presence of eserine longitudinal distension increased the amount of bound ACh in the intestinal wall without increasing the free ACh, while circumferential distension or mucosal rubbing increased free but not bound ACh. These effects were evident within 30 sec. In the eserine-free medium the amount of bound ACh was increased in either direction of distension. Addition of more than 5 X 10(-8) g/ml ACh to the bathing medium completely blocked the distension-induced increase. It is concluded that the release and the synthesis of ACh may be both augmented by the circumferential and the longitudinal distension in the physiological conditions. In the presence of eserine, however, the presence of unphysiologically high extracellular ACh levels presumably inhibits the distension-induced augmentation of ACh synthesis in the tissue.


Pharmacological studies of caerulein. II. The possibility of mediation through the central nervous system. With low doses of caerulein given intravenously or subcutaneously, vomiting could be induced. Although vomiting was not inhibited by chlorpromazine or atropine, a strong inhibition was evident when metoclopramide was administered subcutaneously at such doses as inhibit vomiting induced by oral administration of CuSO4. Even high doses of caerulein failed to induced vomiting in vagotomized and splanchnicotomized dogs. With intraventricular injection, no effects were observed on blood pressure, respiration or gastrointestinal motility, and vomiting was not induced. Therefore, a reflex mechanism appears to be involved in vomiting induced by caerulein. It is suggested that the actions of caerulein may not be mediated through the central nervous system.


Toxicological approaches to the toxic metabolites of Fusaria. VIII. Acute and subacute toxicities of T-2 toxin in cats. Acute and subacute toxicities to cats of T-2 toxin, 12-13 epoxytrichothec mycotoxin from fungi Fusarium species and others, were investigated. Major symptoms of toxicity in cats as the result of T-2 toxin were emesis, vomiting, diarrhea, anorexia, ataxia of the hind legs, discharge from the eyes and ejection of hemorrhagic fluid. Consecutive administration of the crude and pure sample of T-2 toxin in a sublethal dose caused a marked decrease in the number of circulating white blood cells. In the early stage of intoxication, a temporal leukocytosis was observed after each administration. Autopsy revealed extensive cellular damages in the bone marrow, intestine, spleen and lymph nodes. Greatly evident were meningeal hemorrhage of the brain, bleeding in the lungs and vacuolic degeneration of the renal tubles. Mycotoxicological significance of T-2 toxin and related trichothecenes is discussed in relation to the food-borne diseases in humans and farm animals.


Cortisol-binding protein in the cytosol of rat carrageenin granuloma. Cortisol-binding protein was prepared and partially purified by (NH4)2SO4 fractionation and DEAE-cellulose column chromatography from 105,000 g supernatant fraction of cytoplasm in rat carrageenin granuloma, which is assumed to be one of the most appropriate experimental models of inflammation. The cortisol-binding protein in the inflammatous tissue, although similar to transcortine, was not transcortine itself. The binding protein was eluted at 0.12 M NaCl by DEAE-cellulose column chromatography with a shallow salt gradient. Sedimentation constant and dissociation constant of the binding protein were 4-5 S and 1.0 X 10(-9) M, respectively. Optimum pH for binding to cortisol was 8.0. Binding ability of the binding protein to cortisol was very sensitive to pronase E and trypsin but resistant to RNase. Specificity of the protein for binding other steroids revealed that 17beta-estradiol did not bind to the protein, while androstenedione and testosterone had one sixth as much affinity to the binding protein as that of cortisol. There was good a correlation between the amount of the binding protein in the inflammatory tissue and anti-inflammatory effect of cortisol. Namely, the maximum cortisol-binding ability was seen on a 5 day old granuloma which is the so called 'steroid sensitive stage'. Thereafter, the binding ability decreased with the increasing stage of granuloma.


Distribution of renin in subcellular fractions from the rabbit kidney. Subcellular localization of renin in the rabbit kidney cortex was investigated using two centrifugation techniques. Renin was indirectly assayed on the basis of pressor activity and the reference enzymes such as succinic dehydrogenase, acid phosphatase and D-glucose-6-phosphatase for the other subcellular particulates were biochemically determined. Renin activity was found mainly in the mitochondrial fraction with very little in the microsomal fraction by a differential centrifugation. By a discontinuous sucrose density gradient centrifugation, renin granules were mainly recovered in the fraction corresponding to 1.5 M sucrose, while most of mitochondria, lysosomes and microsome equilibrated in the upper fractions. This renin granular fraction contained approximately 50% of total granular renin activity having a specific activity about six times that seen in the homogenate. After recentrifugation of the renin granular fraction, most of renin activity was recovered in the sediment. Repeated freezing and thawing of this fraction resulted in an increase of renin activity. On the basis of these experimental data it is assumed that renin located in the different subcellular particulates from mitochondria, lysosomes and microsomes in the rabbit kidney cortex.


Drug metabolizing function of isolated perfused liver. How closely the isolated liver of the rat would simulate the in vivo function of the organ in terms of the metabolic pattern of the compounds such as bromosulphophthalein, p-nitrophenol, hexobarbital, and indocyanine green was investigated. In order to produce tissue with the stimulated function, the animal was pretreated with phenobarbital and, for the reverse purpose, with ethionine. Some of the indices of the function employed herein, such as the appearance pattern of the compound, the rate of biochemical transformation or the biliary excretion, showed that the perfused liver would generally well reflect the in vivo situation. The method with isolated and perfused liver could exclude the participation of other organs and also the influence of the factors unavoidable in an in vivo experiment. Thus, it is suggested that the isolated perfused liver is useful for studying directly the functional level of the organ as drug metabolizing tissue.


Effect of fentanyl, a narcotic analgesic, on two components of the jaw opening reflex. An action of fentanyl, a short-acting narcotic, on the reflex discharge in the digastric nerve induced by the inferior alveolar nerve stimulation was investigated in alpha-chloralose anesthetized cats. In the ipsilateral digastric reflex discharge, there were an early phase induced by stimulus exciting Aalpha fibers and a late phase appearing when Adelta fibers were also stimulated. Following dorso-lateral cordotomy at the obex level, an isolation of the spinal trigeminal nucleus caudalis, a total area in the digastric reflex discharge decreased, while its first peak amplitude was little affected, indicating a disappearance of the late phase and a preservation of the early phase. Fentanyl depressed both the total discharge area and the first peak amplitude. After dorso-lateral cordotomy, the depression of the area decreased considerably, whereas that of the amplitude decreased slightly. Results indicate that fentanyl depressed both the early phase which is activated by the Aalpha fiber stimulation, not via the subnucleus caudalis and the late phase which is activated by the Adelta fiber stimulation via the sub-nucleus caudalis or its surroundings. The latter action would be related to the analgesic action of fentanyl.


Traumatic pericardial hematoma simulating tricuspid valve obstruction. A large pericardial hematoma caused profound hypoxia, cyanosis, and hypotension in a patient who had sustained trauma in an automobile accident. Angiographic and cardiac catheterization findings suggested intracardiac obstruction at the level of the tricuspid valve. This case emphasizes that localized accumulations of blood or fluid within the pericardial space can simulate intracardiac masses or valve obstruction. Partial pericardiectomy was curative in this patient.


Destructive monarthritis and granulomatous synovitis as the presenting manifestations of Crohn's disease. A twenty-two-year-old woman and a fourteen-year-old boy with Crohn's disease presented with progressive monarticular arthritis with radiologic evidence of altered articular cartilage and subchondral bone. In one individual, granulomatous inflammation of the synovium was demonstrated. Intestinal symptoms were not prominent. In both individuals, the development of the monarthritis led to the discovery of the underlying inflammatory bowel disease.


Mechanisms of enhancement of cardiac output during paced tachycardia in conscious dogs. The mechanisms of enhancement of cardiac output of unanesthetized dogs from 2.7 to 3.6 l min-1 during paced heart rate increase from 92 to 178 beats min-1 were studied in 92 trials with 5 dogs. This enhancement of cardiac output was accompanied by a 0.6 mm Hg fall in right atrial pressure and a 3.3 mm Hg fall in left ventricular end-diastolic pressure. The results are compatible with the hypothesis that an isolated rise in cardiac function shifts blood from the heart and lungs into the systemic circulation which increases the degree of filling of the peripheral vessels and hence increases mean systemic pressure. We postulate that decompression of both atria reflexly raises the tone of the peripheral vessels while the increase in arterial blood pressure reflexly lowers the tone. Apparently a balance is achieved that results in an elevated mean systemic pressure, displacement of the venous return curve to the right, and an increase in the amount of venous return that matches the enhanced cardiac output.


The clinical management of bronchogenic carcinoma-- A progress report. A number of new concepts in the clinical management of bronchogenic carcinoma have been introduced since an original review of this problem in The Johns Hopkins Medical Journal in 1967. Four specific problems in the updated management of patients with bronchogenic carcinoma are discussed: 1) the patient with cytologic evidence of malignant cells in the sputum and a normal chest radiograph; 2) the patient with an asymptomatic peripheral pulmonary nodule; 3) the patient with symptomatic bronchogenic carcinoma or bronchogenic carcinoma in a lobar or main stem bronchus; 4) the assessment of operability. Tantalum bronchography and fiberoptic bronchoscopy have proven effective in localizing the source of malignant cells shed from a radiologically occult bronchogenic carcinoma. Percutaneous needle biopsy and transbronchial biopsy under fluoroscopic control permit pathological examination of peripheral nodules. Transcervical mediastinoscopy and left parasternal exploration, as well as increased use of angiography and more sophisticated pulmonary function tests, allow better determination of the resectability of central lesions. As a result, fewer patients are subjected to unnecessary thoracotomies, and if thoracotomy is undertaken it usually offers the patient a reasonable chance of cure.


[New method of stroke volume measurements by means of radioactive isotopes]. A new radioactive method of measuring the stroke volume called "radiocardiometry" is described, and the results of a clinical trial of the method are presented. The results were compared with those obtained by means of radiocardiography that was conducted simultaneously with the stroke volume measurements performed according to the suggested method. The results coincided with an approximation of +/- 10% in all cases, with the exception of those with mitral insufficiency in which the results obtained by means of radiocardiometry were 12--31% higher than those calculated from radiocardiography. The circulating blood volume was measured by the administered activity and by the activity of the sample without any preparation of standard solutions. The error in the measurements of this parameter did not exceed +/-5%.


[Method of continuous monitoring of stroke and minute cardiac volume by the aortic pressure curve]. A new method of determining the cardiac output and stroke volume on the basis of the aortic pressure curve by way of a direct pressure-volume calibration is suggested. For this purpose two catheters are introduced into the ascending aorta, and via one of them saline is supplied with a constant volume rate (delta V). At the same time the augmentation of the diastolic pressure in the aorta (delta P) caused by the administration of the saline is recorded by means of the second catheter which tip is located some 3--4 cm below the first one along the blood flow. The mean pulse pressure in the aorta (Pp) also corresponds to a definite flow in the aorta (V). The relationship between the volume and pressure in the aorta within the physiological range is a lineal function. Hence, V = Pp-delta V divided by delta P cm3/sec. By multiplying this value times the duration of the cardiac cycle in seconds, the stroke volume is obtained. By dividing the volume of the administered saline (delta V.t) into the pressure augmentation area (delta S), the volume corresponding to each unit of the pressure area is found. Then by multiplying this calibration value times the area under the pressure curve in any cardiac cycle (S) again the stroke volume is obtained: Vstr = S-deltaV-t divided by delta S cm3. By a continuous recording of the mean pulse pressure in the aorta and of the full pressure curve it is possible to conduct a continuous control of the stroke volume and cardiac output using the preliminarily obtained calibration value. The suggested method permits to determine the filling of the aorta below the coarctation, the blood return from the aorta into the left ventricle in cases of aortic insufficiency, as well as the elastic properties of the aorta. An attempt was made to substitute the recording of the volume pulse and left arm rheopletysmography for the recording catheter.


[Results and perspectives of the use of echocardiography and ultrasonic scanning of the heart]. The results of echocardiography and ultrasonic scanning of the heart in over 600 patients with ischaemic heart disease, hypertension, heart diseases and other pathology are presented. The high diagnostic value of these techniques in terms of detection of acquired and congenital heart failures, exsudative pericardites, left atrial tumors is demonstrated. The methods permit to evaluate myocardial hypertrophy, left ventricular dilatation, and to reveal myocardial contractility disorders at their early stages. The prospects of the employment of ultrasonic techniques in cardiological practice are analysed.


[Comparison of the data of intravital selective coronarography with anatomical studies of the coronary vessles]. A comparison of the data of intravital selective coronary angiography and of the anatomic study of the coronaries conducted in 30 patients with ischaemic heart disease was made. Intravital selective coronary angiography gives precise information about the localization and extent of the coronary pathology in 89.4% of the cases. In 10.6% of the cases discrepancies were found between the data of intravital coronary angiography and of the anatomic studies. The causes of such discrepancies may be: diffuse lesion, beginning with the ostium of the vessel, excentric location of the vascular lumen in case of its atherosclerotic changes, as well as the fact that the commonly used projections for coronary angiography are not always optimum for detecting the changes in the coronary arteries.


[Evaluation of functional state of myocardium after open-heart surgery]. The intracardiac and central hemodynamics was studied in patients with secondary atrial septal defects pre- and post-operatively. After surgery continuous catheterization of the heart chambers was employed which permitted to receive the information directly from the right ventricle. Following a statistical processing of the obtained data, regression lines were formed that reflected the relationship between the work-load of the right ventricle and the end-distolic pressure. It was demonstrated that the development of latent myocardial insufficiency requires certain limitations in the amount of the infused fluids and enhancement of cardiac therapy.


[Evaluation of the results of ergometric studies]. An evaluation of some standardized and relative indices of ergometry is presented: heart rate and oxygen consumption as percentage of individual values, indices of chrono-, isotropic, aerobic and coronary reserves. The investigation is based on the study of 113 normal individuals, 363 hypertonic patients, and 100 patients with ischaemic heart disease. In all cases the maximum tolerable workload was tested by way of its step-wise increase, conducted under pulse, arterial pressure, ECG and oxygen consumption control. Some patients were examined after Obsidan and Dopegit therapy. The use of the relative values of the heart rate and oxygen consumption was shown to neglect the role of individual factors (sex, age, body weight). The determination of the relative augmentation of these indices, as well as of the arterial pressure permits to precise the state of functional reserves of the cardiopulmonary system, and can be used for the diagnosis and evaluation of therapeutic results.


[Certain hemodynamic indicators during rest and after intensive physical exercise at high altitude]. For 5 years 364 normal males, aged 19--25, were studied at the altitude of 3800--4200 m, along with local inhabitants of the mountain region; the hemodynamic shifts and arterial blood oxygenation were studied with the base metabolism conditions preserved both at rest, and after intensive physical exercises performed according to the step-test method with the maximum tempo of the work (cardiological motion test, WHO, 1967). The initial reaction of the cardiovascular system to the high altitude conditions manifested itself in an increased stroke volume and cardiac output, of the volume speed of blood ejection, of the cardiac index in a decrease of the total peripheral resistance and oxygen saturation of the arterial blood. This reaction was interpreted as a compensatory one. In the course of acclimatizing, the cardiac output and the pulse amplitude of the arterial pressure gradually decreased, and the total peripheral resistance increased. These hemodynamic changes must be of an adaptative nature. The maximum physical workload caused a distinct intensification of the circulatory reactions, especially in those living for considerable periods of time at high altitude and in local inhabitants. The general state of the examined remained good. Hence, these persons have a considerable reserve of functional capacities of their cardiovascular system, and can perform hard muscle work at high altitude. Individuals staying at high altitude for only short periods of time react to intensive physical workloads by a less distinct intensification of the contractile capacity of the heart and by a sharp decrease of blood oxygenation, considerable acceleration of the heart rate and respiration rate, as well as by a deterioriation of their general state. Such muscular efforts cause overloading of the heart only in persons with a short-term acclimatizing.


[Role of excessive phosphorus consumption in the development of aortic calcinosis]. The calcium and phosphorus content was studied in the blood serum and in the aorta of rats fed with varying Ca:P ratio in their diets (2:1; 1:1; 1:2; 1:3). In rats kept on a 1:3 Ca:P diet hypocalcemia, hyperphosphotemia and intensive calcination of the aorta was observed. Some accumulation of calcium in the aorta was noted also with a 1:2 Ca:P diet. The possible role of excessive phosphorus consumption is discussed as a factor contributing to the development of aortic calcinosis, emphasizing the need to precise and carefully maintain an optimum Ca:P ratio in the diet of normal individuals and in that of cardiovascular patients.


[Characteristics of lipid metabolism depending on the nature of occupational activity]. The examination was conducted on 630 normal males when at rest in a sanatorium, their permanent jobs being characterized by different nervous and emotional strain (pilots, ground aviation specialists). The lipid metabolism parameters of the pilots appeared to differ from the normal ones. The differences in the metabolic indices of the two profession groups are traced both in the younger, and in the older age-groups, which gives ground to believe that the typical peculiarities of the metabolism are formed in individuals with nervous-emotional jobs as early as in the young age under the effect of professional factors. This should be kept in mind when undertaking preventive measures against atherosclerosis in persons working under high nervous and emotional strain.


[Blood circulation in the cerebral cortex, reticular structure and hypothalamus in myocardial infarction in non-anesthetized animals]. The local cerebral blood flow and oxygen tension in the brain cortex, the reticular formation of the mesencephalon and the posterior hypothalamus were studied in chronic experiments in non-anesthetized rabbits with experimentally induced myocardial infarction. During the initial hours after the occlusion of the coronary artery a distinct reduction of the blood flow and oxygen tension was noted in the mentioned structures of the brain, against the background of an arterial pressure fall; in the subsequent days a varying dynamics of the re-establishment of the cerebral blood flow and arterial pressure was observed. It is suggested that in myocardial infarction not only the general hemodynamics undergoes certain changes, but the reserves of the autoregulation mechanisms of the cerebral blood flow get sharply reduced, resulting in brain tissue hypoxia and disorders in the regulation of cardiac activity and the peripheral vascular tone.


[Possibilities of measuring the dynamics of the stroke volume according to the data of ultrasonic Doppler-cardiography]. The possibility of determining the relative changes in the stroke volume of the left ventricle on the basis of ultrasonic Doppler-cardiography was studied in animal experiments and in tests with volunteers. The dynamic measurements of the cardiac output by means of ultrasonic Doppler-cardiography were performed on the basis of recording the amplitude of excursions of the posterior wall of the ventricle during the ejection phase by way of integrating the Doppler frequencies in the 150--800 cycles range. Simultaneously the dynamics of the cardiac output was studied electromagnetically (in animal experiments) and rheographically (in volunteers). The results of both the methods correlated closely: the reciprocal correlation coefficient in animal experiments comprised r=0.89 (p less than 0.001), in volunteers r=0.78 (p less than 0.001). The authors concluded that ultrasonic Doppler-cardiography can be used for measuring the relative changes in the stroke volume.


Comparative investigation on the influence of human and bovine collagen types I, II and III on the aggregation of human platelets. Collagen types I, II and III from man and calf are distinctly different with respect to their effect on the induction of the aggregation of human platelets. Collagen type III was found to be a particularly potent inducer of platelet aggregation. The pathogenetic implications of these observations are briefly discussed.


[Experimental investigations on cell resorption from the peritoneal cavity by use of the scanning electron microscope (author's transl)]. 1. It is well known that microscopically small particles may be absorbed from the peritoneal cavity via the large lymphatic vessels. The present experiments were carried out in order to elucidate the site of the absorption. In addition, the role of transperitoneal transport of neoplastic cells as a possible cause of cancer metastases was studied. 2. The peritoneal surface of 40 rats and mice was studied with the scanning electron microscope (diaphragm, lateral abdominal wall). The investigations were carried out in 8 rats and 3 mice 24 hrs following the intraperitoneal injection of washed homologous erythrocytes and in 20 rats and 5 mice 24 hrs after the intraperitoneal injection of Ehrlich ascites tumor cells. 2 rats and 2 mice served as controls. 3. In the control animals no stomata could be shown in the peritoneum of the diaphragm or in the lateral abdominal wall. 4. The i.p. injection of erythrocytes was followed by the appearance of stomata in the peritoneal surface of the diaphragm, and absorption of erythrocytes could be demonstrated. No stomata were found in the peritoneum of the lateral abdominal wall. 5. Tumor cells were found in the stomata following the i.p. injection of ascites tumor cells. It is concluded that a lympho-hematogenous spread of tumor cells seems probable at least in the early stage of tumor infiltration of the peritoneum. This stage is followed by implantation of the tumor cells on the peritoneum.


HB-antigen in serum and synovialis in acute hepatitis with and without polyarthritis. In 27 patients suffering from acute hepatitis serum and synovial-fluid were tested for HB-Ag. It was detected in the serum in 19 cases, in the synovial fluid in 2 cases, but never in both serum and synovial-fluid. HB-Ag was not found in 6 patients. Polyarthritis was seen in 10 cases; 5 of them carried HB-Ag in the serum, 2 in the synovial-fluid. A hepatitis B however, was also suspected in the 3 cases with polyarthritis lacking HB-Ag. The results suggest that virus B may persist in joints too and that polyarthritis associated with acute hepatitis is coupled to an infection with virus B.


Anesthesia of marmots with sodium pentobarbital, ketamine hydrochloride, and a combination of droperidol and fentanyl. Three different anesthetics were tried on wild marmots to immobilize them sufficiently for intra-oral physiologic measurements and dental examination. Essentially the same procedure was performed or attempted on 15 animals. The droperidol (20 mg/ml) and fentanyl (0.4 mg/ml) combination gave better results than sodium pentobarbital or ketamine hydrochloride and was therefore used in most instances. We concluded that the dose rate should be adjusted to the nutritional state of the animal as well as to the absolute weight.


Renal microvasculature in spontaneously hypertensive rats. The renal microvasculature was studied in normotensive rats and in rats with spontaneous hypertension. The microvascular pattern was normal in both groups of animals, suggesting normal renin secretion. This may or may not indicate a role for renin in the cause of spontaneous hypertension.


Deep anesthesia in the rat with the combined action of droperidol-fentanyl and pentobarbital. A combination of droperidol-fentanyl and pentobarbital, administered ip, was used to obtain a state of deep anesthesia in rats for purposes of radionuclide imaging, as well as for various surgical procedures. Two or more hr of anesthesia were easily obtained. A 7.2% mortality rate (3/42) was experienced in a 3-mo study in which 5.2 procedures per rat were performed. The duration of anesthesia was found to vary both with sex and with the time of day at which the drugs were administered.


The effects of parity, litter size, season, and breeding protocol on the number of DBA/2J Ten mice available for weaning. Data on the reproductive behavior of DBA/2J Ten mice, collected from October 1970 through March 1973 and utilizing a 2-female, 1-male breeding system, with the mice remaining together throughout their reproductive life indicates: a) Litter size tends to increase through the fourth litter, the first litter being much smaller than successive litters; b) Survival rates of litters with 2--4 pups increase with successive deliveries; c) Survival rates of litters with 5--9 pups are approximately the same regardless of parity; d) There is a circannual rhythm in the number of pups available for weaning da 21, which is attributable to changes in postnatal viability. Data collected using a breeding pen system, with isolation of females pre- and post-delivery (March 1973 to March 1974) indicates: a) There is a reduction in live litter sizes in later litters with this system; b) There is a large reduction in the proportion of pups surviving to weaning with this system when compared with the other breeding system.


Pneumoperitoneography: a special radiological technic used in nonhuman primate medicine. Visualization of abdominal structures was difficult in survey radiographs of nonhuman primates due to the paucity of intra-abdominal fat and the presence of gastrointestinal contents. Simple pneuoperitoneography combined with contrast gastrointestinal studies provided valuable information, ie, size, shape, and position, of abdominal structures. After ip injection of carbon dioxide, a series of positional radiographs were exposed to delineate the various abdominal organs. The positioning device used in the examination was illustrated and described and the clinical indications and diagnostic value of pneumoperitoneography discussed.