Effect of aldosterone on ion transport by rabbit colon in vitro. Segments of descending colon obtained from rabbits, that had been maintained on drinking water containing 25 mM NaCl and an artificial diet which contains 1% Na and is nominally K-free, respond to aldosterone in vitro (after a 30 to 60-min lag period) with a marked increase in the short-circuit current (Isc), an equivalent increase in the rate of active Na absorption (JNa net) and a decline in tissue resistance (Rt). Aldosterone also brings about a marked increase in the unidirection influx of Na into the cells across the mucosal membrane ("zero-time" rate of uptake) which does not differ significantly from the inrease m Isc. Treatment of control tissues with amphotericin B brings about sustained increases in Isc and JNa net to levels observed in aldosterone-treated tissues. However, addition of amphotericin B to the mucosal solution of aldosterone-treated tissues does not result in a sustained increase in Isc or JNa net and these values do not differ markedly from those observed in control tissues treated with amphotericin B. These findings, together with other evidence that Na entry in the presence of amphotericin B is sufficiently rapid to saturate the active Na extrusion mechanism at the baso-lateral membrane, are consistent with the notion that the aldosterone-induced protein increases the permeability of the mucosal membrane to Na but does not increase the "saturation level" of the active Na "pump" within the time-frame of these studies (3 hr). Finally, aldosterone has no effect on the bidirectional or net transepithelial movements of K under short-circuit conditions, suggesting that the enhanced secretion of K observed in vivo is the result of increased diffusion of K from plasma to lumen via paracellular pathways in response to an increased transepithelial electrical potential difference (lumen negative).


A comprehensive examination of protein sequences for evidence of internal gene duplication. We have implemented a routine procedure for screening protein sequences for evidence of intragenic duplications. We tested 163 protein sequences representing 116 superfamilies of unrelated proteins. Twenty superfamilies contain proteins with internal gene duplications. The intragenic duplications detected can be divided into two major types. (1) One or more duplications of all or part of a gene produce a protein with two or several detectable regions of sequence homology. Sequences from 18 superfamilies contained this type of duplication. (2) Repeated reduplication of a small DNA segment can produce a protein that is repetitive over most of its length. Three superfamilies contain such repetitive sequences. We also investigated the limits of detection of ancient duplications using sequences derived by random mutation of a model sequence consisting of ten 10-residue repeats. The original repetitive nature of the sequence was usually detected after 250 point mutations even though the ancestral segment could not be accurately reconstructed.


The evolution of histones.

The evolution of histones. The amino acid sequences of bovine histones H2A, H2B, H3, and H4 and the first 107 residues of rabbit thymus histone H1 were examined using newly developed procedures designed to detect and evaluate weak similarities (de Haën et al., 1976). Using the McLachlan scoring system, regions of statistically significant similarity were found between several pairs of the four smallest histones. The probability that this set of similarities could result simply from chance was estimated to be less than 10(-5). No similarity was found between the H1 sequence and the other histones. The results are interpreted to indicate that at least the C-terminal portions of the core histones evolved from a common ancestral protein.


Rate of polymer formation and entropy production during competitive replication. The rate of increase in the mean polymer formation rate constant during competitive replication by Qbeta RNA variants (Kramer et al., 1974) has been shown to agree statistically with the variance in their formation rate constants. This result demonstrates that Fisher's fundamental theorem of natural selection (Fisher, 1930) can define time variations in the mean rate of synthesis for a heterogeneous population of replicating polymers. It was also revealed that RNA replication, far from equilibrium, accompanied a progressive decrease in the order of the entropy production derivative, with respect to time, that reached a maximum (with the next higher order being zero). Maximization of entropy at equilibrium, in compliance with the second law of thermodynamics, therefore appears as a natural extension of the earlier non-equilibrium pattern of entropy production within the system. The order of the zero-valued entropy production derivative was shown to be determined by the chemical affinity, and its rate of decrease was specified by the mean polymer formation rate constant.


Generalization and simplification of the Moore-Goodman test for significant of alignment homologies. A test given by Moore and Goodman (1977) that checks the significance of a homology between protein sequences is generalized to any type of distance measure and to any classification of codon pairs or amino acids according to this measure. A normal distribution is shown to approximate satisfactorily the probability distribution underlying this test for the examples chosen, and supposedly for any distance measure. The test accordingly reduces to a simple standard procedure.


Surface charge characteristics of peripheral blood lymphocytes in chronic lymphatic leukemia and malignant lymphoma. Peripheral blood lymphocytes from patients with chronic lymphatic leukemia (CLL) and malignant lymphoma (ML) were tested for their surface negative charge characteristics and compared with lymphocytes from normal subjects by use of measurements of lymphocyte agglutination with a positively charged poly-L-lysine (PLL) molecule and by use of electron microscopic observation of lymphocytes labeled with cationized ferritin (CF). Unfixed lymphocytes from CLL and ML patients exhibited clustering and patching of CF particles, whereas normal lymphocytes had a uniform, continuous CF-labeling pattern. Lymphocytes from CLL patients had significantly higher agglutination with PLL than did normal lymphocytes.


Ultrastructural study of the normal mucosa-adenoma-cancer sequence in the development of familial polyposis coli. Ultrastructural changes that occurred in the colon epithelia of patients with familial polyposis coli were investigated. Criteria of gradation of the crescendo changes from the mucosa in the controls, through the "normal" mucosa between polyps and adenomas in various stages of dedifferentiation, to invasive carcinoma were established. Our criteria were based on the following requirements: a) vesiculation and increasing numbers of small electron-dense bodies (secretory granules) and lysosomes in the mature and immature absorptive cells, b) presence of immature and undifferiated cells, c) variation in the globlet cells and appearance of atypical secretory cells, and d) nuclear changes. The results illustrated the adenoma-carcinoma sequence and added strong evidence to support its occurrence. Furthermore, this ultrastructural study revealed cellular changes that preceded adenomatous growth and may be of value as markers of early stages of cancer. However, this study also revealed a close link between the function and morphology of the mucosal epithelium.


Replicative epithelial cell cultures from normal human prostate gland. Epithelial cell cultures of the normal human prostate gland were established. The subculturing of these cultures was accomplished with a novel nonenzymatic technique. These cultures were defined as normal epithelial cells on the basis of ultrastructure, karyotype, and inability to grow in soft agar.


Friend virus-induced inhibition of eosinophil granulocyte exudation in mice. Exudation of eosinophil polymorphonuclear leukocytes (E-PMN) in response to tetanus toxoid (TT) was studied in DBA/2HaD mice with erythroleukemia induced by Friend virus (FV). The inhibition of exudation that developed was independent of increased levels of serum corticosteroids and occurred in surgically adrenalectomized mice. Thus it was independent of steroid-induced effects on E-PMN. The accumulation of neutrophil polymorphonuclear leukocytes (N-PMN) in TT-induced exudates was unaltered. Furthermore, N-PMN exudation in response to other inflammatory stimuli was similarly unimpaired in virus-infected mice, which confirmed the specificity of the inhibition for E-PMN. The virus entity in the FV complex responsible for the effect was not identified. Friend murine leukemia virus, the indigenous helper virus for the defective spleen focus-forming virus, alone, was incapable of inducing the inhibition. It is possible that the lack of participation of E-PMN in TT-induced immune inflammatory exudates in FV-infected mice reflects an unresponsiveness that contributes to the development and progression of leukemia in FV-infected mice.


Further studies on the relationship between large glycoprotein molecules and allotransplantability in the TA3 tumor of the mouse: studies on segregating TA3-HA hybrids. In a series of six TA3-HA/A.CA hybrid cell lines formed by the fusion of the TA3-HA mammary carcinoma of a strain A mouse with a normal embryonic fibroblast of an A.CA mouse and then converted to the ascites form in parental strain A, the capacity to grow in foreign strains was inversely related to the ability to absorb anti-H-2a antibody. The absorptive capacities of the hybrid cell lines were intermediate between the low absorptive capacity of the non-strain-specific parent TA3-HA ascites cell line and the much higher absorptive capacity of the strain-specific ascites line TA3-St of the same tumor. Each hybrid cell line possessed an abundance of large endogenous cell-surface glycoprotein molecules similar to epiglycanin, a glycoprotein detected at the surface of the parent TA3-HA cell. The results suggested that the amount of epiglycanin-like material at the hybrid cell surfaces, determined by chemical and immunochemical methods, may have been directly related to the capacities of the cells to grow in foreign mouse strains and inversely related to their capacities to absorb anti-H-2a antibody.


Tobacco-specific nitrosamines: formation from nicotine in vitro and during tobacco curing and carcinogenicity in strain A mice. The formation of tobacco-specific nitrosamines from the major tobacco alkaloid nicotine was examined. Detached leaf tobacco was fed either [2'-14C]nicotine or [2'-14C]nornicotine and air cured. The cured leaf was then analyzed for [2'-14C]N'-nitrosonornicotine ([2'-14C]NNN). The yield of [2'-14C]NNN was 0.007% from nornicotine and 0.009% from nicotine. Because the ratio of nicotine to nornicotine in conventional nicotine-type tobacco is 20-100:1, nicotine is considered to be the major precursor for the carcinogen NNN in tobacco. The formation of other nitrosamines from nicotine in vitro was then studied. Reaction of nicotine with NaNO2 gave rise to NNN, as well as to two other nitrosamines, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal (NNA). Analysis of market products revealed the presence of NNK (0.6-24 microgram/g) in chewing tobacco and snuff. The tumorigenic activity of NNN, NNK, and NNA in strain A mice was studied. NNK induced more lung adenomas per mouse than did NNN, whereas NNA was less active than NNN. In addition, two cases of undifferentiated carcinoma of the salivary glands occurred in the NNN experimental groups.


Tissue enzyme changes in parabiotic rats with subcutaneous lymphoma or fibrosarcoma. A solid lymphoma implanted into normal inbred Kx rats and one partner of parabiotic pairs caused appreciable decreases in hepatic ornithine aminotransferase and arginase about a week earlier (4-6 days after implantation) in single hosts than in parabiotic hosts. By 18-21 days significant decreases in both enzymes were apparent in the host partner also. The hepatic thymidine kinase showed a fivefold elevation in single hosts 4 days after implantation; by 14 days in its levels were about 200 times above normal and had also risen in the parabiotic hosts (20-fold) and host partners (fourfold). Implantation of fibrosarcoma caused qualititatively similar but generally less pronounced changes in these three enzymes in livers of single hosts, parabiotic hosts, and host partners. The splenic thymidine kinase 14 days after implantation was increased from control levels of about 3 U/g to 50.6, 44.8, and 13.5 U/g in single hosts, parabiotic hosts, and host partners, respectively. At later stages, 17-20 days after implantation of the lymphoma, appreciable amounts of thymidine kinase appeared in the plasma: The units of activity per milliliter were 6.2 in single hosts, 0.79 in parabiotic hosts, and 0.55 in host partners (control less than 0.05). Our observations on the changes in hepatic and splenic enzymes in parabiotic rats suggest that effects of neoplasms on distant host tissues are mediated by humoral factors. The less pronounced responses in parabiotic than in single hosts indicate that the tumor-free partner affords some "protection" against these systemic effects.


Measurement of mammary tumor blood flow in unanesthetized rats. Blood flow to mammary tumor MT-W9B in minimally disturbed, unanesthetized inbred WF rats was measured with radioactively labeled 25-mu (diameter) microspheres. The distribution of the blood flow estimates was not described by a normal probability density function but could be normalized with a natural log transformation of the data. The relative blood flow to the tumor tissue was always greater than that to the surrounding normal tissue and was dependent on the tumor size, transplantation site (axillary vs. inguinal), and physiologic state of the animal. The growth of this tumor did not alter the blood flow to the adjacent normal tissues. However, the cardiac output and coronary blood flow increased with increasing tumor size. Two blood flow estimates could be performed on the same animal within a time-span of 15 minutes.


Modification of radiation responses of murine tumors by misonidazole (Ro 07-0582), host immune capability, and Corynebacterium parvum. The hypoxic cell sensitizer misonidazole (Ro 07-0582),1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol, significantly enhanced the local control of the weakly immunogenic C3H mouse mammary carcinoma MDAH-MCa-4 (8-mm diameter) by single doses of radiation. The dose modification factor (DMF) was 2.33 when the drug was given ip to inbred C3Hf/Bu mice in a dose of 1 mg/g body weight 30 minutes before irradiation of the tumor. The DMF in a highly immunogenic 3-methylcholanthrene-induced C3H fibrosarcoma (FSa) was 1.65 in normal mice and 1.86 in mice immunosuppressed by 600 rads whole-body irradiation 1 day before tumor transplantation. In mice treated iv with 0.25 mg Corynebacterium parvum when tumors were 6 mm in diameter and irradiated at 8 mm, local control of FSa was enhanced at low doses of radiation but was similar to that in normal mice at higher doses. In mice treated with both misonidazole and C. parvum, local control at lower doses of radiation was similar to that in mice treated with C. parvum alone but was enhanced at higher doses in mice that failed to respond to C. parvum. Cytotoxicity of misonidazole, as reflected in tumor growth, was not detected.


Metabolism of the pancreatic carcinogen N-nitroso-bis(2-oxopropyl)amine after oral and intraperitoneal administration to Syrian golden hamsters. The levels of N-nitroso-bis(2-oxopropyl)amine (BOP) and its metabolites in the urine, blood, bile, and pancreatic juice were compared after ip and oral administration of BOP to Syrian golden hamsters to explain the differing organotropic tumor spectra resulting from treatment by these two routes. The levels of BOP and its metabolites N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitroso-bis(2-hydroxypropyl)amine in the urine, blood, bile, and pancreatic juice were generally less after oral administration than after ip administration. The results suggested that HPOP may be a proximate pancreatic carcinogen in hamsters administered BOP, inasmuch as it was the major metabolite in the blood and pancreatic juice after ip administration. However, the results did not indicate a mechanism for the increased incidence of bile duct tumors that after oral administration of BOP.


DNA synthesis and thymidine kinase activity of rat colon epithelial cells fractionated by discontinuous Ficoll gradient. Epithelial cells from colons of adult Sprague-Dawley rats were fractionated on a discontinuous Ficoll gradient at low centrifugal forces (170 x g) for approximately 60 minutes. Epithelial cells were separated into three distinct zones, whereas cell debris, yeast, and bacteria remained at the top of the gradient. The percentage of cells in each zone was inversely related to the density of the gradient. More than 95% of the cells were morphologically intact and viable (excluded trypan blue). Cells sedimenting at higher densities of Ficoll exhibited higher thymidine kinase activity and DNA synthesis, suggestive of active cell division. The cells sedimenting at lower densities of Ficoll showed the least thymidine kinase activity and DNA synthesis, properties that are compatible with those of mature absorptive cells. Tall columnar cells with vesicular nuclei were predominant in the fraction sedimenting at the lowest density (top fraction). At higher densities (middle and lower fractions), most of the cells were short and columnar with basally located condensed dark-staining nuclei.


Conversion of a poorly differentiated human adenocarcinoma to ascites form with invasion and metastasis in nude mice. Cells (1 X 10(7)/0.5 ml) from a Borrmann type III poorly differentiated adenocarcinoma of the human stomach were injected ip into nude mice. The injection resulted in ascites carcinoma with invasion (carcinomatous peritonitis) and liver metastasis. The inoculum was obtained from subcutaneous tumors at passage 9 in nude mice that had received serial transplants from the patient with Borrmann type III poorly differentiated adenocarcinoma of the stomach. Serial transfers of 1.5 X 10(6) dispersed cancer cells/0.5 ml into the peritoneal cavity of nude mice converted this adenocarcinoma to an ascites form. Hemorrhagic ascites accumulated within 3 weeks at the first passage and 4-6  weeks in serial passages. Carcinomas peritonitis occurred consistently and was observed in the diaphragm, mesenteries, omentum, and pancreas; metastases were seen in the liver and spleen. Subsequently, iv injection of ascites at passage 3 (6 X 10(5) cells/0.2 ml) into nude mice produced metastatic lesions in the lung and the heart. The histology of the invasive and metastatic lesions in the nude mice was similar to that of the original tumor in the patient with stomach carcinoma.


Proof of in vivo fusion of murine tumor cells with host cells by universal fusers. Two mouse cell lines (A9HT CI.3C and 501-1), each carrying both a recessive and a dominant mutation (and therefore designated "universal fusers"), were utilized for selection of in vivo hybrids from tumors produced intraperitoneally and subcutaneously in appropriated hosts. The double selective medium eliminated both parental (tumor and host) cells but allowed the survival and proliferation of the fused product. This proved that hybridization between tumor and host cells occurred in vivo.


Mechanism of Fusarium mycotoxin action in mammary gland. The interaction of the Fusarium mycotoxins zearalenone and dihydrozearalanol with specific estrogen binding sites was studied by using cytosol preparations of mammary glands from lactating rats. Both substance inhibited [3H] estradiol-17beta association with its binding site in a competitive fashion. This inhibition was a result principally of an effect on estrogen binding by the 8S species of receptors separated by density gradient centrifugation. These data suggest that the biological action of Fusarium mycotoxins with estrogenic activity is mediated by intracellular estrogen receptors.


Influence of laying on lead accumulation in bone of mallard ducks. Paired mallard ducks (Anas platyrhynchos) were given No. 4 lead shot, and bone lead concentrations were compared in drakes and in laying and nonlaying hens. Lead accumulation was significantly greater in bones with a high medullary content (femur and sternum) compared with bones with a lower medullary content (ulna-radius or wingbones). In dosed groups, hens always contained higher bone lead residues than drakes. After dosage with one shot (approximately 200 mg lead), lead in femurs of laying hens averaged 488.4 ppm compared with 113.6 ppm in nonlaying hens. Femurs of drakes averaged 9.4 ppm lead. Dosage with the second lead shot did not result in further accumulation of bone lead in hens, but increased bone lead concentrations threefold in drakes, suggesting that saturation levels for bone lead had already been reached in the hens after ingestion of one shot. There was no demonstrable relationship between egg production and bone lead residues. The high lead residues, found in medullary bones of laying hens indicate that sex and physiological condition are major factors influencing lead absorption by bone.


Conditioned avoidance responses of young mice and offspring of mice treated with neuroleptic or mutagenic agents. Conditioned avoidance response (CAR) tests were used to determine the effects of perinatal exposure to three neuroleptic drugs and an antineoplastic agent in mice. In one experiment, mice were given sc injections of haloperidol at 1.25 mg/kg.d or trifluoperazine at 12.5 mg/kg.d for 2 wk, starting when they were 4 d old. In additional groups, nursing dams were given haloperidol at 5 mg/kg.d or trifluoperazine at 25 mg/kg.d for 2 wk during lactation. CAR tests were begun when offspring were 40 d of age. No statistically significant evidence of impairment in the learning ability of any group was found. In a second experiment, hybrid male mice were treated with a single ip injection of triflupromazine at 50 mg/kg or triethylenemelamine at 0.2 mg/kg and were mated 2, 4, and 6 wk after dosing. The male offspring were tested for learning ability at 40 d of age. No statistically significant differences in CAR values were observed in offspring of triflupromazine-treated males. CAR values of offspring of triethylenemelamine-treated males mated 4 wk after dosing were significantly higher than those of controls.


Carcinogenicity of vinyl chloride and vinylidene chloride. Exposure of mice to 50, 250, or 1000 ppmm of vinyl chloride (VC) in the air for 6 h/d, 5 d/wk, caused a high incidence of bronchioloalveolar adenoma, mammary gland tumors, and hemangiosarcoma. Mammary gland tumors occurred in the females and included ductular adenocarcinoma and squamous and anaplastic cell carcinomas with metastasis to the lung. Hemangiosarcoma occurred in the liver and, to a lesser extent, in various other organs. The incidence and severity of these tumors increased with the concentration of VC and the length of exposure. Malignant lymphoma involving various organs was observed in several mice. Rats were more resistant to the carcinogenic effects of VC. Exposure of rats to 250 or 1000 ppm of VC caused hemangiosarcoma in the liver. Many rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Extrahepatic hemangiosarcoma also occasionally occurred in other organs. Exposure to 55 ppm of vinylidene chloride (VDC) caused hepatic hemangiosarcoma and probably bronchioloalveolar adenoma in mice. Hemangiosarcoma also occurred in the mesenteric lymph node or subcutaneous tissue in two rats exposed to 55 ppm of VDC.


Oxidative metabolism of dimethylnitrosamine: correlation with toxicity. The relationship between oxidative metabolism and acute toxicity of dimethylnitrosamine (DMN) was examined in neonatal and adult rats to take advantage of developmental changes in activity of the metabolizing enzymes. The objective was to determine the extent to which CO2 production from DMN is correlated with toxicity. Neonatal rat liver and kidney demonstrated the ability to metabolize DMN. This ability progressed to a maximum activity in liver between the 5th and 21st d of age and in kidney between the 15th and 21st d of age. After weaning, the activity of DMN oxidation decreased with age in both tissues. Evidence is also presented to suggest that more than one enzyme may be responsible for the oxidation of DMN to CO2 and that the predominance of individual enzymes varies as the neonate develops. Estimates of LD50 values, used to quantitate the acute toxicity of DMN at various ages, suggest that the rat is most sensitive to DMN toxicity at 5 d of age; however, conversion of DMN to CO2, both in vitro and in vivo, was not well correlated with acute toxicity.


Isolation of mutagens from bacterial nutrients containing beef extract. The enhanced rate of mutation of Salmonella strain TA1538 (Ames) by microsomes results from the presence of about 2--5 ppm of microsome-activatable mutagens in bacterial nutrient broths that contain beef extract. Since mutagens toward Salmonella are likely to be carcinogenic, the data have significant implications for the problem of carcinogenesis.


Effect of alkane tumor-promoting agents on chemically induced mutagenesis in cultured V79 Chinese hamster cells. Linear alkanes of specific chain length between 6 and 16 carbon atoms, an aryl derivative of dodecane, and a phorbol diester were tested in a cell culture system for relative ability to enhance mutagenesis induced by a chemical carcinogen, methylazoxymethanol acetate (MAM). Mutation frequencies at the ouabain-resistance locus were measured. Results indicated an excellent correlation between the relative activities of the above compounds in enhancing mutagenesis in the in vitro culture system and their tumor-promoting activities in mouse skin. None of the compounds tested showed mutagenic activity per se, further lending support to the theory that promoters act via derepression of latent carcinogen-induced damage to the genome.


Effects of dietary vanadium in mallard ducks. Acult mallard ducks fed 0, 1, 10, or 100 ppm vanadyl sulfate in the diet were sacrificed after 12 wk on treatment; tissues were analyzed for vanadium. No birds died during the study and body weights did not change. Vanadium accumulated to higher concentrations in the bone and liver than in other tissues. Concentrations in bones of hens were five times those in bones of drakes, suggesting an interaction between vanadium and calcium mobilization in laying hens. Vanadium concentrations in most tissues were significantly correlated and increased with treatment level. Lipid metabolism was altered in laying hens fed 100 ppm vanadium. Very little vanadium accumulated in the eggs of laying hens.


Interrelationships of glutathione reductase, 5-aminolevulinic acid dehydratase, and free sulfhydryl groups in the erythrocytes of normal and lead-exposed persons. Blood lead, erythrocyte glutathione reductase (GSSG-R), 5-aminolevulinic acid dehydratase (ALA-D), and free sulfhydryl (SH) groups were measured in normal subjects and in those with occupational exposure to lead. With increasing blood lead concentration the activity of GSSG-R rises and that of ALA-D decreases. There is also a fall in the level of free SH with rising blood lead concentrations. There is a high degree of correlation between these parameters, and it is suggested that the changes represent part of a biological control mechanism to compensate for the reduction of available sulfhydryl groups by lead ions.


Environmental mutagens in urban air particulates. A bioassay capable of detecting carcinogenic substances that are associated with the elevated incidence of cancer in the urban environment would be important for epidemiologic and environmental analyses. The feasibility of using the Salmonella mutagenesis system developed by Ames for this purpose has been tested by analyzing Chicago air particulate samples. Active material, as evidenced by enhanced rates of mutation, both in the presence of microsomes and in their absence, is readily extractable from samples of air particulates. Dose-response curves have been obtained from such extracts of 15 successive samples, taken at intervals during 1975 from a sampling site in South Chicago. A method for analyzing such data in order to evaluate the relative mutagenic activity of different samples is described. The presence of a number of mutagenic constituents has been demonstrated by means of thin-layer chromatography of particularly active samples, in which the active material is located by mutagenic analysis of successive chromatographic zones. Mass spectrometer analysis of material isolated from an original sample in this way indicates that benzo[a]pyrene and benzo[e]pyrene, which are known to be mutagenic and carcinogenic, are present. It is concluded that within certain constraints, which are described, the methodology can serve the purpose of an environmental bioassay for organic carcinogens.


Simultaneous determination of cellular mutagenesis and transformation by chemical carcinogens in Fischer rat embryo cells. Thirteen chemicals, eight carcinogenic and five closely related noncarcinogenic analogues, were tested to establish the validity of a simultaneous procedure for the in vitro assay of potential carcinogens and mutagens. The assay utilizes Fischer rat embryo (FRE) cells infected with Rauscher leukemia virus and simultaneously measures the induction of cellular transformation (growth in soft agar) and mutagenesis (ouabain resistance) by chemicals. An activation procedure for the metabolic conversion of the procarcinogens and promutagens to biologically active forms is described. All chemicals that produced transformation in the FRE system also induced a significant increase in ouabain resistance. The significance and the potential uses of this assay are discussed.


Biliary excretion of [14C]penicillic acid by rats. Adult male rats were given [14C]penicillic acid by oral intubation, and the biliary excretion of the compound was monitored. The significance of bile as an excretory route was confirmed and compared by using open and recycle cannulation of the bile duct. The biological half-retention life of [14C]penicillic acid in the bile was 3.63 h.


Oral toxicity of ferric dimethyl-dithiocarbamate (ferbam) and tetramethylthiuram disulfide (thiram) in rodents. Single oral doses of ferbam, thiram, zineb, or maneb produced central nervous system stimulation followed by depression and alopecia. Ferbam and thiram were more toxic on the basis of weight than zineb; maneb was relatively nontoxic. There was no species difference in acute toxicity between rats and mice. In 13- and 80-wk feeding studies, the toxic effects of ferbam and thiram in rats were similar; however, thiram was more toxic on the basis of weight than ferbam. During the 80-wk feeding study, weight gain was reduced in ferbam-treated rats starting at daily doses of 8 mg/kg in males and 37 mg/kg in females and in thiram-treated rats staring at daily doses of 5 mg/kg in males and 26 mg/kg in females. Food consumption was reduced in proportion to the reduced weight gain. Death occurred in males fed 109 or 331 mg/kg.d ferbam and in males fed 58 or 132 mg/kg.d thiram. Female rats fed 96 mg/kg.d ferbam or 67 mg/kg.d thiram developed alopecia and ataxia, which led to paralysis of the hind limbs. Male rats fed ferbam or thiram had a more severe incidence of squamous metaplasia in the thyroid and fatty infiltration in the pancreas than control males. Ferbam or thiram reduced the incidence of spontaneous nephritis in both males and females. The male rats that were fed 109 or 331 mg/kg.d ferbam and died betweeen 1 and 5 wk had golden pigment in the reticuloendothelial cells of the spleen and in the enlarged mesenteric lymph nodes, associated with hemosiderosis. Moderate tubular degeneration of the testes with atypical spermatids in the epididymis occured in some rats fed 132 mg/kg.d thiram for 13 wk but not in rats fed up to 52 mg/kg.d for 80 wk. Periodic hematologic examination and terminal clinical blood tests did not reveal any severe changes. Ferbam and thiram did not alter the occurrence or latent period of the spontaneous tumors seen in control rats.


Abnormal heme-protein patterns in hemorrhagic shock. Allegedly toxic heme pigments have been described in the serum of animals bled to hemorrhagic shock (5,7). In addition, Sears et al. (9), and Braun et al. (1) have shown that the products derived from the degradation of hemoglobin following intravascular hemolysis were toxic (heme carried by hemopexin and albumin). The accumulation of metabolites, caused by the impeded circulation, degrades free hemoglobin into heme pigments and their concentration then reaches a level which exceeds the normal heme-carrying capacity of serum proteins. We have already demonstrated the presence of abnormal heme pigments in clinical cases of shock using scanning spectrophotometry (3). We have endeavored to identify these pigments by serum electrophoresis, and to relate the appearance of some of these compounds to mortality rates. There were no deaths associated with the presence of haptoglobin-hemoglobin alone in serum. As shock deepened and mortality rose, hemopexin-heme and methemalbumin appeared. The highest mortality rate (4 out of 5 cases) was found when both hemopexin-heme and methemalbumin were present. It appears, therefore, that the administration of serum proteins in shock may reduce the toxicity of the products of degradation formed in low-flow states.


Plasma lipids, coagulation factors, and fibrin formation after severe multiple trauma, and in adult respiratory distress syndrome. Following severe multiple trauma, decreases were observed in a) Free cholesterol, b) Cholesteryl esters, c) Total phospholipids, and d) Lysolecithin. Comparatively slight changes in coagulation parameters did not differ regardless of whether pulmonary complications developed. In contrast, increased fibrin lipid complexing was more closely correlated with clinical data, because: a) Plasmatic lipids, particularly triglycerides complexed with fibrins, were elevated severalfold in patients with adult respiratory distress and fat embolism syndromes when compared with multiple trauma patients without pulmonary complications. This was independent of plasma lipid levels. b) Plasmatic triglycerides complexed with fibrins were significantly higher in patients who died than in those who survived. The considerable changes in the plasma lipid pattern following severe trauma suggest the presence of an abnormal lipoprotein with increased affinity to fibrin, thereby inhibiting fibrinolysis. This might well be one pathogenic mechanism in the development of post-traumatic respiratory distress syndrome.


Early diagnosis of the fat embolism syndrome. One hundred consecutive cases of trauma with associated fractures of the lower limb long bones were studied for the subsequent development of the fat embolism syndrome (FES). This is to be differentiated from the intravascular fat embolism which often occurs without clinical FES becoming manifest. Seventeen of the patients developed the clinical picture, with a further 16 patients being considered to have had the syndrome subclinically. Clinical and biochemical features were studied to determine pointers to the early diagnosis and patient "at risk" of developing FES. Young males under the age of 30 with significant hypoxemia occurring early in the course of the disease were considered the most likely candidates "at risk" for developing FES. These results favor the concept that FES is essentially a form of respiratory insufficiency syndrome similar to that which occurs following trauma in other situations, e.g., shock lung.


The study of burn wound edema using dichromatic absorptiometry. Burn wound edema is a source of major morbidity and mortality. To quantitatively study this edema, we have devised a noninvasive method called Dichromatic Absorptiometry (DA) which is precise (2-3%) and accurate (r equal to 0.99) in measuring changes in tissue fluid. A scanning technique using a dual photon source, 125I and 241Am, is used. The variable attenuation of the two photon energies allows for selective mass measurements of fluid, protein, lipid, and bone. In limbs with thermal injury the correlation of DA changes in fluid mass with circumference was (r equal to 0.97), but DA was more sensitive. In deep second- and third-degree burns, edema formation was maximum between 12 and 18 hours postburn with 80% of maximum already present at 4 hours. Resorption was complete by 1 week in second-degree burns, but significantly delayed in third-degree burns. Superimposed infection produced persistent edema.


Alterations of complement system following thermal injury: use in estimation of vital prognosis. Complement system has been investigated in the first 15 days postburn. Complement titer (measured by a kinetic method of immune hemolysis) decreases immediately after thermal injury. This depression is mainly explained by mechanical leakage and is related to burn surface. No anticomplementary effect has ever been found in this period. After 48 hours complement titer rises. Magnitude and rate of rise are inversely related to the severity of burn trauma (depth and surface). Infection occurrence is statistically related to but somewhat independent of complement levels and interferes with the rate of increase of complement levels. The basis of the rise to normal or elevated complement levels remains unexplained.


Rupture of the bronchus: Case report of successful resection and anastomosis in a 13-month-old infant. An unusual case of rupture of the bronchus in a 13-month-old child is reported. It is believed that this is the youngest reported case of successful repair and it is documented by an 11-year follow-up.


Immediate revascularization of the popliteal artery and vein: report of a case. A case demonstrating the successful use of Silastic shunts for immediate limb revascularization is presented. Temporary limb revascularization may reduce the rate of amputation in combined popliteal vessel injuries. A major cause of limb loss is delay between injury and revascularization, including transport time and time spent dealing with other injuries. Repair of the popliteal vein increases the chance of successful limb salvage. Temporary Silastic shunts can alleviate time loss while others problems are dealt with and allow rapid venous, as well as arterial, revascularization. The technical ease and rapidity of shunt placement converts a catastrophic vascular emergency into a manageable problem.


Acute leukopenia associated with silver sulfadiazine therapy. A patient with a 30% scald burn was treated with topical silver sulfadiazine (Silvadene). On two occasions, within 48 hours of treatment, the patient developed acute leukopenia. Bone marrow aspiration revealed cell maturation arrest. The possible mechanisms of this leukopenia are discussed. It is recommended that daily leukocyte counts be done in burn patients being treated with silver sulfadiazine.


Fluid overload and post-traumatic respiratory distress syndrome. A series of dogs was given massive fluid infusions at two dose levels, 60 cc/kg and 100 cc/kg. The dogs were prepared in three ways: shock induced by bleeding; intravenous injection of oleic acid; and combined oleic acid injection and shock. The studies showed that type of injury was a more important determinant of lung dysfunction than the fluid dose. Shock animals were not hurt by fluid infusion; in oleic acid-injected dogs, the fluid infusion magnified the effect of oleic acid. When shock, oleic acid, and high fluid dose were combined, all animals died. The animals that died had high pulmonary artery diastolic pressures.


Myocardial depression in acute thermal injury. Previous studies have shown myocardial depression to occur secondary to toxic extracts of burned mouse and human skin and secondary to toxins present in acute human burn serum. The present report describes myocardial depression in an arterially perfused rabbit interventricular septum as a result of toxins present in acute burn plasma. New Zealand white rabbits subjected to a 25% BSA full-thickness burn were heparinized and exsanguinated 2 hours postinjury. Cellular elements and plasma were separated and the plasma frozen. Rabbit myocardial septa were then perfused with normal or burn plasma. Rabbit red cells were added to restore hematocrit to 20 degrees, and the plasma-red cell mixtures were equilibrated with 98% O2 plus 2% CO2. Temperature (28 degrees C), pH (7.40), and flow rate (1 ml/min) were constant for all trials. All normal plasma preparations showed an improvement in developed tension (DT) during the 30-60 minute perfusion period with mean % change equal to + 10.5. A corresponding increase in dP/dt was also noted for all normals (mean % change equal to + 14.3); all septa perfused with acute burn plasma showed a decline in myocardial performance during a similar perfusion period. Mean % change in DT for burn plasma preparations was - 57.5, and in dP/dt for these septa was - 59.5. Significant myocardial depression occurs in arterially perfused rabbit septa when acute burn shock plasma is used as the perfusate.


Categorization of hospital emergency capabilities: some empirical methods to evaluate appropriateness of emergency department utilization. Despite the emphasis on appropriateness of emergency department utilization, there is currently no methodology for assessing appropriateness nor measures for a community to evaluate and improve effectiveness of its E.M.S. system in treating emergencies at the appropriate emergency room and nonemergencies at appropriate alternative settings. The writer feels that the one current strategy which is widely accepted, the A.M.A.'s concept of categorization, has substantial methodologic limitations. The present paper suggests a methodology and a set of measures to assess appropriateness of utilization and illustrates them with data from Buffalo, New York, on a chart review of 24,594 emergency department patient medical records and interviews with 888 patients and their attending physicians. The measures include: 1) distribution of ambulance and critically ill patients by A.M.A. category of hospital, 2) utilization, characterized as system under- or over-response or as appropriate utilization, and 3) physician judgments as to indicated alternative treatment sites, which are suggested as evaluative tools to hospital and communities for E.M.S. assessment, and to federal and state agencies as performance standards, for project selection for funding and monitoring for outcome evaluation.


Amoebic liver abscess and clinical experiences with tinidazole in Bangladesh. 35 cases of amoebic liver abscess have been studied and their clinical diagnostic features analyzed. The diagnosis was based on WHO criteria of enlarged tender liver, leucocytosis and aspiration of typical anchovy sauce pus from the abscess. The authors have however, suggested major and minor diagnostic criteria for the condition. These cases were all treated with new nitroimidazole derivative Tinidazole in a single dose of 2 gm daily for consecutive 2 or 3 days. All the cases were followed up for at least 2 months. 100 per cent cure rate was observed. However, in 7 cases the dosage had to be repeated. Minor side effects were noted. The liver function tests and blood chemistry done pretreatment and post-treatment did not show any drug related toxicity.


Growth, school attendance, and serum albumin levels in South African black children of 10-12 years. Studies on representative series of South African Black schoolchildren aged 10-12 years revealed the following. (1) In the age sex groups, mean proportions lying below the Boston 3rd percentile of weight for age were high (a very common phenomenon), ranging from 20-84 per cent. (2) Of total moieties above and below the 3rd percentile, 96 per cent and 95 per cent had normal weight for height (more than 80 per cent of the 50th percentile of reference standards). (3) Both moieties had equally excellent records of school attendance, 94 per cent and 93 per cent. (4) Mean serum albumin levels, also the proportions having relatively low levels, did not differ significantly, either in the respective subgroups above and below the 3rd percentile, or in groups of pupils accustomed and not accustomed to supplementary school-feeding. Accordingly, it is considered that classification, without qualification, of schoolchildren as malnourished simply because of slower growth compared with western norms is unwarranted.


[Two cases of benign polypes of the ureter (author's transl)]. The polyp of the ureter is a tumour which originates in the connective tissue and is covered by normal urothelium. Radical surgery is justified in some of these urothelial tumours but one should also consider a more conservative attitude when one deals with a benign fibro-epithelial polyp of the ureter especially when they are located in the lower or upper third of the ureter. We present two cases, one which represents the eleventh case of benign fibro-epithelial polyp described in children in the literature.


[Indication, technic and results of the rectal bladder]. For the incontinence of urine, when the bladder and the urethra could not be reconstituted: hypospade, épispade, vesico-vaginal fistula with distruction of urethra, neck and trigone. From 1959 we have performed 42 rectal bladder. The total cystectomy for cancer and reconstruction of rectal bladder have bad prognostic. Our technic of reimplantation of ureters into rectum is inspired from Coffey and Nesbit, is also anti-reflux. The mortality after the operations is about 5%. The distant mortality is 0. The continence of urine is good the day, less good by night, some patients urine once or twice by night. The contiguous and distant pyelography are classed as: very good, good and not bad. The results are good, we have never be obliged to practice a nephrectomy for 84 ureters reimplanted. The rectal bladder is continent and respect the upper urinary tract and gives thhe patients good life in the society.


[The vaginal risk in hypogastric surgery of the pelvic ureter and the trigone of the bladder (author's transl)]. Excision of the vagina during an operation involving the pelvic ureter or the lower part of the bladder may result in the development of a urinary fistula into the vagina. This risk would seem to be little known, though perfectly explicable on the basis of the close proximity of the structures involved. Certain procedures on the lower urinary tract, including both the pelvic ureter as well as the trigone of the bladder, which may be combined with unfavourable gynaecological circumstances, natural or acquired, may explain such damage to the bladder, with fistula formation. The treatment of these fistulae will be curative, 0ut attention must also be paid to prevention, i.e., cautions and accurate surgical technique adapted to the difficulties encounterd in this region.


[Traumatic lesions of the ureter in pelvic surgery. 9 cases (author's transl)]. Five cases were related to gynaecological surgery and 4 to operations involving the colon and rectum. In digestive surgery, the ureteric lesion was noted and repaired in 3 cases out of 4. By contrast, in gynaecology, it went unnoticed in all cases and was diagnosed and repaired after an interval varying from 6 weeks to 4 years after the trauma. 4 anti-reflux uretero-vesical reimplantations and one uretero-ureteric anastomosis were carried out, with complete success in all 5 cases. It is particularly striking to note that in gynaecological surgery 4 of the 5 ureteric lesions followed surgery for a non-malignant condition and that the ureteric trauma should have been easy to avoid, in particular by the preoperative insertion of ureteric catheters. By contrast, all the cases in digestive surgery were associated with operations for a carcinoma. In 3 cases out of 4, excision of the tumour necessitated the sacrifice of a segment of the ureter in the pelvis. One end-to-end ureteric suture failed, whilst 2 uretero-ureteric anastomoses were both successful.


Operative nephroscopy with fiberoptic scope: preliminary report. New fiberoptic scopes, originally designed for biliary tract operations, were used in 23 cases for removal of residual calculi at pyelolithotomy and for examination of the renal pelvis and ureter. The external diameters of the scopes are 6.6 mm. (CHF-X1) and 4.5 mm. (CHF-X2). Water irrigation and forceps manipulation can be performed simultaneously with the CHF-X1 scope but only irrigation can be done with the CHF-X2 scope. The scopes were reliable and allowed easy endoscopic forceps manipulation. Improvements for an ideal fibroptic nephroscope are discussed.


Evidence for a new mammalian organ. II. Calcium kinetics. The calcium content and calcium kinetics of the fatty tissue complex comprising the renal sinus organ of the rat kidney are reported. A comparison is made to control brown and white fat in the same animal. The calcium content of the renal sinus tissue is significantly greater than controls. Calcium localization in the mitochondria of the sinus tissue complex is demonstrated. Radioactive isotope studies (45Ca, 85Sr and 99mTc) indicate a dynamic exchange of calcium between the systemic pool and the sinus organ. Active accumulation appears to be operative. Supporting evidence for the existence of a portal vascular system joining the renal sinus complex and the renal parenchyma is presented. The significance of a calcium sink in the renal sinus tissue of the rat kidney is discussed.


Experience with the radioimmunoassay for parathyroid hormone in the diagnosis of primary hyperparathyroidism. Our results with radioimmunoassay studies for parathyroid hormone performed during the last 6 years are compared retrospectively to results of the laboratory tests customarily secured when hyperparathyroidism is suspected. The results obtained in patients with known primary hyperparathyroidism and in patients with unconfirmed but presumptive hyperparathyroidism are compared to the results obtained from a group of normal controls. Despite the fact that certain discrepant results were noted in the earlier assay techniques the over-all results and, in particular, those of more recent years have been highly sensitive and reproducible corroboratives of the existence of primary hyperparathyroidism. About two-thirds of the patients with primary hyperparathyroidism will present to the urologist. All patients with calcium-containing stones should have at least 3 determinations of the serum calcium in screening for primary hyperparathyroidism. The radioimmunoassay for parathyroid hormone provides the most reliable confirmation. The patient with calculous disease, elevation of the immunoreactive parathyroid hormone level and hypercalcemia is virtually certain to have primary hyperparathyroidism.


Intrarenal urinary extravasation with formation of venous polyps containing Tamm-Horsfall protein. Collections of periodic acid-Schiff-positive material are found in the intrarenal veins and in the renal interstitium in certain cases of hydronephrosis and unexplained unilateral hematuria. Using a fluorescent antibody to Tamm-Horsfall protein, a protein secreted by the ascending limbs and distal convoluted tubules, we have demonstrated that the venous and interstitial masses represent urinary filtrate, which probably enters the kidney parenchyma through forniceal or tubular ruptures.


Crossed renal ectopia.

Crossed renal ectopia. Crossed renal ectopia is an unusual congenital anomaly, probably produced by abnormal development of the ureteral bud. The deformity itself produces no symptoms and the clinical presentation generally is for obstruction and infection. In our series the adult patients presented most commonly with urinary tract infections, while the pediatric patients presented most often with multiple congenital anomalies, especially of the skeletal system.


Advances in the diagnosis of renal candidiasis. Candiduria may signify benign saprophytic colonization or true infection of the urinary tract. Histological studies of 64 suspect cases of renal candidiasis, 20 of them positive, suggest that a Candida colony count of 10,000 to 15,000 per ml. or more in a catheterized specimen is a useful cut-off point between infection and colonization. One to 3 Candida per high power field in an uncentrifuged urine specimen equated with a colony count of 10,000 to 15,000 Candida per ml. Colony counts were diagnostically invalid in the presence of an indwelling Foley catheter. Other diagnostic aids included positive serum precipitin tests (83%) and positive blood cultures (47%).


The management of delayed recognized ureteral injuries. Of the 90 cases of ureteral injuries reviewed 51 injuries were recognized immediately, while 39 were recognized in the delayed period. Although the over-all difference in results between those treated immediately and those receiving delayed treatment was relatively small, when the cases  were further subdivided by etiology and time of recognition into immediate and delayed iatrogenic injuries and traumatic injuries the difference in results was striking. This fact had been suspected clinically but not well documented previously in the urologic literature.


Followup study after conservative and surgical treatment of vesicoureteral reflux. Our series of 94 cases (145 ureters) of vesicoureteral reflux is reviewed. The occasional disappearance of reflux during conservative treatment should not be mistaken for cure because of its variable nature. To avoid such a mistake voiding cystography under fluoroscopic monitoring is repeated indefinitely. Those patients who were treated surgically were followed for at least 2 to 3 years before cure was established. Transient ureteral dilatation after reimplantation was eradicated within 3 months. Postoperative urinary infection was observed at various intervals, ranging from 1 week to 5 months, and the erythrocyte sedimentation rate was likely to be influenced by infection. Postoperative chemotherapy was continued until the erythrocyte sedimentation rate was normal and there was no infection and/or dilatation of the upper tract.


Partial cystectomy in the treatment of transitional cell carcinoma of the bladder. Between 1950 and 1974, 35 men and 10 women underwent partial cystectomy for transitional cell carcinoma of the bladder. Indications, contraindications and the principles of technique for partial cystectomy as therapy for transitional cell tumors of the bladder are discussed. All patients were evaluated postoperatively, with cystoscopic examination every 3 months for 1 year, every 6 months for 3 years and then at yearly intervals if no tumors had been detected. None of the patients received preoperative irradiation. Eight ureters were re-implanted and 6 prostate glands were enucleated at the time of partial cystectomy. There was 1 death in the immediate postoperative period. Complications developed in 13 patients, 3 of which were considered major. When recurrences were noted appropriate therapy was performed as indicated. Irradiation was the most commonly used method to treat distant metastases. The over-all 5-year survival rate is 57.7% (26 patients). Thirty-four patients were followed for 10 years. The survival rate for this group of patients was 32.4% (11 patients). The results of this study correlate well with other published reports.


Radical cystectomy for bladder cancer.

Radical cystectomy for bladder cancer. We reviewed 52 consecutive patients who had undergone radical cystectomy for bladder cancer prior to 1962 and have been followed for 15 to 23 years. The over-all survival rates at 5, 10 and 15 years were 38, 27 and 17%. Pathologic staging was the most important prognostic factor in the series.


Followup of abdominal neourethra.

Followup of abdominal neourethra. Abdominal neuroethrostomy is a highly satisfactory form of urinary diversion for patients with irreparable urethral stricture or destruction. Normal renal function, structure and urinary continence have been observed in 7 patients for as long as 17 years.


Evaluation and treatment of patients with failed hypospadias repair. Hypospadias repair is often accompanied by complications, some of which may be major. We herein analyze 70 patients whom we have seen and enumerate the defects, list the operative procedures that have been necessary to correct the lesions and illustrate the use of some of these techniques. Surgeons treating patients with hypospadias should have command of many techniques and use them aggressively with imagination and great care.


Urological and behavioral approach to the treatment of secondary impotence. Psychogenic impotence is far more common than organic impotence and may co-exist with or be a result of it. Psychological principles of therapy may be needed for all impotent patients treated by the urologist. These principles include 1) re-education in sexual function, 2) removal of pressure for male performance, 3) bringing existing performance fears to the surface for therapy, 4) teaching patients techniques to deal with the fears, 5) teaching the partner proper cooperation and 6) improving the communications between the 2 partners.


Significant immunologic factors in male infertility. A number of patients who suffer from involuntary infertility showed a sperm antibody in the blood serum as detected by 2 different methods of sperm agglutination. These techniques are the Kibrick method (gelatin agglutination test) and the F-D method (tube-slide agglutination test). With the former technique 9% of men and 18% of women from infertile couples had a positive result, while the latter technique revealed 5% of men and 15% of women with positive results. Such cases are termed immunological infertility. Several cases of necrospermia also showed sperm antibody activity. In vasectomized men it has been shown that 50 to 60% have sperm antibody during the first year postoperatively. To develop new methods for treatment of infertility immunosuppression by means of corticosteroid medication was applied. A 7-day regimen of 96 mg. per day methylprednisolone was studied. A drastic decrease of antibody level could be seen in some cases and the wives became pregnant. There has been approximately a 30% success rate in a group of 15 such couples.


Estramustine phosphate: metabolic aspects related to its action in prostatic cancer. Estramustine phosphate, a drug effective in a substantial number of patients with cancer of the prostate who had failed on other forms of therapy, has been shown to be split into its constituents, that is estradiol-17beta and the carbamate nitrogen mustard by non-cancerous and cancerous human prostatic tissues. This fact may explain, in part, the mechanism of action and efficacy of the drug in patients with cancer of the prostate. In addition to presenting results on the hydrolysis and its products accomplished by human prostatic tissues we discuss the limitations of extrapolating animal results with estramustine phosphate to the human condition and possible parameters that bear upon the insignificant toxic and estrogenic effects observed in patients given estramustine phosphate.


Bromocriptine and prostatic carcinoma: plasma kinetics, production and tissue uptake of 3H-testosterone in vivo. The influence of the anti-prolactin bromocriptine on plasma kinetics, production rate and tissue uptake of testosterone was investigated in 15 patients with newly diagnosed stages C and D prostatic carcinoma. Bromocriptine was given for 5 days in a daily dose of 15 mg. orally. The studies were performed with the single injection technique using the 2-compartment model. Plasma testosterone, serum prolactin, and luteinizing and follicle-stimulating hormones were determined initially. Blood samples were drawn up to 5 hours after the injection of 3H-testosterone. For tissue studies a transrectal needle biopsy was done 3 hours post-injection. Bromocriptine suppressed prolactin and the endogenous testosterone level. Furthermore, it favored the elimination of 3H-testosterone, lowered the production rate of testosterone and hampered the in vivo uptake of the 3H-label into prostatic carcinoma tissue. Finally, the grading of the tumor lesions affected only the pre-bromocriptine uptake of radioactive androgens and not the uptake in response to bromocriptine. The potential clinical impliications of these observations are discussed.


Clinical significance of serum alkaline phosphatase isoenzyme levels in advanced prostatic carcinoma. The alkaline phosphatase isoenzymes in 105 patients with stage D carcinoma of the prostate who entered the National Prostatic Cancer Study were analyzed and these values were correlated to clinical response. Only patients with at least 3 measurements of alkaline phosphatase were evaluated. In 91% of patients with metastatic bone disease, bone alkaline phosphatase was elevated. Those patients with higher pre-treatment levels of alkaline phosphatase generally showed a poorer response to therapy. The results of alkaline phosphatase isoenzyme estimation indicate that these biological markers may be used in the evaluation of patients with metastatic prostatic cancer to predict and monitor their response to chemotherapy. The evaluation of bone and liver alkaline phosphatase isoenzymes in earlier stages also may be valuable.


Urodynamic patterns in children with dysfunctional voiding problems. Simultaneous measurements of the intravesical pressure, electromyographic activity of the anal sphincter and the urinary flow rate in 17 children with dysfunctional voiding problems have shown a variety of unusual patterns, each distinct for the particular child but all with the common denominator of failure to coordinate detrusor and sphincter activity. We postulate that these patterns represent persistence of the transitional phase in the development of micturitional control whereby the child learns to prevent involuntary wetting by forceful contraction of the external urethral sphincter.


Renal abscess in children.

Renal abscess in children. Ten children with renal abscesses treated during the last 25 years are reviewed following our recent experience with 3 children, each of whom presented with an abscess. The diagnosis was not readily apparent before hospitalization, despite characteristic features of the disease. Excretory urography with nephrotomography proved to be the most valuable diagnostic study. Angiography was useful in differentiating the abscess from other intrarenal processes. Staphylococcus aureus was the most common infecting organism. Upper urinary tract anomalies were noted most frequently with gram-negative infections. Treatment consisted of drainage of the abscess in 8 children. Nephrectomy was required in 2 girls, each of whom had multiple extensive gram-negative carbuncles. The pathogenesis and therapy of a renal abscess are discussed.


Penetrating renal trauma in the neonate. For years the management of blunt and penetrating renal trauma has been the source of controversy in the literature. The indications for a specific therapeutic program vary with each individual case and with the complicating factors involved. An unusual form of penetrating renal trauma in the neonate is presented and the rationale for therapy is discussed.


Dissecting aneurysm of renal artery owing to subadventitial angioma. A case of renovascular hypertension caused by a dissecting aneurysm of the main right renal artery owing to a subadventitial angioma is described. The right kidney was not functioning but, nevertheless, an aortorenal bypass was done and function of the kidney was recovered. Although the hypertension was controlled for 6 months it recurred. A nephrectomy was performed and the hypertension was cured.


Parasitic arterial supply to renal angiomyolipoma. A case of a large renal angiomyolipoma in a relatively asymptomatic female subject without tuberous sclerosis is presented. The case demonstrates a parasitized blood supply from a lumbar artery and the superior mesenteric artery, in addition to the characteristic angiographic features that have been reported previously. A parasitized blood supply to renal masses has been considered previously to be associated with malignant processes. It is emphasized that parasitization of a blood supply by a renal mass lesion is not definite evidence of malignancy.


Disseminated mucormycosis with renal involvement. A case of fatal disseminated mucormycosis causing bilateral renal artery thrombosis, parenchymal and collecting system invasion and destruction, and extrinsic perirenal and proximal ureteral compression is presented. In addition to acute renal failure meningoencephalitis, cerebral hemorrhagic infarction and septic enterocolitis were contributing causes of death.


Segmental nephrogram.

Segmental nephrogram. An obstructive nephrogram involving the entire kidney owing to an acute ureteral obstruction is a well known phenomenon. A nephrogram occurring in half of the kidney (segmental nephrogram) has not been described previously. A patient who presented with acute left renal colic is described. An excretory urogram revealed a segmental nephrogram, which was subsequently found to be caused by acute calculous obstruction of 1 of the 2 limbs of a bifid pelvis. The stone was removed through a left pelviotomy.


Rapid increase in calculous size: a possible hazard of phenazopyridine hydrochloride therapy in the presence of already formed stones. Phenazopyridine hydrochloride is an effective oral urinary analgesic commonly used for the treatment of irritative lower urinary tract conditions. We believe that stones already present may serve as a nidus for significant deposition of phenazopyridine hydrochloride.


Volvulus of an ileal conduit with retroperitoneal urinoma in a child: first reported case. Ileal loop urinary diversion requires long-term followup. A case of an ileal conduit volvulus with a retroperitoneal urinoma 14 years after the initial procedure is reported. A brief discussion of long and short-term complications of ileal loops is presented.


Supravesical hematoma following suprapubic urine aspiration. A newborn undergoing evaluation and treatment for neonatal sepsis was found to have a pelvic mass. Exploration revealed a large supravesical hematoma thought to be secondary to prior suprapubic bladder aspiration.


Polyorchidism.

Polyorchidism. The thirty-seventh case of polyorchidism is reported. A complete compilation of all cases of this rare congenital anomaly, including a brief historical review of the more important ones, is presented for future reference.


Extraosseous multiple myeloma simulating primary prostatic neoplasm. The first case of multiple meyloma presenting clinically with extraskeletal prostatic involvement simulating a primary prostatic neoplasm is reported. The clinical course, pathology, and serum and urine protein findings are discussed.


Abdominal and genitourinary complications following ventriculoperitoneal shunts. Three patients with complications secondary to ventriculoperitoneal shunts for the management of hydrocephalus are described. Abdominal and genitourinary complications that may occur after the shunting procedure usually are owing to abnormal accumulation of cerebrospinal fluid or perforation by the shunting catheter tip.


The acid-base status of lions, Panthera leo, immobilized with four drug combinations. Fifty-eight immobilizations were conducted using 21 lions (Panthera leo) and 4 drug combinations. The combinations used were ketamine-phencyclidine-promazine, xylazine-phencyclidine-promazine, xylazine-ketamine-phencyclidine-promazine, and tiletamine-zolazepam.


The multiplication stages of Trypanosoma (Herpetosoma) xeri in the liver of the Sudanese ground squirrel Xerus (Euxerus) erythropus. Blood and organ smears from 24 of 98 ground squirrels (Xerus erythropus) from the Sudan were infected with a trypanosome resembling Trypanosoma (Herpetosoma) xeri. The developmental stages are described from the liver of one heavily infected ground squirrel. Multiplication was by binary fission and numerous triangular amastigotes, sphaeromastogotes and trypomastigotes were observed. A tentative development cycle in the final host is presented.


Some clinico-pathologic findings in elephants (Elephas maximus) infected with Fasciola jacksoni. Severe submandibular and ventral abdominal oedema was observed in an Asian elephant (Elephas maximus) in which liver flukes (Fasciola jacksoni) were recovered from the bile ducts at post-mortem examination. Clinico-pathologic examination of blood samples and serum from this elephant and another 8 elephants showed that most had anemia and hypoproteinemia. Fecal samples from 6 of the elephants contained from 6 to 83 eggs per gram. Treatment of elephants with nitroxynil (10 mg/kg) by subcutaneous injection produced severe local reactions at the injection site. Feces collected 2 and 4 months after treatment were free of trematode eggs. Hematologic values measured 4 months after treatment showed that the hemoglobin concentration, packed cell volume, erythrocyte count and plasma protein concentration had increased to within the normal range.


Clinical blood values of the northern fur seal, Callorhinus ursinus. II. Comparison of fresh versus stored frozen serum. Analysis of 14 blood components in fresh and stored (107-166 days) frozen serum of the northern fur seal (Callorhinus ursinus) revealed significant changes in the values of all but total protein, globulins, phosphorus and creatinine. While most values decreased during storage, cholesterol and bilirubin showed small but significant increases.


Case report of kidney disease in a wild chinock salmon, Oncorhynchus tshawytscha, in the sea. An immature chinook salmon (Oncorhynchus tshawytscha) that had spent two winters at sea was found in a Puget Sound beach zone. Necropsy indicated the fish was infected with bacterial kidney disease (KD). This is the first report of KD from a wild fish in the marine environment.


Vascular damage caused by Cruorifilaria tuberocauda in the capybara (Hydrochoerus hydrochaeris). Infection with Cruorifilaria tuberocauda caused vascular damage in the kidneys, lungs and heart of the capybara (Hydrochoerus hydrochaeris). The most significant lesions observed were in the renal and pulmonary arteries. They consisted of villous endarteritis, intimal and medial hypertrophy of the vessel walls, and large rugose protuberances that encroached upon the lumen leading to pyramidal infarcts in the kidneys. Coronary vascular lesions were related to dead and calcified parasites.


Bacteria induced shell disease of lobsters (Homarus americanus). Chitin degrading species of bacteria in the genera Pseudomonas, Vibrio, and Beneckea were cultured from the lesions of lobsters (Homarus americanus) with a shell disease. A species of bacterium of the genus Vibrio (Beneckea) produced necrosis characteristics of shell disease in experimental lobsters when the integument had been damaged prior to inoculation.


Laboratory observations on the insusceptibility of raccoons to Dirofilaria immitis. Two raccoons, Procyon lotor, were exposed to Dirofilaria immitis by subcutaneous injection of infective third stage larvae obtained from experimentally-infected Aedes trivittatus. Nematodes were not recovered from either raccoon when examined at necropsy 223 and 254 days postexposure. Large numbers of adult D. immitis were found in six dogs used as controls. These data indicate that raccoons cannot support the development of D. immitis.


Coccidia of whooping cranes.

Coccidia of whooping cranes. Coccidial oocysts were observed in 6 of 19 fecal samples from free-ranging whooping cranes (Grus americana) and 4 of 16 samples from captive whooping cranes. Eimeria gruis occurred in four free-ranging whooping cranes and E. reichenowi in two free-ranging and two captive whooping cranes. Fecal samples from two captive cranes contained oocysts of Isospora lacazei which was considered a spurious parasite. Oocysts of both species of Eimeria were prevalent in fecal samples collected from three free-ranging Canadian sandhill cranes (G. canadensis rowani) from whooping crane wintering grounds in Texas. These coccidia were prevalent also in fecal samples from 14 sandhill cranes (of 4 subspecies) maintained in captivity at the Patuxent Wildlife Research Center in Maryland.


Vulnerability of bot fly (Cuterebra) infected Peromyscus maniculatus to shorttail weasel predation in the laboratory. In the laboratory, Peromyscus bearing a single Cuterebra larva are no more vulnerable to weasel predation than are uninfected control mice, and may be taken less often under certain conditions. Mice bearing two or more larvae appear to be more vulnerable than either controls or singly infected mice. Their increased vulnerability probably results from their failure to use arboreal pathways. Decreased activity may be responsible for the relative advantage of singly infected mice. Previous reports of higher survivorship among mice  with a single bot parasite than among uninfected mice, and of lower survivorship among multiply infected mice, may result in part from differential predation rates.


Degenerative cardiomyopathy in a captive kangaroo (Macropus giganteus). Myocardial degeneration and necrosis in an adult female Australian kangaroo (Macropus giganteus) are described. The animal was housed in a zoo at Kano, Nigeria for approximately five years before death. This is believed to be the first reported case of degenerative cardiomyopathy in a captive marsupial in Nigeria.


Bot fly myiasis of the cottontail rabbit, Sylvilagus floridanus mallurus in Virginia with some biology of the parasite, Cuterebra buccata. Twenty four percent of 2,643 cottontail rabbits (Sylvilagus floridanus) collected in Virginia from 1949-1975 showed evidence of Cuterebra parasitism. Occurrence was seasonal with greatest prevalence from July to November. Some Oryctolagus cuniculus, S. palustris and one S. transitionalis also showed Cuterebra myiasis. Juvenile rabbits had higher infection rates (28%) than did adult rabbits 14.5%, P less than .001). Juveniles had greater numbers of larvae per host than adults, with means of 2.14 and 1.62, respectively. Larval development sites were in the genital region of most hosts. Twenty flies reared from wild cottontails were identified as C. buccata. Duration of induced infections in Oryctalagus was 30-33 days. Minimal generation time for C. buccata is concluded to be 11 weeks, allowing up to four generations of flies to occur annually in the southern and one generation to occur in the northern distributional limits of this bot fly. Peromyscus hosts were refractory to C. buccata infections. C. buccata fecundity averaged 1316 eggs. Field observations of adult flies are described.


Blood parasites of some birds from Senegal. A total of 809 birds from Senegal, including 43 species and 21 families, were examined for hematozoans; 93 birds (11.5%) harbored blood parasites, with only 7 (7.5%) harboring mixed infections. Species of Haemoproteus occurred in 81.7% of the infected birds while species of Plasmodium. Trypanosoma, microfilaria and Leucocytozoon were encountered less frequently. The majority of the sample was composed of species of ploceids and estrildidis and blood parasites were most prevalent in the colonial-nesting ploceids. Prevalence of blood parasites in Senegal was low in comparison to that seen in birds from other parts of Africa.


Hematologic comparisons of shot and live trapped cottontail rabbits. Comparisons were made between hematologic measurements of shot and box-trapped cottontail rabbits (Sylvilagus floridanus). Trapped rabbits had significantly (P less than 0.001) higher serum corticoid levels and segmented neutrophil percentages and significantly (P less than 0.001) lower lymphocyte percentages than did shot rabbits. Trapped rabbits also had significantly (P less than 0.05) higher packed cell volumes and blood urea nitrogen values than did shot rabbits.


Prevalence of meningeal worm (Parelaphostrongylus tenuis) in white-tailed deer from New Hampshire. Parelaphostrongylus tenuis was found in 79 (62.2%) of 127 white-tailed deer heads (Odocoileus virginianus) collected in New Hampshire. Prevalence of infection was higher in fawns and male deer, but older female deer (5.0 + years) had a higher intensity of infection (3.1) than any other age or sex class. Male deer in forest cover type 2 (northern hardwoods-hemlock-white pine) had a significantly greater prevalence of infection than the females in the same habitat (P less than .05). Adult females had a higher prevalence of infection (67.0%) than female fawns (20%) in forest cover type 1 (spruce-fir-northern hardwoods). In the craniums examined, P. tenuis was found most frequently in the tentorium cerebelli (23.6%) while the falx cerebri, the most prevalent site of infection in fawns, was a significantly less frequent site of infection in older deer (P less than .02). Male deer of age class 3.5 years had a significantly higher rate of infection in the dura mater-olfactory lobe than any other age or sex group (P less than .02). The cavernous sinus was the most frequent site of parasitism in male fawns (25.0%) and was the second most common location in all deer (13.4%).


Ecto- and endoparasites of the black bear in northern Wisconsin. Parasites collected from free-ranging black bears, Ursus americanus, in northern Wisconsin included Dermacentor variabilis, D. albipictus, Ixodes scapularis, Demodex sp., Trichodectes pinguis euarctidos, Baylisascaris transfuga and Dirofilaria ursi. Mange, possibly caused by the Demodex sp., also was observed. Dental caries were common and periodontal disease was observed in one animal.


Detoxification of 1,024 alcoholic patients without psychoactive drugs. Most community-referred, ambulatory chronic alcoholics can be detoxified quickly and safety without the use of psychoactive drugs, according to our data. We believe such detoxification can be done most efficiently in a social setting, with the aid of a staff who will provide reassurance and reality orientation and who will monitor the patients' vital signs, general condition, and any specific problems.


Patient-physician negotiation.

Patient-physician negotiation. The low level of patient compliance with physician management regimens is widely recognized. Although numerous studies either have measured levels of noncompliance or have attempted to fathom the essential elements of patient-physician interaction, they do not indicate how complicance may be increased. Negotiation is a process by which two active and equal participants negotiate to obtain their respective goals (which are often at odds). Without appropriate negotiation, which requires the patient's active participation, the physician cannot hope to motivate the patient. Patients will continue to be noncompliant as long as they are treated as inferiors in the process.


Psoriatic spondylitis. Association with advanced nongranulomatous upper lobe pulmonary fibrosis. We describe the case of a patient with psoriasis, peripheral and axial arthropathy, and upper lobe fibrosis. This association of findings has not, to the best of our knowledge, been described in the past. Pulmonary fibrosis is not found to be more common in people with psoriasis than would be expected in a control Veterans Administration population and, while this association may be coincidental, pulmonary fibrosis in psoriatic spondylitis should be searched for in other patients.


Patient participation in a hypertension control program. Hypertension Detection and Follow-up Program Cooperative Group. In the Hypertension Detection and Follow-up Program, the largest standardized hypertension detection, follow-up, and treatment program to date in the United States, participation rates have been high at all stages. More than 75% of those with suspected hypertension at screening attended follow-up rescreening, and more than 80% of the 5,314 hypertensive patients assigned to program treatment remained active at the end of one year. Differences in participation rates were generally small. To accomplish this, intensive efforts were required to maximize attendance, and the program was shaped to reduce known barriers to initial attendance and long-term adherence. Against the background of a high overall program response rate for all sex-race groups, factors that might be associated with variations in response were examined: age, socioeconomic characteristics, health status, and appointment schedule.


Retinal hemorrhages in subacute carbon monoxide poisoning. Exposures in homes with blocked furnace flues. Three incidences of carbon monoxide poisoning occurred owing to defective heating systems. Twelve persons were affected; of these, three lost their lives. Because the symptoms of carbon monoxide poisoning closely resemble flu and other common illnesses, correct diagnosis was not made as promptly as it might have been. Hemorrhages were found in the nerve fiber layer of the retina in all five of the patients who had been exposed for more than 12 hours. It is our contention, therefore, that complete examination of the patient should always include ohthalmoscopy, and that the finding of retinal hemorrhages, in addition to nausea, headache, and dizziness, should aler the physician to the possibility of carbon monoxide poisoning.


International comparison of prevalence of resistance to antibiotics. Prevalence of bacterial resistance to antibiotics was found to be substantially different in two separate regions of the world. The average percent resistant to individual antibiotics was nearly three times greater, and the percent of isolates resistant to six or more antibiotics 14 times greater among isolates at the Hôpital St Joseph in Paris than among those at the Peter Bent Brigham Hospital in Boston or at any of six US hospitals. Differences were not due to culture sampling or susceptibility testing methods used in the hospitals. Differences were nearly as great between isolates from patients recently admitted to the two hospitals, suggesting differences in the bacterial flora of their communities. Similar systematic comparisons of resistance prevalence in different parts of the world might help to define optimal antibiotic usage practices.


Mycobacterium gordonae infection of a prosthetic aortic valve. A patient prviously suspected of having a mycobacterial infection was found to have a Mycobacterium gordonae infection of his prosthetic aortic valve. Following replacement of his infected prosthesis and systemic therapy for two years, the patient has apparently been cured.


Retroperitoneal bleeding hemodialysis patients. A cause for morbidity and mortality. Retroperitoneal bleeding in hemodialysis patients has been rearely reported. The diagnosis of this entity in the nondialysis patient is difficult, and factors such as chronic anemia and hypotensive episodes during hemodialysis are adding difficulty to the early diagnosis and therapeutic approach. A patient receiving long-term hemodialysis anticoagulation therapy had retroperitoneal bleeding and died without having his condition diagnosed: the retroperitoneal bleeding was masked by other events occurring during hemodialysis.


Contemporary use of the disease concept. Six measures were used to assay the degree to which physicians endorsed the disease concept in their practice of ambulatory medicine. For each measure, two series of data were generated: one for patients receiving antihypertensive medication and one for patients receiving psychotropic medication. The disease concept was endorsed by only four of six measures for the patients receiving antihypertensive medication, and it was not endorsed by any of the six measures when patients receiving psychotropic medications were studied. Within the limits of this study, it is concluded that the disease concept is not generally endorsed by physicians.


Estriol in the management of the menopause. Estriol was administered for a six-month period as estrogen replacement therapy to 52 symptomatic postmenopausal women. Assays of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone, and estradiol were performed before and during therapy. During this period of administration, vaginal cytology, cervical mucus, and endometrial studies were performed. Clinical effectiveness was directly related to dosage (2 to 8 mg/day). Estriol (8 mg/day) failed to induce endometrial proliferation and proved a poor suppressor of FSH and LH. This agent's capacity to relieve vasomotor instability and improve vaginal maturation without notable side effects is sufficient reason to include this drug in the management of the postmenopausal syndrome.


M-mode ultrasonic localization of pleural effusion. Use in patients with nondiagnostic physical and roentgenographic examinations. Fifty patients had nondiagnostic physical and roentgenographic examinations and were believed at high risk for exploratory thoracentesis. Negative echograms for pleural fluid were recorded for 13 patients. For 34 patients, the characteristic M-mode display of a central echo-free space, indicative of pleural fluid, was recorded. Aspiration yielded fluid that was localized by echography in 30 (88%). Of the 30 patients, 13 (43%) had normal lateral decubitus views, and 10 (33%) had experienced unsuccessful aspiration before ultrasound localized the fluid loculation. The remaining seven patients, including three receiving mechanical ventilation who were believed to have increased risk for thoracentesis had successful initial tap based on echographic localization of fluid. Ultrasound allows detection and localization of pleural fluid when roentgenographic and physical diagnostic means are not helpful.


Childhood trachoma in a nonendemic area. Danish trachoma patients and their close contacts, 1963 to 1973. During ten years of study of Chlamydia trachomatis eye infections, trachoma was diagnosed in 14 Danish patients with onset during childhood. Clinical findings in the eye were characteristic of classical trachoma. The infecting C trachomatis immunotype was identified in all but one case. At the time of diagnosis, seven patients were still children (6 to 10 years of age), three were teenagers, and four were adults. In five young girls the disease was extremely severe. Delay in proper diagnosis and adequate therapy contributed to the prolongation and severity of the disease. Failure to diagnose is attributed to widespread opinion and teaching of physicians in Western countries that trachoma eye disease has disappeared. Studies of family members and other contacts of the patients contributed to an understanding of the pathogenesis of this disease. The source of initial eye infection with C trachomatis organisms in these cases was thought to be the birth canal. It was further postulated that reinfection of the eyes of these children occurred either from a reservoir in their own or their mother's genital tract.


Conversion of external arteriovenous hemodialysis shunt to internal fistula. The preservation of arteriovenous (AV) access site is important to long-term survival of patient's requiring maintenance hemodialysis life-support therapy. Patients with chronic renal failure and uremia who are not suited for immediate application of a subcutaneous AV fistula or arteriovenous graft and who require an initial Teflon-Silastic AV shunt to initiate urgent hemodialysis need not lose these vessels when the AV shunt is removed. After venous maturation, these patients should have a subcutaneous AV fistula created from the uninfected, unclotted shunt before infection or clotting would cause loss of these vessels.


Pathogenesis and treatment of angina pectoris at rest as seen from its response to various drugs. To twenty six patients with angina at rest (including 13 patients with Prinzmetal's variant angina), propranolol 40--50 mg, dilitiazem 60--90 mg, dipyridamole 50 mg, atropine sulfate 0.6 mg and phenoxybenzamine 10--20 mg were given at 9:00 p.m. and 2:00 a.m. (except phenoxybenzamine which was given only at 9:00 p.m.) to examine the effect of these drugs on the attack. Propranolol was not only ineffective in suppressing the attack but rather tended to aggravate it in all the cases of Prinzmetal's variant angina. It was effective to some degree in 5 of 13 cases of angina at rest other than Prinzmetal's variant angina. Diltiazem suppressed the attack completely and dramatically in all the cases of angina at rest (including Prinzmetal's variant angina). Dipyridamole was ineffective in all the cases except one in suppressing the attack. Atropine sulfate and phenoxybenzamine suppressed the attack in 13 of 21 cases and in 6 of 12 cases respectively. Coronary arteriography was done before and after the intravenous administration of 10 mg of diltiazem in 8 patients and it was demonstrated that diltiazem dilates large coronary arteries in all these patients. It is concluded that diltiazem, a calcium antagonistic drug, is specifically effective in suppressing the attack of angina at rest by dilating large coronary arteries and that the autonomic nervous system plays a role in the genesis of the attack probably by constricting large coronary arteries by way of alpha adrenergic receptors.


Left ventricular performance in various heart diseases with or without heart failure:--an appraisal by quantitative one-plane cineangiocardiography. Quantitative one-plane cineangiocardiography in right anterior oblique position for evaluation of LV performance was carried out in 62 patients with various heart diseases and in 13 subjects with normal LV. Parameters for evaluating both pump and muscle performances were derived from volume and pressure measurements. Of 31 patients with either systolic hypertension or LV myocardial diseases (coronary artery disease or idiopathic cardiomyopathy), 14 had clinical evidence of LV failure before the study. It was found that mean VCF and  EF were most sensitive indicators of impaired LV performance among the various parameters. There was a close correlation between mean VCF and EF, yet discordant changes of both parameters were noted in some patients. Furthermore, wall motion abnormalities were not infrequently observed in patients with coronary artery disease or primary cardiomyopathy. Therefore, assessment of at least three ejection properties (EF, mean VCF and wall motion abnormalities) are considered to be essential for full understanding of derangement of LV function in heart disease. This is especially true of patients with coronary artery disease. LV behavior in relation to different pathological stresses or lesions, such as chronic pressure or volume load, myocardial disease and mitral stenosis, was also studied and possible cause of impaired LV myocardial function in mitral stenosis was discussed.


Significance of measurement of antihyaluronidase activity in rheumatic fever. In recent years, rheumatic fever seems to have decreased but rheumatic heart disease with latent onset appears to persist in similar frequency. Measurement of AH along with ASO is required in rheumatic heart disease with latent onset, for more definite diagnosis, therapy and suggestion for the mode of living. For the diagnosis of rheumatic fever in acute stage, serological reactions for hemolytic streptococcus other than ASO should be done along with ASO. In our cases, ASO titer was high in 84.5% of cases, but either ASO or AH titer was elevated indicating positive reaction for hemolytic streptococcus in 100% of cases.


Cellular immunity in rheumatic heart disease. Cellular immunity to non-specific antigens (PPD, Candida albicans, and streptococcal antigens) and mitogen (PHA) was investigated in patients with valvular heart disease of rheumatic origin. The result disclosed that lowered response in cellular immunity exists in these patients. The possible significance of this finding in occurrence of rheumatic activity was discussed.


Experimental Coxsackie virus B-3 and B-4 myocarditis in mice. Mice were inoculated with recently isolated Coxsackie virus B-3 and B-4 intraperitoneally. Severest lesions in the hearts were observed in mice between the age of 7 and 14 days. Grossly yellow-white patches were seen on the hearts of mice from the 7th day to the 6th month after virus inoculation. Microscopically, the heart showed extensive myocardial necrosis, inflammation with small mononuclear cells and calcification on the day of 7. There were myocardial fibrosis and calcification at the 6th month after inoculation with Coxsackie virus B-3, and at the 3rd month after inoculation with Coxsackie virus B-4, but generally pathologic changes were less severe in the latter. Myocardial fibrosis in the present experiment was most prominent among the experiments we have studied. It was confirmed that chronic myocardial fibrosis follows acute Coxsackie virus myocarditis in mice. Possible role of Coxsackie virus myocarditis in the development of cardiomyopathy was briefly discussed.


Trial of a new cardiac mass screening system in school children: use of portable computer system for heart sound and electrocardiogram--a preliminary report. A portable system for heart screening in school children is deviced and the results of a trial of this machine were reported. This computerized system analyses electrocardiogram and phonocardiogram of school children within two minutes, print out the abnormal codes and simultaneously record the electrocardiogram and phonocardiogram by the visicoder. This system was tried for the primary heart screening in 1,618 pupils and for the secondary heart screening in 372 students. The results were considered to be satisfactory as a primary as well as a secondary heart screening system from the view points of the reliability, the economical condition and the time-saving of the pediatric cardiologist.


[Experimental and clinical study of WPW syndrome--detection of preexcitation site through the use of body surface maps (author's transl)]. The purpose of this experimental and clinical study was to evaluate the utility of body surface maps in detecting the preexcitation site of WPW syndrome. By using the electrical bypass tract, the electrocardiographic patterns of WPW syndrome were simulated by the fusion beat between pre- and normal excitation of the in situ canine ventricle. A comparison was made between the body surface and the epicardial maps of the same fusion beat. Throughout the ventricular activation serial body surface maps represented well the activation sequence on the epicardium. The following three points seem to be important for the detection of the preexcitation site of WPW syndrome through the use of body surface maps; 1) the location of the initial minimum, 2) the time of appearance of the voltage concavity (or the saddle) in the right anterior chest wall (in posterior preexcitation), 3) and in addition, the sequential changes in the pattern of positive and negative areas throughout the ventricular activation. In clinical use, body surface maps also localized well the preexcitation sites of the patients with WPW syndrome who underwent the operation.


Rhabdomyolysis and acute renal failure.

Rhabdomyolysis and acute renal failure. Three cases of rhabdomyolysis, two with acute renal failure, seen in a short period of time in an emergency department illustrate this increasingly recognized entity. Myoglobinuria may result from muscle trauma, ischemia, metabolic causes, drug-induced injury or intrinsic muscle disorders. The diagnosis is easily made by the presence of an elevated creatine phosphokinase, positive orthotoluidine in the urine and pigmented urine casts. Failure to diagnose rhabdomyolysis early will result in increased morbility and mortality from subsequent hyperkalemia, acute renal failure and hypocalcemia. These three cases illustrate the difficulty in predicting the eventual degree of renal failure from the initial assessment.


The MAST suit in the treatment of cardiogenic shock. Based on initial success using the medical antishock trouser (MAST) suit in treating 150 patients in traumatic, hypovolemic shock in the city of Bellingham and Whatcom County, Washington, at St. Luke's Hospital, the indications for its use have been expanded to include certain types of cardiogenic shock. The rationale was based on the frequent inability to differentiate hypo-, hyper-, and normovolemia in patients in cardiogenic shock and the need for a safe, reversible fluid challenge to differentiate these conditions. Changes in the condition of 14 patients in cardiogenic shock after application of the MAST suit were evaluated. Six patients responded with improved cardiac output and blood pressure. Four had no significant change in their condition and four became worse. In all patients whose condition was unchanged or worsened, the fluid challenge was reversed by deflating the suit. Based on these preliminary findings, it would seem that extended indications exist for using the MAST suit.


Medical control--what is it?

Medical control--what is it? Medical control is essentially divided into three phases: prospective, immediate and retrospective. Adequate medical supervision of any paramedic system is necessary to guarantee quality of medical care. Anything short of physician control of prehospital medical care would be to abdicate our responsibilities to our patients.


Treatment of common dog bites: infection risk factors. In a retrospective study of 106 patients with complete follow-up of dog bites treated in the emergency department the following factors greatly increased the risk of infection: age greater than 50 years, delay in seeking treatment, location on an upper extremity, and puncture wounds. Debridement and irrigation decreased the incidence of infection, and sutured wounds were not more likely to become infected than those left open. Prophylactic antibiotics provided no benefit in this series. In the literature, overall infection rates varied widely according to the various patient populations. Up to 50% of infections from dog bites are caused by pasturella multocida, and the remainder by a wide range of organisms, including streptococcus. Ninety-five percent of these organisms will be sensitive to penicillin.