Synthesis of two metabolites of (+)-propoxyphene.

Two minor metabolites of (+)-propoxyphene were prepared in both the (+/-) and (+) forms. The optically pure forms were synthesized by a degradative route from (+)-propoxyphene. The di-N-demethylated metabolite 10a,b had weak analgesic activity while the cyclized oxazine metabolite 7a was inactive.


Experimental antiulcer drugs. 2. 2-Substituted 2,4,5,6-tetrahydro-1,3,4,6,6-pentamethylcyclopenta[c]pyrrole-4-carboxamides.

Condensation of a 1-substituted 2,5-dimethylpyrrole 6 with 2 mol of 2-amino-2-methylpropionitrile in hot acetic acid yielded a 2-substituted 2,4,5,6-tetrahydro-1,3,4,5,6,6-pentamethylcyclopenta[c]pyrrole-4-carbonitrile (4). Hydrolysis of the nitriles to the amides gave a group of compounds which were active as antisecretory agents in the pyloric-ligated rat. Outstanding in this respect was the 2-phenyl derivative 5b, the most active compound in the series. It did not possess anticholinergic properties. In contrast to the indoles and pyrroles reported earlier, 5b demonstrated marked activity in blocking gastric acid secretion in the histamine-stimulated dog.


Hydrogen-bonding parameter and its significance in quantitative structure--activity studies.

When the relative hydrogen-bonding effect of drugs on phases involved in the binding at the site of biological action differs from that in the 1-octanol-H2O partitioning phases used as the reference to estimate the hydrophobicity, a parameter (or parameters) which represents the "extra" hydrogen-bonding effect on the biological activity is required in the Hansch-type correlations. As a first approximation, the effect is analyzed in terms of the ratio of hydrogen-bonding association constants and the ratio of molarities of hydrogen-bonding species constituting the biological and organic phases. Sometimes, the association constants in both phases are so similar that they are not important in determining the extra hydrogen-bonding effect. The net result is that the effect is expressible by an indicator variable term the slope of which corresponds to the molarity ratio. The variable only applies to substituents having appreciable association capability in correlating a certain biological action exhibited by a series of congeners.


Structure--activity relationships in cephalosporins prepared from penicillins. 1. 7beta-Acylamino derivatives of 3-benzyl- and 3-(3-pyridylmethyl)ceph-3-em-4-carboxylic acids.

tert-Butyl 7beta-aminoceph-3-em-4-carboxylates carrying either benzyl or 3-pyridylmethyl substituents at position 3 have been prepared by a multistep modification of the penicillin nucleus. Acylation of either amine, followed by deprotection, gave a range of new cephalosporins. The relationship between structure and antibacterial activity is discussed. D-Phenylglycine proved to be a preferred side chain in both series.


Structure--activity relationships in cephalosporins prepared from penicillins. 2. Analogues of cephalexin substituted in the 3-methyl group.

A previously outlined general procedure for preparing various 3-substituted cephalosporins from the penicillin nucleus has been used, with modifications where required, to prepare a series of analogues of cephalexin with various substituents in the 3-methyl group. The 3-substituents most conducive to broad-spectrum antibacterial activity were 3-pyridylmethyl and m- or p-carboxybenzyl. The compounds were only poorly absorbed by the oral route in mice, but the 3-(carboxybenzyl) compounds gave more prolonged useful serum levels than the usual cephalosporins.


Potential steroidal antiestrogens.

A series of analogues of 17beta-estradiol has been synthesized and the compounds have been tested, using sucrose density gradient analysis, for their ability to compete with [6,7-3H]-17beta-estradiol for the estrogen-receptor protein from mouse uterine homogenates. Active compounds were also tested for antiuterotrophic activity in immature rats and/or mice. 3,17beta-Dihydroxy-6-phenylestra-1,3,5(10),6-tetraene (14) was the most active new compound in the in vitro test suppressing the binding of 17beta-estradiol by 34 and 87%, respectively, at molar ratios of 1 and 3.16. It was significantly more potent than the intermediate 6-oxoestradiol (4) which produced a 52% inhibition of binding at a molar ratio of 3.16. The thiosemicarbazone of 6-oxoestradiol (17) and the derived 3,17beta-dihydroxy-6-(2-imino-4-oxothiazolidinyl-1-imino)estra-1,3,5(10)-triene (19) produced, respectively, only 46 and 16% inhibition of binding at a molar ratio of 10. Introduction of a 1-methyl substituent into either 6-oxo or 6-phenyl compounds reduced affinity for the receptor significantly (compounds 5 and 15) and conversion of the 3-OH into a beta-dialkylaminoethoxy group virtually destroyed all binding activity (compounds 2, 6, 10, and 11). At a molar ratio of 10 compound 14 failed to suppress the uterine weight response of immature rats to 17beta-estradiol, whereas compound 15, at a molar ratio of 200, produced a significant increase in the uterine weight of immature rats but not of immature mice even at a molar ratio of 1000.


Stereochemical studies on medicinal agents. 23. Synthesis and biological evaluation of 6-amino derivatives of naloxone and naltrexone.

Epimeric 6-amino derivatives of naloxone and naltrexone have been synthesized and the configuration at the C-6 chiral center was determined from NMR studies. All of the derivatives possess narcotic antagonist activity in mice, with each of the 6beta epimers having greater potency than the corresponding 6alpha epimers. In vitro binding experiments indicate that the affinities of these epimers parallel thier in vivo potencies. Slight antinociceptic properties were observed with three of the four compounds. The naloxone derivatives 3a and 3b appear to be attractive candidates for investigation as long-acting narcotic antagonists in view of their fourfold greater duration of action relative to the other antagonists (1, 2, 4a, and 4b).


Isomers of erythro-5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril, a new bronchodilator.

The isomers of erythro-5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxycarbostyril (1), a new potent and beta2-selective bronchodilator, were synthesized by optical resolution of compound 1 and inversion of the erythro to the threo isomers. The isomers were tested for activities to inhibit histamine-induced bronchospasm and to increase the heart rate of anesthetized dogs. Racemic and (-)-erythro-1 showed potent and beta2-selective bronchodilater activities. Among the isomers, (-)-erythro-1 showed the highest activities and (+)-erythro-1 showed the lowest.


Potential antitumor agents. 23. 4'-(9-Acridinylamino)alkanesulfonanilide congeners bearing hydrophilic functionality.

From structure--anti-L1210 relationships developed earlier for the 4'-(9-acridinylamino)alkanesulfonanilides it was predicted that congeners bearing both lipophilic 3-acridine substituents and compensatory hydrophilic function(s), together providing an overall molecular lipophilic--hydrophilic balance close to optimum, should have augmented antitumor properties. The acceptability of a variety of hydrophilic functions, and optimum positioning of these, has now been investigated. A variety of sterically demanding, hydrophilic functions may be acceptably appended to the acridine 4(5) position suggesting considerable site bulk tolerance. A variant with both a lipophilic 3-acridine substituent (3-iodo) and a hydrophilic 5-(2,3-dihydroxypropoxy) function is markedly more active than previous examples in the early treated, intraperitoneally (ip) dosed, ip implanted L1210 system, the assay system employed in the structure--activity analyses. However, this latter compound, on ip administration, failed to significantly inhibit subcutaneously implanted L1210 whereas earlier variants, under the same conditions, provided significant tumor inhibition. In this drug series the observed order of relative drug effectiveness alters with changing site of tumor implantation.


Titanium as a metal for implantation. Part 1: physical properties.

The scientific basis for the use of titanium and its alloys in implant surgery is reviewed, including the structural metallurgy, mechanical properties, corrosion resistance and biocompatibility. The clinical application are discussed in relation to orthopaedic, oral, plastic and reconstructive and cardiovascular surgery.


Medical engineering education in Sweden with reference to other Nordic countries.

The education of biomedical engineers in Sweden is examined against the background [corrected] of the organisation of Swedish health care. The history of the introduction of engineers into medicine is briefly recounted, leading on to a description of the academic courses open to both undergraduate and graduate students and to a discussion of the status of biomedical engineering and of biomedical engineers within the health service. Future trends are suggested. The situation in other Nordic countries is also briefly discussed.


Current problems in the standardisation of medical electrical equipment.

The progress towards a coherent policy of international standardisation of electrical equipment used in medical practice is reviewed against the background to existing legislation in Western Europe. The work of the International Electrotechnical Commission and the implications of the EEC in this context are discussed, as well as the general philosophy of the safety of medical electrical equipment in relation to standardisation.


Radio pills: their use in monitoring back stress.

A system for the quantitative assessment of spinal stress during manual materials handling has been developed. This has been achieved using radio pressure pills and is applicable to both laboratroy and field use for establishing safe general handling procedures and defining safe maximum loads.


The proposed 16 amp plug and socket system in UK hospitals?

The 16 amp plug and socket system which has been proposed by the International Electrotechnical Commission as an international system is discussed with particular reference to its use in UK hospitals. The author concludes that in certain respects, particularly safety and routine servicing of equipment, the proposed system is inferior to the 13 amp fused plug system used at present in the UK.


Enterotoxicity of Aeromonas hydrophila.

Live cells and cell-free culture supernates of 50 strains of Aeromonas hydrophila isolated from diarrhoeic and healthy human faeces, drinking water, sewage, the river Ganges and faeces from domestic animals caused accumulation of fluid in ligated ileal loops of adult rabbits. The amount of fluid produced was comparable to that of a toxigenic strain of Vibrio cholerae. Three of the strains gave positive reactions only after two passages in ileal loops of rabbits. Inocula of about 10(3) viable cells and 0-25 ml of culture supernate caused fluid accumulation in the loops. The enterotoxic factor was inactivated at 60 degrees C for 20 min. and 65 degrees C for 10 min., was precipitated with ammonium sulphate and was non-dialysable; these results indicate the protein nature of the enterotoxin. An inoculum of 40 microgram of crude toxin caused as much fluid accumulation as larger inocula. The only histopathological change in the loops was depletion of mucus from the goblet cells.


Electrical parameters in gallbladders of different species. Their contribution to the origin of the transmural potential difference.

Amphotericin B enhances Na+ conductance of the mucosal membrane of gallbladder epithelial cells and in such a way it modifies the brush border electromotive force. On this basis a method to measure cell and shunt resistances by comparing changes of the mucosal membrane potential (Vm) and of the transmural p.d. (Vms) is developed. This method is applied in gallbladders of different vertebrate species (i.e. rabbit, guinea pig, goose, tortoise, toad, trout). The two tested mammals, rabbit and guinea pig, exhibited a lower shunting percentage (89--93%) than the nonmammals (96--97%), but this fact did not bring about a homogeneous positive Vms. This means that shunting percent contributes, but it is not the only source of differences in Vms, in accordance with that reported by Gelarden and Rose (J. Membrane Biol. 19:37, 1974). Moreover, mammals exhibited a lower luminal resistance and a lower ratio between luminal and basolateral resistance than nonmammals. Possible causes of these differences are discussed.


The molecular configuration of inulin: implications for ultrafiltration theory and glomerular permeability.

A space-filling model of the inulin molecule, based solely on physico-chemical data in the literature, indicates that the gross shape of the solvated molecule is a cylinder having semi-length 25 A and radius 10 A. The axial dimensions of this model very nearly equal the equivalent estimates (25 and 10.5 A) previously determined by studying restricted passage of inulin through artificial membranes of known pore size (E. Middleton, J. Membrane Biol. 20:347, 1975). The good agreement between these independent in-vitro studies--neither of which depends on ultrafiltration theory--strongly suggests that glomerular pore size is considerably greater than predicted by the theory.


Oscillations of membrane potential in L cells. I. Basic characteristics.

The membrane potentials and resistances of L cells were measured using a standard electrophysiological technique. The values obtained in physiological media were around--15 mV and 37Momega, respectively. Almost all the large nondividing L cells (giant L cells) showed spontaneous oscillations of the membrane potential between around -15 and -40 mV. Application of an appropriate electrical or mechanical stimulus was also capable of eliciting responses but such were usually induced only once. The total membrane conductance increased significantly and in parallel with such a hyperpolarizing response. Cooling of the cells and application of metabolic inhibitors to the cells completely blocked the spontaneous oscillation despite the fact that the electrically induced hyperpolarizing response remained. Intracellular K+, Na+ and Cl- concentrations were measured by means of a flame photometer and a chloridometer, and the equilibrium potential for each ion was estimated.


Noradrenaline induced secretion of nonelectrolytes through frog skin.

Addition of noradrenaline (4 x 10(-5) M) to the inner bathing fluid in the skin of the frog Rana esculenta results in increased unidirectional fluxes of urea, thiourea, N-methyl-thiourea, N-N'-dimethylthiourea and mannitol. Fluxes towards the external medium (phi o) undergo a much greater increase than those moving the opposite direction (phi i). The effect of noradrenaline on phi o is higher for urea and thiourea than mannitol, while its effect on phi o thiourea derivatives is related to lipid solubility. This phenomenon does not occur for phi i of the same molecules. FCCP (10(-6) M) pretreatment strongly inhibits the noradrenaline effect on phi o. In skin pretreated with colchicine (2 x 10(-5) M) both urea fluxes are increased to the same extent by noradrenaline. Noradrenaline is concluded to exert two separate effects: (1) a change in permeability in both directions; (2) a secretion of nonelectrolytes towards the external fluid. Such secretion is most probably associated with the hormone-induced secretion of fluid and electrolytes, perhaps mediated by an exocytotic mechanism.


The structure of the salivary glands of the human soft palate.

The glandular layer constitutes the greatest bulk of the human soft palate and is composed of individual compound tubulo-acinar salivary glands. Connective tissue partitions of the submucosa divide the glandular layer into lobules of irregular shapes and sizes. The glands are interwoven and bound firmly together by a connective tissue stroma rich in elastic fibers. The secretory units consist of elongated, branched, and sometimes convoluted tubules lined by a single layer of pyramidal mucous cells. Mucous secretion by acini is supplemented to some degree by mucous acinar cells, which were found as epithelial components of all ducts except the main excretory ducts, suggesting a diffuse distribution of progenitor cells. Some mucous acini communicate with highly convoluted intercalated ducts which occupy partially isolated positions within inter- and intralobular connective tissue septa. These ducts follow the connective tissue septa and eventually join the main duct system. The significance of this system of intercalated ducts is not known. A supplemental functional role is hypothesized.


Tooth replacement in the teleost fish Prionurus microlepidotus Lacépède.

Previous studies on tooth replacement in lower vertebrates have been plagued by a lack of common integrative approaches and methods making it impossible to furnish a phylogenetic synthesis. This study is based on serial sections of the jaw of Prionurus microlepidotus. Each Toothgerm was characterized by its developmental stage and its position in the jaw. The relationship between the developmental stage of toothgerm and position in the jaw has been studied and expressed in several graphical illustrations. The following conclusions have been made: (1) The initiation of toothgerms in P. microlepidotus is governed by two Zahnreihen, which respectively initiate toothgerms on the lingual and labial side of the functioning teeth in an alternating pattern. (2) Therefore, functioning teeth in one locus are supplied by the alternate eruption of lingual and lubial toothgerms. (3) Advancing of tooth replacement in each locus is independent of functioning teeth and their successors in adjacent loci. (4) The disorders of replacement patterns are caused by an alternated rate of eruption of successive toothgerms as a response to unusual shedding of the functioning teeth.


Ovarian structure of the marsupial frog Gastrotheca riobambae (Fowler).

The mature ovary of Gastrotheca riobambae presents large oocytes (3 mm in diameter) of pale yellow color. After ovulation and the beginning of embryonic incubation, the empty postovulatory follicles can be recognized in the ovary for about 30 days. The granulosa of these follicles never fills the follicular lumen and this cavity becomes filled with fluid during the first five days of incubation. Later, at 18 days of incubation, the lumen is mostly empty and contains few cells of the granulosa. Shrinkage results in the disappearance of the follicular cavity by approximately the thirtieth day of incubation. The thecae are thick and become separated by a space. This space is filled progressively with cells, blood capillaries and fluid. After the thirtieth to fortieth day of incubation, these follicles become regressive and disappear. The postovulatory follicles of Gastrotheca may correspond to corpora lutea. The evidence suggests that pouch vascularization and the formation of embryonic chambers of pouch tissue may be under ovarian control. In addition, the process of vitellogenesis is influenced by incubation, as most growth of the ovarian oocyte occurs after birth of the tadpoles. Follicular atresia is common and is similar to that of other frogs.


Cytoplasmic bridges within the follicular epithelium of the ovarioles of two diptera, Aedes aegypti and Stomoxys calcitrans.

The cells of the follicular epithelium of the ovarioles of the mosquito, Aedes aegypti (L.), and of the stable fly, Stomoxys calcitrans (L.), have been found to be interconnected by cytoplasmic bridges. Cytoplasmic bridges have been reported between sibling gamete cells of both male and female insects, but these bridges have not been previously reported to exist between somatic cells of insects.


The craniocaudal extent of the glycogen body in the domestic chicken.

All birds have a glial enclosed, glycogen-containing structure in the lumbosacral region of their spinal cords. Recently, a dorsal, central, glycogen-rich area surrounding the central canal in the brachial spinal cord was described in domestic chickens. In order to topographically delineate and histochemically describe this structure, fresh, frozen serial sections of chicken brains and spinal cords were processed for glycogen content, phosphorylase, succinic dehydrogenase and cholinesterase activities. The glycogen-rich area surrounding the central canal in the lumbosacral region is found at all levels of the spinal cord and lower medulla. In the upper medulla, it is located in the medline floor immediately ventral to the ependyma. It persists in this position until the level of the oculomotor complex where it ends. Phosphorylase positive regions closely parallel the glycogen distribution. No succinic dehydrogenase or cholinesterase activities are found in these areas.


Histophysiological studies on the corpus allatum during prepupal diapause in Monema flavescens (Lepidoptera).

The appearance of the corpus allatum, the central endocrine gland of diapause, was examined histologically in the slug moth prepupae, Monema flavescens (Lepidoptera). Before beginning of diapause, the secretory cells of the corpus allatum increase in size with the enrichment of the cytoplasm in quantity and in number of orgenelles, while RNA synthesis also starts. As diapause progresses, the secretory cells have many large unstained vacuoles in the cytoplasm, which were demonstrated to contain some substances of lipoidal nature. It is not clear that the substance is juvenile hormone itself or a material related to juvenile hormone. Agranular ER is the most characteristic organelle connected with mitochondria and situated around the vacuoles during diapause. Electron micrographs show that agranular ER and mitochondria have an essential role for the production of juvenile hormone. The function of the corpus allatum during diapause and the relationship between juvenile hormone and diapause are discussed.


Arrangement and structure of sinus hair muscles in the big-clawed shrew, Sorex unguiculatus.

The arrangement and structure of sinus hair muscles in the snout of the shrew, Sorex unguiculatus, were studied by electron microscopy and serial section light microscopy. Both striated and smooth muscles are directly associated with sinus hair follicles. The striated muscle fibers originate from the base of a follicle and insert onto the superficial portion of adjoining caudally positioned follicles. Some fibers insert into the corium instead of inserting into a follicle. The fibers show a fine structure typical of red fibers. Smooth muscle cells form a network with elastic fibers beneath the corium. Some cells are directly attached to the capsule of the sinus, thus forming a type of M. arrector pili. Striated muscle febers that appear to end in the corium are connected with the smooth muscle network through the elastic fibers which appear to function as the tendon of these two types of muscle cell.


Structure of the sinus hair follicle in the big-clawed shrew, Sorex unguiculatus.

The structural features of sinus hair follicles in Sorex unguiculatus were studied by macroscopic dissection, serial section light microscopy and electron microscopy. The shrew has about 540 sinus hairs regularly arranged on the snout. The maxillary nerves innervating them are extremely thick, while the optic nerves are very thin. Thus the follicle must be one of the most important sense organs in this animal. In the follicle the ring sinus is well-development and the trabeculae of the cavernous sinus are reduced in number and thickness. The ring bulge is not a unified structure but a pair of bodies which consist of head, stalk and attachment plaque. It is characterized by the presence of numerous thick collagen fibrils (400 nm) and appears to be mechanically rigid. Lanceolate nerve terminals, free endings, Merkel cells with nerve terminals and unmyelinated fibers are observed, but encapsulated endings are lacking in and aound the follicles. Straight lanceolate terminals on the posterior side of the follicle are thick and three-sided in cross section, while those on the anterior side are thin and two-sided. Free endings are located on the anterior side of the follicle. These and other findings are discussed on the basis of the assumption that the Sorex sinus hair follicle is more specialized as a vibrating system than in other mammals.


Simulation results with stepwise mutation model and their interpretations.

Monte Carlo simulations are performed to compare the predictions based on the two presently used theoretical models for studying genetic variations in natural populations, the infinite allele model and the stepwise mutation model. Distribution of heterozygosity is noticed to be similar under these models until the product of population size and mutation rate is large. It is seen that electromorphs with high population frequency usually contain older allels (at the codon level) than an electromorph of low population frequency. The interpretations of these results in explaining the allelic variations at electrophoretic level is also discussed.


Recognition of phylogenetic relationships from polypeptide chain fold similarities.

Structural similarities between proteins with no amino acid sequence homology either indicate a phylogenetic relationship, or they are merely the expression of a physically preferred way of folding a polypeptide chain. It is shown that one can distinguish between these alternatives by evaluating the "significance of the similarity". Such significances have been derived for comparison between chain folds containing beta-pleated sheets (Schulz and Schirmer, 1974; Richardson et al., 1976; Sternberg and Thornton, 1976). An extension of this method to comparisons between any two chain folds is outlined here.


Primitive haemoglobin.

The sequences of Petromyzon and Aplysia globins are compared with the postulated vertebrate and mollusc-vertebrate ancestors to see if differences exist in the rates of evolution of different types of residue positions. Between the mollusc-vertebrate ancestor and Aplysia globin there is no very striking pattern of changes except that the interior positions are relatively conserved. In the evolution of Petromyzon haemoglobin, the alpha 1 beta 2 contact area is relatively conserved. The homopolymeric binding of lamprey Hb seems to be a primitive function.


Orthologous nature of mammalian insulin genes.

Investigation of 17 insulin sequences from a bony fish, a bird, and 5 mammalian species showed that guinea pig and coypu insulin, that have a strongly divergent primary and quarternary structure, are not the result of gene duplication in an ancient vertebrate or invertebrate ancestor but they they diverged from the other mammals after divergence of the mammals from the other vertebrates. After this divergence both insulins underwent evolution at a highly increased rate.


Homology of functionally diverse proteins.

Disulphide-rich proteins of widely differing functions were aligned with the aid of their half-cystinyl residues. This led to the grouping of ribonuclease, phospholipase A, lysozyme, snake venom toxins, bee and scorpion venom peptides, and the plant proteins potatoe carboxypeptidase inhibitor, ragweed pollen allergen, mistletoe toxins and pineapple sulfhydryl protease inhibitor into one super-family of proteins. Very few deletions/insertions were needed to effect alignment and probabilities were calculated for random occurrence of the matches that were found.


A comment on methanogenic bacteria and the primitive ecology.

The phenotype and antiquity of methanogenic bacteria suggest them to have been one of the major factors determining a dynamic balance between CO2 and CH4 in the primitive atmosphere.


Comparative chromosome study of normal mammary tissue, carcinogen-induced mammary tumors, and hyperplastic alveolar nodules in the rat: Brief communication.

The chromosome constituents of 101 normal mammary gland cells, 122 hyperplastic alveolar nodule (HAN) cells, and 360 cells from eleven 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in the WF rat were examined. Both mammary gland and HAN had normal diploid karyotype patterns, whereas mammary tumors showed frequent (approximately 30%) abnormalities, e.g., aneuploidy, pseudodiploidy, polyploidy, and structural aberrations such as breakage and translocation. These results suggested that chromosome constituents of HAN cells are essentially the same as those of the normal mammary epithelial cells.


Chronic toxicity of methotrexate in rats: partial to complete projection of the liver by choline: Brief communication.

Methotrexate (MTX) inhibits the enzyme dihydrofolate reductase, which in turn limits the body's ability to perform transmethylation reactions. This study examined the hypothesis that the consequent deficiency of an important methylated compound, choline, may have contributed to the MTX-induced fatty change in the liver of W rats. Groups of rats were given MTX alone or MTX plus choline in varying dose combinations. All groups but one receiving the combined treatment showed a significantly lower triglyceride concentration in their livers and much less visible hepatocytic fat on histologic examination than did those given MTX alone. The protective effect of choline on the liver was dose related, the unaffected group having received a very small amount. Growth rate, survival, and hematopoietic depression due to MTX were unaltered by choline administration.


Effect of immunomodulators on effector cells involved in antibody-dependent cellular cytotoxicity: Brief communication.

The effect of four immunomodulators (BCG, Corynebacterium parvum, pyran copolymer, and levamisole) on the cellular arm of antibody-dependent cellular cytotoxicity (ADCC) was investigated in mice with 51Cr-labeled chicken erythrocytes employed as targets. All these drugs, except levamisole, stimulated the effector cells of ADCC in the spleen, but the kinetics of their effect differed. Stimulation of the effector cells of ADCC peaked on day 15 after injection of BCG and C. parvum and on day 7 after injection of pyran, which was less efficient in this respect than the two bacterial immunostimulants. The increase in ADCC activity caused by BCG and C. parvum was eliminated by treatment with carbonyl iron of the  splenocyte suspensions.


Prevention by splenectomy of thymus weight depletion in the presence of progressively growing tumor in rats: Brief communication.

Groups of inbred rats were inoculated with the Walker 256 carcinosarcoma. The weights of their spleens and thymuses were determined on days 16 and 23 after the tumor inoculation. Spleen weights increased progressively as the tumors grew (P less than 0.001 on day 16 as compared to controls, much less on day 23). Thymus weights decreased at the same intervals (P less than 0.05 on day 16 as compared to controls; P less than 0.001 on day 23). In other groups of inbred rats, splenectomy was performed 5 days prior to tumor inoculation. If splenectomized animals were not inoculated with tumor, thymus weight did not change. Previously splenectomized, tumor-bearing animals also showed no decrease in thymus weight on day 16 or 23. Thymus weight remained greater in splenectomized, tumor-bearing animals than in intact, tumor-bearing animals on day 16 (P less than 0.05) and on day 23 (P less than 0.001). Microscopic examination of thymuses on day 23 revealed some depletion of cortical lymphocytes in splenectomized, tumor-bearing animals and profound depletion of these lymphocytes in intact, tumor-bearing animals. Tumor weights and measurements did not differ between splenectomized, tumor-bearing and intact, tumor-bearing animals. Equal rates of tumor growth provided for a roughly equal tumor burden at termination of the experiment.


Breast neoplasms in women treated with x-rays for acute postpartum mastitis.

Breast cancer has been studied by mail survey up to 34 years in 571 of 606 women treated with x-rays for acute postpartum mastitis. The incidence of neoplasms was compared with that of three nonirradiated control groups--nonirradiated sisters of the treated women, women with acute postpartum mastitis not treated with X-rays, and their nonirradiated sisters. For the irradiated group, with mean dose of 247 rads to both breasts, the overall relative risk of breast cancer was 2.2 for years 10-34 post irradiation and 3.6 for years 20-34. The dose response for malignant and benign breast neoplasms was compatible with a linear fit. For comparable total doses, fractionation of exposure did not reduce carcinogenic action. Women over age 30 years at radiation treatment had as great an excess risk of breast cancer as did younger women. The overall excess risk of developing breast cancer was about 8-10 cases per million women per rad per year, an increase of about 0.5% per rad.


Fetal rat keratinizing epidermal cells in culture: effects of long-term treatment by benzo[a]pyrene on their growth characteristics.

After serial 20-minute trypsinization, skin from near-term fetal MRC rats was separated into epidermis attached to basal lamina and dermis with trapped hair follicles. Fragmentation of the basal lamina by trypsinization caused the epidermal basal cell layer to form cell clumps of various sizes, whereas dermal mesenchymal cells dissociated into single cells, leaving a fibrous network with hair follicles. Clumps of eopdermal basal cells were then isolated with few contaminating hair follicles. At 30-32.5 degrees C, a cornification process caused the clumps to form thickened sheets of nearly pure keratinizing epidermal cells, which were isolated in petri dishes and grew to fill the dishes. The mode of cell differentiation in these sheets resembled an in vivo cornification process; the sheets showed maximum growth at 30 degrees C and failed to survive at 35 degrees C or above. Benzo[a]pyrene (BP) treatment accelerated the growth of cell sheets and enabled them to adapt to 35 and 37.5 degrees C. Keratinizing epidermal cells treated with BP at 35 and 37.5 degrees C were serially subcultured at these temperatures and lost their original dependence on lower temperatures for growth. The cell sheets were still capable of in vitro keratinization; however, some qualitative and quantitative changes were observed.


In vitro studies of chemical mutagens and carcinogens. I. Stability studies in cell culture medium.

A quantitative microbial assay was used to study the stability of known mutagenic and carcinogenic compounds in cell culture medium. Ten direct-acting carcinogens, when incubated in culture medium with 15% fetal bovine serum at pH 7.2-7.4 and 37 degrees C, became inactive at varying rates. Biologic half-lives of the test compounds ranged from 8 minutes to 67 hours. In contrast, six procarcinogens showed no significant inactivation after 3 weeks' incubation. The biologic half-lives of each compound were presented, and the significance of these findings as they relate to cell culture carcinogenesis and mutagenesis assays was discussed.


Altered erythrocyte osmotic fragility in mice with Ehrlich ascites tumor.

The osmotic fragility of erythrocytes from mice with Ehrlich ascites tumor was compared with that of erythrocytes from normal control animals. Erythrocytes collected from mice 15 days after the ip injection of tumor cells exhibited a uniform pattern of abnormal resistance to hemolysis in hypotonic saline, with 50% hemolysis occurring at an average saline concentration of 0.44% compared to an average of 0.49% for 11 controls a significant difference (P less than 0.0001). Erythrocytes from mice with this tumor apparently undergo an alteration in some component of the cell membrane that regulates either permeability to cations and water or distensibility of the cell.


Controvesial aspects of blunt renal trauma.

Eighty-five cases of blunt renal trauma evaluated radiographically at our institution were reviewed. Thirty-eight patients had normal urograms; 47 demonstrated one or more of the following urographic findings: poor visualization, extravasation, intrarenal hematoma, perirenal hematoma, and kidney rupture. Nineteen arteriograms and twelve renal explorations were performed. Three explorations were negative; two were followed by repair of a laceration, three by nephrectomy, and four by heminephrectomy. A review of the factors of influencing the choice of surgical treatment and of the results obtained in patients who did not undergo surgery supports the recommendation of conservative management for stable patient. In the absence of clinical deterioration, neither the presence of extravasation nor the demonstration of renal fracture is an adequate indication for surgery. Angiography is useful to further document and classify renal injuries but is unnecessary for the conservative management of the stable patient. When surgery is contemplated, angiography is useful for surgical planning and for the exclusion of injury to adjacent structures, but it should not supplant clinical judgment in determining whether surgery is necessary.


The renal factor in the post-traumatic "fluid overload" syndrome.

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.


The deep perineal laceration-an injury frequently associated with open pelvic fractures: a need for aggressive surgical management. A report of 12 cases and review of the literature.

The deep perineal laceration indicates major pelvic injury, especially when associated with pelvic fracture. Survival requires hemostasis, which must be established early by whatever means necessary, including emergency hemipelvectomy if required. Twelve patients with deep perineal laceration are reviewed. Seven patients died. Early deaths were caused by uncontrolled hemorrhage. Late deaths were related to infection in the pelvis. Prompt totally diverting colostomy with irrigation and disimpaction of the defunctionalized rectum and primary repair of urethral injuries are essentials in avoiding septic complications. A technique of rapid totally diverting colostomy that facilitates distal washouts without wound contamination is described.


Shock and acute respiratory failure after chest trauma.

Shock or acute respiratory failure developing soon after chest trauma are associated with extremely high mortality and morbidity rates. In a study of 1,136 patients with chest trauma admitted to Detroit General Hospital during a 2-year period (1974-1975), it was found that 218 (19%) had shock or acute respiratory failure when first seen in the Emergency Department. Of these patients, 36% (78/218) died and the survivors had a complication rate of 63% (88/140). Shock was associated with a mortality rate of 7.3% (7/96) but the combination of shock and respiratory failure was particularly lethal, with a mortality rate of 73.1% (57/78)overall. No patient over 45 years of age survived this combination. Efforts to improve results following chest trauma must be directed toward earlier and more aggressive management of both these problems


A new limulus assay for the detection of endotoxin.

The limulus amebocyte lysate (LAL) assay has proven to be a highly sensitive and reliable indicator of endotoxin in most biological fluids; however, it has not been a reliable indicator when used with blood because of different inhibitors present in the blood. To avoid these problems, investigators have used difficult extraction procedures, but but even with these, results were oftentimes not uniform. It was found that a recently developed inert polymer (PSI-HAP 100) has a specific affinity for endotoxin, so that is was possible to develop a simple, reliable, reproducible method for the detection of endotoxin in blood. In the assay procedure, the polymer, compressed into a 3-mm diameter bead, is incubated with 0.2 cc of heparinized whole blood. The bead is then removed from the blood, washed in pyrogen-free saline to remove any inhibitors of the LAL, and placed in a tube containing LAL. The LAL and bead are incubated together; after incubation the LAL is examined for gellation. Using this new method, it was possible to predict Gram-negative septic episodes in burn patients several days before sepsis evolved clinically.


Pneumatic trousers and the management of shock.

Forty-seven patients were brought to the Emergency Department with a good blood pressure which probably would not have existed without the use of MAST Trousers. Most important, not one patient who survived the operation and immediate postoperative period developed adult respiratory distress syndrome or acute renal failure. It is our belief that prevention of prolonged hypotension in the prehospital period was a major factor in achieving this result.


Pancreatoduodenectomy for penetrating pancreatic trauma.

Six cases of pancreatoduodenectomy performed for combined injuries of the pancreas, duodenum, and/or distal common duct are reported. Pancreatoduodenectomy is indicated when there is extensive destruction of the pancreatic head in conjunction with major injuries of the duodenum, distal common duct, and/or retropancreatic portal vein, necessitating complete division of the pancreatic head. Reconstruction is best achieved by end-to-end pancreatiocieiunostomy, end-to-side choledochojejunostomy, antrectomy, and vagotomy.


Weight, height and triceps skindfold in South African black, Indian and White School pupils of 18 years.

In representative series of Sout African Black, Indian and White High School pupils of 18 years, data were secured on weight, height and triceps skinfold. Values among Black boys were significantly lower than those among White boys. Yet, obesity was far commoner among Black compared with White girls. Among Indian pupils, there were no significant differences in mean anthropometric values between groups relatively affluent and relatively poor. Values on Indian boys were similar to those of Black boys, although the former were far more favourably placed socioeconomically. Indian girls, compared with Black girls, had highly significantly lower values for weight and skinfold thickness, but not for height. However, mean weight for height values for Black and Indian boys were similar to values for White boys. Weight for height values for Indian girls were similar to data for White girls, although values on these two ethnic groups were significantly lower than those for Black girls. Findings question the insistence by many (i) of the need to attain maximum potential growth, and (ii) apart from extreme wasting and stunting, of the need to conform to international growth standards.


The importance of spinal anaesthesia in surgical practice in tropical Africa.

Any medical officer or surgeon who intends to practice in tropical or young developing countries must be proficient in the use of local and spinal anaesthetics because of severe shortage of anesthetists and anesthetic machines. We have presented 95 cases operated on by us in three "peripheral" hospitals in the Western State of Nigeria. These cases included gastrectomy; cholecystectomy, vagectomy and pyloroplasty and splenectomy. We have also presented our method of administering spinal anaesthetics and of preventing major complication of cardiac arrest. We have reviewed briefly the physiology and complication of spinal anaesthesia.


Onchocerciasis in Nigeria: observations on the geographical basis of the endemicity in Lagos.

Ninety-five patients suffering from onchocerciasis in Lagos, Nigeria have been presented. The majority were young adults with no ocular complications suggesting the Rain Forest type of African onchocerciasis. Geographical distribution shows that the majority came from endemic foci outside Lagos. The case finding of five patients from Lagos State and in particular two from Lagos City suggests an endemicity of onchocerciasis in Lagos. Furthermore this observation emphasizes a need for prevalence studies of onchocerciasis in this area. The public health importance of this disease is briefly discussed.


Laryngocele--an updated review.

This communication reviews the clinical and pathological features of 121 cases of laryngocele reported in the English literature and the authors experience with 10 cases. A case of an infected laryngocele presenting with airway obstruction and one of an external laryngocele associated with laryngeal cancer are described in detail. An instance of bilateral congenitally long saccules is also presented, and the role of this anomaly in the pathogenesis of laryngoceles is discussed.


Surgical technique--the strap muscle flap.

The authors describe the use of the infrahyoid ("strap") muscles as a muscle transposition flap to obliterate the "dead space" created during resection of the anterior floor of the mouth for carcinoma concomitant with suprahyoid neck dissection or radical neck dissection. The flap is particularly useful if the mandible is partially resected and immediately stabilized with a steel pin or bolt.


Juvenile epithelial malignancy of head and neck.

Children aged 15 years or less usually suffer from mesenchymal malignancies. Observations on four rare cases of juvenile epithelial malignancy in larynx, maxillary antrum, upper lip, and parotid are reported. No particular etiological factor could be found in these cases. Age, as such, had no effect on the clinical presentation of the malignancy, its management and prognosis.


Benign rhabdomyoma of the submandibular region.

A case of benign rhabdomyoma is presented, and the pathology is discussed with reference to its differential diagnosis. The literature is reviewed and the common features of the tumor are described.


Non-hayfever aspects of allergy in otolaryngology.

The importance of the diagnosis and treatment of non-hayfever atopy in the practice of otorhinolaryngology is emphasized. The clinical evaluation primarily includes a thorough history, physical examination, x-rays, routine laboratory work, screening allergen tests, and a selective allergic survey using the Rinkel technique of titration. A multilateral approach to treatment is essential, but specific immunotherapy is of prime importance. A case report illustrating a practical approach to the diagnosis and management of a typical allergic problem seen by the otolaryngologist is included.


Actinomycosis of the parotid. Is it usually a masticator space infection?

Three cases of Actinomycosis involving the facial region are presented with a discussion of the problems which can be encountered in the diagnosis and localization of this infectious disease.


Surgery of the nasal tip.

Three techniques for nasal tip surgery, preserving intact caudal strips of lower lateral cartilage around the nostril rim, are presented.


Progress in vestibular analysis in Omagh.

To sum up, rotational testing forms a valuable role in our system of vestibular analysis. It does not replace history taking, clinical examination, and other vestibular tests, but it does supplement them and in particular it does supplement the caloric test which by itself has many limitations.


Comprehensive presentation of semicircular canal sensitivity.

It is generally agreed that in order to determine any difference in vestibular sensitivity between the two inner ears, the best clinical procedure involves a quantitative expression of the slow phase nystagmus response to standardized caloric (or rotatory) stimulation. The preferred procedure has involved averaging the slopes of a few of the nystagmus responses during the period of most intense activity and this has been accomplished either arithmetically or by means of an electronic computer. Although, such a sampling is often sufficient to enable a reliable diagnosis, occasions do arise when the results can be misleading unless comprehensive total presentations of the responses from the two labyrinths are available for reliable comparative evaluation. Such a procedure has been developed at the University of Toronto and used for clinical assessment at St. Michael's Hospital. The reliability of the method has been established as the result of testing over 800 patients with various vestibular disorders.


Thrombosis of the lateral sinus.

Four cases of lateral sinus thrombosis have been treated at Notre-Dame Hospital, Montreal, since 1960. A review of the literature of this pathology is reported, and two cases treated in the past three months are presented.


Indications for and technique of endaural and post auricular incisions.

The indications for and techniques of tympanotomy, endaural incisions, and post auricular incisions are described. There are specific indications for the use of each approach and the otologist should modify his approach depending upon the disease process and the anatomical variations. Specific points in technique are presented which simplify the procedure and prevent complications.


Changes in macromolecular synthesis in Xanthomonas oryzae infected with bacteriophage XP-12.

Phage XP-12, which has complete substitution of the cytosine residues in its DNA with 5-methylcytosine residues, was shown to inhibit incorporation of uracil into host DNA and RNA during the latent period. This apparent inhibition of host macromolecular synthesis was not accompanied by extensive degradation of the host chromosome. Phage DNA synthesis in infected cells occurred at a faster rate than host DNA synthesis in analogous uninfected cells. However, phage DNA synthesis could not be accurately monitored by incorporation of [methyl-3H]thymidine into DNA because, soon after infection, there was a marked inhibition of utilization of exogenous thymidine for DNA synthesis. Phage infection conferred upon a thymine auxotrophic host the ability to synthesize thymine nucleotides for phage DNA synthesis. It is suggested that a phage-induced thymidylate synthetase activity is partially responsible for the inhibition of thymidine incorporation.


Transcriptional complexity of vaccinia virus in vivo and in vitro.

The transcriptional complexity of vaccinia virus both in vivo and in vitro has been measured by using DNA:RNA hybridization with RNA in excess. In vivo, "early" or prereplicative RNA was found to saturate at 25% or one-half of the viral genome. "Late" or postreplicative RNA from infected HeLa cells saturated at 52% or essentially the entire genome. This well-regulated transcriptional pattern of the virus in vivo was not maintained in vitro. In a number of experiments a range of saturation values from 40 to 50% was obtained for in vitro synthesized RNA. The complexity of polyadenylated and non-polyadenylated RNA, as well as total purified 8 to 12S RNA released from the virus, was indistinguishable from purified high-molecular-weight virion-associated RNA with a sedimentation value of greater than 20S and equivalent to total in vitro synthesized RNA. No additional hybrid formation was observed in experiments in which total in vitro RNA and late in vivo RNA from infected HeLa cells were combined, suggesting that the virus does not transcribe in vitro DNA sequences that are not also transcribed during productive infection. Approximately 15% complementary RNA was detected when radiolabeled total in vitro RNA was allowed to reanneal with late in vivo RNA, while as much as 8% of the in vitro synthesized RNA was found to be complementary.


Adenovirus type 2 early nuclear and mRNA: kinetic estimation of l anf r DNA strand fractions complementary to different abundance classes of viral RNA.

RNA from unfractionated cells, nuclei, and polyribosomes was extracted from adenovirus 2 (Ad2)-infected KB cells early in infection and annealed in vast excess in liquid to purified Ad2 l (heavy) and r (light) [(32)P]DNA strands (specific activity, 3 x 10(6) to 1.5 x 10(7) cpm/mug). The number of abundance classes of Ad2 RNA, their relative concentrations, and the strand fraction from which they arose were determined by a computer-assisted nonlinear regression analysis of hybridization kinetic data. Whole-cell RNA and nuclear RNA annealed to 60 and 40%, respectively, of l and r strands. Well-defined abundance (kinetic) classes were identified: abundant and scarce classes were complementary to 15 to 17 and 40 to 45%, respectively, of l strand, and to 11 to 16 and 17 to 23%, respectively, of r strand. In whole-cell RNA and nuclear RNA the abundant classes were 57 to 208 and 13 to 27 times more concentrated, respectively, than scarce classes. RNA-RNA hybrids were isolated that annealed to about 70% of both strands, indicating that whole-cell RNA and nuclear RNA hybridization values were minimal. Polyribosomal RNA appeared to anneal as three abundance classes to each DNA strand; abundant, scarce, and very scarce classes, respectively, hybridized to 6, 5, and about 10% of l strand and 7 (6 to 8), 10 (8 to 13), and about 19% of r strand. The abundant classes were 41 (11 to 67) times more concentrated than the scarce classes and 10(3) times more concentrated than the very scarce classes. Although the biological significance of these classes is not known, the very scarce classes probably represent nuclear RNA contaminants of polyribosomal RNA. The abundant and scarce classes may comprise mRNA, because together they are complementary to about the same fraction of each DNA strand (11% [10 to 12%] and 17% [14 to 20%] of l and r strands) known to be expressed as early mRNA. Thus, nuclear RNA contains Ad2 RNA sequences not found on polyribosomes; most or all of both DNA strands are transcribed, but only certain transcripts are processed into mRNA. It is not known whether "non-mRNA" transcripts are intermediates in the pathway of early mRNA production.


Bacteriophage T4 virion baseplate thymidylate synthetase and dihydrofolate reductase.

Additional evidence is presented that both the phage T4D-induced thymidylate synthetase (gp td) and the T4D-induced dihydrofolate reductase (gp frd) are baseplate structural components. With regard to phage td it has been found that: (i) low levels of thymidylate synthetase activity were present in highly purified preparations of T4D ghost particles produced after infection with td(+), whereas particles produced after infection with td(-) had no measurable enzymatic activity; (ii) a mutation of the T4D td gene from td(ts) to td(+) simultaneously produced a heat-stable thymidylate synthetase enzyme and heat-stable phage particles (it should be noted that the phage baseplate structure determines heat lability); (iii) a recombinant of two T4D mutants constructed containing both td(ts) and frd(ts) genes produced particles whose physical properties indicate that these two molecules physically interact in the baseplate. With regard to phage frd it has been found that two spontaneous revertants each of two different T4D frd(ts) mutants to frd(+) not only produced altered dihydrofolate reductases but also formed phage particles with heat sensitivities different from their parents. Properties of T4D particles produced after infection with parental T4D mutants presumed to have a deletion of the td gene and/or the frd gene indicate that these particles still retain some characteristics associated with the presence of both the td and the frd molecules. Furthermore, the particles produced by the deletion mutants have been found to be physically different from the parent particles.


Localization of single-chain interruptions in bacteriophage T5 DNA. II. Electrophoretic studies.

Upon denaturation, T5 DNA yields a large number of discrete, single-chain fragments that can be resolved by agarose gel electrophoresis. The positions of the more prominent of these fragments in the T5 duplex were determined by analyzing their sensitivity to digestion with lambda exonuclease and their distribution among EcoRI fragments of T5 DNA. These experiments also provide firm evidence concerning the polarity of the strands in T5 DNA. An analogous study was carried out on the fragments produced by treating exonuclease III-degraded T5 DNA with the single-strand-specific SI endonuclease. This procedure yielded over 40 discrete duplex fragments that could be resolved with considerable precision by agarose gel electrophoresis. The positions of most of these fragments were determined by analyzing EcoRI fragments of T5st(+) and T5st(0) DNA. Over 20 sites where single-chain interruptions can occur in T5 DNA were identified, and the distribution of interruptions within the terminal repetition was shown to be identical at both ends of the molecule. A precise value for the size of the terminal repetition in T5 DNA was obtained by analyzing SI endonuclease digests of ligase-repaired, circular T5 DNA in agarose gels. The repeated segment represented 8.3% of the T5st(+) DNA. The results of this study also provide information concerning the properties of lambda exonuclease. Hydrolysis by this enzyme was not terminated when single-chain interruptions were encountered either in the strand being degraded or in the complementary strand.


Common precursor for Rauscher leukemia virus gp69/71, p15(E), and p12(E).

Rauscher murine leukemia virus glycoprotein gp69/71 and non-glycosylated p15(E) are synthesized by way of a 90,000-dalton precursor glycoprotein, termed Pr2a+b. Peptide mapping experiments showed that Pr2a+b contains all the tyrosine-containing tryptic peptides of gp69/71. Two additional tyrosine-containing tryptic peptides in Pr2a+b that are not detected in gp69/71 are found in p15(E). Thus, gp69/71 and p15(E) peptide sequences account for all the tyrosine tryptic peptides of Pr2a+b. The gene order of the two proteins was determined by pulse-labeling infected cells in the presence and absence of pactamycin at concentrations of the inhibitor that prevent initiation of translation, but not elongation. The gene order was found to be: (2)HN-gp69/71-p15(E)-COOH. A newly identified major viral protein, termed p12(E), migrates in sodium dodecyl sulfate-polyacrylamide gels in the "p12" region. It is related to p15(E) as determined by tryptic mapping experiments. p15(E) and p12(E) are not phosphorylated, and both can be separated from phosphoprotein p12 by guanidine hydrochloride-agarose chromatography. p12(E) and p15(E) elute in the void volume fraction, whereas phosphoprotein p12 elutes between p15 and p10. The two p12 proteins can also be separated from each other by two-dimensional gel electrophoresis involving isoelectric focusing in the first dimension and sodium dodecyl sulfate-gel electrophoresis in the second dimension.


Malignant pheochromocytoma: clinical course and treatment.

We describe 7 patients with 16 malignant pheochromocytomas, with followup for 7 to 21 years. Five patients are free of disease at a mean of 13.5 years and 2 patients died of malignancy at 10 and 13 years. The 3 criteria believed important for a maximum tumor-free interval are: 1) adjunctive lymphadenectomy at the initial operation when 1 or more lymph nodes contain tumor, 2) close followup of all patients with pheochromocytoma by diagnostic biochemical assay for 15 years and 3) an aggressive excision of all single or multiple recurrent pheochromocytomas as soon as a biochemical diagnosis is established.


The changing clinicopathological pattern of abscesses in or adjacent to the kidney.

We reviewed retrospectively 43 patients with various renal and perirenal abscesses. In contrast to previously published data a primary renal etiology was noted for nearly every abscess in or adjacent to the kidney, irrespective of the type of abscess. Currently, the concept that the renal carbuncle is a metastatic abscess whose origin lies at some distant site may be applicable no longer. Despite earlier recognition of symptoms, improved diagnostic techniques and better therapy the morbidity and mortality of abscesses in and adjacent to the kidney remain high, suggesting the important role of associated medical conditions and the need for early aggressive therapy.


Adjuvant antimicrobial therapy with renal calculus surgery.

A randomized prospective study was done, comparing massive penicillin dosage (60 million units) to the recommended dose of ticarcillin (200 mg. per kg.) in the treatment of complicated urinary tract infections. A total of 50 patients with staghorn or multiple calculi who underwent anatrophic nephrolithotomy was entered into the study during a period of 14 months. Bacteriologic results were comparable. No significant toxicity from either massive penicillin or ticarcillin was observed.


Arteriography before needle puncture or renal hilar lesions.

We report on 2 patients with cystic-appearing lesions in the renal hilus that were detected on urography. In 1 case an ultrasound study confirmed a cystic mass but an arteriogram revealed a renal artery aneurysm. The arteriogram before the contemplated puncture of the renal hilar mass prevented an inadvertent puncture. The information about the arterial anatomy helped preoperative planning, which resulted in successful repair of the aneurysm by microdissection and autotransplantation.


Aggressive versus conservative management of stage IV renal cell carcinoma.

Improved modalities to treat metastatic renal cell carcinoma will require an aggressive surgical and chemotherapeutic approach. Nephrectomy with hormonal and non-hormonal chemotherapy does improve median survival and 3-year survival significantly. The use of xenogeneic specific immune ribonucleic acid and Bacillus Calmette-Guerin offers promising immunotherapeutic modalities that may be combined with surgical and chemotherapeutic regimens. Early diagnosis of metastatic disease is important to evaluate properly the results of various modalities of treatment and possibly to improve the efficiency of these modalities. The management of solitary metastatic nodules should involve aggressive resection of the primary and metastatic nodule. Adjuvant hormonal and non-hormonal chemotherapy should be considered in all stages of the disease.


Vesical-related paragangliomas.

A review is presented of vesical-related paragangliomas and 3 cases are reported. Methods for early diagnosis, including selective angiographic demonstration, and treatment of these rare tumors are discussed. A multi-team approach by the urologist, endocrinologist and anesthesiologist is stressed for better control of potentially dangerous vasomotor changes during diagnosis and surgical treatment of this tumor.


Three cases of human bladder cancer following high dose cyclamate ingestion.

Vesical implantation and oral feeding studies in animals raised sufficient suspicion of the carcinogenic propensity of cyclamates to result in their withdrawal from sale throughout the world. The structural similarity to known carcinogens, an effect on human chromosomes in tissue culture and a high carcinogenic potential when combined with non-injurious co-carcinogens gave further support to this ban. On the other hand, numerous epidemiological studies failed to support any statistical relationship between cyclamate ingestion and vesical carcinoma in man. Three patients are described in whom vesical carcinoma developed after a prolonged period of ingestion of an unusually high amount of cyclamate sweetener. Moreover, the severity of the disease appeared to be proportional to the dose ingested. Although this is not a conclusive indictment of the role of cyclamates we believe that patients with bladder cancer should be questioned about intake of cyclamates either directly or in diet soft drinks.


Cystectomy after radiotherapeutic ablation of invasive transitional cell cancer.

Of 282 patients with invasive bladder carcinoma treated by a combined protocol of preoperative irradiation and total or partial cystectomy 84 had no residual carcinoma in the surgical specimens. Of these 84 patients who have been at risk for 12 to 149 months 59 (70 per cent) are alive.


Obstruction of the male reproductive tract.

Anatomic obstruction of the male reproductive ducts may be congenital, inflammatory or iatrogenic in origin. Two cases of congenital obstruction and 1 case of iatrogenic obstruction are presented. Accurate identification of the etiology and location of the obstruction is necessary for patient counseling and choice of treatment.


Demonstration of the existence of canine prostatic lymphatics by radioisotope techniques.

Radioactive 198Au colloid injected into the canine prostate through an opened bladder to avoid violating the prostatic capsule was observed to migrate from the prostate to the regional lymph nodes. Significant isotope uptake in the kidney, liver, rectus muscle and distant lymph nodes was not detected, thus indicating direct spread of the isotope to the regional lymph nodes.


Prostatic adenocarcinoma: relationship of grade and local extent to the pattern of metastases.

In 100 consecutive cases of prostatic adenocarcinoma treated by pelvic lymphadenectomy and interstitial implantation of 125I the relationship of tumor stage, size and grade was analyzed relative to the incidence and site of metastases, and the response of the primary tumor to irradiation. High stage, large size and poor histological differentiation were associated with a significantly higher probability of pelvic node metastases. The response of the primary tumor to irradiation was significantly higher among patients with small stage B tumors and/or those with negative pelvic lymph nodes. Important determinants of metastases subsequent to 125I implantation were the large size of the primary tumor, poor histological differentiation, seminal vesicle invasion, large (more than 3 cc) volume of lymph node metastases and absence of local prostatic response to irradiation.


Prognosis of clinically undiagnosed prostatic carcinoma and the influence of endocrine therapy.

A 10-year series of 100 patients with clinically undiagnosed prostatic adenocarcinoma is presented. In 50 per cent of these patients the tumor was well differentiated and the survival was normal, while the remainder of the patients had moderately to poorly differentiated tumors and survival rates significantly less than normal. Of 8 deaths caused by cancer 7 were associated with less-than-well differentiated tumor. Patients who received endocrine therapy and died of causes other than cancer had a significantly shorter interval to death and a higher incidence of cardiovascular deaths than those who were untreated. While the majority of patients with incidental, clinically undiagnosed prostatic carcinoma is not at risk from the disease a minority exists who may benefit from radical therapy.


Treatment of the severe uninhibited neurogenic bladder by selective sacral rhizotomy.

Patients with severe uninhibited neurogenic bladders are marked with urinary frequency and incontinence of a debilitating nature. Seven patients not responding to various medical regimens were treated by selective sacral rhizotomy. The beneficial effects of the operation upon most of the patients are discussed.


The autonomic innervation of the human male and female bladder neck and proximal urethra.

Neurohistochemical and electron microscopic techniques have been used to determine the autonomic innervation of smooth muscle in the normal human male and female bladder neck and proximal urethra. Numerous cholinergic nerves supply the bladder neck and female proximal urethra, although nerves of the noradrenergic type rarely are observed in these regions. In contrast the male proximal urethra is supplied richly with noradrenergic nerves, indicating that the region is under direct sympathetic control and functions to prevent vesical reflux of ejaculate. The sympathetic innervation of the human bladder neck and female proximal urethra is different from that in other species, a finding that emphasizes the need for caution when results obtained from experimental animals are applied to the human. The sex difference is the innervation of the human proximal urethra has been discussed, particularly in relation to autonomic blocking agents currently used in the treatment of bladder neck and urethral dysfunction.


Multicystic dysplastic kidney.

We reviewed 29 cases of congenital multicystic dysplastic kidneys. Isolated renal pelvic atresia has an excellent prognosis but lower ureteral atresias are associated with a high incidence of contralateral renal disease and have a worse prognosis.


The value of the retrograde urethrogram in the diagnosis of anterior urethral valves.

There have been 14 cases of anterior urethral valves reported in the literature. The main diagnostic test in these cases has been voiding cystourethrography since retrograde urethrography is believed to be useless. Two additional cases of anterior urethral valves are presented to demonstrate the usefulness of the retrograde urethrogram as a valuable adjunctive diagnostic study.


The micropenis syndrome: clinical observations and expectations for growth.

We reviewed 34 genotypic male subjects with a true micropenis to determine the clinical situations in which micropenis is encountered and the types of therapy resulting in growth. The relationship of clinically functioning testicular tissue to growth is noted. Diagnostic modalities, including human chorionic gonadotropin stimulation, are discussed, as well as a plan for individual assessment and therapy.


Anuria secondary to balloon catheters in children.

Two unusual cases of balloon catheter-induced anuria are presented. Certain pediatric patients and neonates, especially those with spastic neurogenic bladders or those who have had bilateral ureteral reimplantation, are more susceptible to this form of urinary obstruction. The use of non-balloon catheters or infant feeding tubes is recommended.


Severe blunt trauma of upper urinary and intestinal tracts in a child.

A 7 1/2-year-old boy sustained severe trauma to the upper abdomen, including transection of the common bile duct, transection of the second part of the duodenum, contusion of the head of the pancreas, traumatic thrombosis of the left renal artery, thrombosis of the right lower pole renal vasculature and avulsion of the right renal pelvis. A staged elective repair of the upper urinary tract, and later the upper gastrointestinal tract, was accomplished when he was referred 5 1/2 months after the initial injury.


Renal carcinoma associated with polycystic kidneys: occurrence after chronic hematuria and hypertension.

A case of polycystic kidneys associated with renal cell carcinoma in a 62-year old man is described. The concept that hematuria in patients with polycystic disease should not give rise to suspicion of malignancy if hypertension is present is questioned.


Partial duplication of the male urethra.

A case of partial duplication of the male urethra (bifid urethra) is presented. This case is unusual because of the late presentation with incontinence, the normality of the primary urethra and the markedly lateral course of the accessory urethra. An anatomic and embryological classification is presented.


Urethral encirclement by sacrococcygeal teratoma.

Obstruction and neurogenic bladder involvement are common with sacroccygeal teratomas but external genital involvement is rare. A genetic (46XY) male infant required cystotomy, colostomy and sex-of-rearing change to enable surgical removal of a sacrococcygeal teratoma that surrounded the hypospadiac urethra and deviated the penis. An associated ventral congenital transposition of the scrotum allowed partial coverage of the defect. Renal and bladder manifestations secondary to sacrococcygeal teratomas commonly require urologic management.


Myxoid neurofibroma of the testis.

A case of an intratesticular myxoid neurofibroma is reported. These tumors, which arise from perineural and Schwann cells, commonly occur throughout the body but have not been reported previously to originate within the testis. The mucoid material within the tumor is translucent, which may confuse the diagnosis with that of a hydrocele.


Association of transverse testicular ectopia and seminal vesicle cyst.

The first case of simultaneous transverse testicular ectopia and a congenital seminal vesicle cyst is reported in a patient with coexistent upper urinary tract disorders. The literature relevant to these anomalies is reviewed and the rationale for complete urologic evaluation of the patient with a lower urinary tract anomaly is encouraged.


A unique combination of congenital genitourinary anomalies in a child.

A case of solitary crossed renal ectopia with concomitant, severe vesicoureteral reflux and a rudimentary ipsilateral ectopic ureter draining into the vas deferens is presented. In addition to these anomalies the patient had complete urethral duplication and right cryptorchidism, as well as right congenital dislocation of the hip. To our knowledge this is the first such case to be documented in the medical literature.


[The general pharmacological actions of KW-1062, a new aminoglycoside antibiotic (author's transl)].

The general pharmacological actions of KW-1062 were investigated in order to estimate the effects on the host animals. KW-1062 showed little or no effect on the central nervous system, cardiovascular system, smooth muscle, skeletal muscle, hemolysis, blood coagulation, dermal tissue permeability and antigenicity tests at high doses. KW-1062 showed urinative effect and ototoxicity. But ototoxicity of KW-1062 was less potent than that of gentamicin. KW-1062 has been proved to have a safety margin wider than that of other aminoglycoside antibiotics.


[Safety evaluation of KW-1062. III. Investigation of maximum safety dose on subacute toxicity studies in dogs (author's transl)].

In previous subacute toxicity studies by intramuscular administration carried out in Beagle dogs for 30 days, its maximum safety dose was not confirmed because renal tubular disorder was observed slightly at the dose of 25 mg/kg. Therefore subacute intramuscular toxicity studies were carried out again to investigate maximum safety dose using lower doses (4, 10 mg/kg). As the result of studies, the maximum safety dose was considered to be 10 mg/kg because there were no abnormal changes at both doses.


Measures of emergency ambulance effectiveness: unmet need and inappropriate use.

For Health Systems Agencies to fulfill their needs assessment and facility regulation functions under the National Health Planning and Resources Development Act of 1974 (PL 93-641), process measures are needed to evaluate the overall efficiency of an emergency ambulance system. In Erie County, New York, unmet ambulance need, defined as the proportion of emergency patients who clinically need ambulance transportation but do not receive it, was found to be 55%. Inappropriate ambulance use, defined as the proportion of emergency patients receiving ambulance care who did not clinically need it, was found to be 30%. These two measures were cross-tabulated with patient and visit characteristics to identify the determinants of unmet need and inappropriate use and to generate recommendations for system changes to reduce both types of ambulance ineffectiveness.


The Illinois Trauma System: changes in patient survival patterns following vehicular injuries.

To assess the impact of the Illinois Trauma Program on Region 5, Southern Illinois, samples of vehicular injuries and deaths were compared for a four-year study period: two years prior to system implementation (FY 1970-1971) and two years after system initiation (FY 1972-1973). Trauma center hospitals exhibited a statistically significant decrease in mortality rate during FY 1972-9173 while other hospitals (those in the region not designated as trauma centers) had no change in mortality rate. Decreases in mortality rates were statistically significant at trauma hospitals for weekends and patients between the ages of 45 and 64. The methodology of conducting such a study as well as the implications of the study are discussed.


Peritoneal lavage and scintigraphic evaluation of blunt abdominal trauma.

The emergency management of blunt abdominal trauma requires rapid assembly of accurate information. But history, physical findings and conventional tests may be unreliable. As a result, peritoneal lavage is an integral part of the initial diagnostic protocol in many centers. However, confusion in interpretation, especially of "weak positives," can result in delayed or unnecessary celiotomy. In our regional trauma center, lavage is now reserved for selected cases based on experience with 1,833 cases "scanned" during a five-year period. The indications, contraindications, techniques, interpretation, advantages, disadvantages, and complications of lavage and scanning are presented. A protocol using radionuclide imaging for initial evaluation of blunt abdominal trauma is proposed and representative case studies are included to support this approach.


The bacteriology of pneumococcal otitis media.

The bacteriologic findings of 1205 episodes of pneumococcal otitis media are analyzed. Capsular types 6, 14, 19 and 23 have been found to account for more than half the initial and subsequent infections of the middle ear. Initial infection has been shown to be related to age, and recurrent infection with pneumococci of heterologous capsular types has been found to occur most often within six months of the initial attack. Nasopharyngeal carriage of the pneumococcal types most frequently causing otitis media may occur without causing infection, may antedate infection by as long as 13 months and may persist after infection for as long as 30 months. Recurrence of infection with a given capsular type has been identified following intervening infection with one or more heterologous capsular types. Simultaneous infection of the middle ear with two pneumococcal capsular types has been observed in 1% of the infections studied. The potential, but as yet unestablished, value of prophylactic vaccination against pneumococcal otitis media is considered.


Renal vein renin activity: a prospective study of sampling techniques and methods of interpretation.

Seventy patients undergoing renal arteriography were studied prospectively to define optimal techniques of renal venous sampling and to establish the most appropriate methods for interpretation of renal vein renin and activity (RVRA). Plasma renin activity values from the aorta, the antecubital vein and the lower inferior vena cava were nearly identical. The relationship between renal vein renin activity in the two renal veins was not influenced by lack of simultaneous sampling or by contrast administration. Thirty-one patients with normal arteriograms had a mean RVRA ratio (right over left) of 1.12 +/- .11 (mean +/- SEM) but RVRA difference (right minus left) of only 0.02 +/- .11 ng/ml/hr. In contrast 16 patients with "significant" (greater than 70%) narrowing of the main renal artery had a mean RVRA ratio (involved over uninvolved) of 4.3 +/- 1.2 and a mean RVRA difference (involved minus uninvolved) of 3.9 +/- 1.4 ng/ml/hr. Seven patients (22%) with normal arteriograms had "abnormal" RVRA ratios (greater than or equal 1.5) but corresponding RVRA differences within one standard deviation of the group mean. Thus the difference inRVRA between both renal veins may more accurately reflect a patient's renovascular status than does the corresponding RVRA ratio. An "abnormal" RVRA ratio alone inadequately indicates the presence of renal ischemia.


Development and evaluation of a compliance test for patients taking disulfiram.

A breath test for carbon disulfide, a major excretion product of disulfiram, is described and evaluated. All breath excretions were standardized by collecting a fixed amount based on CO2 control. Excretion of CS2 falls rapidly (half life 8 to 18 hours), so that 20 to 30 hours following the last dose of disulfiram the test becomes negative. Approximately 300 tests in hospitalized patients taking disulfiram were positive; 40 tests in patients not taking this drug were negative. In an active disulfiram outpatient clinic more than one third of the patients who claimed to have taken disulfiram on the previous day had, as determined by this test, failed to do so. Of subjects judged by the professional staff to be almost certainly compliant 20% were not taking medication. Of the total of 52 patients tested in clinic only 25 were taking disulfiram.


Clinical course, management, and long-term sequelae of respiratory failure due to influenza viral pneumonia.

Eleven patients with severe influenza viral pneumonia were seen over a six-week interval. Five patients survived after prolonged respirator and oxygen therapy. Follow-up chest roentgenograms and pulmonary function testing one year after recovery showed development of diffuse pulmonary fibrosis in the four survivors reexamined.


Computerized calculation of platelet counts obtained with particle counters.

Three mathematical manipulations of raw data are necessary in order to use a small programmable calculator to compute platelt counts obtained with particle counters. Two of these manipulations use constant parameters and are easily incorporated into programmable calculators, which are in use in many laboratories. The third is a correction fro the excess concentration of platelets in supernatant plasma that results from sedimentation of red cells; it requires a large table of correction factors. This table often exceeds the storage capability of programmable calculators, and mathematical approximation is necessary. Two methods for close approximation of the table were developed by using a cosine function and a third order polynomial function of the hematocrit value.


The perils of medical education.

Medicine and medical education have always faced the uncomfortable necessity of making decisions on the basis of incomplete information. In recent years far more intense social pressures have been added. Some of these are technical and theoretically can be solved logically, for example, equitable financing of medical care and education. However, some of the pressures have their roots in a more general malaise, the loss of philosophical faith and trust in our institutions. The task of the medical educator is to encourage rational changes, but to resist irrational ones. Medicine at its best is in itself for those in this and related professions, at least, a partial response to the abiding human need to feel fulfillment in an altruistic cause.


[Activity of enzymes controlling adenosine metabolism in ischemic heart disease].

It is shown that patients with acute myocardial infarction and with chronic coronary insufficiency present an elevated 5'-nucleotidase and adenosine-desaminase activity. In clinically healthy persons examined after a physical exercise test the activity of 5'-nucleotidase and adenosine-desaminase declines. In most patients with chronic coronary insufficiency an increased activity of enzymes responsible for the metabolism of adenosine, above all of 5'-nucleotidase, is registered after a graded physical exertion test.


[Early diagnosis of cardiac insufficiency in patients with ischemic heart disease and hypertension in medical jurisprudence].

Results of a study into the myocardium function in 440 patients with ischemic heart and hypertensive diseases are presented. In the study poly-kineto-apex-cardiography, rheography of the aorta and lungs, ultrasonic cardiography at rest in 123 of 440 patients were used after veloergometric loading. The application of the mentioned methods in conjunction with the veloergometric test helped diagnose a latent cardiac insufficiency that proved most frequent among patients with myocardial infarction in their past history (84.5%) and among those suffering from hypertensive disease with prevalence of the cardiac syndrome. An inference is drawn on the need for a complex investigation of patients at the clinic and especially in the practice of the medical expert testimony on the work capacity.


[Diagnosis and clinical course of occlusive lesions of the main trunk of the left coronary artery].

A total of 50 patients with the left coronary artery trunk stenosed by more than 50 per cent were examined. General clinical methods, ECG under physical efforts and selective coronarography were employed. According to the authors this amounts to 6.4% of all corronarographically investigated patients. A comparison of the results derived from these investigations furnished fairly reliable clinical signs suggesting the existence of the stenosed trunk prior to coronarography. The authors feel that a preliminary diagnosis of such a lesion dictates an urgent coronarography. A careful and reserved approach to the investigation and a number of modifications in the procedure used by the authors are factors substantially diminishing the risk of this investigation.


[State of the contractile apparatus of myocardial cells in ischemic injury].

Micrometric studies of the sarcomeres of myocytes in the zone of experimentally induced myocardial ischaemia in rats, histological, polarization-microscopic and micrometric studies of the myocardial cells in the zone of infarction in dead humans and model experiments with fixation of distended papillary muscles demonstrated that relaxation of the sarcomeres is characteristic of the myocardial cells damaged by ischaemia. This sign indicating the loss of the contractile function in the injured cells develops in early ischaemia when other histological changes typical for the ischaemic lesions are absent. The percentage of relaxed and distended sarcomeres changes with the increasing duration of ischaemia, and therefore it can be used as an indirect index of the term of ischaemia and, consequently, as a criterion of the irreversibility of the ischaemic lesion of the myocardium.


[Assessment of coronary/blood flow according to the indicators of the pressure-time ratio].

The results of heart catheterization in 116 patients with different heart diseases, ischaemic lesions and arterial hypertension were processed. The diastolic pressure-time index characterizes the main part of the coronary flow, while the systomic pressure-time index of the corresponding ventricle--the myocardial requirements in the blood supply. The ratio of these indices corresponds to the demand/supply ratio. In normals, for the left ventricle it comprises 0.75+/-0.07; for both ventricles--0.95+/-0.07. This ratio grow in cases of ventricular hyperfunction and myocardial ischaemia.


[Characteristics of hemodynamics of the lesser circulation in chronic pneumonia according to ergometric data].

Rheopneumographic examinations were conducted in 54 patients with chronic pneumonia (stage I and II pulmonary insufficiency) prior to and following exercise tests. It was demonstrated that in normal individuals physical exercises cause a compensatory increase of the pulmonary blood flow without elevating the pressure in the pulmonary circulation system. The progression of pulmonary insufficiency is accompanied by a reduction of the adaptation capacity of the heart, of the pulmonary vessels, by an increase of pulmonary hypertension, and impairment of the contractile function of the right ventricular myocardium. The severity of changes in the pulmonary system haemodynamics, as shown by rheopneumography, correlates with the disorders in the oxygen regimen (oxygen consumption and oxygen pulse).


[Differential diagnosis of ischemic heart disease and cardialgia by means of pharmacological tests in the polyclinical practice].

The possibility of differential diagnosis of ischemic heart disease and cardialgia at a polyclinic is analyzed. A total of 1110 patients with a preliminary diagnosis of ischemic heart disease were examined. In 214 of them the data gathered during many years of observations have cast doubt on the validity of this diagnosis. The patients of this group were made to undergo tests with potassium chloride and obsidan. Subject to appraisal were the ECG reaction and an analysis of angular variations of the vectors in the terminal portion of the ventricular complex. The described tests were shown to help determine the significance of "functional" or "organic" changes of the myocardium in the genesis of repolarizational ECG perturbances.


[Hyperlipemia and functional state of the myocardius according to the analysis of the polycardiograph under conditions of submaximal physical exercise].

An analysis of polycardiographic parameters prior to and following treadmill exercises was conducted in 124 males, aged 39-59 years; in 57 of them the blood lipids level was normal, in 67--elevated (cholesterol level 260 mg% and higher in those aged 39--49 and 280 mg% and higher for those aged 50-59, or triglycerids--300 mg% and higher for both age-groups). In persons with elevated levels of lipids in blood during early restitution (after 2 min.) following submaximal physical exercises polycardiogrammes demonstrated a phase syndrome of hypodynamia irrespective of the fact whether an ischaemic depression of the ST segment appeared on the ECG tracings in response to the exercises or not. The functional deficiency of the myocardium in patients with hyperlipidemia is most probably explained by the hampered oxygen transport from the erythrocytes via the hyperlipidemic plasma to the heart muscle.


[Socio-hygiene examination of male middle-aged population in connection with primary prevention of ischemic heart disease].

The presented results are based on an analysis of a socio-medical examination of males born in 1922-1931 comprising a 5% randomization from the population of this age group in one of the Moscow districts. 30.2% of the males volunteered their participation in the possible prophylactic measures, but only 20.3% were willing to participate in drug preventive therapy. The obtained data indicate that the examined population group was insufficiently prepared for preventive measures against cardiovascular pathology, and that extended differentiated health education programs are needed.


[Genetic heterogeneity of ischemic (coronary) heart disease].

Results are presented on a study of the blood coagulation system and some indices of serum lipids and proteins in 133 normal individuals and probands with ischaemic heart disease and their 681 relatives. The examination of the relatives of probands with different types of biochemical disorders revealed a similar biochemical background in the probands and the members of their families. The disorders in blood biochemistry in the probands were most similar in the parents, the children of the probands' siblings, and less distinct in more distant relatives (cousins, nephews and nieces, etc.), biochemical disorders similar to those of the probands being found in young persons (14-16 years old) and reappearing in several generations. The author concludes on the genetic heterogeneity of ischaemic (coronary) heart disease and underlying coronary atherosclerosis.


Renal response to phosphorus deprivation: effect of the parathyroids and bicarbonate.

Plasma inorganic phosphate (Pi) and Pi reabsorption were compared in intact and chronically thyroparathyroidectomized (TPTX) rats stabilized on a high or low-phosphorus diet after volume expansion with equivalent sodium bicarbonate or sodium chloride. Phosphate infusion after sodium chloride-loading resulted in greater hyperphosphatemia and diminished phosphaturia in TPTX rats than intact high-phosphorus rats. After sodium bicarbonate-loading, however, there was no difference between intact and TPTX high-phosphorus animals because bicarbonate inhibited Pi reabsorption extensively in both. In contrast, phosphate infusion after sodium chloride-loading in phosphorus-deprived rats elicited greater degrees of hyperphosphatemia and increased Pi reabsorption, irrespective of the presence or absence of the parathyroids. Sodium bicarbonate-loading inhibited Pi reabsorption significantly less in phosphorus-deprived rats than in high-phosphorus animals. Paradoxically, this inhibitory effect of bicarbonate in phosphorus depletion was greater in TPTX rats than in intact animals. Therefore, the presence of the parathyroids did not interfere with Pi reabsorption during phosphate infusion in sodium bicarbonate-loaded phosphorus-deprived rats. Sodium bicarbonate-loading interfered with Pi reabsorption most prominently in phosphorus-deprived rats when the parathyroids were absent.


Immunologic characterization of plasma membranes from the renal proximal tubule of the dog.

Plasma membrane fractions from the brush border (BBM) and antiluminal (ALM) surfaces of the dog's renal proximal tubule cell were separated using free-flow electrophoresis. Rabbits immunized with BBM rapidly produced antibody, but rabbits immunized with ALM did not respond. Indirect immunofluorescence and immunoferritin studies showed that the antibody reacts with the brush border of the proximal tubules in the normal kidney of the adult dog. It also reacts with the surface membranes of certain other absorptive and secretory epithelia, such as gall bladder, small intestine, epididymis, and lacrimal gland. The antibody has affinity for the membrane maltase without affecting its catalytic activity, but does not appear to have affinity for the membrane alkaline phosphatase or the high affinity binding site for phlorizin present in the BBM. Polyacrylamide electrophoresis of solubilized BBM showed approximately 37 protein bands and four glycoproteins. We conclude that the proximal tubule cell is immunologically polarized with respect to the distribution of antigenic proteins, and that the BBM is highly antigenic. The antigenic components appear to be high molecular weight glycoproteins present in the glycocalyx.


Biocarbonate and fluid absorption by renal proximal straight tubules.

Rabbit proximal straight tubules from superficial nephrons were perfused in vitro in order to elucidate the mechanism of fluid and bicarbonate absorption. Both processes were greatly inhibited when sodium was replaced in the perfusate and bath by other cations, when ouabain was added to the bath, or when potassium was removed from the bath. We infer that these experimental manipulations inhibit active sodium tranport, and that active sodium transport is a primary process leading to fluid and bicarbonate absorption. Fluid absorption also decreased (but only by 22 to 36%) when bicarbonate was replaced by chloride in the perfusate and bath or when acetazolamide (10(-3)M) was added, suggesting that fluid and sodium transport depend in part on bicarbonate. We infer that the links between fluid, sodiu, and bicarbonate transport are complex and involve at least two mechanisms: 1) a sodium for hydrogen ion exchange mechanism located in the brush border membrane and 2) the transepithelial concentration difference for bicarbonate, which results from its absorption and which acts as an additional driving force for fluid and sodium absorption. Finally, bicarbonate absorption was unaltered when chloride was replaced by nitrate in the perfusate and bath, suggesting that chloride is not necessary for acidification in this nephron segment.


Origin of hypercholesterolemia in chronic experimental nephrotic syndrome.

Sixteen nephrotized rats and eight controls were submitted to a continuous sterol balance for two weeks. During the whole experiment (two months) the rats were pair-fed a balanced sterol-free diet and their proteinuria regularly measured as a parameter of the nephrotic state. Serum cholesterol and albumin were also measured at the end of the experiment. Liver and carcass (excluding intestine and central nervous system) as well as feces were submitted to sterol analysis by gas-liquid chromatography. Sterol losses were corrected for by adding radioactive cholesterol and cholic acid at the beginning of the methodological procedures. The results showed that while fecal sterol excretion was similar in the nephrotic group as compared to controls, a definite increase in serum, carcass, and liver cholesterol was observed in the nephrotic animals, indicating that a real enhancement of synthesis had occurred. The meaning of increased cholesterol hepatic content is discussed, as well as the possible relationship between enhanced protein and cholesterol hepatic synthesis.


Kinetics of hemodialysis: a theoretical study of the removal of solutes in chronic renal failure compared to normal health.

A theoretical comparison of various treatment strategies for the dialysis of patients with chronic renal failure has been made covering a wide mol wt spectrum (60 to 5250 daltons) of metabolites. A two-compartment model has been used with the generation rate in the appropriate pool. The comparison for any given metabolite is made, keeping the same level of predicted intracellular concentration as in traditional Kiil treatments, and it is found that the number of treatment hours per week may be reduced pro rata as the dialyzer clearance is increased. This result is independent of the assumed site of metabolite generation, of the distribution volumes, and of the level of the cell wall permeability. The cyclic fluctuation in intracellular concentration and the mean level of intracellular concentration, in relation to the level in normal health, are both predicted for a given metabolite to be lower if thecell wall permeability is assumed to be on the low side rather than on the high side. The clinical implications of the variations in intracellular and extracellular concentration are discussed, and considerable elevation compared to normal health is predicted for both compartments for large molecules, larger than or equal to 1,000 mol wt, which are generated effectively in the extracellular compartment.