Cultivation of Leishmania donovani and Leishmania braziliensis in defined media: nutritional requirements. Nutritional requirements of promastigotes of Leishmania donovani and Leishmania braziliensis were studied in modifications of a simple defined culture medium. "Continuous growth," considered as propagation through 10 successive passages, was supported by inorganic salts, 14 l-amino acids (arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine, valine), glucose, adenosine, and a mixture of 11 vitamins and related growth factors. Purified defatted bovine serum albumin proved beneficial. The nutritional needs of the above species of Leishmania differ from those of 2 other hemoflagellate species, Leishmania tarentolae and Crithidia fasciculata, for which glucose, proline and glutamine were found to be nonessential. It is suggested that lower hemoflagellates may be capable of synthesizing these substrates de novo. Leishmania donovani and L. braziliensis required higher levels of folic acid than L. tarentolae, probably due to the fact that folates are involved as cofactors in the biosyntheses of pyrimidines and serine. Although the mixtures reported here cannot be regarded as "minimal essential" media, they are considerably less complex than the ones employed so far for cultivating hemoflagellates, and are therefore well suited for studies related to nutrition and biosynthetic capabilities of Trypanosomatids.


Effect of berenil on growth, mitochondrial DNA and respiration of Leishmania tarentolae promastigotes. Incubation of Leishmania tarentolae promastigotes in 1.0 microgram/ml Berenil for 96 hr resulted in approximately 33% inhibition of cell growth and approximately 42.5% dyskinetoplasty in the cell population. The buoyant density of kinetoplast DNA (kDNA), p = 1.703 g/ml, remained unchanged after 96-hr exposure to the drug. Endogenous respiration as well as proline- and glucose-induced respiration dropped markedly after 36-hr exposure to Berenil. This drop occurred approximately 12 hr before the onset of dyskinetoplasty, a result which suggests that this drug adversely affects mitochondrial respiratory activity of the promastigotes.


Inter-strain variability of structural proteins in Tetrahymena. The high molecular weight proteins found in isolated pellicles of Tetrahymena have been compared in several individual strains within the genus using SDS polyacrylamide gel electrophoresis. Three variants of the beta-protein of epiplasm (MW 174,000; 155,000; 145,00) and 2 of the C-protein (MW 140,000; 122,000) were found among the strains examined. No variation was observed in the major kinetodesmal fiber protein (MW 250,000). The variation found between strains in the proteins of a structure which is (as far as we know) the same in all strains indicates a disjunction between evolutionary change at the 2 levels of organization. The taxonomic implications of the observed variation in structural proteins in Tetrahymena are discussed.


Identification of Leishmania spp. by radiorespirometry. Preliminary investigation of the application of radiorespirometric technic to protozoan parasites of man indicates a potential for rapid identification. This technic, developed for identification of bacteria, was modified for use with culture forms of Leishmania. Five strains of Leishmania were compared: 2 of L. donovani, 2S and K; L. brasilensis, 2936 and B; and 1 of L. tropica, A. Consisent and rapid (approximately 2 hr) identification was obtained by the radiorespirometric procedure. A computer-type analysis of the radiorespirometric profiles of the 5 strains permitted correct identification of each isolate at the strain level 100% of the time. This technic offers several advantages over many current procedures for identification of protozoan parasites: (A) It is simple, rapid and highly reproducible, (B) Since it does not rely on visual or spectrophotometric determination, it may be conducted in the presence of optically complex substances. (C) It requires relatively low numbers of organisms (approximately 2 x 10(5)/14C-labeled substrate). (D) It is based on differential enzymic activity between species and strains of organisms and therefore, ultimately, on inherent genetic determinates of the parasites. (E) Further development of the procedure and accumulation of a data reference "bank" would allow automation of most of the identification process.


Effects of the optical isomers of alpha-chlorohydrin on glycolysis by ram testicular spermatozoa and the fertility of male rats. When 0-1 mM-S alpha-chlorohydrin was present in incubations, glycolysis by ram testicular spermatozoa was almost completely inhibited whereas 10 mM-R alpha-chlorohydrin had no effect. Male rats dosed orally with S alpha-chlorohydrin (3-25 mg/kg/day) became much less fertile than controls but those dosed with R alpha-chlorohydrin (13 mg/kg/day) did not. The loss of fertility was associated with a reduced ability of spermatozoa from the cauda epididymidis of these rats to oxidize glucose. It is concluded that the S enantiomer is responsible for both the inhibition of sperm glycolysis and the reduction in fertility caused by the racemic mixture of alpha-chlorohydrin.


Membrane potential of guinea-pig spermatozoa. The membrane potential of guinea-pig spermatozoa was investigated by using the fluorescent dye, diS-C3-(5). The potential did not vary when K replaced Na in the suspending medium, and in a physiological salt solution the resting potential was found to be about +13 mV.


Ovarian atrophy resulting from urethane injection of neonatal mice. Treatment of neonatal mice with urethane (0-5 or 0-75 mg/g body wt, i.p.) caused a lack of follicular development beyond the primordial stage. An effect of the thymus on ovarian development is inferred.


Fertility of dairy cattle after artificial insemination with semen frozen in a lipoprotein diluent. A lipoprotein separated from egg yolk by centrifugation and column chromatography was used to prepare a diluent containing 2-9% trisodium citrate. 2H2O (pH 7-0) and 7% glycerol. Ejaculates from Friesian bulls were split between this and two control diluents containing egg yolk, glycerol and citrate or lactose and used to inseminate once 1782 unselected Friesian cows. By 16 weeks after insemination with semen frozen in the egg yolk-lactose, egg yolk-citrate or lipoprotein-citrate diluents, 66-4, 67-1 and 66-1% of cows, respectively, had not returned to service.


Relationship between testicular blood flow, testosterone secretion and spermatogenic activity in young and adult wild red foxes (Vulpes vulpes). Testicular capillary blood flow (TCBF) was measured by the radioactive inert gas clearance technique throughout the reproductive life of young adult foxes and was related to the spermatogenic and androgenic activities of the testis. Mean (+/-S.E.M.) blood flow (ml min-1 g-1) was maximal in January in adults during the mating period (0-65 +/- 0-03), and in pubertal animals (0-62 +/- 0-04). At this time spermatozoa were observed in the testes of all animals, but testicular weight and circulating testosterone levels were lower in the pubescent foxes than in the adults. TCBF was minimal during immaturity (0-29 +/- 0-03) and during the resting period of the adult (0-12 +/- 0-01). These values were associated with a low testosterone level and with the multiplication of gonocytes in the young or with the seasonal very low spermatogenic activity in the adult. During the prepubertal period, TCBF slowly increased and was accompanied by testicular growth. In the adult, in September, TCBF rapidly increased without changes of testicular size and then slowly increased as the testes enlarged. High plasma testosterone concentrations occurred later. During the period of testicular regression, TCBF, testicular size, spermatogenic and androgenic activities decreased together.


Changes in the composition of maternal plasma, fetal plasma and fetal extraembryonic fluid during gestation in the rat. The changes in the biochemical composition of maternal plasma, fetal plasma and fetal extraembryonic fluid were studied in Wistar rats from Days 13 1/2 to 21 1/2 of gestation. During this period, there was an increase in maternal plasma volume and total blood volume. The total protein concentration decreased, but little change was observed in the protein pattern, total alpha-amino nitrogen, urea nitrogen and sodium concentration. In fetal plasma, total protein concentration increased progressively with a prominent increase in albumin near term. The albumin:globulin ratio was lower than that in maternal plasma because of the presence of two alpha-fetoproteins and four transferrins. The concentration of alpha-amino nitrogen was higher than that in maternal plasma but the urea nitrogen level did not change significantly. The fetal extraembryonic fluid reflected the changes in composition of fetal plasma, especially in the protein pattern, and concentrations of alpha-amino nitrogen and sodium. Total protein and urea nitrogen increased markedly in concentration near term but there was reduction in the fluid volume at this time.


Reproductive potential in female cattle discarded as infertile. Dairy cattle were served at consecutive heats up to three times each; they were then slaughtered, and the genital tracts were examined. Seventy-four cattle had been discarded from herds because they had not bred; 14 had never calved, and 14 were primiparous. Of these 28 animals, 12 (43%) conceived readily, and had normal pregnancies; normal genital tracts were found at slaughter. Eleven of the 16 animals that did not conceive had normal genitalia. The remaining 46  animals were mature cows, with a mean parity of 4-9; 9 (19-6%) became pregnant and had live embryos at autopsy, while in 7 other cows (15-2%) conception had been followed by embryonic death. Five of the uteri associated with these 16 conceptions showed pathological changes. Thirty of the 46 mature cows (65%) did not conceive; 12 (40%) had normal genitalia, and 18 (60%) showed severe pathological changes in the uterus and/or oviduct. Nine 'control' cows discarded because of poor milk yield were infertile, but 5 cows, discarded for various other reasons, all bred normally.


Evidence for the facilitated diffusion of glucose into rabbit oviductal fluid. Glucose movement into the oviductal fluid of rabbits was studied in anaesthetized animals. The oviducts were cannulated at each end, and 2 ml 0-9% NaCl at 37 degrees C were recirculated through the lumen for 4 h. D-Glucose appeared linearly in the fluid, reaching an average concentration of 2-6 mM. The rate of D-glucose appearance was 17 times greater than that of L-glucose, infused intravenously, suggesting that a component of the D-glucose movement operated by facilitated diffusion. The oviduct was unable to move glucose against an adverse plasma to lumen concentration gradient. We suggest that the glucose entering the oviductal fluid originates in the plasma and that the mucosal portion of the oviduct is responsible for this sugar transfer.


Pregnancy in patients with hemoglobinopathies and thalassemias. The availability of sophisticated laboratory procedures has made the diagnosis of many hemoglobinopathies and thalassemias simple. Structural alteration of the polypeptide chains and defects in the rate of synthesis of any of the polypeptide chains are the most common abnormalities: hemoglobins S, C and D are examples of the former, and the thalassemias are examples of the latter. The pathophysiology, clinical manifestations and individual variation of each abnormality are significantly different. Early diagnosis and the knowledge of the pathophysiology together with careful and frequent follow-up are necessary for providing better medical care. Pregnancy in a patient with a diagnosis of hemoglobinopathy or thalassemia certainly speaks for risks to both the mother and fetus. Management of each case has to be planned individually to provide optimal medical and supportive care. We have found a special combined hematology-obstetrics clinic to be helpful in the follow-up of these high-risk patients.


Disseminated intravascular coagulation in pregnancy. The DIC syndrome is the most common cause of an abnormal hemorrhage tendency during pregnancy and the puerperium and reflects systemic activation of the coagulation cascade by circulating thromboplastic material, with secondary activation of the fibrinolytic system. Its presence in a pregnant patient almost invariably is evidence of an underlying obstetric disorder such as abruptio placentae, eclampsia, retention of a dead fetus, amniotic fluid embolism, placental retention or bacterial sepsis. Diagnosis of the DIC syndrome rests on the demonstration of reduced levels of fibrinogen and platelets, prolongation of the thrombin, prothrombin and partial thromboplastin times, and the presence of fibrin/fibrinogen degradation products (FDP) in the serum. Therapy consists of prompt removal of the source of procoagulant material, replacement of depleted clotting factors and, in some cases, anti-coagulation with heparin.


Feline infectious peritonitis in South Africa. The clinical, clinical pathological and pathological findings in ten natural and two experimental cases of feline infectious peritonitis are described. The literature is reviewed and compared with the findings of these cases. It is concluded that feline infectious peritonitis occurs as a distinct clinical disease entity in domestic cats in the Republic of South Africa.


Ovarian autograft as an alternative to ovariectomy in bitches. The literature on autotransplantation of the ovary is briefly reviewed with emphasis on the portal vein drainage area as the transplant site. An experiment is reported whereby bitches hearing such grafts were compared to entire and ovariectomised subjects with regard to endocrine status and behaviour. It is concluded that autotransplantation of the ovary to the portal vein drainage area may be a promising method of abolishing oestrus and yet avoiding the eunuchoid syndrome as is seen in ovariectomised subjects.


The induction of oestrus in recently weaned sows with low doses of gonadotrophins. Trials in a large scale commercial piggery indicated that use of a combination of hormones played a significant role in synchronising and expediting the onset of oestrus. The litter sizes in the treated group were significantly larger than in the controls.


The regularity of cycles and ovarian efficiency in a group of Friesland cows. Delayed ovulation was recorded in 17,34% and anovulation in 17,66% of 623 oestrus periods in 32 Friesland cows. Cycle length was abnormal in 19,19% of 568 cycles and was associated with an increase in the incidence of defective ovulation. Inseminations failed in 24,6% of cases despite normal ovulatory function at oestrus while in nine out of 134 inseminations sperm retained its fertilizing capacity in the female tract between 24 and 72 hours.


Schistosoma mattheei in the ox: the chronic hepatic syndrome. A Friesland steer infested on four occasions at intervals of 4--6 weeks with 20 000 cercariae of Schistosoma mattheei developed progressive hepatic failure and died after 74 weeks. The condition was characterised by enlargement and induration of the liver with portal fibrosis, inflammation of the portal veins and "piecemeal necrosis", and was associated with a severe circulating eosinophilia and hypergammaglobulinaemia. Similar cases were encountered in two natural outbreaks. The syndrome is considered to be of immunological origin, initiated by the reaction in the portal veins to antigen from schistosomes killed by the immune response of the host. It is usually seen in animals exposed to repeated heavy infestation but may occur occasionally after light infestation.


Haematological changes caused by Trichostrongylus colubriformis in lambs fed a dystrophogenic diet. The effect of Trichostrongylus colubriformis on lambs maintained on a ration containing a low level of selenium and on animals receiving vitamin E and Se supplementation was investigated. The pathological changes seen in control animals slaughtered at the start of the experiment and in the animals which died during the course of the investigation revealed a high level of nutritional muscular dystrophy (NMD) in the lambs. There were no marked haematological changes in the control or infested sheep. Infestation was characterized by slight hypoalbuminaemia and gamma-globulinaemia. Serum levels of the enzymes AAT and CPK, which are important indicators of muscle necrosis and NMD, were greatly increased in sheep infested with T. colubriformis and not receiving supplementary Vit. E + Se. Data from this study therefore indicates that trichostrongylosis may aggravate the degree of muscle necrosis in lambs prone to the development of NMD.


Antitumor septacidin analogues.

Antitumor septacidin analogues. In the first approach by total synthesis to the structure of the antitumor antibiotic septacidin, analogues have been obtained which show similar inhibition of RNA-DNA synthesis in cultured leukemia L1210 cells and similar activity against transplanted leukemia P388 in mice. In these analogues, the natural aminoheptose moiety is replaced by 4-amino-4-deoxy-and 4-amino-4,6-dideoxy-L-glucose, to retain the natural configuration of the pyranose ring. Also retained is the lipophilic fatty acid-amino acid side chain attached to the 4-amino group and glycosylation at the 6-NH2 of adenine. If the fatty acid chain was shortened from C16 to C6, if the fatty chain was shifted to the glycine unit, or if the glycine unit was omitted, activity was completely lost. However, activity was retained if the C16 chain was shortened only to C12 or if the glycine unit was extended to beta-alanine. Both active and inactive analogues were nonbinding to DNA and nonmutagenic to Salmonella strains. The synthetic approach was to start with a suitably protected sugar (L-fucose and L-galactose), construct the adenine moiety at C-1 introduce a 4-amino group, and finally attach the preformed side chain.


Biological active polycycloalkanes. 4. Phosphoric esters of trimethylenenorbornyl alcohols. Secondary (6) and tertiary (8) phosphates of exo-5,6-trimethylenenorborn-exo-2-yl alcohol (exo-tricyclo-[5.2.1.0(2,6)]dec-exo-8-yl alcohol, 3) and a secondary ester (9) of a mixture of exo-tricyclo[5.2.1.0(2,6)]dec-3-en-8- and -9-yl alcohol (2) were prepared. The most convenient route to 6 was direct esterification of phosphoric acid with 3. 9 was obtainable by the addition of phosphoric acid to endo-dicyclopentadiene (1). These phosphates were tested in vitro for antiviral activity against Newcastle disease virus using a monolayer culture of chick embryo fibroblasts. 6 was found ca. twice more potent than, while 8 was as active as, amantadine hydrochloride under the present test conditions.


Synthesis and hypotensive activity of some cyclopentano-1,2,3,4-tetrahydroisoquinolines. A series of derivatives of the novel cyclopentano[f]- and [h]-1,2,3,4-tetrahydroisoquinolines has been synthesized and screened by hypotensive properties in the unanesthetized DCA hypertensive rat and for acute toxicity in the mouse. Substitutions were made in the parent structures at both the heteroatom and the 5 and 6, and 7 and 8 positions. Bulky lipophilic substitutions on the heteroatom yielded compounds producing moderate depressions in blood pressure over extended periods of time. One member of the series produced a significant hypertensive response. Some heart stimulant properties (unaccompanied by effects on blood pressure) were observed with some compounds. In general, the compounds were relatively toxic. The introduction of the bulky lipophilic groupings on the heterocyclic nitrogen appeared to be associated with a reduction in toxicity.


Hypolipidemic analogues of ethyl 4-benzyloxybenzoate. A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure--activity relationships are discussed in terms of cholesterol-lowering activity together with effects on weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl-4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoates, and 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.


Sycnthesis of quinazoline analogues of folic acid modified at postion 10. The quinazoline couterpart of folic acid (5,8-deazafolic acid) as well as its 10-methyl analogue has been shown to be an effective inhibitor of thymidylate synthetase from several different sources. This paper describes the synthesis of modifications in which the nitrogen atom at position 10 is replaced by sulfur, oxygen, or methylene affording 10-thia-5,8-deazafolic acid, 10-oxa-5,8-deazafolic acid, and 5,8,10-deazafolic acid, respectively. In preliminary testing, each of the target compounds displayed marginal activity against L1210 leukemia in mice.


(Acylaryloxy)acetic acid diuretics. 1. (2-Alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids. The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocyclic parent compound, lacked the double bond adjacent to the carbonyl group. More importantly, they possessed both saluretic and uricosuric properties. The optimal single 2-substituents for maximal saluretic and uricosuric activity were determined. In general, better activity was observed when a second 2-alkyl substituent (especially methyl) was present in the molecule. Replacement of the carboxy substituent by 5-tetrazolyl generally resulted in a reduction in activity.


Neurotensin analogues. Structure--activity relationships. A series of neurotensin (NT) analogues in which each amino acid has been successively replaced by its D isomer, as well as analogues involving modifications at positions 3 and 11 and a cyclic compound [Cys2,13]-NT, has been synthesized by solid-phase methodology. After purification by conventional techniques the compounds were characterized by thin-layer chromatography, amino acid analysis, and optical rotation. Further characterization of the analogues by high-pressure liquid chromatography demonstrates the high resolving power of this new method. Each analogue was studied for its ability to induce hypothermia in cold-exposed rate (4 degrees C) in vivo and to bind to mast cells in vitro. Although close correlation in potencies was not found for all the analogues tested in both assay systems, they substantiate the basic observation that substitutions in positions 1-9 produced active peptides whereas modification of residues 10-13 considerably decreased biological response in vitro and in vivo. One exception is the higher potency of [D-Phe11]-NT and [D-Tyr11]-NT in vivo. The differences between the efficacies of these analogues in vivo and in vitro are discussed.


Quantitative structure-activity relationship of chymotrypsin-ligand interactions. Quantitative structure-activity relationships (QSAR) have been formulated for the interactions of a variety of ligands with chymotrypsin. The parameters Km, k2, k3, kcat, and Ki are found to be strongly dependent on molar refractivity as well as steric and electronic character of the substituents in structures of the type R2CH(COOR3)NHCOR1 where R may be H. A model for binding of D and L esters is presented which gives a consistent view of the binding step, acylation, and deacylation. The model suggests new avenue for exploration.


Improved delivery through biological membranes. 4. Prodrugs of L-dopa. Various classes of transient derivatives of L-Dopa have been synthesized, systematically protecting one or more of the main sites of metabolism in the molecule: the carboxy function, the amino, and/or the catechol system. The derivatives studied include carboxy esters, phenol esters, amides, peptides, and various combinations of these functions. A number of these derivatives effectively prevent the metabolism of L-Dopa prior to and/or during the absorption process, resulting in a significantly better bioavailability of the drug. In vivo studies using dogs showed up to 2.5-fold increase in L-Dopa blood levels. The metabolism as well as toxicity aspects of the prodrugs is also discussed.


Conformation-activity studies of oxytocin. Effects of structural modifications at corner positions of the beta-turns on the uterotonic activity. Replacement of the aliphatic isoleucine residue in position 3 of oxytocin (the first corner position of the beta-turn in the 20-membered ring of the solution conformation of the hormone) by phenylalanine has been shown to result in analogues with reduced affinity and intrinsic activity when tested by the individual dose-response procedure on the isolated rat uterus. Studies of effects of structural modifications have been extended to include two additional beta-turn corner positions. First, the dose-response behavior of [Leu4]oxytocin and [Phe4]oxytocin, two analogues in which the Glu4 side chain in the second corner position of the beta-turn in the 20-membered ring has been substituted by hydrophobic and bulky groups, was compared with that of oxytocin. Second, the solid-phase synthesis and biological properties of [Phe3,Leu4,Met8]oxytocin and [Phe3,4,Met8]oxytocin are described. The presence of leucine or phenylalanine in position 4 evokes a drastic reduction in both the affinity and intrinsic uterotonic activity of the resulting analogues, with phenylalanine significantly more effective in reducing intrinsic activity than leucine (p less than 0.001).


Synthesis and pharmacological properties of the N-terminal decapeptide of the vasoactive intestinal peptide (VIP). The decapeptide derivative, L-histidyl-L-seryl-L-aspartyl-L-alanyl-L-valyl-L-phenylalanyl-L-threonyl-L-aspartyl-L-asparaginyl-L-tyrosine methyl ester, corresponding to the N-terminal sequence of both porcine and chicken VIP was synthesized in solution, by the stepwise strategy. Its pharmacological properties resemble those of VIP itself, but with a much lower potency, comparable to that of peptides with C-terminal sequences. The presence of two independent sequences carrying similar instructions was recognized in VIP.


Proteinase inhibitors. I. Inhibitors of elastase. A series of peptides and depsipeptides containing 2-methylcarbazic acid (H-Mec-OH), the 2-aza analogue of alanine, was prepared and tested as inhibitors of pancreatic and human granulocyte elastases. A requirement for a minimum chain length as well as specific amino acid sequence was observed which correlates well with both substrate and inhibitor studies by others in this field. The most active inhibitors have the structure Ac-Ala-Ala-Pro-Mec-Lac-R. When Lac-R is an ester, only the pancreatic enzyme is inhibited. When Lac-R is an amide or hydrazide, then both enzymes are inhibited. The inhibitory activity is reversible; the inhibitors are not hydrolyzed by the enzyme and the inhibition is noncompetitive with synthetic substrates of similar structure, suggesting that binding at the sites adjacent to the carboyl group of the amino acid analogue, 2-methylcarbazic acid, is important for this inhibition. The data further demonstrate the differences between pancreatic and granulocyte elastases.


Ergot alkaloids. Synthesis of 6-alkyl-8-ergolenes and 6-methyl-8-aminoergolines as potential prolactin inhibitors. The synthesis of several N-6 derivatives of elymoclavine (3) and potential alkylating derivatives of 6-methyl-8-aminoergolines (12) is described. These compounds were screened for prolactin-inhibiting ability and 6-propyl-8-hydroxymethyl-8-ergolene (9) was found to be as active as the most potent prolactin inhibitors reported to date. The total synthesis of racemic methyl dihydrolysergate I (23), having a trans C, D ring fusion, from the tricyclic ketone 18 is also described.


Selective inhibition of the monosynaptic spinal reflex by a series of hydroxylated alkylaminoindans. 5-Hydroxy-2-piperidino-4,5,6,7-tetrahydroindan (5) and a number of related tetrahydro and dihydro compounds were prepared by selective mono- and dihydroxylation of the dihydro products from the Birch reduction of various alkylaminoalkylindans, tetralins, benzenes, and isoindolines. Some of these compounds showed a remarkably selective inhibition of monosynatpic spinal reflex in the segmental cat preparation.


Synthesis of 3-(4-acylaminopiperazin-1-ylalkyl)indoles as potential antihypertensive agents. A series of 3-(4-acylaminopiperazin-1-ylalkyl)indoles was synthesized and tested for antihypertensive activity. Compounds with no substituents in the indole portion of the molecule were generally most effective in lowering blood pressure in the spontaneous hypertensive rat model. Of these several analogues were very potent and lowered blood pressure more than 55 mmHg at oral doses of 100 mg/kg.


Structure of warfarin in solution.

Structure of warfarin in solution. Warfarin in solution is shown to consist of three interconverting tautomeric structures, two of which are cyclic diastereomeric hemiketals, while the third and minor component is the open-chain intermediate form. The configurations of all the tautomers as well as the major conformations of the cyclic tautomers are assigned. The assignments are supported by comparison with the chemical shift and coupling constant parameters of structurally fixed model compounds.


Azabicyclo chemistry. 6. An investigation of one of the chemical parameters for analgetic activity. Synthesis of 2-methyl-2-azabicyclo[3.3.1]non-6-ene and -non-7-ene. The olefins 2-methyl-2-azabicyclo[3.3.1]non-6-ene (3) and -non-7-ene (6) were prepared in order to evaluate their analgetic activity. The reduction of 2-methyl-2-azabicyclo[3.3.1]nonan-7-one (4) with NaBH4 gave, stereospecifically, the axial alcohol 5. Reaction of 5 with CH3SO2Cl-pyridine gave directly the olefins 3 and 6, both of which upon hydrogenation gave the known 2-methyl-2-azabicyclo[3.3.1]nonane (7). The structural proof of 3, 5, and 6 was ascertained by spectral methods. Of the compounds prepared, 3, 5, and 6 were essentially inactive as analgetics when tested in mice by the hot-plate method, while 4 had marginal activity.


Dibenz[b,e]oxepinalkanoic acids as nonsteroidal antiinflammatory agents. 3. omega-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)alkanoic acids. Omega-(6,11-Dihydro-11-oxodibenz[b,e]oxepin-2-yl)butyric, -hexanoic, and -octanoic acids were evaluated in the carrageenan paw edema assay. The most active compound, the butyric acid analogue, was 1.80 times more potent than the hexanoic compound, 1.15 times more potent than the octanoic analogue, and 0.43 times as potent as indomethacin.


Isoquinolines. 6. Potential central nervous system antitumor agents. Nitrogen mustards of 3-amino-4-(p-aminophenyl)isoquinoline. A series of 3-amino-4-(p-aminophenyl)isoquinolines bearing the bis(2-chloroethyl)amino group was synthesized as potential CNS antitumor agents. Diol precursors 1e and 1f were prepared by the treatment of 1b and 1c with ethylene oxide. Diol precursors 5a-c and 9 were prepared by the treatment of 4a-c and 8 with diethanolamine. The reaction of these diols with SOCl2 yielded target mustards 10-15 which were evaluated in the intraperitoneal murine L1210 tumor. No intermediates or target mustards were active in this tumor system.


Antimycotic imidazoles. 2. Synthesis and antimycotic properties of 1-[2-(arylalkyl)-2-phenylethyl]-1H-imidazoles. Synthesis of 1-[2-(arylalkyl)-2-phenylethyl]-1H-imidazoles was accomplished starting from the corresponding phenylacetonitriles. Via successive alkylation, conversion to the corresponding ester, and sodium borohydride-lithium iodide reduction, beta-phenylalcanols were obtained. These alcohols were mesylated and then refluxed with imidazole in dimethylformamide to yield the title compounds, which were active in vitro against dermatophytes, yeasts, other fungi, and gram-positive bacteria. Some were also active in vivo against Candida albicans.


4-Substituted semicarbazones of mono- and dichlorobenzaldehydes as antihypertensive agents. Twelve 4-substituted semicarbazone derivatives of o- and p-chloro- as well as 2,6-dichlorobenzaldehyde were synthesized and investigated for antihypertensive activity in spontaneously hypertensive rats. Several of the compounds synthesized (viz. 1, 6, 7, and 15) exhibited potent antihypertensive effects when orally administered. The same compounds were not hypotensive in the normotensive dog.


Synthsis and antitumor properties of bis(quinaldine) derivatives. A series of 7-nitro- and amino-N,'-bis(4-quinaldinyl)-alpha, omega-diaminoalkanes related to the 6-amino derivative 1 was synthesized and tested in the mouse P-388 lymphocytic leukemia screen. There of the 7-nitro derivatives (12, 14, and 15) were found to have moderate activity (T/C 140-150%), while other nitro derivatives (11 and 13) were devoid of any antitumor properties. All five 7-amino compounds (2-6) were moderately to strongly active (T/C 134-196%). In addition, binding of amino derivatives 2-6 to DNA was examined by their ability to (1) stabilize DNA to thermal denaturation and (2) inhibit the DNA-dependent RNA polymerase reaction in vitro. Tm data suggest that these compounds bind to DNA and are strong inhibitors of the polymerase reaction (I50 = 6-9 X 10(-6) M).


Student decision-making and performance in a flexible-time curriculum. Three consecutive classes (213 students) entering the University of Arizona College of Medicine under a flexible-time three-year curriculum were provided the option of extending their program by a year or more. Of the 30 percent who availed themselves of this option, a majority did so because they desired a better personal or academic "life-style" rather than for specific academic reasons. Most continued to pursue medical interests during the free time which became available to them. Through none of the usual admission data was it possible to predict which students would choose to extend their program. At the time of graduation students completing the curriculum in three years achieved scores on the Part II examination of the National Board of Medical Examiners comparable with those earned by students who extended for a four-year program. Nonacademic factors may be of greater importance than academic factors in student acceptance of accelerated curricula.


Evaluation of clinical training in the community. An evaluation approach is presented that is designed to deal with the complex educational problems associated with community-based teaching. Such problems include using instructors with limited training in teaching, ensuring comparability of student experiences, monitoring students' performance in dispersed settings, and maintaining adequate communications among involved parties. The approach is based on a careful delineation of information needs and data sources followed by the design and strategic combination of evaluation instruments in order to promote efficiency in data collection. An application of the approach is described for an undergraduate clerkship in family medicine taught at multiple sites at the University of Washington School of Medicine. Nine instruments are described for eliciting information from four sources to satisfy the needs of five groups associated with the course. Sample results are presented suggesting that the approach is effective and may prove useful to others involved with teaching in dispersed settings.


A new teacher in medical education: the family nurse practitioner. At the University of California, Davis, family nurse practitioners who are faculty members in the Department of Family Practice have proven to be effective teachers of medical students and family practice residents. These faculty members, new to the medical school scene, have demonstrated competency in the teaching of clinical medicine within their area of expertise, are extremely well received and sought after by students are effective role models as clinicians in the education-service settings, and expose trainees to and prepare them for the team concept in the delivery of care.


A national survey of medical school obstetrics and gynecology departments, 1965 to 1975. Representatives of 108 departments of obstetrics and gynecology completed a written questionnaire in 1976 designed to assess the changes that had occurred in the teaching resources of the departments for the years 1965, 1970, and 1975. There was a statistically significant increase in the number of students per clerkship during that decade. In addition, there was an increase in the numbers of full-time faculty members, residents, beds, and patients. As a consequence, the teaching ratios improved. This might explain in part the increased numbers of medical students selecting obstetrics and gynecology as a career.


Q-band polymorphism in a family of pygmy chimpanzees (Pan paniscus). A polymorphic condition for the Q-band intense region of chromosome number 22 is identified in the pygmy chimpanzee (Pan paniscus). This polymorphism allows us to trace the pattern of inheritance of a number 22 chromosome in a family of pygmy chimpanzees. Previous Q-band findings are verified.


Temperature-jump experiments on thin lipid membranes in the presence of valinomycin. Temperature jump relaxation experiments on planar lipid membranes in the presence of valinomycin were performed using the absorption of a strong light flash as an energy source for the generation of the T-jump. The relaxation of the current carried by valinomycin/Rb+ complexes was measured. The results were interpreted on the basis of a transport model which was also analyzed by voltage jump relaxation experiments. The study shows that the application of the T-jump technique provides valuable information about transport kinetics as well as the dynamics of the membrane structure. At the given experimental conditions the relaxation of the current is believed to reflect a temperature-dependent transition of the membrane to a new conformational state of low order. The relaxation could be resolved with the present technique only at low temperatures and for membranes of high microviscosity.


Reduction of background [corrected] due to backscattered electron in energy-dispersive X-ray microanalysis. When energy-dispersive X-ray microanalysis is practised in a scanning electron microscope, most of the spectral background may come from electrons entering the detector. This background can be eliminated by deflecting magnets. Alternatively, the electrons can be blocked by a plastic film but only at the cost of suppression of the low-energy end of the X-ray spectrum.


Effects of anions on amiloride-sensitive, active sodium transport across rabbit colon, in vitro. Evidence for "trans-inhibition" of the Na entry mechanism. Replacement of Cl in the solutions bathing partial mucosal strips of rabbit descending colon with sulfate, isethionate, hydroxypropane-sulfonate and, to a lesser degree, ethanesulfonate stimulates active Na absorption (JNanet) when the baso-lateral pump mechanism is not saturated. These effects are rapid in onset and are readily reversible. Our findings indicate that these stimulatory anions decrease the resistance of the amiloridesensitive Na entry step at the mucosal membrane (RmNa). However, when the active Na pump mechanism at the baso-lateral membrane is saturated these stimulatory anions do not decrease the resistance of the Na entry process. These findings suggest the presence of a negative feedback between the activity of the pump mechanism and the resistance of the Na entry step which may be mediated by the size of the intracellular Na transport pool. In other words, it seems that when the baso-lateral pump is operating at its maximal rate the resistance to Na entry across the mucosal membrane through the amiloride-sensitive pathway is at a minimum and cannot be further decreased.


A simple method for holding electron microscope grids during autoradiography of serial sections. A simple, reliable, and inexpensive method is described for holding electron microscope grids during the application of photographic emulsion and during subsequent storage and processing. This method has proved to be especially useful in autoradiographic studies using serial sections.


Using simultaneous three colour X-ray mapping and digital-scan-stop for rapid elemental characterization of coal combustion by-products. A system is described for rapid, simultaneous three colour elemental mapping with a scanning electron microscope (SEM) and an energy dispersive X-ray analyser. The technique, which use a SEM scanning at TV rate, minimizes the disadvantages of long scan times such as inefficient use of linear amplifer and observable dead-time shadowing. The system also employs a digital scan-stop assembly utilizing a light pen to rapidly and reproducibly direct the beam to an object of choice for spot-mode analysis. Application of the system to analysis of fine particulates with emphasis on fly ash derived from coal-fired electric power plants is discussed. Chemical heterogeneity of fine particles in standard reference material fly ash and in phagocytized fly ash within pulmonary macrophages is demonstrated. This system combines the morphologic capability of the SEM with X-ray multielement mapping to provide a needed tool for particulate source identification.


Oxytalan fibre organization in marsupial mandibular periodontal tissues. The arrangement and distribution of oxytalan fibres in Australian marsupials has not previously been reported. Periodontal tissues of wombat, wallaby, possum, and marsupial mouse were examined to ascertain oxytalan fibre organization. Despite adaptation of the marsupial masticatory apparatus to different diets the oxytalan fibre organization in the periodontal ligament shows a basic pattern which corresponds with that reported in other animals. The oxytalan system forms a continuous meshwork of fine, branching fibres which completely invests each tooth root and connects adjacent teeth. Thick ribbon-like apico-occlusally orientated oxytalan fibres, thought to form by the coalescence of thinner fibres, are restricted to the periodontal ligament. The oxytalan fibres are embedded in cementum and attached to blood vessels in the pariodontal ligament. Oxytalan fibres do not insert into alveolar bone. Histological evidence indicates functional remodelling of the oxytalan fibre system in continuously erupting teeth.


Development of dorsoventral polarity and mesentoblast determination in Patella vulgata. In Patella vulgata the 32-cell stage represents a pause in the mitotic activity prior to the differentiation of the mesentoblasts mother cell 3D. At the onset of this stage, the embryo is radially symmetrical. Nevertheless, the plane of bilateral symmetry is indicated as it passes through the macromeres forming the vegetal cross-furrow. From the early beginning of the 32-cell stage, all four macromeres introdude far into the interior and tough the centrally radiating cells of the first quartet of micromeres. The two cross-furrow forming macromeres (3B and 3D) intrude the farthest and come into contact with the greatest number of micromeres. Finally, the contacts are extended significantly and maintained with only one of these macromeres. From that moment, this cell can be called the macromere 3D and the dorsoventral axis is determined. The evolution of the internal cell contacts between the micromeres of the first quartet and the macromeres indicates an essential role of the former in the determination of one of the latter as the masentoblasts mother cell, and thus in the determination of dorsoventral polarity.


Avian scale development. Absence of an "epidermal placode" in reticulate scale morphogenesis. Timed-sequence studies have shown that reticulate scales on the ventral footpads of birds do not undergo "epidermal placode" formation during their morphogenesis, but arise as symmetrical evaluations similar to the scales of snakes and lizards. Unlike the scutellate scales on the dorsal surface of the foot, in which the formation of an "epidermal placode" and its subsequent morphogenesis result in disticnt outer and inner epidermal surfaces, the reticulate scales elaborate only one type of epidermal surface.


Experimental automobile-pedestrian injuries. Fifteen fresh cadaver impacts were conducted in simulation of pedestrian-automobile accidents. The test sled configuration simulated an automobile bumper and hood in "standard" and "nosedive" situations as well as "hard" and "soft" impact surfaces. Instrumentation and film demonstrated large axial compression forces in the struck leg and considerable angular velocity of the torso in all modes. Dissection revealed primary injury at the impact site at low velocities with added remote injury at high velocities. Fracture of the lateral tibial plateau was most common. Lowering the bumper height offered the greatest protection against injury at moderate impact velocities.


Tracheobronchial cytologic changes and abnormal serum heme pigments in hemorrhagic shock. Significantly elevated numbers of iron laden histiocytes have been shown to appear in the tracheobronchial secretions of subjects in hemorrhagic shock and in patients undergoing open heart-surgery during cardiopulmonary bypass (3,4). Abnormal heme pigments have also been demonstrated in the serum of dogs bled to hemorrhagic shock (6) and have been felt to be toxic. Because the ingestion of abnormal heme pigments by histiocytes may be part of a defense mechanism, we have attempted to correlate the percentage of iron laden histiocytes found in the tracheobronchial secretions of patients in hemorrhagic shock (Prussian blue method) with the presence of degradation of products of hemoglobin found in their serum by scanning spectrophotometry. There were, generally speaking, few iron laden histiocytes when hemoglobin degradation was advanced, and always numerous iron laden histiocytes when abnormal heme pigments were absent or spectrophotometric findings revealed minor degrees of degradation. Our findings probably reflect the process in the reticuloendothelial systems which eliminates toxic products accumulating in the circulation in low-flow states.


Specific patterns of inflicted burn injuries. By retrospective review of 1,061 charts and prospective analysis of all accidental injuries seen in a Pediatric Emergency Room over a 5-year period, criteria were developed to identify the source of an injury as either specific or nonspecific, i.e., whether a unique causative mechanism was clear or not from the clinical or radiologic signs. These criteria were then used to diagnose 712 cases of child abuse, of which 43 were burns. There were four specific burn patterns. Readily evident were contacts with hot objects; the other were caused by various applications of hot liquids. In these latter cases, the position of the body at the time of burning could be precisely detected by analysis of the depth, configuration, distribution of the burns, and the reciprocal relation to flexion creases and joints of the spared areas. This information is a powerful tool for assessing the veracity of the history presented by the child's caretaker when considering a diagnosis of child battery.


Upper buccal sulcus approach to reduction of zygomatic fractures. Thirty selected patients with simple zygoma fractures over a 15-year period have been treated by elevation and reduction with the use of a zymgomatic elevator from an intraoral upper buccal sulcus approach. No patient suffered a recurrence of the fracture of deformity or required an open reduction. This little publicized procedure is easy, fast, and effective in carefully chosen cases of zygoma and zygomatic arch fractures in the first 72-96 hours postinjury. It should be considered by the surgeon along with the more complex procedures.


The "battered alcoholic syndrome".

The "battered alcoholic syndrome". The Battered Alcoholic Syndrome is here defined by the presence of three or more fractures in the same individual but in differing chronological stages of healing. These may be identified either on the basis of radiographs or by history. Because only three per cent of alcoholics are of the skid-row stereotype, and because the treatment of an alcoholic may differ from that of a nonalcoholic, the recognition of this syndrome is of value in the initial and long-term management of such individuals. In 100 consecutive fracture patient admissions at Harborview Medical Center the incidence of this syndrome in Seattle was eight per cent of fracture patients admitted to the hospital; 62% of patients with a third discrete fracture were alcoholics. Etiologic factors which may play a role in its development include greater exposure to trauma, psychologic predisposition, nutritional depletion, and the direct toxic effects of alcohol itself.


Some medicolegal aspects of gunshot wounds. While we concede that sleuthing is not the realm of a surgeon, we believe that there is a clear need for better communication among all concerned with shooting injuries. Along with good medical management we make a plea for more accurate case documentation and better preservation of evidence. Not only will better records greatly aid police investigations, but more understanding of the medical aspects of these wounds will also doubtless ensue. We recommend the use of photography whenever possible, and careful preservation of all physical evidence. Finally, to facilitate documentation in gunshot cases we suggest the routine use of a standardized checklist.


Central venous catheterization via the supraclavicular approach. The versatility and usefulness of central venous catheters in the management of critically ill patients cannot be questionned. Various methods of placement have evolved, each with its own advantages and potential complications. Little attention in recent years has been given to the supraclavicular approach, the details of which are described and its usefulness compared with other techniques. This method is highly recommended due to its high degree of simplicity, comfort, safety, and reliability.


A study of ankle instability utilizing ankle arthrography. A preclinical and clinical study of ankle arthrography for chronic ankle instability was performed. In the first study, ankle arthrograms were done on 50 cadaver ankles to demonstrate the limits of the normal ankle joint, and it was demonstrated that contrast in tendon sheaths is not a sign of a torn ankle ligament. The second study consisted of investigating ten cases of chronic ankle instability utilizing ankle arthrography. It was concluded that ankle arthrography is helpful in diagnosing torn ankle ligaments if all remaining investigative procedures are negative. A positive ankle arthrogram is proof that a torn capsule and ligament has occurred. However, in this small series a negative a negative arthrogram and a normal talar tilt was still associated with a torn ligament of the ankle.


Open anterior dislocation of the shoulder. An open dislocation of the shoulder is a very uncommon and serious injury. The sequelae of open glenohumeral dislocation include infection, avascular necrosis, and limited motion. The patient with such complications will have serious compromise in shoulder function, as illustrated in this case report and reference to another report in the literature.


Traumatic vertebral arteriovenous fistula associated with cervical spine fracture. A case of a traumatic vertebral arteriovenous fistula associated with a high cervical fracture-dislocation is reported. The fistula was not suspected clinically but was fortuitously diagnosed by brachial arteriography carried out for a deteriorating level of consciousness. The patient's complex injuries were managed by conservative treatment of the fracture-dislocation and later by ligation of the proximal and distal vertebral artery for trapping of the fistula. The indications and the various surgical procedures for the treatment of vertebral arteriovenous fistula are discussed. The report emphasizes the value of cerebral angiography in head and neck injuries.


An unusual complication of fracture of the lower femur. False aneurysm is an unusual complication following fracture of the lower femur. Diagnosis is difficult, and in the case reported arteriography was performed despite failure to appreciate any pulsatile component to the swelling.


[Analysis of 830 case histories of male sterility of which 282 are usable. Results of our diagnostic investigations and therapeutic procedures]. Overall results are given of the investigation and treatment of 282 cases of male sterility: 245 cases of secretory and 37 of excretory sterility; 126 cases in which treatment produced no change, 110 cases showing biological improvement and 45 cases in which pregnancy occurred; 128 of the 282 men had varicoceles. There were three groups of patients; 1) Those with azoospermia: 59 cases, predominantly with excretory problems, bilateral atrophy and chromosomal anomalies: of these, eight showed an improvement, of which two resulted in pregnancy; 2) Those with oligo-asthenospermia: 110 cases, with predominantly solitary varicoceles, intoxications and unknown causes: 66 per 100 showed improvement, and in 23 of these cases pregnancy resulted; 3) Those with varicoceles associated with another cause, predominantly unilateral atrophy and intoxications: 62.8 percent showed biological improvement, and 12 of these cases resulted in pregnancy. Also mentioned is the group of patients with solitary asthenospermia; solitary oligospermia and hyperzoospermia of more than 200 million per ml. Varicocele is the predominant pathology in these three groups.


[Perineal urinary fistula after excision of the rectum 3 cases]. On the basis of three cases, the authors study the problem of perineal urinary fistula secondary to rectal surgery. They first note that little attention has been devoted to these lesions. The clinical and radiological features are described and analysed, in a pathological context. Treatment of these fistulae is difficult if a conservative approach is sought, and the best solution is perhaps nephrectomy or bypass by a Bricker operation carried out either initially or after an attempt at repair has failed.


[Evaluation split renal function and compensatory hypertrophy using a radio-isotopic technique]. Using a new method for the determination of split renal function with a radio-isotopic technique (FG Hipaque I131 and PRP Hippuran I131) we sought to determine residual renal function with pre-operative studies, especially in preparation for nephrectomy, and secondly with postoperative studies of compensatory renal hypertrophy after total or partial nephrectomy and the restoration of function in the kidneys following surgery of the urinary tract. A total of 20 cases was studied. We noted marked compensatory hypertrophy after total and partial nephrectomy and the prompt return of function after procedures involving the urinary tract, on condition that any acute infection be prevented.


[Isolated angiomyolipomas of the kidney. Diagnostic difficulties]. The authors report 4 cases angiomyolipomas in which the preoperative diagnosis was that of a malignant tumour. They stress the difficulties of arteriographic and even histological diagnosis of these rare tumours of the renal parenchyma.


[Xantho-granulomatous pyelonephritis. 3 cases (author's transl)]. Amongst infective lesions of the kidney, xanthogranulomatous pyelonephritis has a place of its own. Whilst some consider it to be a distinct entity, others classify it within the broad group of the pyonephroses. From a clinical standpoint, lithiasis is common and urinary infection quasiconstant. Radiological appearances and the therapeutic approach differ according to whether it is, as is most common, a generalised form or the much rarer localised form. On the basis of 3 cases, the authors review the principal features of this curious condition.


[Treatment of tuberculous stenosis of the ureter by use of a modelling ureteral catheter. Apropos of 11 cases]. The authors' experience involves 11 cases. In four instances, insertion of the ureteral catheter via endoscopy was impossible. Two of these patients were not subjected to surgery because of their great age. In the other two, anti-reflux uretero-vesical reimplantation and insertion of a modelling ureteral catheter was carried out by an open surgical approach. A good result was obtained in both. In the other six patients, it was possible to insert the catheter via endoscopy. This gave five successess and one failure. The single failure was a case of long standing tuberculous stenosis of the ureter. The modelling ureteral catheter, when inserted by endoscopy, gives, in combination with corticosteroids and anti-tuberculous therapy, almost constantly successful results in recent cases of stenotic tuberculosis of the ureter in young patients.


[Unilateral implantation of the ureter into the posterior urethra in boys. 5 cases (author's transl)]. The authors report five new cases of unilateral implantation of the ureter into the posterior urethra in boys. Study of these cases confirms the classical data, i.e.: --The chief presenting symptom is infection. There is no urinary incontinence. --The principle examinations useful in diagnosis are the I.V.P. and urethroscopy. --The ectopic termination is in most cases associated with a double ureter, arising from the upper pelvis. However, the ureter may be single (1/5). --In three cases out of five the upper kidney was dysplasic, necessitating partial nephrectomy. In two cases out of five the kidney corresponding to the ectopic ureter was functional, making possible conservatrice surgery with reimplantation of the pathological ureter into the bladder.


[The echotomographic diagnosis of renal expansive processes (author's transl)]. The authors carried out a study of renal echotomography as a diagnostic technique for renal expansive processes. The reliability of the results obtained, the simple technique, its absolute harmlessness and the low cost are tending to give echotomography an increasingly important place in the differential diagnosis of renal masses. This limits, without eliminating, the indications for arteriography and exploratory surgery. It should in no way be considered to be in competition with radiography, but rather as an excellent complementary technique. By the use of apparatuses giving moving images, our group obtained 96.4 per cent of success in liquid masses and 90.3 per cent of success in solid masses.


[The value of ultrasonic flow measurement in the postoperative surveillance and observation of arteriovenous fistulae for chronic haemodialysis (author's transl)]. Measurement of instantaneous circulatory rates by Doppler effect per-operatively, at the 6th hour, the 8th day and the 2nd month was used to observe haemodynamic changes in 20 arteriovenous fistulae created for the purpose of chronic haemodialysis. Blood flow rates, initially low, increased up to the 8th day and were subsequently stable. A circulatory rate of 22 cm/s in the drainage vein 6 hours after the operation would seem to guarantee the permeability of the therapeutic arteriovenous anastomosis. To some extent, the authors have described the course of therapeutic arteriovenous fistulae during the first two months. Criteria of permeability have been determined making it possible to spare the vascular capital of these patients.


[Testosterone and prostatic cancer (author's transl)]. Hormono-dependent epithelial cells of the prostate gland loose their histologic and cytologic differentiation when becoming neoplastic. Such loss of differentiation is related to a change in testosterone metabolism measured by the testosterone metabolites ratio (17 beta-hydroxy/17-oxometabolites). This ratio decreases with differentiation losses and increasing independence from androgenic steroids. Knowledge of that ratio is suggested, prior to the starting of antiandrogenic therapies.


Enzymatic properties of viral replication complexes isolated from adenovirus type 2-infected HeLa cell nuclei. When HeLa cell nuclei, isolated 17 h after infection with adenovirus type 2 (Ad2), were extracted with 200 mM ammonium sulfate, Ad2 nucleoprotein complexes were selectively released. These complexes contained a DNA polymerase activity that corresponded to DNA polymerase molecules actively engaged in Ad2 DNA replication. Under our high-salt (200 mM ammonium sulfate) incubation conditions, where no reinitiation occurred, full-length Ad2 DNA chains were synthesized by elongation of chains that had been initiated in vivo. This conclusion was further supported by density labeling experiments indicating that the in vitro DNA synthesis was semiconservative. Evidence is presented suggesting that at least part of the DNA polymerase molecules engaged in Ad2 DNA replication belong to the gamma class.


Distinctive protein requirements of replication-dependent and -uncoupled bacteriophage T4 late gene expression. This paper further explores the relationship of viral DNA replication to bacteriophage T4 late gene expression. It is shown that replication coupled and -independent late transcription make different qualitative or quantitative demands on phage protein synthesis. In further analysis of these different protein synthesis requirements, experiments were performed with a temperature-sensitive mutant in T4 gene 55 (ts553). It is known that the gene 55 product regulates T4 late gene expression and binds to RNA polymerase. In the experiments presented here, it is shown that the temperature sensitivity of the ts553 gene 55 protein depends on whether it is involved in replication-coupled or -independent T4 late transcription. This is evidence that the proteins constituting the transcription apparatus interact differently with late transcription units in T4 DNA, depending on whether late transcription is replication coupled or independent.


Isolation of the viral DNA replication complex from adeno-associated virus type 1-infected cells. The replication complex active in adeno-associated virus type 1 (AAV-1) DNA synthesis in vitro was solubilized, with a nonionic detergent, from the nuclei of human embryonic kidney cells coinfected with AAV-1 and an early temperative-sensitive mutant (ts125) of human adenovirus type 5 at the nonpermissive temperature (40.5 degrees C). The complex sedimented with a mean size of 23S and contained parental AAV-1 DNA. Most of the DNA synthesized with the AAV-1 DNA replication complex in vitro was AAV-1 DNA, as revealed by DNA-DNA hybridization and sedimentation in a neutral sucrose gradient. However, it sedimented in an alkaline sucrose gradient as molecules smaller than AAV-1 DNA (14.4S). The AAV-1 DNA replication complex was not formed in cells infected with AAV-1 alone.


Inhibition of viral DNA synthesis in stationary chicken embryo fibroblasts infected with avian retroviruses. Previously, we reported (Fritsch and Temin, J. Virol. 21:119-130, 1977) that infectious viral DNA was not present in spleen necrosis virus-infected stationary chicken cells. However, a stable intermediate was present in such infected stationary cells as evidenced by the appearance of infectious viral DNA shortly after serum stimulation of these cells. After serum stimulation of infected stationary cells, the infectious viral DNA appeared first in the nucleus. In contrast, in infected dividing cells the infectious viral DNA appeared first in the cytoplasm. Significantly reduced amounts of complete plus- or minus-strand viral DNAs were detected by nucleic acid hybridization in stationary chicken cells infected with spleen necrosis virus or Schmidt-Ruppin Rous sarcoma virus compared with the amounts detected in infected dividing cells. These experiments indicated that infected stationary cells did not contain complete noninfectious copies of viral DNA. Furthermore, 5-bromodeoxyuridine labeling and cesium chloride density gradient centrifugation analysis of the infectious viral DNA that appeared after serum stimulation of infected stationary cells indicated that most viral DNA synthesis occurred after addition of fresh serum.


Isolation and mapping of t gene mutants of bacteriophage T4D. A procedure for selective isolation of T4 t mutants is described. At 120 min after infection of Escherichia coli cells with a low multiplicity of T4 bacteriophage, the mixture was sedimented through a linear sucrose gradient, and infected cells that remained intact were collected as the fastest sedimenting fraction. Ten to 50% of the phage released by chloroform treatment of this fraction were t mutants. Collection of a high proportion of t mutants depended on efficient elimination of cells that would survive because of superinfection lysis inhibition. This was accomplished by early addition of anti-T4 serum and heat-killed cells to inactivate progeny wild-type phage released at the normal burst time. Of 85 t mutants that were isolated and mapped, 23 new mutations were found, 14 of which are suppressible by an rII mutation and 9 of which are suppressible by rII or amber suppressors. Two hot-spot sites for spontaneous mutations were found; 14 mutants at one site, represented by a frameshift mutation, and 12 mutants at a second site were obtained from 39 spontaneous mutants independently isolated from different parental plaques. On our map of the t gene, the distance between the farthest t mutations is 6% recombination. A nonreverting triple t mutant, constructed to contain a frameshift mutation between two amber mutations, exhibited the same t mutant phenotype observed with revertible t mutants.


Physical organization of subgroup B human adenovirus genomes. Cleavage sites of nine bacterial restriction endonucleases were mapped in the DNA of adenovirus type 3 (Ad3) and Ad7, representative serotypes of the "weakly oncogenic" subgroup B human adenoviruses. Of 94 sites mapped, 82 were common to both serotypes, in accord with the high overall sequence homology of DNA among members of the same subgroups. Of the sites in Ad3 and Ad7 DNA, fewer than 20% corresponded to mapped restriction sites in the DNA of Ad2 or Ad5. The latter serotypes represent the "nononcogenic" subgroup C, having only 10 to 20% overall sequence homology with the DNA of subgroup B adenoviruses. Hybridization mapping of viral mRNA from Ad7-infected cells resulted in a complex physical map that was nearly identical to the map of early and late gene clusters in Ad2 DNA. Thus the DNA sequences of human adenoviruses of subgroups B and C have significantly diverged in the course of viral evolution, but the complex organization of the adenovirus genome has been rigidly conserved.


Persistent infection of cultured mammalian cells by Japanese encephalitis virus. Persistent infections were established by serial undiluted passage of flavivirus Japanese encephalitis virus in a line of rabbit kidney cells (MA-111). The persistently infected cells resembled uninfected cells in most respects. Low levels of infectious virions were released from a small percentage of cells, and a larger and more variable percentage was shown to possess viral antigen by fluorescent-antibody staining. Released viruses were shown to interfere with replication of wild-type Japanese encephalitis virus. Persistently infected MA-111 cells could not be superinfected with homologous wild-type Japanese encephalitis virus but could be superinfected with two heterologous viruses. Transfer of cell culture medium from persistently infected MA-111 cells to a line of African green monkey kidney cells (Vero) resulted in similar persistent infections in the latter cells. Temperature sensitivity and host-cell interferon production were not involved in establishment or maintenance of persistence. Determination of ratios of physical particles to infectious particles revealed that many defective, noninfectious viruses were present, suggesting that defective interfering particles may be responsible for persistency.


Evidence for two nucleotide sequence orientations within the terminal repetition of adeno-associated virus DNA. Duplex adeno-associated virus (AAV) DNA, produced by annealing plus and minus virion single strands, has been digested with several bacterial restriction endonucleases. These studies reveal the existence of alternate secondary structures at the termini of duplex AAV DNA. Analysis of the sites of endo R-Hpa II cleavage, the products of complete endo R-Hpa II digestion, and the multiple terminal secondary structures leads to the conclusion that there are two possible nucleotide sequences at each end of AAV DNA. A model that attributes the terminal nucleotide sequence heterogeneity to two possible orientations of the first 120 nucleotides at each end of the DNA is proposed; in one case the sequence is 1 to 120; in the other case the sequence is inverted. An origin of the inversion is suggested based on previously described intermediates in AAV DNA replication.


Unique peptide maps of the three largest proteins specified by the flavivirus Kunjin. Tryptic digests of four polypeptides found in Kunjin virus-infected Vero cells, NV5, NV4, V3, and NV3, were compared by peptide mapping. The polypeptides to be analyzed were labeled with radioactive methionine and separated by electrophoresis through polyacrylamide gels containing sodium dodecyl sulfate. Because infection of Vero cells by Kunjin virus does not inhibit host cell protein synthesis, radioactively labeled viral polypeptides prepared from infected cells migrate coincidentally during sodium dodecyl sulfate-gel electrophoresis with some of the labeled host proteins. Thus, the genuine viral methionine-containing peptides in tryptic digests of viral proteins have been identified by co-analyzing polypeptides from [3H]methionine-labeled uninfected cells and [35S]methionine-labeled infected cells and determining the 35S/3H ratio in the peptides resolved in two dimensions on thin-layer chromatography plates. The peptide map of NV3 demonstrated that it is host coded, whereas NV5, NV4, and V3 have unique peptide maps and, therefore, account for approximately one-half of the coding potential of Kunjin virus RNA.


Comparisons of the peptide maps of Kunjin virus proteins smaller than the envelope protein. We analyzed the maps of [35S]methionine-labeled tryptic peptides of the Kunjin virus-specified proteins NV2 1/2, NV2, V2, NV1 1/2, NV1, and V1. The peptides of NV1 1/2 are identical to those of V2, except for one peptide contained only in the latter. The maps of each of the other proteins are unique and, consequently there is no evidence of any one protein being derived from another by proteolytic cleavage. The tryptic peptide maps of the above polypeptides were also compared with those of the larger Kunjin proteins, NV5, NV4, and V3. The resolution of the peptides of NV2 1/2 and NV1 is adequate to exclude any relationships with NV5 and NV4, but a possible relationship with V3 remains, although it seems unlikely in the light of other evidence. Since the peptide map of V1 is comprised of only two methionine-containing peptides similar in mobilities to two peptides found in the maps of NV5, NV4, and V3, a precursor, if any, of V1 has not been positively identified. The peptides of NV2 and V2 (NV1 1/2) are not contained in digests of NV5, NV4, or V3, and therefore, like the latter, NV2 and V2 (NV1 1/2) are independent products of translation from the positive-strand genome.


Electron microscopic studies of bacteriophage M13 DNA replication. Intracellular forms of M13 phage DNA isolated after infection of Escherichia coli with wild-type phage have been studied by electron microscopy and ultracentrifugation. The data indicate the involvement of rolling-circle intermediates in single-stranded DNA synthesis. In addition to single-stranded circular DNA, we observed covalently closed and nicked replicative-form (RF) DNAs, dimer RF DNAs, concatenated RF DNAs, RF DNAs with single-stranded tails (theta, rolling circles), and, occasionally, RF DNAs with theta structures. The tails in theta molecules are always single stranded and are never longer than the DNA from mature phage; the proportion of theta to other RF molecules does not change significantly with time after infection. The origin of single-stranded DNA synthesis has been mapped by electron microscopy at a unique location on RF DNA by use of partial denaturation mapping and restriction endonuclease digestion. This location is between gene IV and gene II, and synthesis proceeds in a counterclockwise direction on the conventional genetic map.


Evidence for frequent lysogeny in lactobacilli: temperate bacteriophages within the subgenus Streptobacterium. A total of 17 of 21 Lactobacillus strains of the subgenus Streptobacterium were lysogenic. Two different temperate phages isolated from such lysogens are very similar to Lactobacillus casei phage PL-1. The narrow host range of bacteriophage PL-1 appears to be caused by homoimmunity.


Superinfection exclusion by bacteriophage T7. Only two of the early genes of bacteriophage T7 were found to play a significant role in exclusion of superinfecting bacteriophage T3 particles; genes 0.3 and 1. Protein synthesis by the preinfecting phage particle was not required for efficient exclusion. These findings are discussed with regard to the known functions of these genes during T7 development.


Recombination between temperature-sensitive mutants of the arenavirus Pichinde. High-frequency recombination was obtained with temperature-sensitive, conditionally lethal mutants of the arenavirus Pichinde.


DNA injection and genetic recombination of alkylated bacteriophage T7 in the presence of nalidixic acid. Marker rescue experiments with alkylated T7 bacteriophage carried out in the presence and in the absence of nalidixic acid suggest that the gradient in rescue is due to two alkylation-induced causes: a DNA injection defect and an interference with DNA synthesis.


Semen cryopreservation: an update.

Semen cryopreservation: an update. Cryopreservation of semen has a place in reproductive medicine. It is done best using liquid nitrogen as the refrigerant and the pre-freeze semen should be of good quality. High quality spermatozoa survive the freezing-thawing process and ordinarily result in good babies. Abnormal sperm generally do not survive the freezing-thawing process, which, consequently, results in a more viable union and outcome from the germ cells. Cryopreservation of semen can be used to preserve semen before medical or surgical sterilization, to augment the sperm count in patients with certain types of oligospermia and to manage the childless couple by donor semen artificial insemination in those instances in which the husband is infertile. Cryopreserved semen produces babies and perhaps thousands of humans have been the result of conception that resulted from cryopreserved spermatozoa.


Revascularization of the chronic totally occluded renal artery with restoration of renal function. Nine patients with non-functioning kidneys and complete renal artery occlusion discovered on arteriographic investigation for hypertension underwent renal artery revascularization with successful restoration of renal blood flow. Of these patients 7 experienced recovery of renal function and 2 showed no evidence of improvement. One patient had a creatinine clearance of 38 cc per minute from the revascularized kidney 2 years postoperatively. Predictive determinants of salvageable renal parenchyma were the histologic evidence of intact viable glomeruli and the angiographic features of a rich perihilar collateral circulation in the presence of a proximal occlusion with a patent distal renal artery.


Results of non-operative management of blunt renal trauma. A study of 84 patients with blunt renal trauma has revealed that expectant, non-operative management of the clinically stable patient with either minor or more severe injuries (excluding vascular pedicle trauma) gives satisfactory results and entails few subsequent complications. The nephrectomy rate with angiographic delineation of devascularized tissue and would seem to be comparable to that of patients afforded immediate surgical intervention, without the threat of loss of the renal unit that appears to be entailed by early operation.


Renal carbuncle: the use of ultrasound in its diagnosis and treatment. The use of ultrasound in the diagnostic and therapeutic management of 5 patients with renal abscesses is described. A spectrum of ultrasonic findings was noted, with the majority of the lesions being anechoic (3 cases). However, a few lesions showed a mixed pattern (2 cases). Ultrasonic aspiration of abscess fluid for culture and sensitivity obviated an operation in 1 case. For the first time, ultrasonically guided, percutaneous, indwelling catheter drainage of a renal carbuncle is reported. Since the patient had failed to respond to systemic antibiotic therapy this technique saved the patient from undergoing an operation. The clinical and ultrasonic findings in the 6 previous case reports of abscesses are reviewed.


Hemangioma in the wall of a cyst.

Hemangioma in the wall of a cyst. Two cases of hemangioma are reported. In the first case a hemangioma was found inside a benign renal cyst. The confusion of this unusual lesion with carcinoma is discussed. The second case is another example of the segmental radiographic sign that is useful in the preoperative diagnosis of hemangioma.


Renal cell carcinoma involving the inferior vena cava: radiologic evaluation and surgical management. The evaluation and management of 3 patients with renal cell carcinoma and varying degrees of vena caval involvement are described. Extrinsic compression, intraluminal tumor thrombus and direct invasion have characteristic features on the inferior venacavograms. With knowledge of the nature and extent of vena caval disease total removal of the tumor is possible in most cases with an acceptably low morbidity. Extensive vena caval pathology by no means precludes long-term survival and should not be regarded as a sign of inoperability.


Idiopathic regression of metastases from renal cell carcinoma. Herein we review 48 acceptable cases of idiopathic regression of metastases from renal cell carcinoma culled from the literature and present 3 additional cases. The data are analyzed and the issue of organ specificity in coping with metastases is discussed.


Renal cell carcinoma presenting with metastases to pulmonary hilar nodes. Mediastinal and hilar renal cell carcinoma metastases are reported in 9 patients, representing an incidence rate of 8 per cent in the series. This observation indicated an ominous prognosis since the mean survival of these patients was only 1.4 months after the discovery of the neoplasm. It is postulated that this poor prognosis is attributable to the size of the primary lesion, with direct extension into retroperitoneal structures and perhaps to an associated exhaustion of immunologic defense mechanisms of the patients. Dissemination from the involved retroperitoneal lymphatics to the thoracic duct and then in retrograde fashion via the bronchomediastinal and paratracheal trunks is advocated as the pathway for this tumor dissemination.


Pelvic lipomatosis: 5-year followup.

Pelvic lipomatosis: 5-year followup. Followup of 5 cases presented in 1971 and report of 8 additional cases confirm the initial conclusions that pelvic lipomatosis is a benign but potentially progressive process leading to ureteral obstruction. Young black subjects are affected most commonly. More than 40 per cent of the patients have required permanent urinary diversion.


Gunshot wounds of the ureter: 5 years of experience. During 5 consecutive years 20 patients with ureteral gunshot wounds were treated at the Detroit General Hospital. Among the 19 patients treated surgically 4 unrelated deaths occurred and 3 patients underwent a second exploration. No kidney was lost. Our surgical technique involving a tension-free, watertight anastomosis and diversion is emphasized. We believe that better results are obtained with stented repairs.


The advantages of routine use of nephrostomy drainage with pyeloplasty. Pyeloplasty by a dismembered Y-V plasty technique to correct congenital ureteropelvic junction obstruction has been used for 8 years with uniform success. The routine use of a neophrostomy and splinting catheter offers many advantages and no significant disadvantages.


A simple non-touch technique for continuous suprapubic urinary drainage. A simple non-touch technique for urinary paracentesis with a standard intracath is described. The application of this method for continuous urinary drainage in the relatively contaminated bedside environment may reduce the chance of bladder injury and infection in gravely ill patients until a more definite procedure is feasible.


Injury to the male posterior urethra in fractured pelvis: a new classification. The present criteria to diagnose a ruptured posterior urethra in cases of a fractured pelvis do not provide accurate information on the degree and site of the urethral injury. A method of retrograde urethrography in such patients is described and the results obtained in 15 cases are reported. On the basis of these results a new classification of membranous urethral rupture in cases of fractured pelvis is proposed: type 1--the prostate or urogenital diaphragm is dislocated but the membranous urethra is merely stretched and not severed, type 2--the membranous urethra is ruptured above the urogenital diaphragm at the apex of the prostate and type 3--the membranous urethra is ruptured above and below the urogenital diaphragm. The clinical significance of these lesions is discussed and a plea is made for the more widespread use of retrograde urethrography in patients with a suspected posterior urethral rupture.


Primary carcinoma of the male urethra developing after urethroplasty for stricture. Most investigators agree that a urethral stricture is a predisposing cause of primary carcinoma of the urethra. The etiology of the carcinoma is probably chronic irritation. The role of squamous metaplasia in the etiology is discussed briefly. A case of primary squamous cell carcinoma of the urethra occurring 4 years after a first stage urethroplasty is reported and 2 cases from the literature are described. The suggested origins of urethral malignancy after urethroplasty are 1) unrecognized malignancy at operation, 2) premalignant mucosal changes that progress postoperatively, 3) recurrence of stricture with continued irritation leading to malignant metaplasia and 4) malignant change in the urethroplasty skin flaps. Although rare, primary male urethral carcinoma is a deadly disease. The hope for early diagnosis is a high index of suspicion during urethroplasty and in subsequent followup studies. The patient presented herein also exhibited pseudohyperparathyroidism as a result of the malignancy.


New hinged silicone penile implant.

New hinged silicone penile implant. A new paired hinged silicone prosthesis is described. The hinge allows the penis to move freely and hang in a dependent position without constrictive clothing and permits satisfactory coitus. A conical tip more nearly conforms to the distal corpus and the proximal end may be trimmed during the operation to fit the individual patient.


Corpus cavernosography in conditions other than Peyronie's disease. The value of corpus cavernosography in the management of conditions other than Peyronie's disease is discussed. The procedure should be done under fluoroscopic control.


Elevated urinary levels of 5-hydroxyindole acetic acid and its relationship among levels of plasma follicle stimulating hormone, testosterone and testicular pathology in patients with severe oligospermia and/or azoospermia. Plasma follicle stimulating hormone, testosterone and urine 5-hydroxyindole acetic acid levels were measured in 300 patients seen at an andrology clinic. Testicular biopsies were obtained from many of the severely oligospermic or azoospermic patients. Plasma follicle stimulating hormone concentrations were related inversely to sperm cell concentration, while plasma testosterone concentrations were depressed as the sperm count decreased to 5 times 10(6) per ml. The urine levels of 5-hydroxyindole acetic acid followed the same pattern as follicle stimulating hormone and were elevated in the group of individuals with sperm counts less than 10 times 10(6) per ml. Elevations in 5-hydroxyindole acetic acid often were associated with abnormalities in the testicular biopsy. Only 30 per cent of the patients who had elevated 5-hydroxyindole acetic acid also had elevated follicle stimulating hormone or depressed testosterone levels. The factors responsible for the elevation in 5-hydroxyindole acetic acid levels as the sperm count declines remain unclear.


Diagnostic ultrasound in the evaluation of scrotal masses. Evaluation of 27 patients with scrotal masses was done with gray scale ultrasound. Given the clinical diagnosis ultrasound proved reliable in almost all cases.


Autoantibodies following vasectomy.

Autoantibodies following vasectomy. The incidence of 7 different autoantibodies was determined in 904 men 3 months to 6 years after vasectomy operations and in 700 control subjects. There was no clinically significant increase in autoantibodies in the vasectomized group nor was any autoimmune disease detected that could be related to the vasectomies.


Pulmonary dysfunction after lymphangiography. Pulmonary function tests were done on 15 patients before and after bipedal lymphangiography. Lymphangiography was associated with an approximate 10 per cent reduction in lung volume. This phenomenon persisted for 48 to 72 hours. The probable mechanism for this reduction is closure of terminal airways or alveolar ducts or both and is reversible by beta-adrenergic drugs. The reduction does not correlate with the severity of pre-existing pulmonary disease. The degree of pulmonary impairment can be assessed roughly by measurement of the vital capacity. An operation can be performed safely 3 to 5 days after lymphangiography.


Cystometry: detrusor reflex activation, classification and terminology. Changes in the concept of neural organization for micturition and the use of high flow gas cystometers have altered the performance of clinical cystometry and test interpretation. Detrusor reflex activation procedures in carbon dioxide cystometry include rapid bladder distension, change in postural states, use of bethanechol, urethral and anal distension, and sleep. Sleep cystometry requires the use of electroencephalography. These procedures have permitted specific delineation of the syndrome of detrusor reflex instability. Test interpretation is based upon detection of the presence of detrusor reflex instability or end organ denervation.


Balanced bladder function in spinal cord injury patients. A urodynamic assessment was done on 55 patients with spinal cord injuries treated with intermittent catheterization and therapy for autonomic dysreflexia and external sphincter spasm. While 95 per cent of the patients with upper motor neuron lesions achieved balanced bladder function they were not necessarily free of a catheter. The results obtained in male patients compare favorably to those reported from specialized spinal cord injury centers. Female spinal cord injured patients generally were unable to achieve a catheter-free status.


Combined radiographic and manometric assessment of urethral sphincter function. A technique combining manometric, radiographic and electromyographic data to investigate primary urethral sphincter weakness is presented. These data indicate that closure of the intraabdominal urethra by smooth muscular activity is of critical importance in passive continence.


Sympathetic dyssynergia in the region of the external sphincter: a possible source of lower urinary tract obstruction. Voiding cystourethrography demonstrated urethral constriction at the level of the external urinary sphincter in 10 patients with neurological dysfunctions. Ten mg. phentolamine mesylate intravenously alleviated this constriction, permitting better flow and reducing residual urine in 5 patients with a traumatic spinal injury, 2 with transverse myelitis and 1 who had had a cerebrovascular accident. Oral therapy with phenoxybenzamine hydrochloride, used in 7 of the 8 patients, reduced the post-void residual urine and produced improvement in hydronephrosis when present. These observations are consistent with the presence of a significant sympathetic component to obstruction at the region of the external sphincter in certain neurological disorders.


Kidney biopsy: analysis of patient data and indications for kidney biopsies. To evaluate the use of the facilities of a teaching renal unit patient data during the last 33 months were studied. A total of 534 patients. The pattern of referrals, the major categories of renal diseases and the results of the kidney biopsies were examined to offer the urologist a profile of a new clinic and some guide lines concerning referrals for kidney biopsies.


Pediatric hypertension as a delayed sequela of reflux-induced chronic pyelonephritis. Chronic pyelonephritis secondary to vesicoureteral reflux has been shown to cause occasionally systemic hypertension. The hypertension may occur in the presence or absence of bacterial urinary infection, is renin-mediated and may develop years after ureteral reimplantation. Surgical excision of a scarred atrophic renin-producing segment may result in amelioration of the hypertension or at least provide better medical control with less toxic antihypertensive agents. Surgical removal of renal tissue is not recommended in patients with depressed renal function unless the hypertension is malignant and uncontrolled.


A xanthine stone in a xanthinuric boy: a biochemical case study. A xanthine urinary stone is rare. A case of a xanthine stone in the bladder of a xanthinuric boy is presented. The literature is reviewed and biochemical studies are discussed.


Neurofibromatosis of the bladder in children: case report and literature review. A case of plexiform neurofibroma of the lower urinary tract is presented as well as a review of all previously reported cases in childhood. We suggest aggressive management in patients with diffuse disease.


Complications of single and multistage operations for hypospadias: a comparative review. From 1970 through 1975, 198 children with hypospadias were operated upon at our clinic. Three basic types of primary urethroplasty were used: 1) a modified 2-stage Cecil urethroplasty after separate straightening, 2) a modified 1-stage Denis Browne procedure after prior correction of chordee and 3) a 1-stage combined repair of hypospadias and chordee. A comparative review of early complications is presented.


Five-year survival after disseminated paratesticular rhabdomyosarcoma. A 5-year survivor of disseminated metastatic rhabdomyosarcoma arising from the paratesticular tissues is reported. Each of the 6 patients with paratesticular rhabdomyosarcoma treated at this hospital has been free of disease from more than 2 months to more than 7 years. The unusually good prognosis associated with this site may be owing to early detection, predictable pathways of initial lymphatic dissemination and aggressive surgical treatment followed by radiotherapy and multiple agent chemotherapy.


Hemolytic-uremic syndrome with prolonged anuria. Total cessation of urine formation beyond 4 days with ultimate survival is a rare occurrence. A child with the hemolytic-uremic syndrome was anuric for 27 days and renal function improved. the metabolic effects of acute renal failure require careful control of water and electrolyte balance and, when indicated, peritoneal and/or hemodialysis until renal function returns.


Successful delivery of a patient on hemodialysis for acute renal failure: a case report and review of the literature. A case of hemodialysis for acute renal failure during the thirty-fourth week of gestation is reported. Subsequently, the patient delivered a normal viable baby, weighing 1,790 gm. Maternal renal function returned to normal after delivery.


Mid-ureteral leakage: an unusual complication of ileal conduit. Peritonitis after ureteroileal urinary diversion usually occurs from urinary leakage caused by disruption at the ureteroileal anastomosis. A case of leakage localized at the mid ureter is reported.


Intestinal obstruction: a complication of percutaneous cystotomy. A case report. The percutaneous suprapubic bladder catheter has become an important tool for the urologist because of its efficacy, simplicity and wide range of applications. A case of intestinal obstruction secondary to percutaneous cystotomy with the Bonanno suprapubic bladder drainage catheter is reported.


Anuria following silver nitrate irrigation for intractable bladder hemorrhage. Intravesical silver nitrate has been used for intractable bladder hemorrhage. A case of anuria resulting from this technique is reported. The etiology of anuria in this patient was probably owing to obstruction from deposition of silver salts. The level of obstruction was the ureterovesical junction on 1 side and the collecting ducts at the renal papillae on the other side. Therapy consisted of vigorous endoscopic evacuation of deposited silver salts from the bladder and hemodialysis with good results.


Y-type urethral duplication in male subjects. A case of Y-type urethral duplication is described with urethrograms showing the anterior and posterior channels arising from the prostatic urethra. Postmortem studies revealed the dominant posterior channel and its relationships to the stenotic anterior channel and anus.


Y-type urethral triplication.

Y-type urethral triplication. A case of Y-type urethral triplication is reported. Urethrograms and urodynamics revealed the stenotic anterior urethras and a functional posterior urethral channel with a normal urethral pressure profile.


Inflammation of the periurethral glands of Littre simulating tumor. A young man presented with a subfrenular nodule of the penis that proved to be ectasia and chronic inflammation of the periurethral glands of Littre. Pathological processes involving these glands are rare but must be considered in the differential diagnosis of penile or urethral lesions.


Hidradenitis suppurativa of the scrotum. A patient with hidradenitis suppurativa of the scrotum is described. The clinical presentation and treatment are discussed.


Thoughts on the prevention of urologic liability claims. We have approached the problems of increasing urological liability claims with a superficial study of their causes and some suggested solutions. We believe that this approach is important because it is one that the urological community can take immediately rather than waiting for changes in state and federal laws that may be of benefit in decreasing the impact of these suits. It seems to be the common disease and the simple operation that lead to the lodging of a claim.


Adult polycystic kidney disease: a review of 100 cases. Herein we review 100 cases of adult polycystic kidney disease. Flank pain was the most common presentation in these cases. In 20% of the patients calculi were noted and 10% had obstruction. The average patient age at death was 57 years. The importance of tomography is emphasized with key radiographic features, such as bilateral large kidneys, inhomogeneous nephrogram, caliceal distortion and poorly defined renal margins. Cystic involvement of the liver and spleen may help to confirm the diagnosis. Differential diagnosis includes bilateral multiple simple cysts, angiomyolipomatosis and bilateral renal carcinomas.


Primary renal artery dissecting aneurysm: a review. Primary dissecting aneurysms of the renal artery are exceedingly rare. Our recent encounter with a patient with this condition prompted a review of the literature. The diagnostic and therapeutic problems in 30 patients were analyzed and guide lines for proper management were discussed. The triad of flank pain, hematuria and hypertension of acute onset in the absence of urinary obstruction should suggest this rare condition.


Prostaglandin: increased production by renal cell carcinoma. The syndrome of hypercalcemia in patients with renal cell carcinoma without metastasis to bone, in association with elevated levels of immunoreactive prostaglandin E and normal parathyroid hormone levels, prompted the investigation of an etiologic relationship of increased prostaglandin in this syndrome. Ethyl acetate extracts of tissue culture effluents, primary and metastatic renal cell carcinoma, and plasma were chromatographed on silicic acid columns and assayed by double antibody immunoprecipitative methods for immunoprecipitative methods for immunoreactive prostaglandins A and E. Increased levels of immunoreactive prostaglandins A and E were found 1) to be generated in parallel with cell growth during a period of time by renal cell carcinoma in monolayer growth, 2) in extracts of primary and metastatic renal cell carcinoma tissue and 3) in the venous effluent of a kidney bearing a renal cell carcinoma. These findings support the hypothesis that renal cell carcinoma can produce prostaglandins. Furthermore, reported syndromes of patients with renal cell carcinoma associated with elevated prostaglandin levels may result from the autonomous production of prostaglandins in vivo by the tumor.


Continent cecoileal conduit: preliminary report. A continent cecoileal conduit to improve rehabilitation after external urinary diversion is described. The isolated cecum functions as a reservoir. The continence mechanism is constructed by intussuscepting the terminal ileum into the isolated cecum to form a nipple, preventing leakage of urine. The kidneys are protected from cecoureterorenal reflux by ureterocecostomies with submucous tunnels. We have used this technique on 4 patients, 2 of whom need no external urinary pouch since the urostoma is absolutely continent. One patient became incontinent 3 months postoperatively and is wearing a conventional bag and 1 patient died. There is no refluex into the kidneys. The upper urinary tract, which is dilated slightly 4 weeks postoperatively, tends to become normal after a few months.


Open ureterocolonic anastomoses.

Open ureterocolonic anastomoses. A simple technique for open ureterocolonic anastomosis is presented. This technique provides adequate exposure for mucosal-to-mucosal approximation and allows the construction of an antireflux ureterocolonic anastomosis.