On spatial visualization in college students.

This study investigated two questions: (a) Do individuals with distinct career orientations have different spatial reasoning abilities? (B) Is there a sex difference in the spatial reasoning abilities of people with a similar career orientation? A spatial visualization test was administered to university students enrolled in four different types of mathematics courses: calculus (n=37), business statistics (n=72), remedial mathematics (n=58), and mathematics for elementary school teachers (n=56). The examination covered four forms of spatial visualization. Comparison of performance between groups and within groups (e.g., males in elementary education) scored higher than the expected sex on a majority of the variables. Sex differences were observed within each of the courses. On three of the four variables students in the calculus courses scored higher than students in the other courses.


Colchester revisited: a genetic study of mental defect.

This reanalysis of a classic survey leads to inferences about design of genetic studies, resolution of heterogeneity, and the role of autosomal and sex-linked genes in mental retardation, which is no longer refractory to segregation analysis. By discriminating between sociofamilial and biological types we estimate that at least 351 autosomal loci can produce mental retardation, with an inbred load of 0.83 detrimental equivalents and a mutation rate of 0.008 per gamete, or less than 2.4 X 10(-5) per locus. The distribution of probands was estimated as: 7 per cent medical, 60 per cent sociofamilial, and 33 per cent biological. Simple genetic mechanisms account for virtually all the biological category. Within the sociofamilial group cultural inheritance and polygenes could not be resolved.


Height and seriousness of crime in XYY men.

The case histories of XYY males in two security settings were ranked by degree of seriousness of crime. The correlations of these scores with height were either zero (for data of Daly with the history of the propositus excluded) or positive (for data of Jacobs et al., P less than 0.05). For both studies, the results were contrary to the expectation of negative correlation which would be found if, in accord with Hunter's suggestion, authorities were biased to place XYYs in security settings because of the more threatening appearance associated with larger stature.


Muscle nuclear changes in fetuses at risk for Duchenne muscular dystrophy.

Muscle nuclear size was found to be significantly greater in fetuses at risk for Duchenne muscular dystrophy than in normal male fetuses of comparable gestational age. This supports the contention that the disease is already manifest in utero by the second trimester of pregnancy.


Immunoglobulin levels in dystrophia myotonica.

Levels of immunoglobulins IgG, IgA, and IgM were measured in 38 patients with myotonic dystrophy, in normal members of their families, and in matched controls. Log IgG was significantly reduced in the patients. IgG investigation provides a further parameter to appraise the status of apparently unaffected members of myotonic dystrophy families.


Heterozygote advantage for the phenylketonuria allele.

Mean weight at birth of unaffected (normal homozygous and PKU heterozygous) offspring of parents heterozygous for the phenylketonuria (PKU) allele averages significantly above that of Norwegian neonates, with no significant difference in mean age of mothers or in mean parity. It approaches the optimal birthweight--that which confers the minimum overall mortality in the pre-, peri-, and postnatal periods. This near-optimal birthweight together with the possibly higher effective fertility observed in PKU heterozygous couples (at least in those who married before 1940), has apparently more than outweighed the disadvantages of the allele in PKU homozygous offspring as shown, for example, in an excessive number of pre- and perinatal deaths among the total offspring of PKU heterozygotes, to say nothing of the PKU survivors who, often, used to die young. The two effects--fertility and viability--apparently both contribute in the same direction, to give a biological fitness in excess of 1 for the heterozygote. This heterozygote advantage presumably explains the presence of the allele at frequencies above those to be expected from the simple replacement of a homozygously-lethal allele by mutation alone.


A simple non-graphic method for pedigree description and analysis.

The graphic representation of family data for the computation of the coefficients of inbreeding [F] and relationship [r] can be replaced by an algebraic method. The organization of family data is facilitated by a data form which can be easily, thoroughly, and correctly completed, even by a layman. The computation of the coefficients is practically automatic and greatly reduces the possibility of error.


Unusual occurrence of dextrocardia with situs inversus in succeeding generations of a family.

In three cases of dextrocardia with situs inversus affecting a father and his two sons, the father had married his first cousin, the daughter of his father's sister, so that the two sons were the products of a consanguineous marriage. The general and familial incidence of the condition and the genetic influences responsible for it are discussed.


Two cases of Ellis-van Creveld syndrome in a small island population.

Two individuals showing features typical of the autosomal recessive Ellis-van Creveld syndrome have been diagnosed in a population of 1340 individuals living on a small island off the west coast of Scotland. Clinical features and family relationships of the affected individuals are described.


Prenatal diagnosis: techniques used to help in ruling out maternal cell contamination.

The combined findings from a number of different analytical techniques increases confidence that the cells analysed in amniotic fluid cell cultures are fetal in origin. Three hundred and twenty four fluids were processed using in situ processing of cultured amniotic fluid cells, allowing for analysis of mitoses from multiple colonies derived from multiple culture dishes. Screening of the same samples for fluorescent Y-chromatin was of help in indicating the genotypic sex of the primary cells. This was found to be accurate in 96% of the fluids checked. In cases where an XX complement is found, Q-polymorphism comparisons can be made between mitoses from the amniotic fluid cells and maternal lymphocytes. Of 29 such studies, 19 showed pronounced differences in their polymorphism constitution.


Familial X-linked mental retardation with an X chromosome abnormality.

An X-linked pattern of transmission observed in four families with familial mental retardation in several generations was associated with a probable secondary constriction at the distal end of the q arms of the X chromosome. Twenty retarded males and no retarded females were observed. All available live retarded males and most of their normal mothers were found to have the abnormal X chromosome. The marker chromosome was shown to be the X chromosome in each case by Giemsa banding. In affected male and female carriers the marker chromosome varied in appearance and was not present in all metaphases. The significance of this study in relation to previously reported pedigrees showing non-specific X-linked mental retardation is discussed.


Myotonic dystrophy, syringomyelia, and 2/13 translocation in the same family.

The present report describes a sibship with 2 individuals affected by myotonic dystrophy and a third with syringomyelia. The mother was affected by myotonic dystrophy. A balanced 2/13 translocation was detected in the individual with syringomyelia, in one affected by myotonic dystrophy and in their clinically normal father. The association between the phenotypic anomalies and the chromosome alteration is coincidental.


Four new cases of ring 21 and 22 including familial transmission of ring 21.

Four new cases of ring G chromosomes are presented including one family in which the ring 21 is present in a mother and in her daughter, who has 47, XXX, r(21) chromosomes. The clinical and dermatoglyphic findings in r21 and r22 syndromes are reviewed.


Physical retardation is associated with ring chromosome mosaicism: 46, XX,r(10)/45, XX,10 minus.

Cytogenetic analysis of peripheral leucocytes of a 9-year-old girl presenting with retardation of physical development indicated mosaicism for a ring 10 chromosome. Serum aspartate transaminase was within normal limits. A survey of eight markers failed to show syntenic relations with chromosome 10.


46,XX/46,XX,r(15) mosaiciam: report of a case.

Mosaicism of cells with a normal karyotype or with a ring chromosome no. 15 was found in a girl with hypoplasia of the thumbs, club feet, mental retardation, and short stature, which seems to be a feature of this chromosomal aberration.


Stable dicentric autosome, tdic (8:22)(p23:p13), in a mentally retarded girl.

A dicentric autosome, tdic(8:22)(p23:p13), was found in all metaphase cells examined from the peripheral blood of a mentally retarded girl. It is suggested that the centromere of chromosome 22 was inactive, allowing the dicentric to behave as a monocentric element. The involvement of acrocentric chromosomes in the stable dicentric autosomes of man is discussed.


Mental retardation with 45 chromosomes 45,XX,--5,--14,+der(5) t(5,14)(p15;q13) mat due to familial balanced reciprocal translocation.

A girl with severe mental retardation and odd facies and some features of the cri-duchat syndrome was found to have only 45 chromosomes. Her karyotype was 45,XX, -5, -14,+der(5) t(5,14)(p15;q13) mat. Her mother and her two sisters were found to be balanced reciprocal translocation carriers having 46 chromosomes, one of which was a very small (14pter leads to 14q13::5p15leads to 5pter) that was missing in the proposita.


Sex linked hydrocephalus.

A family showing the syndrome of X-linked hydrocephalus is presented and the relevance of this condition in genetic counseling discussed. A method of decompressing a grossly enlarged after-coming head is described.


Crossed asymmetry in Russell-Silver syndrome.

Since the initial report by Silver et al (1953), more than 50 examples of the Russell-Silver syndrome have been reported. Unilateral congenital asymmetry of the extremities has been considered one of the major features of this disorder (Silver, 1964). We recently observed a child with otherwise typical features of the Russell-Silver syndrome who had enlargement of the right hand and of the left lower extremity. We know of no other recorded example of crossed asymmetry in this clinical entity.


A new syndrome of cleft palate associated with coloboma, hypospadias, deafness, short stature, and radial synostosis.

A new syndrome characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis has been described. The family history suggests either an autosomal dominant mode of inheritance with limited expression in females or X-linkage. Other syndromes with similar phenotypes and modes of inheritance are discussed. The need for accurate and complete family histories in cases involving cleft palate and cleft lip/palate is discussed in relation to genetic counselling and recurrent risk estimates.


A student-run course in interprofessional relations.

The topic of working relationships among health professionals is one which has long been neglected in professional school curricula. During the winter of 1976 students from four health professions--medicine, nursing, occupational therapy, and physical therapy--initiated a course designed to improve their knowledge of one another's training and skills, with the larger aim of preparing themselves to work in health care teams. The nine weekly meetings are described in terms of their content and students' reactions. In the discussion the underlying themes of legal responsibilities and of sex-roles as factors in health care team functioning are identified. Suggestions are made about format and techniques that seem to be useful for courses of this type.


Operational definitions for service, training, education, and learning.

The terms "service," "training," "education," and "learning" are ambiguous and lead to confusion in medical education. An alternate method of defining the terms is explored from the point of view of the role changes which students experience as they become medical practitioners. New definitions are developed. Repetitive activities or role changes not based on the acquisition of new knowledge and skills or supervision are called "noneducational." Role refinements and changes based on the acquisition of new knowledge and skills only are called "educational." Role refinements and changes based on the acquisition of new knowledge and skills and guided by supervision are called "training." These operational definitions permit new approaches to program evaluation and a new basis for discourse between students and their teachers.


Language as a tool in medicine: methodology and theoretical framework.

Since language is the predominant instrument by which information is transmitted between doctor and patient, an understanding of the uses and functions of language in medicine is crucial to effective medical care. This paper describes a framework for the study of language as a tool in medicine. The work is based on a large volume of doctor-patient conversations tape-recorded in natural settings. A method of cataloging recorded material has been developed which allows rapid access to segments of interest on the tape itself. The writers' framework of analysis suggests that, in addition to the knowledge of social speech conventions, seven levels of linguistic information are necessary for successful communication. Based on this research, a curriculum is being designed to teach medical students the use of language as a tool in medicine in order to refine their skills as effective listeners and speakers.


Predictors of rural practice location.

Attitudes toward the urban environment and place of origin were found to be the best predictors of an optometrist's practice location. When urbanism attitude and origin were scaled and placed in an equation to predict practice location, identification of an optometrist's practice location as rural or urban was highly accurate. Most important, scores on the equation were predictive of optometry students' future practice location. A single cutoff point on the equation correctly identified 79 percent of students who entered a rural or isolated small city practice and 81 percent of those who entered urban practice. The findings imply that optometry students most likely to enter rural practice can be objectively identified early in their training. If certain factors affecting choice of practice location are common to all health professions, the predictive equation presented here may be useful in the selection of students for rural practice in medicine.


An assessment of a non-invasive technique for measuring deep body temperature.

The assessment of a non-invasive technique for measuring deep body temperature is described. An experimental system, in which the insulating effect of subcutaneous fat thickness could be simulated, was designed to test the deep body thermometer (DBT). The assumption that the instrument produced zero temperature gradient was found to be incorrect, and a mathematical model was developed which showed that the cyclically varying output of the device is an inherent property of its design. The accuracy and response time were investigated as a function of tissue thickness to assess the instrument's clinical usefulness.


A baby incubator designed for conditions in Ghana.

The prototype is described of a baby incubator, designed to be manufactured and used in Ghana, but of high enough quality to complete directly with imported models. A novel design is used, in which the usual all-round hood, with a sealed control unit underneath it, is replaced by a one-sided configuration, with the control system built into the back. It is much easier to manufacture, but still allows good access and temperature control.


Resolution of parameters in the equivalent electrical circuit of the sodium transport mechanism across toad skin.

In amphibian epithelia, amiloride reduces net sodium transport by hindering the entry of sodium to the active transport mechanism, that is, by increasing the series resistance (Rser). Theoretically, therefore, analysis of amiloride-induced changes in potential differences and short-circuit current should yield numerical estimates of all the parameters in the equivalent electrical circuit of the sodium transport mechanism. The concept has been explored by analysis of such changes in toad skins (Xenopus laevis) bathed in hypotonic sulphate Ringer's, after exposure to varying doses of amiloride, or to amphotericin, dinitrophenol or Pitressin. The estimated values of Rser, of the electromotive force of the sodium pump (ENa), and of the shunt resistance (Rsh) were independent of the dose of amiloride employed. Skins bathed in hypotonic sulphate Ringer's exhibited a progressive rise in ENa. Amphotericin produced a fall in Rser, while dinitrophenol caused a fall in ENa; washout of the drugs reversed these effects. Pitressin produced a fall in both Rser and Rsh, with a rise in ENa. These results are in accord with earlier suggestions regarding the site(s) of action of these agents.


Van der Waals interactions between cell surfaces.

Van der Waals energies of interaction between model cell surfaces are calculated for various distances of separation, layer thicknesses and compositions of cell surfaces and intercellular media. In these calculations the cell peripheries are considered to consist of two layers: (1) A phospholipid-cholesterol-protein plasma membrane and (2) a surface coat, which consists of protein, sugar and water. The required Van der Waals parameters of sugars, phospholipids and cholesterol are derived from refractive indices of their solutions in the visible and ultraviolet regions. Polarizabilities and Van der Waals parameters of these substances are determined and shown to be almost independent of concentration of solutions. Resulting isotropic polarizabilities differ by less than five percent from values obtained by the addition of bond polarizabilities. The magnitude of Van der Walls interactions between cell surfaces has been found to vary with composition according to the following sequence: water less than phospholipid less than cholesterol, protein less than sugar. A decrease in the concentration of a given substance in the cell surface at the expense of a corresponding increase in the concentration of a substance preceding it in this sequence lowers the magnitude of attractive interactions, whereas a similar change in the extracellular medium would have an opposite effect. A consideration of experimentally found variations in composition of cell surfaces results in calculated values of Hamaker's coefficients between 8 X 10(-15) ergs and 6 X 10(-14) ergs at 50 A distance of separation, which corresponds to free energies per unit area of 210-1600 kT/mu2.


Na and Cl transport and short-circuit current in rabbit ileum.

Na and Cl fluxes and short-circuit current (Isc) in rabbit ileum have been studied as a function of ionic concentrations in HCO3-free solutions. Both net Na flux (JNanet) and Isc show similar saturation functions of [Na] at fixed [Cl]. They show no significant difference between zero and 112 mM Na but at 140 mM Na Isc is significantly greater than the JNanet. Net Cl transport, secretion, is observed only at 140 mM Na and is approximately equivalent to the difference between the Isc and JNanet. The transcellular mucosa-to-serosa Na fluxes measured at 140 and 70 mM Na do not differ significantly from the corresponding Isc. The net Cl flux varies with [Cl] at fixed [Na] while Isc is virtually not affected by [Cl]. These results suggest that the absorptive Na transport process is electrogenic and responsible for the Isc and that the secretory fluxes of Na and Cl are coupled, require high [Na], vary with [Cl], and do not contribute to Isc. K-free solution abolishes the Isc after a prolonged lag. Finally, the effect of a low resistance shunt pathway on active Na absorption is examined with a four-compartment model.


Regional differences in K channels of abdominal and circumesophageal segments of the crayfish medial giant axon.

Intracellular recordings reveal that the membrane of the circumesophageal region of the medial giant axon of crayfish responds to replacement of C1 with propionate differently from that of the abdominal region of the same axon. The connective hyperpolarizes in the propionate saline, whereas the abdominal region undergoes the transient depolarization that is expected when a permeant anion (Cl) is replaced with an impermeant one (propionate). The hyperpolarization of the connectives is accompanied by an increased conductance, a decreased length constant, and an increase in threshold current for intracellular stimulation. These effects are specific for the connectives and for propionate. They do not occur on replacing Cl with other large anions, isethionate, methane sulfonate, or glucuronate. The effects of propionate are independent of Na or Ca and result from an increased K conductance. The hyperpolarization induced by propionate is increased in a K-free saline, where the resting potential (EM) is considerably positive to the emf of the K battery (EK). It is abolished in elevated Ko when EM=EK.


Charge ulse studies of transport phenomena in bilayer membranes. II. Detailed theory of steady-state behavior and application to valinomycin-mediated potassium transport.

The charge-pulse technique is applied to a study of valinomycin-mediated potassium transport across glycerol monooleate (GMO) bilayers. The theory, based on the Läuger-Stark model, is developed for the steady-state domain. The voltage dependences of the surface complexation reactions are also considered. The analysis of the data yields the folowing values for the rate constants: (see article). With the exception of this last ratio, all the values agree well with previously published data. The implication of the exponential term, 0.045, is that the plane of reaction for the surface complexation actually occurs a small distance within the membrane dielectric. If one presumes that the reaction plane is about half way between the plane of adsorbed complex and the membrane-water interface, one deduces that the complex "feels" only about 80% of the applied voltage across the membrane.


Hodgkin's disease in Turkish children: a clinical and histopathologic analysis.

Fifty-one cases of Hodgkin's disease in Turkish children under 15 years of age were clinically analyzed, and 40 cases were evaluated histopathologically according to the Rye Conference classification. Complete clinical, laboratory, and radiologic findings for each patient were examined. Most patients were of low socioeconomic class, and nearly all were Caucasian. The most common presenting clinical sign was cervical lymph node enlargement; hepatosplenomegaly was noted in 18 patients. Nearly three times as many males as females were found among the patients whose diseases were histologically analyzed, and most of the children with Hodgkin's disease were in the first decade of life. Classification of the cases revealed a predominance (67.5%) of the mixed cellularity (MC) type. Of 40 patients analyzed, 34 had disease in clinical stage IV, mostly of the MC type. The data indicated a correlation of the high incidence of the MC type of Hodgkin's disease with the socioeconomic and environmental conditions in Turkey.


Leukocyte migration inhibition in human pulmonary neoplasia.

Peripheral blood leukocytes from 65 lung cancer patients, 69 healthy donors, 33 patients with malignant disease outside the lung, and 24 patients with nonmalignant pulmonary conditions were examined for immune reactivity, as measured by the leukocyte migration inhibition assay, to antigens in homogenates of lung tumor tissue and material derived from tumor-free lung areas and a nonmalignant lung lesion. A low level of reactivity with apparent specificity was detected in the lung cancer patient group, with 17/52 showing migration inhibition with extracts of lung tumor tissue. Reactivity was also detectable in this group against homogenates of tumor-free lung and nonmalignant lung lesion. The data supported the conclusion that sensitization at least in some patients with lung cancer might be directed not only against tumor-specific antigens but also against antigens of less confined disease association.


Carcinogenicity of fibrous glass: pleural response in the rat in relation to fiber dimension.

Seventeen fibrous glasses of diverse type or dimensional distribution induced different incidences of malignant mesenchymal neoplasms when implanted in the pleurae of female Osborne-Mendel rats for periods of more than 1 year. Neoplastic response correlated well with the dimensional distribution of fibers. Fibers less than or equal to 1.5 mu in diameter and greater than 8 mu in length yielded the highest probability of pleural sarcomas, and probability trends suggested that pleural sarcoma incidence increased with increasing lengths of fibers with diameters of less than 1.5 mu, Morphologic observations indicated that fibers less than or equal to 8 mu in length were inactivated by phagocytosis. In fibers greater than 8 mu in length, the correlation of carcinogenicity witth increasing length was difficult to explain. Since neoplastic response to a variety of types of durable fibers, particularly asbestos fibers, was similar, our experiments reinforce the idea that the carcinogenicity of fibers depends on dimension and durability rather than physicochemical properties and emphasize that all respirable fibers be viewed with caution.


Prolonged inhibition of protein and glycoprotein synthesis in tumor cells treated with muconomycin A.

Several agents were compared for their ability to inhibit protein synthesis for long periods in tumor cells growing in culture. Mouse B16 melanoma cells, treated with high concentrations of cycloheximide or pactamycin for 1 hour and then washed repeatedly, recovered their ability to incorporate [3H]leucine into protein in about 4 hours, while cells treated with emetine recovered in 12 hours. After similar treatment with muconomycin A, however, incorporation of [3H]leucine remained inhibited for at least 30 hours. During this time the cells remained attached to the culture dishes, were able to exclude trypan blue dye, and retained nearly normal levels of rubidium-86 content. When another, untreated, population of cells was added to the muconomycin-treated cells, protein synthesis was not inhibited in the untreated population; action of the drug was thus shown to be confined to the treated cells. In melanoma cells treated with neuraminidase and muconomycin, measurement of glycoprotein synthesis (as determined by sialic acid analysis) showed that muconomycin also inhibited restoration of sialic acid content. Brief treatment with muconomycin, therefore, appeared to be sufficient for prolonged inhibition of protein and glycoprotein synthesis.


Standardization of the chromium-51 release, cell-mediated cytotoxicity assay: cryopreservation of mouse effector and target cells.

Utilizing controlled cryopreservation techniques, we were able to standardize the 51Cr release cytotoxicity assay and thereby ensured reliable comparisons between results obtained on different days. Optimal conditions for freezing of both effector and target cells were quite similar. Dimethyl sulfoxide (DMSO) at a concentration of 7.5-10.0% was employed as the cryoprotective agent and cells were frozen at the rate of -1 degrees C/minute. The handling procedures for the cells before and after freezing were important. Factors affecting recovery of functional reactivity were related to toxicity of DMSO for the cells, the osmotic stress placed upon the cells as the DMSO was being removed after thawing, the handling temperature of the freshly thawed cells, and the susceptibility of cells to mechanical damage immediately after thawing. The recovery of lymphocytes after freezing was about 70%; the recovery of cytotoxicity was around 85%. Syngeneic cytotoxic reactivity induced by inoculation with the Moloney strain of murine sarcoma virus was cryopreserved, as were allogeneic cytotoxicity and natural cytotoxic reactivity. Multiple tests employing effector cells from the same frozen pool gave reproducible results; the standard error of the mean percent cytotoxicity was less than 1.5%. Cryopreserved target cells gave decreased day-to-day variability in susceptibility to lysis, since the same population of cells could be employed in each assay. These results demonstrated conclusively that we can now have a constant source of effector cells and target cells, which can be used from assay to assay as an internal standard.


Effects of pyrazole and 3-amino-1,2,4-triazole on the metabolism and toxicity of dimethylnitrosamine in the rat.

Pretreatment of rats with pyrazole or 3-amino-1,2,4-triazole (3-AT) known inhibitors of alcohol metabolism, profoundly inhibited the metabolism of dimethylnitrosamine (DMN), both in terms of [14C]CO2 excretion and of the decline in the blood concentration. Additionally, 4-methylpyrazole, tetraethylthiuram disulfide (disulfiram), methanol, and ethanol inhibited the metabolism of DMN in the whole animal. In parallel experiments with [14C]aminopyrine, no substantial inhibitory effect was found with pyrazole, 3-AT, or disulfiram pretreatment. Investigations into the effects of pyrazole and 3-AT pretreatment on the acute toxicity and hepatotoxicity of DMN showed that pyrazole significantly increased the median lethal dose (LD50) of DMN and provided substantial protection against the hepatotoxicity of DMN, in that centriblobular necrosis was not seen at dose levels of DMN up to 25 mg/kg and early histochemical changes indicative of liver injury were not observed at a dose level of 15 mg DMN/kg. In contrast, 3-AT pretreatment did not affect the LD50 of DMN or provide any protection against the hepatotoxicity of DMN. Further, although both inhibitors delayed the incorporation of radioactivity from [14C]DMN into hepatic subcellular organelles, pyrazole was significantly more effective than was 3-AT.


Chemical evaluation of the beeswax pellet implantation bioassay model for studies of environmental carcinogens.

The release properties of a number of constituents of cigarette smoke condensate in a condensate--beeswax matrix were characterized by an in vitro study. Eighteen compounds that were representative of several classes of condenate components were tested. Equal quantities of condensate and beeswax, mixed with tracer quantities of the 14C-labeled test compounds, were formed into rod-shaped pellets similar to those used for trachea implant studies, and the rate at which the 14C was removed from the pellet by a flowing saline stream was monitored. Results indicated a wide range in the rates of which the test compounds were released from the pellets. The smaller and water-soluble molecules were released rapidly; about 90% of the nicotine and phenol were leached out in the first 24 hours. Larger and less soluble molecules were released slowly or not at all. Only about 10% of the stearic acid and essentially none of the benzo[a]pyrene was released in 28 days. The effects of such an uneven release of components from an implantation of biologically active material in an inert carrier matrix are discussed with regard to bioassay systems.


Metabolism of N-nitrosohexamethyleneimine to give 1,6-hexanediol bound to rat liver nucleic acids.

Rats were gavaged with the liver carcinogen H-nitrosohexamethyleneimine labeled with 3H or 14C and killed 16 hours later. The liver RNA and DNA were isolated and hydrolyzed with 1 M HCl at 100 degrees C. Chromatography of the 3H-labelled RNA hydrolysate on a cation exchange resin (NH4+ form), with water elution, separated five radioactive peaks, with peak "E" containing 27% of the bound 3H. There were no radioactive peaks in the 7-substituted guanine region. Hydrolysis of the 3H-labeled DNA gave a similar profile, but E contained only 5% of the 3H. The major component of E was identified as 1,6-hexanediol by its behavior and/or that of its benzoate derivative on cation exchange, anion exchange, thin-layer and gas-liquid chromatography, and by recrystallization of a mixture of the E and diol benzoates to constant specific radioactivity.


Cell killing, kinetics, and recovery responses induced by 1,2:5,6-dianhydrogalactitol in dividing and nondividiing cells in vitro.

The survival and cell kinetics effect of 1,2:5,6-dianhydrogalactitol, NSC-132313 (galactitol), were studied on mammalian cells. Nondividing or plateau-phase cells were almost two times more sensitive to galactitol than were cells treated in the dividing state (dose required to reduce survival by 63% on the exponential part of the survival curve (DO)=4.2 mug/ml/hr for dividing cells vs. DO=2.4 mug/ml/hr in nondividing cells). The survival curves were characterized as having shoulder regions, followed by exponential decreases in survival as the drug doses were increased above 12 mug/ml for 1 hour. Synchronized mitotic and G1 phase cells were equally sensitive to galacitol, with approximately 90% of the cells killed by 1-hour exposures to 12.5 mug galactitol/ml. Cells in early S phase were the least sensitive to this drug dose (survival greater than 20%); however, the cells became more sensitive as they progressed through the S phase and into the G2 phase. There were no large differences observed in survival sensitivities anywhere in the cell cycle, suggesting that galactitol was not a cell-cycle phase-specific agent. Cells in mitosis or G1 phases of the cell cycle at the time of treatment with galacitol progressed normally into the next stage of the cell cycle; however, cells exposed to galactitol in S or G2 phases exhibited dose-dependent delays in those phases of the cell cycle. Nondividing cells exposed to high doses of galactitol could not recover from potentially lethal damage (PLD); however, nondividing cells exposed to lower galactitol doses (lethal dose to 10% of the cells) did exhibit slight recovery from PLD. Dividing cells did not recover from PLD at any of the doses tested. Both dividing and nondividing cells were more sensitive (cell kill) to galactitol when it was administered in two dose fractions 4-8 hours apart than when the same total integral dose was given as a single exposure. A 25-50% greater cell kill was achieved in nondividing cell populations given two dose fractions versus a single exposure to galactitol. Up to 60% greater cell kill was obtained with fractionalated doses in dividing cell populations. These responses to fractionated dose treatments were also dose-dependent.


Carcinogenicity of N-nitrosodiethylamine in hibernating and nonhibernating European hamsters.

Hibernating European hamsters reacted differently to sc injections of N-nitrosodiethylamine (DEN) than did European hamsters that were not hibernating. Hibernating animals tolerated higher dose levels but developed fewer neoplasms. In contrast, hibernating males had more pulmonary tumors than did the respective nonhibernators. However, the hibernating females of the low dosage group developed fewer lung tumors. The survival times were longer for the male hibernators than for the male nonhibernators. The organ specificity of DEN, as well as the morphology and histogenesis of the neoplasms, showed no differences between the hibernating and nonhibernating groups.


Alkylation of rat liver DNA by dimethylnitrosamine: effect of dosage on O6-methylguanine levels.

Alkylation of liver DNA was studied following administration to Sprague-Dawley rats of doses of dimethylnitrosamine (DMN) varying from 0.25 to 20 mg/kg body weight. Measurements were made of the amounts of O6-methylguanine and 7-methylguanine present in liver DNA at 4 and 24 hours after treatment with the carcinogen. There was a linear relationship between 7-methylguanine levels and dose of the nitrosamine at both of these times. In contrast, the corresponding levels of O6-methylguanine were not directly proportional to dosage but were less than expected, particularly at low doses below 2.5 mg/kg. This discrepancy was significant at 4 hours, but was even more marked at 24 hours. Only doses above 4 mg/kg at the 4-hour time point gave rise to a 0.11 ratio of alkylation of guanine at the O6-position to that at the 7-position. This ratio was that expected for the initial interaction of the alkylating species derived from DMN with DNA. Evidence was obtained to support the hypothesis that these results were due to an enzymatic removal of O6-methylguanine from liver DNA, which occurred much more efficiently at lower initial levels of alkylation. Repeated daily injections of DMN up to 11 days alos gave rise to O6-methylguanine levels that were not proportional to dosage but were relatively greater at higher dose levels. The significance of these findings in the induction of liver cancer by feeding or repeated injection of DMN was explored.


In vivo suppression of EL 4 lymphomas by rabbit antitumor sera.

Three of more than 50 batches of rabbit antisera raised against the mouse EL 4 lymphoma could inhibit the growth of the tumor in the syngeneic C57BL/6J mice either after exposure of the tumor cells to the antitumor globulin (ATG) in vitro or after the administration of ATG in mice preinoculated with various numbers of EL 4 cells, even though the ATG was not cytotoxic to the tumor cells in the presence of complement. The outcome of immunotherapy with ATG in tumor-bearing C57BL/6J mice depended on the tumor load, the interval between tumor inoculation and the institution of therapy, the total dose, and the schedule of administration of ATG. Complete tumor suppression could be obtained in a proportion of mice preinoculated with 10(5) EL 4 cells, i.e., 10(4) times more than the minimum number of EL 4 cells necessary for 100% tumor takes. Whole-body irradiation (400 rads) or complement depletion of tumor host by cobra venom factor had no effect on tumor suppression by ATG. No evidence of immunity against the EL 4 lymphoma could be detected in EL 4-bearing mice that survived after serotherapy. Anti-EL 4 sera raised in goats and goat and rabbit antisera raised against a lymphoma in the AKR mice have, so far, failed to show any tumor inhibition.


Chronic toxicity of methotrexate in mice.

Daily (five times/week) administration of 0.25-2 mg methotrexate (MTX)/kg to 5- to 6-week-old male C57BL/6, DBA/2, and C3H mice for 12-18 months was well tolerated, apart from minimal cellular suppression in the lymphoid tissues, testes, and skin. Larger doses of MTX (3-6 mg/kg) given to 5- to 6-week-old mice produced well-known acute to subacute hematopoietic and gastrointestinal damage that leads to early death. These young mice did not develop other lesions that were described in humans after long-term MTX administration, nor was the toxicity cumulative. A large difference was observed in the ability of mice of different ages to withstand the toxic effects of MTX; 16-week-old mice were able to survive daily doses of 3-6 mg/kg up to 18 months. Histologic studies of these mice showed a more pronounced cellular depression of the lymphoid tissues, testes, and skin. Osteoporosis was also observed in these older mice that tolerated the drug for 10 months or longer, thus providing a laboratory animal model for further study of this MTX-induced lesion.


Tumorigenicity of intraspecific somatic cell hybrids in nude mice.

Intraspecific somatic cell hybrids between normal mouse peripheral blood lymphocytes and a highly tumorigenic L-cell line (C1-1D) produced tumors in nude mice. While the hybrid cells were tumorigenic, the length of time necessary for tumor appearance and the size of the tumor varied. Correlation between the growth rate of the parenteral and hybrid cells in vitro or their plating efficiency in methyl cellulose with the rapidly of tumor growth in vivo was not found.


C19-steroid metabolism by spontaneous adenocarcinoma of the A X C rat ventral prostate.

Specimens of ventral prostate from 37- to 46-month-old Andradurin-treated A X C rats demonstrated three primary morphologic patterns, each being divisible into two sub-groups based upon the extent of glandular alteration. The principal groups were: group 1, hyperplasia; group 2, atypical hyperplasia; and group 3, adenocarcinoma. The secondary classifications were: subgroup (+), few glands involved; and subgroup (++), most glands involved. Multiple parameters of ventral prostate testosterone metabolic potential failed to distinguish the morphologically diverse prostate specimens of groups (1+). 1(++), 2(+), 2(++), and 3(+) which predominantly metabolized testosterone to 5alpha-reduced 17beta-hydroxysteroids. By contrast, testosterone metabolism by ventral prostate specimens predominantly composed of neoplastic epithelium, group 3(++), was distinct from all other prostate specimens. The distinguishing feature was a shift to more prominent elaboration of 17-ketosteroids, principally delta4-androstenedione, and a cteroids. The change in this biochemical parameter of prostate epithelial cell function was indicated to be an early manifestation of the neoplastic transformation.


Effect of dietary polyunsaturated fat on the growth of a transplantable adenocarcinoma in C3HAvyfB mice.

Weaning male and female C3HAvyfB mice were fed a low-fat (4.5%) diet until they were 60-70 days of age when they were fed high-fat (18.6%) diets containing either sunflower-seed oil (polyunsaturated fat diet) or tallow (saturated fat diet). After receiving either of the high-fat diets for 4 weeks, each mouse received an inoculum of approximately 1,700 single cells from a transplantable mammary adenocarcinoma. The cumulative incidence of tumor-bearing mice was significantly greater among both males and females fed the polyunsaturated fat diet than among males and females fed the saturated fat diet. The mean times elapsed before palpable tumors developed were less when mice were fed the polyunsaturated fat diet than when mice were fed the saturated fat diet, but these differences were not statistically significant. The cumulative incidence of tumor-bearing mice was also significantly greater among females than males. The results supported the suggestion from previous work in this laboratory that the polyunsaturated fat diet exerts its effect on the promotional stage of carcinogenesis rather than on the initial event of neoplastic transformation.


RNA:DNA ratios in human tumors.

A study has been made of the quantitative relation existing between the RNA:DNA ratios in benign and in malignant human tumors. It has been demonstrated that a significant difference (Student's t-test) existed between malignant and benign human tumors within the different groups studied: a) malignant and benign breast tumors (t=2.22, P less than 0.05); b) Hodgkin's disease in spleen and its controls (t=2.39, P less than 0.02); and c) malignant and benign thyroid tumors (t=4.23, P less than 0.01). The diagnostic value of this finding is discussed.


The Gardner syndrome: a family study in cell culture.

The occurrence of tetraploidy was studied in skin cultures containing both epitheloid and fibroblastic cells derived from 137 members (28 clinically affected, 50 normals at risk and 59 normals not at risk) of 6 families with the Gardner syndrome (3 classical, 3 variant). The cultures from all 28 affected members showed increased tetraploidy. Among the 50 normal members at risk for inheriting the Gardner gene, the cultures from 19 had increased tetraploidy and those from 31 did not. Cultures from 56 of the 59 family members not at risk did not show increased tetraploidy. Although the families were divided into subgroups (classical and variant) on clinical phenotypes, no such subdivision could be made on the basis of increased tetraploidy in skin cultures.


Chemoattractant properties of Corynebacterium parvum and pyran copolymer for human monocytes and neutrophils.

Both pyran copolymer and the Burroughs-Wellcome vaccine of Corynebacterium parvum were able to elicit a migratory response by human neutrophils or monocytes when incubated with serum. However, in the absence of serum, neither agent elicited such a response. The generation of the chemotactic factor by pyran was dependent on heat-labile components in the serum, while suggested involvement of the complement sequence. Conversely, the migratory response of C. parvum in heated serum was equivalent to that in normal serum. No specificity for either monocytes or neutrophils was observed.


Vitamin A-induced density-dependent inhibition of L-cell proliferation.

Retinoic acid, the acid form of vitamin A, was found to have an inhibitory effect on the proliferation of L-929 mouse cells. Cultures treated with retinoic acid (5.0 mug/ml) were shown to cease proliferation at cell densities corresponding to confluent monolayers (10.0+/-1.0 X 10(4) cells/cm2). Control cultures, however, continued to proliferate and consistently reach densities two to four times higher than those of treated cultures. Viability was determined by trypan blue exclusion, and the results (80-90 percent viable) excluded cytotoxicity as an explanation of decreased proliferation. Replenishing the medium on confluent retinoic acid-treated cultures failed to stimulate further proliferation, while control cells continued to grow exponentially with each medium change. Therefore, the cessation of cell proliferation at confluence did not result from medium depletion. Studies of cell growth after seeding at relatively low cell densities have indicated that retinoic acid-treated cultures had greater nutritional requirements than did control cultures. Cell-cloning experiments have shown that DNA synthesis was not blocked, since clones formed by cells seeded with retinoic acid contained an average of 27 cells after 9 days of incubation (indicating between four and five cell divisions). However, clones developing from treated cells had fewer cells per clone (27 vs. 54) and were less dense than control clones. These data suggested the restoration of contact inhibition (topoinhibition) to L-929 cells treated with retinoic acid.


Studies in sickle cell anemia: Preliminary observation on gastrointestinal digestion and absorption.

This study investigates certain aspects of the adequacy of digestion, absorption, motility, and morphology of the gastrointestinal tract of children with sickle cell anemia. Medical literature contains a paucity of information on this subject.


Ventricular tachycardia in acute myocardial infarction. Clinical features of 113 patients.

This study was undertaken to evaluate the clinical significance of ventricular tachycardia as a complication of acute myocardial infarction in a large public hospital. An analysis of the clinical, electrocardiographic, therapeutic, and prognostic implications of this large patient group is presented and several unique features emphasized.


Consumer participation in community health programs: a comparative analysis of two programs.

Two model inner city health-care delivery systems are examined in terms of their organizational structure, the role of the consumer within them, their strategies for change, and their ultimate impact and effectiveness. A group practice prepayment plan in Baltimore had consumers on its governing board and, in alliance with a powerful medical institution, successfully organized around political, economic, and social issues. An Office of Economic Opportunity (OEO) grant-supported, neighborhood health center in Washington, D.C. was less effective due to its lack of community representation in the decision-making process. The Baltimore model influenced the federal, state, and local governments, while the Washington, D.C. model had stronger local, than national, effects.


Childhood congenital diaphragmatic hernia of Bochdalek.

Congenital pleuroperitoneal diaphragmatic hernia usually presents in neonates. Children manifesting symptoms and signs after the neonatal period constitute a distinct, uncommon, and infrequently recognized group of patients. Occurrence in adults is also uncommon, with fewer than a hundred patients reported in the literature.


Torsion dystonia: a case report.

A 35-year-old black female with typical torsion dystonia is discussed. Tremors in the right upper extremity began with a febrile illness at age eight. Difficulty in using the extremity began two years later. Overt writhing movements and torticollis began at age 17. The disorder has been progressive, but not disabling. Neurological examination revealed only extrapyramidal motor system dysfunction. Serum dopamine Beta hydroxylase levels were normal, and an evaluation for Wilson's disease was negative. A sibling has minor writing difficulties.


Intravenous renal angiography revisited.

A non-catheter technique to visualize the renal arteries during conventional excretory urography is re-emphasized. By rapid injection of the contrast agent and immediate filming satisfactory visualization can be obtained in many cases. This technique is useful in the evaluation of vascular impressions and other urographic findings when intra-arterial catheter examination is not indicated.


Role of hormones in growth kinetics of renal cell carcinoma in vitro.

Medroxyprogesterone acetate has been used to treat metastatic renal cell carcinoma largely because of its observed inhibitory effects on the growth of estrogen-induced tumors in male Syrian golden hamsters. The absence to date of any successful, established chemotherapeutic regimen in the management of metastatic renal cell carcinoma has led to the continued application of medroxyprogesterone acetate in the majority of patients with this disease because of the occasional regression witnessed (particularly in male patients) and the absence of untoward side effects. To examine the mechanism of action of medroxyprogesterone acetate renal cell carcinoma tumor cells from a patient who had responded to medroxyprogesterone acetate therapy were established in tissue culture. Cells were cultured in control medium, and in the presence of therapeutic and pharmacologic levels of medroxyprogesterone acetate. Tumor cell growth kinetics were determined by the incorporation of 3H thymidine. There was no growth inhibition effected by medroxyprogesterone acetate at therapeutic or pharmacologic levels. Therefore, the proposed salutary effect of medroxyprogesterone acetate in regression of metastatic renal cell carcinoma results from factors other than direct inhibition of renal cell carcinoma growth.


A new technique for catheterless cutaneous ureterostomy.

A new technique for cutaneous ureterostomy is described. Essential conditions for the successful avoidance of stomal stenosis are the firm fixation of the anastomosis to the skin and healing by first intention. Nipple formation is not an absolute must. In order to fulfill these requirements I devised a new technique in which the distal end of the ureter is cut longitudinally to make a fish-mouth-like opening and each separated ureteral segment is sutured to the corresponding skin area. This area is deprived of its epidermis and dermis. Results of the technique have been satisfactory to date.


Ultrasonic diagnosis of the bladder as a symptomatic pelvic mass.

Diagnostic ultrasound for pelvic masses is now a well established modality. Its ability to distinguish between fluid-filled and solid lesions is important in the diagnostic study of pelvic masses. Two cases are presented of bladder distension causing clinical symptoms suggesting pathology outside the urinary tract, which when finally evaluated by ultrasound proved bladder distension as the etiology of the symptoms.


The Small-Carrion prosthesis for male impotency.

Small-Carrion penile prostheses were implanted in 61 patients who have been followed for 3 to 21 months. Of these 61 patients 55 have achieved satisfactory results, with a return of normal sexual function. The importance of preoperative evaluation and preparation is stressed.


The use of the Doppler stethoscope in the evaluation of varicoceles.

Twenty-eight clinically detectable varicoceles of various sizes were examined with a Doppler ultrasonic stethoscope. Retrograde blood flow through the left internal spermatic vein was confirmed in all cases irrespective of size of the vascular abnormality. The Doppler stethoscope also was used to evaluate 13 patients suspected of having varicoceles but with inconclusive physical examinations. Retrograde flow through the internal spermatic vein could likewise be auscultated in 5 of these patients. Finally, the Doppler stethoscope was used to determine the adequacy of internal spermatic vein ligation in 5 postoperative patients whose seminal dysfunction persisted despite what appeared to be a surgically effective correction of aberrant gonadal venous flow.


Microscopic vasovasostomy and spermatogenesis.

Initial clinical experience with a new microscopic 2-layer anastomosis for vasovasostomy shows that normal patency can be achieved almost every time. Histologic and electron microscopic studies on initial specimens and subsequent ejaculates indicate that stricture is a common cause of failure with conventional vasovasostomy techniques, obstruction of the vas deferens inhibits spermatogenesis and relief of obstruction allows return of spermatogenesis in the vast majority of cases.


Prostatic caruncle: a urethral papillary tumor derived from prolapse of the prostatic duct.

Tiny papillary tumors of the prostatic urethra in and around the verumontanum were demonstrated by urethroscopy in 21 patients who presented with hematuria. Histopathologic study revealed evagination of prostatic glands with polypoid, papillary and angiectatic patterns in varying degrees. We suggest that these lesions may be called prostatic caruncles because of their close similarity to female urethral caruncles. The mild inflammatory changes noted in our patients were considered secondary reactions to the local circulatory disturbance and erosion.


Hydraulic hemostasis in transurethral resection of the prostate using the Iglesias continuous suction resectoscope.

An intravesicoprostatic hydrostatic pressure less than 10 mm. Hg maintains normal anatomy and physiology of the muscular and vascular prostatic structures. An increase in hydrostatic intravesicoprostatic pressure to more than 10mm. Hg produces a distortion in the musculature of the prostate, especially at the true capsule, opening the cut vessels and making possible the absorption of the irrigant free of electrolytes (transurethral resection syndrome). A low hydrostatic intravesicoprostatic pressure permits the compression of cut vessels by the inflow hydraulic pressure of 90 cm. water, achieving hydraulic hemostasis during transurethral resection of the prostate. Less electrocoagulation is necessary, resulting in more rapid patient recovery.


The measurement of androgen receptors in human prostatic tissue utilizing sucrose density centrifugation and a protamine precipitation assay.

Methods have been established for the measurement of androgen receptors in the cytosol and crude nuclear extract of human prostatic tissue using sucrose density gradient centrifugation and a protamine precipitation assay. These studies have demonstrated the presence of a high affinity, heat labile protein that binds preferentially to dihydrotestosterone and that is present only in androgen target tissues. In studies of prostatic tissue from 15 patients sucrose density gradient centrifugation appeared more sensitive than the protamine precipitation assay in the identification of androgen receptors. These findings appear promising and suggest that in the near future a reliable assay may be available for the measurement of androgen receptors in prostatic carcinoma.


Granulomatous prostatitis: confusion clinically with carcinoma of the prostate.

Non-specific granulomatous prostatitis is an inflammatory response of a foreign body type to extravasated prostatic fluid. Its significance is incident to its frequent confusion with carcinoma of the prostate. Noteworthy is the rapidity of onset of irritative and obstructive symptoms in a relatively younger age group than one generally sees in carcinoma of the prostate. Tissue diagnosis in those suspected of carcinoma of the prostate should be established by needle biopsy and conservative measures used for at least 4 weeks in the treatment of obstructive symptoms to allow the inflammatory response to subside before intervening surgically . Most patients frequently have associated benign prostatic hyperplasia with persistent obstructive symptoms and significant residual urine. Transurethral resection of the prostate has been performed in this study without postoperative complications.


Carcinoma of the prostate: a critical look at staging.

To stage accurately the extent of the disease comprehensive investigations were done on 75 patients with histologically documented carcinoma of the prostate. Estimation of bone marrow acid phosphatase appears to be the most sensitive test to detect blood-borne metastases. Serum acid phosphatase appears to be of little value in the detection of early blood spread and may have a role only in monitoring the effect of treatment on advanced disease. Bone scanning with technetium compounds has the disadvantage of non-specificity but has far greater sensitivity than a skeletal survey. Bone marrow cytology was not rewarding in the detection of early metastatic disease. Pedal lymphangiography is a highly inaccurate method to detect lymphatic spread of carcinoma of the prostate and pelvic lymphadenectomy, when indicated, remains the only truly adequate method to assess lymph node involvement. There was a 37 per cent incidence of metastatic lymph node pathology in 30 patients undergoing this procedure before either radical prostatectomy or deep x-ray therapy. A close correlation was found between stage and grade of disease and incidence of nodal pathology. There was some correlation between degree of nodal involvement and evidence of blood spread as detected by elevated bone marrow acid phosphatase levels. The significance of this finding remains unclear.


The clinical spectrum of prostate cancer.

Review of 206 consecutive patients with prostatic carcinoma and a potential for 10-year followup indicates the efficacy of vigorous surgical or hormonal management. Satisfactorily documented followup was achieved in 88 per cent of the group for 5 years and 82 per cent of the group for 10 years. Among 33 patients undergoing radical perineal prostatectomy survival rates were 84 per cent at 5 years and 58 per cent at 10 years. In the entire series, irrespective of modality of treatment, approximately half of the patients survived 5 years and a fourth for 10 years. Hormonal therapy of choice was orchiectomy combined with relatively high doses of estrogens, with no indication of significant cardiovascular morbidity or mortality. Interestingly, stage A disease (often diffuse, anaplastic and unsuspected) demonstrated a significantly increased mortality risk when compared to stage B (localized and usually well differentiated) carcinoma of the prostate.


Total prostatectomy for stage B carcinoma of the prostate.

We reviewed 67 cases of total prostatectomy for localized stage B carcinoma of the prostate. There were no operative deaths. Significant morbidity was limited to the well known complications of impotence and incontinence. The over-all survival rates were 92 per cent for 5 years (42 of 46 cases), 79 per cent for 10 years (19 of 24) and 62 per cent for 15 years (8 of 13). Total prostatectomy continues to be the preferred method of therapy for this stage of prostatic cancer.


Radical retropubic prostatectomy for cancer: a 20-year experience.

A review of 159 patients treated by radical retropubic prostatovesiculectomy from 1951 through 1970 has reinforced our belief that this is a satisfactory method of treatment for prostatic cancer confined to the prostate. A 10-year survival of 55 per cent and a 15-year survival of 45 per cent compare well to the results reported for perineal prostatectomy. The postoperative mortality rate was 2.5 per cent and total incontinence was 12.5 per cent after radical retropubic prostatectomy. Completely normal voiding occurred in 108 of the 159 patients. Stress incontinence but no need for an incontinence device occurred in 31 patients. Improved methods for preoperative staging of the disease give promise for even higher cure rates in the future.


Combined therapy of advanced prostatic carcinoma with estramustine and prednimustine.

We treated 21 patients with stage D prostatic adenocarcinoma who had had unsuccessful hormonal therapy with a combination of 600 mg. per M.2 per day estramustine phosphate (Estracyt) and 15 mg. per M.2 per day prednimustine (Stereocyt, Leo 1031) in daily oral doses. Estramustine is a combination of estradiol and nitrogen mustard, and alone has shown objective responses in advanced prostatic cancer. Prednimustine is an ester of chlorambucil and prednisone. The preliminary results (after 2 to 9 months of therapy) show 5 patients (24 per cent) did not benefit from the drug and 7 patients (33 per cent) are stable. These preliminary results indicate the possible advantage of adding an alkylating agent (prednimustine) to estramustine in advanced prostatic carcinoma. Currently, a national randomized trial by the National Prostatic Cancer Project is evaluating this therapeutic innovation.


Observations on the ultrastructure and genesis of urinary calculi.

Conventional and scanning electron microscopy of calcigerous renal calculi discloses typical concentric laminations, radial striations and microspherules. Random axial distribution of oxalate crystals and their coating by electron-dense matrix fibers with a definite parallel orientation and cross-linkages are evident. The biochemical relationship of uromucoid to matrix substance A is described. It is suggested that renal sialidase may convert the urinary uromucoid to matrix substance A, whose apatite-covered fibers may be responsible for epitaxial nucleation of some crystal systems. Our studies indicate that the intimate apatite-matrix relationship occurs in the human nephron, probably as an intracellular phenomenon. Subsequent extrusion of these mineralized complexes into the lumen of the nephron (intranephronic calculosis) may, in some instances, represent the initial microanatomic stage of renal calculogenesis.


Techniques and results of urodynamic evaluation of children.

Simultaneous recording of intravesical pressure, urine flow rate and anal sphincter electromyography was undertaken in 25 children with a variety of urological problems. Urethral pressure profile measurement was obtained in 3 of these patients and was used as an adjunct to cystometry alone in 5 others. The diagnostic patterns that emerged were useful in selecting specific pharmacologic and surgical therapeutic measures.


Microanatomy of the intravesical ureter in children with and without reflux.

The microscopical appearance of 37 distal ureteral resection specimens from 27 children with recurrent urinary tract infections and vesicoureteral reflux are compared to postmortem specimens of 51 distal ureters from 28 children with no history or urinary tract disease. The degree of fibrosis and inflammatory change varied a great deal in both groups and it was not possible to find any differences between them.


Extravesical repair of primary vesicoureteral reflux in children.

An operative procedure for the repair of primary vesicoureteral reflux in 51 children (83 renal units) is described, its merits are discussed and its advantages are stressed. Reflux was prevented in 90.2 per cent of the children and 74.5 per cent of the patients remained free of infection. No obstruction has occurred in our series as compared to a 5 per cent incidence rate in cases of ureteroneocystostomy. Our procedure is not recommended for megaureters with reflux or for recurrent vesicoureteral reflux.


Strictures of the ileal loop.

Intrinsic ileal loop strictures in children are much more common than previously reported. They occur late and are usually clinically silent. Their etilogy is inflammatory rather than ischemic and a local immunosuppressive effect of urine also may play a role. Periodic urography, continued indefinitely, is the only certain method of early detection.


Complications of urinary undiversion.

Complications of urinary undiversion may be divided into those related to patient selection and those pertaining to the operation. A detailed understanding of the anatomic and physiologic alterations in the dynamics of urine transport is an essential prerequisite for the selection of suitable candidates. Two illustrative cases emphasize the necessity for complete evaluation of the upper and lower urinary tracts as well as meticulous attention to intraoperative detail.


Hematuria in childhood: significance and management.

Of 164 children presenting with gross or microscopic hematuria during a 5-year period 111 (68 per cent) were proved by clinical features or renal biopsy to have glomerulonephritis. Extraglomerular origin of hematuria was documented in only 25 (15 per cent). No definite diagnosis could be made in the remaining 28 (17 per cent) with isolated hematuria but the clinical picture was similar to that of the patients with mild glomerular lesions. Followup in 59 of 68 children confirms previous reports that isolated hematuria in childhood is usually a benign condition. Although excretory urography, urine cultures and serum complement measurements should be done to eliminate uncommon causes of hematuria, invasive studies, such as renal biopsy and cystoscopy, are not indicated routinely.


Primary hyperparathyroidism with triple cancers consisting of renal cell carcinoma, nasopharynx carcinoma and thyroid carcinoma.

The first case of primary hyperparathyroidism associated with renal cell carcinoma, nasopharynx carcinoma and thyroid carcinoma is reported. Selective venous sampling with radioimmunoassays for parathyroid hormone was helpful in the differentiation of primary hyperparathyroidism from hypercalcemia associated with malignancy.


A case of nephrobronchial and colonobronchial fistula presenting as lung abscess.

A nephrobronchial fistula is an uncommon clinical entity and perinephric abscess in the most common etiological lesion. At times, pulmonary symptoms may dominate the clinical picture and the diagnosis of an associated renal lesion may be overlooked. An unusual case of a coexisting nephrobronchial and colonobronchial fistula is reported. The patient had been treated for chronic lung abscess for 4 years before the final diagnosis was made.


Persistent acute renal failure with renal artery stenosis: cure following reconstructive arterial operation.

A case of acute renal failure is reported in which renal function returned after surgical correction of renal artery stenosis to the sole functioning kidney. Acute renal failure associated with renal vascular lesions is reviewed. Although often clinically apparent vascular obstruction may be asymptomatic and should be considered in cases of prolonged acute renal failure.


Parasitic blood supply from the inferior mesenteric arteries to the hypernephromas.

A case of left hypernephroma obtaining its blood supply from the inferior mesenteric artery is reported. The origin of the blood supply was demonstrated by selective arteriography. It was proved at operation that the hypernephroma can extend beyond the renal capsule and invade the mesentery of the colon.


Skene's duct cyst in a newborn: case report and review of the literature.

The diagnosis of a rare Skene's duct cyst in a newborn was made based on its location in relation to the urethra and the demonstration of transitional epithelium in the cyst wall. A through urologic evaluation was required to differentiate it from an ectopic ureterocele, urethrocele, urethral diverticula, and benign or malignant urethral and paraurethral tumors. Other uncommon vaginal cysts may be of müllerian duct origin and lined with stratified squamous epithelium or from persistent mesonephric (Gartner's) ducts and lined with columnar epithelium. Many cysts drain spontaneously but if treatment is indicated, marsupialization or simple transvaginal excision usually is adequate.


Recurrent varicocele: radiographic documentation and surgical management.

A case of recurrent varicocele documented by a selective venogram and surgically corrected is presented. The need to investigate systematically recurrent varicoceles and surgically remove the recannulized collaterals is emphasized.


Mesothelial hyperplasia in hernia sacs.

Mesothelial hyperplasia is a benign condition, which simulates a neoplastic process. Since it may occur in hernia sacs this entity must be recognized by the urologist to prevent over-treatment.


Severe metabolic acidosis as a complication of intravenous tetracycline therapy.

Tetracycline generally is believed to be a safe drug with relatively minor side effects. Serious irreversible renal damage and metabolic acidosis can occur in patients with azotemia. While the exact mechanism is unknown, the commonly reported nephrotoxic and metabolic effects of tetracycline are reviewed and an illustrative case is presented.


Unusual complication of therapy with sulfamethoxazole-trimethoprim.

The first case of an obstructing stone composed of a pure metabolite of the sulfamethoxazole-trimethoprim combination is reported. Its coincident occurrence with an obstructing calcium oxalate stone, producing oligura and acute azotemia, is noteworthy.


Heavy metal concentrations in kidneys of estuarine raccoons from Florida.

Concentrations of lead, zinc and cadmium in the kidneys of 14 adult raccoons from an estuarine environment were determined. The mean concentrations in ppm wet weight and standard deviation for the metals were lead--0.47 +/- 0.22, zinc--75.88 +/- 16.54 and cadmium--2.48 +/- 1.66.


Histopathology of an acute fin lesion in the summer flounder, Paralichthys dentatus, and some speculations on the etiology of fin rot disease in the New York Bight.

The histopathology of acute fin rot disease in summer flounder, Paralichthys dentatus, from the New York Bight is described. Grossly, caudal and dorsal fin lesions appeared ragged or frayed with no evidence of resolution. Microscopically, there was epidermal and dermal necrosis, congestion, edema, focal and diffuse hemorrhage, and Zenkers necrosis of underlying muscle. Gram-negative bacteria were present in the fin tissues as well as in heart muscle and liver parenchyma. The inflammatory response consisted mostly of macrophages. The significance of the acute disease in summer flounder is discussed in relation to the etiology of fin rot disease in winter flounder from the Bight.


Trypanosoma cervi Kingston and Morton, 1975 from mule deer, Odocoileus hemionus, in Wyoming.

Mensural values of blood stream stages and cross-transmission studies defined the trypanosome species from mule deer, Odocoileus hemionus, as con-specific with Trypanosoma cervi, the trypanosome found in elk from the same locality. Trypanosomes were found in eight mule deer sampled in the spring and eight sampled in the winter in southeastern Wyoming.


Mycobacterium avium serotype 1 infection in a sandhill crane (Grus canadensis).

Tuberculous lesions were observed in the liver of an adult sandhill crane (Grus canadensis); Mycobacterium avium serotype 1 was isolated. Chickens inoculated intravenously with the culture had granulomas in the liver and spleen at necropsy 62 days after inoculation.


Nematodes in terrestrial gastropods from central Maine.

Seventeen-hundred terrestrial gastropods collected in central Maine were examined for Parelaphostrongylus tenuis and other nematodes. Prevalence of nematodes was 4 to 7% in most gastropod species, but was 19% in Pallifera spp. Cosmocercoides dukae and Rhabditis spp. were the most common nematodes recovered. Only four P. tenuis larvae (prevalence 0.1%) were found. Foci important for transmission of P. tenuis in Maine have not yet been found.


Plasma cell tumor in an East Indian water lizard (Hydrosaurus amboinensis).

A neoplasm involving the stomach, liver and lungs was seen in an East Indian water lizard (Hydrosaurus ambionensis). The largest mass was in the stomach, with smaller nodules in the lung and liver. The tumor was diagnosed as a plasma cell tumor by its histologic and ultrastructure characteristics.


Intratracheal injection of antibiotics in the California sea lion, Zalophus californianus, and bottlenosed dolphin, Tursiops truncatus.

Gentamicin and cephaloridine were administered by intratracheal injection to the California sea lion, Zalophus californianus, and the bottlenosed dolphin, Tursiops truncatus. Uptake and clearance of these antibiotics in the blood were monitored. In all cases, absorption through the respiratory mucosa resulted in blood levels approaching therapeutic concentrations despite low dosages.


Naturally occurring neurologic disease in a fallow deer infected with meningeal worms.

Neurologic disease resulting from infection with Parelaphostrongylus tenuis was diagnosed in a fallow deer (Dama dama) from Georgia, with clinical signs and histopathologic lesions similar to those reported for other accidental hosts of P. tenuis. Early fifth stage parasites were found in the spinal meninges and immature parasites were found in the neural parenchyma, but none were recovered from the brain and cranial meninges.


Parasites of waterfowl from southwest Texas: I. The northern cinnamon teal, Anas cyanoptera septentrionalium.

Seventeen northern cinnamon teal, Anas cyanoptera septentrionalium were collected in Hudspeth County, Texas: 10 in January, 1974, and seven in September, 1974. Fifteen parasite species were recovered: 11 were new host records. Three species of parasites were recorded from spring migrants and 15 from fall migrants.


An outbreak of toxoplasmosis in wallaroos (Macropus robustus) in a California zoo.

Four wallaroos (Macropus robustus) from a central California zoo colony of 22 died within a three week period. Histopathologic findings in all four cases were suggestive of toxoplasmosis. Brain, lung and heart were the most frequently involved organs. Within 4 months of the last death sera from nine colony members were tested for antibodies against Toxoplasma gondii using the indirect hemagglutination test. All nine had serological titers ranging from 1:64 to 1:131,072.


Isolation of a hemolytic Actinobacillus from waterfowl.

A previously undescribed species of hemolytic Actinobacillus was isolated from six waterfowl, three with periocular serous exudation and two with airsacculitis and bronchopneumonia. Cultural and biochemical characteristics were compared with those of Actinobacillus and Pasteurella spp, using a numerical technique.


Epidemiological evaluation of funduscopic findings in cerebrovascular diseases. III. Observer variability and reproducibility for funduscopic findings.

In order to evaluate observer variability and reproducibility for the funduscopic findings, the color slides of one hundred cases in Akabane and Asahi town in Japan were investigated and the following were revealed: 1. Observer variability for Keith-Wagener's classification was the least in the grade 3 and the most in grade 0. The variability of diagnosis between observers was the least for retinal bleeding and the most for anteriolar reflex and remarkable for lateral displacement and arteriolar narrowing. In general, the observe variability was one grade at most. 2. Reproducibility for Scheie's hypertensive classification was 73 per cent and that for Scheie's arteriosclerotic and Keith-Wagner's classifications was 66 per cent. Fairly good reproducibility was observed in retinal bleeding and poor reproducibility in arteriolar reflex and vertical and lateral displacements, In general, the intra-observer variability for the funduscopic findings was one grade at most. 3. Observer variability and reproducibility for the funduscopic findings would be improved by establishment of the detailed diagnostic criteria of various funduscopic findings, taking color pictures in focus and systematic training for the fresh doctors or technicians without enough experience. 4. The cases with definite narrowing of arteriole revealed smaller A/V ratio than 0.70.


Studies on sodium and calcium contents of cardiovascular tissue in experimental hypertension.

Sodium and calcium contents of cardiovascular tissue in spontaneously hypertensive rats (SHR) and DOCA hypertensive rats were investigated. The effect of salt loading on these contents of SHR and control Wistar rats was also investigated. Calcium content increased with the development of hypertension, but not sodium content particularly in salt loading rats and at the sustained stage of DOCA hypertensive rats. These results suggest that calcium rather than sodium is more intimately related to the increase in blood pressure.


[Studies on the spatial velocity electrocardiogram in ventricular septal defect (authors's transl)].

The QRS waves of the spatial velocity electrocardiogram (ECG) were investigated in 94 cases of the ventricular septal defect (VSD). The relationship between the amplitudes and the time intervals of QRS waves of the spatial velocity ECG and the various hemodynamic parameters obtained by the right heart catheterization and the defect area ascertained during the operations were evaluated.


[Studies on the normal polarcardiogram using the posteroanterior axis as the polar axis (author's transl)].

Polarcardiograms using the posteroanterior axis as the polar axis were recorded in 112 cases of the clinically healthy subjects. QRS wave with small notch or slur both in front and behind of the main triangular configuration with narrow base were most frequently observed in the frontal magnitude ECG. T wave showed simple monophasic upright wave with the mildly sloping ascending limb and the relatively rapidly sloping descending limb. The magnitude of the maximum QRS vector and the maximum QRS vector time in frontal plane were very similar with those of the spatial QRS vector. The quantitative values obtained by the measurement of the polarcardiograms agreed well with those obtained by the vectorcardiograms reported by the various authors. Polarcardiography made possible not only to know the polar coordinates of the cardiac vector at any instant very easily, but also to express the time-related curve of the polar coordinates, which vary as a function of time, in easily understandable analogue pattern. QRS and T waves of the magnitude, the alpha-longitude and P-A latitude ECG in the normal subjects were classified into the several definite patterns.


[Studies on the reliability of the polarcardiographic records (author's transl)].

Reliability of the polarcardiogram obtained by the newly constructed polarcardiograph, in which the vector sum circuit applying absolute value operations were used for the computation of the magnitude curve, were examined in fifty normal subjects. There was no statistically significant difference between the means of the measured values of the polarcardiogram and of the corresponding polar components calculated from the three scalar ECG concerning all twenty items, namely spatial magnitude, magnitudes in each plane, each longitude and latitude at the time of the spatial maximum QRS and T vectors, except alpha-longitude. Highly significant positive correlations were observed between these two sets of values in all twenty items. Configurations of the pattern obtained by plotting the instantaneous polar components, which were calculated from the three scalar ECG, on the linear time scale were very similar with those of the polarcardiographic records. These findings showed that the records obtained by the newly constructed polarcardiograph were reliable.


[Clindamycin-2-phosphate in the field of dermatology (author's transl)].

1. MIC against 20 strains of staphylococcus isolated from skin infections was studied. MIC was less than or equal to 0.05 mug/ml in 11 strains and greater than 100 mug/ml in 9 strains. 2. Clindamycin-2-phosphate was injected intramuscularly to rats at the dosis of 10 mg/kg in solution of 10 mg/ml. The serum and skin levels of this drug were determined at 0.5, 1, 2, 4 and 7 hours. Mean serum levels of 4 rats were 0.893, 0.578, 0.463, 0.268 and 0.167 mug/ml respectively at 0.5, 1, 2, 4 and 7 hours. The corresponding skin levels were 0.500, 0.707, 0.431, 0.313 and 0.269 mug/g. 3. Clindamycin-2-phosphate was used clinically in 7 patients of skin infection with the following result: excellent in 2 cases, fair in 3 cases and poor in 2 cases. Abdominal pain was complained in one case and loose stool in one case.


[Clinical studies with amoxicillin in patients with biliary tract infections (author's transl)].

Six patients with biliary tract infections who came to our hospital were administered 1.5 g (potency) per day of amoxicillin, a synthetic penicillin for oral use, to examine its clinical effects. The results were as follows. 1) Out of six patients with biliary tract infections, amoxicillin proved to be effective in four patients, ineffective in one patient, and unknown in one patient. 2) Oral administration of amoxicillin gave the same success in treatment as injection of other synthetic penicillin preparations in mild cases with the exception of acute deterioration of chronic with subjective symptoms such as nausea and vomiting. 3) No noteworthy side effects were observed in any cases examined this time.


[Clinical experience with amoxicillin (Pasetocin) in urology (author's transl)].

Amoxicillin, a synthetic penicillin with a broad antibacterial spectrum, was administed in a daily dose of 1.0 g (in potency) to 47 patients who came to the department of urology (6 patients in whom the antibiotic was used for the prevention of infections included). The results are summarized in the following. 1. The patients with urological infections who were treated with amoxicillin included 20 patients with acute cystitis, 1 with acute urethritis, 18 with chronic prostatitis, 1 with epididymitis, 1 with pyelonephritis and 6 patients in whom the antibiotic was used for the prevention of infections. Amoxicillin was remarkably effective in 27 patients (58.7%), effective in 7 patients (15.2%), but ineffective in 12 patients (26.1%), with the overall effectiveness of 73.9%. The therapy was withdrawn in one patient because of side effects. 2. A patient with acute cystitis showed eruption which was probably associated with allergic reaction to penicillin, and the administration was discontinued. Other side effects worth mentioning were not observed.


[Therapy for severe anaerobic infections with clindamycin (author's transl)].

Ten adult patients with severe Bacteroides infections were treated with 0.9 approximately 1.8 g/day of parenteral or oral clindamycin, and a child was treated with 0.3 g/day orally. Remarkable responses and cures were obtained in all the patients, who had no underlying diseases and pure anaerobic infections; a case of sepsis, two cases of liver abscess, a case of subcutaneous abscess and a case of spinal epidural abscess. The other six patients who had ultimately fatal underlying diseases or mixed infections did not respond well to the combination of clindamycin and the other antibiotics therapy, althought bacteriological cures were obtained in all but two cases. Clindamycin was well tolerated and generally nontoxic, nevertheless it was administrated for long term (34 approximately 49 days). But transient development of transaminase was seen in a patient. The data suggested that clindamycin should be considered a first choice antibiotic for the treatment of an aerobic, especially, Bacteroides infections.


[A case of subacute bacterial endocarditis treated with clindamycin-2-phosphate (author's transl)].

A sixty-three years old female patient with subacute bacterial endocarditis was treated with clindamycin-2-phosphate parenterally, because she had a history of hypersensitive reaction to penicillins. She had received erythromycin, cephaloridine and cephalexin previously, but had no bacteriological response. When clindamycin-2-phosphate was given intramuscularly, the bacteremia disappeared for the first time. However, after the cessation of this treatment Streptococcus viridans grew in her blood again. It was suggested that this drug was bacteriostatic rather than bactericidal. During this therapy, local tenderness was noticed at the injected sites and a transient maculopapular rash developed which resolved in a few days.


[Preclinical and clinical studies of clindamycin-2-phosphate (author's transl)].

Preclinical and clinical studies of clindamycin-2-phosphate developed as an infectable were conducted, and the following results were obtained: 1) Clindamycin-2-phosphate administered by the intravenous drip in a dose of 600 mg over one hour showed a peak blood clindamycin level of 10.5 mcg/ml at the end of administration. Though the blood level then decreased rapidly, it stayed at 0.7 mcg/ml at 8 hours later. 2) The blood level of clindamycin following intramuscular injection of 300 mg of clindamycin-2-phosphate reached a peak of 3.3 mcg/ml at one hour later. The blood level of 6 hours after injection was 1.0 mcg/ml. 3) Clindamycin-2-phosphate 300 mg was given intramuscularly 2 to 4 times daily for 5 approximately 14 days in 4 cases of pneumonia. The drug proved effective in two cases of pneumonia due to Mycoplasma; fairly effective in another case of mixed infection caused by pneumococci, Hemophilus and N. meningitidis; and ineffective in the fourth case of infection due to Hemophilus parainfluenzae. 4) No such adverse reactions as hepatic disorder, renal disorder and colitis were noted following administration of clindamycin-2-phosphate.


Peripheral and optic neuritis in a patient with hemoglobin SC disease during treatment of salmonella osteomyelitis with chloramphenicol.

Peripheral and optic neuritis developed in a girl with hemoglobin SC disease, during long-term high-dose treatment of Salmonella osteomyelitis with chloramphenicol. Although the neurotoxicity of this antibiotic is well documented, the child's pain was initially considered to be a form of sickle-cell dactylitis.


Effect of perfusion rate on the fluxes of water, sodium, chloride and urea across the proximal convoluted tubule.

Studies were undertaken to examine the mechanism whereby changes in intraluminal flow rates after reabsorption in the isolated perfused proximal tubule of the rabbit. All protocols employed the technique of in vitro perfusion of isolated segments of the proximal convoluted tubule. Stepwise elimination of d-glucose and l-alanine from an artifical perfusate stimulating ultrafiltrate decreased the unidirectional flux of sodium, transtubular potential difference, and net water absorption. Using isosmolal ultrafiltrate as the perfusate, net fluid reabsorption and the unidirectional lumen-to-bath flux of sodium and chloride decreased with a decrease in flow rate below 11 nl/min, but neither net fluid reabsorption nor the unidirectional fluxes of sodium and chloride increased further as the perfusion rate was increased above 11 nl/min. The unidirectional flux of 14C-urea was not affected by changes of perfusion rate from 1.6 to 44 nl/min. The dependence of net fluid reabsorption and unidirectional fluxes of sodium and chloride on flow rate per se, and not on intraluminal hydrostatic pressure or geometry, was established by demonstrating their decrease despite a rise in intraluminal pressure and inside diameter produced by counterpressure at the collecting end of the tubule, while flow was decreased. Ouabain decreased net fluid reabsorption to near zero at all flow rates, but ouabain had no effect on the flow-dependency of unidirectional sodium anf sodium was eliminated with a decrease in bicarbonate concentration and removal of d-glucose and l-alanine from the perfusate. Thus, the present studies demonstrate that net water and unidirectional sodium and chloride fluxes are flow-dependent. At flow rates somewhere below 11 nl/min, unidirectional fluxes decreased with decreasing perfusion rates; however, at perfusion rates greater than 11 nl/min, there was no further effect of perfusion rate on either net water absorption or the unidirectional fluxes of sodium or chloride. These effects may be partly mediated through the flow-dependent changes in the intraluminal concentration of bicarbonate, d-glucose, and 1-alanine.


Dissociated effect of sodium intake on glomerular and pressor responses to angiotensin.

The influence of chronic and acute changes in sodium intake on pressor and glomerular capillary responses to angiotensin was studied. Scanning electron microscopy was used to observe the capillary changes in the superficial glomeruli. The results showed that both responses was sodium-dependent but in opposite directions. Low sodium intake diminished the pressor effect but enhanced the glomerular capillary response to administered angiotensin. On the contrary, a high sodium diet or a short perfusion of 0.9% NaC1 considerably diminished the sensitivity of the glomerular capillaries to angiotensin, whereas the systemic hypertensive effect was enhanced. Our results demonstrate that the systemic circulation and the capillaries of the superficial glomeruli react independently to angiotensin. This suggests that the superficial glomerular receptors differ from the systemic ones.


Renal hemodynamics in uranyl acetate-induced acute renal failure of rabbits.

The role of renal hemodynamic alterations in the curtailment of renal function was studied in rabbits with uranyl acetate-induced acute renal failure. The day following the i.v. injection of uranyl acetate (2 mg/kg of body wt), renal blood flow (RBF) and clearance of creatinine (Ccr) decreased to approximately 60 and 20% of controls, respectively. Intracortical fractional flow distribution, estimated by radioactive microsphere method, did not change. The extraction ratio of para-aminohippurate (EPAH) decreased and the renal extraction of sodium (CNa/Ccr) increased, with minimal structural change in the kidney. Urine output increased to two to three times that of the control. After three days oliguria appeared despite complete recovery of RBF. The zonal flow redistributed toward the deep cortex. CCr and EPAH reached their minimums, concomitantly with tubular necrosis and intratubular casts. After seven days animals could be divided into the oliguric and diuretic groups. CCr and EPAH were higher in the diuretic group, while there was no significant difference in RBF and the flow distribution between groups. Regeneration of damagee tubular cells was found in the diuretic group but not in the oliguric group. The findings suggest the minor roles of RBF and the intracortical flow distribution, and a fundamental role of back leakage of filtrate across damaged tubular epithelium in the maintenance of reduced CCR and urine output during the oliguric stage in rabbits with uranyl acetate-induced renal failure.


Glomerular permeability: in vivo tracer studies with polyanionic and polycationic ferritins.

The influence of molecular charge on glomerular permeability to the globular ferritin molecule in vivo was investigated. Mice (Charles River CD strain) and rats (Munich-Wistar strain) were injected intravenously either with native anionic ferritin or various cationized derivatives with different isoelectric points (pI) and the kidneys were examined by electron microscopy. Native anionic ferritin was almost completely restricted from entry into the glomerular filter at the level of the endothelium and subendothelial layer of the glomerular basement membrane (GBM). Cationized derivatives penetrated the filter in increasing amounts depending on the pI of the tracer. Regardless of charge, all molecules that filtered through the lamina densa of the GBM and reached the subepithelial layer were completely restricted from entry into the urinary space at the level of filtration slits and appeared in phagosomes present in podocytes. Reduction of arterial pressure of cessation of renal blood flow did not influence the movement of ferritin molecules into the GBM. The results are consonant with physiological studies indicating charge dependent restriction of polyanion transport by the mammalian glomerulus. These tracer studies, in conjunction with cytochemical and biochemical evidence for the presence of polyanionic glycoproteins in the glomerular filter, suggest that glomerular restriction of plasma proteins occurs in part by a process similar to that which exludes negatively charged macromolecules in polyanionic gel systems.


Chronic progressive renal disease: rate of change of serum creatinine concentration.

The rate of change of the serum creatinine concentrations in 63 patients with chronic progressive renal disease of varied etiology was examined by linear regression analysis using the logarithm or the reciprocal of the serum creatinine concentration versus time. A single straight line was described by one or the other of these relationships in 53 patients. Six patients had an accelerated rate of nephron destruction terminally (two slopes) regardless of the mathematical analysis. The remaining four patients had course changes either due to apparent spontaneous remissions or temporally related to therapy. These data suggest that (functional) nephron loss in chronic progress disease is orderly and mathematically definable. The theoretical implications are that functional nephron loss is either exponential (log Cr) or constant (1/Cr).


Micropuncture studies of the filtration and absorption of albumin by nephrotic rats.

The proximal tubular fluid albumin concentration of rats with immunologically induced nephrotic syndrome rose from 0.60 +/- 0.11 (SEM) mg/100 ml to 7.42 to 0.87 mg/100 ml. The glomerular filtration rate (GFR) was slightly depressed (P less than 0.001) and fractional water absorption unchanged (P greater than 0.45). Urinary albumin excretion rose from 0.18 +/- 0.03 (SEM) mg/100 g of body wt/24 hr to 78.5 +/- 39.5 mg/100 g/100 g of body wt/24 hr (P less than 0.001). The concentration of albumin in glomerular filtrate, calculated as the product of proximal tubular albumin concentration and fractional water absorption (4.53 +/- 0.60 mg [SEM]/100 ml), equalled that calculated from urine albumin concentration and whole kidney water absorption (4.14 +/- 0.84 mg/100 ml, P greater than 0.30). The data are interpreted to reflect a significant increase in filtered albumin and only a modest (if any) tubular albumin absorption in this study. Thus, the concept that tubular absorption plays a major role in the catabolism of albumin and the genesis of hypoalbuminemia in the nephrotic syndrome could not be confirmed.


Evaluation of hypercoagulability in users of oral contraceptives.

Soluble fibrin monomer complexes (SFMC) were determined in users of different oral contraceptives. Quantitative gel filtration of beta-alanin precipitated plasma samples yielded the relative (per cent of total fibrinogen content) and absolute (mg per 100 ml plasma) amount of SFMC. Increased levels of SFMC were observed in users of oral contraceptives, when compared to age, parity and socioeconomic background matched control groups. This increase was more pronounced in users of Neogynon (0.05 mg ethinyl estradiol, 0.25 mg norgestrel) than in the one using Microgynon (0.03 mg ethinyl estradiol, 0.15 mg norgestrel). Users of Ovulen (0.1 mg mestranol, 1 mg ethynodiol diacetate) in addition to the rise of SFMC levels exhibited elevated fibrinogen levels in plasma. The data presented indicate a limited state of hypercoagulability in users of oral contraceptives.


[Microzone electrophoresis of non concentrated CSF (author's transl)].

This paper reports on a method which allows the separation of proteins of non concentrated CSF by means of the microzone technic. Pherograms of high quality were possible when the CSF contained more than 10 mg/dl total protein. Protein separation is completed in 16 min when one cellulose acetate strip with 150 V and 2 mA or when 150 V and 4 mA with two strips are used. Proteins were stained with nigrosine. The theoretical basis, technical details and error range of this method of protein separation are discussed.


[Effect of space flight on rat skeletal bones (an optical light and electron microscopic study)].

By light and electron microscopy long tubular bones of white Wistar rats were examined after a 22-day space flight and ground-based synhcroneous experiment. Approximately half of the flight rats showed loosened spongiose of metaphyses which was normally combined with a reduced area of the primary spongiose near the cartilaginous growth plate. This was suggestive of inhibited growth of bones in-flight. The light and electron microscopic examination of bones of flight rats revealed wide osteocyte cavities (lacunae) that could be associated with perilacunar osteolysis. The study of synchroneous animals demonstrated a less expressed spongiose of metaphyses found only in one third of the rats which was not usually combined with a reduced area of the primary spongiose near the cartilaginous growth plate. The histological examination of bones of flight rats on the 27th postflight day indicated that that period of time was insufficient for the normalization of all the changes.


[Effect of space flight factors on rat skeletal musculature].

Morphological and histochemical examinations of skeletal muscles of flight rats demonstrated atrophic and dystrophic developments in M. soleus which were followed by metabolic disorders in the muscular tissue. The changes were reversible, although they did not disappear entirely on the 27th postflight day. Early signs of atrophic developments were found in M. gastrocnemius, M. quadriceps, M. extensor digitorum longus and M. biceps brachii on the 2nd postflight day. The comparative study of the data obtained from flight and ground-based synchroneous rats showed that muscular pathologies developed as a result of hypodynamics and were enhanced by weightlessness-effects.