Novel bis(benzamidino) compounds with an aromatic central link. Inhibitors of thrombin, pancreatic kallikrein, trypsin, and complement. A series of novel aromatic diamidines was synthesized and evaluated for antiproteolytic activity. The compounds were distignuished by inclusion of an aromatic ring structure--either benzene or bisbenzene or naphthalene--in the link between two amidinobenzene moieties. A highly potent inhibitor of bovine thrombin was discovered in alph, alph'-bis(4-amidino-2-iodophenoxy)-p-xylene with a Ki value of 1.1 X 10(-7) M (pH 8.1, 37 degrees), while alpha, alpha'-bis(4-amidino-2-iodophenoxy)-m-xylene was found to be an outstanding inhibitor of porcine pancreatic kallikrein (Ki = 3.1 X 10(-8) M). Several of the compounds investigated also demonstrated a considerable blocking effect on typsin and on the complement-dependent immune lysis of red cells.


Synthesis and anticancer activity of 5-diethylaminomethyl derivatives and nitrogen mustards of uracil and 2-thiouracils. Several 5-diethylaminomethyl derivatives and nitrogen mustards of uracil and 2-thiouracil have been synthesized and tested for their potential anticancer activity in vitro on KB cells and in vivo on Ehrlich carcinoma. Among the alkylating derivatives tested several showed cytotoxic activity in vitro and compound V [5-[bis(2-chloroethyl) amino] methyl-6-propyluracil hydrochloride] showed both in vitro and in vivo anticancer activity.


Metabolic formation and synthesis of 1-(3-chlorophenyl)-2(4-hydroxyphenyl)-1-methyl-2(2 pyridine)ethanol. A potential hypocholesteremic agent. 1-(3-Chlorophenyl)-2-(4-hydroxphenyl)-1-methyl-2(2-pyridine)ethanol (8a) has been synthesized and found to be the major urinary metabolite following intraperitoneal administration of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1) to rats. This metabolite has a hypocholesteremic effect in rats similar to that of the parent drug.


Cellular pharmocodynamics of several anthrocycline antibiotics. Alterations in the C-9 side chain of the anthracycline antibiotics, adriamycin and daunorubicin, have a profound effect on antibiotic uptake and accumulation by cultured L1210 cells. The degree of inhibition of DNA and RNA biosynthesis in the L1210 cells is directly related to the cellular uptake and accumulation of the drug analogues. Polar drug metabolites, daunorubicinol and adriamycinol, retain inhibitory activity against nucleic acid metabolism but have a decreased membrane binding and permeability. Cellular uptake and accumulation of the C-9 analogues are inversely related to drug polarity. We propose that the polarity of the anthracycline analogues contributes heavily to the differences in therapeutic index and in vivo activity through fundamental effects on membrane permeability, metabolism, and macromolecular binding.


Analogues of S-adenosylhomocysteine as potential inhibitors of biological transmethylation. Synthesis of analogues with modifications at the 5'-thioether linkage. The synthesis of S-adenosylhomocysteine analogues, in which the 5'-thioether linkage is replaced by an oxygen or nitrogen isostere, has been investigated. These compounds were disigned to be resistant to enzyme-catalyzed hydrolytic cleavage of the 5'-substituent. The amine analogue Id and two amide analogues 20 were prepared via alkylation or acylation of appropriately blocked adenosine derivatives. These new analogues were evaluated as inhibitors of catechol O-methyltransferase and tRNA methylases and found to have poor inhibitory activity.


Conformations and "nictinic" activites of cyclic analogues of choline aryl ether. The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the minimum torsional angles about the aryl-oxygen gond geing 20, 20, 80, and 27 degrees, respectively. Since the piperidinium compound stimulates ganglia, it is concluded the either planarity of the aryl--O--C system is not essential for this type of activity or receptor interaction can involve appreciable bond distortion. The absence of ganglion-stimulant activity in the remaining compounds indicates the need for a transoid arrangement of the O--C--C--N+ system.


Sulfamylurea hypoglycemic agents. 6. High-potency derivatives. Synthetic methods for a series of novel sulfamylurea derivatives have been developed. The hypoglycemic activity of simple 1-piperidinosulfonylureas is greatly enhanced by attaching an acylaminoethyl function in the 4 position of the piperidine ring. Optimum activity is achieved when the acyl radical is 5-chloro-2-methoxybenzoyl, 2-methoxynicotinyl, 5-chloro-2-methoxynicotinyl, 1,2-dihydro-1-methyl-2-ketonicotinyl, 2,3-ethylenedioxybenzoyl, quinoline-8-carbonyl, or 6-chloroquinoline-8-carbonyl. Optimal substituents on the terminal urea nitrogen are cyclohexyl, bicycloheptenylmethyl, and in certain cases propyl, 7-oxabicycloheptanylmethyl, and adamantyl. One of these compounds (81, gliamilide) was found to be well tolerated in man and it displayed a very short plasma half-life.


Drugs derived from cannabinoids. 6. Synthesis of cyclic analogues of dimethylheptylpyran. Two cyclic analogues 8 and 9 of dimethylheptylpyran (DMHP, 1) were synthesized by the Pechmann condensation of the resorcinol 4 with ethyl 4-methyl-2-cyclohexanone-1-carboxylate followed by Grignard addition with MeMgI. In selected pharmacological tests both analogues 8 and 9 were considered inactive compared to DMHP as CNS and cardiovascular agents.


Prepartion of 16alpha-alkoxy and 16alpha-acyloxy derivatives of 21-chloro-17-acyloxy corticosteroids and determination of their vasoconstrictor activities in humans. A number of number of 16alpha-alkoxy and 16alpha-acyloxy derivatives of 21-chloro-17-acyloxy corticosteroids have been prepared. The synthetic routes used were (a) reaction of the 16alpha,17-disubstituted 21-mesylate with lithium chloride and (b) reaction of the 16alpha-substituted 17,21-cyclic ortho ester with triphenylmethyl chloride. The vasoconstrictor activities in humans exhibited by these compounds were significantly lower than that of a 16beta-methyl analogue.


Conformationally rigid amphetamine analogs as inhibitors of monoamine uptake by brain synaptosomes. Four 3-phenyl-2-amino-trans-decalin isomers were synthesized in order to obtain derivatives of phenylethylamine with a rigid conformation between the phenyl ring and the amino function. The stereoisomers were tested as inhibitors of catecholamine uptake by rat brain synaptosomes, and their potency was compared with that of amphetamine. The most potent inhibitor of catecholamine uptake was the diaxial 2(a)-amino-3(a)-phenyl-trans-decalin, which was one-fourth to one-third as potent as (+/)-amphetamine. As a dopamine uptake inhibitor in the stiatum, this compound was competitive. The results differ from those obtained earlier with similar analogs with a norepinephrine moiety incorporated into the decalin structure, since a gauche derivative [2(a)-amino-3(e)-3,4-dihydroxyphenyl-3-trans-decalol] was then the most potent and over 20 times as potent as the diaxial anti derivative. It remains to be seen whether this indicates that the mode of binding of phenylethylamines is different from that of catecholamines.


Partition coefficients and surface areas of some alkylbenzenes. The experimentally measured log P values (logarithms of partition coefficients) of a number of alkylbenzenes are shown to be quantitatively related to the hydrocarbon surface area HSA of the molecule by pi = 0.0275 X HSA - 0.863 (correlation coefficient =0.996, standard deviation = 0.071). The use of surface area as a correlating parameter eliminates the need for correction factors to account for branching, cyclization, ring fusion, and "backfolding". Futhermore, surface area calculations provide a conceptual basis for understanding how conformation can effect partitioning.


Metabolic and photochemical hydroxylation of 5-nitro-2-furancarboxaldehyde derivatives. The potassium salt of 1-[[(5-aco-nitro-4,5-dihydro-4-oxo-2-furanyl)methylene]amino]-2,4-imidazolidinedione (4) was isolated from the urine of rats fed nitrofurantoin. An aldehyde absorbing at 400 nm was synthesized photochemically, in less than 1% yield, from 5-nitro-2-furancarboxaldehyde diacetate (1), and the hydroxylamine (2), 3-amino-2-oxazolidinone (3a-c), and 1-amino-2,4-imidazolidinedione (4) derivatives were prepared. On the basis of ir and NMR data 2, 3b,c, and 4 are considered derivatives of 4-hydroxy-5-nitro-2-furancarboxaldehyde which are mainly in the aci-nitro form. Methyl and ethyl nitronic esters of 3b were synthesized. The photochemical hydroxylation of 1 also yields 3,4-dihydroxy-5-nitro-2-furancarboxaldehyde, isolated as 3-[[(3,4-dimethoxy-5-nitro-2-furanyl)-methylene[amino[-2-oxazolidinone (7).


Antidepressant and anticonvulsant activity of 1-(5-phenyl-4-oxazolin-2-yl)-4-substituted piperazines. 1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-substituted cinnamoylpiperazines and 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were synthesized and evaluated for antidepressant activity in the mouse Dopa potentiation test. 1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were further evaluated for anticonvulsant activity in the audiogenic seizure test in mice.


Aspects of pre-eclamptic toxaemia of pregnancy, consanguinity, twinning in Ankara. It appears that women classed as having pre-eclamptic toxaemia are less frequently consanguineous with their husbands than all other mothers and in particular those mothers classed as having pregnancies complicated by chronic hypertensive disease. Search revealed no evidence for possible biases which could have stimulated such findings. Further evidence is advanced suggesting that, though pre-eclamptic toxaemia is more common in all types of twin pregnancies than in single births, it is more common where the twins are dizygous than where they are monozygous. It is pointed out that both these findings would be expected if there was a contribution to the aetiology of pre-eclamptic toxaemia by maternal/fetal immunological incompatibility. However, if such a mechanism exists it is not always determined at the same gene locus.


Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia. Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out.


Consanguinity and familial mental retardation. Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for studies in the general population in order to understand the biological significance of consanguinity.


Behaviour of cell cultures from human amniotic fluid. The growth pattern of cell cultures originating from 11 amniotic fluid specimens have been observed. From each specimen 2 to 12 primary cultures were set up. In most cases growth started simultaneously in the primary cultures originating from one sample. The primary cultures lasted from 7 to 30 days. A variation was found both between cultures from different pregnancies as well as among cultures obtained from single amniotic fluids. The growth period from setting up the cultures until harvest of the cell lines for biochemical analysis ranged from 20 to 54 days. No connexion was noticed between the time spent in primary culture and the behaviour of the cell line before harvest. The effects of two types of serum (fetal calf serum and pooled human serum) on the behaviour of the cultures were compared. The cells grown in human serum were harvested a few days before those grown in fetal calf serum. The influence of different batches of medium was also examined; no significant effect of the growth pattern was found. The appearance of epithelial-like and fibroblast-like cells in cultures from 6 specimens was observed concurrently. At the time of  harvest the cell lines originating from the same amniotic specimen contained the cell types in different proportions.


New allele at cholinesterase locus 1.

New allele at cholinesterase locus 1. A family (H-J pedigree) segregating for the A and F alleles at cholinesterase locus 1 is described. Apparent anomalous results led to the recognition of a new allele (E1j) also segregating in the family. The data are consistent with the hypothesis that the the E1j causes reduction of 'usual' (E1u) molecules by about 66%. Whether this is because of retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.


Prenatal diagnosis of Wolman's disease.

Prenatal diagnosis of Wolman's disease. Amniocentesis was performed in the 15th week of a pregnancy at risk for Wolman's disease. The cultured amniotic fluid cells were found to have a severe deficiency of acid esterase activity consistent with homozygosity of the fetus. The pregnancy was terminated in the 19th week and the prenatal diagnosis confirmed by enzymic and chemical evaluation of the fetal tissues.


The Gardner syndrome: increased tetraploidy in cultured skin fibroblast. Tetraploidy was increased in skin fibroblast cultures grown in the laboratory at the same time under the same conditions and derived from 2 probands with the Gardner syndrome and 9 affected members of one family as compared to that occurring in cultures from 5 relatives by marriage and 10 normals. Tetraploidy was present at the first subculture (2 weeks after the initial biopsy was cultured), and for each line studied the percentage of dividing cells showing tetraploidy remained constant. The relation of the observed tetraploidy to the increased risk of such patients to develop abnormal growths and cancer has not been established. The increased tetraploidy should be of value in identifying the presence of the gene for the Gardner syndrome in high risk families.


An XX female with sexual infantilism, absent gonads, and lack of Müllerian ducts. A patient with a 46,XX chromosome constitution showed the following main characteristics: lack of secondary sexual development, female external genitalia with absence of vagina, no gonadal structures, and complete lack of internal genitalia. This is a variant of the gonadal agenesis syndrome so far only described in association with and XY chromosome component. Endrocinology demonstrated that in the absence of gonadal feedback the pituitary responsiveness to synthetic luteinizing hormone-releasing hormone was increased.


Further observations on the Birmingham chimaera. The appropriate ABH-gene specified glycosyltransferases in the plasma of the Birmingham chimaera were estimated. These observatiions and the demonstration of A1Leb blood group specific glycosphingolipid in the plasma indicate that the minority population of red blood cells probably represents the true blood groups of the patient.


A case of hypogonadotrophic hypogonadism with anosmia (Kallmann's syndrome) in a male, with familial incidence of a small metacentric chromosome (47,XX, mat?+). A case of Kallmann's syndrome in a male is reported. Besides the classical picture of hypogonadotrophic hypogonadism (demonstrated both  by endocrine investigation and a testicular biopsy) with anosmia, a number of other unusual features are present including gynaecomastia, agencies of the anterior brachial muscles, some dental abnormalities, and dyschromatopsy. The karyotype, studied on peripheral lymphocytes, shows, in the propositus as well as in his mother, the presence in all mitoses of an extra small metacentric chromosome; its derivation is uncertain.


Trigonocephaly and associated minor anomalies in mother and son. A mother and her son are described with neonatal trigonocephaly, multiple suture synostosis; shallow orbits; unusual nose; deviation of the terminal phalanges of  fingers 1, 2, and 5; and broad toes which radiologically may show duplication of the terminal phalanx. Untreated, the condition leads to a disfiguring oxycephaly with hypotelorism. This appears to be the first documented instance of autosomal dominant trigonocephaly. The importance of the minor anomalies in its recognition and its good prognosis are emphasized.


Loans for medical students: the issue of manageability. Unless there is a shift in student aid policy for medical students to a greater proportion of scholarships or grants, increased student borrowing is inevitable. This paper is concerned with the structure of student loan programs and with altering the repayment features of the programs for the convenience of the student borrower. In this context the Guaranteed Student Loan Program is analyzed and its current limitations discussed. A variant of the GSL program having an income contingent repayment feature is proposed. Computer simulations of loan repayments with the proposed income contingent variant and the current program using current and projected data on physicians' incomes are developed. Based on the results of these simulations, some conclusions regarding the manageability of repayments with the proposed loan program are presented.


Selecting a few residents from many applicants: a new way to be fair and efficient. Selection of residents from among the large number of qualified applicants is an annual task requiring a significant commitment of resources by teaching hospitals. A method based on sound principles of decision-making and utilizing a computer analysis for initial ranking of applicants was developed to improve the selection process. The result was satisfactory selection with significant savings of time and effort for the residency program faculty.


What happens to creative medical students? A psychometric index of creative potential was devised by relating test scores to ratings of creativity in samples of architects, engineers, mathematicians, psychologists, and research scientists. A correlation of .45 was obtained between scores on this index and the criterion ratings in the total initial sample of 350 men. The tests used to compute scores on the index were also available for 284 first-year medical students being studied as physicians in a longitudinal inquiry on speciality choice and location of practice. The mean creativity score of the medical students was higher than that for any of the other samples. Within the array of means for medical specialty groups, psychiatrists ranked first and internists second. Students who failed to complete medical school also scored high, suggesting that dropping out is not just a matter of poor academic potential or unsuitability for a career in medicine.


Effectiveness of an international health elective as measured by NBME Part II. A total of 434 third- and fourth- year medical students from 80 U.S. medical schools participate between 1968 and 1974 in Yugoslav or Israeli international fellowship programs sponsored by the Association of American Medical Colleges and the U.S. Public Health Service. Subsequently, the scores of these fellowship student on Part II of the examinations of the National Board of Medical Examiners (NBME) were compared with the scores of rejected applicants and  with the national average to determine the cognitive impact of the fellowship experience on the  participants. The results show that the international fellows scored significantly higher than the rejected applicants and the national average in only the preventive medicine/public health portion of the examination. The conclusion is drawn that the fellowship programs enhanced the participants' knowledge of preventive medicine and public health.


Evaluating student performance in a decentralized basic science program. The results of the evaluation of the basic science curriculum in a regionalized medical education program in the states of Washington, Alaska, Montana, and Idaho (WAMI) are presented and discussed. The hypothesis that students taking the first quarter of basic science at universities remote from the Unversity of Washington School of Medicine (UWSM) will be no different in academic performance from those who remain at the UWSM is tested. The variables considered were student performance on (a) common tests in Anatomy/Histology, Biochemistry, Mechanisms of Physiology, and Epidemiology; (b) subsequent course work at the UWSM; and (c) the mini-tests and Part I of the examinations of the National Board of Medical Examiners. The developement of the common tests is described. Analysis of variance indicates that the null hypothesis cannot be rejected at the .05 level.


A computer-assisted admission matching system for the University of Texas medical schools. The feasibility of a computer-assisted admission matching system was investigated in 1973-74 at the Medical and Dental Application Center at the request of the four University of Texas medical schools. Preference data were gathered from applicants and from schools, and matching simulation was conducted concurrently with actual admission action for 1974 entering classes. Implementation of a matching system for admission of the 1975 entering classes was demonstrated to be feasible, and  a decision to implement such a system was made. Data indicating the need for a matching system are briefly reviewed, and the matching concept is discussed. Results of the 1974 feasibility study are presented, and the first year of implementation for the 1975 entering classes is described. Admission matching improved the efficiency  of the admission process by reducing the number of unproductive offers of admission and by providing more applicants earlier decisions from participating schools regarding their applications.


Cancer centers: their relationship to the academic community. During the past decade one important change that has occurred in medical education has been the development of multidisciplinary research, education, and treatment efforts by new groups of scholars drawn from multiple disciplines. In their daily activities members of such groups have more in common with their new affinity group than with their traditional discipline. Yet important adminstrative functions such as appointment, assignment of space, and allocation of budget are conducted by separate administrative units. This has produced stress and conflict within many academic institutions. Some of the lessons learned by institutions participating in the cancer center program may be generally applicable. Comprehensive cancer centers have evolved several types of administrative sturctures, but there is a common characteristics among the most successful. Each has developed some modification of a matrix system with delegation of significant administrative authority to the center. If the matrix approach is successful in cancer, it may become a pattern for other programs in the future.


The lecture: increasing student learning. This  study involved a single lecture given to second-year medical students.  Its purpose was to detemine whether significant learning of the lecture content could occur during the lecture. The author's criteria for "significant" learning was mastery of 75 percent of what he predetermined to be the important of "required" content plus T-test analysis of pretest-posttest learning. The class divided into Groups A and B. At the commencement of the lecture Group A took Test 1 as its pretest and Group B took Test 2.  Immediately following the lecture Group A took Test 2 as its posttest and Group B took Test 1. Comparing Test 1 with Test 2 as pretests and again as posttest, they were not significantly different at the .05 level. However, Group A's posttest scores were significantly higher than its pretest scores (p less than .005). The same was found for Group B, with both groups' averaging over 90 percent mastery of the required content and demonstrating that significant learning occurred during the lecture.


The use of test results from ASA workshops to evaluate workshop effectiveness. Results of tests given to participants in  six American Society of Anesthesiologists workshops were analyzed to detemine whether attendance at the workshops increased the participants' scores on sequential tests. Those who attended the workshops took the  same test prior to, immediately after, and three months after the workshop. Two control groups of anesthesiologists took the tests in the same time sequence for comparison. Both workshop and control  groups increased their scores with each successive test. In only one instance did those who attended the workshop improve their scores significantly more than did the control group. Because of difficulties inherent in designing valid and reliable tests, further development of the testing technique currently used at the workshops is necessary to make it a useful measure of workshop effectiveness.


The teaching of child psychiatry in U.S. medical schools: results of a survey. The major results of this survey are that most schools have special programs in child psychiatry and that these are distinct from the adult psychiatry course. The course content involves clinical evaluation of children, information on child development and psychopathology, assigned reading, and liaison with pediatrics. Most schools have full-time psychiatrists on their faculty, and the child psychiatry course is taught by child psychiatrists; but less than 20 percent of the psychiatric faculty are child psychiatrists in a majority of the schools in the country. Finally, although evaluation by students and faculty is common in most of the schools, only slightly more than one-third of the institutions gave grades in child psychiatry and slightly fewer than one-third gave examinations in this subject.


Feasibility studies of evoked response audiometry in the mentally subnormal. Evoked response audiometry was attempted on a group of seventy-seven unsedated severly subnormal patients up to the age of twenty-two years. Data of some clinical value were obtained in fifty-seven cases. It is suggested that sedation need only be used if the initial attempt at E.R.A. is unsuccessful. Over twenty per cent of the subjects appeared to have significant hearing loss.


Resistance to extinction as a function of IQ and reinforcement ratio among retarded children. Children at three levels of mental retardation (IQ ranges of 50-60, 30-40 and 20-below) were trained to bar-press on one of two variable ratio (V.R.) schedules. Responses were reinforced twenty-five times on either a V.R.2 or V.R.4 schedule. Analysis of the number of responses during extinction indicated an inverse relationship between IQ and resistance to extinction. The period reinforcement extinction effect was found, but there was no interaction with IQ level. The results support the position that inhibitory control is an important parameter along which intelligence may be ordered.


The syndrome of Coffin, Siris and Wegienka: report of a case. A severely subnormal male with the syndrome of Coffin, Siris and Wegienka is described and compared with previously reported cases. The possible aetiology is discussed.


Spontaneous fluctuation in rate of body rocking: a methodological note. Descriptive data are presented on the natural occurrence of stereotyped body rocking in three institutionalised, mentally retarded children. Both ward and test situation observations suggest that there is spontaneous fluctuation in rate of body rocking. These findings raise a serious methodological problem pertinent to the evaluation of experimental data on stereotyped behaviour: rate change attributed to experimental manipulation may in fact only be an instance of spontaneous fluctuation.


Short-cycle manic depressive psychosis in mental defectives: a clinical and physiological study. The clinical features of four cases of short-cycle manic depressive psychosis occurring in mentally defective patients are described. Behavioural fluctuations are correlated with alterations in sleep pattern, pulse rate and temperature. The diagnostic problems and significance of the observations are discussed.


Obesity in an institutionalised adult mentally retarded population. The frequency of obesity, as defined by standards based on triceps skinfold, and selected body measurements are reported in an institutionalised adult mentally retarded population. Among 161 adults, aged eighteen to seventy-three years, twenty-two out of 108 males (20.4 per cent) and nine out of fifty-three females (17.0 per cent) were obese. These findings suggest that obesity is a significant health-related problem in institutionalised retarded adults. Although differences were not statistically significant, the frequency of obesity was higher in moderately retarded than in mildly or severely retarded residents. Further surveys are needed of larger samples, along with studies of possible contributory factors (e.g., dietary habits and level of physical activity).


Sex is a family affair: sources of discord and harmony. Sexuality is a central source of communication and growth in the development of relationships between an individual and his parents, spouse, and children. It is both a vehicle for and manifestation of crucial interpersonal links. In the physical sense, this is seen when the adolescent or adult's physical sexual expression is evidence of closeness to another and it also a way of achieving such closeness. In the psychological sense, sexual behavior in current relationships may be hindered by carrying the image of internalized aspects of past relationships; it may also afford a new setting for further work on them. This paper explores family aspects of sexual issues in several areas, demonstrating that when sexual dysfunction represents the distillation of a couple's relationship to their own parents, successful resolution of their own sexual relationship may be a crucial first step in rebuilding family harmony and providing a culture of intimacy for their children.


Issues and dilemmas in sexual treatment. Five concrete issues and dilemmas typically confronted in the practice of treatment of sexual problems are discussed. These are: (a) the issue of therapeutic values and conflict in values that may arise for the therapist; (b) the phenomenon of the desperation of the impotent male and its relationship to coping techniques and cultural expectations; (c) masturbation as a development stage in sexual responsiveness, based on evidence from historical, cross-cultural, human, and animal studies and clinical practice; (d) the positive aspects of the self-concept of nonorgasmic women that may serve as resistance to sexual responsiveness; and (e) a specific value conflict for women therapists that is a reflection of the change in values promoted by the women's movement.


New data about female sexual response.

New data about female sexual response. This paper reports on a 195-subject pilot study of female sexual responses. The questionnaire used in the study is described, and the data obtained are discussed and integrated with established research and theory. Discussion focuses on the relatively low frequency with which women actually experience orgasm in sexual relations and the need to understand the reasons for this phenomenon. The concept of the normality of this varied capacity for orgasm is presented in contrast to the usual tendency to evaluate female responses by male standards. Several sexual patterns and different types of orgasms in the female are identified, and the relationship between the type of responses perceived and various other factors is discussed. Responses indicated that, on the average, the strength and degree of gratification provided by an orgasm is not related to the method of induction or to the subjective localization of the pulsating sensations.


Persistence, planning, patience, and prevention: aspects of sex education in medicine. This paper emphasizes the rapid response of American medical schools to the absence of sex education in their curricula, which has led to diversity of design, strategy, and evaluation of human sexuality courses. It further points out that most such courses are inadequate to teach physicians knowledge and skills that will be required when they leave medical school. Major areas of resistance to full implementation of comprehensive sex education programs are cited, with one method outlined to overcome institutional resistance. The authors cite case examples of the variety of sexual conflicts that become accessible in students and faculty as a result of such instruction. They suggest that groups of persons who are sexually knowledgeable and possess counseling skills in sex therapy could greatly improve sex education in the medical institution.


Sex education for adolescents and their families. This paper describes a unique, 2-day experiential program in sex education for adolescents and their families. The program is adapted from a similar teaching program for medical students and is a highly focused, intense emotional experience wherein participants are presented, via a multimedia approach, with a planned sequence of explicit sexual material on all areas of human sexuality. During the program, six small group sessions with family members in separate groups enable participants to share impressions and examine anxieties aroused by the presentations. The entire process is monitored by evaluative instruments and questionnaires. Results of the data support the hypothesis that communication is possible between generations, and assists rather than inhibits the development of an adult identity.


Accumulation of calcium in kidney and decrease of calcium in serum of rats treated with tin chloride. Effect of tin on the kidney calcium and serum calcium concentration was studied in rats intraperitoneally administered with tin chloride. The calcium concentration in kidney was significantly increased by administration of tin (1.0 mg/100 g), and this increase was dose dependent. A significant increase in the level of kidney calcium was not exhibited by the administration of zinc, manganese, or lead. The increased calcium after the administration of tin predominantly accumulated in the cortex of kidney. The administration of tin did not show a significant alteration of sodium and potassium concentration in the kidney. The level of serum calcium was significantly decreased by the administration of tin (2.0 mg/100 g), and this reduction was dose dependent. The decrease of serum calcium by the administration of tin was associated with the accumulation of calcium in the kidney by treatment with tin.


Metabolism of a new herbicide, tebuthiuron (1-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]- 1,3-dimethylurea), in mouse, rat, rabbit, dog, duck, and fish. Orally dosed tebuthiuron was readily absorbed in mice, rats, rabbits, dogs, and ducks. The compound was extensively metabolized and the metabolites were  rapidly excreted in the urine of mice, rats, rabbits, and dogs and in the mixture of urine and feces in ducks. The major metabolites of tebuthiuron were formed by N-demthylation of the substituted urea side chain in each species examined, including fish. Oxidation of the dimethylethyl group occurred in mice, rats, dogs, rabbits, and ducks. The N-demethylation reaction at the 3-position of the urea proceded through  an N-hydroxymethyl intermediate. No accumulation of tebuthiuron or its metabolites was observed in the animals, a finding consistent with the low order of toxicity observed in other studies.


Toxicity of delta9 -tetrahydrocannabinol (THC) administered subcutaneously for 13 days to female rabbits. Delta9- Tetrahydrocannabinol (THC) was administered subcutaneously to female New Zealand white strain rabbits for 13 days. The animals were randomly divided into  six groups of five animals each of which consisted of untreated controls, vehicle (undiluted propylene glycol)-treated, and THC treatment at dose levels of 100, 30, 10, and 3 mg/kg/day. All animals survived for the duration of the study. The THC-treated rabbits did not gain significant body weight which seems to be due to a decreased food consumption. There were some variations in various hematologic values, but they all were within the normal range for our laboratory. Blood chemistry evaluations showed decreased serum levels of potassium, glucose, blood urea nitrogen, alkaline phosphatase, and albumin/globulin (A/G) ratio and an increase in cholesterol levels of all treated animals. A significant increase in billirubin values was noted in the animsls of the 3- and 10-mg/kg groups. The injection site in the skin of the THC-treated rabbits showed signs of local irritation (erythema and subcutaneous abscesses). There was a reduction in absolute and percent of body weight of the liver and absolute weight of the lungs of the treated animals. However, no histopathologic alterations were observed. It may be concluded that THC treatment subcutaneously for 13 days in rabbits up to a dose level of 100 mg/kg/day did not produce any significant toxicity, except anorexia and some local dermal irritation.


Lymphatic tissue response in chickens treated with tri-o-tolyl phosphate. Indices of immunologic response elicited by tri-o-tolyl phosphate (TOTP) in chickens were investigated. Histopathologic evaluation of lymphatic organs (spleen, cecal tonsil, bursa of Fabricius) and selected immuno-related visceral organs containing lymphatic infiltrations (liver, kidney, duodenum, pancreas) was conducted. Liver and spleen showed a consistent and definite increase of diffuse lymphatic tissue in TOTP-treated animals. Total plasma protein levels of treated animals were increased from 7 to 20% over 4-14 days after TOTP administration. A similar increased pattern was noted in gamma-globulin:albumin ratios of the treated group. The data suggested stimulation of immunologic response in chickens treated with TOTP.


Effects of 1,1,1-trichloroethane administered by different routes and in different solvents on barbiturate hypnosis and metabolism in mice. A 24-hr inhalation of 1,1,1-tricholoroethane (methylchloroform), 3,000 ppm, reduced pentobarbital hypnosis and increased hexobarbitaloxidation by the 9,000 x g liver supernatant fraction in male mice.  On the other hand, an ip injection of methylchloroform, l ml/kg, increased the duration of pentobarbital hypnosis and reduced hexobarbital metabolism by the liver microsomal enzymes.  The potentioating effect of methylchloroform on pentobarbital hypnosis as diminished when it was diluted with olive oil, but was markedly enhanced when diluted with dimethysusoxide (DMSO) before injection. Three local applications of methylchloroform )1:1 dilution with DMSO) had an effect similar to that of inhalation on pentobarbital hypnosis.


Lack of effect of dietary diethylstilbestrol on reproductive performance. Groups of male or female mice were pretreated for 2 wk and 1 wk, respectively, with flesh (liver or muscle) diets prepared from steers. In one experiment diethylstilbestrol (DES) was added to the diet at 0.5 or 5.0 ppb. In a second experiment diets prepared from DES-implanted steer flesh (liver or muscle) were fed. Tissues used in the control diet and DES-added diets were from DES-free steers. The animals were allowed to mate and diets continued until the first litter was delivered. Increasing DES levels in either liver or muscle diets or flesh from DES-implanted steers resulted in no significant differences either in litter size or in the number of fertile male or female mice between the control group and experimental groups. The offspring from each litter were mated and showed no significant difference in their reproductive performance. No abnormalities were noted in any offspring.


Deldrin and parathion interaction in the prostate and liver of the mouse. The oral administration of dieldrin (1.25 mg/kg daily x 5 or 10) and/or parathion (5.2, 2.6, or 1.3 mg/kg daily x 5 or u0) caused significant alterations in the metabolism of [1,2-3H]testosterone by the anterior prostate gland and by the hepatic microsomal enzyme system in the mouse. A 5-day parathion treatment followed by another 5-day treatment with dieldrin led to significant increases in the levels of [3H]androstanediol a [3H]androstenedione formed by the prostate gland in vitro. Dieldrin alone, dieldrin plus parathion, or dieldrin administration followed by parathion treatment caused significant reductions in the levels of [3H]androstenedione formed by hepatic microsomal enzymes. Concomitantly, significant increases were observed in hepatic 7alpha-and 6beta-testosterone hydroxylase activities in animals treated with parathion followed by dieldrin administration. The present findings revealed that the administration of parathion or dieldrin leads to changes in the metabolism of male sex hormones in mouse liver and sex accessory organs. In addition, the simultaneous administration of parathion and dieldrin leads to an interaction that can alter the biologic effects of either compound.


Toxicology of vindesine (desacetyl vinblastine amide) in mice, rats, and dogs. Comparative acute intravenous toxicity studies of vinblastine sulfate (VLB), vincristine sulfate (VCR), and vindesine in mice and rats indicated that vindesine was more toxic than VLB and less toxic than VCR. Rats were able to tolerate larger repeated doses of vindesine than dogs. Rats given intravenous doses totaling 0.15 mg/kg-wk vindesine for 3 months developed no remarkable signs of toxicity. Doses of 0.3 mg/kg-wk or greater produced anorexia, depressed blood cell counts, atrophic intestinal mucosa, inhibition of spermatogenesis, extramedullary hematopoiesis, and infections. Dogs were given total weekly intravenous doses of 0.04, 0.08, 0.1, or 0.16 mg/kg vindesine for 3 months. The only observed effect in the two lower dose groups was inhibition of spermatogenesis. Groups receiving 0.1 or 0.16 mg/kg developed leukopenia, slight erythropenia, inhibition of spermatogenesis, focal skeletal muscle degeneration, elevated lactic dehydrogenase, and an increase in bone marrow myeloid: erythroid ratio. No evidence of functional or structural changes in neural tissues was found. The above effects are common to animals given VCR at lower doses and for a shorter test period. It is therefore concluded that vindesine is less toxic in animals than VCR.


Teratological evaluation of FD&C Red no. 2 -a collaborative government-industry study. II. FDA's study. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.


Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. III. IBT's study. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No.2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel stran rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River stain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.


Teratological evaluation of FD&C Red No. 2-a collaborative government -industry study. IV. NCTR's study. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA),Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.


Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. V. Combined findings and discussion. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, anad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrail Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but  the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities of other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.


The pathophysiology of acute electric injuries. Results of the present investigation indicate that an electric burn is simply a thermal injury. The tissue damage associated with an electric injury occurs when electric energy is converted to thermal energy or heat. An electric burn is self limiting: once the current arcs, no further skin and muscle damage is possible because amperage falls to zero. Tissue temperature is the critical factor in determining the magnitude of tissue injury before the current arcs. With the exception of skin resistance, resistances of individual tissues seem not relevant to amount of tissue damage in electric injuries. Living tissue acts as a volume conductor; once skin resistance has been overcome all internal tissue resistance, with the exception of bone, is negligible to current flow. In the present study the volume of tissue traversed by the electric current was more closely related to the extent of tissue injury than the internal resistance of the individual tissues. Muscle injury occurred at the time of initial thermal insult and progressive or de novo muscle necrosis was not seen in this model.


Fat emboli syndrome.

Fat emboli syndrome. A review of the medical records of 30 patients with major trauma was undertaken. One third had fat emboli syndrome characterized by hypoxemia, confusion, and petechiae. Fluid balance was similar for all patients in the study. Hematologic indices had no prognostic value in identifying patients who were to become symptomatic from fat embolization. The serum albumin concentrations were significantly lower in the symptomatic group. The free fatty acid binding capacity of albumin is discussed.


A comparative study of four materials in local burn care in rabbit model. In rabbits, a second-degree burn model with partial tangenitial excision of necrotic tissue was used to compare four dressing materials for effectiveness of promoting wound healing. The time of complete epithelization of the 2 X 4 cm large defect, changes in wound area, adherence of the dressings to the wound, and histology of the wound bed and dressings were measured. Dressings were changed twice weekly. Experiments showed that as a local dressing for burns, non-laminated collagen sponge was significantly better than pigskin or xeroform. Infection did not occur under it. It was very adherent to the burn wound and was actively permeated by inflammatory cells. This factor allowed early debridement of the wound. Effective debridement was probably responsible for the shorter healing time shown. Laminated collagen sponge was the poorest of the four dressings tested.


Ninety-eight penetrating vascular injuries: a review of a two and one-half year experience. In a review of 55 patients with 98 penetrating vascular injuries over more than 2 years (most were gunshot wounds), the mortality rate was 46% in patients with intra-abdominal vascular injuries and 7% in those with extra-abdominal injuries. There were no major amputations. One patient had two fingers amputated.


Fracture healing in rats treated with diphenylhydantoin (Dilantin). Fibula fractures were surgically made in mature male rats. Experimental animals received 4 mg/kg body weight of DPH (Dilantin) injected intraperitoneally, and equivalent volumes of sterile saline were injected intraperitoneally in controls. Fracture healing was assessed by a histologic method 5, 10, 15, 20, 25, and 30 days following the fracture. Thirty days following the injury, the DPH-treated animals showed a statistically significant increased rate of union. A comparison in trends of fracture healing for experimental and control animals showed similar enhancement of fracture healing in the experimental animals throughout the entire observation period.


Femoral shaft fractures in brain-injured children. Thirty-nine head injured, initially comatose children with 44 femoral shaft fractures were treated by various methods. Thirty-two eventually ambulated. Tibial skeletal traction and skin traction were ineffective methods of management. Internal fixation or distal femoral traction are advised.


Trauma or treatment? The role of intermittent traction in the treatment of cervical soft tissue injuries. Neurophysiology does not provide a satisfactory theory which explains the phenomenon of muscular "spasm" which is said to be present in the neck following soft-tissue injury. Lacking knowledge as to whether long continued intermittent traction--ranging from 10 pounds to total body weight pull--is therapeutic or traumatic, such treatments nevertheless are prescribed in physiotherapy departments and at home for months. They are believed to be non-physiological and irrational and, in the author's opinon, represent the persistence of several medical myths associated with the "rear-end" collision. The question is moot whether the intractable complaints following such injuries are not caused, in large part, by the repeated traumas to muscles, disks, and joints produced by strong intermittent distraction. Experimental anatomical studies also argue against the hopes expressed in favor of such treatment, namely: to relieve spasm and/or traumatic fibro-myositis (?), to enlarge the neural foramina and relieve "radiculitis," and to hasten recovery by means of a conjectured internal massage.


The hazard of the unrestrained occupant. A review of 208 cases involving injuries sustained by vehicle occupants was extracted from the computer storage at the Highway Safety Research Institute, University of Michigan, Ann Arbor. In addition, 157 new car crashes investigated by the authors were separately analyzed. Data analysis indicates injuries are sustained by direct occupant-to-occupant contact and by one occupant forcing another into or against one or more interior car structures. All body areas can be involved in this previously unreported injury mechanism, with the upper portion of the body more susceptibel to injury. Case histories from field accident investigations document a variety of these injury mechanisms.


Roll seat belt induced injury of the duodenum. A case of duodenal rupture with a roll three-point seatbelt is described. It is apparently the seventh reported case of duodenal rupture in safety belt users. A female driver fell asleep, and her car went off the road, rolling forward in a ditch, slowing slightly, and then came to a sudden stop. The rupture was unusual: on the first part of duodenum, intraperitoneal, and longitudinal. The rupture mechanism is discussed, and the deficiencies of the roll seatbelt pointed out in accidents like the one described.


Acute leukopenia as an allergic reaction to silver sulfadiazine in burn patients. Of 68 burn patients at the University of Wisoncsin Burn Center treated with silver sulfadiazine cream over 2 years, two (about 3%) developed fever and marked leukopenia. The symptoms disappeared 1-2 days after discontinuation of the cream. The two cases are described and possible mechanisms of allergic response to this agent are discussed.


Dislocation of the talonavicular joint: case report. Dislocation of the talonavicular joint is rare, caused by severe abduction or adduction of the forefoot. Proper reduction is necessary to avoid equinovarus deformity, ankylosis, or degenerative arthritis. A case of talonavicular dislocation with fracture of the head of the talus in a 52-year old woman is reported, with delayed treatment by open reduction using Kirschner wires and casting for 7 weeks. This patient is successfully employed as a waitress 2 years postinjury.


Unstable hemipelvic fractures with internal rotation displacement. Two cases of unstable hemipelvic fractures with internal rotation displacement successfully treated by outward (external lateral) rotation and continuous skeletal traction by wires passed through the crest of the ilium are described. X-rays show both patients before and 2 years after treatment.


Gastric necrosis from blunt abdominal trauma. Two patients with ischemic necrosis of a portion of the gastric wall resulting from blunt abdominal trauma are reported. This gastric injury results from avulsion of the mesentery from the injured area or from a shearing force. Careful inspection of the stomach during exploration is emphasized and gastrotomy advocated if injury is suspected. Treatment consists of resection of the ischemic portion of the stomach.


Stab wound causing mesenteric-portal arteriovenous fistula: an unusual case with a spontaneous closure. A case of spontaneous closure of a mesenteric-portal arteriovenous fistula secondary to a stab wound is described. Although a variety of clinical complications can result from such fistulae, it is not always possible to perform an immediate closure of such lesions. The patient described was unable because of his condition to undergo surgical repair of his fistula: when readmitted after 2 months the fistula had closed and the artery was normal.


Lacerations of the lacrimal apparatus, parotid duct, and facial nerve: case report. Diagnosis and surgical treatment of a male patient with severe facial lacerations involving the lacrimal duct, parotid duct, and buccal branch of facial nerve are presented. Careful wound care and localization of severed nerves and ducts, and repair under microscope are emphasized.


The Montenegro reaction in guinea pigs infected by Leishmania enriettii and the effect of antigens prepared from various Leishmania isolates. All antigens (leishmanin) prepared from nine isolates of Leishmania gave positive skin tests in guinea pigs infected with L. enriettii. However, variation in potency was observed and ascribed to batch variation. It is recommended that biological testing of leishmanin is considered before use in field surveys or as an aid to clinical diagnosis.


Acute renal failure following hornet stings. Reports of acute tubular necrosis following envenomation by hornets are rare. A 38-year-old farmer presented with evidence of haemolysis and acute renal failure following multiple hornet stings (Vespa orientalis). Biopsy of skin from the site of the stings showed evidence of vasculitis. Renal biopsy showed characteristic changes of acute tubular necrosis. Intravascular haemolysis due to haemolytic properties of the hornet venom was considered to be chiefly responsible for the renal lesions in this patient.


Synthesis of the adenovirus-coded DNA binding protein in infected cells. Synthesis of the 75K (75K indicates a moleculatr weight of 70,000 to 75,000) DNA binding protein, an early virus-coded protein in adenovirus 2-infected KB cells, and its regulation were studied by using a radioimmune precipitation inhibition assay. The protein was first detected at 4 h postinfection and accumulated at an expoential rate. An arrest of further synthesis (accumulation) was observed at 10 to 11 h postinfection, coinciding with the onset of synthesis of late virion proteins. In contrast, when the infected cells were treated with 25 mug of arabinosyl cytosine per ml to block viral DNA replication, the synthesis of 75K protein did not cease but continue for up to 36 h postinfection. The synthesis of 75K protein in cells after release from  a  cycloheximide block (2 to 9 h postinfection) was analyzed. Increased amounts of early adenovirus-specific mRNA accumulate in infected cells during a cycloheximide block (Parsons and Green, 1971). However, cycloheximide treatment did not produce increased levels of 75K protein, and an abrupt arrest of 75K protein formation was again observed at the time of synthesis of late virion proteins. Partition of the 75K protein between the nuclear and cytoplasmic fractions during the course of infection was studied. The 75K protein appeared first in the cytoplasm and then in the nucleus after a slight lag. Accumulation of the 75K protein continued both in the cytoplasm and nucleus, with higher levels being found in the cytoplasm.


Cell-free translation of influenza virus mRNA. Cytoplasmic poly (A)-rich RNA extracted from fowl plague virus-infected cells was found to program efficiently the translation of two major peptides in the wheat germ cell-free system. These peptides have the same electrophoretic mobility, on polyacrylamide gels, as the two major virion proteins M and NP. [35S] methionine tryptic peptide analysis by one-dimensionalthin-layer ionophoresis and finger printing by two-dimensional thin-layer ionophoresis and chromatography show a high degree of similarity between the two in vitro products and the authentic viral proteins M and NP. Although virion RNA is devoid of any poly (A) sequence, it is confirmed here that the viral complementary cytoplasmic RNA contains poly (A) stretches of varying lengths. Intact purified virion was found to promote the synthesis of very low amounts of the same NP and M proteins in  this cell-free system. Quantitative aspects of data would indicate that this is due to minute amounts of complementary viral RNA associated with the virion or with the virion RNA itself. In conclusion, it is shown diectly by cell-free translation of authentic viral products that the influenza virion is "negative stranded" (Baltimore, 1971), at least for its two major structural proteins.


Translation of murine leukemia virus RNA in cell-free systems from animal cells. The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. All three polypeptides were precipitable with antiserum to detergent-disrupted MuLV. Fingerprint analysis of tryptic digests indicated that all three contain anino acid sequences in common with each other and with the major methionine-containing structural proteins of the virion.


High-voltage electron microscope study of the release of vaccinia virus from whole cells. High-voltage (1,000-kV) electron microscope examination of whole BSC-1 cells infected with vaccinia virus at different times after infection revealed the presence of increasing numbers of virions no longer confined to factories but situated along the cell periphery of monolayer cells. Stereoscopic images showed each virus enclosed within a membrane-like component of the host cell cytoplasm. Viruses within factories appeared to lack similar enclosures. Cytochalasin B, but not vinblastine, caused the enclosures to disrupt. Vaccinia viruses were observed to escape the host cell individually from the tips of microvillie and within packets of cytoplasm. Observations suggest that the intracellular movement and release of vaccinia virus utilize a host cell cytoplasmic network that involves microfilaments for stability.


Multiple structures of adeno-associated virus DNA: analysis of terminally labeled molecules with endonuclease R-Hae III. The double-stranded form of adeno-associated virus (AAV) DNA has about 20 sites sensitive to endonuclease R.Hae III from Haemophilus aegypitus; the fragments produced fall into about 13 size classes, 8 of which contain single fragments. The location of the Hae III-produced AAV fragments relative to the three EcoR1 fragments was determined. Using revised figures for the molecular weights of the Hae III cleavage products of phiX174 replicative form DNA, we calculated that AAV DNA contains about 4,000 nucleotides. After Hae III digestiion of duplex DNA terminally labeled with 32P using polynucleotide kinase, the majority of fragments containing a 5' 32P label were about 40 nucleotides in length, and fragments of similar size were generated from each end, suggesting that the Hae site closest to the end is within the terminal repetition. Two more-slowly-migrating cleavage products also bore 5' 32P end label. These three terminally labeled species were also generated from single-stranded AAV DNA by digestion with Hae III, and evidence that one may have a nonlinear ("rabbit-ear") structure is presented. The predominant 5' terminal base was identified as thymine for both the plus and minus strands of AAV. Single-stranded AAV molecules could not be efficiently covalently circularized by incubation with polynucleotide ligase or ligase plus T4 DNA polymerase.


DNA-protein complex in circular DNA from Bacillus bacteriophage GA-1. DNA prepared from bacteriophage GA-1 contains circular DNA molecules, which are converted to linear molecules by treatment with trypsin.


Method for the isolation of bacteriphage T4 mutants that produce particles with giant capsids. An efficient procedure is described for isolating bacteriophage T4 mutants that produce particles with giant capsids. The selective parameters of the technique rely primarily on the giants' characteristic density in cesium gradients and on their resistance to UV radiation.


Neurovirulence and induction of hydrocephalus with parental, mutant, and revertant strains of measles virus. The relationship between neurovirulence and induction of hydrocephalus was investigated for a measles virus temperature-sensitive mutant and its revertant. The revertant regained the neurovirulence of the parental strain. At appropriate doses the parental, mutant, and revertant strains induced hydrocephalus.


Message activity of influenza viral RNA. The message activity of influenza virion RNA in the wheat germ cell-free protein-synthesizing system was investigated. RNA extracted from purified virions was found to direct the synthesis of a polypeptide that had the mobility of viral nucleocapsid protein on sodium dodecyl sulfate-polyacrylamide gels. Further characterization of the protein indicated it was not the nucleocapsid protein. No other polypeptides were detected. We conclude that influenza virion RNA is inactive as a template for the synthesis of virus-specific proteins.


Excision and duplication of su3+-transducing fragments carried by bacteriophage phi 80. I. Novel structure of phi 80sus2psu3+ DNA molecule. DNA molecules of phi 80sus2psu3+ and phi 80dsu3+ isolated by Andoh and Ozeki (1968) were studied by the electron microscope heteroduplex method. The phi 80sus2psu3+ and phi 80dsu3+ DNA lengths were found to be 108.7 and 103.3% of the phi 80 DNA, respectively. The phi 80sus2psu3+/phi 80 heteroduplex shows an insertion loop of 8.7% of the phi 80 DNA which migrates from 7.7 to 9.7%, as measured relative to the left (0%) and right (100%) termini of the mature phi 80 DNA molecule. The region of loop migration occupies the central region of the phi 80 head gene cluster. The presence of su3+-containing Escherichia coli DNA of 6.7% phi 80 unit flanked by two homologous regions of phage DNA of 2.0% of phi 80 unit gives rise to a movable insertion loop. In phi 80dsu3+, from which phi 80sus2psu3+ was derived, 50.5% of the phi 80 DNA at the left arm was replaced by E. coli DNA containing the su3+ gene, equivalent to about 53.8% phi 80 unit in length. The phi 80sus2psu3+/phi 80dsu3+ heteroduplex appears as a double-stranded molecule that bifurcates into two clearly visible single-stranded regions, rejoins, bifurcates, and rejoins again. The middle double-stranded stretches of 6.7% phi 80 unit correspond to the E. coli DNA inserted in phi 80sus2psu3+. Therefore the transducing fragment carried by phi 80sus2psu3+ originates from the inside region of the transducing fragment of defective phage phi 80dsu3+ by at least two illegitimate recombination events.


Cleavage maps of the filamentous bacteriophages M13, fd, fl, and ZJ/2. The replicative form DNAs of bacteriophage M13, fd, f1, and ZJ/2 were found to be sensitive to cleavage by the restriction endonucleases endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII, endoR-AluI, endoR-Hha, and endoR-Hinf. With respect to M13 DNA the number of cleavage sites varied from 21 for endoR-Hinf, 18 for endoR-AluI, 15 for endoR-Hha, 13 for endoR-HapII, 10 for endoR-HaeIII, 3 for endoR-HaeII, to only a single site for endoR-HindII. In contrast to M13, fd and f1, the ZJ/2 DNA molecule was not cleaved by the endoR-HindII endonuclease. No cleavage site on either phage DNA was detected for the endonucleases endoR-Hsu, endoR-EcoRI and endoR-Sma. When compared with M13 DNA, several differences were noted in the number and size of cleavage products obtained with DNA of phage fd, f1, and ZJ/2. From the results of these analyses, using the M13 enzyme cleavage maps as a reference, the endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII and endoR-AluI maps of phage fd, f1, and ZJ/2 could be constructed. As is expected for very closely related phages, the enzyme cleavage patterns exhibit a high degree of homology. Phage f1 and ZJ/2 are most related since an identical pattern was obtained with seven different restriction endonucleases. Evidence is provided also that f1 is more similar to M13 than to fd. Furthermore, characteristic differences exist within the endoR-Hinf enzyme cleavage pattern of all the four phages tested. Digestion of phage DNA with this enzyme, therefore, provides a new and sensitive method of distinguishing these closely related filamentous coliphages .


Bacteriophage and bacteriophage-like structures carried by Bacillus medusa and their effect on sporulation. Bacillus medusa was found to carry three phages or phagelike structures named phi med-1, phi med-2, and phi med-3. phi med-1 is a minute, 25-nm-diameter particle without a tail. It was extracted from the sporulation lysate of a phi med-2-minus strain of B. medusa and purified by differential centrifugation. The nucleic acid from this structure was shown to be orcinol positive, alkali sensitive, RNase sensitive, and DNase resistant. An RNase-resistant core of nucleic acid was not found, indicating that it was single-stranded RNA. A host strain has not yet been found for phi med-1. Phage phi med-3 was induced with mitomycin C or UV light and consisted of empty heads of 57 nm in diameter, whereas phi med-2 induced with mitomycin was a phage of 60-nm head diameter and 220-nm tail length. The sporulation sequence proceeded faster in those mutants lacking phi med-2, and when the phage was reintroduced to B. medusa the extended wild-type sporulation sequence was observed. B. thuringiensis var. schwetzova was sensitive to phi med-2 and yielded small turbid plaques. B. medusa produced small numbers of phi med-2 during growth. The other phage may be produced at the same time but were not detected. Phi med-1 was found in sporulating cells by electron microscopy techniques. Its release from these was demonstrated by both electron microscopy techniques and a radioactive assay. It appears to participate in the formation of a surface layer on the parasporal inclusion of B. medusa.


Effect of 5-bromodeoxyuridine on vaccinia virus-induced polypeptide synthesis: selective inhibition of the synthesis of some post-replicative polypeptides. The effect of 5-bromodeoxyuridine (BrdU) on vaccinia virus-induced polypeptide synthesis in BSC-1 cells has been investigated. Most virus-induced pre- and post-replicative polypeptides were synthesized in concentrations of 5-bromodeoxyuridine that inhibited virus growth. The synthesis of a few post-replicative polypeptides, however, was severely inhibited under these conditions; included in this group was the precursor of a major core component, polypeptide P4b. A delay in the switch-off of pre-replicative polypeptide synthesis and in the onset of post-replicative polypeptide synthesis was also observed. The significance of these observations is discussed.


Infectious center assay for complementation and recombination between mutant of reovirus. An infectious center assay has been developed to measure recombination and complementation in L cells mixedly infected with ts mutants of reovirus. The mutants studied so far fall into complementation groups that correspond to the recombination groups previously defined by other laboratories (B. N. Fields, 1971; B. N. Filds and W. K. Joklik, 1969).


Isolation and preliminary characterization of temperature-sensitive mutants of Newcastle disease virus. Temperature-sensitive (ts) mutants of Newcastle disease virus have been isolated and characterized genetically (complementation), biochemically (RNA synthesis) and biologically (fusion from within and hemadsorption). Fifteen of these mutants have been divided into five complementation groups. Groups A (five mutants) and E (one mutant) are ts for RNA synthesis (RNA-) as well as for the other functions. Group B contains four RNA+ mutants of which one is ts for fusion, one for hemadsorption and two for neither function. Group C contains one RNA+ mutant which is a poor cell fuser. Group D contains two RNA+ mutants which are ts for fusion. In addition, two noncomplementing mutants (group BC) fail to complement both group B and group C mutants while exhibiting complementation with mutants in groups A, D, and E.


Absence of interparental recombination in multiplicity reconstitution from incomplete bacteriophage T4 genomes. Interparental recombination between injected T4 DNA molecules is indetectable for incomplete petite phages (carrying a terminally deficient genome and therefore unable to circularize) as well as for genetically complete phages. The nonvialbe petite phages can individually replicate their DNA repeatedly, and they aso undergo multiplicity reconstitution, producing complete phages, provided that a host bacterium is infected by several petite particles that carry genetically complementary segments of DNA. The formation of complete phages in multiplicity reconstitution must be due to recombination among incomplete progeny fragments, i.e., partial replicas of the T4 genomes. It evidently does not result from interparental recombination. To test for interparental recombination, light bacteria (containing no bromouracil) were simultaneously infected in light medium with light radioactive phage in minority (usually less than one per cell) and heavy (bromouracil-labeled) phage in majority (usually about nine per cell). Any interparental recombination should, under these circumstances of infection, head to movement of the radioactive label of the minority light phage DNA to a position of higher density. That possibility was not observed.


Identification of gene products required for in vitro formation of the internal peptides of bacteriophage T4. In vitro formation of both bacteriophage T4 internal peptides (II and VII) from preexisting precursor protein was shown to require the product of T4 gene 21. The proteolytic factor was detectable in extracts of cells infected with certain phage mutants blocked in early steps of head assembly but could not be demonstrated in extracts of T4 wild-type infected cells. This finding suggests that the proteolytic factor is inactivated during normal phage assembly. The product of T4 gene 22 appears to be the precursor of peptide VII but not of peptide II.


Replication of mycoplasmavirus MVL51. IV. Inhibition of viral synthesis by rifampin. The effect of rifampin on the replication of MVL51, a bullet-shaped mycoplasmavirus with single-stranded circular DNA of molecular weight 2 X 10(6), has been examined in a rifampin-resistant host cell. Rifampin does not block the early steps in MVL51 infection but does decrease the total amount of parental viral DNA taken up. The single-stranded parental viral DNA that enters the cell is found in membrane-associated, double-stranded DNA replicative forms I and II. Rifampin had no significant effect on the synthesis of progeny viral DNA RFI and RFII early in infection and SSI (single-stranded progeny viral chromosomes) later in infection. The rifampin block in virus synthesis was found to be in the step converting SSI into assembled virions. Rifampin was shown to affect the synthesis of virus-specific RNA, Which suggests that viral transcription is necessary for virion assembly.


Analysis of radiohippuran renogram by subtraction of extrarenal radioactivity. A method is presented for the simple, non-computerized analysis of the radiohippuran renogram by subtraction of the extrarenal radioactivity as monitored simultaneously by a detector centered over the manubrium sterni. This method requires the application of a calibration factor, relating the level of radioactivity recorded by the sternal detector to that over each kidney area at the end point of the phase of initial rise on each side separately. The results in 15 normal individuals showed a narrow range of values, indicating a high degree of resolution. Verification of the basis of this method of analysis was obtained by accounting for all of the counting rate as extrarenal sources in the tracings of nephrectomized subjects. A further advantage is that the tracing recorded by the sternal detector may be used to calculate renal blood flow.


Renal papillary necrosis in sickle cell hemoglobinopathies. Approximately 65 per cent of patients with clinical manifestations of S-hemoglobinopathies show urographically demonstrable changes of renal papillary necrosis, regardless of the presence of urinary symptoms. With a more precise excretory urographic technique these changes can be diagnosed with greater accuracy without the need for sophisticated equipment. Excretory urography should be performed routinely in the evaluation of all patients with manifestations of S-hemoglobinopathy in order to diagnose papillary necrosis before the onset of urological symptoms.


Extensive nephrolithotomy in previously operated solitary kidneys. The surgical management of 2 patients with large dendritic calculi in previously operated solitary kidneys is presented. Complete nephrolithotomy was accomplished in situ using the anatropic nephrotomy technique of Smith and Boyce. Postoperatively a circle tube nephrostomy was used. The surgical management as described is recommended as an alternative to extracorporeal nephrolithotomy with autotransplantation or simple nephrectomy and dialysis.


The case for a more aggressive approach to staghorn stones. The treat to the patient and kidney of leaving a large staghorn stone in situ in 60 cases is compared to the risk of operative removal in 125 cases. The over-all mortality rate in patients treated conservatively was 28 per cent, carcinoma developing in 4 cases and a life-threatening pyonephrosis in 16. Of patients treated by removal of the stone the mortality rate was 7.2 per cent (during 10 years of observation) and stones recurred in 21 cases. These studies refute the notion of the silent staghorn calculus and demonstrate that operative removal is safer for the patient and kidney.


Urinary tuberculosis: a review of 44 cases treated since 1963. We are reporting on a decade of experinece with cases of renal tuberculosis treated at a large tuberculosis hospital. Most patients were men less than 50 years old. The most frequent symptoms were dysuria, back or flank pain, nocturia and hematuria. Physical examinations were generally normal and hypertension was not seen. Most patients had acid urinary pH, pyuria and/or hematuria. Excretory urograms were abnormal in 86 per cent of the cases, the most common finding being preserved function but calicectasis or abscess. Most patients had abnormal chest x-rays and nearly half of them had coexisting, active pulmonary or miliary tuberculosis. Tuberculin tests were positive in 85 per cent of the cases. In our experience urinary tuberculosis was almost always responsive to multi-drug chemotherapy, even in patients with a non-functioning, tuberculous kidney. An asymptomatic, non-functioning kidney need not be removed, provided documentation of urine culture conversion is obtained and a prolonged period of multi-drug chemotherapy is completed.


Clinical comparison between vascular and avascular renal cell carcinoma. Of 72 patients with renal cell carcinoma 19 were found to have an angiographic avascular neoplasm. These avascular tumors have a lower incidence of vein and capsule invasion than vascular tumors. Among these avascular cancers papillary adenocarcinoma was the predominant histologic pattern. Patients with papillary tumors seem to have a lower clinical stage and increased survival rate than patients with non-papillary tumors.


Retroperitoneal teratoma: historical review. A case of retroperitoneal teratoma in an unusual location is presented. The tumor occurred in the right iliac fossa of a 17-year-old girl and proved fatal within 18 months, despite a seemingly adequate initial operation. The literature on the subject has been reviewed from an historical perspective.


Retroperitoneal fat necrosis producing ureteral obstruction. We present 3 cases of a rare syndrome of extrinsic ureteral obstruction produced by retroperitoneal fat necrosis and compare the medical records and histopathology to 19 cases of classic idiopathic retroperitoneal fibrosis. Clinical similarities include average age of onset in the fourth and fifth decades, male preponderance, abdominal or back pain as the presenting symptom, elevation of the blood urea concentration prior to diagnosis and tendency toward bilateral involvement. Histologically, the 2 conditions were different. Retroperitoneal fat necrosis is characterized by coalescence of fat cells into fat cysts bordered by foreign body giant cell granulomas, foam cells, light chronic inflammatory infiltrate and unimpressive fibrosis. The microscopic pathology of idiopathic retroperitoneal fibrosis is dominated by densely collagenized fibrous tissue of varying cellularity without evidence of fat necrosis. Of the 3 cases of retroperitoneal fat necrosis 2 featured prior ischiorectal abscesses and this is considered in a discussion of the etiology of this unusual cause of ureteral compression.


Condyloma acuminatum of the bladder.

Condyloma acuminatum of the bladder. Condyloma acuminatum in the bladder of 2 patients on immunosuppressive therapy after kidney transplantation is described. The successful treatment was transurethral electroresection and coagulation. We do not recommend radical operations in cases of condyloma acuminatum. Resected specimens should be examined pathologically to exclude papillary epithelial tumors.


Abnormal monocyte function in bladder cancer patients. We evaluated 39 patients with various stages of bladder carcinoma to determine alterations in monocyte function. Since the monocyte plays an important role in the effector arm of the immune system defective function may explain the host's inability to destroy neoplastic cells. As a group these 39 patients demonstrated defective monocyte monocyte function. There was no correlation between tumor stage and degree of chemotactic defect. Patients with invasive carcinoma had a significant return of monocyte chemotactic response toward normal postoperatively (p less than 0.005). Monocyte function was improved also in 3 patients who received Bacillus Calmette-Guerin immunotherapy (p less than 0.05).


Squamous cell carcinoma of the bladder.

Squamous cell carcinoma of the bladder. Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial.


Sympathetic activity in the proximal urethra in patients with urinary obstruction. The effect of 10 mg. phentolamine intravenously on the urethral pressure profile was studied in male and female patients with lower urinary tract obstruction. A significant decrease of pressure occurred along the whole length of the urethra in both sexes, including the peak pressure zone in the male patient. This zone has been traditionally attributed to the external sphincter. It was concluded that the sympathetically innervated smooth muscle exerts a certain activity along the whole length of the proximal urethra. The phentolamine test may prove to be a useful adjunct to urethral profile studies in patients with lower urinary tract obstruction.


Excision of the urogenital diaphragm: a method of repair of the completely obstructed membranous urethra. A 15-year experience with 16 patients who suffered complete rupture of the membranous urethra and obliteration of the apex of the dislocated prostate gland is described. In 2 cases repair was done immediately after injury. The technique is described. Entrance into the perineum follows the path of the bulbous urethra rather than that of the rectal wall. After the bulbous urethra is mobilized the urogenital diaphragm is excised. The end of the bulbous urethra is approximated to the mobilized distal half of the prostate, via the shortest route between the 2 organs.


Vesical neck suspension under vision with cystotomy enhances treatment of female incontinence. Failure to surgically correct incontinence usually results from inadequate screening of patients with hyperreflexic incontinence, improper fixation of the urethra or yielding of tissues that have supported the repair. A surgical approach is described which fixes the bladder neck to the rectus tendon and adjacent pubic periosteum, under direct vision, through a cystotomy incision. The procedure achieves good continence in more than 90 per cent of the cases. Temporary postoperative voiding dysfunction occurred in about half of the patients.


Stress incontinence: conservative therapy with sympathomimetic drugs. There were 77 women with mild to moderate stress urinary incontinence treated with the sympathomimetic agent, phenylpropanolamine hydrochloride, combined with chlorpheniramine maleate and isopropamide iodide in a sustained release capsule (Ornade). The majority of these patients achieved significant improvement 3 months to 3 years after beginning therapy. A trial of conservative therapy is advisable for stress incontinence, especially when symptoms are mild or when the patients are in a poor risk category. Similar management of post-prostatectomy stress incontinence in men was disappointing. However, the occasional excellent results in patients with mild symptoms appear to justify a trial of conservative therapy before considering operative intervention in this group of patients.


Hemihypertrophy of the human corpus cavernosum. Hemihypertrophy of the right corpus cavernosum and its accompanying thickened tunica albuginea are responsible for the left lateral deviation in congenital curvature of the penis. Surgical correction is more predictable when the lengths of the dorsal and ventral curvatures of the corpora cavernosa are known.


Varicocle in oligospermic patients: pathophysiology and results after ligation and division of the internal spermatic vein. We have followed for up to 32 months 51 oligospermic patients with varicoceles who underwent high ligation and division of the left spermatic vein. Of these patients 59.9 per cent had improvement in total sperm count, 47.1 per cent in sperm motility and 42.1 per cent in the morphological pattern of the spermatozoa. Pregnancies were reported by 13 patients. Improvement in sperm motility occurred first, followed by improvement in morphology. The last improvement was in total sperm count. We suggest that the observation period after a varicocele operation be restricted to 9 months, in which time about 75 per cent of the expected improvement takes place. A clinical classification for the degree of varicocele is proposed. No correlation between size of the varicocele and treatment results could be observed. A classification of sperm analysis is proposed, using a 3-digital index that might enable better comparison of sperm analysis and better communication among physicians. We could not define a specific group of oligospermic patients who might benefit more than other groups from a varicocele operation. Pathophysiological pathways leading to impaired spermatogenesis in patients with varicoceles are discussed.


Dyssynergic vesicourethral responses during bladder rehabilitation in spinal cord injury patients: effects of suprapubic percussion, credé method and bethanechol chloride. Five normal men and 70 spinal cord injury male patients underwent 100 studies with the multiple pressure recording technique, incorporating the continuous infusion principle for sphincter pressure monitoring. Gross cystosphincteric dyssynergia was noted in the majority of patients with complete upper motor neuron bladders less than 2 years in duration. Some form of synergic voiding patterns was noted, mostly in patients with incomplete upper motor neuron bladders. The external sphincter tends to be synergic in late cases of upper moto neuron bladders. Internal sphincter dyssynergia is uncommon in cases of injuries less than 2 years in duration, with the exception of patients who have autonomic dysreflexia. Bladder neck obstruction seems to be more common in late lesions secondary to global hypertrophy of the bladder. Rehabilitation maneuvers and bethanechol chloride administration may exaggerate detrusor sphincter dyssynergia and injudicious use of such procedures could be detrimental to the urinary tract.


Segmental renal vein renin assay and segmental nephrectomy for correction of renal hypertension. Selective segmental renal vein catheterization was used to obtain venous blood samples for renin assay. With this technique a localized source of hypersecretion of renin was identified in 2 patients. Using samples from the main renal veins we found no significant difference in renin activity and, therefore, the etiology of the hypertension in these 2 patients would have been missed. Segmental nephrectomy resulted in a cure of the hypertension in both patients who were followed for a minimum of 14 months.


Ureterocalicostomy: an alternative to nephrectomy. Ureterocalicostomy is a procedure with limited indications but with important application in the infrequent patient in whom the more desirable methods of creating unobstructed ureteropelvic drainage cannot be used. Three children are described in whom successful ureterocalicostomy was performed. The most common condition in which ureterocalicostomy has been useful is in the obstructed and scarred, intrarenal pelvis in which a classic type of ureteropyelostomy is not possible. The most important technicalconsideration seems to be sufficient amputation of the lower pole renal cortex in order to free the ureterocaliceal anastomosis from the surrounding cortical tissue. The 3 cases illustrate the difficult situations in which ureterocalicostomy may be indicated and the value of this procedure in preserving maximal renal function in children.


Management of severe hydroureteronephrosis in infants and young children. Loop cutaneous ureterostomy and cutaneous pyelostomy are safe and effective means of temporary diversion with few complications. Reconstructive operation is delayed until the upper urinary tract has shown maximum improvement in form and function and the patient's tolerance for elective operation has improved. Results of reconstruction may be less than optimal and serious complications may arise. However the staged approach has been shown to be safe and effective. Experience with 29 patients has led to a reassessment of the approach to patients with posterior urethral values and a stronger inclination to primary valve resection, thus avoiding many of the reconstructive procedures ultimately associated with temporary diversion. Patients with posterior urethral valves who have hydronephrotic upper urinary tracts, normal or near normal serum chemistry studies and are free of infection may receive initial valve ablation. All patients with massive hydroureteronephrosis require long-term followup to ensure preservation of renal function regardless of the approach used.


Ileal conduits in children at the Massachusetts General Hospital from 1955 to 1970. The 45 ileal conduits performed on children at the Massachusetts General Hospital from 1955 to 1963 are reviewed and compared to the 45 ileal conduits performed from 1964 to 1970. Late complications involving the conduits occurred in 60 per cent of the early group and in 51 per cent of the late group. Of the renal units judged normal pyelographically preoperatively in the early group 77 per cent went on to at least some deterioration, while 62 per cent of the late group judged normal later deteriorated. Combining all renal units, 34 per cent remained unchanged, 26 per cent improved and 41 per cent showed some degree of deterioration after ileal conduit urinary diversion. The late complication and renal deterioration rates seem to increase progressively with time. There was no apparent urinary obstruction in 13 per cent of the renal units that deteriorated. Theoretical and experimental considerations indicate the reflux of infected urine as the etiology of the renal deterioration. Because of the late complications and the unacceptably high rate of renal deterioration we no longer perform ileal conduits in children. Instead every effort is made to reconstruct the urinary tract or if urinary diversion is necessary, a colon conduit with non-refluxing ureterocolonic anastomoses is performed.


Meconium granulomas of the tunica vaginalis. Meconium peritonitis results from perforation of the gastrointestinal tract during fetal life. Involvement of the tunica vaginalis may be the sole presenting clinical manifestation of the disease in the unusual event of the gut perforation resolving spontaneously. In such instances radiologically detectable calcification in the abdomen and scrotum is an essential diagnostic point. A case is described in which a baby had hydroceles and bilateral intrascrotal nodules but in which calcification was radiologically undetectable, presumably owing to its having undergon resolution. The typical histology of the nodules provided the diagnosis in this otherwise clinically undiagnostic case.


Long-term assessment of genital reconstruction in female pseudohermaphrodites. The cases involving 32 women who had undergone early revision of ambiguous genitalia were reviewed 5 to 22 years postoperatively. Seven clitoridectomies, 25 clitoral recessions, 17 Y-V introitoplasties and 10 midline episiotomies were performed. There were 16 patients available for followup. The results of clitoral recessions were cosmetically and functionally satisfactory. Introital revisions done before puberty all required further revision and suggested that vaginoplasty should be deferred until after puberty.


Atypical unilateral acute pyelonephritis initially diagnosed by scinti-studies. A patient with vague and atypical symptoms is described in whom the radionuclide dynamic and static imaging studies proved to be more useful than a preceding excretory urogram for the diagnosis of unilateral pyelonephritis.


Emphysematous pyelonephritis.

Emphysematous pyelonephritis. Emphysematous pyelonephritis is a rare complication of urinary tract infection and generally occurs in patients with diabetes mellitus or urinary tract obstruction. We recently treated an 81-year-old diabetic woman with Klebsiella pneumoniae urinary tract infection and septicemia whose abdominal roentgenogram demonstrated a striking left pneumonephrogram as well as intraureteral and perirenal gas. The patient died despite intensive therapeutic efforts. Unfortunately, the prognosis for this severe necrotizing infection process remains unfavorable.


A problem in hemodialysis management: fibromuscular dysplasia of radial and ulnar arteries--report of a case. Fibromuscular dysplasia (medial type) of the radial and ulna arteries, hitherto unreported, has been demonstrated angiographically following the malfunction of an arteriovenous shunt created for dialysis. Retrograde dilatation of the segmental stenoses caused some improvement in flow. No causal relationship is claimed between fibromuscular dysplasia and the arteriovenous shunt.


Correlation of selective angiography and pathology in cavernous hemangioma of the kidney. Angiographic and pathologic findings are presented and correlated in a case of renal cavernous hemangioma, and considered in relation to 3 other cases published previously. A normal angiogram does not exclude a cavernous hemangioma. Those tumors with a large arterial component may be demonstrated in the arterial phase of the angiogram. A discrete tumor may show an area of hypovascularity by displacing normal renal tissue but a diffuse cavernous hemangioma is likely to yield a normal angiogram.