Dorsal horn cells that respond to stimulation of distant dorsal roots.

Experiments were carried out to find if there were post-synaptic effects produced by impulses in the long ranging primary afferents, which had been shown by Wall & Werman (1976) to extend from upper lumbar dorsal roots to the sacral segments. Dorsal rootlets were stimulated in decerebrate low-spinal adult cats.1. The dorsal root potential and ventral root reflex were recorded on S1 root filaments, in response to stimulation of dorsal rootlets extending from L1 to S1. With increasing distance between stimulating and recording segments, these potentials became smaller and more delayed. In two animals, there was no response at S1 to stimulation of L1 and L2 dorsal roots.2. In all animals, stimulation of L3 or L4 dorsal roots produced cell responses in dorsal horn segments L7 or S1. The density of such cells was variable, from animal to animal. Responding cells were mainly concentrated laterally in the dorsal horn.3. The latency and response variability of L7-S1, dorsal horn cells to L3-L4 stimulation was consistent with at least some of them being fired monosynaptically.4. Cells that respond to stimulation of one distant rootlet respond to many closer rootlets as well.5. The receptive fields of L7-S1 dorsal horn cells, responsive to stimulation of L3-L4 rootlets, were typical of those generally found in the L7-S1 segments, and were at some distance from the L4 dermatome. Only twenty cells had receptive fields which extended into the dermatome of the rootlets stimulated.6. It was established that some L4 cells respond to S1 dorsal root stimulation, just as the main study had shown that S1 responds to L4.7. It is concluded that substantial numbers of dorsal horn cells, including cells with many types of cutaneous receptive field, respond to two classes of synaptic in-put: one effective in firing the cell upon natural cutaneous stimulation, and one relatively ineffective, capable of driving the cell only when stimulated electrically and thus carrying a synchronous volley from a number of highly convergent axons. The contribution of this secondary afferent channel to normal and pathological cord physiology has now to be determined.


Collecting duct dlow rate as a determinant of equilibration between urine and renal papilla in the rat in the presence of a maximal antidiuretic hormone concentration.

1. Antidiuretic hormone (ADH) was infused into normal male rats at a rate of 60 muu./min. 100 g body wt., to maintain an effectively constant maximal circulating level. Four groups of rats were used; they were water-loaded by receiving together with the ADH, I.V. infusions of hypotonic dextrose (2.5 g/100 ml.) at different rates (1.0, 4.5, 9.0 and 12 ml./hr, respectively), over an infusion period of 4 hr.2. Urine flow rate increased in all groups, the rate and extent of the increase being related to the volume rate of infusion. The differences in urine flow rates between the four groups were due almost entirely to increases in free water clearance, with no consistent differences in osmolal clearance between the groups. At the end of the 4 hr infusion period, osmolal clearances were closely similar in the four groups.3. Papillary and medullary tissue solute concentrations were progressively reduced at the higher rates of infusion. The changes were due to small increases in the water content, together with a profound decrease in urea concentration and a smaller decrease in sodium concentration. However, papillary osmolality was consistently higher than urine osmolality at the three highest rates of dextrose infusion.4. As urine flow rate increased, there was a progressive reduction in the degree of osmotic equilibration between the final urine and the papillary tip. For urea, however, the degree of equilibration remained high.5. It is concluded that, in the rat, the rate of flow per se, along the collecting duct, is an important determinant of final urine concentration; even if there is an osmotic driving force for water re-absorption in the renal medulla, and the collecting duct walls are permeable to water, osmotic equilibration is restricted by tubular flow rate.


Separation of sodium and calcium currents in the somatic membrane of mollusc neurones.

1. Characteristics of the transmembrane ionic currents under controlled changes in ionic composition of extra- and intracellular medium were studied in isolated neurones from the ganglia of molluscs, Helix pomatia, Limnea stagnalis and Planorbis corneus. The neurones were investigated by a new technique which allows for dialysis of their interior and for clamping of the potential at the surface membrane without using micro-electrodes.2. Replacement of K ions by Tris inside the neurones eliminated the outward K current so that the actual time course of the inward current could be measured. The latter was separated into two additive components, one of which was carried by Na ions and the other one by Ca ions.3. Both inward currents were unaltered by tetrodotoxin (TTX); however, Ca current could be separately blocked by externally applied Cd ions (K(d) = 7.2 x 10(-5)M) and by the use of fluoride as an intracellular anion.4. No reversal of Na inward current could be achieved in neurones dialysed with Na-free solution, indicating the absence of outward current carrying ions through the corresponding channels. With 5 mM-Na inside the cell, the equilibrium potential was close to the value predicted by the Nernst equilibrium.5. A non-specific outward current could be detected in K-free cells at membrane potentials exceeding 20-40 mV. Its time course was proportional to 1 - exp (-t/tau(ns)). Cd ions depressed this current. The presence of the non-specific outward current made an exact measurement of the equilibrium potential for the Ca inward current impossible.6. The kinetics of Na inward currents could be described by m(3)h and those of the Ca current by m(2)h law. The corresponding values for V(m) = 0 are: tau(m)(Na) = 1.1 +/- 0.5 msec, tau(m)(Ca) = 2.4 +/- 1.0 msec, tau(h)(Na) = 7.9 +/- 2.0 msec. The inactivation of Ca current included two first-order kinetic processes with tau(h1) = 50 +/- 10 msec and tau(h) = 320 +/- 30 msec.7. The data presented are considered to be a proof of the existence of separate systems of Na and Ca ion-conducting channels in the nerve cell membrane.


Responses of visual, somatosensory, and auditory neurones in the golden hamster's superior colliculus.

1. The response characteristics of visual, somatosensory, and auditory neurones in the golden hamster's superior colliculus were investigated.2. As has been noted for other mammalian species, a distinct difference between the functional organizations of the superficial and deeper layers of the superior colliculus was observed.3. Neurones in the superficial layers were exclusively visual, with small receptive-fields, and generally did not show response decrements with repeated stimulation. The sizes of the receptive-fields did not vary appreciably as a function of retinal eccentricity.4. In the deeper layers, visual receptive-fields were large, or could not be accurately delimited, and response habituation was often evident. In addition, many cells in the deeper layers of the colliculus responded only to somatosensory stimuli. Far fewer cells, which appeared to be confined to the caudal portions of the colliculus, responded to auditory stimuli. Polymodal cells were also encountered.5. Selectivity to opposing directions of movement was tested for ninety-four visual cells. Using a ;null' criterion, 27.7% of these cells were judged to be directionally selective. A distribution of the preferred directions of these cells showed a significant preference for movement with an upper-nasal component. With a statistical criterion, 60.6% of these cells were considered to show a significant asymmetry in responding to movement in opposing directions.6. Directional selectivity was also tested for ninety-two cells following acute, unilateral, lesions of the visual cortex. For the eighty cells recorded, homolateral to the ablated cortex, 27.5% were judged as directionally selective using the statistical criterion, while 12.5% were selective with the ;null' criterion. Of the twelve cells isolated in the colliculus, contralateral to the lesions, seven were judged as directionally selective with the statistical, and three with the ;null' criterion.7. The effects of visual cortical lesions upon directional selectivity appeared to be confined to cells in the superficial layers of the colliculus. It was suggested that directional selectivity of many cells in the superficial layers of the tectum of the hamster is organized cortically.8. A clear spatial correspondence was observed for the receptive-fields of visual, somatosensory, and auditory neurones.9. As has been suggested for other species, the hamster's superior colliculus appears to play an important role in orienting the animal toward visual, somatosensory, and auditory stimuli.


The effect of lung inflation on the control of respiratory frequency in the neonate.

1. We have measured the relationship between tidal volume (V(T)) and the duration of inspiration (T(i)) and expiration (T(e)) for individual breaths (30 in each steady state).2. Ten pre-term and ten term infants were studied during steady state while breathing 21% O(2), then 21% O(2) plus 2 and 4% CO(2).3. In all infants, the average T(i) at the various chemical drives was remarkably constant, and did not decrease as the tidal volume increased. However, at any given level of respiratory drive, there was a slightly positive correlation of V(T) with T(i) and T(e) in 95% of the cases.4. In four pre-term and two term infants, T(e) increased with increasing respiratory drive. In these infants, therefore, instantaneous respiratory frequency (1/(T(i) + T(e))) actually decreased as lung volume increased.5. We suggest that T(i) is independent of V(T) within the range of volumes studied (up to 2 times the resting V(T)) and that changes in instantaneous respiratory frequency (1/(T(i) + T(e))) result from changes in T(e).


Training induced adaptation of skeletal muscle and metabolism during submaximal exercise.

1. Six subjects were trained using a one-leg bicycle exercise for 2 months. The untrained leg served as control. After the training period, muscle oxidative capacity, determined as succinate dehydrogenase activity, was 27% higher in the trained (as opposed to the control) leg (P < 0.05).2. When the subjects in this situation performed a 1 h two-legged submaximal bicycle exercise bout (150-225 W), determinations of V(O2) of the single leg (leg blood flow x (A-V)(O2) difference) revealed that they appeared to choose to work harder with their trained than with their untrained leg, so as to make the relative loads for the two legs the same.3. Determinations of O(2) and CO(2) on femoral arterial and venous blood demonstrated that the R.Q. was lower in the trained as compared to the untrained leg, 0.91 cf. 0.96 (10 min) and 0.91 cf. 0.94 (50 min) (P < 0.05).4. That metabolism of fat was more pronounced in the trained leg was further supported by the finding of a significant net uptake of free fatty acids in this leg only. Moreover, a lower release of lactate from the trained leg was demonstrated.5. It is suggested that the shift towards a more pronounced metabolism of fat in the trained leg is a function of an increased muscle oxidative capacity.


The morphology of spinocervical tract neurones revealed by intracellular injection of horseradish peroxidase.

1. The morphology of physiologically identified spinocervical tract neurones was studied using the intracellular injection of horseradish peroxidase in anaesthetized cats.2. Thirty-six spinocervical tract neurones were reconstructed from serial sections of the lumbosacral spinal cord, cut in either the transverse or longitudinal planes.3. Horseradish peroxidase provided a more complete picture of the dendrites of spinocervical tract neurones than earlier experiments using Procion Yellow injection (Brown, House, Rose & Snow, 1976a). The longitudinal (rostro-caudal) spread of dendrites from an individual cell was much greater in the present material; neurones in the medial parts of the dorsal horn had dendrites extending for about 500 mum from the soma (1 mm total spread) and neurones in the lateral horn had dendrites extending for about 1 mm from the soma (2 mm total spread). However, the conclusions of the earlier work, on the medio-lateral and dorso-ventral extents of dendritic trees, together with the shapes of dendritic trees viewed as reconstructions in the transverse plane, have been confirmed. Dendrites of spinocervical tract cells barely entered lamina II of Rexed: they often ran in the longitudinal direction along the border between laminae II and III for several hundred mum. Dendritic spines were observed on many spinocervical tract neurones.4. Horseradish peroxidase reaction product stained up to 2.5 cm of the axon of spinocervical tract neurones. Axons usually pursued a tortuous path through the grey matter close to the cell body, giving off up to six collaterals before entering the ipsilateral dorsolateral funiculus. In the funiculus, further collaterals often arose at distances of up to 5.5 mm from the soma; these collaterals ran back into the dorsal horn. Collaterals could be traced sometimes to presumed terminal boutons. The majority of collateral terminal arborizations was between the level of the cell body and 500 mum ventral to it (in laminae IV and V). They were, however, in the same medio-lateral and rostro-caudal region as the dendritic tree of the parent cell.5. It is concluded that the spinocervical tract must now be considered as having a segmental function, in addition to its function of forwarding information towards the cerebral cortex.


Monomethylthio analogues of 1-(2,4,5-trimethoxyphenyl)-2-aminopropane.

Regiospecific syntheses of the three monomethylthio analogues of 1-(2,4,5-trimethoxyphenyl)-2-aminopropane are described. The three isomeric amines were evaluated for potential psychotomimetic potency using the rabbit hyperthermia assay. Enantiomeric compositions and time-concentration curves in rat brains were determined following intraperitoneal administration of each compound. The biological data are contrasted with the corresponding results obtained with the potent human psychotogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM).


Synthesis and evaluation of alpha-hydroxythiol esters as antitumor agents and glyoxalase I inhibitors.

Synthesis of a series of alpha-hydroxythiol esters made available, for the first time, product-like molecules that were evaluated as inhibitors of the enzyme glyoxalase I and as potential antitumor agents. All the alpha-hydroxythiol esters tested were competitive inhibitors of the enzyme, albeit weak; however, the relative [I]50 values suggested information about the active site. Antileukemic activity in L1210 lymphoid leukemia indicated no significant activity by these alpha-hydroxythiol esters.


Potential antitumor agents. 25. Azalogues of the 4'-(9-acridinylamino) methanesulfonanilides.

Tumor inhibition inhibition produced by isomeric, nitro-substituted 4'-(9-acridinylamino)methanesulfonanilide analogues of low base strength (pKa=4.79-5.72) might result from in vivo reduction to the corresponding, higher pKa (7.15-9.80), tumor active amines. The aza analogues,-N=in place of -C(NO2)=, have been prepared as nonclassical bioisosteres and screened in the L1210 system. Significant L1210 inhibition produced by isomeric 3- and 4-azalogues, of similar base strength to the corresponding nitro-substituted derivatives, demonstrates that weakly basic analogues can provide biologic activity when there is no prospect of in vivo reduction to more strongly basic products. Obligatory reduction of nitro function, for biologic activity, need not be postulated in this drug series.


Synthesis of nitrosourea derivatives of sucrose as central nervous system anticancer agents.

Nitrosourea derivatives of sucrose have been synthesized for the purpose of obtaining anticancer agents with activity against brain cancer. Two such compounds, 6,6'-dideoxy-6,6'-di(3-methyl-3-nitrosoureido) sucrose (13) and 1', 6,6'-trideoxy-1',6,6-tri(3-methyl-3-nitrosoureido) sucrose (14), and their respective acetylated derivatives 15 and 16 have been prepared from sucrose. Compounds 13 and 14 have demonstrated antitumor activity against both L1210 leukemia and ependymoblastoma brain tumor in mice.


Synthesis and antimineralocorticoid activities of some 6-substituted 7 alpha-carboalkoxy steroidal spirolactones.

Several analogues of the previously reported steroidal spirolactone 1a were synthesized. These analogues bear C-6 substituents and include the 6beta-deuterio (1c), the 6beta-bromo (1d), the 6beta-methyl (1e), and the 6alpha-methyl (7) compounds. The 6beta-hydroxy compound 1b, a human and animal metabolite of 1a, was also synthesized. On subcutaneous administration to adrenalectomized rats, all these compounds exhibited the ability to block the effects of administered deoxycorticosterone acetate (DCA) (MED less than or equal to 0.58 mg). Only 7 failed to show anti-DCA effects at the standard test level on oral administration. None was significantly superior in potency to the parent compound 1a.


Compounds with gastric antisecretory activity. 1. Phenoxyalkylamines.

A series of 0-alkylphenoxyalkylamines, derived from classical H1 antagonists, has been found to inhibit histamine-induced gastric acid secretion. The most potent compound was trans-1-[2[2-[2-(1-adamantyl)vinyl] phenoxy] ethyl]pyrrolidine (54). The 0-acylphenol 23 required for the preparation of 54 was obtained by the novel reaction of 1-bromoadamantane (21) with 4-hydroxycoumarin (20) using diethyl phosphonate as solvent. The product 22 was then hydrolyzed under basic conditions to give 23 in high yield. 54 was not an H2 antagonist and its mode of action remains unknown. The compound had no significant anticholinergic, antiinflammatory, anticonvulsant, sedative, or H1-antihistaminic activity.


Antifilarial agents. 1,2-Cyclobutanediamines as analogues of diethylcarbamazine. Status of structure-activity relationships among diethylcarbamazine analogues.

cis-and trans-1,2-cyclobutanediamines bearing appropriate N-methyl and N-acyl substituents were prepared as analogues of diethylcarbamazine (DEC). None displayed activity against Litomosoides carinii in the gerbil despite substantial structural and sterochemical similarities to the parent drug. The inactivity of these drugs is rationalized in terms of eclipsed pharmacophore configurations and the increased population of unfavorable rotational conformations made possible by the exocyclic position of both pharmacophores. To provide perspective for these conclusions, the literature on DEC analogues is briefly summarized and structure-activity data are discussed in terms of critical structural factors associated with microfilaricidal activity. Generalizations on structural principles governing activity are advanced which encompass test results for the large majority of DEC analogues.


Antifilarial agents. 3-Aminopyrrolidine and 1,4-diazabicyclo[3.2.1]octane derivatives as analogues of diethylcarbamazine.

3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like antifilarial activity does not require that both pharmacophores be incorporated into one ring. Results with the 1,4-diazabicyclo[3.2.1]octanes establish that an axial conformation of the alkyl substituent corresponding to the equatorial N-methyl group of diethylcarbamazine is fully consistent with high activity. Other conformational consideration pertinent to DEC analogues are discussed.


Quinoline derivatives as antiallergy agents. 2. Fused-ring quinaldic acids.

A series of compounds containing two or more 4-oxo-1,4-dihydropyridine-2-carboxylic acid units fused to a central aromatic nucleus was synthesized and tested in the rat passive cutaneous anaphylaxis (PCA) assay for potential antiallergy activity. Most of the compounds of this series showed significant activity in the PCA assay. Three of these compounds. 11d, 13f, and 21, were more than 250 times as active as the standard drug, cromolyn sodium. The synthesis and biological activity are discussed.


Nonsteroidal antiinflammatory agents. 2. Synthesis and biological activity of 2-chloroindolecarboxylic acids.

The Vilsmeier and the Arndt-Eistert reactions have been employed for the synthesis of 1-phenyl-2-chloroindole-3-acetic acid (4). The antiinflammatory activity of 2-chloroindole-3-carboxylic acid (1), 1- methyl-2-chloroindole-3-carboxylic acid (2), 1-phenyl-2-chloroindole-3-carboxylic acid (3), and 4 was compared with the activity of indomethacin in the carrageenin rat edema. The best results are given by compounds 1 and 2 bearing H or CH3 at position 1 and COOH at position 3.


Lysergic acid diethylamide. Photoelectron ionization potentials as indices of behavioral activity.

The photoelectron spectrum of lysergic acid diethylamide (LSD) reveals five ionization potentials (IP's) between 7.25 and 9.75 eV arising from the aromatic (pi) portion of the molecule and IP's of 8.4 eV arising from the tertiary amine and 8.5-9.0 and 9.1 eV arising from the amide group. Comparisons of the IP's of LSD, and of phenethylamines and tryptamines reported by us elsewhere, with activities of these compounds in rat and human behavioral tests show that increasing activity is paralleled by decreasing IP.


Physician conduct and other factors that affect consumer satisfaction with medical care.

Major dimensions of consumer perceptions regarding physicians and medical care services were identified using factor analysis of survey data, as follows: accessibility, availability of family doctors, availability of hospitals/specialists, completeness of facilities, continuity of care, and physician conduct (art and technical aspects of quality). Scores for these dimensions and multivariate statistical methods were used to predict general satisfaction ratings for a cross section of adults and for groups differing in age, education, health status, and sex. Physician conduct was clearly the most important factor in relation to general satisfaction with care for the total sample and for all groups studied. Other factors also were important, suggesting that more than one interpretation of general satisfaction scores should be considered when consumer satisfaction surveys are used to support the planning of educational programs in medicine and the delivery of services.


Comparisons of medical student experiences in rural and university settings.

This paper is a report of the results of the Patient Encounter Project, which was designed to document all clinical experiences of medical students (N = 36) for seven months in the Rural Physician Associate Program (RPAP) and to compare these experiences with those of a control group of third-year students (N = 26) enrolled in the regular curriculum during the same time period at the University of Minnesota Medical School, Minneapolis. The purpose of RPAP is to provide education and clinical experience in rural health care for a limited number of third-year medical students for nine to 12 months and to encourage the eventual practice of medicine in a rural setting. Subjects completed one standardized form for every clinical encounter with a patient throughout the seven months' data collection period. Statistical differences between the two groups were found on all variables but one, including the numbers and kinds of clinical problems encountered, the skills reported, levels of responsibility, continuity of patient care, and types of patients.


Venomous animals and their victims: a program for sophomore medical students.

As Americans increase their outdoor activities, the possibility of contact with venomous animals becomes greater. At the University of Arkansas for Medical Sciences a program has been developed for sophomore medical students to help meet this potential health threat. Lectures are given on the recognition and general biology of dangerous reptiles and anthropods, the nature of animal venoms, immunological aspects of envenomation, and the treatment of bites and stings. Both first-aid and clinical management are included. Laboratory demonstrations consist of both live and preserved specimens of venomous animals. Live specimens of reptiles, as well as informed curators, are provided by the Little Rock Zoological Gardens in what may be a unique cooperative effort between a medical school and a zoo. The program has been judged to be a success on the basis of the response of the medical students.


Evaluation of the Arizona Medical Student Exchange Program.

In this article the authors describe and present an evaluation of the Arizona Medical Student Exchange Program of the Western Interstate Commission for Higher Education. The program is designed to help defray the cost that an Arizona student faces in attending an out-of-state medical school by paying, in the student's behalf, the difference between the resident and nonresident tuition at the out-of-state school. Furthermore, the accepting medical school is paid an additional sum as an inducement to accepts more Arizona students in the future. The program's goal is to increase the number of graduating physicians who will return to practice in Arizona, especially in areas of medical need. While the program apparently has been successful in increasing the number of Arizona students studying medicine and the number of physicians returning to the state--both to metropolitan areas and to areas of medical need--these increases have not kept pace with Arizona's growing population.


An administrative and curricular model for behavioral science teaching.

Various models of faculty organization for teaching behavioral science in medical schools have been advanced. Three of these are reviewed and compared with regard to their effects of curricular structure and content. Some significant variations on existing models are described in the context of a behavioral science curriculum in a new medical college. Several recurrent issues are addressed: How shall behavioral scientists be organized for maximum curricular effectiveness? How shall a curriculum be organized and administered to provide comprehensive yet integrated presentation of a broad spectrum of behavioral science knowledge and skills? What might constitute a model curriculum in the behavioral sciences? A basic science curriculum is described which spans the first two years of medical education, introducing students to fundamental concepts, behavioral skills, human development, behavioral pathology, and special topic seminars.


Pelvic examination instruction and the doctor-patient relationship.

Nonphysician women instructors from a women's health center taught the pelvic examination to second-year Harvard Medical School medical students. They demonstrated the procedure and acted as subjects for the students' examinations. In addition to teaching standard techniques, the instructors showed how the patient could be offered explanation of the procedure and information about her health during the performance of the examination. The exercises are described in terms of their implications for teaching the doctor-patient relationship during physical examination instruction. The following aspects are discussed: the use of nonphysicians as "practical instructors," improving attitudes toward women and promoting patient autonomy, and redefining aspects of the student-patient relationship in clinical training.


A sophomore physical diagnosis course in an outpatient setting.

A program designed to teach sophomore medical students physical diagnosis in an outpatient setting was evaluated as an alternative to an inpatient-oriented course. A comparison of the ability of 12 students trained in an outpatient setting to examine hospitalized patients with that of students trained in the traditional inpatient-oriented program revealed no difference between the two groups. These results are consistent with the hypothesis that the clinical status of the patient and the clinical setting have little impact on students' acquisition of physical diagnosis skills. Thus, the ambulatory care setting can provide an effective alternative for inpatient-oriented physical diagnosis programs. This finding has implications for curriculum planners who are seeking ways to restructure fundamental courses that emphasize development of primary care skills.


Internal and external application of photodynamic sensitizers on squid giant axons.

Squid giant axons were photosensitized by dyes applied internally or externally in air saturated solutions and photochemically modified by visible light. For most dyes the modifications included an irreversible block of sodium channels, a destruction of inactivation in some of the unblocked channels, and a slowing of inactivation. Internal application was up to 100-fold more effective in blocking sodium channels than external application, suggesting a site of block nearer the internal surface. Rose Bengal sensitized channel block and destruction of inactivation when applied internally, but sensitized only channel block when applied externally. In contrast, externally applied Eosin Y sensitized a clear slowing of inactivation plus channel block. Beta-carotene, an effective agent for quenching photochemically generated excited singlet oxygen, inhibited most of the modification sensitized by internally applied Methylene blue but not by Rose Bengal or Merocyanine 540.


Comparison between the size of granular vesicles in intact cells and vesicles obtained by fragmentation of biomembranes.

Preparations of biomembranes, consisting of membrane vesicles, were analyzed with the analytical ultracentrifuge. Under certain conditions depending on the speed of rotation and the temperature, a sedimentation profile was observed that was highly characteristic for membranous material. From the sedimentation coefficients obtained, we calculated particle weights for the various well-defined membrane components. In certain types of preparations the particle weights of two adjacent components differed on average by a factor of 2. When vesicles obtained by fragmentation of biomembranes were compared with the granular vesicles present in intact cells, the accordance in diameters was striking. This may indicate that the size of vesicles is determined by purely physical factors.


Some proposed improvements in the scanning ion microprobe.

Three improvements, which we have investigated, promise to lead to a scanning ion microprobe with a space resolution of about 15 nm. The improvements are: (1) use of a field-evaporation (EHD) ion source with liquid gallium to give a brightness exceeding 10(10) A m-2 sr-1 at 21 KeV, (2) a high efficiency (10%) collecting system for secondary ions, and (3) enhancement of the secondary-ion yield by cesium deposition. With this instrument, tracing with stable isotopes would offer a number of advantages over autoradiography.


Anatomical observations on the ending of the human thoracic duct.

Fifty-one cadavers of human adults of both sexes were examined for the ramifications and site of opening of the cervical segment of the thoracic duct. It was found that the duct opened into veins of the neck through either one (84.31%) or two branches (15.69%). The most frequent site of opening was in the junction of the left internal jugular vein with the subclavian vein (18 individuals), but another frequent site (15 individuals) was in the internal jugular vein. The duct opened at the angle formed by the internal jugular vein and the internal posterior jugular vein in five individuals, and at a variety of the other locations in the remaining cadavers. These results are compared with the findings of previous investigators.


Role of acid phosphatase in the breakdown of yolk platelets in developing amphibian embryos.

Yolk platelets in differentiating embryonic amphibian cells degrade by a membranous "unraveling" or "delamination" process. Acid phosphatase activity was demonstrated at the peripheries of those platelets which were in the process of degrading and thus this lytic enzyme appears to be involved in the breakdown process. We believe that this relationship provides a means by which early cells obtain the nutrients necessary for early differentiation.


The relation between size of motoneurons and their position in the cat spinal cord.

Experiments were performed to test whether motoneurons in the plantaris and medial gastrocnemius muscles of the cat are arranged in the spinal cord according to their sizes. It was found that motoneurons are randomly distributed with respect to size in their motor nuclei. Evidence is also presented that motoneuron density in these pools is irregular, and that there is considerable variability of position of medial gastrocnemius and plantaris motor pools from animal to animal.


The concept of cellular evolution.

A central evolutionary question is whether the eucaryotic cytoplasm represents a line of descent that is separate from the typical bacterial line. It is argued on the basis of differences between their respective translation mechanisms that the two lines do represent separate phylogenetic trees in the sense that each line of descent independently evolved to a level of organization that could be called procaryotic. The two lines of descent, nevertheless shared a common ancestor, that was far simpler than the procaryote. This primitive entity is called a progenote, to recognize the possibility that it had not yet completed evolving the link between genotype and phenotype. This concept changes considerably the view one takes toward cellular evolution.


Polymerization of alanine in the presence of a non-swelling montmorillonite.

Alanine, starting from alanine-adenylate, has been polymerized in the presence of non-swelling Al-montmorillonite. The yield of polymerization is much lower than that obtained in the presence of swelling Na-montmorillonite. The possibility that the changing interlayer spacing in Na-montmorillonite might be responsible for its catalytic properties, is discussed.


Evolutionary adaptability of biological macromolecules.

The degree of gradualism with which tertiary structure and function of protein changes with stepwise changes in primary structure (assumed to be influenced by redundancy of weak bonding) is both a precondition for and consequence of evolution. The resulting selection for degree of gradualism has implications for a number of structural and functional properties of modern proteins as well as for the significance of neutral (so-called non-Darwinian) phenomena in relation to selection.


Cytologic evaluation of breast fluid in the detection of breast disease.

The availability and cell content of aspirated breast fluid from 1,706 women were evaluated to determine the usefulness of breast fluid cytology as an indicator of breast disease. A newly developed aspirator was used to obtain cells adequate for diagnosis from approximately 50% of the women tested. Fluids were most readily available from women between the ages of 30 and 50 years. Although abnormal cytologies were observed in all age groups, the relative proportion of abnormal specimens as well as the degree of abnormality increased as a function of age. More women over 40 years of age with a high risk of breast cancer had cells classified in the more abnormal categories than did women in the normal risk group. To localize otherwise occult lesions, contrast ductography was performed on all women with very abnormal ductal cells. Women with atypical hyperplastic cytologies most commonly had benign and premalignant breast disease at subsequent biopsy. Of 27 women with fluids classified as suspected carcinomas 18 (66%) had small carcinomas. These observations strongly suggested that the presence of atypical cells in aspirated breast fluids has important clinical application for early detection of breast cancer. One limitation of cytology was that the technique rarely detected carcinomas greater than 1 cm.


Leukocyte migration inhibition in patients with Ewing's sarcoma by 3-M potassium chloride extracts of fresh and tissue-cultured Ewing's sarcomas.

Leukocyte migration inhibition (LMI) assays were performed to detect cell-mediated immune reactions against tumor-associated antigens (TAA) of Ewing's sarcoma. With the use of crude antigen preparations obtained by 3M KCl extractions of fresh Ewing's sarcoma or of tissue culture cells derived from a pleural effusion of a Ewing's sarcoma patient, assays were performed with leukocytes from these patients, patients with other cancers, and normal donors. The results demonstrated approximately 60% or greater positive LMI reactivity in Ewing's sarcoma patients, as compared to less than 10% reactivity of normal donors, with the use of extracts of either fresh or tissue-cultured Ewing's sarcoma cells. A lower proportion of positive reactivity was observed in patients with breast and lung cancer. Further specificity tests indicated that a smaller proportion of patients with Ewing's sarcoma had LMI reactivity with KCl extracts of tissue-cultured cells derived from breast cancer of fresh lung cancer cells than did patients with the homologous disease. The results indicate that many patients with Ewing's sarcoma have cell-mediated immunity toward TAA on Ewing's sarcomas. Inasmuch as all the LMI assay were performed with allogeneic extracts, the data also suggested that different Ewing's sarcomas possess common antigens and that some breast and lung cancers may share some TAA with Ewing's sarcoma.


Cancer in asbestos-mining and other areas of Quebec.

Employing incidence data from the Quebec Tumor Registry, we examined the relative risks of cancer of all sites for the years 1969-73 in the asbestos-mining, rural, and metropolitan counties of Quebec Province, Canada. Generally, rates for males exceeded those for females, and the relative risks in the asbestos-mining counties for 7-10 different sites of cancer, all of low incidence, were from 1.50 to 8.08 times those of other rural counties of the Province for both sexes. Metropolitan counties exhibited equally high risk for many of these sites. We discovered higher risks among males in asbestos-mining counties for cancer of the pleura, peritoneum, lip, tongue, salivary gland, mouth, and small intestine and higher risks among females for cancer of the pleura, lip, kidney, salivary gland, and for melanoma. Because of the likelihood of a long latent period for asbestos-related cancers, the risks we observed were possibly the product of since-altered occupational and environmental conditions existing 20-30 years ago in the asbestos-mining areas. The similarities in risks for most cancers in asbestos-mining and urban areas were noteworthy.


Associations of cancer site and type with occupation and industry from the Third National Cancer Survey Interview.

From the Third National Cancer Survey (TNCS) Interview Study of 7,518 incident cases, lifetime histories of occupations and industries were studied for associations with specific cancer sites and types while controlling for age, sex, race, education, use of cigarettes or alcohol, and geographic location. Lung cancer patients were found more often than expected among several categories including trucking, air transportation, wholesaling, painting, building construction, building maintenance, and manufacturing (furniture, transportation equipment, and food products). Controlling for cigarette smoking did not change these associations. Leukemia and multiple myeloma were associated with sales personnel of both sexes, whereas lymphomas and Hodgkin's disease were excessive among women working in the medical industry. Other associations included rectal cancer with several retail industries; prostate cancer with ministers, farmers, plumbers, and coal miners; malignant melanoma with school teachers; and invasive cervical cancer with women working in hotels and restaurants. Breast cancer patients were more common among women who were teachers or other professionals and who worked in business and finance (even after controlling for education). Many other findings are presented in detailed tables. Results are reported mainly as a research resource for use by other investigators doing work in this field. Suggestions are given for future studies.


Virus-like particles in placentas from normal individuals and patients with systemic lupus erythematosus.

Nineteen human placentas, obtained from 9 normal women and 10 women with diagnosed systemic lupus erythematosus (SLE), were extensively examined by electron microscopy for the presence of virus-like particles. Free and budding viral forms were found in the placentas of 4 of the normal women and 3 of the women with SLE. In every case, these virus-like particles were found in the basal infoldings of the syncytiotrophoblast cells of the chorionic villi. These particles could be distinguished from typical mammalian type C viruses by the absence of a space between the envelope and the nucleocapsid.


Cell kinetics in vivo and in vitro for C3H/He spontaneous mammary tumors.

Cell kinetics in spontaneous C3H/HeJ mammary tumors of retired-breeder mice was studied by in vivo and in vitro techniques. The [3H]TdR labeling index (LI), the DNA synthesis time (TS), and the primer-dependent DNA polymerase assay LI [an in vitro estimate of tumor growth fraction (GF)] were compared to similar measurements made in vivo. These measurements as well as the calculated cell kinetic parameters derived from these data were not different in in vivo and in vitro studies. Furthermore, the cell kinetic parameters in tumors classified histologically as type A or type B mammary tumors were also similar. Although considerable variation in volume doubling times (Td's), [3H]TdR LI's, potential doubling times, cell cycle times (Tc's), and cell loss was found, Ts's were similar in all mammary tumors. No correlation between tumor volume or tumor weight and cell kinetic parameters was seen. However, the most slowly growing tumors (i.e., tumors with the longest Td's) tended to have the lowest [3H]TdR LI's, the longest Tc's, and the highest cell loss factors. No correlation was found between the GF and Td. However, tumors with the most rapidly proliferating cell populations tended to have the highest GF's.


Immune responses to mouse neuroblastoma C1300. I. Preliminary observations on cell-mediated immune responses.

In vitro cell-mediated cytotoxicity (CMC) for [3H]proline-labeled target cells was demonstrated with the use of unfractionated populations of regional lymph node, spleen, and peritoneal cells (RLNC's, SPC's, PC's, respectively) from C57BL/6 and strain A mice. Syngeneic and allogeneic hosts were immunized sc or ip with C1300 tumor or syngeneic SPC's. The syngeneic and allogeneic host effector lymphoid cells showed various degrees of cytotoxicity for C1300 target cells 3-9 days after one immunization with C1300, whereas the effector lymphoid cells of hosts immunized with syngeneic SPC's generally showed less CMC for C1300 and frequently increased the growth of C1300 target cells when compared to C1300 targets plus media controls. Effector cells obtained from lymphoid organs in the region nearest the immunization (i.e., RLNC from sc-inoculated hosts) demonstrated significantly more CMC than did effector cells from more remote lymphoid organs. The PC's and SPC's of C1300 ip hyperimmunized allogeneic hosts produced greater CMC than did those of mice immunized once. This was not observed if syngeneic C1300 or SPC's were used as hyperimmunizing antigens. The CMC of nonimmunized host effector lymphoid cells for syngeneic labeled target cells was demonstrated.


In vitro reactivity of macrophages and lymphocytes from ultraviolet-irradiated mice.

In these experiments we examined the ability of lymphocytes and macrophages from UV-treated mice of the inbred strain C3H/HeN(MTV-) to respond in vitro to nonspecific stimuli. Spleen and lymph node cells from UV-treated mice exhibited blastogenic responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide that were equal to those of lymphoid cells from normal animals. Neither the induction of peritoneal exudate cells by inflammatory agents nor the phagocytic activity of peritoneal macrophages was affected by UV irradiation. Furthermore, no reduction occurred in the in vitro tumoricidal capacity of peritoneal macrophages from UV-treated mice after in vitro activation with xenogeneic lymphokines or endotoxin. We concluded that chronic UV irradiation does not lead to a generalized suppression of the immune system in mice.


Analysis of thymidine kinase activity and glucocorticoid-binding capacity in the thymuses of healthy and tumor-bearing chickens.

Thymidine kinase activity in the lymphoid organs of healthy and tumor-bearing chickens was studied after hydrocortisone or dexamethasone treatment. Glucocorticoid hormones (10 mg/100 g body wt) administered twice in 48 hours resulted in an 80% decrease in thymidine kinase activity in the thymuses of healthy chickens, whereas birds with transplantable MC 29 chicken hepatoma failed to respond to the hormones. In the bursae of Fabricius of healthy or tumor-bearing chickens, thymidine kinase activity did not change considerably after administration of hydrocortisone or dexamethasone. The steroid-binding capacity in cellfree systems prepared from thymuses of tumor-bearing birds was significantly decreased. Thus the difference in steroid-binding capacity between thymuses of healthy and tumor-bearing chickens correlated well with, and could account for, the failure of hydrocortisone and dexamethasone to reduce the thymidine kinase level in tumor-bearing birds.


Maintenance of ectopic chorionic gonadotropin and alpha subunit secretion by a human lung cancer cell line (ChaGo) transplanted into nude mice.

ChaGo cells, derived from a human primary carcinoma of the lung, were successfully transplanted into nude mice without any change in morphologic characteristics over four generations and with continued ectopic secretion of human chorionic gonadotropin (HCG) and HCG alpha subunit (HCG-alpha). The concentration of free HCG-alpha was 1,100-fold higher than that of complete HCG in the original ChaGo culture medium but only 35-fold higher in nude mouse plasma, possibly due to slower metabolic clearance of complete HCG. Tumor weights correlated with plasma HCG-alpha but not with HCG. Tumor-bearing mice had significantly heavier uteri than did control mice.


Cellular and humoral immunity to leukemia cells in BCG-induced growth control of a murine leukemia.

The antitumor effects of weekly iv injections of 1.0 mg BCG and/or sc injections of 10(7) irradiated leukemia cells were studied in an isogeneic, transplantable lymphoid leukemia in the C57BL/6 mouse. The injections were started at day 1 after ip inoculation of 10(5) leukemia cells. BCG prolonged the survival time of most animals and cured 22%. BCG plus irradiated cells cured only about 10% of the mice, and irradiated cells alone had no curative effect. Individual tumor-bearing mice in the various experimental groups were examined with respect to ascites tumor cell number; complement-dependent cytotoxic antibodies in sera; direct and antibody-dependent cytotoxicity to tumor cells of lymphoid cells from peritoneal fluid, the spleen, and peripheral lymph nodes; and the cytology of ascites, the spleen, and lymph nodes. Only the antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) was correlated with the ascites tumor cell number, since the ADLMC was high only in mice with a tumor cell number less than that of the controls. Furthermore, since mice with a low tumor cell number had predominantly only lymphocytes as the nonmalignant cell type in their peritoneal fluid, ADLMC may have had an important role in BCG-induced control of tumor growth.


Lymphocyte cytotoxicity in X-irradiation-induced adenocarcinoma of the rat small bowel. I. Measurement of target cell destruction by release of radioiodinated membrane proteins: brief communication.

A cell-mediated immune response as denoted by lymphocyte cytotoxicity was detected in Holtzman rats with X-irradiation-induced adenocarcinomas of the small bowel. Cytotoxicity was measured by target cell destruction as determined by release of intracellular 51Cr or radioiodinated (125I) membrane proteins. The radioiodination assay possessed an important advantage over the 51Cr technique in that the radiolabel was spontaneously lost slowly, thus permitting long-term studies.


Cytotoxicity inhibition assay: cryopreservation and standardization: brief communication.

The cytotoxicity inhibition assay is an extremely useful tool for examination of the specificity of cell-mediated cytotoxicity. With this demonstration of cryopreservation of the attacker, target, and inhibitor cells, a powerful new tool is available for the standardization of this assay to better examine the specificity of cytotoxicity assays. Not only can cryopreservation be used to standardize the assay within a single laboratory, but also reagents may now be exchanged between laboratories to better understand the differences in cell-mediated cytotoxicity as observed by different investigators.


Construction of a DBA/2.Fv-2r congenic strain. Apparent lethality of the homozygous Fv-2r genotype: brief communication.

From the (C57BL/6 X DBA/2)F1 cross, 13 serial backcrosses to the DBA/2 parental mouse strain were bred with selection by progeny testing in each generation for the Fv-2s/Fv-2r heterozygous genotype. Intercrossing heterozygotes of the 13th backcross generation produced no Fv-2r/Fv-2r homozygotes. Homozygosity for the Fv-2r allele thus appeared to be lethal on a DBA/2 background and in the absence of protector gene(s) of the C57BL strain.


Traditional admissions variables as predictors of minority students' performance in medical school. A cause for concern.

This study explored the relationship between traditional admissions criteria, performance in the first semester of medical school, and performance on the National Board of Medical Examiners' (NBME) Examination, Part 1 for minority medical students, non-minority medical students, and the two groups combined. Correlational analysis and step-wise multiple regression procedures were used as the analysis techniques. A different pattern of admissions variables related to National Board Part 1 performance for the two groups. The General Information section of the Medical College Admission Test (MCAT) contributed the most variance for the minority student group. MCAT-Science contributed the most variance for the non-minority student group. MCATs accounted for a substantial portion of the variance on the National Board examination.


A description of Walter Reed Army Medical Center's in-patient psychiatric service population 1973 to 1975.

A three-year evaluation of demographic and diagnostic patterns in a large Army psychiatric in-patient facility is described. Active duty personnel accounted for 83.6 percent of patient episodes. No simple catchment area could be defined for this facility. Active duty patient episodes tended to be with younger, junior enlisted men whose sicknesses were most frequently diagnosed as schizophrenia. The diseases of blacks were diagnosed as paranoid schizophrenia more frequently than in whites. Latent schizophrenia or undifferentiated schizophrenia were diagnosed more frequently in whites than in blacks. The illnesses of active duty female military personnel were more frequently diagnosed as neurotic than as schizophrenic. Of the patient episodes during the three-year period, 12.1 percent were about dependents. They were usually the wives of older, senior enlisted men or senior officers and they stayed an average of 12 days in the hospital. On the other hand, 4.3 percent of the patient episodes were about retired personnel. They came from Walter Reed Army Medical Center (WRAMC) as did their dependents, and the most frequent diagnosis was alcoholism. Their median stay was 15 days. Subsequent studies will attempt to further clarify these initial findings.


Diploid/tetraploid mosaicism in the offspring of a 46XX/47XXX mosaic mother.

A 10½-year-old boy with an IQ of 71, short stature, and isolated growth hormone deficiency was found to have diploid/tetraploid mosaicism. He was born to a 46xx/47xxx mosaic mother. The mother was found to be moderately mentally retarded but showed no other abnormalities. A review of literature pertinent to this case is presented.


Polycystic kidney disease at Howard University Hospital.

Adult polycystic kidney disease treatment at Howard University Hospital is summarized. The cases are taken from autopsies performed between January 1955 and November 1975 and from the Hospital's dialysis population. Polycystic kidney disease was identified in six adults and four infants. Only two dialysis patients were clinically thought to have the disease. A review of the major clinical features of the disease is presented.


Pleural effusion in sickle cell disease.

Pneumococcal and mycoplasma infection of the lung or pleura, infarction of lung or pleura, local abscess below the diaphragm, and heart, kidney, or pancreas involvement are among the many causes of pleural effusion. Several of these have an increased likelihood of occurrence in sickle cell disease as a direct consequence of sicklemia or of the functional asplenia which develops. A patient is presented in whom many of these considerations arose.


Thyroid diseases in black patients.

During the 26-year period, January 1, 1950 to December 31, 1975, inclusively, there were 680 thyroidectomies for clinical evidence of primary thyroid disease performed at the Howard University Hospital (0.6 percent of routine surgicals). There were 595 female and 85 male patients (ratio 7:1). All of the patients were black. In the 680 cases, the incidence of carcinoma was 4.6 percent, adenoma 11.3 percent, nodular goiter 51.9 percent, diffuse hyperplasia 21.3 percent, various thyroiditis 7.1 percent, and miscellaneous conditions 3.8 percent. A statistical analysis, together with a brief review of the literature on each entity, will be presented.


Aspirin for reducing cancer metastases?

Distant metastases are the principal cause of death from cancer. Many animal experiments in the last 25 years have shown consistently that distant metastases can be significantly reduced by anticoagulants and fibrinolytic agents. Since aspirin inhibits platelet function and increases fibrinolytic activity in humans, it may be effective in preventing metastases in cancer patients. It is suggested that aspirin be offered as an option to cancer patients who are at risk for distant metastases.


The use of the Zickel device for a malunited subtrochanteric femur fracture.

Surgical treatment of adult subtrochanteric femur fractures by internal fixation, using the Jewett nail, has been associated with a high degree of major complications. Jewett nail failures in these fractures can produce functionally disabling varus deformities. The Zickel device is an effective means of providing internal fixation following subtrochanteric osteotomy. A case is presented in which the Zickel device was effectively used.


Centralized vs. decentralized child mental health services.

One of the basic tenets of the Community Mental Health Center movement is that services should be provided in the consumers' community. Various centers across the country have attempted to do this in either a centralized or decentralized fashion. Historically, most health services have been provided centrally, a good example being the traditional general hospital with its centralized medical services. Over the years, some of these services have become decentralized to take the form of local health centers, health maintenance organizations, community clinics, etc, and now various large mental health centers are also being broken down into smaller community units. An example of each type of mental health facility is delineated here.


Some problems of sexual growth in adolescent underprivileged unwed black girls.

The adolescent female experiences many problems associated with sexual growth. These are greatly compounded in underprivileged black girls, particularly the unwed. Meharry Medical College has established comprehensive programs for the management of special health problems involving adolescent girls. This study presents an overview and statistical study of the psychological and psychosocial forces that confront these underprivileged girls.


Bereavement: the role of the family physician.

Much has been written regarding attitudes of patients, families, and physicians in managing death and subsequent grief reactions. Here at Howard University College of Medicine, we are constantly aware of our educational responsibility to insure that our students and residents achieve certain levels of awareness, acquire certain basic and specific information, and be afforded an opportunity to ventilate and discuss issues of death, dying, and bereavement as they relate to their current or future encounters with patients and their families. We are specifically interested in the roles and responsibilities of the family physician.


An approach to the evaluation of hemostasis.

Effective hemostasis may be adequately and quickly evaluated using tests that are readily available in the usual hospital laboratory. This evaluation includes peripheral smear for platelet morphology and number, platelet count, bleeding time, activated partial thromboplastin time (aPTT), prothrombin time (PT), and clot retraction. Normal results of these tests exclude all but the mildest disturbances of hemostasis.


Vagotomy for relief of pain in some upper gastrointestinal neoplasms.

At the University College Hospital, Ibadan, Nigeria, upper gastrointestinal neoplasms are usually seen very late when they have become unresectable. The resectable upper gastrointestinal neoplasms seen in this institution are less than ten percent of all the cases seen. The reasons for such delay before presentation are ignorance and fear of hospitals.Following an editorial by Merendino,(1) a study was conducted on ten patients who had inoperable upper gastrointestinal neoplasms. Even though the assessment of pain sensation has many variables, and there is a significant suggestive effect in any pain-relieving procedure, it is felt that vagotomy combined with any indicated diversion procedures definitely reduces the pain associated with terminal upper gastrointestinal neoplasms, while not affecting patient mortality.


High pressure injection injury of the hand.

Attention is called to the importance of prompt and adequate treatment of high pressure injection injury of the hand.


Localization of minor protein components of the head of bacteriophage T4.

The bacteriophage T4 capsid contains a number of minor proteins that are required for head assembly but whose detailed function and position in the head are unknown. We have found that by systematically varying the conditions of extraction, some of these minor proteins can be removed while the main capsid structure is left substantially intact. Electron microscopic examination of the residual capsids showed that the extraction of the product of gene 20 is correlated with the loss of a plug that distinguishes one vertex position (presumably the tail attachment site) from the others. Extraction of the product of gene 24 is correlated with the loss of the other 11 (nonproximal) vertexes of the capsid. We further show that antibody to P24 binds specifically to the nonproximal vertexes of both T4 preheads and T4 phages. On the basis of our findings, we suggest that P20 is located at or near the tail attachment site of the capsid, whereas P24 forms the 11 nonproximal vertexes of preheads and P24 forms the nonproximal vertexes of the mature head.


Role of the T5 gene D15 nuclease in the generation of nicked bacteriophage T5 DNA.

The processing of newly replicated concatameric T5 DNA into both single stranded DNA changed of unit length and single-stranded fragments of sizes comparable to those found in mature T5 virion DNA occurs in the absence of late T5 protein synthesis. The formation of unit-length, single-stranded DNA chains does not require the early T5 gene D15 nuclease: however, the subsequent formation of the single-stranded fragments does require that the D15 nuclease be functional. A reexamination of the properties of the purified D15 nuclease under a variety of conditions showed that, in addition to functioning as a 5' leads to 3' exonuclease, the enzyme can also introduce endonucleolytic scissions into mature T5 DNA in a reaction that requires duplex T5 DNA and preexisting, single-stranded interruptions.


Physical map of the bacteriophage T5 genome based on the cleavage products of the restriction endonucleases SalI, SmaI, BamI, and HpaI.

A physical map of the bacteriophage T5 genome was constructed by ordering the fragments produced by cleavage of T5 DNA with the restriction endonucleases SalI (4 fragments), SmaI (4 fragments), BamI (5 fragments), and HpaI (28 fragments). The following techniques were used to order the fragments. (i) Digestion of DNA from T5 heat-stable deletion mutants was used to identify fragments located in the deletable region. (ii) Fragments near the ends of the T5 DNA molecule were located by treating T5 DNA with lambda exonuclease before restriction endonuclease cleavage. (iii) Fragments spanning other restriction endonuclease cleavage sites were identified by combined digestion of T5 DNA with two restriction endonucleases. (iv) The general location of some fragments was determined by isolating individual restriction fragments from agarose gels and redigesting the isolated fragments with a second restriction enzyme. (v) Treatment of restriction digests with lambda exonuclease before digestion with a second restriction enzyme was used to identify fragments near, but not spanning, restriction cleavage sites. (vi) Exonucleases III treatment of T5 DNA before restriction endonuclease cleavage was used to locate fragments spanning or near the natural T5 single-chain interruptions. (vii) Analysis of the products of incomplete restriction endonuclease cleavage was used to identify adjacent fragments.


Properties of the nonlethal recombinational repair x and y mutants of bacteriophage T4. II. DNA synthesis.

The bacteriophage T4 recombination-deficient mutants x and y exhibited decreased rates of DNA synthesis as compared to wild-type T4. Mutant-induced DNA synthesis was more sensitive to mitomycin C than was wild-type synthesis. However, DNA synthesis in mutant- and wild-type-infected cells exhibited the same sensitivity to UV light and X-irradiation. When high-specific-activity label was administered at various times postinfection, mutant DNA synthesis resembled that of wild type for 12 min. after which time mutant-induced incorporation was greatly decreased and sensitive to mitomycin C as compared to that of the wild type. Rifampin and chloramphenicol studies indicated that the gene products necessary for synthesis measured at 15 min postinfection, including those of x+ and y+ were transcribed within 2 min and translated within 8 min postinfection. Administration of chloramphenicol to mutant x- or mutant y-infected cells exactly 8 min postinfection, however, allowed for increased synthesis at 15 min that was sensitive to mitomycin C. Cells coinfected with T4+ and T4x or T4x and T4y retained a reduced mutant-type synthesis, whereas cells coinfected with T4+ and T4y exhibited a synthesis more closely resembling that of wild type.


Ultrastructural studies of H-1 parvovirus replication. IV. Crystal development and structure with the temperature-sensitive mutant ts1.

Electron microscopy was used to study the development and structure of viral crystals of ts1, a temperature-sensitive mutant of H-1 parvovirus. At early times postinfection, at the restrictive temperature, empty H-1 capsids aggregated to form conspicuous noncrystalline conglomerates in human NB cell nuclei; these particles did not associate with euchromatin as in wild-type H-1 infections. Later on, the capsid aggregated appeared to form polycrystals exhibiting rod-like, hexagonal, and cubic patterns that were interconvertible using a goniometer specimen stage. The unit cell of this crystal was cubic, consisted of 16 empty particles, and measured 50 nm on each side. Full particles made at the permissive temperature were never observed under restrictive conditions. Experiments in which cultures were shifted form the permissive to the restrictive temperature showed that full virions were not incorporated into crystals. The crystals dissociated into individual particles when changes were made from restrictive to permissive conditions. Correlations between the formation of crystals at the restrictive temperature, their dissociation into capsid components after shifting from the restrictive to the permissive state, and the extent of host cell damage were also observed. Possible roles of cellular functions in regulating ts1 H-1 polycrystal assembly and dissociation are discussed.


Ultrastructural studies of H-1 parvovirus replication. V. Immunocytochemical demonstration of separate chromatin-associated and inclusion-associated antigens.

Electron microscopy and immunocytochrome c staining were used to define the phenotypes of several temperature-sensitive (ts) H-1 mutants. They were classified into three separate groups based on the properties of their capsids at the restrictive temperature (rT): (class 1) ts2 did not assemble capsids but produced spherical and irregular amorphous inclusions; (class 2) ts1 and ts7 exclusively synthesized empty particles which all aggregated and crystallized; and (class 3) ts8 and ts10 formed noncrystalline aggregates of empty virions, but many individual full, as well as empty, capsids were associated with euchromatin. Synthesis of progeny DNA and hemagglutinin at rT were normal for class 3 mutants, but defective for those in classes 1 and 2. The immunospecific staining patterns of these mutants indicated that the H-1 capsid proteins probably form two separate intranuclear antigens: (i) a thermostable chromatin-associated antigen present in proteins that have not formed capsids and are concentrated on heterochromatin and nucleolar-associated chromatin and (ii) a thermolabile inclusion-associated antigen found in the proteins of assembled empty capsids that compose H-1 inclusions.


Defective Friend spleen focus-forming virus: interfering properties and isolation free from standard leukemia-inducing helper virus.

Defective Friend spleen focus-forming virus (SFFV) is able to interfere with the ability of its naturally occurring leukemia-inducing helper virus (LLV-F) to induce XC plaque formation in several different strains of mouse embryo cells. This interference has been observed by using two different SFFV preparations, one contained in an NB-tropic stock of Friend virus (FV) complex, and the second present in a C57BL-adapted strain of FV complex containing an associated B-tropic LLV-F helper. The LLV-F in NB-tropic FV complex effectively induced XC plaques in C57BL/6 (Fv-1(bb); Fv-2(rr)) mouse embryo fibroblasts (MEF) only in the absence of coinfecting SFFV, indicating that Fv-2-associated resistance to SFFV-induced focus formation in vivo does not necessarily extend to the restriction of SFFV function(s) in vitro (i.e., in Fv-2(rr) C57BL MEF). SFFV interference appears to be an intracellular event since LLV-F can adsorb onto, penetrate, and rescue defective murine sarcoma virus (MSV) from transformed 3T3FL S(+)L(-) cells with equal efficiency in the presence and absence of SFFV. However, significantly fewer LLV-infected S(+)L(-) cells released LLV-F progeny if SFFV was present. These observations suggest that Friend SFFV may be classified as a defective, interfering (DI) particle. Further support for this conclusion has come from studies designed to investigate two physical properties of defective SFFV particles. SFFV layered onto a 0 to 20% sucrose sedimentation gradient was recovered as a symmetrical band of virus that sedimented more slowly than standard LLV-F particles. Pooled SFFV-containing gradient samples contained visualizable type C virus particles and occasionally small amounts of detectable LLV-F. In an attempt to determine the buoyant density of sedimentation gradient-purified SFFV, pooled SFFV samples were layered onto a 25 to 50% sucrose equilibrium density gradient and were centrifuged to equilibrium. Greater than 50% of the infectious SFFV originally layered onto this gradient was recovered and seen as a narrow symmetrical band with peak SFFV infectivity at a sucrose density of 1.14 g/ml. The observed difference between SFFV and LLV-F buoyant densities appears to be related to an inherent physical property of each virus. Mixtures of these two viruses express the buoyant density of that virus population which is in excess in fabricated FV complexes probably due to the formation of SFFV-LLV aggregates. Finally, gradient-purified SFFV failed to induce XC plaques in MEF and did not function to rescue MSV as expected since SFFV itself is replication defective.


Bunyamwera virus-induced polypeptide synthesis.

Bunyamwera virus-induced polypeptide synthesis in BSC-1 cell has been studied using polyacrylamide gel electrophoresis and autoradiography. Four virus-induced polypeptides were identified. Their molecular weights were 200 X 10(6) (L), 128 X 10(6) (G1), 31 X 10(6) (G2), and 23 X 10(6) (N). Pulse-chase experiments, short labeling experiments, and experiments using amino acid analogs failed to show evidence of polypeptides processing by proteolytic cleavage. Analysis of the kinetics of synthesis of these polypeptides showed that a clear division into early and late categories could be made, the onset of synthesis of polypeptide N and L rapidly reached a peak and then declined. Polypeptides G1 and G2 were made for several hours; their rate of synthesis then declined. All four polypeptides then continued to be made in relatively small amounts for many hours.


Phosphorylated protein component present in influenza virions.

The nucleoprotein of the WSN strain of influenza was found to be phosphorylated in vitro. The phosphate-protein bond was stable to hot trichloroacetic acid, RNase, DNase, succinic acid, and succinic acid-hydroxylamine, but sensitive to hydrolysis by bacterial alkaline phosphatase. This suggested that the nucleoprotein is in the form of a phosphomonoester. Acid hydrolysis of the isolated nucleoprotein followed by thin-layer electrophoresis identified the phosphorylated amino acid residue as phosphoserine.


Evidence of a repetitive sequence in vaccinia virus DNA.

Analysis of vaccinia DNA by reassociation kinetics revealed that 7% of the genome contains a sequence repeated 10 times. This sequence does not contain any host cell DNA, is viral specific, and is found in virions passed at either high or low multiplicities of infection.


Further characterization of the complementation group B temperature-sensitive mutant of respiratory syncytial virus.

ts-2, a temperature-sensitive and plaque morphology mutant of respiratory syncytial virus and sole representative of complementation group B, was compared with members of the other complementation groups of respiratory syncytial virus (group A [ts-1] and group C [ts-7]). ts-2 was found to be 10- to 1,000-fold more restricted in growth and ability to spread at restrictive temperatures (37, 38, and 39 degrees C) than at the permissive temperature (32 degrees C). In temperature shift-up experiments, the ts defect of ts-1 and other members of complementation group A was found to effect a late function that was required for at least 13 h in the replicative cycle. The ts lesion of ts-7 affected a function early in the replication cycle. In contrast, ts-2 was not temperature sensitive when studied by the shift-up technique. The discrepancy between the ts plaque property and failure to detect temperature sensitivity during the shift-up experiment was resolved when it was shown that ts-2 had a defect in adsorption or penetration or both at the restrictive temperature. Clonal analysis of revertant ts-2 showed a coordinate restoration of ts+ phenotype ans syncytium-forming capacity. It appears that ts-2 has a defect in a protein that is involved in adsorption and/or penetration of virus and is also responsible for cell fusion activity.


Adenovirus type 12 DNA sequences in primary hamster tumors.

In five out of six primary hamster tumors induced by adenovirus type 12, less than 55% of the adenovirus type 12 genome is present. Various fragments of the integrated viral DNA were present in non-equimolar amounts.


Struvite staghorn calculi in crossed fused ectopia.

Two patients with a struvite staghorn calculus in crossed fused renal ectopia are described. The susceptibility of these patients to urinary tract infection is discussed as is the anomalous extrarenal arterial vasculature to the ectopic and non-ectopic kidneys. Both patients were treated successfully with anatrophic nephrolithotomy and each has remained free of recurrent calculous disease to date.


Therapeutic renal infarction.

Pre-nephrectomy therapeutic renal infarction by injecting gelfoam into the renal artery was done in 10 patients with hypernephroma. This technique facilitates nephrectomy and decreases blood loss. A post-infarction syndrome characterized by flank pain, fever and nausea occurred in most patients. In addition, a dialysis patient underwent bilateral renal infarction with improvement of blood pressure control. Distal embolization of gelfoam occurred in this patient, resulting in significant gangrene of 1 foot.


Replacement of the damaged or neoplastic ureter by ileum.

Ileum was used as a ureteral replacement in 12 patients, 7 of whom had solitary kidneys. The conditions that necessitated an operation included renal pelvic and ureteral complications of calculi, a variety of traumatic ureteral injuries, retroperitoneal fibrosis and ureteral neoplasms. Renal function has been well preserved and electrolyte imbalance has been minimal.


Terminal loop cutaneous ureterostomy: an experimental study and its clinical application.

Terminal loop cutaneous ureterostomy is a technique to enhance the blood supply and, thereby, decrease the complication rate with stomas. An animal study and experience with 20 patients with long-term followup support this contention.


Ureterosigmoidostomy after pelvic irradiation.

The records of 34 patients who underwent ureterosigmoidostomy after pelvic irradiation were reviewed and the incidence of complications was found to be similar to that in other series of ureterosigmoidostomy without prior irradiation. No difference was established between the use of linac or cobalt 60 therapy in relation to postoperative complications. No conclusions could be reached concerning the effect of the preoperative dose of radiotherapy on the operation because of the small number of patients but it did appear that the incidence of postoperative complications was great after doses in excess of 5,000 rads. Ureterosigmoidostomy after pelvic irradiation is considered to be a feasible procedure with doses of less than 5,000 rads.


Solitary cystic lymphangioma of the retroperitoneum.

We present 2 cases of solitary cystic lymphangioma of the retroperitoneum. The non-specific clinical picture is demonstrated again but the pathologic features of both tumors are characteristic. Surgical treatment was successful in both instances.


Circle tube cystostomy drainage.

An unfavorable experience with the adaptation of the circle tube for cystostomy drainage is presented. The primary disadvantage is the dissatisfaction of patients with the presence of 2 tubes emerging from the lower abdomen.


Cystostomy drainage: its efficacy in preventing residual urine and infection.

Residual urine volume was measured in patients with cystostomy drainage by injecting phenolsulfonphthalein in saline solution through the tube. Subsequent drainage yielded an average volume of 25 ml. residual urine. The cause for the presence of residual urine and its consequences--promotion of infection--are discussed.


Transurethral external sphincterotomy and its effect on potency.

A series of 43 male patients who underwent external sphincterotomy because of vesicosphincteric dysfunction is reviewed. There were 6 patients who subsequently noticed absence or a marked decrease in erectile ability. Various factors are considered that might have affected potency, and the theoretical reasons for this occurrence and subsequent recovery are discussed.


Post-traumatic priapism.

Review of 7 cases of post-traumatic priapism indicated that, despite the type of initial therapy, all patients expressed dissatisfaction with the total efforts, although erections were resumed. A surgical effort directed at drainage of fluid collections and correction of the ruptured tunic seems warranted and may aid the patients in further sexual activities.


Prostatic involvement by transitional cell carcinoma: pathogenesis, patterns and prognosis.

Prostatic involvement by transitional cell carcinoma of the bladder includes a spectrum of histologic patterns. Ductal only or ductal and acinar involvement occurs with or without stromal invasion. Stromal invasion may exist without glandular involvement. Invasive prostatic patterns are most frequent in the setting of high stage invasive bladder tumors and 5-year survival rates for these patients are low. Non-invasive in situ prostatic patterns are usually associated with low stage bladder tumors and 5-year survival approaches that predicted from radical cystectomy for low stage bladder tumor alone. When an invasive pattern is associated with a low stage bladder tumor the 5-year survival rate is determined by the prostatic lesion and is low. Although the survival rate is severely jeopardized by stromal prostatic invasion the prognosis is not hopeless. Preoperative radiotherapy followed by cystoprostatourethrectomy can be expected to produce a 20 per cent 5-year survival rate.


Adaptation of swivel valve and closed drainage system to a standard resectoscope sheath.

A central 3-way swivel valve and a drainage outlet have been adapted to a standard resectoscope sheath. The modifications to the sheath enable the resectionist to operate with the advantages of a closed drainage system.


Pressure studies and dynamics of ileal conduits in children.

The pressures generated in the ileal conduits of 20 children and their relation to conduit ureteral reflux are investigated. The resting pressure in the ileal conduits was generally low but peaks of high pressure were observed occasionally. Reflux occurred mostly at low pressure. Whether reflux occurred at any one moment depended on the position of the peristaltic wave in the ureter at that time. There was no consistent relationship between the conduit pressures and deterioration of the upper renal tract.


Functional striated sphincter component at the bladder neck: clinical implications.

Anatomical proximal extension of the striated urethral sphincter muscle towards the bladder neck was assessed functionally in normal male subjects and in patients with upper motor neuron lesions. Synchronous cystosphincterometric studies were performed and urethral pressure responses were studied (contraction complexes) at the vesicourethral junction, the supramontane prostatic urethra and the membranous urethra to repeated bulbocavernosus stimuli. All subjects demonstrated positive responses at the membranous urethra. Contraction complexes with amplitudes of less magnitude were elicited at the vesicourethral junction and at the supramontane prostatic urethra in 48 and 71 per cent of the total number of subjects, respectively. The functional significance of the striated muscle component at the bladder neck in patients with detrusor-striated sphincter dyssynergia is described.


Electroencephalography and bladder innervation.

Combined electroencephalography and cystometry provides the only method presently available to analyze central micturition reflex disturbances. When these techniques are used in sleep cystometry they provide a rational method to evaluate nocturnal enuresis.


The use of sacral nerve blocks in the evaluation and treatment of neurologic bladder disease.

We describe the use of sacral nerve blocks in conjunction with air cystometry and sphincter electromyography to determine the functional innervation of the bladder and sphincters. This technique has aided in the selection of patients for sacral rhizotomy. Phenol sacral nerve blocks have been used successfully in treating hyperactive bladder disease and intractable perineal pain.


Rare urologic pathology presenting as abdominal masses in children.

The key to correct diagnosis of abdominal masses in children is awareness of all the possibilities. Three children with abdominal masses of uncommon urologic origin are described. The lesions were adrenal cortical carcinoma, a pancake pelvic kidney and a non-functioning hydronephrotic segment of a horseshoe kidney. Management of these patients is discussed and the literature is reviewed.


Diffuse xanthogranulomatous pyelonephritis in children: an unrecognized variant.

Xanthogranulomatous pyelonephritis in childhood has been thought to exist only in focal form. We encountered 2 cases of diffuse xanthogranulomatous pyelonephritis in children and have found 3 others reported in the literature, making it necessary to change this concept. The essential radiologic and pathologic differences between focal and diffuse xanthogranulomatous pyelonephritis are reviewed.


Variations in the bladder exstrophy complex associated with large omphalocele.

Two newborns with a large omphalocele associated with the bladder exstrophy complex are presented. In 1 case the omphalocele was combined with a musculoskeletal defect and imperforate anus with an anovulvar fistula. The other patient had a musculoskeletal deformity and a duplicated bladder with exstrophy. Surgical treatment was successful in both cases.


Paratesticular rhabdomyosarcoma in childhood.

Ten boys with paratesticular embryonal rhabdomyosarcoma were treated in a 44-year period. Two prognostically distinct stages of the disease and appropriate treatments are described. Children with non-infiltrating tumors (stage IA) are curable (3 patients are alive and free of tumor after 8 to 44 years) and radical orchiectomy with adjunctive radiation or, preferably, chemotherapy is adequate for these patients. Conversely, in those children with infiltrative tumors retroperitoneal nodal metastases invariably develop. Early retroperitoneal lymphadenectomy with adjuvant radiation and multidrug cyclic chemotherapy is life-saving (3 are alive and free of tumor after 2 1/2 to 4 years). However, delayed recognition and treatment of retroperitoneal disease, despite agressive therapy, is frequently disappointing--2 of 4 patients died after 2 and 6 years; another, who had advanced disease, is lost to followup and also is presumed dead and 1 is alive and free of tumor after 6 1/2 years.


Emphysematous pyelonephritis.

Emphysematous pyelonephritis is an uncommon infection of the renal parenchyma found most often in diabetic patients. The fortieth case of emphysematous pyelonephritis is reported and a plan for management is proposed based on differentiating this condition from gas-forming infections of the perinephric space and the renal collecting system.


Late return of renal function after correction of chronic obstruction.

A 57-year-old man presented with renal failure secondary to bilateral interstitial nephritis and left hydronephrosis owing to a calculus in the renal pelvis, creatinine clearance being 2.4 cc per minute. Renal function did not improve after left pyelolithotomy and hemodialysis was instituted. No demonstrable change in renal function could be detected until 10 weeks postoperatively when creatinine clearance was 25 cc per minute.


Renal vein thrombosis in a newborn: a case report with emphasis on pathological and radiological features.

A case of renal vein thrombosis in a newborn is presented. Trauma during pregnancy is suggested as an etiological factor. In contradistinction to most cases reported the newborn showed no signs of acute illness except for a palpable abdominal mass. Therefore, surgical intervention was delayed for 10 months but this did not impair the infant's growth and well-being.


Aspergillus mycetoma of the renal pelvis associated with ureteropelvic junction obstruction.

A case of aspergillosis of the kidney is described that could not be attributed to any of the factors that classically predispose to fungal infection (immunosuppressive, antibiotic or steroid therapy and diabetes). The patient did have severe obstruction of the ureteropelvic junction, which we believe caused stasis of urine and, in turn, the propagation of a colony of Aspergillus.


Hypernephroma of the right kidney with inferior vena caval and right atrial thrombosis: case study and successful removal.

A case is described in which a neoplastic thrombus extending into the right atrium was removed through a renal vein incision. This procedure can be performed provided the tumor has not infiltrated the walls of the vena cava. The risk of embolic dissemination and cardiocirculatory complications is decreased.


Successful extraction of intracardiac tumor thrombus of renal carcinoma.

Successful management of a patient with an intracardiac tumor thrombus of renal carcinoma is described. Important considerations in the management include precise localization of the upper limits of the tumor thrombus preoperatively, early ligation of the renal artery, control of the circulation through the inferior vena cava by temporary occlusion of the vena cava below the renal veins, the left renal vein and the hepatic circulation, and a team approach, using the expertise of the urologist and the cardiac surgeon, as well as cardiopulmonary bypass.


Spontaneous closure of ureterocolic fistula secondary to diverticulitis.

An 88-year-old woman with spontaneous closure of a ureterocolic fistula secondary to sigmoid diverticulitis is described. Initially, the patient was subjected to proximal transverse colostomy to divert the fecal stream. She was rehospitalized for a sigmoid colectomy, and left ureteral catheterization as well as a retrograde pyelogram showed spontaneous closure of the ureterocolic fistula. A review of the literature reveals that specific involvement of the ureter secondary to inflammatory bowel disease is rare. Most of the cases reported previously have alluded to active and radical measures. We do not recommend a radical resection in the acute stage, especially when the tissue planes may be obliterated owing to inflammation and difficulty in structure identification may lead to inadvertent injury.


Vesical endometriosis in a postmenopausal woman: a case report.

A case of endometriosis of the bladder extending into the bowel in a postmenopausal woman is reported. The origin of the tissue is mere conjecture. Five years before the onset of bleeding the patient had had an abdominal hysterectomy that may have seeded the adjacent vesical and small bowel tissue. It is hypothesized that the exogenous estrogen stimulated this tissue until it penetrated the bladder mucosa.


Malacoplakia associated with transitional cell carcinoma of bladder.

Malacoplakia is an uncommon granulomatous condition, usually involving the bladder but occasionally affecting other organs. A case of malacoplakia associated with transitional cell papillary carcinoma of the bladder is reported. This association has not been documented previously.


Focal infarction of the testicle in a child simulating testicular tumor.

Enlargement of an undescended testicle in a 6 1/2-month-old-child resulted in radical orchiectomy. Pathological diagnosis was focal infarction of the testicle. This disorder must be considered in the differential diagnosis of testicular enlargement in the infant and child.


Sarcoidosis and testicular neoplasm: an unusual association.

A case of sarcoidosis of the mediastinal lymph nodes with concomitant teratoembryonal carcinoma of the testis is presented. It is important to differentiate these entities from mediastinal metastases of testicular tumors and testicular sarcoidosis, respectively. We favor mediastinal biopsy in appropriate cases, in addition to testicular exploration.


Secondary testicular tumors.

A case of bilateral testicular metastases from carcinoma of the colon is reported. A review of the literature on secondary testicular tumors reveals their rarity and speculation is made as to the routes of metastases.


Case report: dermatomyositis of the scrotum.

Necrotic lesions of the scrotum usually result from infectious processes, vascular occlusion or trauma. The first case of necrotic non-purulent skin changes associated with dermatomyositis is reported.


Scrotal panniculitis in the prepuberal male patient.

A case of unilateral panniculitis with fat necrosis of subcutaneous scrotal fat tissue is reported. The typical presentation is that of unilateral or bilateral swelling, pain and a palpably tender mass in the scrotum located beneath the testicle. Conservative, non-operative treatment is successful.


Androgen therapy of a varicocele.

A case of asthenospermia and decreased semen volume with consequent infertility is reported. The patient had large bilateral varicoceles but refused an operation. Significant improvement of volume and motility occurred after treatment with fluoxymesterone and pregnancy was achieved.


Pheochromocytoma of the spermatic cord: a case report.

A case of pheochromocytoma arising from the left spermatic cord in a 52-year-old man is presented. The tumor had been present for about 10 years without hormonal symptoms. A diagnosis of pheochromocytoma was presumed because of a marked elevation of blood pressure at operation.


A study of cognitive and technical skill deterioration among trained paramedics.

Thirty trained paramedics were studied to measure cognitive and technical skill deterioration 6 to 30 months after completion of their individual training programs. The group of 30 paramedics included those with six months and those with one year of training. The purpose of the study was to identify areas in need of continuing education and to see if the rate of skill deterioration correlated with the time from completion of the training program. The trained paramedics were given the same final written and technical skill examination they had taken at the end of their training and the individuals' two scores were compared. The skills requiring the most technical knowledge deteriorated the fastest. Also, basic skills, despite frequent use in the field, had deteriorated. The amount of skill deterioration was greatest among the group of trained paramedics that had completed their training 30 months prior to this study.


Comparative analysis of emergency department treatment of patients with chest pain.

A vital function of the emergency physician is separating patients with chest pain who require intensive immediate treatment from those who require minimal care. The care of 701 patients presenting with chest pain in two Baltimore hospitals was evaluated using medical record data and follow-up questionnaires to discharged patients. Twenty per cent were admitted. There was a significant difference between the two hospitals in admission rates. Thirty-five per cent of the discharged patients felt no better two weeks after emergency department discharge. Plans for further research include a study to clarify the difference in admission rates and the characteristics of individuals who remained symptomatic at two weeks.


Patterns in the number of patients seen hourly in a community hospital emergency department.

The hourly and daily patient load data from Tri-City Hospital was analyzed using statistical and graphic analysis for the period between April 1, 1976 and October 31, 1976. This analysis revealed repetitive patterns in the patient load data, both in the daily data, with a seven-day cycle peaking on Saturday or Sunday, and the intraday data with a bimodal daily cycle with peaks between 10:00 am and 1:00 pm, followed by a high evening peak between 7:00 pm and 8:00 pm. Methods were introduced which, by simple calculation, can determine these cycles and those deviant days that exceed the norm early in the day.


[Statistical methods in medicine: in instruction, consultancy and research (author's transl)].

This survey covers the use of statistical methods in three areas of medicine: (1) the obligatory instruction of students in statistics, (2) the statistical consulting of clinicians and their candidates for a doctor's degree and (3) the modification and creation of statistical methods by the statisticians in the departments of medical statistics and documentation. Moreover some factors are discussed that reduce the effectiveness of statistical consulting, may it be service, advisory work or collaboration. Other sections of this paper cover the calamity of utilization and evaluation of old clinical records, the avoidance of fallacies and of errors committed by the inappropriate and incorrect application of statistical methods in medicine. Supplementary questions are given as a "first help" in tackling problems in medicine.


[Diagnostic procedures in hereditary fructose intolerance (author's transl)].

In order to diagnose hereditary fructose intolerance up to now, there were only the dangerous fructose-load and the biochemical evidence of this metabolic defect from biopsies of liver, intestine or kidney. Since there are no screening tests nor tests for heterocygote carriers or prenatal diagnostic procedures, we tested a simple method to determine serum activities of the two enzymes concerned in this defect (fructose-1-phosphate aldolase, fructose-1,6-diphosphate aldolase). Even in completely healthy children we could measure both activities in a good range. Children with known liver lesion caused other than HFI had significantly increased activities of both enzymes. In 4 cases with HFI we could not measure any activity of fructose-1-phosphate aldolase and a decreased activity of fructose-1,6-di-phosphate aldolase in serum, despite an apparently damaged liver. We propose to define those two serum activities in any case of an obscure liver lesion, frequent vomiting and postprandial hypoglycemia in early childhood, in order to exclude HFI or to demonstrate its possible presence.


[The role of inter-alpha-trypsin-inhibitor (concentration of serum of childhood) (author's transl)].

The feeble monovalent, humoral protease inhibitor inter-alpha-trypsin inhibitor has to be regarded as inhibitogen for different secretory, low-molecular, polyvalent inhibitors. Kallikreine acts as inhibitor-releasing enzyme. The inhibitor levels in the serum were determined for children of different ages. Contrary to adult patients not showing a lack of inhibitogen as consequence of the disease, inhibitogen insufficiencies are rather frequent, particularly for prematures and newborns with respiratory distress and inflammatory diseases. Obviously, in early childhood the production of inhibitogen is not yet in full progress. In case of increased inhibitor consumption or excessive kallikrein consumption this condition results in an inhibitogen insufficiency.


[Individual reaction to stress with former concentration camp immates (author's transl)].

The individual disposition to react to different stressors to play an important role in an extreme stress situation, i.e. the incarceration in concentration camps. Ten to fourteen years after their liberation, 219 former concentration camp inmates now living in Bavaria, New York and Israel were given semi-structured interviews. Since no statistically significant correlations between psychic and somatic complaints and incarceration could be found, we computed a factor analysis on illness dimensions. We found high correlations between these and the stress induced by concentration camp incarceration. An important answer to the above mentioned questions was the fact that there was no homogeneous reaction syndrome, such as it has always been described in the literature on concentration camp syndromes. We found four patterns of delayed reaction to stress. According to the contribution of somatic and psychic complaints, the factors were named as follows: 1. psycho-physical syndrome, 2. internal disease, 3. gynaecological illness, 4. psychic (social) syndrome. Personality factors played an important role in the development of these syndromes, because they modified the degree of stress endured. Personality factors were shown to be dependent on life history. The importance of these results for mastering stressors is being discussed.


[State of rat liver and spleen DNA after space flight on the "Cosmos-605" satellite].

The effect of space flight on the content of nucleic acids and the structure of DNA in the rat liver and spleen was studied. The 22-day exposure did not influence the DNA content in tissues, whereas the RNA content decreased by 14% and 19% in the liver and spleen, respectively. The flight did not induce changes like one-stranded or paired breakages in the DNA structure. Studies of the liver showed a minor trend towards a fall of elastic viscosity of the DNA supermolecular structure (difference between the flight and control rats was statistically insignificant). The above changes in the state of nucleic acids in the liver and spleen were transient.


[Medical provisions for the immediate post-flight period following long space flights].

At the final stage of long-term space flights first aid should be rendered in a specific way in cases of critical situations. Resuscitation and anesthesiology measures should be applied, if necessary, after study of flight-induced changes in the vital organs and systems. The paper describes the most important factors that should determine the tactics of resuscitation-anesthesiology support of the immediate postflight stage, if theoretically feasible acute life-endangering states develop. It also presents substantiated correction of routine clinical protocols of resuscitation aid.