Comparison of therapy in severe systemic lupus erythematosus employing stratification techniques. Randomized studies, attempting to clarify the role of combined azathioprine and prednisone therapy versus prednisone alone in severe systemic lupus erythematosus have sustained rather than mollified a clinical controversy. No differences have been detected in some studies, while others have appeared to show benefit with addition of azathioprine. The present study suggests that neither small random trials nor uncorrected clinical experience can be expected to provide truly comparable control groups in conditions as variable as systemic lupus, but that stratification techniques can yield relatively similar groups. Patients meeting different entry characteristics are demonstrated to come to different outcomes. Depending upon the specifications of a subgroup, one therapy or another appears better.


Arthritis inflammation monitored by subcutaneous millimeter wave thermography. A new technique for remote, noninvasive mapping of temperature elevations of the human joints is described; it uses the mm wave radiation emitted by the human body. A solid state switched scanner for 68 GHz is described which overcomes the depth limitations of conventional, infrared thermographs and can measure to subcutaneous depths of several mm with a temperature resolution of 0.25 degrees C. Measurements on rheumatoid arthritic knee joints are presented which show little correlation with simultaneously measured skin temperatures. Significant longterm thermographic changes induced by steroid injection indicate a potential for objective patient monitoring and development of new treatment methods.


Auranofin: an oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. Auranofin, an oral chrysotherapeutic agent, administered at 3.0 mg. b.i.d., p.o. to eight rheumatoid arthritic patients produced improvement in objective and subjective clinical signs, as well as biochemical and immunological parameters. Adverse effects reported were minimal and generally limited to gastrointestinal disturbances. During auranofin administration, gold concentrations in the blood gradually increased to a mean level of 0.70 microgram Au/ml by week 12 of treatment. Daily oral administration of auranofin appears to provide constant blood gold levels over longer periods of time compared to existing parenteral gold therapy and may provide an improved method of controlling chrysotherapy in rheumatoid arthritic patients.


The ultrastructure of urate crystals in gout. Using correlative scanning and transmission electron microscopic techniques, we studied the ultrastructure of natural and synthetic monosodium urate crystals. The internal architecture of both natural and synthetic urates consists of an interconnecting electron lucent network. This network is different in crystals from tophi, suggesting crystal formation about an electron lucent nidal matrix. Urate crystals from articular cartilage surfaces have smooth faces supporting the hypothesis that acute goat is a two phase process involving first the precipitation of urate crystals in the synovial fluid and second the adherence to the crystals of proteins and cells with the consequent inflammatory response.


Pachydermoperiostosis: studies on the synovium. Pachydermoperiostosis (primary hypertrophic osteoarthropathy) is a familial disorder characterized by clubbing, periosteal bone changes, and furrowing of the skin. A 40 year old male with this syndrome and chronic arthritis was recently studied. The synovial fluid was non-inflammatory. Histologically the synovium exhibited hyperplasia and microvascular alterations. Immunofluorescent staining failed to identify deposits of immunoglobulin. Electron microscopy revealed multilayered basement laminae around small subsynovial blood vessels but no electron-dense deposits as described in studies of hypertrophic pulmonary osteoarthropathy. The pathogenesis is obscure and appears to be non-immunological.


Exacerbation of mixed connective tissue disease during Salmonella gastroenteritis--serial immunological findings. A patient with mixed connective tissue disease is described who developed fever and polyserositis after the onset of Salmonella gastroenteritis. Antiribonucleoprotein antibodies, serum complement, and circulating immune complexes were studied quantitatively throughout the course of her illness. If the Salmonella infection were responsible for the exacerbation of mixed connective tissue disease, as the sequence of events suggests, the mechanism appeared to involve deposition of previously circulating immune complexes in affected tissues.


Report on pilot study of treatment of breast cancer by quadrantic excision with axillary dissection and no other therapy. This paper is a report on a pilot study designed to test the hypothesis that with a negative node status minimal surgery and conservation of the breast is indicated. The preliminary figures giving the recurrence rate and survival time tentatively suggest that this is true.


Shifting genetic patterns in anencephaly and spina bifida. The long-term decline in the incidence of the neural tube malformations, anencephaly and spina bifida (ASB), ended in the mid-1950's in New York State. Since that time, the rate of these birth defects has remained between 1 and 1.5/1000 births. In this low incidence population, we tested the basic tenets which support a genetic aetiology. We found that the full sib recurrence rate (1.8%) was higher than the half sib recurrence rate (0.8%) and the twin concordance rate (6.8%) was higher than the full sib recurrence rate. We found the incidence of ASB in twins to be the same as the incidence of ASB in singletons. Our findings are compatible with polygenic inheritance aetiology for ASB. The genetic molecular pathway of these birth defects may be identifiable through biochemical screening of families with one or more ASB children.


Use of overlapping normal distributions in genetic counselling. If a numerical variable can be assumed to be normally, but differently, distributed in each of two or more populations, then for an 'unknown' individual whose numerical value is known the relative probability of his belonging to each of the populations can be simply calculated. We briefly review the method and its application in genetic counselling.


Genetic counseling of consanguineous families. Use of Smith's method to calculate recurrence risks in multifactorial inheritance in consanguineous matings. A modification of Smith's method is described for deriving recurrence risks for multifactorial conditions when parents are related. Using cleft palate as an example, the possible increased risks caused by consanguinity are discussed.


Unusual inheritance of Becker type muscular dystrophy. A family with Becker type muscular dystrophy is described, in which two females were severely affected, giving the family tree the appearance of dominant inheritance.


Hereditary brachydactyly with nail dysplasia. A family is described in which sometimes asymmetrical brachydactyly, with nail dysplasia of the involved fingers, has been transmitted through 6 generations affecting 6 males and 15 females. The thumbs and feet have been normal. This previously unreported condition is inherited as an autosomal disorder with full penetrance and variable expressivity, and causes only minor inconvenience.


Recessively inherited costovertebral segmentation defect with mesomelia and peculiar facies (Covesdem syndrome): A new genetic entity? Two sibs of a consanguineous mating are described. Both have a gross costovertebral segmentation defect affecting nearly all the thoracic vertebrae, and mesomelia of the limbs, with the upper limbs being obviously more affected than the lower. The facial appearances of the two are identical, with hypertelorism, depressed nasal bridge, large bony upper lip, constantly open mouth, and peg-like teeth. We believe this combination has not been described before and represents the effect of a 'new' recessive gene. We would like to name this combination Covesdem syndrome (costovertebral segmentation defect with mesomelia).


A new type of chondrodystrophic mutant in the mouse. Stumpy is a new chondrodystrophic mutant in the mouse. The condition is inherited as a fully penetrant Mendelian recessive, and is not allelic with brachymorphic, achondroplasia, or stubby-three similar, previously described mutants. No chromosomal position has yet been assigned to the gene. Phenotypically, stumpy mice are chondrodystrophic dwarfs with all cartilage-formed bones in the skeleton affected. The condition differs from the usual chondrodystrophy described in mice in that proximal elements in the limbs are affected more than distal ones.


Fertility in 47,XXX and 45,X patients.

Fertility in 47,XXX and 45,X patients. Female patients with a sex chromosome abnormality may be fertile. In patients with a 47,XXX cell line there appears to be an increased risk of a cytogenetically abnormal child but the extent of this risk cannot yet be determined; it is probably lower in the non-mosaic 47,XXX patient than the mosaic 46,XX/47,XXX one. Patients with a 45,X cell line rarly become pregnant, and when they do they appear to have a high risk of an abnormal child or repeated unsuccessfuly pregnancies; this risk is certainly exaggerated by the method of reporting; when the poor reproductive perforamcne is first identified leading to the recognition of the maternal cytogenetic fault, the reproductive failure rate is naturally high; when the maternal fault is first identified and the reproductive history then established far better results are evident.


Significance of detection of extra metacentric microchromosome in amniotic cell culture. A metacentric bisatellited microchromosome was detected in all metaphases from an amniotic culture performed because of maternal age. A wide-ranging survey of the literature failed to disclose any consistent anomaly associated with such a marker, but did reveal that the clinical picture of patients manifesting it could range from complete normality through mental retardation to a variety of deformities. The parents elected for termination, and the only deformity detected in the abortus was fixed talipes equinovarus. The implications of the finding of this marker chromosome on amniocentesis, believed to be reported for the first time here, are discussed particularly in the context of genetic counselling.


Partial trisomy for short and long arm of chromosome no. 5: Two cases of two possible syndromes. We report 2 patients from different families with malformation-retardation syndromes caused by a partial trisomy of the long and of the short arm of chromosome 5, respectively (case 1: 46,XX,der(3),t(3;5)(p27;p13)mat; case 2: 46,XY,der(22),t(5;22)(q33;q13)pat). Several members of these families were balanced translocation carriers. Our cases are compared with those cited in the literature. The possibility of delineating a 5p- and a 5q-partial-trisomy syndrome is discussed.


Partial trisomy 18 in a family with a translocation (18;21)(q21;q22). A family is described in which 2 sibs had similar congenital abnormalities. Chromosome investigation of the mother and another child disclosed they were carriers of a translocation t(18;21)(q21;q22). The karyotype of one of the abnormal infants was determined and was found to be consistent with partial trisomy 18,46,XY,-21,+der (21),t(18;21) ((18pter leads to 18q21::21q22 leads to 2 lqter)mat.


De novo simultaneous reciprocal translocation and deletion. A female infant with severe mental retardation, general hypotonicity, and a history of generalised oedema, cyanosis, heart murmur, and nystagmus in the first days of life was found to have both a translocation and a deletion. Her karyotype was 46,XX,del(21)t(18;21)(18p ter leads to 18q11::21q21 leads to 21qter;21pter leads to 21q11::18q11 leads to 18q ter). The karyotype of both parents was normal. The proposita is the result of a three break point exchange and is monosomic for part of the dark band q11 q21 of chromosome 21. It is suggested that in cases with mental retardation and apparent balanced de novo reciprocal translocation a small undetected deletion in one of the chromosomes involved in the translocation could explain the mental retardation.


Y autosome translocation and complex chromosome rearrangement in cri du chat syndrome. An unbalanced Y autosome translocation t(5;Y) and an apparently balanced translocation t(2;13) are identified with the Q and R banding in a 7-year-old boy with severe encephalopathy and a multiple malformation syndrome. At birth, the clinical diagnosis of 'cri du chat' syndrome based on the characteristic crying was not confirmed after karyotyping, using conventional staining techniques.


Erythropoietic protoporphyria, heterozygous cystinuria, and reduced peptidase A activity in a patient with 46,XX/46,XX,18q--mosaicism. An interesting patient with a deletion of the long arm of chromosome 18 is presented. Her symptoms are severe in comparison with some other 18q--patients, yet she was found to have a mosaicism with a normal 46,XX karyotype in about 20% of her cultured lymphocytes. In addition, she had erythropoietic protoporphyria, was heterozygous for type II or III cystinuria, and had reduced levels of peptidase A activity. Detailed studied on the patient, her family, and two additional 18q--patients suggest that the association with erythropoietic protoporphyria is coincidental and that the cystinuria gene was inherited from the patient's father. The reduced peptidase A activity, however, supports earlier observations that the peptidase A locus maps in the q22 to terminus region of chromosome 18.


Familial radioulnar synostosis.

Familial radioulnar synostosis. A family with proximal radioulnar synostosis segregating in three generations is described. Familial radioulnar synostosis is a rare anomaly; however, the sporadic form is a frequent feature in cases of sex chromosome abnormalities and other syndromes. This disorder has been reported in several ethnic groups, but this is apparently the first example from the black population.


Cleft palate and accessory metacarpal of index finger syndrome: possible familial occurrence. A case of cleft palate and accessory metacarpal of index finger syndrome is described and related to the presence of Pierre Robin syndrome in a stillborn sibling. The significance of this relationship is discussed.


Some predictive implications of premedical scientific competence and preferences. Current medical school admissions criteria favor candidates with superior scientific aptitude and strong interests in scientific subjects. Four measures of this cluster were studied: Medical College Admission Test Science subtest scores, premedical grades in scientific subjects, preference for scientific subjects, and an equally weighted composite of these three. In a sample of 1,135 medical school graduates the four predictors were moderately related to academic performance in the first two years of medical school but almost completely unrelated to performance in the fourth year and to faculty ratings of general and clinical competence. The scientifically oriented graduates tended to enter specialties such as anesthesiology, pathology, and surgery, whereas graduates ranking lower on the overall index showed a slight tendency to prefer internal medicine, pediatrics, and psychiatry. Ratings and adjectival descriptions of premedical students with above average scores on the four measures revealed them to be narrower in interests, less adaptable, less articulate, and less comfortable in interpersonal relationships than their lower scoring peers.


Medical education for practice in nonmetropolitan areas. A study of patient records sampled from the office practices of 28 family practitioners and general surgeons in a 16-county nonmetropolitan area revealed that a sizable percentage of the diagnoses of problems encountered by family practitioners concern conditions the management of which is primarily taught on a residency service other than family practice, internal medicine, or pediatrics. Surgeons, conversely, are seeing a large percentage of patients with conditions the management of which is generally taught on a primary care residency service. Data from office records were augmented by interview responses of 32 family practitioners and general surgeons to questions about the training that family practice and general surgical residents should receive if they are to be well prepared for practice in nonmetropolitan areas.


A conceptual model for attitude assessment in all areas of medical education. In most medical schools attitudinal goals are confined to special courses in the curriculum and, as such, remain isolated. Failure to attend to both psychosocial and physical factors of disease are compounded by faculty failure to integrate both principles into teaching strategies. Here a conceptual model is proposed to ensure that psychosocial factors, age, and physical illness are all considered in the planning of educational units. Examples are given of skill impairment pitfalls that, when included in a patient-management problem (PMP), allow faculty to assess potential student attitudinal bias and identify students for additional learning experiences. Further application of this model can help educators plan course work in order to narrow the present gulf between the physical and behavioral sciences.


A prototype 'fifth pathway' program for Americans studying abroad. A problem of American citizens studying medicine abroad is reviewed along with that of foreign medical graduates who are foreign nationals, and a prototype "fifth pathway" program is briefly described. The objective of the program is the return of qualified American students who study medicine abroad to the mainstream of contemporary American medical education and the preparation of these students for further graduate education and the fulfillment of responsible roles in the delivery of health care.


Attitudes of a sample of California physicians toward criteria of high-quality care. The criteria of high-quality care as determined by a sample of practicing Californian physicians were analyzed. In addition, the effects of year of graduation and specialty choice were examined relative to choice of criteria. As a group these physicians perceived the cognitive competencies of the doctor, the traditional doctor-patient relationship, and the outcome of treatment as the essential ingredients in high-quality care. They paid considerably less attention to criteria reflecting sensitivity to costs, geographic availability of care, and differences in cultural expectations regarding care. Specialty choice exerted very little influence on the selection of criteria; year of graduation from medical school was more influential. Physicians graduating in 1970-71 were more sensitive to the place of preventive medicine in ensuring quality as well as more aware of social and economic factors affecting care.


The professional values and expectations of medical students. This paper, presenting the findings from a 1975 survey of first-year medical students in the state of North Carolina, describes medical students' professional orientations by focusing on specific values and expectations which may have relevance for health care problems. The professional orientations concern four problem areas: physicians' relationships with patients, political and economic change in the medical profession, the treatment of women physicians and patients, and geographic and specialty maldistribution of physicians. The data suggest that incoming medical students are concerned with helping people but not necessarily through political means, committed to some geographic and specialty areas of patient need, choosing medicine for reasons other than economic rewards but not opposed to physicians' large income and status, and somewhat unaware of discrimination toward women physicians and patients.


Performance documentation: how to confirm a resident's progress. Family medicine faculty members are accountable for the quality of training and the level of proficiency that residents attain. Determination of board certification and hospital privileges is dependent on technical and affective skills as well as cognitive testing. Self-evaluation and self-education behaviors will result from placing the responsibility for documentation of satisfactory performance with the resident. "Performance documentation" is defined as those parts of an evaluation system combining a cumulative record of patient care experiences with proficiency ratings indicating performance at or above the criteria specified in a program's behavioral objectives.


An ambulatory training model for an obstetrics and gynecology residency program. An important educational objective of an obstetric-gynecologic residency program is to provide an ambulatory experience from which residents can develop attitudes and skills that will enable them to provide high-quality comprehensive care to their patients. Often traditional outpatient clinics hold second-class positions in a training program, with surgical or obstetrical procedures being more highly valued experiences. From the patients' point of view many of these clinics are uncomfortable, noisy, and unattractive; and the patients in many instances receive depersonalized, discontinuous care. There is, therefore, a pressing need to implement efficient strategies to meet the increasing community demands for outpatient services while at the same time providing an innovative and effective ambulatory experience for residents. This paper describes how in a cooperative effort between a hospital's Department of Ambulatory Services and Department of Obstetrics and Gynecology these educational objectives were successfully integrated with those of continuous and comprehensive patient care.


Nucleoside transport in mammalian cell membranes. III. Kinetic and chemical modification studies of cytosine-arabinoside and uridine transport in hamster cells in culture. Transport of the nucleoside analog cytosine-arabinoside (CAR) in transformed hamster cells in culture has been studied in conditions of minimal metabolic conversion. Uptake (zero-trans in) properties at 20 degrees C over a limited range of CAR concentrations were characterized by a Km of 350 micrometer and a maximal velocity (V) of 780 micrometer.min-1 (V/Km = 2.28 min-1). Equilibrium exhcange at 20 degrees C over a wider range of concentrations was best described by a saturable component with a Km of 500 micrometer and a v of 1230 micrometer.min-1 (V/Km = 2.26 min-1) and either a saturable component of high Km or a nonsaturable component of k = 0.3 min-1. For the saturable component, the v/Km values were similar in both procedures. CAR transport was inhibited by various metabolizable nucleosides. Uptake of some of these nucleosides was inhibited by CAR. CAR transport and uridine uptake were inhibited in a reversible but partially competitive fashion by high affinity probes like S-(p-nitrobenzyl-6-mercaptoinosine (NBMI) (Ki less than 0.5 nM) and in an irreversible fashion by SH reagents such as N-ethylmaleiimide (NEM). The organomercurial p-hydroxymercuribenzene sulfonate (pMBS) markedly stimulated transport of these nucleosides, but also markedly potentiated the inhibitory effects of either NBMI or NEM. The effects are interpreted either in terms of models which invoke allosteric properties or in terms of two transport systems which display distinct chemical susceptibilities to externally added probes.


Intracellular gradients of ion activities in the epithelial cells of the Necturus gallbladder recorded with ion-selective microelectrodes. In Necturus gallbladder epithelial cells the intracellular electrical potential, as recorded with microelectrodes, varied from -28 mV in the mucosal end to about -50 mV in the serosal end of the transporting cell. The Na+ activity varied concurrently from about 39 mM to between 8 and 19 mM. Thus, within the cell both the recorded electrical and chemical gradients caused Na+ to move towards the serosal end. Serosal addition of ouabain (5 X 10(-4) M) caused the intracellular Na+ activity to attain electrochemical equilibrium within 30 min. However, the intracellular electrical potential gradient was only slowly affected. In cells from animals stored at 5 degrees C, the Cl- activity varied from about 55 mM in the mucosal end to 28 mM in the serosal end, and the K+ activity from 50 mM to between 95 and 131 mM. Both ions were close to electrochemical equilibrium within the cytoplasm but were too concentrated to be in equilibrium with the mucosal solution. Bubbling CO2 through the mucosal solution caused the intracellular gradients to vanish. When Na+ in the bathing solutions was exchanged for K+, the intracellular electrical potential became roughly constant at about -5 mV. The Cl- activity became constant in 65 mM, and the K+ activity became constant at 109 mM, both close to equilibrium with the mucosal solution. The Na+ activity was reduced to about 1 mM. The ratio of cytoplasmic resistivities between cells bathed in K+-rich saline to cells bathed in Na+-rich saline was measured by means of triple-barreled electrodes and compared to the same ratio as assessed from the activity measurements. The two values were equal only if one assumes the mobility of Na+ inside the cell to be less than 1/10 of the mobility of K+ or Cl-. The same conclusion was reached by comparing the intracellular Na+ flux calculated from the gradient of electrochemical potential to that flux assess from the net solute absorption. Animals kept at 15 degrees C had lower intracellular Na+ activities, higher Cl- and K+ activities, and higher rates of absorption than animals stored at 5 degrees C. Finally, the degree to which the intracellularly recorded electrical and chemical potentials could reflect an electrode artefact is discussed.


Morphological factors influencing transepithelial permeability: a model for the resistance of the zonula occludens. Epithelial cells are joined at their apical surfaces by zonulae occludentes. Claude and Goodenough (1973) demonstrated a correlation between the structure of the zonula occludens as seen in freeze-fracture preparations and the passive electrical permeability of several simple epithelia. In epithelia with high transepithelial resistance, the zonula occludens consisted of many strands. In epithelia with low transepithelial resistance the zonula occludens was much reduced, sometimes consisting of only one strand. Evidence is reviewed here that indicates that in a number of simple epithelia the structure of the zonula occludens is largely responsible for the magnitude of transepithelial conductance. An equation is derived relating transepithelial junctional resistance to the number of junctional strands: R = RminP-N where R is the transepithelial resistance of the zonula occludens, Rmin is the minimum resistance of the junction (as when there are no strands in the zonula occludens), p is the probability a given strand is "open" and n is the number of strands in the junction. Using published experimental values of R and n for different epithelia, the calculated value of p was found to be as high as 0.4, which suggests that the strands in the zonula occludens are remarkably labile. Other morphological parameters relevant to transepithelial permeability are also considered, such as the width and depth of the intercelllar spaces, and the size of the epithelial cells themselves.


Interaction between cell sodium and the amiloride-sensitive sodium entry step in rabbit colon. Ouabain abolishes the short-circuit current (Isc) and decreases the transepithelial conductance (Gt) of rabbit colon. In contrast, amphotericin B elicits a maximum Isc and markedly increases Gt. However, in both instances the amiloride-sensitive Na entry step is completely blocked, presumably due to an increase in cell Na. Conversely, when Na-depleted tissues are suddenly exposed to 140 mM Na, the amiloride-sensitive Isc and the amiloride-sensitive component  of Gt (alphaGNa) increase abruptly to their maximum values and then decline to steady-state plateaus with a half time of approximately 6 min; throughout the decline (Isc/alphaGNa) = ENa is constant at a value of 95 mV. In the presence of amphotericin B, the Isc abruptly rises to the same maximum but does not decline. These findings indicate that in the presence of 140 mM Na the conductance of the amiloride-sensitive Na entry step can vary from a maximum value of approximately 1.6 mmhos/cm2 when cell Na is depleted, to zero when cell Na is abnormally elevated (e.g., in the presence of ouabain or amphotericin B). Our findings are consistent with a system in which the pathway responsible for transcellular Na transport parallels another cellular compartment with which it communicates. The Na capacity of the active transport pathway appears to be very small so that this compartment fills rapidly after exposure of Na-depleted cells to 140 mM Na, and active transepithelial Na transport is initiated and reaches steady-state levels quickly. The Na capacity of the second compartment is much larger; the Na content of this compartment appears to be responsible for the negative feedback effect on the permeability of the amiloride-sensitive entry step.


Cyanine dye structural and voltage-induced variations in photo-voltages of bilayer membranes. Flash illumination alters the voltage across bilayer lipid membranes in the presence of certain cyanine dyes. The waveforms of the photo-voltage vary systematically with dye structure and imposed transmembrane voltage. Experimental results are reported for 27 positively charged cyanine dyes, primarily oxazole derivatives, using lecithin/oxidized cholesterol bilayer membranes and 10-mM sodium chloride solutions. Several dyes do not induce any photo-voltages. Examples are 3,3' diethyl 9 ethyl 2,2' oxacarbocyanine iodide, 3,3' diethyl 2 oxa 2" thiacyanine iodide, and 3,3' dimethyl 2,2' indocarbocyanine iodide. Several dyes, when added to one side of the membranes, induce monophasic waveforms. Examples are 3,3' dimethyl 2,2' oxacarbocyanine chloride, and 3,4,3',4' tetramethyl 2,2' oxazalinocarbocyanine iodide. Other dyes induce a photo-voltage only if transmembrane voltages are imposed. These waveforms are biphasic with some dyes (3,3' diethyl 2,2' oxacarbocyanine iodide, for example) and monophasic with other dyes (3,3' dibutyl 2,2' oxacarbocyanine iodide, for example). The photo-voltage waveforms are explained by models that consider the movement of charged dye molecules within the membrane, following optical excitation. The dye movements are probably induced through charge rearrangements in the dye associated with long-lived triplet states, isomerization, or through excimer formation. These results provide information on the location and orientation of the dye molecules within bilayer membranes. The variations which occur in the waveforms with applied voltage indicate that these membranes are fluid in the direction perpendicular to the membrane plane.


Membrane potential and resistance changes induced in salivary gland acinar cells by microiontophoretic application of acetylcholine and adrenergic agonists. The effects of microiontophoretic applications of catecholamines and acetylcholine on parotid acinar cell membrane potential and resistance were investigated using intracellular microelectrode recording in superfused segments of mouse parotid or rat submandibular glands. Short pulses of acetylcholine and alpha-adrenergic agonists had similar effects, consisting of a marked decrease in membrane resistance accompanied by an initial depolization or hyperpolarization depending on the level of the resting membrane potential. This initial response was followed by a slow hyperpolarization occurring at a time when the resistance was increasing towards the prestimulation level. The equilibrium potential for the initial potential change caused by excitation of the cholinergic receptors was investigated directly by setting the membrane potential at different levels by injecting direct current and stimulating the same cell repeatedly with equal doses of acetylcholine. The equilibrium potential was found to be about -55 mV. The delayed hyperpolarization could not be reversed by passing hyperpolarizing current, but actually increased in size with higher membrane potentials. The minimum latency of the effect of acetylcholine or alpha-adrenergic agonists was 200-500 msec. Excitation of beta-adrenoceptors caused, after a long latency of several seconds, a small depolarization. Epinephrine induced a combined alpha- and beta-adrenergic response, with the alpha-component predominating. Blocking the alpha-adrenoceptors with phentolamine revealed the beta-adrenergic depolarization, while blocking the beta-adrenoceptors with propranolol caused the components of the alpha-adrenergic response to become more pronounced. All three receptors (alpha- and beta-adrenoceptors and cholinergic receptors) were present in individual acini.


Electron microprobe analysis of frog skin epithelium: evidence for a syncytial sodium transport compartment. For elucidation of the functional organization of frog skin epithelium with regard to transepithelial Na transport, electrolyte concentrations in individual epithelial cells were determined by electron microprobe analysis. The measurements were performed on 1-micron thick freeze-dried cryosections by an energy-dispersive X-ray detecting system. Quantification of the electrolyte concentrations was achieved by comparing the X-ray intensities obtained in the cells with those of an internal albumin standard. The granular, spiny, and germinal cells, which constitute the various layers of the epithelium, showed an identical behavior of their Na and K concentrations under all experimental conditions. In the control, both sides of the skin bathed in frog Ringer's solution, the mean cellular concentrations (in mmole/kg wet wt) were 9 for Na and 118 for K. Almost no change in the cellular Na occurred when the inside bathing solution was replaced by a Na-free isotonic Ringer's solution, whereas replacing the outside solution by distilled water resulted in a decrease of Na to almost zero in all layers. Inhibition of the transepithelial Na transport by ouabain (10(-4) M) produced in increase in Na to 109 and a decrease in K to 16. The effect of ouabain on the cellular Na and K concentrations was completely cancelled when the Na influx from the outside was prevented, either by removing Na or adding amiloride (10(-4) M). When, after the action of ouabain, Na was removed from the outside bathing solution, the Na and K concentration in all layers returned to control values. The latter effect could be abolished by amiloride. The other cell types of the epithelium showed under some experimental conditions a different behavior. In the cornified cells and the light cells, which occurred occasionally in the stratum granulosum, the electrolyte concentrations approximated those of the outer bathing medium under all experimental conditions. In the mitochondria-rich cells, the Na influx after ouabain could not be prevented by adding amiloride. In the gland cells, only a small change in the Na and K concentrations could be detected after ouabain. The results of the present study are consistent with a two-barrier concept of transepithelial Na transport. The Na transport compartment comprises all living epithelial layers. Therefore, with the exception of some epithelial cell types, the from skin epithelium can be regarded as a functional syncytium for Na.


The use of low temperature X-ray diffraction to evaluate freezing methods used in freeze-fracture electron microscopy. Two methods of freezing samples for freeze-fracture electron microscopy have been compared using X-ray diffraction and freeze-fracture results from lipid-water model systems. Perturbations of the molecular organization of hydrocarbon chains and the extent of ice crystal formation have been evaluated for lamellar phases of egg lecithin containing 16% water and egg lecithin-phosphatidylinositol containing 55% water, both freeze quenched in liquid Freon-22 near its melting temperature (113 K). Very thin samples sandwiched between copper sheets separated by an electron microscope grid show much less freezing induced structural rearrangement than small smaples contained on conventional Balzers-type gold planchettes. These results show that the rate of freezing in the very thin preparations is greater than in the conventional ones, which is probably due in part to the improved dissipation of heat from a poorly conductive sample through highly conductive copper sheets.


Structure determination of frozen, hydrated, crystalline biological specimens. Low temperature transmission electron microscopy can be used to study the structure of biological materials in the hydrated state. Spatial averaging techniques are necessary to overcome the radiation damage problems, and for this reason the techniques described are most applicable to crystalline objects. However, with thin, crystalline biological specimens there are no difficulties with preserving periodicity during the freezing process. Improved specimen preparation methods are described which achieve the production of very thin aqueous films with the hydrated specimen embedded in them. Defocused bright field images of frozen, hydrated protein crystals possess a surprisingly high contrast, presumably due to the difference in density of the protein and the aqueous phase. The techniques described have been used to study the crystal structure of hydrated catalase and the outermost cell wall of Spirillum serpens.


The direct measurement of temperature changes within freeze-fracture specimens during rapid quenching in liquid coolants. We have evaluated the cooling rates of specimens mounted in a variety of freeze-fracture holders when plunged into a series of liquid coolants. these rates were measured using miniature thermocouples placed within the mounted specimens. The most rapid cooling rates were obtained using propane at 83 K as the coolant. When mounted on a newly devised 'copper sandwich' holder, specimen cooling rates in excess of 4500 K/s have been recorded. A simple guillotine-like device for quenching freeze-fracture specimens under reproducible conditions is presented.


Stabilizing ultrathin cryo-sections by freeze-drying. Cryo-sectioning of specimens with high water content often proves to be especially difficult, as the sections of freeze-shocked samples with their minimal thermal capacity warm up easily. The resultant recrystallization of the included water causes considerable damage in the structure of the frozen specimens. The method described in this paper enables cryo-sections to be transferred from the microtome to a precooled high vacuum plant without contamination and at a temperature below the recrystallization point of ice. In this device the cold sections can be stabilized by freeze-drying, sandwiching or electron-bombardment for subsequent observation in the transmission electron microscope.


Instrumentation and specimen preparation for electron beam X-ray microanalysis of frozen hydrated bulk specimens. A cooling chain for the handling of frozen hydrated bulk specimens is described. Use of this method permits the specimen to be kept fully hydrated. After quench freezing, the specimen is transferred to a freeze etch apparatus, freeze fractured, carbon coated and transferred onto the precooled cold stage of the SEM by means of an airlock. The specimen is examined in the secondary electron mode and analysed using an energy dispersive X-ray analyser. The midgut of Chironomus thummi larvae and frog skin epithelium were used to test the performance.


Quantitative X-ray microanalysis of diffusible ions in the skeletal muscle bulk specimen. X-ray microanalysis in the scanning electron microscope (SEM) is used to obtain information about the distribution and mobility of electrolyte ions in the skeletal muscle tissue. In order to localize the diffusible ions in their physiological state, so far as possible, any chemical fixative is avoided. A special 'cooling chain' preparation method is applied which enables studies on cryofractured bulk specimens at low temperatures. Quantitation of the obtained X-ray spectra is done by the use of glycerol-treated tissue specimens which are incubated with electrolyte solutions of defined ion concentration.


Preparation of biological material for X-ray microanalysis of diffusible elements. II. Comparison of different methods of drying ultrathin cryosections cut without a trough liquid. The appearance of ultrathin, dry-cut cryosections of brown adipose tissue and liver was found to be strongly dependent upon adequate freeze-drying. If freeze-drying was inadequate, diffusion of substances could be demonstrated and freezing damage was not apparent. Diffusion was manifested as an electron dense film over structural features such as triglyceride droplet profiles and the edges of the section; when this film was thick, X-ray signals for P, S, Cl, K and Ca could be detected from it, in different proportions to those found in the section. The frequency and intensity of diffusion were lowered by decreasing the temperature in the cryochamber from about 200 K +/- 5 K to 163 K +/- 5 K by forced evaporation of liquid N2 using an extra heater. The lowest incidence of diffusion was obtained in conjunction with this device, by leaving the sections in the cryochamber for at least 2 h during drying, either over a drying agent or under moderate vacuum. Such sections showed a narrow zone (A) at the edge that lacked obvious ice-crystal damage, a thicker zone (B) of moderate ice-crystal damage and the bulk of the interior (zone C) severely damaged by freezing. Qualitatively different, reproducible X-ray spectra could be obtained from ultrastructural features even in areas showing some signs of diffusion.


Holographic microscopy of glycerination of Amoeba proteus. The process of glycerination of Amoeba proteus was observed under the holographic microscope with coherent noise elimination. It was found that during glycerination redistribution of cell material occurs, and is accompanied by reversible deformation of the cell cortex. The rôle of the cortex in shape maintenance in glycerinated models was demonstrated.


Direct deposition autoradiography: can it really be detecting radioactivity? The literature concerning the 'direct deposition method' of electron microscope autoradiography has been examined and certain calculations made. Studies have been made on the interaction of gold chloride with protein films, tissue sections and ultrathin sections. It is concluded that in its present form the direct deposition method does not offer an autoradiographic approach of practical value.


An electron microscopic study on the type I pneumocyte in the cat: pre-natal morphogenesis. This investigation describes the pre-natal morphogenesis of the type I pneumocyte subsequent to its differentiation from pulmonary epithelium. Cells lining subpleural alveolar septa were photographed from serial sections with the electron microscope, and a three-dimensional representation of each cell was obtained by transferring the contours of the cell membranes from montages to transparent plastic sheets which were then spaced to scale and stacked. The results of this study indicate that: The nascent blood-air barrier of a 50-day reconstructed cell was twice as thick as the average definitive barrier; definitive barrier thickness was observed in some areas in a 63-day reconstructed cell; the amorphous component of elastic tissue which appears peripherally in septal connective tissue during pre-natal morphogenesis may be directly juxtaposed to the basal lamina of the alveolar epithelium; the orientation of the cell junction between a pneumocyte and its neighboring cells, as observed in sections of alveolar septa, changes as the contour of the pneumocyte changes from simple abutment to overlapping patterns.


Oocyte development in the mouse: an ultrastructural comparison of oocytes isolated at various stages of growth and meiotic competence. An ultrastructural comparison of mouse oocytes isolated at various stages of growth and meiotic competence has been carried out. Progressive changes in the nucleoli, ribosomes, mitochondria, endoplasmic reticulum, Golgi complex, and other organelles and inclusions of the oocyte have been examined as a function of oocyte size by transmission electron microscopy. The observations presented support the idea that growth of the mammalian oocyte involves not just tremendous enlargement of the cell, but extensive alterations in its overall metabolism as reflected in the ultrastructure of the oocyte at various stages of growth.


Functional analysis of the shoulder girdle of cats during locomotion. The movements of the shoulder girdle of eight adult cats during overground stepping were studied, using standard slow motion cinematographic techniques. The patterns of activity of shoulder muscles were examined, using simultaneous intramuscular electromyography. Walking, trotting and galloping steps were analyzed from digitized single motion picture frame images. Angular movements of the shoulder girdle consist of biphasic flexion and extension of the shoulder joint and a monophasic flexion-extension alternation of the scapula on the thorax during each step cycle. In addition, the center of the scapula moves craniad during the swing phase and caudad during the stance phase with respect to a fixed reference point on the animal. Similar vertical movements of the center of the scapula also occur in each step cycle. Results of EMG studies of the 17 muscles capable of acting on the shoulder girdle indicate that three overall patterns of activity are found: (1) a pattern typical of extensor muscles, active during all the extension epochs; (2) a pattern typical of flexor muscles, active during the flexion epoch; and (3) a biphasic pattern of activity, active twice in each step. There data are used, along with a re-examination of previous models of the mechanics of the shoulder girdle of carnivores to examine the function and mechanics of shoulder motion. It is concluded that the rotary and translatory movements of the shoulder girdle during stepping combine to enhance step length.


Comparison of the densities of clonogenic cells from EMT6 fibrosarcoma monolayer cultures, multicell spheroids, and solid tumors in ficoll density gradients. The densities of viable EMT6 cells grown in vitro as monolayer exponential and plateau-phase cells or as multicell spheroids or in vivo as a solid tumor in BALB/c mice were determined with the use of isopyknic centrifugation in linear Ficoll gradients. Exponential cells banded at a density of 1.069 g/ml, whereas plateau-phase cells appeared at 1.073 g/ml. Cells grown as spheroids were more dense than the monolayer cells and were recovered mainly at 1.081. Solid-tumor cells, separated under the same conditions, banded at 1.080. Narrowing the range of the Ficoll gradient failed to resolve more than one band of cells in the solid-tumor separation. This provides evidence that the density of cells obtained from the spheroids is greater than that of the monolayer cells but agrees well with the density of the solid-tumor cells. Ficoll was demonstrated to be nontoxic to the cells, and plating efficiency assays showed similar cell viabilities between noncentrifuged and centrifuged cells. The plating efficiency of the peak fraction of exponential cells after centrifugation was 68%, and that of plateau-phase cells was 50%. Corresponding figures for the multicell spheroid and solid-tumor cells were 62 and 28%, respectively. The recovery of cells after centrifugation in the Ficoll gradients ranged from 62 to 83%. The effects of cell load and centrifugation time on the density distributions of the EMT6 cells were also investigated.


Effect of lucanthone hydrochloride on the radiation response of intestine and bone marrow of the Chinese hamster. A sublethal dose of 100 mg lucanthone hydrochioride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters [median lethal dose for 30-day survival (LD50/30) of 315 mg/kg] reduced the radiation tolerance of the small intestine and had little or no effect on the radiation tolerance of the bone marrow. Lucanthone hydrochloride was administered at various times before and after whole-body 60Co gamma-irradiation. The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively. The LD50/30, indicative of death from bone marrow stem cell depletion, remained unaltered at approximately 990 rads over the entire treatment scheme, which indicated that the radioresponsiveness of bone marrow stem cells was unaffected by lucanthone hydrochloride. The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation. Serum concentration of lucanthone hydrochloride in the Chinese hamster, determined spectrophotometrically, reached a peak of 8 microgram/ml by 1.5 hours post inoculation and then decreased exponentially with a half-life of approximately 6 hours, so that by 30 hours post inoculation it was unmeasurable.


Biochemical parameters of resistance of an adriamycin-resistant subline of P388 leukemia to emetine, an inhibitor of protein synthesis. The effects of emetine on protein and DNA synthesis in vitro and in vivo were compared in P388 leukemia cells (P388/S) and in an adriamycin-resistant subline of P388 leukemia (P388/ADR), which was completely cross-resistant in vivo to emetine. In P388/ADR cells in vitro no apparent resistance to emetine was found; no difference in cytotoxicity was evident in P388/S or P388/ADR cells exposed to emetine in vitro for 1 or 6 hours. Protein and DNA synthesis was inhibited to a similar extent in P388/S and P388/ADR cells at equivalent concentrations of the drug. However, inhibition of protein synthesis by emetine in P388/ADR cells was more reversible than in P388/S cells when the cells were exposed to emetine and subsequently incubated in drug-free medium for 1 hour prior to addition of labeled L-leucine. Differences between P388/S and P388/ADR cells were evident in vivo. The duration of inhibition (greater than 90%) of protein and DNA synthesis in P388/ADR cells was about 8 hours compared to 24 hours in P388/S cells following administration of a therapeutic dose of 25 mg emetine/kg to tumor-bearing mice. The level of radioactivity in the P388/ADR cells 24 hours after in vivo administration of the emetine analog, (+/-)-[3'-14C]2,3-dehydroemetine, was only 26% of that in P388/S cells. This evidence suggests that the resistance of P388/ADR to emetine is due to decreased retention of the drug.


Effect of phospholipids on maintenance of the cytotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in aqueous suspension. Although the chemotherapeutic agent 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) is highly unstable in aqueous suspension, polar glycerophospholipids, notably phosphatidyl choline, had a protective action on the drug's cytotoxicity in aqueous suspension. The cytotoxicity of CCNU against C-6 glioma cells in monolayer culture was maintained longer when the drug was preincubated in the presence of phosphatidyl choline (0.5 mg/ml) than when it was preincubated in medium alone or with serum or when other phospholipids were added. Preservation of drug action may have been due to the formation of common micelles between CCNU and the phospholipid. The importance of the lipid interaction to the effectiveness of the nitrosoureas in vivo is unknown, but such interaction could be a factor in the duration of drug action, its access to the central nervous system, and its attachment to cell membranes.


Immunity against MOPC 104E plasmacytoma: effects of tumor size and time post therapy on in vivo tumor immunity. BALB/c mice with the plasmacytoma MOPC 104E were cured of palpable tumors (6-15x10(7) cells) with a single injection of cyclophosphamide (10 mg/kg). Animals cured of tumor showed a considerable increase in their ability to reject secondary challenge with graded numbers of viable tumor cells. Mice with palpable subcutaneous tumors were cured therapeutically and rechallenged 22, 44, or 120 days post therapy. The ability of such animals to reject secondary tumor cell challenge was similar in all groups, which implied that in vivo tumor immunity remained relatively constant for at least 4 months post therapy. A second group of animals was treated therapeutically (10 mg cyclophosphamide/kg) 4, 11, or 20 days post tumor cell injection. These therapeutically treated animals were then rechallenged with various numbers of viable tumor cells 30 days post therapy. Mice given cyclophosphamide 4, 11, or 20 days post tumor injection rejected 6, 60, or 400 times as many tumor cells, respectively, as did control animals. These results implied that, over the range of tumor sizes investigated, exposure to greater amounts of tumor antigen resulted in increasing amounts of residual tumor immunity following cure.


Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice. Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carconogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in gamma-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H2O2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H2O2.


Cell-cycle-specific chromosome damage following treatment of cultured Chinese hamster cells with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl. The induction of chromosome damage in Chinese hamster (line CHO) cells by 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl (MAC) (NSC-141549) was studied in cell populations growing exponentially and at various stages of the cell cycle following release from isoleucine-deficient G1-arrest. Autoradiographic analysis demonstrated that cells in S-phase at time of drug addition (2 microgram MAC/ml for 2 hr) were delayed 8 hours before entering mitosis. Cells in G1 at the time of MAC treatment were not as severely delayed, which resulted in a rather sharp increase and decrease in a percent labeled mitosis curve. Chromosome damage occurred differentially during the cell cycle. Cells in late G2 during MAC treatment contained incompletely condensed chromosomes with occasional chromosome interchanges at the next mitosis. Early G2 cells were severely damaged (greater than 20 breaks/cell). Damage to cells in S or G1 at the time of MAC addition was less severe, whereas cells in G1-S traverse had intermediate levels of chromosome breaks. Thus MAC appeared to be particularly effective at times when chromatin was undergoing structural modifications (G1-S and S-G2 boundaries). Low concentrations of MAC (0.05 microgram/ml) increased the rate of sister chromatid exchange to almost eight times the background rate. The cellular effects of MAC were compared with previously reported studies of other antitumor agents.


Immunotherapy of bilateral lymph node metastases in guinea pigs by intralesional or paralesional injection of Mycobacterium bovis (BCG). Bilateral axillary lymph node metastases occurred after intradermal (id) injection of line 10 hepatocellular carcinoma cells over the thoracic spine of inbred guinea pigs. Excision of the dermal tumor 7 days after injection of tumor cells did not prevent the development of metastases. Injection of BCG into dermal tumors without surgery led to their regression and prevented the growth of microscopic metastases in both right and left superficial distal axillary lymph nodes. Bilateral id injection of BCG between the dermal transplant and each of the regional lymph nodes followed by excision of the dermal tumor also prevented progression of metastases. Unilateral id injection of BCG before excision of dermal tumors failed to retard metastases in contralateral superficial distal axillary lymph nodes. These results suggested that elimination of microscopic lymph node metastases required delivery of adjuvant to or near each metastatic site. Systemic tumor immunity alone may be inadequate to eradicate lymph node metastases.


Tumorigenic effect of an organomanganese compound on F344 rats and Swiss albino mice. Trioctanoin suspensions of manganese dioxide and manganese powder were injected im into inbred F344 rats and Swiss albino mice. The manganese powder was also administered orally to the rats. No difference in tumor incidence was noted between treated and control animals. In contrast, manganese (manganous) acetylacetonate administered im to rats produced a statistically significant number of fibrosarcomas at the sites of injection.


Sister chromatid exchanges and growth inhibition induced by the flame retardant tris(2,3-dipromopropyl) phosphate in Chinese hamster cells. The effects of the flame retardant tris(2,3-dibromopropyl) phosphate (Tris-BP) on growth, sister chromatid exchanges (SCE), and chromosome aberrations of Chinese hamster V79 cells cultured either in vitro or in diffusion chambers (DC) implanted into mice were studied. Tris-BP caused a dose- and time-dependent reduction of cell growth as measured by colony-forming activities. A significant dose-dependent increase in SCE was observed in V79 cells either in the cultures treated with Tris-BP or in DC in mice given injections of the chemical. In contrast, Tris-BP in V79 cells in culture, in V79 cells in DC in mice, in two human lymphoid cell lines, or in mouse bone marrow cells in vivo did not significantly increase chromosome aberrations.


Effects of progesterone on human endometrial carcinoma cells in vivo and in vitro. The effects of progesterone on the growth and differentiation of human endometrial adenocarcinoma cells (cell lines SNG-P and SNG-M derived from primary and metastatic tumors, respectively) were assessed in vitro and in vivo. Progesterone suppressed their growth and induced cell differentiation in vitro. The suppressive effect of progesterone was stronger in the primary tumor cells than in the metastatic ones. Progesterone produced morphologic changes such as multinucleation, multinucleolation, vacuolation, extensive Golgi apparatus, and papillary arrangement of cells. The cells were transplanted sc into nude BALB/c mice where they produced undifferentiated adenocarcinomas in untreated mice and well-differentiated adenocarcinomas in progesterone-treated ones. Progesterone reduced tumor growth and decreased transplantability in nude mice. This hormone produced no change in the distribution of the chromosome numbers or in the karyology.


Estrogen profiles in young women: effect of maternal history of breast cancer. To examine the hypothesis that familial breast cancer risk is related to estrogen metabolism, we analyzed urines of daughters of breast cancer patients and their matched controls for estrone (E1), estradiol (E2), and estriol (E3). From this, we computed estriol proportions (E3/E1 + E2 + E3). "Patient-daughters" and the matched controls showed no differences in estriol proportions. Our results failed to support the hypothesis that high-risk women (those with a family history of breast cancer) have relatively lower estriol proportions, and we concluded that whatever family history contributes to breast cancer risk, that risk is not likely to be transmitted by the estrogen profile.


Incidence of endometrial carcinoma in King County, Washington: a standardized histologic review. Previously diagnosed tumor specimens from 35- to 74-year-old female patients with endometrial cancer who were residents of King County, Washington, during the first 6 months of 1975 were reviewed by a single pathologist using uniform criteria for the assessment of cancer. Routinely reported incidence of this tumor in this population was judged to be inflated, the annual incidence rate (excluding carcinoma in situ) falling from 108.2 to 88.5 per 100,000 women after the exclusion of cases found not to be unequivocally malignant. This rate nonetheless represented a large increase over the rate of 47.3 per 100,000 observed in the U.S. Third National Cancer Survey just 5 years earlier. We concluded that U.S. pathologists in the 1970's may have been using more liberal criteria by which to diagnose endometrial cancer, but that such a change could only account for a small part of the rising incidence of the disease.


The continuing challenge of duodenal injuries. Thirty-four cases of duodenal trauma, 23 caused by gunshot wounds, are reviewed. All but three patients had associated major organ injuries, a total of 97 injuries. Postoperative mortality was 14% for injuries into the duodenal lumen. Techniques for operative repair included simple primary closure, use of omental or serosal patches, controlled fistula with a duodenostomy tube, decompressive and feeding ostomies, "diverticulization", segmental duodenal resection and anastomosis, and total duodenectomy and pancreatectomy. It is emphasized that the surgeon finding duodenal injury must be familiar with all of these techniques, each of which has its indications. Treatment of duodenal injuries perhaps more than any other bowel trauma must be individualized.


Blunt maternal trauma: a review of 103 cases. One hundred three pregnant women hospitalized following blunt trauma had injuries classified as: major (20%); minor (17%); or significant (63%). Maternal mortality related only to the severity of maternal injuries: 24% of women who sustained major injuries died. Pregnancy ended unsuccessfully in 18% of all women with known pregnancy outcome. The incidence of unsuccessful pregnancy was 61% following major injuries and 27% following minor injuries. Insignificant maternal injuries did not affect pregnancy outcome. Fetal survival did not relate to gestational age per se. Pregnancy uniformly ended unsuccessfulla in the presence of maternal death, placental injury, uterine injury, and direct fetal injury, and occurred in 80% of women admitted in hemorrhagic shock. An understanding of the ways that the anatomic and physiologic changes of pregnancy alter the nature and frequency of maternal injuries and that maternal response to injury is altered is essential. The best chance for fetal survival is to assure maternal survival.


Brain death, apneic diffusion oxygenation, and organ transplantation. This paper presents a simple method of maintaining good donor organ oxygenation during a prolonged test of apnea used to determine brain death prior to cadaver transplantation. Apneic diffusion oxygenation can maintain arterial pO2 above 200 torr for periods exceeding 15 minutes, thereby allowing a more definitive determination of brain death without concomitant tissue hypoxia and possible damage to donor organs.


Open pelvic fracture: a lethal injury.

Open pelvic fracture: a lethal injury. Twenty-two of 604 patients (4%) with pelvic fracture (PF) had open fractures. Eight per cent of all pedestrian and motorcycle accidents resulted in open PF, compared to 0.8% of all vehicular accidents. With one exception, all patients sustained multiple injuries. The mortality rate for an open PF was 50%, in marked contrast to 10.5% for a closed PF. Of more importance, the pelvic fracture was the primary cause of death in 73% of those dying with an open PF and in 30% of those dying with a closed PF. The higher mortality is due to an increased risk of infection and to massive hemorrhage because of a high risk of concomitant major vessel injury, as well as increased diffuse retroperitoneal hemorrhage, in these open fractures. Therapy directed to restoring blood volume, identifying and repairing major vessel injury, and attempting to decrease the diffuse retroperitoneal hemorrhage is essential. If drainage is necessary, it should be accomplished with a closed system. Immediate colostomy and use of antibiotics should decrease the infectious complications.


Replantation of untidily amputated finger, hand, and arm: experience of 99 replantations in 66 cases. Three problems the authors think important in replantation of untidy amputations are discussed based on our 99 replantations with the success rate of 92.6% over a 4-year period. To restore circulation in this type of amputation, such techniques as transfer of blood vessels, use of a neurovascular island flap with neurovascular anastomoses at its distal margin, vein graft, and free split-skin graft directly on the anastomosed blood vessels are recommended. Recovery of tendon gliding when replanted proximally to the MP joint was reasonably good but not when replanted distally to it. Recovery of intrinsic muscles was generally poor. Protective sensation was usually regained, although occasionally accompanied by paresthesia. Amputation of single digit was found not to be an absolute indication for replantation except for the thumb. In multiple digital amputation, more important digits should be restored by amputated digits in better condition. Replantation for cosmetic improvement may be justified in such cases as unmarried young females. In infants, replantation is especially worthwhile because good functional recovery and good further growth can be expected.


External skeletal fixation in severe limb trauma. Ten patients with 12 severe limb injuries managed by external skeletal fixation over 2 years are presented. Two major indications for external skeletal fixation divided the fractures into groups: A) extensively open fractures requiring wound care and closure by other than primary methods, and B) grossly unstable fractures requiring stabilization for soft-tissue support and fracture alignment. Group A was composed of five extremity fractures with skin and muscle loss and deep tissue contamination. Wound management was the primary problem. Wound closure, prevention of an infection, and limb salvage were the treatment goals in this group. Group B was seven severely comminuted extremity fractures with significant swelling and in some cases, questionable soft-tissue survival. Five were open, but not extensively. Instability was the primary problem. Fracture control, soft-tissue support, and limb salvage were the treatment goals in this group. Mean followup period for all fractures was 9.4 months. No amputations, deep infections, or deaths resulted. Wound care and closure were facilitated in all open fractures. Loss of contused tissues with marginal vascular supply was felt to be minimized. Delayed unions were common in both groups. Two malunions and one nonunion occurred. Treatment goals in both groups were accomplished.


Selective conservatism in penetrating abdominal wounds: a continuing reappraisal. Our experience with 829 patients with penetrating abdominal trauma treated in an Adult Trauma Service over 8 1/2 years managed by "selective conservatism" is reviewed, and 207 additional patients with blunt abdominal trauma handled in the same fashion were also studied. This pattern of management prompted exploratory celiotomy in only 29% of stab wounds and 54% of gunshot wounds. Overall mortality for penetrating abdominal wounds, including patients moribund on admission, was 2.5%. Overall mortality was 19.3% for blunt abdominal trauma. There were no deaths or errors in management in  those patients definitively selected for nonoperative management. The philosophy of using specific objective indications for abdominal exploration in both penetrating and blunt abdominal trauma, especially when bolstered by routine abdominal paracentesis and lavage, is safe and reliable, and is  adaptable to all clinical facilities.


Hypertension in children with burns.

Hypertension in children with burns. Hypertension has been observed to occur frequently in children with burns. In a series of children admitted to the St. Agnes Burn Treatment Center, sustained systolic and diastolic hypertension occurred in 31.5%, and 57.4% of the children demonstrated episodic periods of hypertension which were unsustained. The only clinical finding which significantly correlated with the hypertension was the presence of tachycardia, which persisted into the late healing phase of the thermal injury. Hypertension was more prevalent at younger ages. However, there was no other correlation of the development of hypertension with sex, race, or extent of thermal injury. The development of hypertension in itself did not worsen the prognosis for survival in the cases presented in this series. Possible pathogenic mechanisms which result in hypertension (elevated catecholamines, norepinephrine, renin secretion) are discussed.


Treatment and traumatic hemobilia with angiographic embolization. Hemobilia is an uncommon but devastating complication of liver trauma. The recommended treatment is surgical resection of the involved liver lobe, but this is associated with high mortality and morbidity. An alternate treatment using emboli directed selectively into the involved hepatic artery was successful in obliterating the false aneurysm and eliminating the liver cavity. Since arteriography is generally performed during the diagnostic workup of such patients, embolization may provide a simple, safe, and effective treatment for hemobilia.


Ligation of the main hepatic artery for exsanguinating liver laceration in an adolescent. An adolescent with blunt injury to the liver was found to have bilobar posterior hepatic laceration. Hemostasis was achieved only after ligation of the hepatic artery proper. Postoperative liver function changes were minimal and transient. Her recovery was complete.


Fracture of the navicular sesamoid bone: a case report. The case history of a 45-year-old female patient who sustained a fracture of the right navicular sesamoid bone, probably due to sudden stretching of the tibialis posterior muscle, is described, and the literature briefly reviewed.


Hepatic trauma and amoebic liver abscess. A patient with a history of severe trauma over the hepatic area followed 2 weeks later by a large amoebic liver abscess of the right lobe is described. The possible role of hepatic trauma in the genesis of liver abscess is discussed. A history of hepatic trauma should not distract the clinician from diagnosing an amoebic liver abscess when suggestive symptoms and signs occur.


Roles of bacteriophage lambda gene products O and P during early and late phases of infection cycle. Ring-to-ring (early) replication of bacteriophage lambda DNA was blocked after heat inactivation of the P protein. Rolling circle (late) replication continued for several rounds at the rate reached when the temperature shift was carried out. The same differential effect was observed after inhibition of RNA or protein synthesis during the two different phases of replication. In contrast, inactivation of the O protein resulted in a fast stop of lambda DNA synthesis at early and late times after infection. The results were consistent with the following interpretations. (i) The lambda P gene product plays a role in the initiation of the ring-to-ring replication. (ii) Ring-to-ring replication continues parallel to rolling circle replication, possibly diminishing with time after infection. (iii) The O function is stable in and necessary for the structural integrity of an elongation complex. It is unstable in free form and probably released from such a replication complex after each round of replication at the ring-to-ring stage.


Effect of low-NaCl medium on the envelope glycoproteins of Sindbis virus. Lowering the NaCl concentration of the medium inhibits the release of Sindbis virus from infected chicks cells at a stage after the nucleocapsids have bound to the membranes of the infected cells. The failure of trypsin treatment to release the inhibited virus and the ratio of the proteins in the inhibited cells make it seem likely that the inhibited virus is all intracellular. Experiments using antisera specific for E1 and E2, the envelope glycoproteins of Sindbis, suggest that the inhibitory effect of low-salt medium is mediated through an effect on E2. Lactoperoxidase radioiodination experiments indicate that, even when cleaved from PE2, E2 is not exposed on the surface of low-NaCl-treated chick cells.


Characterization of an RNA-dependent RNA polymerase activity associated with measles virus. An RNA-dependent RNA polymerase activity has been found copurifying with measles virus infectivity and complement-fixing antigen in three Vero cell-grown variants of measles virus: the attenuated Edmonston B strain, the natural non-attenuated Edmonston strain, and a subacute sclerosing panencephalitis isolate, IP-3. Incubation of purified measles virions with immunoglobulin G derived from sera of monkeys hyperimmunized against measles specifically removes activity sedimenting in the density region of measles virions. The requirements of the reaction, which is RNase sensitive, are similar to those reported for other paramyxovirus-associated activities, including detergent, divalent cation, ribonucleoside triphosphates, and a reducing agent. The size classes of RNA synthesized correspond to those found in measles-infected cells, including 50, 35, and 16 to 20S. The product RNA of the Edmonston B virus-stimulated reaction was rendered RNase resistant by annealing with RNA extracted from purified Edmonston B virions. RNA from uninfected Vero cells was ineffective in the annealing reaction.


Evidence from UV transcription mapping that late adenovirus type 2 mRNA is derived from a large precursor molecule. The UV inactivation of labeling of various late adenovirus type 2 mRNA's is as great or greater than the inactivation of labeling of the same sequences that are present in a large primary RNA transcript in the cell nucleus. Thus, the large nuclear adenovirus type 2-specific RNA appears to be the obligatory precursor of cytoplasmic mRNA. The majority of the mRNA's derived from the large precursor apparently require the synthesis of the whole nuclear molecule. A UV-sensitive target necessary for proper processing of all the mRNA's may exist near the end of the transcription unit.


Groups of adenovirus type 2 mRNA's derived from a large primary transcript: probable nuclear origin and possible common 3' ends. Late in adenovirus type 2 infection, a number of mRNA's apparently arise by processing a large nuclear transcript that represents the right-hand 85% of the genome (summarized in Evans et al., Cell 12:733-739, 1977). Hybridization of labeled late mRNA to a series of DNA restriction fragments representing the right-hand 70% of the genome demonstrates at least 12 discrete mRNA's that appear to fall into five groups, each possibly containing a common 3' terminus. The processing necessary to generate these mRNA's apparently occurs in the nucleus. All the mRNA's appear to contain a sequence of approximately 100 nucleotides complementary to a fragment with coordinates 25.5-27.9. This fragment contains one of the regions found by Berget et al. (Proc. Natl. Sci. U.S.A. 74:3171-3175, 1977), Chow et al. (Cell 12:1-18, 1977), and Klessig (Cell 12:9-22, 1977) to the "spliced" onto the 5' end of late adenovirus type 2 mRNA's. Because the sequences to be spliced exist only once per large transcript, any of the mRNA-specific regions might only be preserved from a small fraction of the transcripts. Measurement of the transport efficiency of regions of the large nuclear transcript, if fact, shows that only 15 to 25% of any particular region is transported to the cytoplasm. The overall conclusion of these experiments is that the large late nuclear transcript can be processed in the nucleus to yield any one of many (approximately 12) mRNA's; the unused portions of the primary transcript then accumulate in the nucleus or are destroyed.


Head maturation pathway of bacteriophages T4 and T2. III. Isolation and characterization of particles produced by mutants in gene 17. We have isolated and characterized two types of particles produced in comparable amounts by mutants in gene 17: the empty large particle and the empty small particle. Dimensions, morphology, stability, and protein composition of the empty large particle are very similar to those of the capsids or empty heads of mature phage. The other type of particle (empty small particle) is very similar in dimensions and stability to the prehead, but differs in that it is composed of processed proteins (gp23, gp24, IpIII). Structural analysis has shown that the protein subunits of the empty small particles are arranged in an unexpanded type of lattice (11.2 to 11.3 nm), whereas the empty large particles have an expanded lattice (13 nm). The characterization of the empty small particle as being composed of cleaved proteins, but still unexpanded, shows that the expansion of the T4 head shell is not necessarily linked to the cleavage of the structural proteins.


Adenovirus type 2 late mRNA's: structural evidence for 3'-coterminal species. Adenovirus type 2-infected HeLa cells were labeled with 32PO4 during the period 14 to 17 h postinfection. Viral mRNA's with polyadenylic acid were isolated by polyuridylic acid Sepharose chromatography and fractionated according to size by electrophoresis through an acrylamide-agarose slab gel. Messenger bands were eluted and partially degraded with alkali. RNA fragments from each band that contain polyadenylic acid were isolated by polyuridylic acid Sepharose chromatography and fingerprinted two-dimensionally after T1 RNase digestion. Three bands, with mobilities of approximately 26S, 21S, and 18S, shared two large characteristic T1 oligonucleotides in common in the fingerprints of their 3'-terminal sequences. These oligonucleotides were mapped with a Hpa II restriction fragment of adenovirus type 2 DNA with coordinates 49-50.2. We conclude that the three mRNA's are coterminal in sequence at their 3' ends and overlap at internal positions. Implications for the protein-coding potential of these mRNA's and the mechanisms of adenovirus tyep 2 late RNA processing are discussed.


A report on the present status of undergraduate urologic teaching in medical schools and some resulting recommendations. At the request of the Education Council of the American Urological Association a survey of urologic teaching in America's medical schools was done. The most startling and distressing finding, based upon the study of 99 medical schools, was that more than half (52 per cent) of the schools do not require any clinical exposure to urology before graduation. Suggestions are offered, based upon the documented importance of urology in the delivery of primary care, for an approach to medical school curriculum committees to mandate the return of urology as a required subject in our schools.


Validity of 99mTc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function. 99mTc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a 131I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. 99mTc dimercaptosuccinic acid scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.


Commercial fibrinogen, autogenous plasma, whole blood and cryoprecipitate for coagulum pyelolithotomy: a comparative study. Coagulation pyelolithotomy provides an effective means to remove multiple calculi from the renal collecting system. The strength of the coagulum is directly proportional to the concentration of fibrinogen and inversely proportional to the concentration of thrombin. Because of the fear of hepatitis fibrinogen may soon be unavailable commercially. It will then become necessary to use plasma from the patient as the source of fibrinogen. By the process of cryoprecipitation fibrinogen levels can be increased about 10-fold, yielding clots of greater tensile strength than would be obtained from non-concentrated plasma.


New approach to the splenic vessels.

New approach to the splenic vessels. The transperitoneal approach is used systematically for an arterial or a venous splenorenal anastomosis. However, this approach is associated with high morbidity and mortality rates. Because of our anatomical and surgical findings we have used the retroperitoneal approach to the splenic hilus by means of the lumbar region. The first splenorenal arterial anastomosis with this approach was done in 1972. The approach has proved to be less aggressive since it avoids the danger of damaging the pancreas, it is a more direct approach to the splenic vessels and it provides better exposure and facilitates the anastomosis. In addition, the loss or infection of ascitic fluid in cirrhotic patients is avoided with this approach, as well as intraoperative hemorrhaging caused by the great surplus circulation. There has been neither mortality nor complications in the 13 cases of arterial and venous splenorenal anastomoses that we have done with this method.


An incision for extended suprahilar retroperitoneal lymphadenectomy. To fulfill the necessary criteria for adequate exposure for extended suprahilar retroperitoneal lymphadenectomy we have used a thoracoabdominal midline extraperitoneal incision that affords the high exposure of a thoracoabdominal incision without sacrificing the broad exposure afforded by a midline incision and maintains the advantages of the extraperitoneal approach.


Semi-closed basket extraction of ureteral calculi. A method is described for ureteral stone extraction using a partial closure of the Dormia stone dislodger. Of 97 attempted extractions 89 (91.8 per cent) were successful. No major complications occurred. The over-all morbidity rate was 3 per cent. The technique is especially useful in removing larger ureteral calculi.


Ureteral trauma: effects of ureteral ligation with and without deligation--experimental studies and case reports. Inadvertent ureteral ligation is a well recognized risk during abdominal, retroperitoneal and pelvic operations. The feasibility and the safety of ureteral ligation treated with deligation have been documented. Herein is presented an over-all evaluation of the experience with ureteral ligation treated by deligation in 32 dogs and 4 women.


The role of ureteral stenting in the management of surgical injury of the ureter. From 1965 through 1976, 35 patients with surgical injury of the ureter were treated by operations requiring ureteral anastomoses. Stenting devices were used in 31 patients with only 2 failures. Stents were omitted in 4 patients with 2 failures. We have been satisfied with and prefer stenting ureteral anastomoses in the management of surgical ureteral injury, particularly when there is delayed recognition of the injury or previous irradiation. Previous objections to stenting are unjustified.


Paraganglia of the bladder.

Paraganglia of the bladder. Normal paraganglia containing high amounts of catecholamines are a constant feature of the wall of the bladder in elderly men. The paraganglia in this location might give rise to pheochromocytomas. The importance of the local endocrine effects in the regulation of the muscular tone in the bladder is discussed.


Adenosine deaminase activity in patients with carcinoma of the bladder. Adenosine deaminase is an important enzyme in purine metabolism, and patients with abnormal lymphocyte and erythrocyte adenosine deaminase levels have been shown to have impaired immune competence. Since immune factors have been shown to be important in patients with transitional cell carcinoma of the bladder we studied adenosine deaminase activity in the hemic cells of 48 patients with this tumor. Lymphocyte adenosine deaminase levels were elevated in patients with transitional cell carcinoma and correlated with stage, activity, clinical course and tumor resection but not with tumor grade. Erythrocyte adenosine deaminase levels also were elevated in patients with transitional cell carcinoma but did not correlate with other disease parameters. Lymphocyte adenosine deaminase activity in patients with transitional cell carcinoma may be a sensitive indicator of disease activity and further studies may provide insight into the host-tumor relationship at the enzyme level.


The current status of the inflatable penile prosthesis in the management of impotence: Mayo Clinic experience updated. During the last 2 years the inflatable penile prosthesis has been implanted at the Mayo Clinic in 63 organically impotent male subjects. Over-all functional success is between 90 and 95 per cent. Experience indicates that 25 per cent of the patients require a second surgical procedure to correct a mechanical problem. Further experience with the technique and improvement in the product design have significantly decreased the number of mechanical problems encountered. Patient partner acceptance of this device continues to be excellent.


Small-Carrion penile prosthesis: a report on 160 cases and review of the literature. The use of the Small-Carrion penile prosthesis in 160 patients is evaluated. Methods to determine those patients who will benefit from the use of this prosthesis and the size prosthesis needed are discussed. Suggestions are made on how to handle problems or complications that may occur during or after the operation, as well as the antibiotic regimen. The literature is reviewed.


Synergistic gangrene of the scrotum and penis secondary to colorectal disease. We recently encountered 5 patients with synergistic gangrene of the genitalia secondary to colorectal disease. This number of cases suggests that there may be an increasing incidence of this entity that has been reported only several times in the past. Pseudomonas was one of the organisms cultured in all cases. Because of the high mortality rate we advocate aggressive therapy, consisting of early and repeated radical débridement into normal tissues and appropriate management of the colorectal source of contamination. Our experience indicates that the lower gastrointestinal tract should be considered as a possible cause of infection in all cases of synergistic gangrene of the scrotum and penis.


Testicular biopsies in 101 cases of varicocele. Testicular biopsies were done on 101 patients who underwent ligation of the internal spermatic vein as primary treatment for infertility. Retrospective analysis included evaluation of tubular thickening, Leydig cell hyperplasia, premature sloughing, maturation arrest and decreased spermatogenesis. A comparison was made of biopsy profiles, sperm counts and pregnancies in an attempt to determine further the value of testicular biopsy in the subfertile man. The pregnancy rate was 40 per cent over-all, with 32 per cent of the patients with tubular thickening reporting pregnancies. There was only 1 pregnancy in patients with Leydig cell hyperplasia. The controversial finding of premature sloughing had no consistent relationship to results.


Antiandrogenic effects of spironolactone: hormonal and ultrastructural studies in dogs and men. A decrease in the level of plasma testosterone and an increase in the level of plasma progesterone were noted after spironolactone had been administered for 20 days in 5 patients with prostatic carcinoma, as well as in 8 male dogs. Electron microscopic observation disclosed myelin-like bodies in the cytoplasm of Leydig and adrenocortical cells in dogs, contributing to a resolution of the mode of antiandrogenic action of spironolactone.


The prophylactic use--or misuse--of antibiotics in transurethral prostatectomy. One hundred non-infected patients undergoing transurethral prostatectomy were randomized prospectively into a controlled study to determine the influence of a prophylactic aminoglycoside (kanamycin) on the clinical course. In the non-risk patient prophylactic kanamycin had no beneficial influence on the incidence of bacteriuria, fever or length of hospitalization. Its use was associated with the development of a resistant Pseudomonas super infection in 1 patient. Prophylactic kanamycin did not protect the patient with carcinoma of the prostate from bacteriuria. There was no identifiable advantage in the use of routine prophylactic kanamycin in the uninfected, non-risk patient who was undergoing elective transurethral prostatectomy.


A solid phase radioimmunoassay for prostatic acid phosphatase. The sensitivity of a recently developed solid phase radioimmunoassay for human prostatic acid phosphatase was compared to that of an enzymatic method using p-nitrophenylphosphate as substrate. In 109 histologically verified untreated stages I to IV prostatic cancers and 200 men without such cancer the solid phase radioimmunoassay method demonstrated substantially greater sensitivity and specificity than the enzymatic technique. In the 109 prostatic malignancies the immunochemical method correctly classified 80 (73 per cent) versus 34 (31 per cent) for the p-nitrophenylphosphate enzymatic technique (p less than 10(-6). In 44 stages I and II cancers confined to the prostate the radioimmunoassay was abnormally elevated in 19 (43 per cent) with only 4 (9.1 per cent) enzymatic elevations (p less than 10(-3). In 65 stages III and IV extraprostatic cancers correct classifications were noted in 61 (94 per cent) of the radioimmunoassays and 30 (46 per cent) enzymatic tests (p less than 10(-6). The radioimmunoassay in 200 male controls yielded 11 (5.6 per cent) and the p-nitrophenylphosphate enzymatic test yielded 7 (3.5 per cent) falsely positive results. In 90 non-prostatic human cancer sera 85 (94.5 per cent) were correctly classified as negative by the radioimmunoassay for prostatic acid phosphatase versus 66 (73 per cent) as negative by the enzymatic method. These data are discussed in terms of the merits of a radioimmunochemical approach for the measurement of human serum prostatic acid phosphatase.


Suppressive effects of regional lymph node cells and extracts of antibody-dependent cellular cytotoxicity. Lymphocytes from regional lymph nodes that drain tumors and extracts of such lymphocytes suppress antibody-dependent cell-mediated target cell lysis by effector cells from cancer patients and controls. In contrast, lymph node cells from control patients are not suppressive. Control extracts from normal lymphocytes and 2 immunologically inert tissues, muscle and kidney, exhibit some suppressive activity but significantly less than extracts from lymph nodes that drain tumors.


Effect of dantrolene sodium on the spastic external urethral sphincter recorded by sphincterometry. An improved method of sphincterometry is described, which is easy to perform in men and also may be used in women. It gives reproducible results in the individual patient. The maximum pressure was found by radiographic and reflexological examinations of the external urethral sphincter. When 0.5 mg./kg. body weight dantrolene sodium was injected intravenously the resistance of the external urethral sphincter was found to be reduced significantly, presumably reflecting a reduction of reflex activity.


Urethral striated sphincter responses to electro-bulbocavernosus stimulation. Electric stimuli of known strength, duration and frequency were applied to the glans penis, and the cystosphincterometric and electromyographic responses of the urethral striated sphincter were recorded. Studies performed on male subjects, including normal men, patients with a neurologic deficit and patients who had undergone prostatectomy, indicate the usefulness of this technique in evaluating the striated sphincter excitability via the pudendal reflex arc. The intravenous administration of diazepam produced a notable increase in the striated sphincter threshold, indicating the applicability of this technique to evaluate the effect of various neuropharmacologic agents on the striated sphincter activity. In addition, the transit time through the pudendal reflex arc was measured with this method to assess the somatic neural integrity of the lower urinary tract. Also, studies on patients with post-radical prostatectomy incontinence have suggested that our technique of striated sphincter evaluation could be applied to the prediction of postoperative urinary incontinence.


Early angiography in the management of post-renal biopsy hematuria. A case is reported in which the value of early angiography in the management of post-renal biopsy hematuria is exemplified. The decision of whether treatment should be conservative or surgical is based on the precise anatomical delineation of the cause of hematuria and the chances of spontaneous remission. When necessary an operation guided by the angiogram can be limited to partial resection of the lesion-bearing region.


Congenital posterior urethral perineal fistula: a case report. A case of congenital posterior urethral perineal fistula is reported. The English literature is reviewed and anatomical findings, embryology, presenting signs and symptoms, and treatment are discussed.


Posterior urethral trauma and strictures: an attempt to solve a controversy. Three cases of traumatic partial or complete posterior urethral rupture and subsequent stricture are reported. Treatment consisted of early suprapubic cystostomy, with/or without concomitant primary realignment of the urethra over a catheter, followed by urethral dilations and internal urethrotomy when indicated. Followup of 4 or more years showed excellent results.


Assisted ventilation for patients with cystic fibrosis. Forty-six patients with cystic fibrosis (CF), 1 month to 32 years of age, had 51 episodes of assisted ventilation. Thirty-five (69%) died after 1 to 395 days of mechanical ventilation and six others (12%) died in the hospital 1 to 42 days after assisted ventilation therapy was discontinued. Only three patients survived longer than one year after discharge. These results are much poorer than those reported for patients with chronic obstructive pulmonary disease of other causes probably because of the different natural history and response to therapy in CF. Patients with CF whose conditions progressively deteriorated despite optimal therapy and no longer respond to antibiotic and physical therapy are not good candidates for mechanical ventilation. The occasional patient with good baseline status in whom acute respiratory failure develops should be considered for assisted ventilation.


Ventriculographic-echocardiographic correlation in patients with asynergy. The ability of echocardiography to detect segmental ventricular asynergy was evaluated in 41 patients before cardiac catheterization. Of 24 normal posterior wall segments by echocardiography, 23 were also normal by ventriculography, while one was hypokinetic. Of 17 asynergic posterior wall segments by echocardiography, 15 were asynergic and two were normal by ventriculography. Posterior wall excursion for the normal group was 1.30 +/- 0.18 cm (SD), while those demonstrating hypokinesis on ventriculography showed an excursion of 1.05 +/- 0.19 cm (P less than .005), and akinetic segments showed an excursion of 0.97 +/- 0.13 cm (P less than .005). In 15 patients, septal motion as determined by echocardiography was compared with the left anterior oblique ventriculogram. Of nine normal septal motions by echocardiography, seven were also normal by left anterior ventriculography (septal excursion, 0.84 +/- 0.25 cm). Of six patients with decreased echocardiographic septal motion, four were normal and two were abnormal by ventriculography. Although normal echocardiographic septal motion correlated well with ventriculography, decreased septal excursion by echocardiography did not.


Circulating thrombin time anticoagulant in a procainamide-induced syndrome. Circulating anticoagulants are unusual in drug-induced syndromes. We evaluated the prolonged thrombin time of plasma from a patient with a procainamide-induced syndrome. This defect was shown to be due to a circulating anticoagulant that was not of fibrin or fibrinogen origin and that prolonged thrombin and reptilase clotting times of plasma. Subclinical doses of heparin sodium induced hemorrhagic manifestations in this patient. Following cessation of heparin therapy, the circulating anticoagulant persisted but the bleeding tendency abated. All clinical and laboratory manifestations of this syndrome abated gradually following cessation of procainamide therapy.


Tetracycline. Another example of generic bioinequivalence. Because of the Food and Drug Administration batch certification assurances, state government systems generally purchase antibiotics from the lowest bidder. A tetracycline hydrochloride tablet purchased in this manner is shown to be inferior to the innovator capsule product.


Hypercalcemia in squamous cell carcinoma of the skin. Squamous cell carcinoma of the skin is an extremely rare cause of hypercalcemia associated with malignant neoplasms. The case of a patient with extensive squamous cell carcinoma of both buttocks and thighs, with severe hypercalcemia is reported. The data presented indicate secretion of a humoral factor by the tumor, producing hypercalcemia.


Latent and chronic infections imported from Southeast Asia. This review is intended to remind physicians of exotic infections with latency of at least one year that could cause illness in refugees or US citizens exposed in Southeast Asia. Tuberculosis, melioidosis, and leprosy are the major chronic infections of bacterial origin. Intestinal protozoa, roundworms, and flatworms are considered with regard to pathogenic, potential and duration of infection. Malaria, filariasis, and schistosomiasis may be seen on occasion. Paragonimiasis and Chinese liver fluke infections are more common and may simulate other less exotic diseases.