Some additional observations relating to the mechanism of trypan blue induced teratogenesis. The mechanism and site of teratogenic action of trypan blue on mammalian embryos was reinvestigated. The experiments to be presented include (1) an analysis of the effect of trypan blue treatment on the morphology of the early mouse egg cylinder, (2) a demonstration of the effect of dye treatment on the enzyme acid phosphatase of yolk sac epithelium using histochemical procedures. Results obtained from these experiments indicate that trypan blue injected into mothers on day 7 of gestational age leads, within 12 to 24 hours after treatment, to dramatic abnormalities in 90-95% of egg cylinders examined. The frequency of gross malformations obtained by this treatment is considerably less when litters are examined at later stages of gestation. Acid phosphatase activity in yolk sac epithelium is depressed by the dye treatment, but there is no difference between enzymatically depressed yolk sacs of malformed embryos and yolk sacs surrounding normally appearing litter mates both obtained from trypan blue treated mothers. The hypothesis that trypan blue may exert its teratogenic effect by the direct exposure of egg cylinder stages to the dye, and that some of the egg cylinders affected may subsequently repair, is recommended for further testing.


Development and life cycle of the parthenogenetically activated sea urchin embryo. A method is reported for inducing parthenogenetic development in eggs of the sea urchin Lytechinus pictus, a species which previously could not be artificially activated. NH4OH or the calcium ionophore A23187 are used as activating agents followed by hypertonic treatment. The ionophore is superior in activating large numbers of unfertilized eggs, whereas NH4OH produces a larger percent of embryos able to undergo gastrulation. Both feeding larvae and urchins arising from these artificially activated eggs are diploid. All individuals in which sex has been identified have been female. The viability of these completely homozygous organisms is low compared to their fertilized counterparts.


Visual receptive fields and their images in superior colliculus of the cat. 1. The receptive fields of collicular neurons in the cat, recorded in a single microelectrode penetration, were not centered on a point in visual space, but nested eccentrically with the smaller fields displaced toward the area centralis. The eccentric nesting was not eliminated by correcting the fields for the tangent screen distortion or by making penetrations normal to the collicular surface in coronal and parasagittal planes. These findings do not support the idea that collicular cells form topographically organized columns oriented normal to the collicular surface. 2. When the receptive fields were plotted in the visual coordinate system of the collicular map, the nesting became much more concentric, suggesting that the eccentric nesting of the receptive fields in visual space was largely a product of the retinotectal coordinate transformation. 3. The profile of a collicular receptive field, plotted in the collicular visual coordinate system is called the receptive-field image. Receptive-field images tended to have oval shapes with the long axis oriented mediolaterally. Clusters of receptive-field images, plotted for single penetrations, appeared similar wherever they occurred in the collicular map, suggesting that a common pattern of neural convergence determines the geometry of the receptive-field images in all parts of the colliculus. 4. The neural substrate of the receptive-field images was examined by tracing the theoretical patterns of neural activity which a point stimulus would produce in the retinotectal system. This analysis suggested that the shape and dimensions of the receptive-field images, and consequently the receptive fields, might be accounted for in large part by the geometry of collicular dendritic fields, the dimensions of the visual receptive fields of afferent fibers, and the retinotectal coordinate transformation. 5. Because it adjusts for the retinotectal distortion of visual space, the receptive-field image may be used to outline the distribution of collicular cells excited by a point stimulus. This makes it possible to show that a point stimulus activates large-field cells in the superficial gray layer over an area of about 2.5 by 1.5 mm in the central parts of the colliculus. It is suggested that such cells may organize the directional signals required by the oculomotor system for visual orienting behavior.


Representation of cochlea within primary auditory cortex in the cat. The representation of sound frequency (and of the cochlear partition) within primary auditory cortex has been investigated with use of microelectrode-mapping techniques in a series of 25 anesthetized cats. Among the results were the following: 1) Within vertical penetrations into AI, best frequency and remarkably constant for successively studied neurons across the active middle and deep cortical layers. 2) There is an orderly representation of frequency (and of represented cochlear place) within AI. Frequency is rerepresented across the mediolateral dimension of the field. On an axis perpendicular to this plane of rerepresentation, best-frequency (represented cochlear place) changes as a simple function of cortical location. 3) Any given frequency band (or sector of the cochlear partition) is represented across a belt of cortex of nearly constant width that runs on a nearly straight axis across AI. 4) There is a disproportionately large cortical surface representation of the highest-frequency octaves (basal cochlea) within AI. 5) The primary and secondary field locations were somewhat variable, when referenced to cortical surface landmarks. 6) Data from long penetrations passing down the rostral bank of the posterior ectosylvian sulcus were consistent with the existence of a vertical unit of organization in AI, akin to cortical columns described in primary visual and somatosensory cortex. 7) Responses to tonal stimuli were encountered in fields dorsocaudal, caudal, ventral, and rostral to AI. There is an orderly representation of the cochlea within the field rostal to AI, with a reversal in best frequencies across its border with AI. 8) Physiological definitions of AI boundaries are consistent with their cytoarchitectonic definition. Some of the implications of these findings are discussed.


Apnea of prematurity. Comparative therapeutic effects of cutaneous stimulation and nasal continuous positive airway pressure. It has been suggested that idiopathic apnea of prematurity is related to hypoxia from pulmonary instability or an immaturity of central respiratory control mechanisms. To explore these hypotheses, 18 preterm infants were studied to examine the therapeutic effects of prophylactic cutaneous stimulation (6) and continuous positive airway pressure(12). The frequency of apnea using each procedure was reduced by 35 and 69 percent, respectively. These findings constitute the basis for new therapeutic measures for treatment of idiopathic neonatal apnea.


Minoxidil in refractory hypertension.

Minoxidil in refractory hypertension. A life-threatening, severe, hypertension refractory to conventional antihypertensive drugs developed in a 10-year-old girl in association with a functional renal transplant. Minoxidil, a new vasodilator, proved to be a life-saving antihypertensive drug and prevented the removal of the functional transplant. During 9 months of minoxidil therapy the blood pressure remained controlled and the renal transplant function excellent. No serious side effects except a moderate hypertrichosis have been observed. It appears that minoxidil can be used to control refractory, life-threatening hypertension in children.


An outbreak og gastroenteritis due to E. coli 0142 in a neonatal nursery. A nursery outbreak of gastroenteritis casued by Escherichia coli 0142/K86/H6 is described. Over a period of nine months, 59 epidemiologically linked cases of diarrhea occurred, including 21 intractable cases with four deaths. The epidemic strain, which was not agglutinated by commerical diagnostic antisera, was isolated from the hands of personnel in five instances directly incriminated hand carriage as the mode of spread. Acquisition of illness, which was especially high among low-birth-weight infants less than 17 days old, did not correlate with any treatment modality investigated and appeared to be related to a host factor. Noninvasive small intestinal colonization, production of enterotoxin, and multiple antibiotic resistance of the epidemic strain were demonstrated and helped to explain the intractability of clinical illness in many infants, despite intensive parenteral antibiotic therapy. Surveys of fecal coliforms on the hands of nursery personnel revealed no change in prevalence after introduction of a policy of "triple" handwashing with 3 percent hexachlorophene soap, but a significant decrease occurred during the use of disposable gloves. The frequent occurrence of E. coli 0142 in throat swabs of affected infants suggested that pharyngeal colonization may serve as an important diagnostic clue in E. coli diarrhea.


Reappraisal of kanamycin usage in neonates. This study documents an important change in the kanamycin in susceptibilites of Escherichia coli strains cultivated from neonates. Whereas some nurseries have in the past experienced resistance rates as high as 70 per cent recent survelliance of seven North American nurseries demonstrated that 90 percent or more of E. coli strains are currently susceptible to kanamycin. Pharmacokinetic studies of 65 babies treated with either 7.5 or 10 mg/kg kanamycin doses revealed that peak serum values varied with dosage, birthweight, and chronologic age. Peak serum levels were below the desired therapeutic range in many babies treated with 7.5 mg/kg doses of kanamycin every 12 hours. Concentrations in cerebrospinal fluid specimens from 21 infants were 0.5 to 12 mu/ml after 7.5 mg/kg kanamycin doses. Calculated distribution volumes, plasma clearances, and serum half-life values were used in formulating a revised kanamycin in dosage and frequency of administration schedule.


Effects of red cell extract on in vitro growth and multiplication of malarial parasites. An extract of red blood cells was prepared from monkey blood. Red cell extract (RCE) of Aotus monkeys was beneficial for the in-vitro cultivation of 2 strains of P. falciparum. The active material(s) in Aotus RCE was not sedimented by centrifugation at 34,800 g for 1 hr. Rhesus monkey RCE improved the growth of P. knowlesi for in-vitro cultivation through 4 schizogonous cycles (88 hr).


Cell volume and DNA content of Trypanosoma lewisi and T. mega in vitro. Two species of trypanosomes were harvested at a comparable stage in vitro development, just as cell division was ceasing and cell length had become maximal and its variability minimal. At this stage, T. mega displayed both a larger cell volume than T. lewisi (27.5 vs. 14.3 mu-2) and a greater DNA content (0.23 vs. 0.048 pg/cell).


The use of removable partial denture splints in the treatment of postsurgical tooth mobility. The theory and clinical use of removable partial denture splints has been offered as a tenable solution to the problem of postsurgical tooth mobility. The close cooperation of the periodontic and prosthetic specialties is in many cases vital to the ultimate success of treatment and longevity of the dentition. Although not presented as a panacea, it is hoped that clinicians will bear this clinical entity in mind as an option in the treatment of periodontally debilitated dentitions.


Synthesis and antimalarial activity of heterocyclic alkyl disulfides, thiosulfates, and dithio acid derivatives. Based on the antimalarial activity in mice of bis(4-rho-acetamidobenzenesulfonamidophenyl) disulfide, a series of N-heterocyclic alkyl disulfides and thiosulfates was synthesized and screened for antimalarial activity. Several related dithio acid dianions and S- blocked derivatives were also screened to provide an indication of the possible role that thiol anions might play in malaria chemotherapy. Activity was limited by toxicity with these compounds, and none of those tested, with the exception of bis(4-rho-acetamidobenzenesulfonamidophenyl) disulfide, showed curative activity in either a mouse or chick test.


The effects of variations in the opposing dentition on changes in the partially edentulous mandible. Part III. Tooth mobility and chewing efficiency with various maxillary dentitions. Tests were conducted using a mobilometer to determine the effects of the opposing dentition on mobility of selected teeth in the partially edentulous mandible. In addition, the effect of the opposing dentition and the presence or absence of a lower removable partial denture on chewing efficiency was evaluated. Results indicated an increase in mobility of abutment teeth following placement of removable partial dentures. The mobility decreased as the teeth became stabilized by the removable partial dentures. The amount of mucosal and bone-contour change was directly related to the degree of mobility of the abutment teeth. Comparisons in chewing efficiency indicated no particular difference between subjects with unilateral or bilateral distal-extension removable partial dentures or in the type of opposing dentition. However, the use of a lower removable partial denture does increase chewing efficiency to a level of about 50 per cent of that found for subjects with all of their natural teeth.


The processed provisional splint in periodontal prostheses. A technique has been described whereby a heat-processed provisional splint was fabricated with the factors of esthetics and long-term serviceability being of prime importance. Additional advantages of the use of a well-adapted provisional restoration in a periodontal prosthesis are as follows: (1) They facilitate periodontal treatment by allowing total visibility and access to surgical sites when the splint is removed. (2) The splinting effect may enhance healing and periodontal-ligament reattachment by stabilizing mobile abutments. (3) The patient's ability to render adequate home care for a fixed prosthetic restoration may be evaluated and reinforced before making case restorations. (4) The patient's cooperation is assured during an extended period of restorative care when an esthetic, comfortable, provisional splint is provided.


Complete denture technique using natural anterior teeth. A technique has been described which permits the use of desirable natural anterior teeth in complete dentures (Fig. 3). The main characteristic of this technique is the use of cast copings with dowels to which the natural teeth are attached. The cast copings securely fit the natural teeth to the base of the denture (Fig, 4). The use of NATURAL teeth in a denture may encourage discoloration of fracture. Discoloration of the natural teeth may be prevented by the immediate removal of the pulp tissue, the attentive cleaning of the pulp chamber with normal saline, and the storage of the teeth in an atmosphere of 100 per cent humidity. Adequate vertical and horizontal overlaps insure stability of the denture and suitable protection of the natural teeth from cracknig or curshing during function of the denture. If accidental fracture or discoloration of a natural tooth should occur, ti may be replaced by an acrylic resin tooth duplicated from the natural tooth or by an artifical tooth of proper size and color.


Methods to preclude aspiration or swallowing of dental appliances. A technique which precludes the swallowing of dental restorations during fitting and cementation has been described. An alternative technique is to spot-weld a small loop or wire to the finished crown. Dental floss may be attached to the loop. Another method is to attach a piece of unwaxed floss to the completed crown with Eastman adhesive 910. The floss is removed after the restoration is cemented.


Hot-pressed porcelain process for porcelain-fused-to-metal restorations. A technique has been described that simplifies the production of full-coverage, porcelain-fused-to-metal restorations. The process utilizes a furnace-flask system in which the restoration is invested in a high-temperature refractory material and processed at an elevated temperature (1,850 degrees F.) under pressure. Shrinkage of 0.001 to 0.005 inch at the supporting cusp tips and fossae has been recorded. Tests indicate that the porcelain produced has a tensile strength and wear rate similar to those of porcelain processed by conventional methods.


[Pathological, clinical and radiological study of colonic lympho-reticulosarcoma. Report of 8 cases (author's transl)]. The authors report 8 cases of lympho-reticulosarcoma of the colon and emphasize the rareness of this tumour (10 percent of cases) compared with other localisations in the stomach and small intestine. Whether primary or secondary, lymphosarcoma of the colon has various radiological appearances, depending on the mode of development of the sarcoma in the wall of the colon. Mainly sub-mucosal, it may remain localised or extend to the whole of the colon, predominating in the ileo-coecal and recto-sigmoid regions. Localised tumour forms present either in the form of large polycyclic lacunae, sometimes invaginated or as vast ulcerations with irregular nodular margin, or as due to parietal infiltration and exoluminal development of the tumour mass and neighbouring adenopathy. It is sometimes confused with carcinoma of the colon, e.g. vegetating carcinoma, colloid carcinoma, or peritoneal metastases, or with a regional abscess, e.g. appendix abscess or diverticulosis. The correct diagnosis is made on operation. The extensive colonic forms rarely take on the appearance of lymphoid pseudopolyposis, more often that of a very unusual nodular form formed of hazy lenticular lacunae. It may be confused with nodular colitis, it differs from this, however, by the absence of ulceration, changes in caliber and the persistance of normal haustration, a reticulated appearance of the mucosal outline during evacuation of the barium. In all cases, the discovery of a colonic lympho-reticulosarcoma implies complete digestive radiological investigation in order to seek gastric, duodenal or intestinal localisations, together with a search for other extra-digestive localisations. In fact, the great diffusion of the lesions modifies the prognosis and the therapeutic attitude. These lymphosarcomas and reticulosarcomas of the colon have a similar pathological and radiological appearance but differ by their sensitivity to treatment with cobalt, as reticulosarcomas are more resistant.


[Osseous anomalies of centrofacial lentiginosis (39 cases) (author's transl)]. The authors present the results of an investigation on 39 cases of centrofacial lentiginosis. Eleven patients urged to be examined because of their alarming health condition, and 28 cases were found out following an inquiry within some collectivities. With centrofacial lentiginosis the cutaneous hereditary polydysplasia (characterized by typical lentigines), the dysraphic state and neuro-psychic troubles are usual and awaken the interest of the radiologist due to the frequency of various dysmorphoses, growth disturbances and a trend for arthrosis. The radiologist has to pay a due attention to these aspects representing as many manifestations of a disease of a hereditary-family type since a possible centrofacial lentiginosis also means a possible disabling potential associated with education and vocational training problems.


Progesterone levels following treatment of seasonally anoestrous ewes with synthetic LH-releasing hormone. Plasma progesterone determinations were carried out on blood samples collected daily from Clun Forest ewes during the normal oestrous cycle and also after administration of LH-releasing hormone (LH-RH) during seasonal anoestrus. Levels of plasma progesterone at oestrus ranged from 0.1 to 0.5 ng/ml and luteal phase levels from 3 to 6 ng/ml. Levels found during seasonal anoestrus were within the range of those observed as oestrus. Following treatment with LH-RH, there was in increase in the plasma LH level in a-l cases and ovulation occurred in twenty-three out of twenty-seven treated ewes. In the animals which ovulated, the plasma progesterone concentration either remained basal (eighteen animals) or rose to a lower level (2 ng/ml is greater than) than that found during the luteal phase of the cycle.


Properties of strains of Escherichia coli isolated from a variety of sources. Strains of Escherichia coli causing urinary-tract infections were found to be more commonly haemolytic than were faecal strains. Strains from the introitus that subsequently gave rise to urinary-tract infections resembled urinary strains and those that did not give rise to infections resembled faecal strains. alpha-Haemolysin production was closely associated, in strains from a variety of different sources, with the production of a haemolysin detectable in liquid medium and with cytotoxicity in tissue culture.


An erythrocyte-sensitising antigen from Vibrio cholerae. Erythrocyte-sensitising antigens (AE) were prepared from Vibrio cholerae serotypes, from EL-Tor vibrio, Escherichia coli and Salmonella enteritidis by digesting the organisms with NaOH followed by precipitation with alcohol. When AE was used in indirect haemagglutination (IHA) tests, the results in a number of cases were somewhat more sensitive and more specific than those obtained in classical agglutination tests. No cross reactions occurred between V. cholerae serotypes and E. coli and S. enteritidis. Much of the reactive part of the AE was not sedimentable at 100,000 g for 1 h. The eluant from the B. cholerae AE on Sephadex G-200 yielded three fractions, one of which was the most active in IHA tests. Treatment of the AE with trypsin resulted in an appreciable increase in the heterotypic serum titres in IHA tests. The spectrophotometric absorption of the AE at 260 nm showed a hump that may have been indicative of the presence of nucleic acid. Treatment of the antigen with ribonuclease reduced its nucleic acid content but did not change to any significant extent the reactivity of the preparation. The AE antigen of V. cholerae was Molisch-positive and was capable of sensitising untanned erythrocytes in IHA tests. It is suggested that the reactive part of the AE antigen is a carbohydrate complex.


Pigment production by Bacteroides species with reference to sub-classification. All six reference strains of Bacteroides species, 36 laboratory isolates conforming to this group, and individual strains of Escherichia coli, Proteus mirabilis, Salmonella typhimurium and Clostridum welchii produced a dense black pigment, identified as ferrus sulphide, when grown in cooked-meat media containing cystine and ferrous sulphate. This was an indicator effect resulting from the production of H2S by the bacteria in the presence of ferrous ions and was unrelated to the characteristic pigment produced by strains of B. melaninogenicus when grown on blood agar. A pigment was extracted by ultrasonic disintegration of washed cells of three reference strains of B. melanino-genicus grown for 1 week in horse-blood broth and on human-blood agar. It was intracellular or cell-associated, soluble in water and had the spectrophotometric characteristics of a derivative of haemoglobin. No such pigment was extracted from strains of B. fragilis or B. necrophorus by similar procedures. Pigment production is a stable characteristic of those strains of Bacteroides called B. melaninogenicus and it is a significant property in the classification of the Bacteroides group. However, the pigment-producing strains are not a homogenous species, and there were considerable differences between the results of biochemical tests and antibograms obtained with the three strains of B. melaninogenicus.


The pathogenesis of infections of the mouse caused by virulent and avirulent variants of an influenza virus. A virulent variant of the normally avirulent Kunz strain of influenza virus was obtained by serial passage in mice, and the pathogenesis of the infections caused by the two strains was studied. The virulence of the passaged variant did not appear to result from increased growth in lungs, from acquisition of resistance to non-specific inhibitors or from inadequate immunogenicity, but from its greater ability to replicate in alveolar cells. The apparent adequacy of defence mechanisms to protect against mucosal infection but their failure to protect against infection of alveolar cells in discussed.


A new biotyping scheme for Salmonella typhimurium and its phylogenetic significance. A new, two-tier system for biotyping Salmonella typhimurium gives a finer and more reliable differentiation of strains than the Kristensen scheme and is capable of future extension by the addition of new types and new tests. Strains are allocated to a primary type (1-32) by their reactions in five primary tests with Bitter's xylose medium, meso-inositol, L-rhamnose, d-tartrate and m-tartrate. Subtypes are distinguished within the primary types by reactions in ten secondary tests, which include observations for flagella and type-1 (haemagglutinating) fimbriae. Full biotypes are designated by letters indicating the subtype reactions appended to the primary-type numbers. A series of 2030 strains of S. typhimurium collected from many different sources and countries during 53 years was classified into 19 of the 32 potential primary biotypes and into 144 full biotypes. Of the series, 14% (275) were non-fimbriate inositol-nonfermenting rhamnose-nonfermenting (FIRN) strain in primary biotypes 29-32. Most other strains were fimbriate and rhamnose fermenting. Observations on several series of cultures isolated from different human or animal sources in the same epidemic showed that the biotype characters of a strain were generally stable during its growth in the natural environment and in the unselective media used for isolation and storage. Most non-fermenting strains gave rise to fermenting mutants on prolonged incubation in the substrate-containing--and therefore selective--test medium, and false-positive results from this cause were avoided by making the definitive readings of tests after a short, carefully chosen period of incubation. A genealogical tree has been drawn to show how eighteen observed primary biotypes may have evolved from a presumed archetypal ancestor of biotype 1.


A defined medium for the growth of Clostridium tetani and other anaerobes of clinical interest. The growth of six strains of Clostridium tetani was assessed in a chemically supplemented commercially available defined medium. All strains grew reliably even after 12 serial passages, and two strains produced demonstrable toxic activity after passage. Consistent growth of the test strains could also be obtained on a solid version of this medium ("CA109-S" medium), and the strains could be serially passaged on this medium. Preliminary evidence is presented that the medium supports the surface growth of some other test anaerobes. Such a defined solid medium might prove of value in further studies on the surface growth of C. tetani and of other anaerobes of clinical interest.


A simple single-step immunoimmobilisation method for the detection of Salmonella in the presence of large numbers of other bacteria. A single-step disk immunoimmobilisation method for the detection of motile salmonellae is described. It combines in a single step the use of the motility of these bacteria in soft agar, their selective growth on Salmonella-Shigella media, and their immobilisation by polyvalent H antiserum. The method is shown to be 10 to 10,000 times more senstitive than a standard method for detection of Salmonella under the experimental conditons used. The time required for detection is shortened to 24-48 h.


Enteropathogenicity of Aeromonas hydrophila and Plesiomonas shigelloides. Aeromonas hydrophila was enteropathogenic in ligated ileal loops of rabbits, causing a fluid accumulation of 1-0 - 2-0 ml per cm of gut length. Gut reaction could be produced with an inoculum as low as 10-4 viable bacteria. There was no difference in the nature of the positive reactions given by strains isolated from diarrhoeal and non-diarrhoeal children and adults and from water. Plesiomonas shigelloides, on the other hand, did nt cause a significant gut reaction. A. hydrophila multiplied in the ileal loop by about 10-5 wheras P. shigelloides did so at only 10-2-3. These experiments on a animal model thus indicated the enteropathogenic nature of A. hydrophilia, but no definite conclusion could be drawn from this study on P. shigelloides.


Lysis enhancement: a novel form of interaction between beta-lactam antibiotics. A novel form of synergy has been observed to occur between cephalexin and certain other beta-lactam antibiotics. In the presence of cephalexin a reduction was found in the concentration of other beta-lactam agents needed to induce lysis of Escherichia coli; the effect was particularly marded when cephalexin was allowed to act for a short time before the addition of the second agent. The basis of this type of synergy--which is not likely to be of therapeutic value--is discussed in terms of a theroy perviously put forward, whcih suggests that penicillins and cephalosporins have two distinct sites of action in Gram-negative bacilli.


Chemotherapeutic implications of early tumor cell growth in an animal brain-tumor model. The onset of tumor cell proliferation was determined in an animal brain-tumor model in which tumor cells had been injected into the cerebrum of rats through a hollow stainless steel screw implanted stereotactically. Tritiated thymidine uptake in the DNA at various periods after injection of tumor cells indicated no significant proliferation of tumor cells until 168-192 hours post implantation, after which tritium uptake increased exponentially. Control rats with screws alone or screws through which balanced salt solution had been injected showed an increased uptake at 72 hours, a phenomenon not observed in animals given tumor cells. Our findings suggested that, in the tumor model described, experimental chemotherapy tests should be deferred until at least 7 days post implantation.


Marek's disease in immunosuppressed chickens: growth of a transplantable lymphoma and development of the disease by natural exposure. Evidence indicated that treatment of chickens with Cytoxan at hatching (bursectomy) had little effect on the development of transplantable Marek's disease (md) lymphoma. Cytoxan treatment of chickens at 2 and 3 weeks of age, however, apparently reduced the incidence of visceral tumors in chickens naturally exposed to MD. Amelioration of MD in immunosuppressed chickens was possibly mediated through suppression of MD-induced T-cell proliferation.


Variations in carcinoembryonic antigen localization in tumors of the colon. The localization of carcinoembryonic antigen (CEA) in 78 tumors of the human colon was studied with the use of antibody to CEA in an indirect Coons test. The neoplasms differed morphologically and could be divided into two types: a) tissues in which CEA was localized in cells, and b) tissues in which malignant cells secreted CEA in greater or lesser quantity. In the first type of tissue, five forms of cells were observed: goblet-like, small vacuolar, limbic, those with intracellular accumulation of antigen, and diffuse. Tumor tissue secreting CEA could also be divided into five forms: holocrine-like, aprocrine-like, intraglandular, apical-basal, and lacunar-infiltrative. The change in CEA localization in pathologically altered cells were designated 'antigenic translocation."


Interaction of BCG-activated macrophages with neoplastic and nonneoplastic cell lines in vitro : quantitation of the cytotoxic reaction by release of tritiated thymidine from prelabeled target cells. Peritoneal cells from mice infected ip with Mycobacterium bovis, strain BCG, were cytotoxic to syngeneic tumor cells in vitro. Cytotoxicity was estimated by measurement of release of tritiated-thymidine (3-H-TDR) from prelabeled target cells. The cell responsible for tumor cytotoxicity was the macrophage. Macrophages from uninfected mice or from oil-, starch-, or thioglycollate-induced peritoneal exudates had little effect on labeled tumor monolayers. Tumoricidal macrophages were present at 3-7 days and persisted through 6 weeks after a single BCG injection. Two neoplastic/nonneoplastic cell-line pairs, all four of the cell lines derived from a cloned syngeneic embryo cell line, were used as target cells for BCG-activated macrophages. Both tumor cell lines released significantly more 3-H-TDR than did the two nonneoplastic lines. In a mixed neoplastic/nonneoplastic target cell population, BCG-activated macrophages selectively destroyed the neoplastic cells; nonneoplastic cells were not affected as "innocent bystanders".


Progressive pulmonary insufficiency and other pulmonary complications of thermal injury. Progressive pulmonary insufficiency appears to be a universal response to the lung to a variety of injuries which damage the pulmonary-capillary emdothelium. Persistent hyperventilation, unresponsive to the administration of oxygen, is the earliest clinical sign of this complication of trauma and should prompt close monitoring of pulmonary function (measurement of arterial blood gas and pH levels, Vd/Vt A-aDo2, minute ventilation, vital capacity and inspiratory force) to assess the severity of the disease, the need for mechanical ventilatory support and the effectiveness of treatment. Other pulmonary complications of burn injury range from carbon monoxide poisoning and narcotics overdosage in the immediate postburn period through marked hyperventilation directly related to burn size occurring in the absence of significant parenchymal change to later occurring hematogenous and airborne pneumonia. Inhalation injury, a chemical tracheobronchitis which significantly increases the mortality of a given-sized burn, may be present immediately postburn but clinically inapparent for 48-72 hours. 133Xenon lung scans permit early diagnosis of this pulmonary injury and the timely institution of a graduated therapeutic response keyed to the severity of pulmonary disability. Knowledge of the pathogenesis of each of these complications is requisite for the physician caring for burn patients and permits the employment of rational preventive and therapeutic measures.


Transnavicular perilunate dislocations.

Transnavicular perilunate dislocations. A complex injury of the wrist, the transnavicular perilunate dislocation, is analyzed along with a review of the literature. A method of management is proposed for this injury based on experience gained with nine such injuries. Our conclusion is that open reduction and internal fixation is a necessity unless an anatomic manipulative reduction can be accomplished. It is proposed that a navicular bone graft be employed at 6 weeks if avascular necrosis of the navicular and early signs of nonunion are evident. The rationale for these proposals is discussed.


New developments in the diagnosis and treatment of urinary tract infections. Not long ago it was customary to expect an atmosphere of confrontation and controversy when urologic surgeons and infectious disease physicians met at conferences and symposia. Even more often each group exhibited an attitude of "benign neglect" towards the other. Times have changed in large part because of the efforts of the leadership group in urology. The establishment of an Advisory Board for this Journal, drawn from non-urological disciplines, is one example of the effort being made to draw together all concerned with urinary tract infections and pyelonephritis. I have been asked to review some practical up-to-date matters relating to the diagnosis and treatment of urinary tract infections and pyelonephritis from the point of view of an infectious disease physician. However, it may be helpful to begin with a synthesis of current concepts of the natural history of urinary tract infection, since the need for early diagnosis and the tactics for treatment depend largely on our expectations for the patient. This synthesis requires definition of terms that are acceptable to a wide variety of disciplines. The review would then focus on new methods for screening and office diagnosis, antimicrobial sensitivity tests, localization of infection and indications for urologic investigation, particularly in relation to vesicoureteral reflux. New developments in treatment of urinary tract infections will be discussed. Special attention will be given to areas in which we are ignorant and require more information. Last, I will direct my attention to the problem of the urinary catheter, hoping to arrive at a synthesis of the situation which will tell it like it is but avoid overstating the case.


Psychological factors in hypospadias repair. Children undergoing hypospadias repair and their parents have anxieties related not only to the operation but to future expectations. These anxieties are expressed by children through their drawings and by parents through interviews. They are enhanced by the fact that the hypospadias defect is only noticeable to the parents and child and is kept as secret information. Other defects, such as cleft palate, are obvious and cannot be hidden. The anxieties associated with hypospadias appear to be different whem compared to those associated with more obvious deformities.


Effects of gentamicin on the intestinal bacterial flora of rats. 1) Normal intestinal microbial flora (NF) in feces of rats were examined before and after administration of gentamicin (GM). Although GM caused no influence on NF after 6 hours, the number of NF decreased markedly 24 hours after GM, viz., the count of coliforms, enterococci and lactobacilli was reduced to 1/10-1/100 of the control value while proteus and fusobacteria declines in number down to 1/100-1/1,000 times as low as the control value. 2) The decreased count of NF tended to recover to some degree at the end of the 1st therapeutic week and the considerably recovered count continued thereafter indicating about 1/10 times as low as the control value until a 12-week experimental period, except that the count of lactobacilli returned to almost normal. 3) Susceptibility of coliforms isolated from GM-treated rats to GM was nearly equal to that of the bacteria isolated from the untreated control rats, which revealed no development of drug resistance to GM. 4) The increasing rate of body weight was higher in GM-treated rats than in the control, and the feed intake was consequently great in the former.


Pathophysiologic responses of the subhuman primate in experimental septic shock. The grave clinical aspects of septic shock have stimulated the search for an experimental animal model which more closely relates to human pathophysiology. This study of the cardiovascular-pulmonary-morphologic responses of the baboon to slow infusions of live Escherichia coli organisms was designed to approximate more closely the human clinical entity. Anesthetized young adult baboons received 3-hour intravenous infusions of organisms at an average dosage of 8 times 10-9 organisms per kg. body weight. Responses of animals were followed during a period of 6 hours in the anesthetized state. There was progressive systemic hypotension and steadily decreasing cardiac output. Total peripheral resistance was uniformly depressed during the infusion, but was variable during the post-infusion survival period. Increases in heart rate, alveolar-arterial oxygen tension gradient, and oxygen uptake were uniformly present. These alterations bear close resemblance to those seen in other subhuman primates administered short term doses of live organisms. There were extensive morphologic changes in pulmonary, cardiac, and renal beds. Glomeruli contained multiple fibrin thrombi and disrupted platelets, and the glomerular capillary endothelium was focally edematous and disrupted. The myocardium exhibited capillary endothelial edema and fluid accumulation in interfiber and intrafiber spaces. There were sequestration, degranulation, and fragmentation of polymorphonuclear leukocytes and platelets, and characteristic endothelial lesions within the pulmonary vascular bed. Findings demonstrate both cardiovascular-pulmonary dysfunction and renal, cardiac, and pulmonary morphologic lesions. The baboon shock model appears to be well suited for studies of experimental septic shock and bears close resemblance to the human clinical entity.


Oxygen toxicity in the newborn. The effect of prolonged 100 per cent O2 exposure on the lungs of newborn mice. A comprhensive morphologic study of pulmonary oxygen toxicity was undertaken on 78 newborn mice of a single, highly inbred strain continuously exposed to 100 per cent oxygen at normal atmospheric pressure for 7 days. The survival rate was 95 per cent through the first 4 days and 75 per cent through the 7th day. Our findings indicate that response to continuous exposure to 100 per cent oxygen can be divided arbitrarily during the first 7 days into three different phases. During the first, or acute toxic, phase (which generally extends into the 3rd day of exposure), mechanisms, probably adaptive in nature, are sufficiently developed in some of the newborn animals to permit them to survive a continuous 7-day exposure. The acute toxic phase is followed by the critical, high mortality phase, which lasts 3 to 4 days. During this phase, which can be subdivided into a continuum of several stages, the changes seen in the initial, acute toxic phase may progress to more pronouced injury. If the injury is severe, massive pulmonary edema and hemorrhage occur, accounting probably for the deaths of most of the animals in previous similar experimental studies and of 25 per cent of our animals by the 7th day. The second stage of this high mortality phase, being more clearly reactive, consists of a progression of reactive mitochondrial changes, proliferation of granular pneumocytes, and a return to normal of the features of the membranous pneumocytes. The beginning of the third phase, the chronic injury and repair phase, is characterized by the appearance of fibroblasts and a concomitant moderate increase in the amount of collagen.


Progression from minimal or focal to diffuse proliferative lupus nephritis. Histologic classification of renal glomerular lesions in 46 patients with systemic lupus erythematosus revealed 17 as having either focal proliferative (10 patients) or minimal mesangial proliferative (7 patients) glomerulonephritis. Six of the 17 have progressed to a diffuse proliferative glomerular lesion on subsequent renal biopsies, 9 months to 5 years later. Five had clinical deterioration at the time of follow-up biopsies; currently one is undergoing hemodialysis and four others have decreased renal function. Although a comparison of those who progressed with those who are stable revealed greater proteinuria in some of those who progressed, no other clinical features of the initial illness were different in the two groups, nor were differences between the two groups noted on light microscopic examination of initial renal biopsies. However, ultrastructurally, electron-dense deposits, especially those subendothelial in location, were noted along glomerular capillary basement membranes more frequently and in greater number in those who progressed. These findings suggest that lupus patients with a mild proliferative glomerulonephritis may have clinical and histologic progression of the renal disease, and those who progress cannot be clearly defined by clinical or light microscopic features. Ultrastructural demonstration of subendotheial deposits suggests a greater likelihood of subsequent progressive disease.


Bronchographic and angiologic observations in experimental autotransplantation of a lung or lung lobe. Roentgenologic examinations were conducted after 260 experimental autotransplantations of a lung or its lobe in the course of a long-term dynamic observation (maximum follow-up 4 1/2 years). Accentuation and indistinctness of the pulmonary pattern were observed in combination with small focal shadows in the early post-transplant period (up to 15 days) in dogs with an uneventful course. Dynamic observations (maximum follow-up 4 1/2 years) revealed no changes in the pulmonary tissue and no anatomic or functional changes in the bronchial tree and vessels. In the late period after orthotopic and heterotopic autotransplantation of the lower lobe, the changes were due to impaired topographic interrelations of the thoracic organs: Removal of the upper lobe of the intact lung into the upper part of the left pleural cavity. This phenomenon, the so-called mediastinal hernia, is facilitated by the mobility of the cranial part of the mediastinal septum in dogs. Heterotopic autotransplantation of the lower lobe in place of the removed contralateral lung resulted in no shift of the mediastinum and no changes in the autotransplanted lobe in the late follow-up period. The signs of a mediastinalhernia were less distinct than after orthotopic autotransplantation of a lung lobe.


Fatal air embolism during thoracotomy for gunshot injury to the lung. Report of a case. Fatal coronary air embolism occurred during thoracotomy in a patient with a gunshot wound involving the hilum of the right lung. Embolism was observed during a second period of failure of heart action. Evidently, air entered the pulmonary veins from the bronchus, which was receiving positive-pressure ventilation. The literature contains reports of only 3 similar cases, but we suspect that air embolism may be responsible for death and morbidity in additional cases in which accidental or iatrogenic lung trauma has produced a pathway between the bronchial tree and the pulmonary veins.


An overview of research in cancer diagnosis. The diagnostic research program of the National Cancer Institute encompasses detection or screening, methods of diagnosis, and prognosis. The present objective of this program is diagnosis of 75% of all cancers at a time when 90% of these have not metastasized. The Institute's Divison of Cancer Biology and Diagnosis has directed its attention toward general diagnostic methods (immunologic, chemical, cytologic, imaging, and endoscopic) and organ site programs (breast, lung, cervix, bowel, bladder, and pancreas). The organ site programs usually involve multiple diagnostic techniques applied to a specific organ. Screening for asymptomatic cancer seems an important immediate objective. Optimum frequency of screening should be established for individual organ sites and for combinations of sites, to determine whether multi-site screening programs can significantly reduce mortality from cancer.


Hemangiosarcoma of the liver. Spectrum of morphologic changes and clinical findings. Analysis of four cases of hemangiosarcoma of the liver and review of the literature indicate that these tumors are either predominantly cystic and fairly well differentiated or are more solid and poorly differentiated. Well-differentiated hemangiosarcomas may resemble peliosis hepatis or other benign conditions. The tumor was associated disseminated intravascular coagulation and fibrinolysis syndrome in one of our cases. One of our patients had received thorium dioxide (Thorotrast) but none seemed to have been exposed to arsenicals or to vinyl chloride.


Metabolic support for renal sodium reabsorption. Our studies demonstrate that renal substrate metabolism may subserve several functions. 1. Substrate oxidation concerns us all, since it provides the support for the internal and external work functions of the kidney. It appears that only certain of the substrates utilized by the kidney have, as their major fate, oxidation. 2. All the substrates participate in the synthesis and turnover of intrarenal constituents. These rates remain to be quantified. In the case of free fatty acids, are their turnover rates through the intrarenal lipid pools proportional to T-Na+? If so, this phenomenon would be part of the Q-O2 minus T-Na+ correlation. Or, is lipid synthesis related to T-Na+ in a nonlinear fashion? 3. Certain substrates (lactate, glycerol, fructose, and probably free fatty acids) are readily interconverted in kidney. This phenomenon is particularly prominent when the blood concentrations of these substrates rise. Glucose or lactate are the major interconverion products, at least in vitro. Are there significant quantities of these or other products synthesized by kidney in vivo? The in vivo observations with 14-C-palmitate suggest, but do not prove, that this is the case. The prime example of a renal substrate interconversion mechanism is, of course, the one so carefully and completely elucidated by Pitts: minus NH3 production from glutamine. The further questions he has raised in this area will undoubtedly keep him and us interested and active for some time to come.


Distribution and transport of varied substances in the dog kidney in vivo: implications with regard to metabolic activities. Some matters bearing on renal metabolic activities have been reviewed. The distribution of solutes to various regions of the kidneys depends not only on convection by blood and tissue fluid flow but also on diffusion of the solutes in the tissues. Lipid solubility may play a significant role in tissue diffusion in that substances with significant lipid solubility may have access to more direct pathways than strictly hydrophilic substances. Glucose utilization by the kidney is significant. Glucose may contribute as much as 25 per cent and lactate, through decarboxylation, as much as 30 per cent of the renal carbon dioxide production. Together, glucose and lactate may account for about 50 per cent of the total renal carbon dioxide production. There is evidence that there is substantial lactate production by the kidney as well as gluconeogenesis. The conditions for luminal and anti-luminal cell surface interactions with D-glucose differ with regard to configuration, conformation and phlorizin affinity. Possible pathways of entry of glucose into metabolic activities are briefly considered.


Renal metabolism of citrate.

Renal metabolism of citrate. Our studies on renal handling of citrate have shown that: (1) citrate enters renal tubular cells from luminal fluid (reabsorption) and peritubular blood; (2) reabsorption becomes maximal, i.e., Tm-limited, at filtered loads 7 to 8 times the normal; (3) administration of malate stimulates net renal production of citrate, leading to release into urine (net secretion) and into peritubular blood; (4) acute metabolic alkalosis, induced while plasma citrate levels are above normal, depressess net citrate reabsorption, stimulates citrate release into peritubular blood and abolishes overall renal uptake of citrate; (5) essentially all citrate extracted by the kidney is converted to CO2 at endogenous circulating levels. This contribution is 15 per cent of the total renal CO2 production and is independent of chronic alterations in acid-base balance.


Characterization of pancreatic islet monoamine oxidase. Monoamine oxidase (MAO) is present in isolated islets of Langerhans of rabbits, golden hamsters, and rats. Tryptamine, tyramine, serotonin, and dopamine can serve as substrates for this enzyme. We compared the properties of islet and liver MAO in the rabbit. The Michaelis constant (K(m)) for tryptamine of islet MAO (6.5 times 10-5M) is greater than the K(m) of liver MAO (3 times 10-5M). The K(m) for tyramine of islet MAO (1.5 times 10-4M) is similar to the K(m) of liver MAO (1.8 times 10-4M). Islet MAO appeared to be more susceptible to heat inactivation (50 degrees C) than did liver MAO. This may be an artifact produced by the collagenase technique used in the preparation of the islets, as collagenase treatment of liver increased the thermal lability of the MAO in this tissue. Liver and islet MAO have a comparable sensitivity to MAO inhibitors such as clorgyline, deprenyl, tranylcypromine, pargyline, and harmine. The present report, along with previous reports that MAO inhibitors alter insulin secretion, suggests that islet MAO may modify insulin secretion.


Pituitary-gonadal function in chronic renal failure: the effect of luteinizing hormone--releasing hormone and the influence of dialysis. Sixteen adult male patients with chronic renal failure undergoing either chronic intermittent hemodialysis (HD) or chronic intermittent peritoneal dialysis (PD) were studied both before and immediately after dialysis. The gonadotropin responses to luteinizing hormone-releasing hormone (LH-RH) was determined, revealing an excessive luteinizing hormone (LH) response with a delayed return to normal in both dialysis groups. No significant alteration in follicle-stimulating hormone (FSH) kinetics was observed. There was no significant difference in the mean gonadotropin responses to LH-RH between the HD and PD groups, and dialysis had no effect on either mean LH or FSH responses. The chronic renal failure patients with testicular atrophy had an excessive FSH response to LH-RH when compared to those patients without testosterone was significantly lower than normal. Chronic renal failure effects testicular function and testicular atrophy is associated with seminiferous tubular destruction and an excessive FSH response. Poor renal clearance may play a role in the abnormal LH response observed.


Gamma-ray densitometry in the analysis of hemodynamic function. An instrument has been developed to record contrast dilution curves by a noninvasive technique. Transthoracic roentgen density alterations are recorded by use of a solid state radiation detector array. A small amount of injected nonradioactive, radiopaque contrast material is distrubuted throughout the central circulation. The detector array positioned over the cardiopulmonary silhouette, records changes in density during the passage of the contrast material, and typical indicator dilution curves are transcribed. These curves reflect changes in blood flow distribution, vascular volume, cardiac function, and intrathoracic vascular shunts; and define the hemodynamic status of the circulatory system.


Double blind evaluation of long acting diethylpropion hydrochloride in obese patients from a general practice. Obese patients encountered in general practice were studied in order to determine whether a long-acting form of diethylpropion hydrochloride (Tenuate Dospan) was more effective than placebo for weight loss. One hundred and two patients completed this double blind, 16-week crossover study. During the first eight weeks, the patients treated with diethylpropion hydrochloride lost significantly (P smaller than 0.001) more weight than the patients treated with placebo (an average of 11-1 lb or 6-4% of their initial weight as compared with 6-2 lb or 3-6% of their initial weight). When the group taking diethylpropion hydrochloride crossed over to placebo for a second eight weeks, they lost an average of 1-5 lb (0-9% of their weight at the start of the second period), while the group who crossed from placebo over to diethylpropion hydrochloride lost an average of 6-7 lb (3-8%). The advantages of diethylpropion hydrochloride over placebo are statistically significant.


A fully automated cardiac output analysis system. An automatic cardiac output analysis system is described in which indicator dilution studies are performed serially without operator assistance. Indicator dye injection, blood sampling, and monitoring for air entry into the system are performed automatically through a present program sequence. Sampled blood is returned to the subject through a venous cannula resulting in an absence of blood loss. This system may be used in performing cardiac output analyses on a serial basis and in infants and small animals where blood loss is critical.


The starch granuloma syndrome.

The starch granuloma syndrome. Starch glove powder is not entirely innocuous when introduced into the peritoneal cavity. Foreign body granulomas formed as relation to starch deposited in the peritoneal cavity may closely resemble malignant seedlings and thus mislead the surgeon in his proposed treatment of bowel cancer. In addition, the occurrence of starch granuloma peritonitis may provoke an unnecessary operation in a patient presenting with fever and peritoneal irritation a few weeks after a seemingly uncomplicated laparotomy.


[The demonstration of twitching motility in Eikenella corrodens]. In 18 out of 39 strains of E. corrodens twitching motility was observed. Spreading colonies were associated with this kind of motility.


An x-ray diffraction study of ribosome structure. Dense gels of E. coli 70 S ribosomes, their 50 S subunits, CM-like particles, RNP strands and their fragments, 38 S particles obtained from RNP strand folding upon addition of Mg2+ ions, and of unoriented salt-free and free rRNA sodium and magnesium salts were studied by X-ray diffraction. It was shown that under dense gel conditions RNA molecules contained in ribosomes unfolded by desalting, like all other particles considered here, have helical regions. Under these conditions free desalted RNA has no helical regions. Experimental data on X-ray scattering at medium angles were compared with the diffraction curves calculated for homogeneous prolate and oblate ellipsoids, for various ellipsoids containing a dense region or an internal cavity, and for ellipsoids containing internal periodic regions. The results indicate that the internal structure of the 50 S ribosome is periodic, i. e., its components form a periodic lattice. The lattice spacings are approximately 42 and 28 A with a 0.8g/g dry weight sample water content. When the 50 S particle water content drops below 0.2 g/g dry weight the periodic structure is disrupted. This disruption is reversible. It was shown that CM-like particles at high ionic strenght (2 M LiCl) have approximately the same internal periodicity as the 50 S particles, but in contrast they lose this periodicity at low ionic strength (10-2M tris-HCl and 5-10-3 M MgCl2).


The selective iodination of yeast phenylalanine transfer RNA with 125-I. Yeast tRNA-Phe has been labelled with 125-I under conditions which conserve the tertiary structure. Significant labelling was only found to occur on specific cytidines in single stranded regions, while other cytidines in single stranded regions and all those in the double stranded region underwent iodination to a very small extent. The pattern obtained from iodine labelling satisfies the conformation of a model recently proposed for this tRNA.


[Reticulosarcoma-like skin lesions in phenylketonuria (author's transl)]. Reticulosarcoma-like skin lesions are described in a boy with phenylketonuria (PKU) who was observed for 11 years. Association of the lesions with PKU is indicated by their dependence on the severity of the latter and their complete healing during treatment with low phenylalanine diet.


Ultraviolet reactivation and ultraviolet mutagenesis of infectious lambda DNA: strong inhibition by treatment of DNA in vitro with UV-endonuclease from Micrococcus  luteus. UV-endonuclease from Microcossuc luteus induces single-stranded breaks in UV-irradiated DNA of phage lambda and the average length of the fragments produced (after UV-doses to DNA of 135 and 675 erg/mm2) is equal to the average spacing between pyrimidine dimers. The plaque-forming ability of UV-irradiated lambda DNA used to infect Ca++-treated uvr A6, uvrB5 or uvrC34 recipient Escherichia coli cells (but not uve+ cells) may be significantly enhanced by treatment of lambda DNA with UV-endonuclease. This enzyme strongly decreases the reactivation of UV-irradiated lambda DNA caused by UV-irradiation of uvr+ or uvrA6 Ca++-treated cells and eliminates most clear-mutations especially if mutations are analysed using Ca++-treated uvr A6 recipient cells. It is concluded that UV-endonuclease switches a significant part of potentially mutagenic pyrimidine dimers from the UV-induced "error-prone" repair pathway to "error-free" excision repair pathway.


A mutant of Eshcerchia coli K-12, URT-43, with a temperature-sensitive defect at the incision step  of the excision repair mechanism. URT-43, which has a defect in excision repair, exhibits a temperature-dependent ultraviolet survival. It was shown that URT-43 requires protein synthesis but not DNA synthesis for recovery, by examining recovery in a growth medium containing chloramphenicol or nalidixic acid. The recovery of irradiated bacteriophage lambda in URT-43 took place in a medium containing nalidixic acid at 30 degrees, but not at 41 degrees, and chloramphenicol prevented this recovery. These results seem to imply that the product of the mutated gene in URT-43 is labile. URT-43 was confirmed to have a temperature-sensitive mutation at the incision step of the excision repair mechanism by examining the nick formation of parental DNA in alkaline sucrose gradients. The release of pyrimidine dimers was reinvestigated directly by one- and two-dimensional paper-chromatography and indirectly by examining the distribution of DNA molecules synthesized after irradiation. Dimers were excised into the acid-soluble fraction when growing bacteria were incubated, but were not excised when in amino acid starved bacteria. These results suggest that URT-43 is a mutant slowly excising pyrimidine dimers because the product of a mutated gene concerned with the incision step of the excision repair mechanism is unstable.


Mutagenic properties of cis-plantinum(II)diammino-dichloride in Escherichia coli. cis-Platinum (II)diamminodichloride (PDD), an anti-tumor agent, induced auxotrophic mutations in Escherichia coli, some of which were reverted to prototrophy by exposure to PDD, 2-aminopurine (2-AP), and N-methyl-N'-nitro-N-mitrosoguanidine (NTG), but not ICR derivatives. Similarly, various 2-AT-, NTG-, and ultraviolet light-induced auxotrophs were reverted to prototrophy by PDD. Some PDD-induced auxotrophs carried nonsense mutations and others could be phenotypically suppressed growth with streptomycin. Although these findings suggest that PDD promotes base substitutions, this mutagen may also cause base subtractions because (like NTG) it induced, at reduced frequency, reversion to prototrophy of certain ICR-induced auxotrophs. Isomeric trans-platinum (II)diamminodichloride, which lacks anti-tumor activity, was an ineffective mutagen. Near-optimal conditions for PDD-induced mutagenesis entailed prolonged cultivation with low levels of mutagen where the frequency of forward mutation to auxotrophy was 10-3 and that of a selected trp isolate to prototrophy was 10-2.


Mutagen screening with bacteria: niridazole and nitrofurans. The mutagenic activity of nitrofuran derivatives and of niridazole is easily demonstrated by spot tests using E. coli WP2 and its uvrA derivative but not by spot tests using the S. typhimurium strains developed by Ames. Quantitative tests show that S. typhimurium TA 1538(but not TA 1535, -36 or -37) is weakly induced to revert by niridazole. However, the maximum yield of revertants is well below that obtained with E. coli WP2 uvrA. None of the S. typhimurium strains respond to the three nitrofurans tested even in quantitative tests. The S. typhimurium strains contain the reductase required for metabolic activation of the nitrofurans and treatment of a uvr+ S. typhimurium strain with niridazole or with nitrofurazone causes single-strand breaks in DNA.


Mutagenicity of sodium hypochlorite for Salmonella typhimurium. Sodium hypochlorite, a standard household item, induces base-substitution mutations in Salmonella typhimurium. Because of its potent bactericidal effect the mutagenicity of hypochlorite could best be demonstrated by short-term exposure to this chemical followed by the addition of ascorbic acid to decompose the hypochlorite.


The mutagenic action of nitroimidazoles. II. Effects of 2-nitroimidazoles. The 2-nitroimidazoles Ro-71051 (N-benzyl-2-nitro-1-imidazole-acetamide) and Ro-5-9963 (3(2-nitro-1-imidazolyl)-1,2-propanediol) increased the mutation rate of a Klebsiella pneumoniae mutant to streptomycin-resistance including streptomycin-dependence in Luria and Delbruck's fluctuation test in concentrations of 0.05-1 mM and 0.02-0.2 mM respectively. The 2-nitroimidazole, azomycin, (Ro-5-9129/001) failed to increase the mutation rate. The results are compared to those obtained with the 5-nitroimidazoles methronidazoles metronidazole, nimorazole and dimetridazole, which caused a degree of increase similar to Ro-7-1051 and Ro-59963.


Identity and cytotoxic capacity of cells infiltrating renal allografts. To determine the identity and cytotoxic capacity of lymphoid cells involved in allograft rejection, we studied viable, monodispersed cells recovered from 10 rejected human renal allografts. A heterogeneous population of cells including macrophages and both bone-marrow (B) and thymus-derived (T) lymphocytes accumulate in rejected grafts. Infiltrating lymphocytes exerted a specific cytolytic effect on 51Cr-labeled peripheral blood lymphocytes bearing donor antigens, ranging from 7 to 44 per cent specific lysis in nine of 10 cases. Cytolysis was closely correlated (r equal 0.91, p less than 0.05) with the histologica grade of cellular rejection but not with humoral rejection, suggesting that cytotoxic lymphocytes are an important element in cellular rejection. Limited fractionation studies showed that both T cells (in early rejection) and non-T cells (in late rejection) may produce cytotoxicity. Since as many as 50 per cent of cells recovered bore Fc receptors, the rejection process may also involve antibody-dependent target-cell lysis.


Effect of temperature on growth and macromolecular biosynthesis in Cryptococcus species. Cryptococcus neoformans, a pathogenic yeast, grows at temperatures between 25 and 37 degrees C. However, the closely related non-pathogen C. albidus exhibits restricted growth at temperatures above ambient with little or no growth at 37 degrees C. The inhibition of growth of the non-pathogen, as measured by turbidity, cell number, and per cent budding, is reversible after 48 hr at the non-permissive temperature (37 degrees C). Growth cessation at 37 degrees C is accompanied by a corresponding decrease in DNA synthesis, which is not observed in C. neoformans. RNA and protein synthesis in C. albidus and C. neoformans are only slightly affected at the elevated temperature. Degradation by nucleases does not seem to account for the differences found in this cumulative DNA synthesis in C. albidus at 25 and 37 degrees C. These facts suggest that C. albidus may possess a thermo-sensitive defect in the machinery responsible for the initiation of DNA replication.


Incidence of yeasts and influence of nystatin on their control in a group of burned children. The incidence of yeasts in the oral cavity, rectum and urine of a population of 60 children hospitalized for treatment of acute second and third degree burns was approximately the same at the time of their admission as would be expected in healthy subjects. After hospitalization, the incidence of yeasts was reduced in the intestinal tract of acute patients who received nystatin orally but increased in the oral cavity. The majority of 418 yeasts were inhibited in vitro by less than 50 units/ml nystatin and only 6 yeasts were resistant to more than 3.1 mug/ml amphotericin B. The oral cavity appeared to act as a significant reservoir from which yeasts spread to cause or contribute to the deaths of 2 of 5 patients who died during the study.


Uremic intoxication.

Uremic intoxication. The toxic effects of metabolites that are known to accumulate in renal failure are described and the role that they may play in causing uremic symptoms is considered. The opinion of the Authors is that all they are likely to take a lesser or greater part in uremic intoxication. Methylguanidine seems to be very important in this context while for some others (like amines) nothing can be stated for studies on their chronic toxicity are lacking. The hypothesis is also considered of the accumulation of unidentified toxic metabolites with a middle molecular weight. It is stated, as to this problem, that the clinical evidence apparently supporting univocally their existence, is instead also consistent with the hypothesis of toxins (like methylguanidine) having a preferential distribution in the intracellular fluid compartment.


Disorders of carbohydrate and lipid metabolism in uremia. Glucose intolerance and hypertriglyceridemia appear to be frequent metabolic concomitants of chronic uremia. Both these abnormalities are ameliorated but not eliminated by intensive hemodialysis and aggressive treatment of the uremic state. The plasma lipid alteration appears to result principally from disturbances in both the production and catabolism of the triglyceride-rich lipoproteins. The persistence of these well-recognized cardiovascular risk factors may contribute to the accelerated premature cardiovascular disease that appears to devastate chronic dialysis patients.


Calcium and phosphorus metabolism in chronic uremia. In chronic uremia, the clinical disorders o calcium and phosphorus metabolism are influenced by the following factors: (1) intestinal absorption of calcium and phosphate, resulting in a negative calcium and phosphate balance at normal dietary intakes; (2) renal handling of calcium and phosphate: the fractional transport of calcium (the isoosmotic reabsorption taking place in the proximal tubule) is not affected by GFR modifications, whereas the Tm-limited reabsorption is severely impaired; the external phosphate balance is kept, even in the presence of a reduced nephron population, by means of a proportional reduction in TmPO4 values; (3) physiochemical state and turnover of body calcium and phosphate: in uremic patients, the distribution spaces, turnover rate of calcium, and accretion rate of bones are increased in comparison with the controls; the calcium infusion test in patients with renal osteomalacia is followed by a regular increase in plasma [PO4], whereas a significant decrease is observed in patients with renal osteitis fibrosa, due to the extreme 'avidity' of bones for calcium phosphate; the role of hyperphosphatemia is critical in keeping the plasma [Ca] lower than the expected values for a given metabolic set; moreover, an increased cell uptake of phosphate could counteract to some extent the reduced renal clearance of phosphate; (4) structural and biochemical modifications of bone tissue: uremic osteodystrophy consists mainly of two components: (a) osteomalacia, with osteoid excess, disappearance of the calcification front, and diffuse pathologic mineralization, and (b) osteitis fibrosa, with severe resorption of normally mineralized bone, slight osteoid excess, and almost normal calcification front; (5) hormonal factors: chronic stimulation of parathyroid glands may result in suppressible or even autonomous hyperparathyroidism. As to vitamin D, it has been suggested that the uremic kidney is not able to synthesize the 1,25-di-OH-cholecalciferol, the active metabolite of vitamin D: this results in an impaired intestinal absorption of calcium. On the contrary, the role of calcitonin in chronic uremia is still uncertain, since low values of plasma [Ca] are usually observed.


Hematologic disorders in renal failure.

Hematologic disorders in renal failure. Anemia is a frequent complication of renal failure. As in anemias of other origin, the resulting tissular hypoxia is partially compensated by an increased production of 2,3-diphosphoglycerate in red cells and a shift to the right of the oxygen hemoglobin dissociation curve. Two mechanisms are implicated in this anemia: increased hemolysis and depressed production of red cells. Decreased production of erythropoietin is probably the cause of reduced erythropoiesis, but the role of uremic intoxication has not been unequivocally excluded.  In the course of chronic hemodialysis, iron deficiency anemia and occasionally hypersplenism develop. It is noteworthy that blood requirements in anephric patients are two to three times greater than those of nonanephric hemodialyzed patients. Accordingly, bilateral nephrectomy should be restricted to carefully selected cases. At the present time, androgens seem to be the best treatment of renal anemia. Qualitative anomalies of platelets are the main factor responsible for uremic bleeding and are corrected by hemodialysis.


Treatment of stage IV carcinoma of the prostate. Accurate diagnosis and staging of carcinoma of the prostate is essential to rational management of this disease. Once dissemination outside the periprostatic area is established, treatment is essentially limited to systemic efforts to control or suppress tumor growth and local efforts to minimize secondary effects of tumor deposits. Disseminated tumor limited to pelvic nodes constitute a possible exception to this statement since excisional and radiotherapeutic efforts to eradicate these foci may be successful. At the present time, changes in a number of objective and subjective parameters are utilized to assess the effect of therapeutic endeavors. When these are taken as a group and combined with a clinical judgement, they undoubtedly have merit. On the other hand, when utilized in a relative fashion as isolated indicators of tumor responsiveness or recurrence, their value is limited. Since most patients with disseminated carcinoma of the prostate die from their disease, critical analysis of survival data is at present likely to provide the most accurate assessment of a therapeutic  endeavor. Estrogen administration or orchiectomy seem to be the systemic measures which combine relatively limited risk of morbidity with the greatest hope of initially controlling disseminated carcinoma of the prostate. Of these, evidence suggests that low dose estrogen therapy, 1 mg stilbestrol daily, provides the best opportunity for long-term control. Although length of survival does not seem to depend on the time at which the therapy is instituted, our prejudice is usually to start treatment when dissemination is recognized. The hope of providing a longer period of a better life by this practice requires evaluation. Combining local measures such as  transurethral resection with systemic measures may add to patient comfort and longevity. Recurrent progression of tumor after initial hormonal measures in often difficult to recognize and accept. In patients with recurrent tumor activity, measures based on the concept of persistence of hormone dependence have produced disappointing results. More sophisticated selection techniques may identify a small group of patients in whom this approach is likely to produce desirable changes. For the most part chemotherapeutic agents hold greater promise of effective therapy in this group of patients.


Chemotherapy of prostatic cancer.

Chemotherapy of prostatic cancer. Until the last few years very little information has been available regarding the potential of chemotherapy in prostatic cancer. Few drugs have been adequately tested to determine their efficacy, if any. Of the little conventional chemotherapy that has been documented, only diethylstilbestrol diphosphate (Stilphostrol, Honvan) has been safe, effective (at least in relieving bone pain) and available for repeat courses of treatment. The several well controlled clinical trials recently embarked upon and described in this article should reveal much about the effectiveness in prostatic cancer of agents already accepted in chemotherapy of other malignancies. Newer drugs will also require thorough testing. At this time no specific recommendations for chemotherpay other than the use of intravenous diethylstillbestrol diphospate can be made. Agents like estramustine phosphate (Estracyt) and flutamide (SCH-13521) with little to no bone marrow, liver, or renal toxicity are very promising. Studies of single-agent, sequential, and combined chemotherapy will necessarily lead to safe effective chemotherapy as adjuncts to surgery and/or radiotherapy for prostatic cancer in all stages.


Hypomagnesemia following the diuresis of post-renal obstruction and renal transplant. Three unusual cases are described which demonstrated hypomagnesemia and symptoms resembling magnesium deficiency syndrome. The hypomagnesemia was most likely secondary to urinary losses from diuresis following release of post-renal obstruction and renal homotransplantation. Heretofore, this association has not been described. Case 1 was unique because of the post-obstructive diuresis in the face of marked renal impairment. Case 2 is noteworthy because of the profound hypomagnesemia, 0.4 mEq/1, and because of the development of congestive heart failure. The rapid improvement noted in cardiac function with magnesium replacement suggests a relationship to magnesium deficiency.


Uremic myocardiopathy.

Uremic myocardiopathy. The authors report on the myocardiopathy of seven patients with end-stage renal disease, characterized by fever, in four patients; tachycardia, gallop rhythm, pericardial rub, in most of patients; signs and symptoms of cardiac failure and increased cardiac area and alterations of the EKG in all patients.  Good remission of the symptoms ws achieved in two patients by hemodialysis and by successful renal transplantation in the others.  The likely etiologic factors of the syndrome are discussed.


Number of nephrons in normal human kidneys and kidneys of patients with the congenital nephrotic syndrome.  A study using a sieving method for counting of glomeruli. A method of graded sieving for counting of glomeruli in removed kidneys is described.  The number of nephrons (glomeruli) in six normal kidneys deriving from sutopsies of three children 22-73 months of age was 1.82 plus or minus 0.35 times 10-6.  The results give a little higher number than most previous studies with which they are compared.  In the kidneys of two 10- and 15-month-old patients with the congenital nephrotic syndrome of the Finnish type the mean number of nephrons was 3.17 plus or minus 0.52 times 10-6 which is on the average 73% higher than in the normal kidneys studied.  The number of nephrons in kidneys of five other patients showed an average of at least 3.42 plus or minus 0.30 times 10-6 the counting method being a little different.  The unusually high number of nephrons in CNF kidneys seems to be fully evident.


[Postoperative pulmonary complications following abdominal surgery. Study on the preventive use of a bronchosecretolytic agent associated with an antibiotic]. The factors leading to post-operative respiratory complications following abdominal surgery are examined. Data relating to a clinical study of laparotomised patients receiving a course of Bisolvomycin in the immediate postoperative period are presented. This treatment led to a marked fall in the incidence of complications, even in a group of subjects with chronic bronchopneumopathy. Its usefulness as systematic management for subjects about to undergo abdominal surgery is urged.


[Benzbromarone in the treatment of hyperuricemias]. Benzbromarone, a synthetic benzofurane, was administered in a series of 23 patients with hyperuricaemia: 5 with gout, 8 with secondary forms, 6 with renal insufficiency, 4 undergoing diuresis with etacrinic acid. The drug was also given to 10 subjects with normal values. A surprisingly rapid and constant hypouricamising effect was noted, together with marked hyperuricuria. These changes were more prompt in the controls and relatively late and protracted in the diseased subjects, expecially those with gout. The drug was also active in renal insufficiency. Its effects ceased on suspension. It cannot be seen as a simple hyperuricuric preparation, since it may have some effect on the metabolic pathways that degrade purines to uric acid. The drug is similar to benziodarone. The replacement of iodine by two bromine atoms in its formula, however, ensures its freedom from side-effects.


[Klippel-Feil syndrome and associated malformations. Comments on an unusual case]. An unusual association of Klippel-Feil syndrome and other abnormalities (Sprengel's deformity, 1st cervical and 1st dorsal spina bifida, homovertebral bone, scoliosis, plagiocephaly, basilar impression, pterygium colli, nanism, hypogenitalism, etc.) together with neurological signs of amyotrophic lateral sclerosis, in a 36-yr-old woman is reported. The clinical and radiological pictures are examined and the exterior morphology is examined. The three types of Klippel-Feil syndrome are discussed, together with the particular alterations observed in the present case: Sprengel's deformity, spina bifida, craniostenosis, basilar impression, etc.


[Computer study of the anatomo-clinical characteristics of breast carcinoma. II]. Data relating to the major and minor clinical features of breast cancer were examined in 200 cases and correlated to obtain an overall picture of the objective picture. The classic pattern was present in most cases. Some data, such as patient occupation and the extent of lymph node invasion expressed different meanings, while various parameters led to dubitative conclusions.


The treatment of chronic renal failure in New Zealand. The treatment of chronic renal failure by centre haemodialysis and home haemodialysis are described. Since 1969 there has been a home dialysis programme at Christchurch. Some 63 patients were treated and 17 have died, six deaths occurred during training, four died after renal transplantation and seven died of other causes. The training time was on average 15 weeks. The implications of this form of management are discussed.


Pilot study on the effect of New Zealand green mussel on rheumatoid arthritis. An extract of the New Zealand green mussel did not show any greater effect than a placebo when given to five patients with rheumatoid arthritis in a double-blind crossover trial.


The early descriptions of the so-called tuning-fork tests of Weber, Rinne, Schwabach, and Bing. II. The "Rhine Test" and its first description by Polansky. Concerning the first description of the so-called tuning-fork test of Rinne the literature refers to a publication by him in 1855. In this work Rinne describes, among many other observations, a method to compare air and bone conduction hearing, and adds the remark that the technique could be used for the diagnosis of deafness. It appears, however, that long before Rinne, Polansky (1842) gave a complete account of the test and its practical use. Polansky's description seems to have been forgotten. Rinne's report, too, was lost for a long period until 25 years later when Lucae (1882) and Schwabach (1885) confirmed the usefulness of the test which - in spite of its earlier discovery by Polansky - has born Rinne's name ever since.


The early descriptions of the so-called tuning-fork tests of Weber, Rinne, Schwabach, and Bing. III. The development of the Schwabach and Bing tests. In the third and last part of this study the development of the so-called tuning-fork tests of Schwabach and Bing is discussed. The attention is called to the work of Schmalz (1849), Lucae (1880) and Emerson (1884). These authors preceeded Schwabach (1885) in using and describing the test which became only generally accepted through Schwabach's extensive study and since then bears his name. As to the so-called Bing or occlusion test, Bing's (1891) work is reviewed and the attention is drawn to an early and apparently forgotten description of this test by Rinne (1885).


Ernst Mach on the vestibular organ 100 years ago. Ernst Mach (1838-1916) performed pioneering research on vestibular function 100 years ago. His experiments were mainly psychophysical and included measurements of threshold and study of the vestibular-visual interaction. Contrary to general belief, he concluded that the adequate stimulus for the semicircular canals must be pressure. He presented evidence specifically against the sustained endolymph flow theory of Breuer (1874) and Crum Brown (1874), with which he is frequently associated. Excerpts from his publications are given and their relevance to current research is discussed.


Obstetrical paralysis.

Obstetrical paralysis. Most patients with obstetrical paralysis have some useful functional return, and early recognition and treatment help prevent rapidly developing shoulder contractures. Initial physical therapy includes passive range of motion exercises. Fixed contractures must be released prior to reconstructive surgery designed to improve funtion. An approach to the diagnosis, evaluation, and treatment of obstetrical paralysis is given.


Fractures of the proximal humeral epiphysis. Displacements of the proximal humeral epiphysis at the epiphyseal plate result from extension injuries. The configuration of the epiphyseal plate and the thickness of the periosteum surrounding the epiphysis make slight to moderate displacements relatively stable injuries, which can be treated successfully with external support. In patients with more severe  displacement, flexion, abduction, and slight external rotation of the distal fragment bring the metaphysis into alignment with the proximal fragment, correcting the anterior angulation.  The thick periosteal sleeve attached to the physis through which the  metaphysis tears out anteriorly has great potential for remodeling the persistant bowing that remains after healing of the fracture. Although shortening and residual angulation results from closed treatment are almost always good and open surgery is rarely  indicated.


Modern concepts of diagnosis and treatment of the thoracic outlet syndrome. Neurovascular compression at the thoracic outlet results from one or several local anatomic abnormalities, all involving the first rib to some extent. The pathologic processes produced involve syndromes usually affecting the ulnar nerve, the subclavian artery, or the subclavian vein. The majority of these cases should be managed in a nonoperative fashion and surgical treatment reserved for patients who are unresponsive to these measures. Initial conservative nonoperative treatment with physiotherapy and patient education produces satisfactory results in 70 per cent of the patients. Operative intervention, when necessary, results in satisfactory results in 90 per cent of the cases and requires first rib resection in conjunction with repair of all other attendant mechanisms. The anterior operative approach is strongly recommended whenever vascular repair is contemplated.


Soft tissue disorders of the shoulder. Frozen shoulder, calcific tendintis, and bicipital tendinitis. The painful periarticular conditions about the shoulder joint-calcific tendinitis, bicipital tendinitis, and frozen shoulder syndrome-are seen commonly in the general practice of medicine or in the practice of orthopedic surgery. Their etiologies are unknown. Their treatment is relatively simple and depends upon a knowledge of the anatomic structures involved and the proper use of rest and exercise. Operative intervention is rarely necessary in any of these conditions. The frozen shoulder syndrome, however, in our experience is best treated in the subacute or chronic stages by infiltration brisement under general anesthesia.


Neoplasms of the shoulder girdle.

Neoplasms of the shoulder girdle. The author has briefly discussed radiation therapy, immunotherapy, and chemotherapy in the treatment of some of the more commonly encountered disease entities affecting the shoulder girdle. Specific operations and their indications are discussed. However, utilizing physical and x-ray examination, arteriography, lymphangiography, and bone scan information, the surgeon may decide that the routine operation is not indicated for a particular tumor problem. He should be able to be flexible and to modify the operation according to the specific presenting problem and not be bound by routine fixed rules. In this way the patient can be assured of the very best treatment.


[Study of human chromosomes using fluorescence technics]. Fluorescent techniques permitted us to draw up a system of banding of human chromosomes, using quinacrine derivatives. This procedure may be used to measure the density of the chromosomes. Recently, other techniques which use various fluorochromes after denaturation, have been developed. The latter, which use acridine orange, give remarkably reliable and reproducible results. These techniques are particularly useful for the analysis of structural changes in the chromosomes. Their use is illustrated by a certain number of observations where they permitted the authors to determine the type of structural change and identify the chromosomes involved. The method of constitution and significance of the fluorescent bands is very controversial. It is not clearly known whether the fluorochromes combine with DNA or with protein bound to the latter. In spite of this uncertainty, the existence of heterogeneity in the structure of the chromatids at the metaphase provides new information for the understanding of chromosome organisation.


[Study of several parameters of hemostasis in Masugi's rabbit nephritis]. During experimental Masugi nephritis in the rabbit, were demonstrated various disturbances in hemostasis: a) during the initial stage: immediate, severe and transient fall in the platelet count without any change in Factor V;b)during the secondary stage, from the 7th to the 8th day onwards, increase in platelets and fibrinogen, in relation with the intensity of the nephrotic syndrome; c) in parallel, appearance of urinary fibrinogen split products in relation to the intensity of the glomerular lesions, evidence for the presence of intraglomerular fibrin. These facts confirm the role played by platelets in coagulation phenomena secondary to the immune reaction. They indicate, furthermore, the existence of hemostasis disorders during the nephrotic syndrome.


[Klebsiella septicemia. Epidemiologic aspects based on antigenic and biochemical studies of strains]. 50 strains of Klebsiella pneumoniae were isolated by blood cultures at Brugmann Hospital (Brussels) between 1967 and 1971. The biochemical and antigenic characteristics of the strains and their sensitivity to antibiotics were determined for epidemiological purposes. With the exception of the strains found in an hemodialysis unit, where the study showed the existence of an epidemic focus caused by serotype 28 biotype d, the strains consisted of a large number of capsular serotypes and of biotypes, excluding a single source of contamination for these septicemic infections. There is no relationship between the serotype of the strains and their sensitivity to antibiotics.


Nocardiosis in children: report of three cases and review of the literature. The clinical illnesses observed in three adolescents with Nocardia asteroides infection are described. The organism has been classified as a bacterium and placed in the Actinomycetaceae family. Sulfonamides remain the first choice for chemotherapy but alternative drugs are available and may be essential in successful therapy. Nocardial infections in children indicate the need for evaluation for an underlying immunological deficiency. Nocardia species should be considered as possible causative agents in immunocompromised patients with infection.


Relationship of diet to lead poisoning in children. Forty-six children, aged 24 to 47 months (25 controls and 21 subjects) chosen according to low and high blood lead levels respectively, were studied to ascertain the presence or absence of a relationship between dietary intake and the occurrence of plumbism (in children of low-income families).  Through single-blind interviews by a nutritionist, dietary intakes were gathered, and the average daily intake of calories, protein, and iron was calculated.  Hemoglobins, hematocrits, heights, weights, blood lead levels, and social demographic data had been gathered during the routine check for lead poisoning and at registration at the clinic.  The mean caloric and protein intake as percent of recommended dietary allowances were equal and adequate for both controls and subjects.  There was no statistically significant difference between the controls and subjects with respect to iron intake which was low in both groups.  Mean hemoglobin and hematocrit levels were in the anemic range for both groups.  The subjects were shorter and weighed less than the control group.  Pica was more prevalent among children with plumbism.  The findings of this study suggest that some factors other than dietary intake must account for the occurrence of lead poisoning in the subjects and that Blacks have a higher prevalence of plumbism in our area.


Observations on effects of a central stimulant drug (methylphenidate) in children with hyperactive behavior. Ninety-eight hyperactive children, ages 6 to 12 years, have been treated with methylphenidate or placebo under double-blind conditions.  Only one of the 48 children receiving placebo (2%) was judged to be a drug success.  Seventy-nine percent of the 94 children receiving methylphenidate were judged to be drug success at the end of the 16-week trial period.  A wide range of dosage (0.2 to 1.9 mg/kg) was required for optimum drug effects.  Drug failures were due either to appearance of withdrawn, apathetic behavior in the child (6 cases) or lack of evidence of drug effectiveness (14 cases).  Overweight children did not respond well to medication even though milligram per kilogram dosage was equivalent to that in children who were categorized as drug successes.  The most dramatic successes were seen in children who might be characterized as exhibiting "developmental hyperactivity," i.e., hyperactivity in the absence of other evidence of neurological or emotional disturbances.  We conclude that a trial of stimulant drugs is clearly indicated in hyperactive children manifesting significant impairment of educational and social progress.  Dosage adjustment and judgement of drug success or failure require regular reports from teachers and parents.


[Is talc a carcinogen? Review of current data]. The authors review the literature concerned with the carcinogenic hazards of a long term exposure to talc. The epidemiological and experimental data are controversial, but, however, seem to be sufficient to draw attention to, and to introduce special precautions for occupationally exposed individuals. Large experimental and epidemiological studies should be undertaken.


[Cardiac hemochromatosis. Anatomic, clinical and hemodynamical data]. The cardiovascular manifestations of idiopathic familial haemochromatosis (I.H.) should be well known. Of 25 patients seen for the most part in a Nutrition-Endocrinology Service, 10 suffered a purely cardiological problem at some point in their course.14 out of 18 patients had definite haemodynamic abnormalities. The discovery of cardiac haemochromatosis necessitates: a) depletive therapy by venesection which in certain cases is associated with the returm to normal of clinical and haemodynamic abnormalities (8-18-25). b) careful investigation of the family which, when positive, gives evidence of the primary nature of the iron excess. In members of the family suffering from I.H., early preventive therapy by vensections avoids the development of cardiovascular complications which are responsible for approximately 10 to 15 p.cent of causes of death in association with I.H.


[Circulatory survival of irreversible comas]. On the basis of a series of 53 cases of irreversible coma maintained in circulatory survival with the aim of removing the kidneys, the authors discuss the mode of treatment, with particular reference to the intravenous fluids used and the use of medications influencing the circulation. Fluid and electrolytes given must be adjusted hourly to ensure the exact replacement of urinary losses. Isoprotenerol is the only medication usually necessary. In the event of circulatory insufficiency, which is difficult to foresee and hence prevent, immediate volume expansion in a  short a time as possible and isoprotenerol most frequently correct the situation (14 out of 17 cases). Thus effective circulation may be maintained until the kidneys are removed (48 out of 53 cases). 92 p.cent of the grafted kidneys functioned from the first day onwards.


[Pneumocystis carinii pneumonia after kidney transplantation. Early diagnosis by distal bronchial brushing]. Distal bronchial brushing is one of the methods used in the in vivo indentification of Pneumocystis carinii, a parasite associated with severe pneumonia, the development of which is induced by immuno-depression, particularly after renal transplantation. In three patients the pathogenic agent was demonstrated in alveolar material obtained in this way. The technique is simple and risk-free. It may be used early and repeatedly.


Binding of lactose repressor to poly d(A-T) : OD AND CD melting of the complex. The binding of lactose repressor to poly d(A-T) at low ionic strength has been investigated by heat denaturation. The poly d(A-T) melting is monitored by optical density and the protein melting by circular dichroism. From the modification of the poly d(A-T) melting curve we estimate a maximum binding ratio of about one tetrameric repressor to about 20 basic pairs. The repressor melting can be interpreted as a global shift from a to b structure of about 25 residues per subunit. The melting curves of poly d(A-T) and repressor have not a shape easy to interpret; nevertheless both show a cooperative transition in the same temperature range where we can evaluate that about 3.8 aminoacid residues shift from a to b structure when 1 bases pair melt.


On the statistical significance of primary structural features found in DNA-protein interaction sites. Probabilities of occurrence for a number of the symmetries and other sequence regularities found in DNA-protein interaction site sequences have been calculated for segments of random DNA sequence. Results show that many of the symmetrical and repetitive features seen in these interaction sites are likely to have occured by chance. Other features are so unlikely to have occurred by chance that they are probably involved in the DNA-protein interaction processes.


The biological activity of bacteriophage DNA, prepared by the cationic detergent dilution technique. The preparation of phage lambda DNA infecting E. coli K 12 with cationic detergent is described. This DNA infects E. coli spheroblasts with the same efficiency as DNA prepared by phenol methods.