Restoration of normal pituitary gonadotropin reserve by administration of luteinizing-hormone-releasing hormone in patients with hypogonadotropic hypogonadism. To elucidate whether diminished pituitary gonadotropin reserve can be restored by repeated stimulation with luteinizing-hormone-releasing hormone, plasma luteinizing hormone and follicly-stimulating hormone responses were studied before and after daily intravenous infusion of 400 mug of luteinizing-hormone-releasing hormone for two to 23 days, in patients with hypogonadotropic hypogonadism of various causes. In five of nine patients with isolated gonadotropin deficiency, the impaired plasma luteinizing hormone response was restored to normal after treatment for seven days or more, whereas it was unchanged in four patients treated for less than five days. However, six patients with anorexia nervosa regained normal responses after three to five days' treatment. Five of nine patients with organic hypothalamopituitary lesions also showed normal responsiveness after five to seven days' treatment. These results suggest that the response to the test after repeated administration of luteinizing-hormone-releasing hormone is of value for the diagnosis of hypogonadism of hypothalamic origin.


Psychiatry: the battered child of medicine. Psychiatry has had a troubled history. After the French Revolution "moral treatment" brought to America a period of effective and humane hospital treatment, but this progress was corrupted by the Industrial Revolution, and psychiatry was rejected by society as well as by medicine. Although the Freudian enlightenment and the introduction of social psychiatry have led to greater acceptance, today's criticisms are strident. Psychiatry is criticized for imprecise diagnosis, conceptual vagaries, jargon, therapeutic impotence and class bias. The American system of mental-health care is seen by many as a disaster. The federal comprehensive Community Mental Health Act has been aborted at an early stage. Skills involved in the practice of psychotherapy are not unique to the profession. Social ills, over which psychiatry has little control, play a large part in causing mental disability and retardation. Nevertheless, though embattled, psychiatry has contributed to medical practice and to the humane consciousness of society.


The nucleotide sequence of an RNA polymerase binding site on bacteriophage fd DNA. The nucleotide sequence of the RNA polymerase binding site at a promotor on fd RF DNA has been determined in comparison with the starting sequence of RNA initiated at this promoter. The RNA polymerase binding site contained the startpoint of transcription in the centre and a region with twofold symmetry in the non-transcribed part.


Prospective bacteriologic study of women undergoing hysterectomy. A prospective bacteriologic study on 67 women undergoing either vaginal or abdominal hysterectomy was done to elucidate causes of debrile morbidity. Forty-one percent of the vaginal and 35% of the abdominal hysterectomy patients met the criteria for febrile morbidity postoperatively. Preoperative and 24-hour postoperative urine samples were obtained by transvaginal bladder tap, and the freshly cut edge of the vaginal cuff was routinely swabbed following removal of the uterus. In addition, the subcutaneous layer was cultured during closure of the abdominal wound. Escherichia coli, Enterococcus, and alpha- and beta-Streptococcus were the predominant organisms recovered. The importance of routine vaginal cuff cultures at the time of surgery for the treatment of postoperative morbidity is discussed.


Pharmaceutic factors affecting pediatric compliance. Evaluation of treatment given at home was studied in children with otitis media who were seen in an outpatient clinic. Full compliance was present in only 5% of the initial 100 patients (Study A). Practical factors limiting their compliance included inadequate dispensing of medication at drug stores, 15%; incorrect therapy schedule, 36%; early termination, 37%; spilled medicine, 7%; therapy shared, 5%. Because of these findings, a plan was implemented (Study B) in which hospital pharmacy personnel gave patient families verbal and written instructions for administering medications that were dispensed, together with a calibrated measuring device and a calendar to record doses taken. Full compliance was raised to 51% in this pilot group (of 33 patients) as compared with 8.5% in 20 concurrent controls who went to neighborhood drug stores. The importance of detailed therapy instructions is stressed. The potential role of the pharmacist in improving compliance is demonstrated.


The Japanese operation for biliary atresia: remedy or mischief? A case illustration is given of an infant with biliary atresia who had the Kasai operation more than 1 1/2 years ago and is now, by all biochemical and histological criteria, cured. The early results with this operation in 14 patients are similar to those reported by the Japanese, that is, 25% have had sustained postoperative bile drainage. Success has never been achieved in infants older than 4 months. A long-held notion in this country to withhold operation in infants with jaundice until after 4 months has thus far militated against a critical and impartial evaluation of the Kasai operation. A plea is made to complete diagnostic work-up for jaundice during the first months of life so that the operation, if elected, may have a genuine chance for legitimate long-term analysis.


A review of five years' experience with rubella vaccine in the United States. National morbidity figures show a decline in reported rubella and congenital rubella syndrome since 1969, concurrent with widespread use of rubella vaccine. In addition, no nationwide outbreak, such as the 1963-1964 epidemic, has occurred, though on the basis of long-term secular trends, one would be expected between 1970 and 1974. Recent rubella outbreaks have occurred in unimmunized students in high schools and universities, and there appears to have been a slight upward shift in the age-specific incidence of rubella in the United States since the beginning of widespread immunization. Currently available vaccines have provided durable protection to date, and, although reinfection is known to occur following vaccination, it has not proven a risk to the pregnant woman. There is a small but significant incidence of adverse reactions and a potential risk to the woman who is vaccinated during pregnancy. These data indicate that rubella vaccines are safe and effective. They also imply that rubella vaccines, as they are currently applied, have been successful in reducing the morbidity of congenital rubella syndrome, although continued surveillance will be necessary to confirm this trend.


Oxygen plus pressure plus time: the etiology of bronchopulmonary dysplasia. Ten infants developed the chronic pulmonary syndrome designated bronchopulmonary dysplasia, following artificial (assisted) ventilation using a volume-regulated positive-pressure respirator. Despite previous reports implicating elevated oxygen concentrations for prolonged periods of time, only two infants required more than 80% oxygen for more than 24 hours, and only one infant required 60% oxygen for more than 100 hours. "Immature" lungs when exposed to inspired oxygen concentrations over 40% for as little as three days via positive-pressure ventilation may develop bronchopulmonary dysplasia. The role of the underlying disease and the relationship with Wilson-Mikity syndrome remain uncertain.


Bronchopulmonary dysplasia and lung rupture in hyaline membrane disease: influence of continuous distending pressure. Review of 158 patients with hyaline membrane disease was undertaken. The introduction of artificial ventilation with a positive end-expiratory pressure (IPPB and PEEP) has doubled the prevalence of pneumothorax, pneumomediastinum and interstitial emphysema from 20.7% to 39.7%). Continuous negative distending pressure during spontaneous ventilation (CNP) was associated with a prevalence of lung rupture similar to that occurring spontaneously (4.8%). No patient treated with CNP alone developed bronchopulmonary dysplasia. Patients treated with IPPB with PEEP had a marked decreased prevalence of bronchopulmonary dysplasia (17.2%) when compared to patients treated with IPPB alone (36.2%), probably related to the enhanced overdistension of relatively normal areas of the lung may be related to the increased prevalence of lung rupture seen during IPPB with PEEP.


The circulating plasma volume of the foetal lamb as an index of its weight and rate of weight gain (g/day) in the last third of gestation. In a series of foetal lambs weighing between 1,100 and 5,228 g, the circulating plasma volume was estimated by the dye dilution method, using Evans Blue, to test the possibility that the plasma volume could be used as an index of foetal weight in chronic studies. The data, analysed by the method of least squares regression, indicate that plasma volume and foetal weight are closely correlated (R-2 equals 0.922) and linearly so in the range of data studied. There was no evidence that the relation differed for singlets and twins. A single equation, Y equals 71.8 plus 10.11 X--where Y is the estimated weight and X the plasma volume, can be used to predict the weight from plasma volume in both. Some results of the application of the method in chronic studies are presented.


Renal localization of gallium-67 citrate. Renal localization of 67Ga citrate has been observed in 1.7% of 2,000 whole-body gallium scans in three major diseases: lymphoreticular neoplasms, leukemia, and malignant melanoma. Correlation of this finding with autopsy data in 13 cases revealed 9 with tumor and 2 with an inflammatory process. Findings in two cases were normal. In the remaining patients, correlation with abnormal urograms and laboratory data was poor. Nevertheless, gallium localization in the kidneys may be the first indicator of renal involvement with either tumor or inflammation.


Changes of the coliform populations of the shoreline waters, Shediac, New Brunswick. This paper presents the results of a survey of the changes in the coliform populations of the shoreline waters, Shediac, New Brunswick. The sanitary quality of these waters showed more than 1000 organisms/100 ml of coliforms thereby indicating post-winter and pre-summer contamination of these waters. The membrane filter method is found to be equally efficient to that of the MPN method. The sanitary quality of these waters in relation to other ecological parameters like temperatures, pH salinity and availability of oxygen are considered.


Vesicular binesis: glucose effect on insulin secretory vesicles. Binesis is a process whereby the membrane of the insuline secretory vesicle in the beta cell forms a lingula that indents the vesicular membrane of an adjoining secretory vesicle of the plasma membrane. Vesicular binesis in beta cells increases when islets of Langerhans are incubated at a stimulatory glucose concentration (300 miligrams per 100 milliliters). These vesicular membrane alterations may be the morphological concomitants of activation of the insulin secretory vesicle, and indicate an active role for the vesicle and its membrane in the release mechanism.


F factor promotes turnover of stable RNA in escherichia coli. Male bacteria that contain and srnA- mutant allele degrade their "stable" RNA massively after RNA synthesis is blocked at 42 degrees C; a normal F- female strain shows no such RNA breakdown unless both the srnA- allele and maleness (F factor) are introduced.


Papilledema: its recognition and relation to increased intracranial pressure. This has been a review on the subject of papilledema from a clinical, pathologic and experimental point of view. Terminology has been clarified. The term papilledema should be reserved for those patients with optic disc edema caused by increased intracranial pressure. The forms of papilledema which are identifiable are: 1. Early (incipient) form which develops into an acute type and then into a fully developed form; 2. Fully developed form, characterized by obscured disc margins, hemorrhages and ischemic infarcts; 3. Chronic papilledema which may persist (the name "vintage" papilledema may be applied to those patients affected in varying degrees up to several years); and 4. Chronic atrophic papilledema which, as the name implies, illustrates a form we do not see as frequently as in years past. It is the type we are now trying to prevent and in this effort we are fortunately achieveing some success. The importance of the intracranial expanding lesions and the influence of the rapidity of elevation and duration of intracranial hypertension on the optic nerve has been considered, based on the clinical and experimental work to date. The pathogenesis of papilledema has been considered in some detail. A unified whole is difficult to arrive at in such a complex situation. Recent advances in our understanding of anatomic, mechanical (sheath space pressure), tissue and vascular pressure as related to increased intracranial pressure have been described. A hydrostatic mechanism brings these factors together in a reasonable, although admittedly not completely proven concept of a mechanism for the development of papilledema. Clarification of terminology and clinical appearance of the various forms of disc edema related to intracranial pressure are of practical value in the diagnosis and management of each patient we see with this clinical entity.


Intraocular reticulum-cell sarcoma: clinico-pathologic study of four cases and review of the literature. Four patients with primary intraocular reticulum-cell sarcoma were presented. All of the patients were followed at the Wilmer Institute for periods of up to ten years. All had decreased visual acuity and a uveitis that was refractory to standard forms of therapy. In one case, the correct diagnosis was made clinically. At autopsy, two of the patients had systemic reticulum-cell sarcoma, a third had intracranial reticulum-cell sarcoma, and in a fourth case the disease process was confined to the eye. The literature is reviewed and the clinico-pathologic features of the total of 14 cases are analyzed. It is emphasized that a recalcitrant uveitis was present in almost all of the cases reported. Differential diagnosis and methods of diagnosis are discussed.


[Usability of methods for the determination of minute cardiac volume under clinical conditions]. Methods for determination of cardiac output are described and their evaluation and possibilities to use them in clinical practice mentioned. Out of the invasive methods apart from the classical Fick's method, the dye dilution method is of advantage during catheterization, being relatively simple and ready to be easily repeated if necessary directly at the bed side. The common disadvantage of all invasive methods is the disturbance of the patient's basal state. Noninvasive methods yield results suitable more or less for orientation only. From these techniques the indirect method of Fick using the rebreathing of CO2 is simple and can be applied at the bed side. So called physical methods are already obsolete at present.


Bone changes in young mice with impaired lymphoid system. Disturbances of osseal growth were observed in young mice with their lymphoid system affected by antihymocyte serum or mitolactol (dibromodulcitol) treatment. These bone changes were similar to those observed in germ-free and neonatally thymectomized mice as well as in mice suffering from a graft vs. host reaction. Their severity was in direct correlation with the disturbance of the thymus dependent lymphoid system. Not only immunological adaptation but also normal bone growth appears to require an intact thymus and thymus dependent lymphoid system.


Chromosome aberrations in cells infected with various strains of measles virus. The incidence of chromosome fragmentation and/or breakage has been studied in cultured human embryonic diploid cells infected with different wild and vaccinal strains of measles virus. It seemed that for wild strains the mean incidence of fragmentation was two times higher, that of breakage two times lower than for the vaccinal strains.


A clinical isolate of Salmonella typhi requiring anaerobic conditions for primary isolation. An unusual isolate of Salmonella typhi from a patient with typhoid fever is described. The organism grew only on anaerobic subculture from multiple blood cultures. After repeated transfer the organism adapted to aerobic growth but still required carbon dioxide.


Cardiobacterium homonis endocarditis. Characterization of the unusual organisms and review of the literature. A case of subacute bacterial endocarditis in which Cardiobacterium hominis was isolated from the blood of a 55-year old woman who had rheumatic heart disease is reported. A survey of the literature revealed very few reports in which this organism has been implicated in human lesions. The colonies grew after 48 hours of incubation in a candle jar. They were small, convex, nonhemolytic, and oxidase-positive. The indole reaction was positive, the catalase and nitrate reactions were negative, and acid reaction was obtained from the following carbohydrates: glucose, maltose, mannitol, sucrose, and sorbitol. The morphologic and biochemical properties served to distinguish these organisms from similar bacteria implicated in human disease, such as Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Streptobacillus moniliformis, and HB-1.


Comparison of isotonic and radiometric-hypertonic cultures for the recovery of organisms from cerebrospinal, pleural and synovial fluids. Two hundred eighteen (218) specimens of body fluids were examined by both isotonic and hypertonic culture methods. The specimens examined included 108 pleural fluids, 43 synovial fluids, and 67 cerebrospinal fluids. Organisms were recovered in 99 instances by means of the isotonic system and in 140 instances by the hypertonic system. The hypertonic system also involved the use of radiometric assay for the detection of positive cultures. In all 140 cases, detection was accomplished within 36 hours after collection of the specimen by the radiometric method, while only 26 specimens showed any visual evidence of bacterial growth. Of the 218 patients involved, 198 were receiving antimicrobial therapy in which the antimicrobial agent attacked the bacterial cell wall.


A simple method of inflation--fixation and air drying of lungs. The various technics for pulmonary inflation are briefly discussed. A method of pulmonary inflation, fixation and drying is described. This preparation provides lung specimens suitable for many modes of study or demonstration, as well as excellent histologic detail. The technic is simple enough to use routinely in the study of pulmonary disease outside of a research center.


Identity conflicts in adoptees.

Identity conflicts in adoptees. A review of the literature, and interviews with a large number of adoptees who have experienced reunions with their birth parents, indicates that adoptees are more vulnerable than the population at large to the development of identity problems in late adolescence and young adulthood.


Hyperactivity in preschoolers and the effect of methylphenidate. Observations of nursery behavior and tests of cognitive style and motor impulsivity were carried out with 28 hyperactive preschool children of normal intelligence and 26 matched control children. The hyperactive group was also observed and tested on methylphenidate and placebo. Methylphenidate was found to reduce hyperactivity at home, but it did not improve nursery behavior or psychological functioning. Unwanted side effects made the drug less useful at this age than in older hyperactive children.


Peer behavior conceptualized as a variable influencing infant and toddler development. It is hypothesized that interaction between infants may serve to facilitate their overall behavioral development, particularly if the environment is structured to maximize the developmental quality of the interaction. The developmental literature, which has largely ignorned the potential value of infant peer interaction is reviewed, and several lines of psychological theory and investigation are cited in support of the hypothesis. Development of a technology for enhancing infant interaction is proposed, and initial research questions are suggested.


Psychiatric training and practice in the People's Republic of China. Improved political relations between the United States and the People's Republic of China have led to closer contact in many areas. The authors trace the development of psychiatric training and practice in China with emphasis on the years after 1949. Since then, China has expanded psychiatric services to meet the needs of a vast population and has developed a theoretical approach to psychiatry that emphasizes sociopolitical factors. Additional information given to the authors in 1973 by psychiatrists in Nanking and Shanghai is presented and correlated with reports by other recent visitors to the People's Republic of China.


Affective disorder: studies with amine precursors. The authors assessed the clinical antidepressant effects of L-tryptophan given alone and in combination with L-dopa in 12 patients with a diagnosis of primary affective disorder; Preliminary results did not demonstrate an antidepressant response when L-dopa was combined with L-tryptophan. Also, the results did not support the catecholamine or biogenic amine hypotheses of affective disorder.


Investigation of the EVI antibody in parasitic diseases other than American trypanosomiasis. An anti-skeletal muscle antibody in leishmaniasis. The specificity of a circulating antibody observed in American trypanosomiasis and reacting with endocardium, blood vessels, and the interstitium of striated muscle (EVI factor) was evaluated in the indirect fluorescent antibody test with 60 sera from patients with malaria, leishmaniasis, echinococcosis, amebiasis, African trypanosomiasis, toxoplasmosis, and trichinosis, collected from areas where Chagas' disease is not endemic. Two sera, 1 from a patient with Plasmodium falciparum malaria and 1 from a patient with a relapse pretreatment post kala-azar dermal leishmaniasis, were positive for the EVI factor. In the leishmaniasis group, 3 of 8 sera reacted with 0ovine, murine, and human skeletal muscle. In this reaction, which differs from the EVI test, the sarcolemma and the intracellular structures were stained.


Studies of in vitro infection by Trypanosoma cruzi. I. Ultrastructural studies on the invasion of macrophages and L-cells. The interactions of Trypanosoma cruzi with L-cells, and with normal and activated macrophages in vitro were studied by ultrastructural techniques. T. cruzi actively invades cultured L-cells and uniformly destroys them. Normal macrophages could control a 1:1 (parasite to host cell) infection, but were destroyed by a 10:1 infection. BCG-activated macrophages, however, controlled a 10:1 infection but not one at a ratio  of 100:1. It appears that parasites that survive within host cells do so outside cytoplasmic vacuoles, whereas when they are relegated to host cell phagosomes they are destroyed. Culture forms of T. cruzi have several means of access into host cells. Marcrophages are better able to survive infection than are non-phagocytic cells. Finally, it is suggested that control of an experimental infection in vitro is dependent upon numbers of parasites to macrophages as well as the state of the macrophages.


Onchocerciasis in Guatemala. II. Microfilariae in urine, blood, and sputum after diethylcarbamazine. Guatermalan volunteers with onchocerciasis were given a dose of diethylcarbamazine to learn if this caused migration of microfilariae of Onchocerca volvulus into urine, blood, and sputum. In 5 of the 10 volunteers, the num0ers of microfilariae in the urine increased considerably following the drug. In the same 5, relatively large numbers of microfilariae were observed in the blood and sputum specimens. Response in the remaining 5 was negligible. Four controls given a placebo did not respond. Interestingly, however, 2 control subjects had onchocercal microfilariae in their concentrated blood specimens and 3 control subjects had microfilariae in the sputum. Therefore, we believe that microfilariae, if searched for, may be found in other parts of the patient not normally associated with the infection.


Effects of pattern of ventilation on pulmonary metabolism and mechanics. Effects of three patterns of mechanical ventilation on pulmonary mechanics, lung phospholipid and surface activity were studied in the normal closed-chest dog. The patterns were continuous mechanical ventilation with: 1) tidal volume (VT)=15 ml/kg; 2) VT=15 ml/kg with 10 cm H2O positive end-expiratory pressure (PEEP); 3) VT=50 ml/kg. THE DOGS IN EACH GROUP WERE VENTILATED FOR 24 HOURS, WITH CAREFUL ATTENTION PAID TO MAINTENANCE OF NORMAL BLOOD GASES, FLUID BALANCE, AND CARDIAC OUTPUT. The animals were sacrificed and the lungs studied to determine pressure-volume curves, dry lung weight/wet lung weight ratios, phospholpid contents and surface activities. The results were compared with control values in acutely sacrificed unventilated dogs. No significant change from controls was found with any pattern of ventilation employed with the exception of the tendency for lungs ventilated with PEEP to retain fluid (decreased dry lung weight/wet lung weight ratio).


Intestinal infusion of endotoxin in adrenalectomized calves. Four adrenalectomized calves, 3 to 4 months old, were allowed to develop adrenocorticosteroid insufficiency and then were given 50 mg of Escherichia coli endotoxin by infusion via cannula into the duodenum. Several physiologic variables were studied to detect changes indicative of endotoxemia. It is concluded that adrenocorticosteroid insufficiency in calves is not an independent factor allowing an intestinal source of endotoxin to cause the development of clinical signs and physiologic changes characteristic of endotoxemia.


A rapid batch method for the production of specific fluorescein isothiocyanate-labeled globulins to Dirofilaria immitis microfilaria. A rapid, reproducible method for the production of specifically labeled anti-Dirofilaria immitis microfilaria (MFF) globulins (MAG) has been devised. These labeled antibodies have made the detection of D immitis in serum possible by a fluorescent-antibody technique.


Relative immunogenicity of streptomycin-susceptible and -resistant strains of BCG. II. Effect of the route of inoculation on growth and immunogenicity. Normal CD-1 mice were infected intravenously, subcutaneously, or aerogenically with live bacille Calmette Guerin (BCG) Tice or BCG streptomycin resistant (SM-res) and growth of the organisms in the footpad, the draining popliteal lymph node, the blood, lung, liver, and spleen was followed for as long as 50 days. The vaccinated mice were then challenged on day 50 with 10-5 viable Mycobacterium tuberculosis Erdman organisms introduced intravenously or subcutaneously. The growth of the Erdman challenge was followed in the appropriate organs for the next 20 days. Measurement of tuberculin hypersensitivity was carried out by footpad tests. The BCG Tice introduced aerogenically or subcutaniously into normal mice induced degrees of antituberculous resistance equivalent to those seen earlier in intravenously infected mice. The BCG SM-res was still nonimmunogenic when introduced subcutaneously or by the aerogenic route. Suspension of the organisms in sterile mineral oil before their injection into the footpad slowed their rate of inactivation and marginally increased the immune response seen later in the host. Introduction of BCG SM-res into T-cell depleted mice by the 3 inoculation routes was associated with no marked improvement in the survival of this organism in vivo, suggesting that BCG SM-res is inactivated in vivo by a nonimmunologically mediated mechanism.


Bronchofiberscopy.

Bronchofiberscopy. Probably no other diagnostic interpretive technique has revolutionized pulmonary medical practice in so short a time as flexible bronchofiberscopy. This state of the art review deals with flexible bronchofiberscopy, as well as comparisons to rigid bronchoscopic techniques. Historic development, specifications, indications, contraindications, sterilization of the instrument, and complications of these methods are discussed. Accessory procedures to bronchofiberscopy including biopsy, brushing, lavage, foreign body extraction, selective bacterial cultures, and research applications are considered. Finally, recommendations are made as to the training of a physician who performs bronchofiberscopy.


Distribution of sodium and potassium in chronic obstructive pulmonary disease. The body electrolyte composition of 34 patients with severe chronic obstructive pulmonary disease and without complications or medications known to influence body sodium or potassium was studied. Exchangeable sodium, exchangeable potassium, extracellular water, and total body water were measured using radioisotope dilution techniques. From these values and serum sodium and potassium levels, the intracellular water, intracellular concentrations of sodium and potassium, and factors to estimate lean body mass were calculated. Normal values were predicted for factors that vary with weight, age, and sex--exchangeable sodium, exchangeable potassium, total body water, extracellular water, intracellular water, and estimates of lean body mass--for each subject using regression equations that took into account the variables. For values that do not vary with weight or age--residual sodium and intracellular concentration of potassium--comparisons were made with values from our control subjects. The patients with chronic obstructive pulmonary disease showed a slower rate of potassium exchange than the control subjects, requiring at least 48 hours. There was also an increase in residual sodium composed of intracellular sodium and exchangeable bone sodium. The possibilities that the abnormalities could be ascribed to congestive heart failure, loss of lean tissue, or to a slowly functioning sodium pump were considered.


Neural regulation of respiration.

Neural regulation of respiration. The main respiratory muscles are under both voluntary and involuntary (automatic) control. These two control systems come from separate sites in the CNS and have separate descending pathways; the final integration of these outputs occurs at segmental levels in the cord. Voluntary control arises from the motor and premotor cortex and descends in the cord in the corticospinal tract. Involuntary control is mediated by both rhythmic and nonrhythmic systems located in the brainstem. Recent studies have associated the classic respiratory centers with specific nuclei in the brainstem. The pneumotaxic center is located in the nucleus parabrachialis, and the medullary respiratory centers are located in the vicinity of the nucleus of the solitary tract (dorsal respiratory group) and the nuclei ambiguus and retroambigualis (ventral respiratory group). Most axons from the medullary nuclei cross in the medulla and descend in the ventral and lateral columns to segmental levels. The classic medullary respiratory centers described by Pitts have been shown to be the site of origin of tonically firing long reticulospinal axons that descend in the ventral and lateral columns. This system is thought to provide a nonrhythmic involuntary biasing of the membrane potential of respiratory motoneurons in the cord. The site of generation of eupnic breathing and the mechanism of rhythm generation remain unknown. However, recent studies indicate that reciprocal inhibition between populations of inspiratory and expiratory cells (bistable oscillator model) does not occur in the medulla; rather we suggest that inhibitory phasing of inspiratory cells generates inspiratory rhythm, and periodic inhibition of tonically active expiratory neurons results in respiratory rhythm. We suggest that the inhibitory phasing occurs in the dorsal respiratory group, which is also the site of integration of respiratory afferents. The main site of integration of the voluntary and involuntary control systems is the cord where the respiratory motoneuron output is determined by descending information from these systems, as well as with intrasegmental and intersegmental reflexes. Separation of the voluntary and involuntary control systems also occurs in man and discrete lesions may interrupt one system without significant alteration of the other.


Allergic bronchopulmonary aspergillosis: evidence of limited tissue invasion. The cause of granulomatous parenchymal reaction in allergic bronchopulmonary aspergillosis has been attributed to a hypersensitivity reaction. A case is reported with Aspergillus fumigatus identified in lung tissue, suggesting that the pathologic changes in some cases can be due to limited parenchymal colonization.


Blood--its derivatives and its problems--factor VIII. Unfortunately, all of the problems of the hemophiliac have not been solved by the availability of concentrated factor VIII products. Patients still are faced with the crippling effects of arthritis, problems with employment, problems with ignorance (both medical and lay), and an increased risk of premature death even in a sophisticated, treatment-oriented, community (Table 3). It can only be hoped that we can solve the problems of hepatitis transmission, availability, and economics so that concentrated forms of factor VIII can be made available to all patients with hemophilia. It seems appropriate to suggest that our severely affected patients should be placed on some prophylactic programs, since this would ease most of the long-term psychologic and physical disabilities common to this disease.


Detachment of Descemet's membrane from grafts following wound separation: light and scanning electron microscopic study. Examination of 4 specimens of failed grafts following wound rupture shows that separation of Descement's membrane from the periphery of the graft in the area of dehiscence is followed by morphological changes in endotelial cells and by the development of fibrous membranes. Defective wound healing after repair is probably caused by persistent edema of graft stroma. With sudden decompression of the globe, rupture and total detachment of Descemet's membrane may occur. Changes in Descemet's membrane and eventual failure of the graft may occur mostly on the basis of anatomical changes in the endothelium of the graft and not necessarily by inflammation which was not present in these 4 specimens.


Anterior segment fluorescein angiography: a simple modification of the Zeiss stereo slit lamp camera. The addition of a small metal housing containing a rechargeable flash to a Zeiss stereo slit lamp camera provides a simple, inexpensive method for obtaining excellent quality anterior segment fluorescein angiograms. By placing a splice in the slit illumination cord the fluorescein flash unit can be hooked up to be existing Zeiss power pack. The easy insertion of the proper excitation and barrier filters completes the temporary conversion. Utilizing this equipment, rapid sequence photographs of high resolution can be achieved. In addition, stereophotography, variable magnification, color photography and a simultaneous combination of fluorescein and infrared angiography for pigmented lesions are possible.


A gastroplasty for short esophagus and reflux esophagitis: experimental and clinical studies. A safe, simple, effective gastroplasty for short esophagus with reflux esophagitis is described. It has been evaluated in dogs for up to three years with flexible fiberesophagoscopy, esophagrams and intraluminal pressure studies. Successful clinical experience has been encouraging.


Roux-en-Y hepaticojejunostomy: a reappraisal of its indications and results. A critical evaluation is made of 131 patients submitted to choledocho or hepaticojejunostomy. The main indications for hepaticojejunostomy were iatrogenic strictures of CBD (60 patients), and choledocholithiasis with markedly dilated duct (41 patients). The overall mortality rate was 4% representing principally renal hepatic failure, bile peritonitis and bleeding. The complications following hepaticojejunostomy included only in one case biliary fistula which required reoperation. The long-term results of 80 patients available for a followup study were as follows: 63 patients (78.7%) were symptom-free at 2-13 years followup; 8 patients had brief episodes of cholangitis which responded to antibiotic and corticosteroid treatment; 9 patients required reoperation for stricture of anastomosis. These overall results are a strong argument for hepaticojejunostomy which, compared with choledochoduodenostomy, avoids the hazards of the so-called sump syndrome and of the reflux of enteric contents in the CBD. An increased incidence of peptic ulcer disease in the patients submitted to hepaticojejunostomy was not observed. In very high strictures and in reinterventions anastomosis between left hepatic duct and Roux-en-Y jejunal limb was carried out. The results achieved with this technique, which was performed in 26 patients, were about the same following hepaticojejunostomy.


Permanent deafness associated with furosemide administration. Six cases of hearing impairment have been presented. Furosemide was administered to all of these patients at the time of the alleged onset of the deafness. None of the known or suspected causes of deafness occurring in transplant patients was evident in these cases. With the experimental evidence that furosemide does induce stria damage and the absence of other recognized causes of deafness in this series of patients, furosemide must be considered the etiologic agent responsible for the permanent sensorineural hearing loss. A characteristic audiometric pattern of hearing impairment emerged and a possible explanation for these features has been given. Certain precautionary steps in the use of ototoxic drugs are suggested.


The precision of a special purpose analog computer in clinical cardiac output determination. Three hundred dye-dilution curves taken during our first year of clinical experience with the Waters CO-4 cardiac output computer were analyzed to estimate the errors involved in its use. Provided that calibration is accurate and 5.0 mg of dye are injected for each curve, then the percentage standard deviation of measurement using this computer is about 8.7%. Included in this are the errors inherent in the computer, errors due to baseline drift, errors in the injection of dye and acutal variation of cardiac output over a series of successive determinations. The size of this error is comparable to that involved in manual calculation. The mean value of five successive curves will be within 10% of the real value in 99 cases out of 100. Advances in methodology and equipment are discussed which make calibration simpler and more accurate, and which should also improve the quality of computer determination. A list of suggestions is given to minimize the errors involved in the clinical use of this equipment.


Changes in the lymphocyte cytoplasmic refractive index following typhoid vaccination. The refractive index of the circulating blood lymphocytes (LCRI) of healthy young adults vaccinated with typhoid vaccine has been measured by immersion refractometry and phase contrast microscopy. A rise in the LCRI preceeds the rise in the antibody titre by two to three days. A more pronounced rise also occurred in one patient prior to a rejection crises following a kidney transplant.


Local anesthesia in otolaryngology. A re-evaluation. Almost a half century following attempts to ban its use, cocaine remains at the pinnacle of topical anesthesia in otolaryngology. To understand how nonaddicting synthetic substitutes such as procaine, dibucaine, tetracaine and lidocaine have not totally supplanted cocaine, requires an in-depth analysis of its unique pharmological properties, untoward effects and potential substitutes. Almost all of the reported cocaine deaths occurred after subcutaneous injection; when used topically, cocaine's toxicity has been confined to an occasional reaction. Certain variables under physician control may be manipulated to reduce the chance of reaction to a minimum. For example, intermittent application of a particular dosage results in lower blood levels, and allowing sufficient time between doses reduces the amount necessary to obtain the desired anesthesia. If total dosage is kept below 200 mg there are few reactions. A singular advantage of cocaine over other topical anesthetics is its inherent ability to cause vasoconstriction, thus retarding its own absorption. The addition of a topical vasoconstrictor such as epinephrine is thus redundant, and may actually be harmful as cocaine sensitizes the patient to exogenous epinephrine. Finally, the usual preoperative dosages of barbiturates are entirely inadequate to prevent or treat cocaine reactions. Why, then, have synthetic local anesthetics not replaced cocaine? Inherent differences in topical effectiveness, duration of anesthesia and toxicity provide the answer. Of other local anesthetics possessing topical effectiveness tetracaine is about six times more toxic than cocaine. Dibucaine is as toxic as tetracaine, and lidocaine, while relatively nontoxic, provides only a 15 minute duration of topical anesthesia. A review of cocaine and its potential substitutes thus leads to the conclusion that cocaine is still a vital and necessary instrument in the otolaryngologist's armamentarium, singularly providing excellent topical anesthesia of usable duration, vasoconstriction, and shrinkage of mucous membranes, all with a quite acceptable margin of safety.


Testicular changes associated with the initiation of spermatogenesis. Testicular changes preceding and accompanying the initiation of spermatogenesis are reviewed. The complex cellular changes occurring in the developing testis are found to be particularly well defined with the use of electron microscopy. The findings suggest that electron microscopic examination may be useful in the evaluation of male infertility, especially in those cases in which clinical and laboratory findings are negative or inconclusive. The amount of tissue required is minimal and can be taken as part of the regular testicular biopsy. The additional information provided by electron microscopy can be used to clarify the observations made on routine light microscopic study and may also lead to better understanding of the pathologic changes occurring in some of the less well understood forms of male infertility.


Improvement in lower esophageal sphincter pressure following surgery for complicated gastroesophageal reflux. A comparison was made of the pre- and postoperative lower esophageal sphincter (LES) pressures in nine patients undergoing a posterior gastropexy for complicated gastroesophageal reflux. LES pressure was increased from 4.4 plus or minus 0.4 mm Hg to 13.9 plus or minus 0.5 mm Hg following surgery (p less than .01). The ratio of the change in LES pressure compared to the change in gastric pressure during increases in intra-abdominal pressure delta S/delta G, was 0.59 plus or minus 0.05 preoperatively and 0.94 plus or minus .01 postoperatively (p less than .01). All patients were asymptomatic after surgery. Both the resting LES pressure and the S/G ratio following surgery were significantly less than the comparable values obtained in an age-matched control population (p less than .01). These studies suggest that the clinical improvement following surgery for gastroesophageal reflux may be due to the increase in resting LES pressure and the improved response of the LES to increased intra-abdominal pressure.


Cellular kinetics in multiple myeloma. A new approach to staging and treatment. Previous studies of myeloma immunoglobulin synthesis and tumor cell number, using a marker kinetic approach, have increased knowledge about body bruden of tumor cells, kinetics of myeloma cell growth, and response to chemotherapy. On the basis of these observations, we have developed a clinical staging system that permits accurate estimation of total myeloma cell number in patients who have not had specialized immunosynthetic measurements. We have incorporated this clinical staging into a nationwide time-sharing computer network called the Myeloma Study System (MSS). With the MSS we are able to establish a file for each patient, keep track of changes in tumor cell number with treatment, and evaluate toxicity. This resource should afford an excellent test of the value of cellular kinetics for the planning and uniform evaluation of cancer chemotherapy.


Monoclonal gammopathy in lymphoma.

Monoclonal gammopathy in lymphoma. Serum protein electrophoresis was performed in 68% of 1,682 consecutive patients with lymphoma. Of 400 patients with chronic lymphocytic leukemia and lymphocytic lymphoma, 2.3% had an IgG peak, a frequency significantly higher than that found in normal individuals of comparable age. IgM peaks occurred in 4.5% of patients with lymphomas characterized by diffuse histologic infiltration of lymph nodes. This frequency was about 100 times greater than predicted and indicated that most IgM peaks detected by electrophoresis are produced by lymphomas. Clinical responses to therapy were associated with reductions of tumor mass usually ranging from 10% to 50% of the pretreatment level. A much greater magnitude of tumor reduction is needed to improve remission duration for patients with chronic lymphocytic leukemia and lymphocytic lymphoma.


Immunochemical, clical, and pathological features of alpha-chain disease. Making the diagnosis of alpha-chain disease in the laboratory is difficult. Immunologic and structural characteristics of the abnormal protein were shown in results of cellular studies. There are clinicopathological features associated with the protein abnormality. The peculiar geographic origin of patients affected with alpha-chain disease and the possible reversibility of the hyperplastic process at its early stage lead to some considerations of cause.


Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Clinical response to imipramine or amitriptyline. The urinary excretion of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured in unipolar depressed patients before and during the fourth week of treatment with either imipramine hydrocloride or amitriptyline hydroxhloride. On the basis of strict rating criteria, 24 patients were selected as either unequivocal responders or nonresponders. In the imipramine group the mean pretreatment MHPG was significantly lower in the nine responders in the seven nonresponders; the converse was found with the amitriptyline patients. Of particular interest is that there was no overlap in individual values between the responders and nonresponders to either drug. Treatment with eigher imipramine or amitriptyline was associated with a significant decrease in MHPG excretion, which was independent of clinical response.


Amine precursors and depression.

Amine precursors and depression. The amino acid precursors, levodopa and L-tryptophan, were given to a group of hospitalized depressed patients in a double-blind placebo controlled study. Relatively large doses were not associated with sufficient clinical improvement to allow the patients to leave the hospital. Previous studies using the precursor-load strategy have produced conflicting findings on the use of these compounds for depressed patients.


Psychoactive drugs in mania. A controlled comparison of lithium carbonate, chlorpromazine, and haloperidol. Lithium carbonate, haloperidol, and chlorpromazine hydrochloride were compared in a double-blind controlled study with severely ill hospitalized manics. Lithium carbonate and haloperidol produced a highly significant improvement of manic symptoms without sedation. Although producing considerable sedation, chlorpromazine did little to alter the underlying mania qualitatively. Qualitative differences between lithium carbonate and haloperidol indicate that, while haloperidol has a more dramatically rapid impact on behavior-motor activity, lithium carbonate acted more evenly on the entire manic picture, with total normalization realized during active treatment. The majority of lithium carbonate-treated patients met discharge criteria at study termination, but not the patients receiving either neuroleptic drug. The rating scales are not sensitive enough to monitor manic psychopathology; this accounts for the lack of statistically significant differences among drug groups at treatment termination, despite the widely disparate discharge rates.


Classification in schizophrenia.

Classification in schizophrenia. Schizophrenia has been defined as an indentifiable disorder based on phenomenologic classification. Support for this concept is derived from consistent observations of a low frequency of the disorder in general populations throughout the world but substantially higher frequency of occurrence in siblings of affected individuals. The rates of concurrence in diagnosis for schizophrenia, surprisingly, vary in similar degree to those found for a series of physical disorders such as cervical cancer, emphysema and bronchitis, and electrocardiographic evaluations of cardiac disorder. The most recent findings from cross-national diagnostic studies of mental disorder uphold the need for a regular, more definitive classification system that is considered from both the service and research points of view.


Intravitreal injection of cephaloridine in the treatment of endophthalmitis. Ocular toxic effects of intravitreal injection of cephaloridine in rabbits was evaluated, and none were produced in doses of 0.25 mg or less. Clinically, intravitreal injection of cephaloridine in doses of 5 mg or more produced small punctate hemorrhages in the vascularized portions of the rabbit retina within two days. With doses of 2.5 mg or less, no clinical changes were seen during the two weeks of observation. Histologically, one day following intravitreal injection of 0.5 to 10 mg of cephaloridine there was clumping of the outer segments of the photoreceptors and destruction of the retinal pigment epithelium. Ten milligrams of cephaloridine intravitreally injected caused definite electroretinogram (ERG) changes ten minutes after injection. After 24 hours, the ERG was extinguished. An experimentally induced Escherichia coli endophthalmitis was successfully treated after six hours by intravitreal injection of cephaloridine.


Haemodynamic effects of the antiarrhythmic quaternary ammonium compound QX-572 in man. The haemodynamic effects of N, N-bis(phenyl-carbamoylmethyl) dimethylammonium chloride (QX-572) in man were studied. A controlled study was performed to rule out a possible influence of the catheterization procedure as such on the results. Ten patients with mild to moderate aortic regurgitation were studied: based on clinical data the patients were divided into 2 groups of 5. Randomly it was decided that one group should constitute a control group receiving saline while the second group received QX-572 , MG/KG BODY WEIGHT. In both groups the administration was performed as a slow intravenous infusion during 30 minutes. Heart rate, pressures in brachial artery and right atrium, cardiac output, stroke volume, and systemic vascular resistance were determined before, during, and up to 30 minutes after completion of placebo or QX-572. These variable remained stable in the control group while QX-572 produced an increase in heart rate most pronounced at the end of the infusion period. A transient decrease in systolic and mean brachial artery pressure during the infusion, and during the same period a decrease in right atrial pressure. Cardiac output and systemic vascular resistance were unchanged by QX-572 but they were not measured during the infusion when the changes in pressures were most pronounced. QX-572 was thought to act as a peripheral vasodilator during the infusion. Left ventricular contractility was studied by means of pressure curves obtained from a catheter tip manometer placed in the left ventricle. The first derivative of the isovolumic left ventricular pressure at the highest level (45mmHg) common to all patients was used (dp/dt-45). No significant difference could be observed when comparing mean changes of dp/dt-45 for the two groups. In the control group there was a slight but significant increase in dp/dt-45 during the time of observation. In the QX-572 group the results varied between individuals. Two of the patients differed from all other patients in the control and QX-572 groups showing a decrease in dp/dt-45 which, when most pronounced at the end of the infusion period, was -31 and -28 per cent of the preinfusion levels, respectively. This decrease probably reflects reduction of contractility. It was concluded that QX-572 in a dose of 8 mg/kg body weight did not have any major haemodynamic drawbacks.


Methylation of the ribosomal proteins in Escherichia coli. Nature and stoichiometry of the methylated amino acids in 50S ribosomal proteins. Methylated ribosomal proteins from Escherichia coli 50S subunit are localized by growing cells in a medium containing (1-14C)methionine and (3H-methyl)-methionine and comparing the 3H/14C ratio for each of the 50S ribosomal proteins. The following proteins are methylated: L11, L1, L3, L5, L7, L8, L9, L12, L18, and L33. The nature and stoichiometry of the methylated amino acid(s) in each of the methylated proteins are determined. Protein L11 is the most heavily methylated of all the 50S subunit proteins. This protein has previously been implicated in the peptidyl transferase reaction during protein synthesis (K. H. Nierhaus and V. Montejo (1973), Proc. Nat. Acad. Sci. U. S. 47, 1588-1602). Three proteins (L1, L3, and L5) have intermediate levels of methylation and contain about 0.4-0.6 methyl groups each per molecule of protein. Five other proteins (L7, L8, L9, L12, and L18) are also methylated to a slight extent (-0.1 methyl group/molecule of protein). One unknown methylated neutral amino acid was detected in protein L11 and at least one and possibly two other unidentified methylated amino acids appeared to be present in protein L33.


Apparent high degree of asymmetry of protein arrangement in the Escherichia coli outer cell envelope membrane. Ghosts from Escherichia coli have been oxidized with CuSO4-o-phenanthroline or ferricyanide-ferrocene. Upon oxidation they became resistant to boiling dodecyl sulfate. The resulting rod-shaped "oxidation containers" apparently held together by disulfide bridges, are practically pure protein. They are soluble in dodecyl sulfate when reduced and they contain a set of about 30 different polypeptide chains. The four major ghost membrane proteins are not represented among the "oxidation proteins." Comparison of data obtained from digestion of ghosts with trypsin or particle-bound trypsin showed that most of the "oxidation proteins" appear to be located at the outer surface of the ghost membrane which is derived from the outer cell envelope membrane. One of the major ghost membrane proteins, II, is partially digested by trypsin, and it is shown that its trypsin sensitive part is also exposed only at the outer surface of the ghost membrane. Native cells could be oxidized only with low yields of "oxidation containers." However, cell envelopes prepared without detergents or chelating agents, as well as cells depleted of phospholipid or treated with sucrose-Triton X-100, are completely accessible to oxidation. In each case, the same set of proteins as that present in "oxidation containers" from ghosts was found to be covalently linked. Treatment of cells with trypsin caused the loss of about five "oxidation proteins" and a complete loss of oxidizability of the ghosts derived from these cells. It therefore appears that arrangement and localization of the "oxidation proteins" are not greatly different in cells and in ghosts, i.e., that these proteins are also situated asymmetrically at the outer cell envelope membrane.


Recognition of the 3' terminus of 2'-O-aminoacyl transfer ribonucleic acid by the acceptor site of ribosomal peptidyltransferase. The interaction of the 3' terminus of 2'- and 3'-O-aminoacyl-tRNA with the peptidyltransferase A site of Escherichia coli ribosomes has been studied using the following aminoacyl oligonucleotides as models of the 3' terminus of AA-tRNA: C-A-Phe, C-A(2'Phe)H, C-A(2'H)Phe, C-A(2'Phe)Me, C-A(2'Me)Phe, C-A(2'Gly)H, and C-A(2'H)Gly. The transfer of Ac-(14C)Phe from the Ac-(14C)Phe-tRNA-oly(U)-70S ribosome complex to puromycin (10-4 and 10-5 M) was inhibited by C-A-Phe, C-A(2'Phe)H, C-A(2'H)Phe, C-A(2'Gly)H, and C-A(2'H)Gly. Kinetic analysis of the inhibition of Ac(14C)Phe-puromycin formation by C-A(2'Phe)H failed to show simple competitive inhibition. Binding of C-A-C-C-A-(14C)Phe to 70S ribosomes in the presence of an excess of deacylated tRNA was also inhibited by C-A-Phe, C-A(2'Phe)H, C-A(2'H)Phe, C-A(2'Phe)Me, and C-A(2'Me)Phe. It appears that the acceptor site of peptidyltransferase can recognize the 3' terminus of either 2'- or 3'-O-AA-tRNA, with preference for the 2' isomer. It therefore follows that 2'-O-AA-tRNA amy be bound to ribosomes prior to peptide bone formation and that 3'-O-AA-tRNA, which is used exclusively by peptidyltransferase as an acceptor, is supplied by 2' leads to 3' transacylation occuring at the peptidyltransferase A site.


Multiple forms of phosphodeoxyribomutase from Escherichia coli. Physical and chemical characterization. Phosphodeoxyribomutase from Escherichia coli has been purified to homogeneity. Chromatography on DEAE-Sephadex revealed three peaks of enzyme activity, designated form I, form II, and form III. Form III could be further separated into form III-1 and form III-2 by polyacrylamide gel electrophoresis. The four different molecular forms of the enzyme thus isolated were shown not to be products of the column chromatography per se. The amino acid composition as well as the N-terminal amino acid were found to be identical for the different forms. Molecular weight determinations demonstrated that all four forms of the enzyme consist of a single polypeptide chain with a molecular weight of 45,000 plus or minus 1000. Measurements of partial specific volumes, sedimentation coefficients, and absorption coefficients for form I and form II did not reveal any differences. It is concluded that the multiple forms of phosphodeoxyribomutase are caused by modifications of the polypeptide chain. Evidence is presented that form II is formed in vitro from form I by deamidation. It is probable that this deamidation occurs in vivo also. The different forms displayed only minor changes with respect to KM for substrate and cofactor. Greater differences seem to exist among the four enzyme forms with respect to VM and to cobalt binding.


Oxidation of methionine residues of porcine and bovine pepsins. By treating porcine and bovine pepsins with H2O2 at pH 3.2, 3.5 of the 4 methionine residues of porcine pepsin and 1.6 of the 3 residues of bovine pepsin were oxidized to methionine sulfoxide. The effect of modification on activity varied with the substrate. There were no significant changes in catalytic constants in the hydrolysis of acetyl-L-phenylalanyl-L-tyrosine by both pepsins and in the hydrolysis of benzyloxycarbonyl-L-glutamyl-L-tyrosine by porcine pepsin. Hydrolysis of benzyloxycarbonyl-L-glutamyl-L-tyrosine by bovine pepsin was too slow to measure. With benzyloxycarbonyl-L-histidyl-L-phenylalanyl-L-tryptophan ethyl ester as substrate, the modification decreased the catalytic efficiency (kcat/Km) by two-thirds for porcine pepsin and by half for bovine pepsin. With hemoglobin substrate, digestion was significantly less than with native pepsin for modified porcine pepsin, and slightly less for modified bovine pepsin. The results are interpreted as indicating the presence of a methionine residue that participates in the binding of long substrates, but is not close enough to the active site to reach short substrates. Cleavage of the modified pepsins with cyanogen bromide identified the methionine nearest the carboxyl terminus of both pepsins as a resiude that remained partially unmodified.


Isolation and characterization of two outer membrane preparations from Escherichia coli. A method was developed for releasing specifically a part of outer membrane during spheroplast formation. A highly purified outer membrane (outer membrane I) was obtained from the spheroplast medium by isopycnic sucrose gradient centrifugation. The remaining outer membrane (outer membrane II) and cytoplasmic membrane was also isolated from the spheroplasts by the isopycnic centrifugation. Two outer membrane preparations were different from the cytoplasmic membrane in protein composition, enzyme localization, phospholipid composition, lipopolysaccharide content and electron micrographs. Although outer membranes I and II were almost the same in various respects, they seemed to be different from each other under electron microscope and in cardiolipin content. It is suggested that the outer membrane I and the outer membrane II, at least a part of the outer membrane II, are integrated in a different fashion in the outer-most layer of Escherichia coli cell surface.


Extracellular bicarbonate ions and insulin secretion. The role of bicarbonate ions in insulin release was studied with incubated and perifused isolated rat islets of Langerhans. In the absence of NaHC03, the early phase of glucose-induced secretion was completely abolished and the second phase inhibited by approximately 65%. The insulinotropic effect of the sugar was totally restored after reintroduction of the ion in the medium. The monophasic secretory after reintroduction of the ion in the medium. The monophasic secretory response to tolbutamide was also markedly diminished by omission of NaHC03, WHereas the release evoked by a high concentration of K+ was very little affected. CO2 wwas unable to substitute for HC03minus, but small concentrations of the anion (3to 5mM) WEre sufficient to ensure a normal response to glucose.


[Focal myofibrillar disorganization in acute metabolic impairment of somatic musculature]. Skeletal muscles of rats and rabbits were studied by the target electron microscoptic and polarization-optic methods after administration of toxic substances and experimental acute ischemia of the extremities. Two types of foci of the myofibrillae disaggregation were described along with contracture injuries. The first occurred on the basis of relaxation and was expressed in total dysaggregation and lysis of myofibrillae; with the second type lysis occurred in the partially contracted fibers and began in the I-discs leading to diastasis of A-discs. The first type of the foci is characteristic chiefly of the white fibers, and the second one--of the red.


[Studies on the Concanavalin A-receptors of rabbit erythrocytes and of erythyrocyte shadows using immunoelectron microscopy]. The authors report on the immuno electron microscopic demonstration of Concanavalin A-receptors on the erythrocyte membrane. Immuno freeze-etching studies evidenced a focal arrangement of Concanavalin A-receptors on intact erythrocytes as well as on erythrocyte ghosts. Obviously hemolysis by distilled water does not produce changes in the pattern of distribution of Concanavalin A-receptors whereas slight aggregation of plasma membrane intramembraneous particles occured. No unambigous spatial relationship between Concanavalin A-receptors and the plasma membrane intramembraneous particles (intrinsic proteins) of erythrocytes could be observed.


The continent ileostomy of Kock (ileal intra-abdominal reservoir). Experience with 9 cases operated on for ulcerative colitis. A series of 9 patients with ulcerative colitis undergoing proctocolectomy and ileal intra-adbominal reservoir is reported. Eight patients are continent and 1 is incontinent. Early and late postoperative complications, work capacity and social and sexual functions are described.


[X-ray diffraction studies of muscles].

[X-ray diffraction studies of muscles]. A brief account of the modern state of X-ray diffraction studies of muscles is presented. Recently many investigaters payed particular attention to concrete changes taking place in structural-executive (protofibrillar) apparatus of muscles at the change of their state. The drawback of these works is the necessity of interpreting the data on the basis of model ideas having definite variability. Our studies here presented differe by the approach to the problem and to a certain extent by the methods applied. Our main task was to study the dynamics of structural changes in muscles while the latter perform their working function. Special attention was payed to the studies of muscles at different shortening eithor on living or fixed samples. The effect of some conventional fixators on structural parameters evaluated by X-ray analysis was studied for the first time. A means of stroboscopic accumulation of X-ray diffraction patterns for periodic fast processes was developed. One of our main tasks was to find the range of applicability sliding mechanism hypothesis for describing muscle shortening. It was observed that the sliding mechanism held true for the desscription of the structure of muscles shortened in a physiological range. X-ray diffraction patterns were obtained which were different for the shortenings according to the sliding mechanism and those with A-disc shortening and during supercontraction. The limits of the sliding model were evaluated by some of these characteristics for muscle of different composition and properties. The problem of the forces realizing muscle shortening is discussed, some of the author's studies being taken into account. Muscle should be assessed as a complex heteromorph biological object and as a complex liquid crystalline system to create the models of its molecular structure and to elucidate the precise mechanism of its functional activity.


Phenol sympathectomy in the treatment of intermittent claudication: a controlled clinical trail. Twenty-five patients with intermittent claudication were randomly allocated to treatment either by injection of phenol into the lumbar sympathetic chain or by injection of local anaesthetic subcutaneously. On the day after the injection, sympathectomy, assessed by skin temperature change, was achieved in 85 per cent of the phenol group. At 1 month subjective improvement was claimed by 45 per cent of the patients in the sympathectomized group and by 64 per cent in the control group; at 3 months the figures were 25 and 45 per cent respectively. Treadmill testing at two exercise loads showed no significant difference in claudication distance or stopping time between the two groups. Calf blood pressure response following exercise was not affected by sympathectomy. There is no subjective or objective evidence that phenol sympathectomy improves intermittent claudication.


A clinical trial designed to discover if the primary treatment of varicose veins should be by Fegan's method or by an operation. 1. The current practice of operating upon patients with varicose veins as the treatment of choice costs more than xi15 million a year. 2. The bulk of this expense is due to the length of time that patients are kept in the ward. If they were treated as outpatients, either by Fegan's method or by operation, the cost would be reduced to one-tenth of what is now spent. Even if the operation were done on a "short-stay" basis the cost would be reduced to one-third or less. 3. Although the long term results of Fegan's method are uncertain there is no doubt that it gives better immediate results than an operation. Moreover, there is no particular type of varicosity of shape of limb which precludes its use.


Combined immunodeficiency disease associated with adenosine deaminase deficiency. Report on a workshop held in Albany, New York, October 1, 1973. Fifty-five children with CID and known ADA status were studies at a workshop held in Albany, New York. Erythrocyte ADA determinations were performed in 22 of the 55 patients, 13 of whom were ADA negative. The ADA defect appears to be transmitted as an autosomal recessive trait. Some patients with CID and ADA deficiency have characteristic radiologic abnormalities of the skeleton, which are not found in other illnesses. The thymus glands of all patients with CID and ADA deficiency who could be examined have evidence of thymic involution manifested by presence of Hassall's corpuscles and differentiated germinal epithelium; this is in contrast to "classic" thymus findings in CID with normal ADA. Adenosine deaminase probably plays an important, although as yet undefined, role in lymphocyte development and/or function. The deficiency of ADA in CID is the first enzyme defect observed in a deficiency disease of specific immunity.


Spina bifida children attending ordinary schools. From September 1971 to September 1973 a policy was actively followed in South Gloucestershire of placing spina bifida children in ordinary schools wherever possible. This was achieved successfully in 14 cases out of a possible 24. Special attention was paid to the selection of children and schools. The main contraindications to attendance at ordinary school were: below average intelligence, special perceptual problems, the need for intensive physiotherapy, and problem incontinence-particularly infaecal continence. Success often depended on special provisions-for example, transport, aids to mobility, peripatetic physiotherapists. Personal attendants (welfare assistants) could be allocated to each of the more severely handicapped children. The lack of facilities for handicapped pupils in comprehensive schools is a matter needing urgent review.


Renal excretion of fluoride in renal failure and after renal transplantation. We have compared the renal excretion of fluoride in a variety of patients with chronic renal failure maintained with and without protein restriction before and during regular dialysis treatment and after transplantation. The patients tended to continue to excrete normal dietary loads of fluoride quite well until renal function was seriously reduced. From a regression of function on excretion the mean level of creatinine clearance when a normal dietary load of fluoride 0.0526 plus or minus 0.019 mmol/2 h (1.0 plus or minus 0.36 mg/24h) has a 90% chance of being excreted lies around 16 ml/min, a level when most patients with renal failure will be symptomatic. Acute loading of such patients with additional fluoride in the form of sodium fluoride from 40 mg to 60 mg/day showed a twofold to threefold increase of serum fluoride concentrations, slight increases in urinary fluoride excretion, and heavy tissue absorption, suggesting that prior fluoride loading of the skeleton had not taken place. These effects contrasted with those in one patient with normal renal function and with those in one patient with skeletal saturation due to prolonged loading. After renal transplantation fluoride excretion increased but reached normal levels within three months of satisfactory function, suggesting that fluoride loading in renal failure and during regular dialysis therapy had not been excessive.


Pituitary sensitivity to 50 micro g LH/FSH-RH in subjects with anorexia nervosa in acute and recovery stages. Gonadotrophic output was measured in response to a 50-mug dose of luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH) in subjects with anorexia nervosa. A diminished response was found in subjects of low body weight, and in some a response occurred with increments of plasma FSH greater than those of LH. With restoration of body weight the response to the releasing factor was similar to that usually observed in healthy men and women.


Effect of different doses of chlorthalidone on blood pressure, serum potassium, and serum urate. Chlorthalidone given to 40 hypertensive women significantly decreased blood pressure and serum potassium levels and increased the serum urate concentration.  There were no individual correlations between the reduction in blood pressure and the decrease in serum potassium or the increase in serum urate.  A reduction in dosage from 50 mg daily to 50 mg three times a week produced no significant changes in the diastolic or mean blood pressures though the systolic blood pressure was moderately increased.  Concomitantly, serum potassium increased and serum urate decreased significantly on the lower chlorthalidone dose.  We conclude that high doses of oral diuretics compared with lower ones are of limited further benefit and may increase the risk of clinically significant hypokalaemia and hyperuricaemia.


Brain stem reticular units: some properties of the course and origin of the ascending trajectory. Experiments were conducted in acutely prepared cats anesthetized with halothane-nitrous oxide. Single units were recorded in the mesencephalic and rostral rhombencephalic reticular core, and their ascending axons were stimulated in the mesencephalon, diencephalon, and telencephalon. The locations of stimulation and recording sites were determined by histological examination of the brains. Antidromic spikes were elicited by electrodes with a stimulus spread of approximately 300 mum and were collided with spontaneous (orthodromic) spikes to confirm antidromicity. Projecting axons were found to be scattered diffusely in the central mesencephalon in both the tegmentum and tectum. At the mesodiencephalic junction, the dorsal extent of the pathway lay in the posterior commissure and the ventral extent in the substantia nigra. More rostrally, a ventral group of axons was found in or near the supraoptic nucleus in the hypothalamus, and near the floor of the forebrain in the basal telencephalon. In agreement with previous reports, a dorsal component was located in the medial thalamus, most often in the nucleus centralis lateralis. The conduction velocity of each axon was determined, and they suggest a wide range of axon size in the ascending pathways. There may be a slight predominance of smaller fibers in the dorsal component and of larger fibers in the ventral component; however, all parts of the pathways were relatively heterogenous. The units from which projecting axons arose were found in the rostral rhombencephalon, and no units sending their axons along the restricted pathways investigated were identified rostral or caudal to this region. However, no conclusion is drawn concerning units within the region extending from 0.0 to 0.6 mm of the midline or other brain stem regions known to be monoamine-rich and to have ascending axons; these cellular populations were not examined.


Rostral projections from the hypothalamic arcuate nucleus. The response of neurones in the medial basal hypothalamus to electrical stimulation in the suprachiasmatic/preoptic region has been studied in rats anaesthetised with urethane. Neurones in the hypothalamic arcuate, periventricular, ventromedial and dorsal premammillary nuclei were antidromically activated by the stimulation showing that such cells send processes in rostral direction outside the median eminence. Tuberoinfundibular and rostrally projecting units were found interspersed in the "hypophysiotrophic" area.


The fine structural localization of glutamate decarboxylase in developing axonal processes and presynaptic terminals of rodent cerebellum. The immunocytochemical localization of L-glutamate decarboxylase (GAD), the enzyme which which forms gamma-aminobutyric acid (GABA), has been studied in developing rodent cerebellum. During the first 3-4 postnatal days, GAD is distributed along non-terminal portions of axonal processes in close association with small vesicles. Some of the axonal processes emanate from profiles which resemble growth cone varicosities, and are presumed to be foliopodia which extend distally from axonal growth regions. At the end of the first postnatal week the GAD-containing axonal processes are seen to form protosynaptic contacts, and GAD is localized around synaptic vesicles and at presynaptic junctional membranes. During the second and third postnatal weeks GAD gradually becomes localized to mature synaptic terminals in association with synaptic vesicle, mitochondrial, and presynaptic junctional membranes. The results suggest that GAD is present in growing neurites in close association with small vesicles prior to the time the neurites make protosynaptic contacts, and that differentiation of these contacts results in a sequestering of GAD into synaptic terminals.


Clinical and clinico-pathological effects of Escherichia coli endotoxin in mature cattle. The effects of intravenous administration of Escherichia coli endotoxin were studied in eight mature lactating cows. Three cows were studied following intrammary infection with E. coli. Significant clinical findings are presented. Significant clinico-pathological findings include leukopenia, decreased blood serum calcium concentrations and increased levels of serum glutamic-oxaloacetic transaminase and serum ornithine-carbamyl transferase. Significant elevations of plasma corticosteroids were also noted.


The effect of antisera on porcine enteropathogenic Escherichia coli in ligated segments of pig intestine. Nineteen antisera produced in pigs against 14 enteropathogenic and five nonenterotoxigenic porcine strains of Escherichia coli were tested for their ability to inhibit gut loop fluid accumulation induced by homologous and heterologous organisms. In addition, four antisera produced in pigs by an intensive series of intravenous inoculations and three by a less intensive series of intramuscular injections of a polyvalent E. coli vaccine were evaluated. Antisera were also produced in rabbits against eight strains of porcine enteropathogens and tested in pig gut loops. Fluid inhibiting activity was detected in prevaccinal sera of pigs but not of rabbits. This activity was significantly increased following immunization. When single strains of E. coli were used for immunization the activity of the antisera against heterologous organisms varied considerably from one test strain to another and was usually much less than that against the homologous organism. The activity against heterologous organisms could not be associated with relatedness of the O, K and H antigens of the vaccine and the test strains. Antisera produced against a vaccine made by combining three strains were shown to exert inhibitory effects on heterologous organisms similar to those against homologous organisms. Considerably less activity against homologous and heterologous organisms was present in antisera produced by the series of intramuscular compared with the series of intravenous injections.


A mixed bacterial population in a continuous culture with and without kaolinite. Chromobacterium lividum and a Pseudomonas sp. were grown in pure and mixed continuous culture with and without the clay-mineral, kaolinite. Irrespective of the growth conditions, C. lividum adhered to the wall of the culture vessel whereas the Pseudomonas sp. showed no such tendency, at least visually. During mixed culture studies, the organism which was initially established in the culture dominated. The ratio between C. lividum and the Pseudomonas sp. was about 20:1 when C. lividum was first established and 1:2 when the Pseudomonas sp. was first grown. The indirect fluorescent antibody technique provided a rapid method for differentiating the mixed cultures when the bacterial concentration was sufficient for microscopic analysis. During both pure and mixed continuous culture studies, the addition of kaolinite reduced the C. lividum but not the Pseudomonas sp. population.


Massive pulmonary gangrene: a severe complication of Klebsiella pneumonia. Massive pulmonary gangrene developed in two patients. Review of the literature reveals 10 other case reports of pulmonary gangrene complicating lobar pneumonia. Among the total of 12 patients whose cases have now been reported, all 4 patients who were treated nonsurgically died and the 8 who underwent surgical resection of the gangrenous lung survived. The present report emphasizes the necessity of early recognition and appropriate surgical treatment for a successful outcome.


Pathogenesis of human cholesterol cholelithiasis. The pathogenesis of cholesterol cholelithiasis in humans has been studied by means of three techniques. The cholesterol-solubilizing capacity of bile may be determined by estimation of the relative composition of the three major lipid constituents of bile. Consistent reduction in the cholesterol-carrying capacity of gallbladder bile of persons with gallstones when compared with normal subjects has not been shown. Normal subjects frequently have supersaturated bile. Secretion rates of biliary lipids have been estimated by two methods; with the method that appears to be more physiologic no change in lipid secretion rates was found in gallstone patients. Bile acid pool size has been measured by isotope dilution techniques; it is reduced in patients with gallstones. It is not clear whether this reduction is important in the pathogenesis of cholesterol cholelithiasis, for the bile acid secretion rate is normal because of an increased rate of cycling of the pool through the enterohepatic circulation. The role of the gallbladder in the genesis of cholesterol cholelithiasis may be more important than has been realized.


The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy. A study was performed to evaluate the clinical and histopathologic characteristics of a distinctive degenerative lesion within the central nervous system (CNS) of children with acute lymphocytic leukemia (ALL). Of the 231 patients in this study, 13 were found to have specific degenerative changes in telencephalic white matter. Morphologically, the principal changes consisted of diffuse reactive astrocytosis and multiple, noninflammatory necrotic foci, often containing varying amount of mineralized cellular debris. Clinical features common to all patients with this leukoencephalopathy were: 1) cranial irradiation of 2000 rads or more and 2) methotrexate administered systemically after irradiation. Comparison of selected clinical features of patients with and without leukoencephalopathy showed that methotrexate administered intravenously after a cumulative dose of CNS irradiation of 2000 rads or more can result in degeneration of CNS white matter in patients with ALL. Age at time of irradiation, bacterial infections, nutrition, and CNS leukemia were not causally related to the development of this disease. This study suggests that chemotherapeutic agents may diffuse through the blood-brain barrier following CNS irradiation of 2000 rads or more.


Non-Hodgkin's lymphoma: patterns of relapse from complete remission after combination chemotherapy. An analysis of patterns of relapse from complete remission in patients with non-Hodgkin's lymphoma treated with combination chemotherapy has demonstrated differences between histologic subgroups. Patients with diffuse histiocytic lymphoma who achieved a histologically proven complete remission after 6 months of treatment without maintenance have remained disease-free whereas those with nodular poorly differentiated lymphocytic and diffuse well-differentiated lymphocytic lymphomas have demonstrated a pattern of continuous late recurrence. The initial sites of relapse from complete remission in lymphocytic lymphoma were lymph nodes and bone marrow which were involved prior to treatment. Aggressive attempts at remission induction appear warranted in patients with diffuse histiocytic lymphoma because of the potential for extended disease-free survival. Patients with nodular poorly differentiated lymphocytic lymphoma may benefit from the use of maintenance chemotherapy, or radiotherapy to regions of previously known involvement after initiation of remission with chemotherapy.


The role of chemotherapy in the management of soft tissue sarcomas. Prior to the use of chemotherapy, survival for rhabdomyosarcoma which had been completely resected was 50-60%. A controled study done by Children's Cancer Study Group showed the effectiveness of combined chemotherapy used as part of primary therapy in similar patients. Children who received actinomycin D (Act D) and vincristine (Vcr) for 1 year after surgery and radiotherapy had a lower metastatic rate than those who received none. This combination resulted in an 89% survival in patients with localized disease which was surgically resectable. Patients with microscopic residual disease had a 91% survival. With more aggressive use of combined chemotherapy, experience has accumulated demonstrating improved response and survival in both localized and gross residual disease. Combinations of Act D, Vcr, and cyclophosphamide can reduce initial tumor size, making large tumor masses more amenable to surgery and radiotherapy. Currently, an intergroup study is testing the response to four different drug combinations and the duration of therapy needed for various stages of the disease.


Role of therapeutic radiology in cancer of bone. Management of patients with Ewing's sarcoma has been discussed with reference to the need to achieve an excellent local result from radiation therapy now that patients are experiencing long-term survival. The technique of biopsy is important: small scar; located within treatment portal; positioning such that there is a good connective tissue bed (e.g. not immediately overlying bone); tissue obtained from soft tissue component and no cortical bone removed. Radiation therapy technique is based upon: special shaping of the irradiated volume to correspond to estimate distribution of tumor; distribution of dose in accordance with tumor cell number (progressive field reduction); precision setup of patient each day; and high total dose (6000-6600 rads in 6-6.6 weeks). This treatment is to be given in combination with multidrug multicycle chemotherapy. For osteosarcoma, special attention was given to lesions of mandible, where preoperative irradiation and hemimandibulectomy appears to be much more effective than surgery alone.


Treatment of lymphoma.

Treatment of lymphoma. Lymphomatous diseases (non-Hodgkin's) of children differ markedly from those of adults in histology, natural history, and response to therapy. Information obtained from treating adults with lymphoma cannot be applied to children with equal success; the progress in treating children has been slow. The following types of non-Hodgkin's lymphoma have been distinguished in children seen at the M. D. Anderson Hospital and Tumor Institute in the past 7 years: 1) diffuse undifferentiated lymphoma (Burkitt's lymphoma); 2) diffuse undifferentiated lymphoma (non-Burkitt's lymphoma lacking leukemic propensity); 3) diffuse poorly differentiated lymphocytic lymphoma (non-Burkitt's lymphoma with leukemic propensity (convoluted cell type); and 4) diffuse histiocytic lymphoma (histiocytic lymphoma). The interrelationships of age, sex, histology, and primary site are presented. The occurrence of mediastinal masses in non-Burkitt's tumor (convoluted cell type) is particularly striking. Therapeutic regimens designed for specific types of non-Hodgkin's lymphoma have improved the outcome of treatment in Burkitt's lymphoma, non-Burkitt's lymphoma (convoluted cell type), and histiocytic lymphoma (Stages I and II) as compared with treatment regimens used prior to 1967.


Effect of digoxin on atioventricular conduction. Studies in patients with and without cardiac autonomic innervation. The effect of digoxin on atrioventricular (a-v) conduction was compared in five patients with an intact cardiac autonomic nervous system (Group I) and seven patients who had undergone cardiac transplantation (Group II), in whom we have previously shown the transplanted heart to be completely denervated. Small decreases in the atrial effective refractory period (ERP) (from 262 plus or minus 12 to 254 plus or minus 11 msec) and atrial functional refractory period (FRP) (from 304 plus or minus 12 msec) were observed in Group I patients after digoxin, but these changes were not significant. However, significant increases in the A-V nodal ERP (from 315 plus or minus 18 msec to 351 plus or minus 17 msec, P less than 0.05), and A-V nodal FRP (from 426 plus or minus 42 to 460 plus or minus 46 msec, P less than 0.01) were produced by digoxin and were unrelated to changes in cycle length. In Group II patients with denervated hearts, changes in atrial ERP (from 246 plus or minus 4 to 243 plus or minus 6 during spontaneous sinus rhythm; from 204 plus or minus 10 to 216 plus or minus 8 msec during atrial pacing) and atrial FRP (from 311 plus or minus 12 to 316 plus or minus 11 msec during spontaneous sinus rhythm; from 254 plus or minus 12 to 260 plus or minus 10 msec during atrial pacing) were not significant. However, in contrast to the Group I patients, the digoxin-induced changes in A-V nodal ERP (from 280 plus or minus 22 to 297 plus or minus 18 msec during atrial pacing) and FRP (from 368 plus or minus 18 to 377 plus or minus 18 msec during spontaneous sinus rhythm; from 334 plus or minus 13 to 346 plus or minus 16 msec during atrial pacing) were also statistically insignificant. Our results demonstrate that the electrophysiologic effects of digoxin on atrioventricular conduction in man are most marked in the atrioventricular node and are dependent on cardiac innervation


The potential of phosphorescence spectrometry in clinical chemistry--the new generation of instrumentation and methodology. We review recent advances in instrumentation and methodology in phosphorimetry that should facilitate the use of phosphorimetry for clinical analyses and recent phosphorescence studies of interest to the clinical chemist. We indicate recent advances, particularly improvements in instrumentation, novel methodologies, and new chemical processes that result in either an increase in sensitivity or selectivity (or both) of measurement of compounds of clinical importance. The greatest use of phosphorimetry in the clinical laboratory will not be for the analysis of very large numbers of samples for one species via automatic instrumentation, but rather will be for the analysis of those molecular species difficult or impossible to measure by conventional methods (colorimetry, fluorometry, etc.). Although various instrumental and methodological advances are discussed separately here, the most important use of these advances in clinical chemistry will undoubtedly be when two or more of them are combined, for example, in the use of time- or frequency-resolved phosphorimetry for the selective measurement of the phosphorescence resulting with inorganic probes and the appropriate choice of solvent and pH (of course, the instrument could contain an image vidicon detector for rapid determination of the spectrum, the decay curve, or both).


Intramammary infections in the sow during the peripartum period. The incidence and ype of aerobic bacteria causing intramammary infection (IMI) in two groups of peripartum sows were determined. The incidence of IMI in 24 sows near farrowing was 30.2 percent; the incidence in 16 machine-milked sows was 81.0 percent. Numerous mixed IMI were detected. The bacterium causing most IMI was Staphylococcus epidermidis, followed by beta hemolytic streptococci, aslpha hemolytic streptococci, Escherichia coli, and diphtheroids. The beta hemolytic streptococci and E. coli cultures were studied in detail. The relationship of bacterial IMI to agalactiae toxemia is discussed.


Surgical treatment of Candida endocarditis. Case reports from a group of 15 patients with Candida endocarditis seen and treated at the Los Angeles-University of Southern California Medical Center between 1960 and 1974, together with a survey of other reported cases, serve to re-emphasize the importance of early diagnosis of this disease and lead to certain conclusions regarding its treatment. With medical or surgical treatment alone, the mortality for Candida endocarditis is 82 per cent. With surgery and medical treatment combined, the mortality is 20 percent. It is important to institute medical treatment as soon as diagnosis of Candida endocarditis is made and surgery must be performed as soon as possible, preferably within 24 to 48 hours or, at most, a few days after the patient has left the hospital. Close observation of the patient after discharge is important.


Increased sensitivity of regional measurements in early detection of narcotic lung disease. Intravascular foreign body thromboembolism and interstitial or vascular granulomata in the lungs are common sequelae to intravenous drug abuse. Early detection of such complications is important, because of the youthful population often involved. Conventional pulmonary function tests, including forced expiratory volumes, diffusion capacity for CO (DLco), chest radiograph and arterial blood gas analysis were performed in 23 narcotic addicts, most of whom had no pulmonary symptoms. The results were compared with radionuclide pulmonary function studies obtained following inhalation of 133Xe gas and injection of 99-mTc albumin microparticles. Thirteen subjects who had normal nonnuclear pulmonary function tests, including DLco and chest radiograph, demonstrated significant abnormalities of regional lung perfusion by lung scan. Of the ten subjects with abnormal DLco all had abnormal perfusion scans and five were noted to have hypoxia at rest. In addition, six of the ten subjects with abnormal DLco revealed a history of concomitant "solid pill abuse" along with heroin abuse, whereas only 2 of 13 subjects with normal DLco admitted tooccasional solid pill abuse. The perfusion lung scan is therefore a sensitive means for detection of early lung disease in narcotic addicts.


Pulmonary function studies in ex-heroin users. Pulmonary function tests were performed on a group of 22-ex-heroin addicts with no known pulmonary disease or symptoms. Vital capacity and total lung capacity were normal in all but four patients. Only two patients had evidence of moderately severe airway obstruction. However, the single breath diffusing capacity (Dco) was significantly reduced in many of the patients and averaged 81 percent of predicted for the entire group. Patients with most severe reduction of Dco also had reduction of lung volumes. In addition, six patients had increased lung recoil force (Pmax) and decreased lung compliance. There was no correlation between degree of functional impairment and duration or amount of durg use, incidence of overdose or intravenous injection of crushed tablets. Followup studies in four patients after several months on methadone maintenance showed improvement in lung volumes and/or Dco. Possible etiologic considerations to explain these abnormalities were previous subclinical pneumonias, foreign body granulomas, previous pulmonary edema or other direct toxic effect on alveolocapillary membrane as the result of use of drugs.


The use of spontaneous ventilation with constant-positive airway pressure in the treatment of salt water near drowning. Constant-positive airway pressure with spontaneous ventilation was successfully used in treatment of a patient who had suffered near-drowning in salt water. The patient was able to maintain adequate respiratory mechanics, although oxygenation without end-expiratory pressure was severely impaired. The rapid improvement in arterial oxygenation obviated the need for mechanical ventilation in this patient. It is suggested that the simplest modality of effective therapy should be used in such patients.


[Bacteriological study of redon drains in accident surgery (author's transl)]. After 'clean' operations, 121 Redon drains from 80 patients were cultured. 17.4% of Redon tips were contaminated, but microorganisms were found in only 7.4% of wound secretions aspirated from them before they were removed. Only Gram-positive cocci, most of them of questionable pathogenicity, were found. Although drains or wound secretions were found to be contaminated in 21 patients, clinical evidence of disturbed healing occurred in only two patients. The presence of microorganisms provided no pointer to later healing difficulties. Culturing Redon tips is, therefore not a reliable method for early recognition of wound infections. Antibiotics should not be used merely on evidence of bacterial contamination of Redon tips without any clinical signs of infection.


[Effect of aprotinin in acute myocardial infarction (clinical double-bind study (author's transl)]. In a double-bind study 164 patients with acute myocardial infarction, admitted to an intensive-care unit within 72 hours of infarction, were randomly treated for three days either with aprotinin (Trasylol-82 persons) or placebo (82 persons). Retrospective analysis proved both patient groups to have been comparable in all other respects. There was no definite influence on the course of the infarction, haemodynamic changes, arrythmias or mortality rate. Trasylol thus has no therapeutic importance in the treatment of acute myocardial infarction.


[Clinical studies on the effect of drugs used in the treatment of angina]. The report is based on a four-centre study on 25 patients with coronary insufficiency (ECG signs). In random sequence the following were given to each patient: a nitrate (isosorbide dinitrate), carbocromene, practolol, and oxyphedrine. The initial criterion for inclusion was S-T depression of 0.2 mV on stepwise exercise (bicycle ergometry). S-T depression, systolic blood pressure and heart rate changes were used as criteria. For each drug there was an acute test and a long-term test of 12 days. The Friedman test was used for the statistical evaluation of the results. Isosorbide dinitrate decreased the extent of S-T depression in the acute tests while practolol did so in the long-term test. Practolol reduced systolic pressure on long-term administration, with no difference in the acute experiment. Heart rate was reduced by practolol both acutely and long-term. These results give no indication for any possible differential treatment of coronary insufficiency, but this may be due to the selection of patients in this study.