[Action of hygromycin B on the producers of levorin and mycoheptin]. The effect of hygromycin B on survival and variation of the levorin and mycoheptinproducing organisms, i.e. Act levoris, strains 28 and PR-52/67 and streptoverticcium mycoheptincium, strain 44B/I was studied. When added to the agarized medium, hygromycin B had a lethal effect on the above strains. The lethal effect increased with an increase in the concentration from 2.5 80 Units/ml. High modification variation of the colony morphology was observed on media with hygromycin B. At the same time hygromycin B induced morphological and hygromycin-resistant mutants. The variation of the property of the antibiotic production in the above cultures increased under the effect of hygromycinB. The maximum rate of the plus variants was observed at high lethal effects of hygromycin B, when the survival rate of the spores was 10(-3) and 10(-4). An individual reaction of the cultures to hygromycin B was found. Formation of the mutation of resistance to the specific phage in the genome of strain PR of the levorin-producing organism increased its sensitivity to hygromycin and variation of the colony morphology and the property of the antibiotic production.


[Transmissivity of the various R factors found among E. coli cultures circulating under natural conditions]. Transmissivity of drug resistance in wild strains of E. coli was shown to be determined not only by the presence of the transmissive factor and r-determinants in the microbial cell, but also by the functional activity of the R-factor. The capacity of the R-factor for transmission depended to a certain extent on the number of the r-determinants in the R-factor and the presence of various r-determinants in the R-factor.


[Suppression of the conjugational transfer of derepressed R factors by the dye, metachrome yellow]. Metachrome yellow widely used for preparation of nutrient media was tested with respect to its effect on conjugation of R-transfer. The standardized kinetic system described by the authors earlier was used. It was shown that metachrome yellow had a pronounced inhibitory effect on conjugation transfer of depressive R-factors RI drd and R 64 drd. The effect was markedly pronounced even in the presence of 100 gamma/ml of metachrome yellow, the concentration which was practically not bacteriostatic as it was shown in the analysis of the microbial growth curve in the presence of 100, 200 and 400 gamma/ml of the dye. The inhibition coefficients for 100 gamma/ml of metachrome yellow in the experiments with the donor of E. coli J 53 (R1 drd) were 11.8 and 12.1 times at 1-hour cultivation and t leads to infinity respectively, while in the experiments with the donor of E. coli J53 (R 64 drd) the respective values were 9.1 and 11.1. It was found that metachrome yellow induced no elimination of R-factors at low concentrations, such as 100 and 200 gamma/ml, which was indicative of the fact that the inhibitory effect on R-transfer was not connected with elimination of R-factors. It was also shown that preliminary cultivation of the donor in the presence of 100 and 400 gamma/ml of the dye did not induce any decrease in its donor competence which did not confirm the assumption of the inhibitory effect of metachrome yellow on synthesis of sex-pilei.


[Prodigiosin in the overall therapy of dysentery and in the prevention of intrahospital viral respiratory infection in children]. Prodigiozan was tested in complex therapy of children with acute dysentery. Comparison of clinical symptoms, specific immunogenesis and child sanation periods from Shigella in the child groups treated (80) and non-treated (74) with prodigiozan showed that prodigiozan lowered the rate of intrahospital acute respiratory virus infection, provided more favourable dysentery progression, more tensed specific immunity and the patient clearance from Shigella.


Human therapeutic and agricultural uses of antibacterial drugs and resistance of the enteric flora of humans. Fecal samples were collected from five groups of people differing in the manner of their exposure to antibacterial drugs. The groups included: (i) people working on farms who were continuously in contact with the predominantly resistant florae of farm animals receiving rations containing antibacterial drugs, (ii) people residing on the same farms with no direct exposure to the farm animals, (iii) people treated with antibacterial drugs, (iv) untreated people residing with treated individuals, and (v) untreated people with no exposure to farm animals or treated individuals. The samples were examined by quantitative plating for proportions of antibiotic-resistant, gram-negative enteric organisms. Individual isolates were also examined for their susceptibility to 11 different antibacterial drugs. The results indicate that enteric florae unexposed directly to the selective effects of antibacterial drugs may be affected by contact with predominantly resistant florae directly exposed to antibacterial drugs.


Minimal inhibitory concentration of dapsone for Mycobacterium leprae in rats. To define the minimal inhibitory concentration (MIC) of dapsone (DDS) for Mycobacterium leprae in rats, we determined the relationship between dietary and plasma levels of DDS in uninfected male and female Lewis rats. This knowledge was applied to the design of experiments using rats inoculated in the footpads with M. leprae. The MIC for DDS in male and female rats, respectively, was 1.5 to 4.0 ng and 1.8 to 3.0 ng of DDS/ml of plasma, even though the sexes exhibited markedly different concentrations of DDS when receiving the same dietary level of DDS. These values for the MIC of DDS for M. leprae in rats are nearly identical to the previously determined MIC of DDS for M. leprae in mice.


Multiplicity reactivation of 5-iodouracil-substituted, nonviable bacteriophage T4td8. Nonviable, 5-iodouracil (IUra)-substituted bacteriophage T4td8 can be multiplicity reactivated. The data indicate that two nonviable, IUra-substituted T4td8 phage can complement each other intracellularly to produce viable progeny. Phage particles in lysates of T4td8-infected Escherichia coli BT(-), prepared in the presence of varying mole fractions of IUra plus thymine, were examined by infecting with low and high dilutions of lysate. The yields of multiplicity reactivable particles were identical, regardless of the mole fractions of IUra present in the growth media. However, the yields of viable phage, measured at low multiplicities of infection, decreased with increasing mole fraction of IUra. The results are consistent with the hypothesis that the lethal effect of IUra is a consequence of its incorporation into DNA. Further, the IUra-induced lesion cannot involve genetic damage that shuts off expression at a single region of the genome.


Treatment of respiratory Klebsiella pneumoniae infection in mice with aerosols of kanamycin. Aerosols of kanamycin resulted in greater survival of mice challenged with respiratory Klebsiella pneumoniae than the same dosage given intramuscularly. Determinations of viable bacteria in the blood and lungs revealed that aerosolized kanamycin was most effective when infection was confined to the lungs. After the organisms had spread to other areas, however, aerosol therapy was still more effective than intramuscular therapy, but only one-half the infected mice survived.


Inhibtory effect of colicin E2 on transport systems of Escherichia coli in the presence of the rex gene of lambda prophage. Purified colicin E(2) was found to cause marked inhibition of the permeation rate of o-nitrophenyl-galactoside (ONPG) in several lambda-lysogenic strains of Escherichia coli in the presence of chloramphenicol to prevent prophage induction. The inhibitory effect of colicin E(2) on transport systems was analyzed with cells of E. coli CP78(lambda). The dose of colicin E(2) for the half-maximum inhibition of the ONPG-permeation rate was about 9 molecules of the colicin per bacterium under the aerobic condition, which corresponded to about 1 killing unit per bacterium. Kinetics of the transport of [(14)C]methylthiogalactoside suggested that colicin E(2) began to inhibit the influx rate of beta-galactosides within a few minutes after the colicin addition, and the maximum inhibition reached more than 80%. Extensive leakage of intracellular potassium ion and inhibition of l-proline transport also occurred at the same time. Acid solubilization of cellular deoxyribonucleic acid by the colicin was apparently delayed to the initiation of the transport inhibition. The extents of the inhibition of beta-galactoside transport and leakage of potassium ion by the colicin were extensive in cells lysogenic for wild lambda phage or lambdaind(-), whereas the extents were slight in the nonlysogenic cells or cells carrying lambdarex(-) prophage. It was concluded that the sensitization of membrane transport systems of E. coli cells to colicin E(2) was achieved by the presence of the rex gene product of lambda phage.


Rifampin susceptibility of ribonucleic acid synthesis in a fragile Saccharomyces cerevisiae mutant. Ribonucleic acid (RNA) synthesis in the sorbitol-dependent, fragile yeast mutant VY1160 (Venkov et al., 1974) is rapidly inhibited by rifampin. The growth of the mutant cells and protein synthesis are more slowly affected by the antibiotic, apparently as secondary phenomena. Lower doses of rifampin (50 to 100 mug/ml) preferentially inhibit ribosomal RNA synthesis in comparison to that of messenger RNA and transfer RNA. Transcription and translation of messenger RNA continues in the presence of low doses of rifampin, as evidenced by the unimpaired induction of alpha-glucosidase. Partially purified RNA polymerase II from this mutant, in contrast to that from the parental strain, is strongly inhibited by low concentrations (1 mug/ml) of rifampin, whereas RNA polymerase I from the two strains is similar in behavior. The mutant may be useful for the study of regulatory mechanisms of transcription in eukaryotes.


Influence of subtherapeutic levels of oxytetracycline on Salmonella typhimurium in swine, alves, and chickens. Subtherapeutic levels of oxytetracycline in animal feeds have been evaluated to determine their influence on the relative quantity, prevalence, shedding, and antibiotic susceptibility of Salmonella typhimurium in swine, calves, and chickens, when compared with nonmedicated controls. The medicated groups were fed rations containing oxytetracycline commencing 5 days prior to oral inoculation with S. typhimurium and continuing through a 28-day post-inoculation period. Colonization of S. typhimurium occurred in all three animal species as evidenced by clinical signs of infection and/or colony counts in feces measured on seven separate occasions over the 28-day observation period. The accumulated data demonstrate that the subtherapeutic use of oxytetracycline did not bring about any increases in the quantity, prevalence, or shedding of S. typhimurium in swine, calves, and chickens. In fact, the medication generally brought about a decrease in the percentage of animals carrying S. typhimurium during the study period. In contrast to results in swine and calves, there was a significant occurrence of S. typhimurium resistance to oxytetracycline in chickens. Resistant colonies were isolated from chickens sporadically but never on more than two consecutive test periods. These isolates were also resistant to streptomycin, but not to the other six antibiotics tested. The population of resistant S. typhimurium isolated from medicated chickens was no larger than that of susceptible S. typhimurium isolated from the nonmedicated animals. It is concluded that no evidence has been obtained which would relate the continuous low-level feeding of oxytetracycline for a 4-week period to an increased incidence of disease in animals or as a hazard to humans.


Antimicrobial effect of simple lipids with different branches at the methyl end group. Various fatty acids of branched nature possess fungistatic and bacteriostatic properties. Some of these, particularly those of iso-configuration, strongly enhance the effect of conventional antimicrobial agents that act inside the cell membrane. A relation between this biological effect and the collapse properties of the corresponding monomolecular surface film on water has been observed. In this work, a series of fatty acids with a slightly smaller end group than iso-propyl, the omega-cyclopropane fatty acids, as well as one possessing a somewhat larger end group, the neo-branched fatty acids, have been examined. The omega-cyclopropane fatty acids were found to be more fungistatic than the iso-acids studied earlier. Furthermore, both cyclopropane and neo-fatty acids of short chain lengths exhibited synergistic effects in combination with tetramethylthiuramdisulfide.


Growth, respiration and cytology of acetate-negative mutants of Candida albicans. A number of acriflavine-induced mutants of Candida albicans, characterized by their inability to grow on acetate as a source of energy, were screened for their cytochrome absorption spectra. Three mutants with different spectra, along with their parent, were selected for comparative studies of their growth, respiratory activities and cellular structure. The spectrum of one of the mutants was the same as that of the wild-type, but the growth rate and yield of cells on glucose medium were only about 60% of the wild-type's; those of a second mutant deficient in cytochromes aa3 were 50%, and those of a third mutant deficient in cytochromes aa3 and b were less than 5% of those of the wild-type. The cytochrome-complete mutant and the wild-type showed respiratory activity both on glucose and ethanol well above the endogenous, the cytochrome aa3-deficient mutant showed only endogenous respiration, and the cytochrome aa3, b-deficient mutant no respiration at all. Electron microscopy of the wild-type cells revealed discrete, regular ovoidal, cristate mitochondria spaced near the periphery of the protoplasm; the cytochrome-complete mutant showed an abundance of large, cristate, but morphologically irregular mitochondria; the cytochrome aa3-deficient mutant had fewer but still large, cristate, somewhat irregular mitochondria; and the cytochrome aa3, b-deficient mutant only a few simple vesicles without discernible cristae.


Effects of stereotactic lesions of the pulvinar and lateralis posterior nucleus on intractable pain and dyskinetic syndromes of man. In a series of 18 patients suffering from intractable pain or different types of dyskinetic syndromes, 28 stereotactic lesions of the pulvinar, associated with six lesions of the laterlis posterior nucleus, have been performed. The evaluation of long-term results in intractable pain reduces the therapeutic benefit of the stereotactic pulvinolysis. Concerning dyskinetic syndromes, the pulvinar does not seem to play an important role in spasticity, while its role in other dyskinetic syndromes can be questionable.


Determination of intracerebral structures using osseous reference points for computer-aided stereotactic operations. Computer-aided sterotactic neurosurgery can be improved and simplified by using craniocerebral parameters for the calculation of subcortical target points and avoiding an air-filling of the ventricles. This was achieved by selecting 403 pneumo-encephalographic studies at random, measuring the craniocerebral parameters according to age and sex. There is a correlation between the bony cranium and the brain axis. We established a formula and a table to determine in the plain X-ray the entrance of the foramen of Monroi with a standard deviation of +/- 1.5 mm and the inclination of the intracerebral basic line we used (foramen Monroi-commissura posterior). With this information various subcortical targets can be determined by means of computer programs.


Survey of stereotactic and functional neurosurgery in the United States and Canada. A survey of the number of neurosurgeons performing stereotactic and functional neurosurgery in the United States and Canada was conducted by questionnaire. Of the 637 respondents, 433 conducted either stereotactic or functional neurosurgery or both. The indications and number of stereotactic procedures done annually are presented. The number of neurosurgeons performing each of the various procedures is outlined, as well as the types of stereotactic apparatus and lesion employed.


A statisticl outline of the subthalamic target for the arrest of tremor. In 60 cases operated on for the treatment of tremor, the insertion of an electrode that measured 1 mm in diameter produced complete arrest (40 cases) or significant decrease (20 cases) of the tremor on the contralateral side. The area where such effect was obtained was studied in AP and lateral radiograms. Using a method of standardization of the size of the thalamus and subthalamus, based on a proportional reucction of the length of the AC-PC line, the cases were found to cover a small area in the subthalamus. A statistical analysis of the position of the electrode tips at the moment the tremor was arrested was carried out in order to determine, with a high degree of probability, the area that includes the mean value of the target for the general population. This work allowed us to outline a small zone in the subthalamus as the target to be destroyed in future cases. The practical implications of the method are discussed and the possibility of reducing the size of the lesion is pointed out.


Improved method of selection for mutants of Pseudomonas putida. Optimum conditions for enrichment of mutants of Pseudomonas putida in liquid culture were established using a procedure which combines N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis with an improved D-cycloserine selection.


Growth potential of Clostridium botulinum in fresh mushrooms packaged in semipermeable plastic film. Fresh mushrooms (Agaricus bisporus) were inoculated in the stem, gill, or cap with Clostridium botulinum spores. They were placed with uninoculated mushrooms in paper board trays, which were then covered and sealed in a polyvinyl chloride stretch film to simulate prepackaged mushrooms available at retail stores. When incubated at 20 C, botulinum toxin could be detected as early as  day 3, or 4, when the mushrooms still appear edible. Mushrooms inoculated in the stem with 1,000 type A spores frequently became botulinogenic; higher spore levels were needed if gills or caps were inoculation sites. Type B spores were less apt to produce toxic mushrooms. Respiration of the fresh mushrooms used up O2 more rapidly than could enter through the semipermeable wrapping film, so that the equilibrium O2 concentration became low enough for growth of C. botulinum. Inoculated mushrooms did not become botulinogenic when held at 4 C.


The role of carrier in sensitivity to chromium and cobalt. Patients suffering from contact dermatitis caused by chromium sensitivity showed positive reactions to intradermal tests with chromium and cobalt chlorides. Patch tests to cobalt in unaffected and in healed eczematous skin areas gave negative results. A large number of chromium-sensitive patients also showed a positive intradermal test reaction to cobalt bound to human serum albumin and a negative reaction to cobalt bound to rabbit liver glycogen. It has been suggested that these positive reactions to cobalt are secondary sensitivities to cobalt, caused by cobalt-denaturated human serum albumin that is so similar to the denaturated product of chromium cations that the competent cells cannot distinguish between them.


Dermatitis herpetiformis and bullous pemphigoid. Intermediate and mixed forms. Nine patients had clinical and histological features suggestive of both dermatitis herpetiformis (DH) and bullous pemphigold (BP).  Five patients responded to treatment with sulfapyridine or sulfones: in two the response was inconsistent, and the disease was controlled by combined treatment with prednisone; in one patient, there was no response to sulfapyridine or sulfones. Immunofluorescence studies showed IgA deposits in a linear homogeneous pattern at the basement membrane zone in all patients, and IgG was present in five. No circulating anti-basement membrane antibodies were detected by repeated immunofluorescence examinations. The authors conclude that the occasional overlapping of BP and DH should not lead to dropping the distinction between the two entities. For overlap cases that cannot be classified as BP or DH, the term "intermediate or mixed form of DH and BP" seems to be most suitable.


Scabies simulating Darier disease in an immunosuppressed host. A patient who had recently had renal transplant was on a maintenance regimen of azathioprine and prednisone. She developed a florid, scaling, papular eruption clinically identical to Darler disease. Biopsy specimens and skin scrapings, however, showed a scabietic infestation. We believe that this highly atypical presenation, which had several features found in Norwegian scabies, was due to  muted inflammatory response that permitted a great proliferation of the mites.


Occurrence of bullous pemphigoid after furosemide therapy. A 78-year-old woman with Parkinson disease developed tense bullous lesions on the chest, arms, and in the groin that were diagnosed as bullous pemphigoid. Histologic examination, as well as immunofluorescence tests, confirmed this diagnosis. The possibility of a drug-induced disease was considered because she was taking seven different medications. Furosemide (Lasix) was suspected primarily. Complete clearing occurred with prednisone therapy, but readministration of furosemide resulted in bulla formation.


Sex-related incidence in proteus infection of the urinary tract in childhood. Over a 2-year period 80% of children found to have significant Proteus bacteriuria were boys. The organism was isolated from the prepuce in 30% of normal boys and 32% of those with balanitis. Proteus urinary tract infection should be carefully confirmed and proved cases thoroughly investigated.


[Defective polymorphonuclear leukocyte function in chronic granulomatous muco-cutaneous candidiasis (author's transl)]. Chronic granulomatous muco-cutaneous candidiasis is reported in a 12-year-old boy who died of pulmonal cryptococcosis. Chemotactic and phagocytic functions of the neutrophilic polymorphonuclear leukocytes were deficient while the cell mediated immunity was not disturbed and no decrease of immunoglobulins and complement factors--especially C3 and C5--was found in the serum. The possibility is considered that the disturbance of lymphocyte mediated immune response is the normal, but not only fundamental aetiological factor of chronic muco-cutaneous candidiasis.


Treatment of chronic renal failure by transplantation and dialysis: two decades of cooperation. The overall transplant experience at the Peter Bent Brigham Hospital which extends over twenty years has been reviewed; the course of all patients was updated to a followup of at least one year (through October 1973). A total of 388 patients received 427 renal isografts and allografts between March 1951 and October 1972. Of these, 58% were still alive at the end of the followup period, 50% with a functioning graft. The results of patient and allograft survival early (1959-1968) and later (1968-1973) in the experience have been compared. The significant decline in patient mortality, especially among recipients of cadaver allografts, demonstrates improved treatment of complications and increased availability of dialysis. The improvement of allograft function during the two time periods is less striking but still significant. Overall social and work rehabilitation following transplantation was evaluated in 284 patients, 86% of whom became at least as well adjusted as they had been prior to the development of renal failure. The incidence and individual causes for mortality and complications of transplantation have been compared to results from the National Dialysis Registry, figures comparable to those of the dialysis program at this institution. Transplantation and dialysis must be used conjointly and in a complimentary manner as part of the total treatment for those with end-stage renal failure.


Heidenhain pouch distension as a stimulus for acid and pepsin secretion. Heidenhain pouches, in dogs with simple gastric fistulae, were distended with saline (30, 60 and 90 ml). Pouch acid and pepsin increased linearly with increasing saline volume. Additional pentagastrin augmented the acid but antagonized the pepsin responses. Atropine depressed both the acid and pepsin responses to distention. Ganglionic blockade and local anesthetization of the secretory mucosa also depressed the acid but spared the pepsin response.


Cardiac output measurement by thermal dilution: reproducibility and comparison with the dye-dilution technique. Cardiac output estimates by the principle of thermodilution (COth) was compared with dye-dilution estimates (COdye) in pigs. For COth estimates a Swan-Ganz 7 F floating thermodilution catheter and a 9500 Edwards Computer, were used. The COdye estimates were obtained by the apparatus constructed by Zijlstra and Mook. The effect of the thermistor position in the pulmonary artery on the COth estimates was also investigated. The reproducibility of COth was examined by duplicate determinations. Based on 101 simultaneous estimates of COth and COdye the correlation was found COth = 1.020 COdye + 0.2378, r = 0.971 for cardiac outputs between 0.65 l/min and 11 l/min. For 111 duplicate determinations of COth between 2 and 9 l/min the coefficient of variation was 4.74%. The thermistor position in the pulmonary artery had no influence on the COth estimates provided an undamped pressure curve could be monitored from the tip of the catheter. Cardiac output can thus be measured rapidly with good accuracy also for low values by means of a blindly inserted thermistor catheter positioned without x-ray control and a computer with digital display.


Acute colitis in the renal allograft recipient. Four renal allograft recipients with evidence of ischemic damage to the colon are presented and compared with 11 cases from 5 major series. Similarities in the patients included: deterioration of renal function, multiple immunosuppressive and antibiotic regimens, the use of cadaver renal allografts, and diagnostic and therapeutic measures requiring frequent enemas with barium and ion-exchange resins. Two of our patients underwent surgery for the removal of segments of necrotic colon after several weeks of fever and abdominal pain initially attributed to either acute rejection, viral infection, or pancreatitis. One patient had three days of melena and responded to non-operative therapy. The fourth patient developed ischemic colonic changes 10 weeks after allograft nephrectomy and was receiving no immunosuppression at the time. Broad spectrum antibiotics were used at various times in all patients. Early aggressive evaluation of gastrointestinal complaints--including barium enema, upper gastrointestinal series with small bowel follow-through, proctosigmoidoscopy or colonoscopy, and arteriography--is indicated, in view of the lethality of the complication of colonic ulceration. The clinical pictures presented emphasize the fact that recipients of renal allografts are commonly heir to many complications which may be considered rare in the normal population.


Historical aspects in the development of venous autografts. During the past 75 years much progress has occurred in the field of vascular surgery. During this period, contributions from clinical surgeons have stimulated new scientific discoveries which have led to further clinical applications in a mutually perpetuating cycle of surgical advancement. One of the major achievements has been the use of the venous autograft employed as an arterial substitute. First used by Goyanes in 1906 to replace a popliteal aneurysm, a venous autograft was first successfully employed in the United States by Bernheim in 1915. The stepwise development of this aspect of modern vascular surgery is presented, and the role of other related contributions in making its use feasible is reviewed.


Innominate artery rupture. A major complication of tracheal surgery. Innominate artery rupture is a life-threatening complication of tracheal reconstructive surgery. Early postoperative rupture of the innominate artery occurred in 8 of 100 consecutive patients undergoing tracheal resection and reconstruction (93, end-to-end anastomosis; 7, Marlex prosthesis). A premonitory transient hemoptysis occurred in 4 of the 8 patients. This sign may permit early diagnosis and effective treatment. When massive hemorrhage occurs, prompt arterial compression, control of the airway, and subsequent ligation of the artery may be lifesaving. Direct repair of the arterial defect is not recommended. If the innominate artery lies in direct contact with the suture line following primary anastomosis, soft tissue interposition is recommended.


Trachea--innominate artery fistula following tracheostomy. Successful repair using an innominate vein graft. This report discusses the first recorded patient in whom a trachea--innominate artery fistula after tracheostomy was treated successfully by resection of the eroded segment of artery followed by graft replacement using the patient's left innominate vein. The mechanism of vessel erosion and its prevention are discussed. Also, suitable methods are presented for obtaining temporary control of the severe hemorrhage associated with a tracheoarterial fistula while simultaneously maintaining an adequate airway.


The surgical treatment of pectus excavatum: an experience with 90 operations. Funnel chest, a congenital hereditary deformity, may lead to impairment of cardiopulmonary function. The predominant motives for operation are psychological and cosmetic. Patients with minor deformities amenable to physiotherapy should not be operated upon, but moderately severe defects justify surgical intervention. Objective photographic documentation is essential. Because of their importance to surgical technique and results, the symmetrical, asymmetrical, localized, and extensive deformities should be distinguished. Ninety operations were performed between 1951 and 1974 according to the various techniques known during that period. Results were irregular until the introduction eight years ago of an operation combining extensive resection according to Ravitch and stabilization by a metal strut as recommended by Adkins and others. Of 24 operations performed during the last eight years, 23 have given excellent long-term results.


Pleural flap closure of pericardial defects following intrapericardial pneumonectomy. Persistent pericardial defects following intrapericardial pneumonectomy are, historically, the major cause of iatrogenic cardiac herniation. This complication is uniformly fatal when unrecognized and untreated and has been associated with a 43% mortality even with surgical correction. Suture approximation of all small defects is recommended, and a technique for routine pleural flap closure of moderate to large-sized defects is described.


Quadruple coronary artery bypass grafting. In our last 150 consecutive revascularization operations, 30 patients (20%) have had 4 or more bypass grafts. One patient died after quadruple grafting (mortality, 3%). Twenty-two (75%) of the survivors have been rehabilitated to active work status and 25 (86%) were considered by their cardiologists to have improved function postoperatively by New York Heart Association criteria. Preoperatively 15 patients (50% of the group) had either a markedly diminished ejection fraction (EF) or extreme elevation in left ventricular end-diastolic pressure (LVEDP) or both. Complete revascularization, with resection of ventricular aneurysms when present, can be carried out successfully in a high-risk group of patients. Elevated LVEDP or diminished EF per se is not a valid contraindication to myocardial revascularization.


Caustic ingestion and subsequent damage to the oropharyngeal and digestive passages. The characteristics, diagnosis, and management of oropharyngeal and digestive passage lesions due to ingestion of caustic agents are presented. Previous experimental and clinical studies are reviewed with discussion of the peculiar qualities of the newer caustics. Differentiation in treatment of burns caused by solid and liquid agents is stressed.


Propranolol as primary therapy for thyrotoxicosis. It has been suggested that propranolol hydrochloride alone is effective in the treatment of thyrotoxicosis. To test this hypothesis, eight mildly thyrotoxic individuals were prospectively studied for an average of eight months, during which propranolol alone was administered and thyroid function tests, cardiac systolic time intervals, and body densities were sequentially measured. Two patients became euthyroid. The others had adequate but incomplete symptomatic control. Weight loss was not corrected, but no changes in lean body mass were induced. The augmented myocardial contractility of thyrotoxicosis, as determined by systolic time intervals, improved but failed to return completely to normal. Thus, systolic time intervals are a practical means of following the peripheral response to chronic beta-adrenergic blockage in thyrotoxic patients. However, these observations do not support the use of propranolol alone as the first choice of therapy for thyrotoxicosis.


Candida endocarditis in two patients.

Candida endocarditis in two patients. On the basis of the data currently available, no dogmatic statements can be made about optimal therapy for Candida endocarditis. In those with valve protheses, early surgery should be carefully assessed even though the differences in outcome (17% vs 53% survival) are not yet statistically significant.


Meningoencephalitis caused by Histoplasma capsulatum: occurrence in a renal transplant recipient and a review of the literature. A case of meningoencephalitis caused by histoplasmosis in a renal transplant patient is described. The diagnosis was made postmortem. The clinicopathological features of 39 additional cases of central nervous system (CNS) invasion by histoplasmosis were reviewed. In the great majority of instances (92.1%), CNS involvement occurred in the disseminated form of the disease. Diagnosis was proved by culturing the fungus from bone marrow, blood, lymph nodes, or liver. Neurological symptoms and signs and cerebrospinal fluid (CSF) changes did not occur until extensive brain damage had resulted. Difficulty in culturing the organism in the (CSF) caused a further delay in making an early diagnosis of CNS involvement. The use of meningeal and brain biopsy specimens in conjunction with the electroencephalogram (EEG) may help in making an earlier diagnosis of CNS involvement.


The life table. A method for analyzing longitudinal studies. The life table is presented as the method of choice for analyzing data from longitudinal studies in which the outcome under study occurs randomly and in which patients are followed up varying lengths of time. We discuss the superiority of the life table to methods typically used, the calculation of its entries, and some of the clinical uses that can be made of its results. The method is applied to follow-up data on manic-depressive patients maintained with prophylactic lithium carbonate or with control regimens, and it is shown to disclose mathematical regularities in the parameters of longitudinal course.


Lithium carbonate and affective disorders. V: A double-blind study of prophylaxis of depression in bipolar illness. The efficacy of lithium carbonate as a prophylactic drug against depression in bipolar manic depressive patients was assessed through a double-blind, placebo-controlled study of patients who had histories of recurrent depressions and hypomanias ("bipolar II"). The results revealed that treatment with lithium carbonate resulted in a reduction in the frequency of depressive attacks was observed with lithium carbonate treatment during the study (mean length of study, approximately 16 months), although there was a suggestion that the depressive attacks that occurred during treatment with lithium carbonate might be less severe than with placebo treatment.


[Morphological aspects of the functional stability of the kidney]. Specific features of the internal architectonics of the secondary kidney have been analyzed from standpoints of main propositions of cybernetics. The high stability of the organ as a biological system is determined by a great number of non-equivalent elements both in the composition of the nephron in the level of coalition of nephrons and in other subsystems. It promotes 1) preservation of a part of neurons under extreme effects, 2) duplication, 3) creation of optimal variants of active functioning coalitions of nephrons, 4) maintenance of optimal regimen of work of the nephron and kidney as a whole. Specialization of cells, their ability to regenerate, control in many levels also contribute to stability. It is supposed that non-equivalence of the elements of subsystems in ontogenesis is sustained by their asynchronous development, while in phylogenesis--by intratissue divergence.


'Figure 8' ipsilateral autokeratoplasty. A modification using standard corneal trephines. A modification of the "figure 8" ipsilateral autokeratoplasty uses a silicone wafer beneath a portion of a standard sized corneal trephine to limit its cutting edge. This procedure eliminates the necessity of a custom-made instrument in a seldom-performed operation.


Cancer of the skin of the nose. Treatment by total skin excision and three-quarter thickness skin graft. We describe a method of treatment and repair of superficial cancers of the skin of the nose. In 124 patients in whom excision of the lesion and a split thickness skin graft were used, 77% were alive and free of their disease after five years of follow-up. Three patients in whom a skin graft was performed were unavailable for follow-up, and 15 patients developed local recurrence either in the area of excision or in the surrounding skin. The method is easy, reliable, and the cosmetic results are satisfactory.


The metallography of a nickel base casting alloy. Three groups of tensile test pieces were produced using a nickel base partial denture casting alloy and employing induction fusion in each case. The first group was produced fro new metal, the second from metal which had been recast four times, and the third from new overheated metal. Samples of alloy were cut from each group, and together with a piece from an original ingot, were mounted, polished, etched, and examined under a metallurgical microscope.


A forcast of requirements for the treatment of chronic renal failure in Victoria. Using a Markov chain mathematical model, dialysis and transplantation requirements for Victoria in the next five to ten years have been predicted. The numerical constants in the model are based on data from past Australian experience. Predictions showed a steady rise in numbers requiring dialysis and transplantation. Home dialysis numbers will probably double within five years but hospital dialysis numbers will only increase by 50% in the same period. If as many patients as possible were trained for home dialysis on entering the treatment programme, home dialysis numbers could triple in five years, but hospital dialysis numbers would be correspondingly reduced. It is hoped that this model will enable planning authorities to allocate resources for renal failure treatment in a more rational manner.


Successful use of combination chemotherapy in pure red cell aplasia associated with malignant lymphoma, histiocytic type. A case of pure red cell aplasia developing in a woman aged 78 is reported. Biopsy of an enlarged axillary lymph node disclosed a malignant lymphoma, histiocytic type. Therapy with intermittent cyclophosphamide and prednisone was instituted. There was rapid remission of the red cell aplasia. Clinical recurrence of the histiocytic lymphoma has not occurred.


Chest injuries in road trauma.

Chest injuries in road trauma. A review of major chest injuries sustained by road crash victims attending the Preston and Northcote Community Hospital over the four-year period 1971 to 1974 highlights the vulnerability of car occupants to this type of injury, particularly those involved in side-impact collisions. In this type of collision seat-belt restraint does not influence the incidence of chest injury. Major injuries to other body areas and the delayed development of serious pulmonary complications call for continuous expert medical cae with the use of the facilities of an intensive care ward. The range of complications in a survey of 60 such patients admitted to hospital in 1974 is highlighted. A regime of management is outlined.


Subcutaneous mastectomy with immediate reconstruction of the breast. The operation of subcutaneous mastectomy is evolving as an alternative to simple mastectomy for diseases of the breast parenchyma where preservation of the skin capsule is thought possible. Simple mastectomy is a mutilating procedure, cosmetically unacceptable to both patient and surgeon. The psychological implications of breast absence in women are now well known, and attempts to preserve the shape and volume of the breast must receive attention.


Omental transfer for the treatment of radionecrosis of chest wall. A technique is described for the treatment of non-healing deep ulcers of the chest wall following radiotherapy. These ulcers are avascular and may involve the costal cartilages. The skin around them is stretched and fixed, so that covering and healing them has been a challenging problem to surgeons. The method used in this patient utilized the transfer of the whole of the greater omentum attached to the greater curve of the stomach, which provides clean, vascular bed for the skin graft, and has been nature's best help to surgeons.


Pregnant stewardess--should she fly?

Pregnant stewardess--should she fly? There is much pressure on the airlines to allow stewardesses to fly while pregnant. Some of them want to fly in quite advanced stages of pregnancy. This paper offers a survey of the problem, the hazards that may occur and some guidelines for the physician. The author outlines the normal changes to be expected with advancing pregnancy and those factors that could have an adverse effect on a pregnant stewardess and her fetus, such as hypoxia, trauma, abortion, the hazards of travel, and flying itself. Certain legal problems of unemployment and medical disability also are discussed. Travel alone offers no real danger to the pregnant stewardess in the first trimester of pregnancy; however, because of the changing mechanics of her size, posture, and increasing unsteadiness, it would be wisest to require a pregnant stewardess to cease flying at 13 weeks, with an absolute prohibition of flying after the 20th week.


Heteropyknosis of the chromosomes in liver cells of different ploidy: a nuclear image study. The chromatin densities of Feulgen-stained diploid, tetraploid, octoploid and binucleate cells of smear preparations of the liver of female field voles, Microtus agrestis, were examined by means of image analysis. The ratio of the areas of flattened nuclei of 2n, 4n and 8n ploidy was about 1 : 1.62 :2.60 and that of the relative DNA content 1 : 2 : 4. In flattened polyploid nuclei, the chromosomes are more densely arranged than in diploid. In diploid nuclei, absolutely and percentually smaller areas of dark chromatin particles were found than in polyploid nuclei. After correction of the grey values with a density factor, the frequency distribution curves of all ploidy classes were found to be nearly identical. The results show that the percentage of heteropyknotic chromosome material is the same in diploid, polyploid and binucleate liver cells.


Regulation of synthesis of ribosomal proteins during pyrimidine starvation in Escherichia coli. The synthesis of ribosomal proteins during pyrimidine starvation was investigated. A progressive turn-off of protein synthesis, with a decay half-time of about 5 min, was observed when Escherichia coli cells were starved of uridine. By means of double-labelling, the syntheses of different ribosomal proteins were shown to be turned off unequally during the starvation. Comparison of the turn-off patterns for some proteins and the known polycistronic organization of the structural genes for these proteins suggests that a major cause of the unequal turn-off was the degradation of mRNA molecules for the ribosomal proteins from the 5'-end toward the 3'-end.


Gene activities for ribosomal components in Escherichia coli B/r. The relative transcriptional activities of genes coding for ribosomal RNA (rRNA) and ribosomal proteins (r-proteins) at a steady-state growth rates ranging from 0.65 to 2.1 doublings/h can be estimated from previous measurements of the synthesis rates of stable and unstable RNA (Pato & von Meyenburg, 1970; Nierlich, 1972a,b; Bremer et al., 1973; Dennis & Bremer, 1973b, 1974b) and ribosomal proteins (Schleif, 1967; Dennis & Bremer, 1974a). Comparison of these transcriptional activities suggests that the expression of the r-protein genes and rRNA genes is controlled seperately.


S-adenosylmethionine decarboxylase from baker's yeast. 1. S-Adenosyl-L-methionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase, EC 4.1.1.50) was purified more than 1100-fold from extracts of Saccharomyces cerevisiae by affinity chromatography on columns of Sepharose containing covalently bound methylglyoxal bis(guanylhydrazone) (1,1'[(methylethanediylidene)dinitrilo]diguanidine) [Pegg, (1974) Biochem J. 141, 581-583]. The final preparation appeared to be homogeneous on polyacrylamide-gel electrophoresis at pH 8.4. 2. S-Adenosylmethionine decarboxylase activity was completely separated from spermidine synthase activity [5'-deoxyadenosyl-(5'),3-aminopropyl-(1),methylsulphonium-salt-putrescine 3-aminopropyltransferase, EC 2.5.1.16] during the purification procedure. 3. Adenosylmethionine decarboxylase activity from crude extracts of baker's yeast was stimulated by putrescine, 1,3-diamino-propane, cadaverine (1,5-diaminopentane) and spermidine; however, the purified enzyme, although still stimulated by the diamines, was completely insensitive to spermidine. 4. Adenosylmethionine decarboxylase has an apparent Km value of 0.09 mM for adenosylmethionine in the presence of saturating concentrations of putrescine. The omission of putrescine resulted in a five-fold increase in the apparent Km value for adenosylmethionine. 5. The apparent Ka value for putrescine, as the activator of the reaction, was 0.012 mM. 6. Methylglyoxal bis(guanylhydrazone) and S-methyladenosylhomocysteamine (decarboxylated adenosylmethionine) were powerful inhibitors of the enzyme. 7. Adenosylmethionine decarboxylase from baker's yeast was inhibited by a number of conventional carbonyl reagents, but in no case could the inhibition be reversed with exogenous pyridoxal 5'-phosphate.


Histocompatibility in ruminants. The production and evaluation of allo-antibodies for GL-A typing in goats. The production of goat lymphocytotoxic allo-antisera by immunization by lymphocytes or allografting is described. Analysis of typing results of several goat families and the correlation between the lengthening of allograft survival and graft exchange between compatible and incompatible animals, suggest the existence of a major histocompatibility system (GL-A) in goats.


Attempt at "immunological castration" as an approach to the problem of the involvement of testosterone in control of expression of certain mouse antigens. Adult male mice of the strain B10.A were immunized with a testosterone-protein conjugate, testosterone 3-(O-CARBOXYMETHYL)-oxime-bovine serum albumin which contained 27-75 steroid residues/mol BSA. Two different immunization doses of the conjugate were used, respectively, 2 x 40 mug and 2 x 200 mug in complete Freund's adjuvant or in alum adjuvant. There were two groups of control males, non-immunized and immunized with BSA in adjuvant. In the pooled immune sera, antibodies to testosterone were determined by radioimmunoassay; their titre ranged between 7 and 10. On histological sections of testes, inhibition of spermatogenesis (manifested by a sower frequency or even absence of tubules producing mature sperm, reduced frequency of tubular cells and their degenerative changes) was observed in almost all males immunized with the higher dose of the conjugate. In such animals, increased frequency of interstitial cells (except vascular elements) and enlarged nuclei of Leydig cells were found. In spite of these signs of a hyperproduction of testosterone by the Leydig cells, the product seemed to have lacked its normal biological activity as suggested not only by the low activity of spermatogenesis, but also by a significantly subnormal level of the androgen-dependent serum protein Ss.


Experimental autoimmune encephalomyelitis in mice: genetic control of susceptibility. Experimental autoimmune encephalomyelitis (EAE) was induced in inbred and congenic strains of mice by injection of mouse spinal cord homogenate (MSCH) in Freund's complete adjuvant (FCA) with pertussis vaccine. Genetic analyses showed that susceptibility to EAE in mice was inherited as a dominant trait and was in part controlled by genes located in the centromeric half of the H-2 complex. Mice with EAE developed cell-mediated immune responsiveness to basic protein of myelin (BPM), as judged by the macrophage migration inhibition assay, using peritonealyexudate cells; this was not observed with mice of resistant strains. However, the migration of peritoneal exudate cells of both susceptible and resistant strains was significantly inhibited in the presence of purified protein derivative (PPD) of M. tuberculosis. Thus, the genes involved in the control of susceptibility to EAE also influence T cell responsiveness to BPM. Antibody to BPM, as judged by radioimmunoassay, was detected in susceptible and resistant strains but there was no correlation between the presence or levels of antibody and susceptibility or resistance to EAE. It is suggested that resistance to EAE is associated with failure of T cells to recognize and/or respond to the encephalitogenic determinant of the BPM molecule.


HL-A antigens in juvenile rheumatoid arthritis. HL-A antigens were examined in sixty-two patients, thirty-one boys and thirty-one girls, diagnosed as having JRA. HL-A 27 was the only antigen with a significantly increased frequency. This increase concerned predominantly male patients in whom the disease developed at the beginning of puberty. In this group of sixteen boys, the polyarticular form was more frequent and tended to be associated with sacroliitis, while the rheumatoid factor was negative in all but one. The frequency of HL-A 27 in this group was 65.5%. The patients were also examined by the lymphotoxic test with anti H-2 alloimmune sera known to exhibit a high degree of association with some HL-A antigens. On JRA lymphocytes these associations were confirmed for HL-A 2 and anti-H-2f and for HL-A 27 and anti-H-2p. The strongest reactions were observed with lymphocytes from male patients around the age of puberty. These data indicate that steroid hormones influence the expressivity of some HL-A associated cell plasma membrane structures.


The training and role of nurse-therapists in a general hospital's psychiatric unit. The author's discuss their experience using nurses as therapists on a small unit at St. Joseph's Hospital, a general hospital in Hamilton, Ontario. They describe the training of the first nurse-therapists and the three-level training system established to make the program self-sustaining. The nurse-therapist system is now used on several psychiatric units in the hospital. Problems in role relationships and schedules occurred, but the authors, noting the patient-care, economic, and staff benefits, believe that the system would be especially useful in small inpatient units.


Using short-term intervention with priests. In ten weekly sessions, each lasting one and a half hours, the authors met with six priests to increase the priests' knowledge of mental health resources, to break down stereotypes concerning both mental health professionals and priests, and to help them deal with the changes that are occurring in the church organization. The priests were able to deal only superficially with issues such as identity and intimacy. But as a result of the experience, they could cope better with their day-to-day work and were better able to use mental health professionals as consultants.


Criteria for releasing patients from psychiatric hospitals. The authors conducted a pilot study to determine the kinds of criteria being used by mental health professionals in discharging patients from mental hospitals. Twenty-one criteria were identified in the first phase of the study, and 43 staff members later rated the items according to their perceived importance. Although there was general agreement on most of the items, reliable differences of opinion were expressed in some instances. The differences were attributed less to the respondents' professional discipline than to their hospital affiliation (VA or non-VA). The authors emphasize the need for developing a standardized list of discharge criteria and discuss uses for such criteria.


The women's liberation movement: its impact on marriage. The author discusses marriages in which a basically insecure husband plays a god-like role and his wife, who initially worshipped him, matures and finds her situation depressing and degrading. With support from the women's liberation movement, many women have found the courage and conviction to challenge such situations. The challenges often bring the husbands' repressed feelings of inadequacy to the surface, which leads to increased turmoil and finally to requests for professional help, first by the wife and later by her husband. During counseling both become more open and develop as individuals. As a result their marriage improves.


The effect of pressure or flow stress on right ventricular protein synthesis in the face of constant and restricted coronary perfusion. Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro by utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 4 ml/min per heart equivalent to 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60 percent increase of myocardial incorporation of (14C)lysine into protein. However, with further increases of right ventricular pressure to 22 mm Hg, protein synthesis dropped back to normal levels. The falloff in protein synthesis was not due to decreased contractility, alterations in intracellular lysine pool specific activity, or alterations in distribution of coronary flow. a 60 percent increase in coronary perfusion was again associated with a similar response of protein synthesis to progressive elevations of pressure despite a rise in the ATP levels and a fall in lactate production. Thus, a deficiency of O2 did not entirely explain the decline of protein synthesis with maximal pressures. At all levels of coronary perfusion, volume loading for 3 h did not result in increased protein incorporation of (14C)lysine. The studies support a relationship between ventricular pressure and protein synthesis unrelated to coronary flow per se. A pressure receptor triggering protein synthesis within the ventricular wall is postulated. Such a relationship is not apparent in short-term volume loading in vitro.


Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol. The role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lipids was investigated by using the isolated perfused rat liver model. Labeled lecithin precursors ((3H)-palmitic acid, (14C)linoleic acid, (3H)choline, and 32PO4) and a cholesterol precursor ((3H)mevalonic acid) were administered with and without sodium taurocholate. The incorporation pattern of these labeled precursors into linoleyl and arachidonyl lecithins and cholesterol fractions of microsomes, bile canaliculi, and bile were examined at 30-min intervals up to 90 min. Marker enzymes and electron microscopy indicated that isolated subfractions of plasma membranes were enriched with bile canaliculi (less than 10 percent microsomal contamination). Taurocholate significantly stimulated the incorporation of 32PO4, (3H)choline, (3H)palmitic acid, and (14C)linoleic acid into linoleyl and arachidonyl lecithin with parallel incorporation curves for microsomal and bile canalicular membranes throughout the 90-min study period. During the 30-60-min period, however, these same lecithin fractions in bile significantly exceeded the specific activity of the membrane lecithins. The enzyme CDP-choline diglyceride transferase was virtually absent from canaliculi relative to microsomes, indicating that canaliculi lack the capacity for de novo lecithin synthesis. Incorporation of (3H)mevalonic acid into membranous and biliary cholesterol followed a pattern similar to that for lecithin. These data provide evidence that (a) biliary lecithin and cholesterol are derived from a microsomal subpool regulated by the flux of enterohepatic bile acids, (b) the role of the bile canalicular membranes with respect to biliary lipids is primarily transport rather than synthesis, and (c) lecithin and cholesterol are transported together from microsomes to bile. The findings are consistent with the existence of a cytoplasmic lipid complex within the hepatocyte which is actively involved in the intermembrane transport of biliary lipid.


Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man. The mode of action of the hypocholesteremic drug neomycin (2 g/day) was studied in four patients. All showed a significant reduction in plasma cholesterol concentrations (mean 25 percent, range 18-31 percent), and in one of three patients with hyperglyceridemia there was a decrease of plasma triglycerides of 26 percent. Cholesterol absorption was measured in three of four patients: there was a marked decrease. Sterol balance studies in four patients showed an unabating increase in fecal neutral steroid excretion (mean increase 345 mg/day, range 323-361) for 3-5 wk after plasma cholesterol levels had reached a new and lower plateau. Fecal acidic steroid excretion increased temporarily in two patients, with a sustained increase of 93 mg/day in only one. Daily stool weights increased significantly in three of four patients, though none had steatorrhea; there was a significant reduction in excretion of secondary bile acids; neutral sterol degradation rates were not affected by the drug. Slopes of plasma cholesterol-specific activity time curves did not change. These results fail to support the suggestion that neomycin acts as a bile acid precipitant. The finding of increased fecal neutral steroid excretion is consistent with decreased cholesterol absorption, but also with increased cholesterol absorption, but also with increased cholesterol synthesis (secondary to release of negative feedback control), with increased flux of cholesterol from tissues, or with a combination of all three actions.


Defect in insulin binding to receptors in obese man. Amelioration with calorie restriction. With insulin at 0.1 ng/ml, the binding of (125I)insulin in vitro to circulating lymphocytes from 11 obese patients was less than that observed with cells from 10 thin volunteers. Furthermore, with obese cells, unlabeled insulin was less effective in competing with labeled hormone for binding, both at low and high concentrations of unlabeled insulin. These differences were not accounted for by the high concentrations of insulin in the circulation of the obese patients at the time fthe blood was drawn, or by differences in degradation of hormone, or in the characteristics of the cell population. The decrease in binding appears to be due to a lowering of the receptor concentration, but some loss of affinity has not been excluded. Institution of a calorie restricted diet (nine patients) which ameliorated the hyperinsulinemia, produced an improvement in hormone binding. Since the insulin receptors of lymphocytes in metabolic disorders seem to reflect the state of insulin receptors or target cells such as liver and fat, the lymphocytes or other leukocytes appear to be ideal for studies of impaired cell responsiveness to hormones in man.


Plasma glucagon and insulin in rat pregnancy. Roles in glucose homeostasis. To determine if pancreatic glucoregulatory hormones can be implicated in the glucose fall of pregnancy, we have measured plasma immunoreactive insulin and glucagon (IRI and IRG) in rats. Fed rats in midgestation show a rise in IRI without a corresponding increase in IRG. In late gestation, IRG rises significantly, but only enough to keep pace with a further rise in IRI. On a molar basis, IRI remains the predominant hormone despite a marked fall in blood glucose. After a 48-h fast IRI falls to comparably low levels in pregnant and virgin rats. A small rise in IRG is seen in virgin but not in pregnant rats despite frank hypoglycemia in the latter. Thus, IRG secretion in pregnancy is diminished relative to IRI in the fed state and fails to increase in the fasted state despite the stimulus of a lower glucose in both instances. To evaluate IRG secretory reserve, the IRG response to i.v. alanine was assessed in late gestation. In fed rats a greater IRG increase is seen in pregnancy; after fasting no difference is seen between pregnant and virgin rats. These results preclude an absolute deficiency in glucagon secretion. Pancreas hormone stores were alos measured in an effort to explain the altered secretory state. We find reciprocal changes in IRI and IRG content favoring IRG in midgestation and IRI in late gestation. Thus, pancreas hormone storage is altered in pregnancy but does not account for the changes in hormone secretion. Rather, pregnancy exerts an effect on the islet secretory process itself. Release of IRI is enhanced relative to IRG regardless of the blood sugar level. These observations suggest that in the pregnant rat circulating levels of insulin and glucagon may act to limit hepatic glucose output. Available evidence from the literature supports the concept of restrained glucose production. It is proposed that a lower blood glucose production. It is proposed that a lower blood glucose in rat pregnancy may be a lesser liability teleologically than would be the obligate nitrogen wasting which accompanies gluconeogenesis.


An efficient optimization technique for recovering ventilation-perfusion distributions from inert gas data. Effects of random experimental error. A variable metric optimization method of numerical analysis has been used to recover known distributions of intrapulmonary ventilation-perfusion ratios from inert gas data. Hypothetical lungs were simulated and corresponding inert gas retentions calculated. By using error-free retentions for seven gases and a 50-compartment model, it was possible to recover distributions containing up to three modes accurately and with greater efficiency than with other numerical methods. When random error of a magnitude consistent with present analytical techniques was introduced into retention data, the recovered distributions differed qualitatively from the original ones. This resulted from the ill-conditioned nature of the mathematical problem, which makes a recovered distribution extremely sensitive to small errors in retention. Thus, present levels of measurement error represent an important limitation in current techniques for deriving distributions from inert gas measurements.


Uterine prostaglandin E secretion and uterine blood flow in the pregnant rabbit. Studies were performed in pregnant rabbits to assess the effect of inhibition of prostaglandin synthesis on uterine blood flow. Cardiac output and uteroplacental blood flow (UPBF) were measured using radiolabeled microspheres. Prostaglandin E (PGE) concentration was measured by radioimmunoassay in the uterine vein and peripheral artery of the pregnant nephrectomized rabbit. Either meclofenamate or indomethacin 2 mg/kg were utilized to inhibit prostaglandin synthesis. Systemic arterial pressure increased from 86 mm Hg to 98 mm Hg (P less than0.0001) after prostaglandin inhibition. Cardiac output was unchanged after the inhibition of prostaglandin synthesis, 326 ml/min to 7.8 ml/min. Uterine vein PGE concentration was extremely high, 172.4 ng/ml, with concomitant peripheral arterial PGE 2.1 NG/ML. Intravenous administration of either meclofenamate or indomethacin reduced uterine vein PGE to 23 ng/ml (P less than 0.01) and arterial PGE to 1.0 ng/ml (P less than 0.05). Male and nonpregnant female rabbits had lower arterial PGE, 0.37 ng/ml (P less 0.05). Studies in non-nephrectomized pregnant animals demonstrated that uteroplacental secretion of PGE was greater than five times renal secretion. These studies demonstrate that the rabbit uteroplacental unit is a rich source of PGE and suggest that production of the vasoactive lipid may have a key role in regulating UPBF during pregnancy.


Regional myocardial blood flow during graded treadmill exercise in the dog. Regional myocardial blood flow was measured in nine dogs at rest and during three levels of treadmill exercise by using left atrial injections of 7-10-mum radioactive microspheres. At rest, heart rate was 76 plus or minus 3 beats/min (mean plus or minus SEM), mean left ventricular myocardial flow was 0.94 plus or minus 0.09 ml/min/g and endocardial flow (endo) exceeded epicardial flow (epi) in all regions (endo/epi equals 1.12-1.33). When treadmill exercise was regulated to increase heart rates from 152 plus or minus 3 to 190 plus or minus 3 to 240 plus or minus 6 beats/min, myocardial blood flow (MBF) to all regions of the left ventricle increased linearly with heart rate (HR) from 1.83 plus or minus 0.11 to 2.75 plus or minus 0.22 to 3.90 plus or minus 0.26 ml/min/g (MBF EQUALs 0.0175 HR - 0.523 PLUS OR MINUS 0.614, R EQUALS 0.87). Exercise abolished the gradient of blood flow favoring the left ventricular endocardium at rest, so that the endo/epi flow ratios were not significantly different from 1.00. Right ventricular flows were consistently less than corresponding left ventricular flows, but showed a similar linear increase with heart rate. Right ventricular endo/epi ratios were not different from 1.00 either at rest or during exercise. Thus, exercise resulted in increased myocardial blood flow to all regions of the left and right ventricles with maintenance of subendocardial flow equal to subepicardial flow.


Prolonged contraction duration in aged myocardium. Isometric performance at 29degreesC was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n equals 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255plus or minus6 ms in the young adult and 283plus or minus6 ms in the aged group (P less than0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 times 10-6 M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P less than0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117plus or minus 4percent of control in the young and 138plus or minus 4percent of control in the aged muscles (P less than0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content.


Regulation of blood flow in Paget's disease of bone. Previous studies have demonstrated an increase in blood flow to extremities involved by Paget's disease of bone. It has been assumed that the increase in blood flow is through bone, but warmth of skin overlying Pagetic bone suggests that cutaneous blood flow might be increased. In three patients with Paget's disease involving one extremity, we compared blood flow in "Pagetic" extremities with flow in the contralateral normal extremities. Resting blood flow (measured with water plethysmographs) was 14.2plus or minus2.9 (meanplus or minusSE) ml/min times 100 ml extremity in the Pagetic limbs. The contribution of cutaneous flow to the increase in extremity blood flow was evaluated with epinephrine iontophoresis, which suppresses flow to skin but not to underlying tissue. Epinephrine iontophoresis of the Pagetic extremities decreased blood flow from 14.2plus or minus2.9 to 3.6plus or minus1.5 ml/min. Local heating (which increases cutaneous flow only) failed to increase blood flow in the Pagetic extremities as much as it did in the normal extremities. This suggests that cutaneous vessels in the Pagetic extremities were already dilated. During heating, blood flow in the normal extremities was similar to resting flow in the Pagetic extremities; this indicates that increases in cutaneous flow could account for most of the increase in total blood flow in the Pagetic extremities. Adrenergic control of blood flow to the Pagetic extremities was compared with that of the normal extremities. Vasoconstrictor responses to reflex stimuli in the Pagetic extremities were reduced; when vasoconstriction occurred it was gradual and sustained after termination of the stimuli, which suggests an exaggerated humoral response but reduced neural response to the stimuli. Intravenous epinephrine produced vasoconstriction in the Pagetic extremities and vasodilatation in the normal extremities. In summary, responses to epinephrine iontophoresis and heating suggest that the increase in blood flow in Pagetic extremities is primarily the result of cutaneous vasodilatation.


Detection of platelet isoantibodies by (3H)serotonin platelet release and its clinical application to the problem of platelet matching. The detection of platelet isoantibodies by the release of (3H)serotonin from platelets has been evaluated. The conditions for optimal release of (3H)serotonin with platelet isoantibodies using a microtechnique have been defined. A group of cardiac surgery patients were followed pre- and post-transfusions, with 48percent developing a positive serotonin release assay. Of these patients, 16percent also had a platelet complement-fixing and/or lymphocytotoxic isoantibody. There was variation in the degree of correlation between (3H)serotonin release and lymphocytotoxicity using individual National Institutes of Health typing serum. The matching obtained between family members by both techniques showed a close correlation when each technique was evaluated separately using the same NIH typing serum. The detection of iso-antibodies in patients with hematological malignancies correlated with the unresponsiveness to unmatched platelet transfusions in 15 out of 17 cases. The use of the patient's isoantibody to matched platelets of family members by (3H)serotonin release correlated well with the clinical response to transfusion with these platelets. The data suggest that (a) platelet isoantibodies can be detected with increased frequency by (3H)serotonin release; (b) (3H)serotonin release is a specific reaction depending on the surface antigen of the platelet; and (c) the method can be used to match compatible family members for platelet transfusions.


Hodgkin's Disease, tonsillectomy and family size. The association of tonsillectomy and Hodgkin's disease was investigated by comparison of 136 young adult patients with their 315 siblings and 78 spouses. On the basis of a case-spouse comparison, the risk ratio of Hodgkin's disease among tonsillectomized persons was 3.1 (1.5 to 7.7, 95 per cent confidence limits); on the basis of a case-sibling comparison it was 1.4 (0.8-2.6). The case-sibling analysis was repeated according to sibship size, and increased risk of disease was associated with tonsillectomy only within the 37 sibships of size two. A similar variation of risk ratio with sibship size was found in data from a prior study. The range of the association implies that the relation beteeen tonsillectomy and Hodgkin's disease either is noncausal or is complex and modified by family size. Risk of Hodgkin's disease was found to increase as a sibship size decreased, suggesting that a cause of Hodgkin's disease is correlated with childhood social class.


Spontaneous regression of friend virus induced leukemia: coinfection with regressing and conventional strains of virus. Mixtures of friend virus (CFV) and the regressing strain of friend virus (RFV) induce leukemia which regresses. The dominance of the regressing phenotype is solely a function of a threshold dose of RFV. The minimum amount of RFV which induced regression of CFV leukemia is below the titer for induction of friend disease, but does correlate ith the titer of lymphocytic leukemia (helper) activity in the these stocks.


Halogenated hydrocarbons in New Orleans drinking water and blood plasma. Volatile organics from New Orleans drinking water and pooled plasma were collected on a solid phenyl ether polymer and analyzed by gas chromatographic and mass spectrometric techniques. Thirteen halogenated hydrocarbons were identified in the drinking water. Five halogenated compounds were found in the plasma. Tetrachloroethylene and carbon tetrachloride were found in both the plasma and the drinking water. Considerable variation in the relative concentrations of the halogenated hydrocarbons was noted from day to day in the drinking water.


Retrograde amnesia: temporal gradient in very long term memory following electroconvulsive therapy. A newly designed remote memory test has been used to assess the temporal dimension of prolonged retrograde amnesia. Patients given a course of electroconvulsive treatments for relief of depressive illness exhibited a temporal gradient of retrograde amnesia after five treatments. Memories acquired up to about 3 years before treatment were impaired, but memories acquired 4 to 17 yearss before treatment were not affected. The results suggest that the neural substrate of memory gradually changes with the passage of time after learning and that resistance to amnesic treatment can continue to develop for years.


Quantitative studies of pinocytosis. I. Kinetics of uptake of (125I)polyvinylpyrrolidone by rat yolk sac cultured in vitro. A method is described for the in vitro culture of 17.5-day rat visceral yolk sac. Tissue survival was good as judged by light and electron microscopy. The rate of pinocytic uptake of 125I-labeled polyvinylpyrrolidone by the tissue was constant both within and between experiments. Within the concentration range 0.15-24 mug/ml, the 125I-labeled polyvinylpyrrolidone neither stimulated nor inhibited pinocytosis. The system offers many advantages in the quantitative study of the physical basis of pinocytosis.


Meiotic DNA synthesis during mouse spermatogenesis. The incorporation of radioactivity into various cells in the sequence of spermatogenesis was measured by preparing highly purified spermatozoan nuclei from the cauda epididymidis of mice at daily intervals after injection of (3H)thymidine. The stages of differentiation of these sperm at the time of thymidine administration were calculated from the kinetics of spermatogenesis. The procedure for purification of sperm nuclei included sonication, mechanical shearing, and treatment with trypsin, DNase, Triton X-100, 2M NaC1, and sodium dodecyl sulfate. DNA was isolated from these nuclei by treatment with dithiothreitol and pronase, followed by phenol extraction and ethanol precipitation. The levels of radioactivity in the epididymal sperm head preparations were low (less than 13 dpm/mouse) for 27 days after injection, and then rose dramatically to over 4 times 104 dpm/mouse. Further experiments demonstrated that the 11 dpm of 3H radioactivity contained in sperm heads at 21 or 26 days after injection of (3H)TdR was significantly above background and contamination levels from other cells or other sources. Most of the radioactivity was in the sperm DNA and represented incorporation of tritium from (3H)TdR into the nuclear DNA of meiotic cells at 0.002 percent of the rate of incorporation into S-phase cells. Little, if any, (3H)TdR was incorporation into the DNA of spermatids. The levels of DNA synthesis during the meiotic prophase in the mouse appear to be much lower than those reported for other organisms.


Actin associated with membranes from 3T3 mouse fibroblast and HeLa cells. A protein component of membranes isolated from 3T3 mouse fibroblasts and HeLa cells has been identified as actin by peptide mapping. Extensive but apparently not total coincidence was found between the peptide maps of these two nonmuscle membrane-associated actins compared to chick skeletal muscle actin. Between 2 and 4 percent of the total membrane protein appears in the actin band on sodium dodecyl sulfate polyacrylamide gels of 3T3 membranes while about 4 percent of the membrane protein appears as the actin band from HeLa membranes. These values represent approximately the same proportion of actin to total protein found in the cell homogenates. Treatment of intact cells with levels of cytochalasin B sufficient to cause pronounced morphological changes did not change the amount of actin associated with the membrane in either 3T3 or HeLa cells. However, incubation of isolated membranes under conditions favoring conversion of actin from filamentous to monomeric form resulted in dissociation of approximately 80 and 60 percent of the actin from 3T3 and HeLa membranes, respectively. Thus, approximately 20 percent of 3T3 membrane actin and 40 percent of HeLa membrane actin remained associated with the membrane even under actin depolymerizing conditions.


Microtubules with 15 subunits in cockroach epidermal cells. Since Ledbetter and Porter (1964) described the 13 subunits which are visible in cross sections of negatively stained plant microtubules, subsequent observations have generally confirmed this number. By using Mizuhira's fixative composed of tannic acid and glutaraldehyde, it is easyto demonstrate the subunits of microtublules without optical reinforcement Cytoplasmic microtubules and sperm axonemes, fixed with Mizuhira's fixtive, similarly show 13 subunits (Mizuhira's and Futaesaku, 1971, 1972; Futaesaky et al., 1972; Tilney et al., 1973). This paper will describe a particular type of microtubule in insect epidermal cells fixed with the above fixative. The number of the subunits is found to be 15 in tranverse sections.


Locations of 18S and 28S ribosomal genes on the chromosomes of the Indian muntjac. The locations of genes coding for 18S and 28S ribosomal RNA have been mapped on metaphase chromosomes of the Indian muntjac M. muntjak by in situ hybridization with (3H)rRNA from the toad X. laevis. The results show that, in the muntjac, rDNA clusters are associated with the prominent secondary constrictions on the X and the Y1 chromos. In addition a cluster of rDNA is found near the tip of one arm on the longest pair of autosomes. The autosomal cluster of rDNAs usually does not express as a secondary constriction at metaphase.


Cytochemical demonstration of hydrogen peroxide in polymorphonuclear leukocyte phagosomes. Phagocytosis by polymorphonuclear leukocytes (PMN) is accompanied by specific morphological and metabolic events which may result in the killing of internalized micro-organism. Hydrogen peroxide is produced in increased amounts during phagocytosis (17) and in combination with myeloperoxidase and halide ions constitute a potent, microbicidal mechanism (8,9,11). There can be direct iodination of micro-organisms (10), or alternatively, other intermediate reaction products, i.e. chloramines and aldehydes (21), can exert a microbicidal effect. The H2O2-peroxidase-halide system is presumed to operate within the phagocytic vacuole (12,18). Myeloperoxidase, present in the primary granules of PMN, enters the phagocytic vacuole during degranulation (1,4,7), and halide ions are probably derived from the extracellular medium or are present in the PMN (see 11, 18). For the operation of this system in intact cells, the presence of H2O2 in the phagocytic vacuole is necessary, and indeed this has been suggested by the work of several investigators (12, 18, 21). In the present investigation, the diaminobenzidine reaction of Graham and Karnovsky (5), modified to utilize endogenous myeloperoxidase and hydrogen peroxide, has been applied to actively phagocytizing PMN to demonstrate cytochemically the presence of H2O2 in the phagocytic vacuole.


Ribosomal RNA metabolism during renal hypertrophy. Evidence of decreased degradation of newly synthesized ribosomal RNA. The degradation rates of kidney rRNA labeled before UNI or sham are unchanged 5 days after the operations (t one-and-a half, 88 h). Therefore, there is no contribution from pre-existing rRNA to the increased amount of rRNA in the stimulated kidney. After labeling with L-(methyl-3H)methionine, the kinetics of incorporation into rRNA precursors, 10-60 min and at the postoperative times of 4, 16, 36, and 96 h. The specific activity of cytoplasmic rRNA after 1-h labeling with L-(methyl-3H)methionine increased occured at 4 or 96 h. Since (a) the rate of degradation of rRNA, (b) the kinetics of incorporation and processing of rRNA precursors, and (c) the rate of RNA synthesis appear unchanged after UNI, the accretion of rRNA must involve decreased degradation of newly synthesized rRNA.


Electron probe analysis of calcium transport by small intestine. Calcium transport in small intestine of rat and chick has been studied at the cellular level using the electron probe X-ray microanalyzer. Tissues were examined directly after removal as well as after incubation in a calcium solution. In both preparations, discrete calcium localizations were found associated with intracellular and extracellular goblet cell mucus. The in vitro preparations showed calcium in transit across the absorptive epithelium in discrete localizations. Although the primary path of transport was along lateral cell borders, some localizations were found in the cytoplasm in a supranuclear position. The effect of vitamin D depletion and repletion was to decrease and increase, respectively, the number of calcium localizations in transit across the epithelium. These results suggest that calcium is transported while in a sequestered form and indicate that goblet cell mucus plays a role in this transport process.


Left ventricular function in patients with and without myocardial infarction and one, two or three vessel coronary artery disease. Ninety-six patients with chest pain were studied to determine the relation between left ventricular function and severity of coronary artery disease in patients with and without a history of myocardial infarction. Coronary arteriography was performed obtaining cineangiograms (60 frames/sec) and large roll film angiograms (2 to 6 frames/sec) for precise definition of the coronary anatomy. The criteria for diagnosis of myocardial infarction were a typical history, a rise and fall in serum glutamic oxaloacetic transaminase levels and evolutionary S-T segment changes associated with Q waves of at least 0.03 second. Left ventricular function was assessed by measurement of left ventricular end-diastolic pressure and volume, and left ventricular ejection fraction, mass and compliance. Fifteen patients had normal findings; 81 were classified according to number of diseased vessels and presence or absence of myocardial infarction. There were no group differences in age or heart rate. Left ventricular end-diastolic pressure was abnormally increased in patients with three vessel disease and myocardial infarction. Left ventricular end-diastolic volume was increased and the ejection fraction was reduced in patients in each vessel disease group with myocardial infarction. Although ejection fraction was reduced in patients with three vessel disease without myocardial infarction, it was further reduced when infarction occurred. Left ventricular mass increased in patients with three vessel disease with or without myocardial infarction. Values for ventricular compliance were reduced in all patients with myocardial infarction and were lower in those with two and three vessel disease and infarction than in those with two and three vessel disease without infarction. These findings suggest that a previous history of myocardial infarction needs to be considered together with anatomic abnormalities of the coronary arteries in assessing cardiac performance in patients with ischemic heart disease, a previous myocardial infarction significantly alters left ventricular performance; the ejection fraction is a more sensitive measurement of left ventricular function than left ventricular end-diastolic pressure or volume.


Internal mammary arteriovenous malformation with communication to the pulmonary vessels. A 25 year old asymptomatic man with a past history of pulmonary tuberculosis presented with a continuous murmur. Selective arteriography revealed a left internal mammary arteriovenous malformation in communication with vessels in the left upper pulmonary lobe. No significant hemodynamic abnormalities were detected. This is the 26th reported case of internal mammary arteriovenous fistula and the 6th with a pulmonary communication. Review of the data in previous cases suggests that surgical indications are limited to symptomatic relief, heart failure during infancy or the possible risk of endarteritis, proximal arterial degeneration or rupture.


Progressive pulmonary vascular disease after surgical correction (Mustard procedure) of transposition of great arteries with intact ventricular septum. Severe pulmonary vascular disease developed 1 year after a Mustard operation in a 2 1/3 year old boy with transposition of the great arteries and intact ventricular septum. The possible etiologic factors responsible for the development of pulmonary vascular disease are discussed, and it is suggested that this disturbing late postoperative complication may occur more frequently than is recognized.


Mechanism of the bradycardia during coronary angiography. Bradycardia occurring during coronary angiography may be due to the direct effect of dye or to reflex vagal effects on pacemaker centers. Fifteen patients were classified according to the origin of the sinus nodal and atrioventricular nodal arteries. In patients with type A anatomy, both the sinus and the atrioventricular nodal arteries arose from the right coronary artery. In those with type B anatomy, only the atrioventricular nodal artery arose from the right coronary artery. Heart rate recordings were made during coronary angiography before and after selective infusion of atropine (0.2mg) into the right coronary artery. In type A patients, the sinus bradycardia observed during right coronary dye injection was caused by a combination of both direct and reflex effects on pacemaker tissue. Sinus bradycardia occurring with left coronary dye injections was entirely reflex in nature and was completely blocked with right coronary arterial injection of atropine. In type B patients, sinus bradycardia with right coronary dye injections was produced by reflex suppression of the sinus pacemaker. A junctional rhythm was consistently produced after administration of atropine. Junctional bradycardia in type B patients was caused by direct suppression of the junctional pacemaker. Thus, angiographic dye appears to decrease heart rate by a direct effect on pacemaker tissue and by reflex vagal suppression of the sinus pacemaker.


Subendocardial ischemia provoked by tachycardia in conscious dogs with coronary stenosis. We investigated the effect that mild coronary stenosis exerts on the ability of the coronary circulation to compensate for the increased extravascular compression that occurs in the subendocardium during tachycardia. An electromagnetic flowmeter transducer and balloon cuff occluder were implanted on the left circumflex coronary artery in seven dogs, and experiments were performed 1 week later with the dogs under sedation but conscious. Stenosis of the left circumflex artery was produced by partial inflation of the cuff occluder. We determined coronary blood flow distribution by the radioactive microsphere technique, injection 200,000 15mu spheres into the left ventricular cavity during (1) a control period, (2) stenosis of the left circumflex artery and a normal heart rate, and (3) stenosis of the left circumflex artery and tachycardia. When the heart rate was normal, the degree of stenosis used caused no change in myocardial microsphere distribution but eliminated postocclusion reactive hyperemia. Thus, reserve coronary vasodilation compensated for the stenosis. With the degree of stenosis kept constant, an increase in heart rate to 196 beats/min caused a marked transmural shift in distribution of microspheres from subendocardium into subepicardium within the region of the left ventricle supplied by the left circumflex artery. There was no significant transmural shift in the region supplied by the uninvolved left anterior descending coronary artery. Myocardial lactate extraction decreased. These results suggest that when reserve coronary vasodilation has already been utilized to compensate for coronary stenosis, the increased extravascular coronary compression from tachycardia causes subendocardial ischemia and hypoxia.


Effects of unipolar cathodal and bipolar stimulation on vulnerability of ischemic ventricles to fibrillation. The effects of unipolar and bipolar stimulation on ventricular fibrillation threshold were studied during acute occlusion of the left anterior descending coronary artery in 13 anesthetized dogs. Values for ventricular fibrillation threshold were determined by delivering trains of rapid bipolar or unipolar pulses (100/sec) during the vulnerable period. The mean threshold value was found to be 13.0 ma for bipolar, 13.9 ma for unipolar anodal and 21.0 ma for unipolar cathodal stimulation. Ventricular fibrillation threshold was significantly lower (P less than 0.01) with both unipolar anodal and bipolar stimulation than with unipolar cathodal stimulation. In these animals, the first premature beats induced by the rapid stimuli occurred significantly earlier with unipolar anodal and bipolar stimulation than with unipolar cathodal stimulation. The effect of competition of unipolar or bipolar pacing stimuli with normally conducted ventricular beats was also studied in a group of 16 dogs. Repeated trials of competitive pacing during coronary occlusion showed that the incidence of ventricular fibrillation was significantly greater (P less 0.05) with bipolar pacing (36 percent) than with unipolar cathodal pacing (15 percent). These results indicate that bipolar pacing is potentially more dangerous than unipolar cathodal pacing and suggest that the incidence of pacemaker-induced ventricular fibrillation might be further reduced by the use of unipolar cathodal stimulation during acute myocardial infarction.


Double outlet right ventricle (S,D,L) with subaortic ventricular septal defect and pulmonary stenosis. Report of six cases. The clinical, hemodynamic, angiocardiographic and pathologic findings are presented in an infrequent but surgically correctable type of double outlet right ventricle. This study is based on six cases, one with autopsy confirmation. In all, the viscera and atria were in situs solitus (S). A ventricular d-loop was present (D). There was I-malposition of the great arteries, the aorta being to the left of, and anterior to, the pulmonary artery (L). Hence, this anomaly may conveniently be represented as double outlet right ventricle (S,D,L,). The ventricular septal defect to the ventricular septum. A bilateral conus was present beneath both the aortic and pulmonary valves, preventing any semilunar-atrioventricular fibrous continuity. The subpulmonary conus was poorly expanded, resulting in pulmonary infundibular and valvular (annular) stenosis. The clinical features were those of cyanosis, clubbing and accentuation of the second heart sound in the pulmonary area (related to aortic valve closure). There was a systolic ejection murmur along the upper left sternal border, related to pulmonary outflow tract stenosis. Selective right and left ventricular angiocardiography was diagnostic. Relatively early surgical correction is suggested to minimize the progression of pulmonary infundibular stenosis and to avoid acquired atresia. In this malformation, pulmonary outflow tract reconstruction is more difficult than in tetralogy of Fallot because of the rather posterior location of the pulmonary outflow tract, and because the right coronary artery crosses the stenotic pulmonary outflow tract in front of the pulmonary valve.


Echocardiography in atrioventricular canal defect: a clinical spectrum. Echocardiographic examinations were performed in 30 children with atrioventricular (A-V) canal defect to determine the diagnostic value of recording A-V valve motion. Although a wide spectrum of abnormal movement was observed, four main diagnostic types emerged. Type 1, prolonged mitral-septal approximation during diastole, resulted from anterior displacement of the cleft anterior mitral leaflet. Type 2, the most diagnostic motion, was recorded when the common anterior A-V leaflet traversed the interventricular septum. Type 3 motion reflected posterior displacement of the septal tricuspid leaflet, which appeared to arise from the interventricular septum. Normal posterior diastolic motion of the septal leaflet was never recorded. Type 4, double contour of the mitral valve during systole and marked duplication of the systolic image, corresponded to irregularities in the mitral valve. When these patterns are recorded in a patient with congenital heart disease the diagnosis of A-V canal defect can be made with confidence.


Clinical implications of warfarin interactions with five sedatives. The intensity, uniformity and time course of anticoagulant interference by phenobarbital, secobarbital, glutethimide, chloral hydrate and methaqualone were systematically investigated in 16 patients receiving coumarin therapy. Each subject received an individualized fixed daily dose of warfarin and served as his own pre- and postsedative treatment control. Prothrombin times were measured four times weekly during five long-term experiments. Anticoagulant inhibition was observed during the administration of phenobarbital, secobarbital and glutethimide; there was no significant change in prothrombin test results during the trials of chloral hydrate and methaqualone. Barbiturates and glutethimide should not be administered to patients receiving coumarin drugs. The concurrent use of drugs from these groups is decreasing according to a survey of 200 hospital medical records. Chloral hydrate and methaqualone interact pharmacologically with orally administered anticoagulant agents, but the effect is not clinically significant. It is concluded that chloral hydrate and methaqualone may be administered safely without additional caution in prothrombin test monitoring during oral anticoagulant therapy.


Hemophilus aphrophilus endocarditis: review of 23 cases. A case of bacterial endocarditis caused by Hemophilus aphrophilus is described, and 22 previously reported cases are reviewed. Eleven patients died and 12 survived; comparison of these two groups reveals that the patients who died were in the older population. The male/female ratio was 3.6:1. The organism was difficult to identify but had a wide range of in vitro bacteriologic sensitivities. This type of endocarditis is frequently associated with emboli and congestive heart failure; each occurred in 9 of 11 fatal cases and 3 of 12 nonfatal cases. Among the nonfatal cases, two patients had both emboli and congestive heart failure, requiring aortic valve replacement despite their precarious clinical condition. Initial drug therapy before results of antibiotic sensitivity tests are known should consist of penicillin combined with streptomycin. When emboli or congestive heart failure appears in Hemophilus aphrophilus endocarditis, early surgical intervention with valve replacement is indicated.


Precordial honk due to tricuspid regurgitation. A systolic honk developed in a woman with idiopathic cardiomyopathy and congestive heart failure. The honk was present only during deep inspiration, disappeared as her cardiovascular status improved, but recurred when her cardiovascular function declined. Further investigation indicated that the honk was the result of tricuspid regurgitation.