So-called neuronal ceroid-lipofuscinosis. Histochemical study with evidence of extractibility of the stored material. Histochemical study of so-called neuronal ceroid-lipofuscinoses (NCL) showed that the stored material is extractable in the unfixed state especially with alkalized or acidified chloroform-methanol mixtures when compared with other solvents. The extractability was strongly reduced or almost abolished by fixation with formaldehyde. Identical results were obtained with the type one storage material (see Elleder, 1977) in all late infantile cases and in a juvenile case studied, in which, contrary to the infantile form, the stored material displayed a significantly higher degree of extractability. As far as the extractability of the type two storage material is concerned insufficient data have been accumulated, but it seems that it does not differ significantly from the first one. In the control group of lipopigments ceroid was found to be much more extractable under identical conditions than matured lipofuscin which was almost entirely resistant to all extraction procedures. The significance of the results is discussed.


Ferritin immune complex deposits in the choroid plexus. Mice injected intraperitoneally with 20 mg of ferritin twice weekly for more than 4 weeks developed proteinuria due to the deposition of ferritin-antiferritin antibody complexes in renal glomeruli. Deposits of ferritin, immunoglobulin G (IgG) and third complement component (C3) also accumulated in the perivascular, extracellular space of the choroid plexus as demonstrated by immunofluorescence and electron microscopy. The findings confirm previous observations on immune complex deposits in the choroid plexus in spontaneous autoimmune disease and persistent viral infections. The occurrence of similar deposits in the human choroid plexus and the possibility of an associated disturbance of the blood-spinal fluid barrier are discussed.


Stilbestrol administration in the puerperium and its effect on the prolactin excretion of non-lactacting patients. The relationship between stilbestrol treatment and placebo treatment was studied in 2 groups of non-nursing patients. Plasma prolactin levels were evaluated in these 2 groups on day 1, 3 and 7 of the treatment, by a radioimmunoassay technique with the double antibody method using Serono hPRL kit. Our results show that prolactin values increased significantly in the stilbestrol-group and decreased in the placebo group. It seems that the main reason for "the drying up of milk" is the lack of stimulation of the nipples, which after a releatively constant time of 5--10 days will lead to decreased prolactin levels. Stilbestrol treatment is not effective in "drying up" the milk more rapidly in patients who do not want to nurse. When patients have symptoms a combination of analgesia and breast support usually brings relief within 24 to 48 hours.


Sex-linked values of E-rosette forming lymphocytes in mother and newborn. The T-cell marker of spontaneous rosettes with sheep erythrocytes was determined in 34 normal term-deliveries on the peripheral lymphocytes of the mother and the corresponding cord-blood lymphocytes of the newborn, immediately after delivery. A consistently lower level of E-rosette forming lymphocytes was observed in male as compared to female newborns in different parity groups and in twin deliveries. When the mean values were calculated for corresponding E-rosettes of maternal and newborn lymphocytes in each group (female and male group of offsprings) they were nearly identical.


A quantitative study of the renal corpuscles in acute renal allograft rejection. A quantitative examination including total and differential counts of nuclei and determination of total glomerular and mesangial areas was carried out in a consecutive series of biopsies from 14 patients with acute renal allograft rejections. The biopsies included in the study were taken within 4--30 days after transplantation because of suspected acute rejection, and histological examination revealed interstitial and vascular signs of rejection without the presence of cortical infarcts. Mesangial area per cent of total area was found to be significantly higher in allografts than in control kidneys, just as a statistically significant increase in the number of mesangial nuclei was demonstrated. Three of the 14 allografts had to be rechanges in these 3 biopsies were more pronounced than those in the remaining biopsies. It is suggested that quantitative glomerular studies might yield data of significance for prediction of the ultimate fate of the graft.


Inhibitory effects of plasma from uraemic patients on human mononuclear phagocytes cultured in vitro. Human mononuclear phagocytes were cultured in plasma from uraemic patients. The presence of uraemic plasma during the engulfment or digestion of 125I-labelled Candida albicans did not inhibit these functions in mononuclear phagocytes cultured for 8 days under normal condition. When normal human macrophages were cultured in the presence of uraemic plasma for 2-4 days, a marked detachment of the cells from the glass coverslips was registered. The phagocytic function of the remaining cells was impaired. Creatinine, urea and methylguanidine in concentrations higher than those usually measured in plasma from uraemic patients did not influence the functional properties of the cells. The inhibitory effect of uraemic plasma on the mononuclear phagocytes is suggested as an explanation for the increased frequency of infections in uraemic patients.


IgA levels, bacterial carrier rate, and the development of bronchial asthma in children. A total of 54 children, earlier hospitalized for asthma, were reinvestigated with regard to immunoglobulin formation in serum and saliva. Furthermore, the carrier rate of pathogenic bacteria in their throats was investigated, and in some of the children, who had their adenoids removed, immunofluorescent studies were performed. The study revealed highly reduced levels of serum and saliva IgA in the younger children with asthma. In addition, in these children a connection between recurring respiratory infections and high carrier rate of presumably pathogenic bacteria was observed. Also in the older children, significantly reduced levels of serum and saliva IgA compared with age related controls were found, but these children did not have an increased frequency of pathogenic bacteria or repiratory infections. In addition, low levels of serum IgM were found in the older children with asthma. The results of the study support the theory that low IgA levels facilitate the entrance of pathogenic bacteria through the epithelial surfaces, resulting in an overstimulation of the IgE system and the development of bronchial asthma in the younger children. In the younger as well as the older patients, a high frequency of atopy among the closest relatives was observed.


Characteristics of the phagocytic process assessed by Coulter Counter. The phagocytosis in suspensions of heat-killed yeast cells, Saccharomyces cerevisiae, by human polymorphonuclear leucocytes was studied in vitro by means of an electronic particle counter, the Coulter Counter, and a 100-channel pulse-height analyzer, the Channelyzer. The two cell populations were separated from each other electronically by the Channelyzer. Phagocytosis was recorded as disappearence of yeast cells. Concomitantly, aggregation and swelling of the PMN-cells were observed, which increased with the concentration of the prey. The process could be inhibited by cytochalasin B and iodoacetamide. With the latter inhibitor, the analysis of the kinetics showed that ingestion, but not adhesion, was affected. The ingestion of yeast cells was augmented on increase of the initial ratio between the number of yeast and PMN cells to around 5:1, but was then reduced on further increase. A ratio of 2:1 and a reaction time of 30 min seemed suitable for studying the phagocytic process. First-order kinetics were obeyed under these circumstances.


Effect of angiotensin on normal renal circulation determined by angiography and a dye dilution technique. Angiotensin in a dose of 0.5 to 1.0 microgran injected into the renal artery of healthy kidneys initially decreased renal blood flow and increased the appearance time and mean transit time of dye and contrast medium as examined by a dye dilution technique and angiography. The initial phase is followed by a reactive hyperemia.  The increased vascular resistance is probably localized peripherally on the arterial side of the vascular tree. Optimum dose is 0.5 to 1.0 microgram angiotensin in diagnosis of renal tumours. Optimum interval between drug administration and angiography is 10 to 60 s.


The effect of clofibrate on glucose tolerance, insulin secretion, triglycerides and fibrinogen in patients with coronary heart disease. The effects of clofibrate treatment have been monitored in a double-blind cross-over study conducted in 16 male patients with coronary heart disease. Most had latent diabetes mellitus with elevated and delayed insulin release after i.v. glucose administration. Blood glucose and insulin levels were measured during repeated i.v. glucose tolerance tests in each patient and serum triglyceride and plasma fibrinogen were estimated at intervals. Clofibrate treatment significantly lowered fasting blood glucose levels (p less than 0.01) and improved the glucose tolerance (p less than 0.01). Fasting plasma insulin levels and those at 30 min after glucose loading were reduced (p less than 0.05). Serum triglycerides (p less than 0.01) and plasma fibrinogen levels (p less than 0.05) were lowered during the treatment period. The change in k-value (glucose utilization) did not correlate to changes in  triglyceride or fibrinogen. This study confirms the beneficial effect of clofibrate therapy on abnormal glucose tolerance observed by other workers. It is suggested that clofibrate acts by reducing peripheral insulin resistance.


A modification of the Guiot-Gillingham stereotaxic frame to allow of angular insertion. A method of modification of the Guior-Gillingham Stereotaxic frame is described, which will allow of angular insertion of a leucotome or electrode. In our experience, this has prevented the complication of radiation damage and hemianopia and it also permits greater flexibility in the operative approach to structures at or near the midline.


Nocardia asteroides primary cerebral abscess and secondary meningitis. A rare case of primary cerebral abscess due to Nocardia asteroides, and its surgical removal, are described. Postoperative meningitis caused by the same fungi was succesfully cured with sulphadiazine and cycloserine. The nocardial disease, its neurological complications, and therapy are reviewed.


Physiologically controlled selective thalamotomy for the treatment of abnormal movement by Leksell's open system. In the course of stereotaxic thalamotomy by Leksell's open system in 20 cases of abnormal movement, recording and stimulation of the subcortical structures have been performed by means of two semimicro-electrodes introduced parallel to the frontal plane. Taking advantage of simultaneous recording and electrical stimulation through these two electrodes, several critical points in the caudate nucleus and thalamus have been clearly delineated. Thus in each individual case an outline of the thalamic configuration in the frontal plane could be obtained, so that the final therapeutic lesion was placed with good precision at the lower-most border of VL or Vim nucleus. It has been shown that the physiologically determined minimum lesion resulted in satisfactory alleviation of the abnormal movements without notable untoward effects.


TQ-ST segment mapping: critical review and analysis of current concepts. Controversy and confusion surround many aspects of TQ-ST segment mapping today. Technical standards pertaining to the recording and measurement of the TQ-ST deflection have not been uniformly established nor has the correlative value of the deflection as an indicator of myocardial injury been clearly ascertained. The TQ-ST deflection is believed to originate primarily although not exclusively as a result of extracellular potassium accumulation in the ischemic region and subsequent establishment of a transmembrane potential gradient during diastole and systole at the ischemic boundary. Nonspatial factors (including electrolytes, antiarrhythmic agents, heart rate) influence the TQ-ST deflection by altering this gradient. Spatial factors (including ischemic area and shape, electrode location) alter the relative position of the ischemic boundary to the electrode site and as such can be analyzed with the solid angle theorem. Further study of the complex behavior of the TQ-ST segment deflection, particularly in the presence of pharmacologic intervention, is necessary before mapping techniques can be used reliably in clinical studies designed to quantitate and modify ischemic damage.


Hemodynamic effects of intravenously administered quinidine on the transplanted human heart. The acute hemodynamic effects of intravenously administered quinidine were studied in five heart transplant recipients with an anatomically denervated heart. Quinidine, 10 mg/kg body weight, was infused over a 20 minute period, and mild wall left ventricular dynamics were measured with a new technique using metallic markers surgically implanted in the myocardial wall. Heart rate was maintained constant with atrial pacing, and aortic blood pressure was measured through an indwelling catheter. In each patient the hemodynamic responses to quinidine were similar. End-diastolic, end-systolic and stroke volumes decreased by an average of 19, 26 and 18 percent, respectively. Cardiac output decreased by a mean 0.92 liters/min (-18%), and the mean aortic blood pressure decreased by 10 mm Hg (-11%). All of these changes were statistically significant. Three indexes of the contractile state of the left ventricle--mean circumferential velocity, mean systolic diameter shortening and ejection fraction--were not significantly changed. We conclude that quinidine exerts no acute inotropic myocardial effects in the human transplanted heart and that, when given intravenously, its hemodynamic action is most consistent with venodilatation.


Diagnosis of myocardial infarction: historical notes from the Soviet Union and the United States. Soviet physicians attribute the first description of the clinical presentation of a nonfatal myocardial infarction to V.P. Obraztsov and N.D. Strazhesko; American physicians attribute the same achievement to James B. Herrick. Investigation of the origins of the conflicting claims reveals that the Russian physicians published an accurate account of the syndrome in 1910. Herrick, in his article published in 1912, cites a German translation of the Russian article. Herrick's major contribution consisted of informing American physicians of the symptoms of infarction, and stimulating development of the electrocardiogram as a diagnostic aid.


Osteopetrosis in the toothless (t1) rat: presence of osteoclasts but failure to respond to parathyroid extract or to be cured by infusion of spleen or bone marrow cells from normal littermates. Osteoclast have been observe for the first time in toothless (t1) rats, a mutation with inherits osteopetrosis as an autosomal recessive. The ability of t1 rats to raise the serum calcium concentration after injection of parathyroid extract was severely limited when compared with normal littermates. In addition, osteopetrosis in t1 rats is not cured by radiation and infusion of normal spleen or bone marrow cells from normal littermates, a method know to cure osteopetrosis in mutants of this and other species. This indirect evidence for a reduction in bone resorption as a cause of osteopetrosis in this mutation and the failure of transplanted cells to cure the disease are discussed in relation to the development and function of osteoclasts.


Effect of mega doses of vitamin C on bactericidal ativity of leukocytes. Effect of ingesting mega doses of ascorbic acid was studied on the leukocyte function in five normal human subjects. During the first 15 days the subjects received daily supplements of 200 mg of ascorbic acid, and during the next 2 weeks they were given 2 g of vitamin C per day. Supplementation of 200 mg as well as 2 g of ascorbic acid stimulated hexose monophosphate shunt activity of resting leukocytes indicating an increase in resting metabolism. Intakes of 200 mg of ascorbic acid per day did not affect bacterial killing by leukocytes. On the other hand, daily intakes of 2 g of ascorbic acid for 2 weeks significantly impaired bactericidal activity. Four weeks after withdrawal of the viatmin supplementation, bactericidal activity returned to normal.


A method for determining in-vitro drug susceptibilities of some Nocardiae and Actinomadurae: results with 17 antimicrobial agents. A simple timesaving method for determining drug susceptibilities in vitro of isolates of Nocardia and Actinomadura is reported. An isolate is considered "susceptible" when the quantity of drug required for inhibition of growth is that concentration which might be obtained in serum by conventional therapy. Sulfonamides remain the drugs of choice for treating disease due to Nocardia species. Although doxycycline and minocycline appear to be very effective against Nocardia species, susceptibility testing may be desirable when a physician is considering substitution of an antibiotic for a sulfonamide. Susceptibility testing also may be desired before a drug is selected for treating disease due to Actinomadura madurae.


Infections in patients with neutropenia. We review published reports and our experience in regard to the causative organisms of infections in patients with neutropenia. The organisms isolated from infected patients were almost exclusively pyogenic and enteric bacteria, and our patients had no history of serious viral or fungal infections, documenting the importance of the neutrophil in normal host defense against extracellular but not intracellular pathogens. Staphylococcus aureus was the single most commonly cultured organism; however, Pseudomonas and Escherichia coli were almost as commonly isolated. Positive cultures were obtained primarily from the blood or cutaneous, subcutaneous, or deep tissue abscesses. In patients with congenital neutropenia, pneumonia, otitis media, and abscesses were the most frequent infections diagnosed clinically. There is a suggestion that recent antibiotic therapy shifted the spectrum of infecting organisms toward enteric bacteria.


Location of food consumption and travelers' diarrhea. Daily food histories for one month were obtained in summer, 1975, from students attending a Mexican university to determine the influence of food consumption on the development and etiology of diarrhea. In newly-arrived students from the U.S. who ate half or more of their meals in the school cafeteria and public restaurants there were significant increases in diarrhea (p less than 0.005); shigella infection (p less than 0.05) and toxigenic E. coli infection (p less than 0.025) compared to the students eating a comparable number of meals in private homes. In the summer U.S. students there was also an association of diarrhea and eating from street vendors (p less than 0.05). In full-time U.S. students who had lived in Mexico a year or longer as well as in Latin American students a relationship between location of meals and occurrence of enteric disease was not apparent. High numbers of enteric bacteria were recovered from food from the school's cafeteria, public restaurants, street vendors and small grocery stores. Shigella were isolated from cooked and uncooked hamburger patties from the school cafeteria. Four shigella carriers were found among kitchen personnel at the school. This study demonstrates that food serves as a major vehicle through which travelers' diarrhea occurs.


Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 3: cephalosporins. Various aspects of the cephalosporin antibiotics are reviewed, including mode of action and mechanisms of bacterial resistance, antibacterial activity, clinical pharmacology, adverse reactions, and therapeutic use. There are no important therapeutic differences between the two oral agents, cephalexin and cephradine. For intramuscular injection, cephaloridine has largely been replaced by cefazolin which is equally well tolerated and not as nephrotoxic; further, cefazolin has a relatively long half-life which permits its administration three or four times daily. There are no substantial therapeutic differences among the cephalosporins most commonly used intravenously--cephalothin, cefazolin and cephapirin. However, cefazolin is administered in a lower dosage and somewhat less frequently.


Echocardiography in ischemic heart disease. Echocardiographic findings in patients with ischemic heart disease are described; their correlations with clinical, hemodynamic and angiographic data are presented and discussed. Regional abnormalities of left ventricular wall motion and/or thickening during systole are detected in 84 per cent of patients with acute myocardial infarction and in a high percentage of patients with larger than or equal to 75 per cent narrowing of a major coronary artery. These abnormalities may occur with stress and may be reversible. Left ventricular wall thinning during systole indicates acute ischemia or infarction and thin, dense myocardial echoes indicate scar. Echocardiographic evidence of left ventricular dysfunction is useful in predicting heart failure and mortality in patients with acute myocardial infarction and in predicting surgical mortality for patients undergoing aneurysmectomy and/or coronary artery bypass surgery. Echocardiography has not proved useful in determining graft patency following coronary artery bypass surgery. Technical difficulties and limitations of echocardiography in patients with coronary artery disease are discussed.


The ocular manifestations of Wegener's granulomatosis. Fifteen years experience and review of the literature. Ocular manifestations of Wegener's granulomatosis may occur secondary to contiguous granulomatous sinusitis or as a result of focal vasculitis. Contiguous granulomatous sinus disease causes nasolacrimal duct obstruction, proptosis and ocular muscle or optic nerve involvement. Focal vasculitis unrelated to contiguous upper respiratory tract disease is manifested by conjunctivitis, episcleritis, scleritis, corneoscleral ulceration, uveitis, and granulomatous vasculitis of the retina and optic nerve. A review of 29 cases of Wegener's granulomatosis and three cases of lymphomatoid granulomatosis studied over the past 15 years at the National Institute of Allergy and Infectious Diseases (NIAID) disclosed single or multiple ocular manifestations of disease in 15 patients (47 per cent). The pattern of ocular disease, its relationship to systemic involvement, diagnostic methods and the response to therapy are discussed.


Echocardiography in pericardial effusion. Echocardiography has become established as the procedure of choice for the detection, confirmation and serial follow-up of patients with pericardial effusion. In this article the technic and pitfalls of recording, and the criteria and their sensitivity for the diagnosis of pericardial effusion are reviewed. In addition, echographic findings in special instances, such as accumulation of pericardial effusion behind the left atrium, the swinging heart syndrome and cardiac tamponade, are discussed.


Echocardiography in congenital heart disease. The utility of echocardiography in the evaluation of congenital cardiac disease is well established. The following discussion will be devoted to the application of single dimensional equipment in the assessment of selected congenital defects which will include secundum atrial defects, endocardial cushion defects, tetralogy of Fallot, Ebstein's anomaly of the tricuspid valve, and the use of systolic time intervals in assessing pulmonary artery diastolic pressures and pulmonary vasculature resistance. Since space is limited, only brief descriptions of these specific applications are possible and the readers are referred to more complete descriptions of the technic.


Effect of prophylactic outpatient administration of fenoterol on the time of onset of spontaneous labor and fetal growth rate in twin pregnancy. A double-blind trial was conducted on outpatients with twin gestations to assess the effect of prophylactic administration of fenoterol on the fetal growth rate and the timing of the spontaneous onset of labor. No significant differences could be shown between the fenoterol-treated group of patients and the control group given a placebo. It is concluded that prophylactic administration of fenoterol does not have a significant effect upon the incidence of preterm labor or growth retardation in twin pregnancy.


Uterine toxoplasma infections and repeated abortions. Serologic testing for Toxoplasma antibodies (dye test, indirect fluorescent antibody test on serum, and complement-fixation test) was done in 96 women with habitual abortions and 61 women with sporadic abortions. In 61 of these women, endometrial biopsies were examined for content of T. gondii (animal inoculation procedures, immunofluorescence microscopy). Control subjects were 59 women with no spontaneous abortions. In seven patients (one control patient and six with habitual abortion), tachyzoites of T. gondii were observed in repeated biopsies from the endometrium and in menstrual blood by the immunofluorescence method. In no case, however, could T. gondii be isolated from the endometrium by inoculations. Moreover, the serologic results obtained among the patients with habitual abortion did not differ significantly from those obtained among the ones with sporadic abortion or among the control subjects. Five of the women with Toxoplasma-positive endometrium were serologically negative. Treatment of the Toxoplasma-positive women with antitoxoplasma drugs led to removal of parasites from the endometrium. T. gondii was not observed in the semen of the husbands.


Methods for quantitative vaginal flora studies. Quantitative bacteriology of the vaginal flora was performed with two techniques: One was a quantitative loop of vaginal secretions and the second was duplicate swabs of the vaginal fornix with one swab for bacteriologic studies and the second to determine specimen weight. Both sampling methods were evaluated for accuracy in weight or volume measurements. Comparison of the two methods in eight volunteers showed reasonably good correlation although the duplicate swab technique gave somewhat higher mean counts and more bacterial species. Advantages and limitations of these methods for quantitative vaginal flora studies are discussed.


Pregnancy in liver cirrhosis and/or portal hypertension. Clinical features of pregnancy in women with liver cirrhosis and/or portal hypertension have been reviewed. Termination of pregnancy is seldom indicated in a woman with compensated cirrhosis or a young woman with extrahepatic venous obstruction. However, the risk of spontaneous abortion is increased in cirrhotic women without shunt even if there is no deterioration of liver function. The risk of bleeding from esophageal varices or deterioration of liver function is usually unpredictable. Shunt surgery can be done with relatively little effect on both the mother and the fetus if conservative measurements fail to control the hematemesis. Vaginal delivery can be anticipated in most women, and cesarean section should be preserved for obstetric indications. The risk of postpartum hemorrhage is greatly increased, particularly in patients with previous shunt surgery. Perinatal loss is high because of the increased rate of premature delivery and stillbirth. Maternal prognosis is grave in women with cirrhosis.


Experimental pancreatic carcinogenesis. I. Morphogenesis of pancreatic adenocarcinoma in the Syrian golden hamster induced by N-nitroso-bis(2-hydroxypropyl)amine. In serial sacrifice experiment, outbred male Syrian golden hamsters were treated once weekly for life with subcutaneous injections of N-nitroso-bis(2-hydroxypropyl) amine (DIPN). The pancreas was examined by high resolution light (1-micro sections) and transmission electron microscopy. Early nonspecific changes in all pancreatic epithelial cellular elements were followed by a progressive proliferation of intra- and interlobular duct cells, with the development of multicentric foci of cystic and papillary cystic adenomas, intraductal carcinomas, and invasive ductal neoplasms. These observations were consistent with multistage morphogenesis of pancreatic adenocarcinoma of ductal origin.


Influence of the ionophore A23187 on the plastic behavior of normal erythrocytes. Previous studies have demonstrated that A23187, an ionophore which selectively transports divalent cations across cell membranes, has profound effects on human erythrocytes: it causes red cells to take up calcium; lose potassium, water, and ATP; convert from biconcave discs to echinocytes and spheroechinocytes; and become more rigid. The present study has explored the influence of calcium uptake induced by the ionophore on the behavior of individual erythrocyte membranes by the micropipette aspiration technique. Exposure of erythrocytes to calcium and A23187 for intervals of up to 30 minutes resulted in marked changes in membrane viscoelastic properties, including the development of increased resistance to aspiration. The most striking manifestation of altered membrane mechanics was apparent after 10 minutes on incubation. Cells pulled into the pipette for a few seconds and the extruded back into the medium retained the deformity imposed by the pipette for several seconds to a few minutes before regaining the form they manifested prior to initial aspiration. The calcium-induced changes in erythrocyte behavior observed in this study strongly support the concept that extrinsic proteins located inside the membrane provide mechanical support to the cell wall, and that increased levels of calcium cause precipitation or cross-linking of the proteins responsible for the increased resistence to deformation and recoil observed after aspiration into micropipettes.


Localization of human T lymphocytes in tissue sections by a rosetting technique. A technique for the formation of sheep erythrocyte (E) rosettes in frozen human tissue sections is reported. The labile nature of the receptor for E rosettes on lymphocytes requires the use of controlled conditions for tissue processing and the reaction with indicator cells. The distribution of E rosettes in sections of normal human thymus, lymph nodes, tonsils, and spleens was comparable to that of the T marker-positive cells identified by immunofluorescence with the specific anti-human T cell serum. There with no overlap with areas positive for 19S EAC and 7S EA rosettes. Erythrocytes treated with a sulfhydryl reagent, 2-aminoethylisothiuronium bromide (AET), and with neuraminidase formed better rosettes in sections than did untreated erythrocytes. E rosettes in tissue sections can determine changes in the distribution of T cells in different lymphoproliferative and infiltrating disorders.


The production of migration inhibitory factor and reproductive capacity in allogeneic pregnancies. Migration inhibitory factor (MIF) is produced during allogeneic pregnancies but not during syngeneic pregnancies. Removal of the paraaortic or paraaortic and renal lymph nodes significantly decreased MIF production whereas splenectomy did not. Removal of these regional lymph nodes decreased the mean litter size and increased the variance in the weights of the offspring, with the greatest changes occurring when both the paraaortic and renal lymph nodes were removed; splenectomy did not alter either parameter. None of the surgical procedures affected the gestation period significantly, but removal of the paraaortic and renal lymph nodes greatly reduced the rate of conception and increased the incidence of stillbirths. These findings support the proposition that a vigorous immune response occurs during allogeneic pregnancies and that this response provides reproductive advantages to the offspring.


Histologic changes in preserved cadaveric renal transplants. The histologic changes in human cadaveric kidneys preserved by either simple hypothermia or continuous pulsatile perfusion were studied by light and electron microscopy and by immunofluorescence in biopsies obtained immediately before (15 kidneys) and approximately 1 hour after (41 kidneys) transplantation. The changes observed in pretransplantation biopsies were largely similar in kidneys preserved by either method with the exception that foreign material was found in the vasculature of perfused kidneys only. Endothelial edema was more frequent and more severe in nonperfused kidneys only. Endothelial edema was more frequent and more severe in nonperfused kidneys. In the 1 hour posttransplantation biopsies, a lesion resembling intravascular coagulation (IVC) was noted in 18 of  the 25 perfused kidneys but was absent from all 16 nonperfused kidneys. Transplants with severe IVC lesions failed to function and had extensive cortical necrosis when removed by the end of the first month. In follow-up biopsies, milder lesions appeared to heal fast and were compatible with transplant function. The IVC lesion is probably due to endothelial cell damage during perfusion of the kidneys.


An analysis of the determinants of nephron filtration rate. Studies on glomerular filtration in the Munich-Wistar rat, a strain with surface glomeruli, have permitted for the first time the evaluation of the four factors that determine filtration rate: 1) the rate of nephron plasma flow (RPF), 2) the glomerular hydrostatic pressure gradient (deltaP) from capillary to Bowman's space, 3) systemic oncotic pressure (piA), and 4) the glomerular permeability coefficient (LpA), and their respective roles in producing change in filtration rate. The process of filtration in the Munich-Wistar rat is characterized by filtration  pressure equilibrium and, therefore, filtration should be highly plasma flow-dependent. Analysis of data from this strain suggests that multiple factors can change LpA, and, at least in animals which do not achieve filtration pressure equilibrium, these alterations in LpA can influence the final filtration rate. Multivariate statistical analysis in a variety of experimental conditions in the Munich-Wistar rat suggest that changes in RPF remain the major mediator of change in nephron filtration rate, both in rats at filtration pressure equilibrium and in disequilibrated animals. Although the glomerulus is an ultrafilter driven by hydrostatic forces, changes in deltaP assume a lesser role in producing alterations in filtration rate.


Rate of heat production related to degree of filament overlap in chick ALD muscle. The anterior latissimus dorsi (ALD) of chicks (2 wk old) was examined for rate of heat liberation when the muscle was reversibly stretched from L0 to about 1.6 L0. The "plateau" forces of isometric tetani were related to the corresponding rates of heat liberation. Presumably, in this region of length change the degree of overlap between the thick and thin filaments is changing. If the amount of overlap is known, the number of heavy meromyosin cross bridges in activity can be estimated. From this information, the amount of liberated energy can be calculated for a single cross-bridge cycling. In all of our measurements, there was heat production even at muscle lengths so great that no filament overlap would have to be assumed. This finding was incorported into the estimate for energy release per cross-bridge cycling.


Uptake of amino acids by islet of Langerhans and other tissues of the toadfish. The uptake of injected radioactive amino acids by the isolated islet and other tissues of the toadfish has been examined. The islet and most other tissues appear to actively transport most amino acids and, of the tissues studied, the islet is one of the most active in this regard. Most tissues accumulated the dicarboxylic acids to the greatest extent, with the basic amino acids and the neutral amino acids with unbranched side chains also being taken up well. However, each tissue showed a unique pattern of uptake of the different amino acids, and islet was distinguished by its high uptake of glycine 15 min after injection. The pattern of uptake of amino acids by toadfish islet does not appear to be related to their relative ability to stimulate insulin release from islets of other species or to their relative rates of metabolism, but does correlate well with the content of free amino acids in mouse islets and with the sum of the amino acid contents of anglerfish proinsulin and proglucagon.


Psychotherapies: an overview.

Psychotherapies: an overview. The author schematically describes the three predominating themes in the development of the psychotherapies: dynamic, behavioral, and experiential. These themes represent different conceptualizations of the fundamental nature of man and his ills, therapeutic processes or change agents, the basic nature of the physician-patient relationship, and the primary techniques and methods used. Although there appears to be some unifying thread connecting the four different areas within each theme, a comparable bond does not exist across the three themes. The author questions the potential unification of the psychotherapies and poses specific dimensions for further exploration.


Life planning: an educational approach to change. Life-planning methods that have emerged over the past several years offer alternatives to psychotherapy for the person experiencing the crises of mid-life and mid-career. The author describes several approaches to life planning and presents details regarding the implementation of life-planning methods.


Brief family therapy may lead to deep personality change. A 15 1/2-year-old boy with a falsetto voice and his family were treated by brief family therapy. The pace and direction of the patient's overall ego integration coincided closely with constant and rapid alteration of his conception of the human body. This change was clearly seen in his drawings done over aperiod of time. The authors suggest that deep personality changes may follow brief family therapy.


Collection of a clean voided urine specimen: a comparison among spoken, written, and computer-based instructions. In an effort to compare different methods of instructing patients, 99 women 18-25 years of age were given computer, spoken, weitten, or no instructions for the collection of a clean voided urine specimen. The group who received computer instructions was the most uniform in its performance (P less than 0.002, F-test) and reported the fewest procedural problems (P less than 0.02, Fisher test). In addition, this group had fewer contaminating bacteria than the group who received written instructions (P less than 0.03 , Mann-Whitney test). The group who received no instructions had more bacteria (P less than 0.0001, Mann-Whitney test) than any of the other groups. The effectiveness of the computer instruction was probably related to numerous attributes, including the individualized quality of the dialogue, self-pacing, self-testing, and privacy.


Further experience with anterior gastric fixation in the management of hiatal hernia. Anterior gastropexy in properly selected patients is a simple, safe, and effective procedure for the surgical correction of symptomatic esophageal reflux in the presence of a sliding type of hiatal hernia not accompanied by fibrosis and secondary shortening of the esophagus. This technic is particularly useful in poor risk, elderly, and excessively obese patients and as an adjunct to other intraabdominal procedures.


Injuries to the inferior vena cava and their management. Injuries to the inferior vena cava are being seen with increasing frequency in the civilian population. A review of the experience at UCLA/Harbor General Hospital Medical Center over a ten year period (1966 to 1976) discloses thirty-four patients with major injuries to the inferior vena cava, with an overall mortality of 53%. The factors that appear critical to patient survival are: (1) level of injury (suprarenal versus infrarenal sites); (2) presence or absence of profound shock on admission; and (3) the speed with which diagnosis is made and treatment carried out. Technical considerations regarding identification and handling of inferior vena caval injuries are presented. The mortality rate for major inferior vena caval injuries remains distressingly high and serves as a challenge for future improvement.


Breast reconstruction after mastectomy.

Breast reconstruction after mastectomy. Reconstruction of the breast contour and areolanipple complex can be undertaken in patients who have had mastectomy for carcinoma of the breast. Although the reconstructed breast is not normal, the restored contour and simulation is gratifying for those patients who have sought this procedure.


Bacteriology of necrotizing fasciitis.

Bacteriology of necrotizing fasciitis. Sixteen patients with necrotizing fasciitis were observed under clinical and laboratory conditions for collection, preservation, and culture that permitted optimal retrieval of anaerobes. The clinical observations of necrosis of fascia, subcutaneous fat and skin with thrombosis of the microvasculature, and absence of myonecrosis were clearly apparent in these patients. Two clear-cut groups of culture and gram stain results were found, suggesting that the clinical entity of necrotizing fasciitis can occur after infection by different infecting organisms. The cultivation of Streptococcus pyogenes (group A), either alone or in combination with staphylococcus, in three patients conforms to the culture results found by Meleney [1] in his original description.


Multiple coronary artery bypass using sequential technic. The relief of symptoms of myocardial ischemia and its lasting effect may be related to completeness of myocardial revascularization. Multiple bypass grafting to arteries with lesser stenosis and to small arteries can be simplified by use of the sequential technic. This can be done with no added risk, but its ultimate effectiveness will have to be determined at a much later date.


Red cell 2,3-diphosphoglycerate and oxygen affinity. The ease with which haemoglobin releases oxygen to the tissues is controlled by erythrocytic 2,3-diphosphoglycerate (2,3-DPG) such that an increase in the concentration of 2,3-DPG decreases oxygen affinity and vice versa. This review article describes the synthesis and breakdown of 2,3-DPG in the Embden-Meyerof pathway in red cells and briefly explains the molecular basis for its effect on oxygen affinity. Interaction of the effects of pH, Pco2, temperature and 2,3-DPG on the oxyhaemoglobin dissociation curve are discussed. The role of 2,3-DPG in the intraerythrocytic adaptation to various types of hypoxaemia is described. The increased oxygen affinity of blood stored in acid-citrate-dextrose (ACD) solution has been shown to be due to the decrease in the concentration of 2,3-DPG which occurs during storage. Methods of maintaining the concentration of 2,3-DPG in stored blood are described. The clinical implication of transfusion of elderly people, anaemic or pregnant patients with ACD stored blood to anaesthetically and surgically acceptable haemoglobin concentrations are discussed. Hypophosphataemia in association with parenteral feeding reduces 2,3-DPG concentration and so increases oxygen affinity. Since post-operative use of intravenous fluids such as dextrose or dextrose/saline also lead to hypophosphataemia, the addition of inorganic phosphorus to routine post-operative intravenous fluid may be advisable. Disorders of acid-base balance effect oxygen affinity not only by the direct effect of pH on the oxyhaemoglobin dissociation curve but by its control of 2,3-DPG metabolism. Management of acid-base disorders and pre-operative aklalinization of patients with sickle cell disease whould take account of this. It is known that anaesthesia alters the position of the oxyhaemoglobin dissociation curve, but it is thought that this is independent of any effects which anaesthetic agents may have on 2,3-DPG concentration. In vitro manipulation of 2,3-DPG concentration with steroids has already been carried out. Elucidation of the role of 2,3-DPG in the control of oxygen affinity may ultimately lead to iatrogenic manipulation of oxygen affinity in vivo.


The basle PEEP weaner. A versatile device for respiratory assistance. A device to modify the physiological impact of the abrupt transition of IPPV and PEEP to spontaneous breathing is described. It consists of a coaxial breathing system with a spring-loaded reservoir bag and underwater pressure limit. Electric alarms are incorporated.


Comparison of the effects of acupuncture and codeine on postoperative dental pain. The analgesic effects of acupuncture were compared with those of codeine in the treatment of postoperative dental pain in 40 healthy male volunteers 18 to 30 years old. Upon the patient's recovery from local anesthesia (lidocaine), he was asked by a trained observer to classify the intensity of his pain as none, mild, moderate, or severe. He then received one of the following treatments: 1. Placebo: lactose, plus acupuncture placebo 2. Codeine: codeine, plus acupuncture placebo 3. Acupuncture (Ho-Ku): lactose, plus 2 Ho-Ku points 4. Codeine-acupuncture: codeine, plus 2 Ho-Ku points. The pain intensity score was recorded by the observer at half-hour intervals for 3 hours. Patients in treatment groups 2, 3 and 4 showed significantly greater pain relief than those in treatment group 1. For the 1st half hour, there was more pain relief with Ho-Ku alone than with codeine plus Ho-Ko (p less than 0.01). However, for the 2, 2 1/2, and 3-hour periods, codeine plus Ho-Ku produced more pain relief than any of the other treatments.


A comparison of droperidol, diazepam, and hydroxyzine hydrochloride as premedication. A double-blind comparison of the efficacy and safety of droperidol (5 mg), hydroxyzine  HCl (50 mg), diazepam (5 mg), and saline placebo, given concomitantly with meperidine (50 or 75 mg) for preoperative medication, was conducted in 280 female patients scheduled for minor gynecologic procedures. Droperidol proved to significantly superior to the other study drugs in alleviating apprehension (83% of patients calm versus 54, 46, and 34% for hydroxyzine, diazepam, and placebo, respectively). Some drowsiness, occurred in 68 percent of the droperidol-treated patients versus 31, 30, and 21 percent of the other 3 groups, respectively. Global evaluations were consistent with these findings. No clinically significant changes were observed in vital signs in any of the study-drug groups. Adverse reactions were unremarkable in all groups. Significantly less nausea occurred with droperidol than with other treatments, and signficantly less vomiting occurred with droperidol or hydroxyzine. Significantly fewer patients in the droperidol group than in the diazepam group required postoperative antiemetics.


[Dysimmunologic and pseudolymphomatous adenopathies. I. Immunoblastic and plasmocytic lymphadenopathies]. The authors report 9 cases with pseudo-lymphomatous lesions associated with dysimmunitary features. They discuss the correlations between these cases and similar entities, for instance angio-immunoblastic lymphadenopathy (LAID). It seems that all these anatomoclinical syndromes could be referred to as dysimmunitary and pseudolymphomatous adenopathies (ADPL). The first type--ADPL type I--rich in immunoblasts and plasmocytes is defined. LAID is the most common form. The term "dysimmunitary" reflects not only the biological disturbances which accompany these lesions, but also their possible physiopathological mechanism, type I ADPL being apparently due to problem chiefly affecting humoral immunity.


[Silent pyloroduodenal gastrinomas. Apropos of 3 cases]. The authors report three anatomoclinical studies concerning apparently moderately aggressive endocrine tumors developped in the sub-mucosa of the duodenal bulb (2 cases) and of the pyloro-bulbar region (1 case), not connected with the pancreas, and occuring in the absence of a parietal ectopic pancreas. Two of these tumors were ulcerous but the associated syndromes (pains and hemorrhage) did not evoke, clinically, a Zollinger-Ellison syndrome. However, examination with immunofluorescence showed the presence of immunoreactive gastrine in a large number of cells. Having found some similar cases in the literature, the authors precise the features of these silent pyloro-duodenal gastrinomas: it is a variety of carcinoids or of "carcinoid-islet cell tumors". The cells contain argyrophile granules (Grimelius stain) which correspond in electron microscopy to neuro-secretory granules that may be quite different from G. granules. In the absence of significant clinical signs and of a radio-immunologic blood test, the presence of immunoreactive gastrin in the cells is the main feature for the diagnostic of these tumors. These tumors seem to arise from the gastrin cells of the mucosa or from their precursors as is suggested by the transitional forms with the fundus of the glands. Whatever the reason of the peculiar functional behavior, these neoplasms can be easily isolated from the anonymous group of duodenal carcinoids.


[Dysimmunologic and pseudolymphomatous adenopathies. II. Lymphadenopathies rich in epithelial cells]. Besides the dysimmunitary and pseudo-lymphomatous adenopathies rich in immunoblasts and plasmocytes (ADPL type I) five cases showed similar clinical and biological data but with frequently otorhinolaryngologic location. The lesions are characterized by important structural changes and abundant epithelioid cells are comparable to Lukes' type III immunoblastic lymphadenopathies and to Lennert's lymphoepithelioid lymphomas. They must be distinguished from Hodgkin's granulomas which are rich in epithelioid cells. They are perhaps due to a disturbancy bearing mainly on the cellular immunity.


Changes of resistance of enteric bacteria in mice given tetracycline in drinking water. Tetracycline given to mice via their drinking water for long periods changed the gram-negative enteric flora and increased the minimal inhibitory concentration of tetracycline for Proteus and Escherichia coli in the feces.


Immunosuppression in deer mice with experimentally induced trypanosomiasis. Light and electron microscopic examinations of deer mice (Peromyscus maniculatus) chronically infected with Trypanosoma equiperdum revealed hyperplasia of germinal center lymphocytes (germanocytes) in the lymph follicles of spleen and lymph nodes and infiltration of the splenic red pulp cords and nodal medullary cords with plasma cells. Proliferation and infiltration of plasma cells caused disruption of the B- and T-lymphocyte areas in these organs. Stimulation of splenic lymphocytes in vitro by phytohemagglutinin and concanavalin A revealed marked depression in T-lymphocyte response; stimulation with lipopolysaccharide and pokeweed mitogens showed depression of B-cell response. Deer mice infected with virulent trypanosomes had decreased immunologic response to injection of sheep red blood cells, whereas deer mice given radioattenuated trypanosomes had normal to enhanced immunologic response to injection of sheep red blood cells.


Flow rates from an intermittent positive pressure breathing-anesthetic delivery apparatus for horses. Inspiratory flow rates were measured and compared in an equine intermittent positive pressure breathing-anesthesia delivery apparatus powered by a positive phase ventilator, a positive-negative phase ventilator, and a modified positive phase ventilator with automatic flow acceleration at driving pressures of 2,600, 4,400, and 5,200 mm of Hg (50, 85, and 100 psi). The last-named apparatus consistently produced the highest flows for a given ventilator setting and driving pressure. Regardless of the unit used, the greater driving pressures and high ventilator range settings produced the greatest flows.


R factor types found in Salmonella typhimurium and Escherichia coli isolated from calves in a confined environment. Typing of R factors by genetic properties was done with Salmonella typhimurium and Escherichia coli isolated from calves on a feedlot where epizootics of clinical or subclinical calf salmonellosis had repeatedly occurred during 5 years. Forty-nine R factors from S typhimurium were fi- (no fertility inhibition) and spp- (no restriction against phage lambda vir). Twenty-three (46.9%) of them belonged to compatibility group Ialpha and the remainder were nontypable. Fourteen R factors from E coli belonged to different genetic types: fi+ (11=78.6%) and fi- (3=21.4%); spp+ (1=7.1%) and spp- (13=92.9%); compatibility groups FII (5=35.7%), N (1=7.1%), and nontypable (8=57.2%). In contrast to the R factors of S typhimurium, 9 (64.3%) of the 14 R factors of E coli carried resistance against aminobenzyl penicillin with or without kanamycin resistance. The compatibility groups of R factors of S typhimurium seemed to be useful as a subsidiary epizootiologic marker in this feedlot.


Frequency of ovarian follicular cysts, reasons for culling, and fertility in Holstein-Friesian cows given gonadotropin-releasing hormone at two weeks after parturition. Holstein-Friesian cows (n=204) were given saline solution or 200 microgram of gonadotropin-releasing hormone (GnRH) by intramuscular injection at 8 to 23 days after parturition. Of cows culled, fewer GnRH-treated cows were culled for infertility, compared with number of cows given saline solution (26 vs 57%; P less than 0.05). Frequency of ovarian follicular cysts was reduced from 15.2% in controls to 5.7% for cows given GnRH (P less than 0.01). The interval to 1st insemination, interval to conception, and inseminations per conception did not differ among saline solution or GnRH-treated cows which remained in the herds. These data provide evidence for reduction in infertility and reproductive disorders in early postpartum dairy cows given GnRH as a prophylactic.


Migration-inhibition response of peripheral leukocytes to tuberculin in cats sensitized with viable Mycobacterium bovis (BCG). Delayed hypersensitivity reactions to antigens injected intradermally are reported as not occurring in the cat. Cats infected with viable Mycobacterium bovis (BCG) organisms developed a transient migration-inhibition response of their leukocytes to tuberculin. The migration-inhibition response subsided in 6 weeks in spite of the persistance of viable BCG. Significant intradermal reactions to tuberculin 60 days after BCG injection did not occur. The response of the cat differs from that of many mammalian species in which strong in vivo and in vitro delayed hypersensitivity type reactions persist with mycobacterial infections. Despite the lack of continued measurable delayed hypersensitivity, the cat appears to have adequate resistance to mycobacterial infections.


Isolation of Mycobacterium bovis from the prepuce of a herd bull. A tuberculous lesion was found in the prepuce of a 5-year-old tuberculin-positive herd bull at necropsy. Microscopic examination revealed granulomas with Langhans'-type giant cells; Mycobacterium bovis was isolated. The bull had been used in artificial insemination procedures and for natural breeding.


[Treatment with Chloranphenicol of neonatal sepsis-meningitis by gram-negative bacteria (author's transl)]. Eight newborn infants having previously received broad spectrum antibiotics were treated with intravenous chloranphenicol succinate for sepsis-meningitis during a klebsiella neumoniae outbreak. Five of them survived without sequelae. Over the third week of treatment two infants developed a transient bone marrow suppresion accompanied by a "pseudo-septic" clinical picture; this syndrome, that we have not found previously reported, was benign, disappearing when the drug was discontinued.


The literature and history of internal medicine: an annotated bibliography. This bibliography includes 58 books on the history of various medical subspecialties and general reference works useful in obtaining historical and biographical material relevant to internal medicine and related areas. In addition to a brief review of the contents of each volume, information is included on their publication and availability. It is designed to serve as an introduction to the history of internal medicine as well as a source of reference.


Amyloid deposition in a renal transplant in familial Mediterranean fever. A patient with familial Mediterranean fever and amyloidosis who received a cadaver renal transplant 6 1/2 years ago was studied to determine the relation of the serum precursor of secondary amyloid (SAA) to the clinical course and to the deposition of amyloid in the transplant. Amyloid fibrils extracted from the patient's kidneys contained protein AA as a major constituent, which identified the amyloid as secondary. Protein AA antiserum was used in an indirect immunofluorescent technique to stain amyloid deposits in sections of the original kidney. A renal biopsy at 2 years showed no amyloid, but a renal biopsy at 4 years showed amyloid. Serum levels of SAA from 3 years before transplant to 6 years after transplant were elevated throughout most of the course.


Lymphoma presenting in bone: results of histopathology, staging, and therapy. Lymphoma presenting in bone (that is "reticulum cell sarcoma of bone") is a form of extranodal lymphoma historically described as frequently localized (this is, stage IE or stage IIE). Between 1970 and 1975, 14 patients with this entity were seen at the National Cancer Institute. This group had a variety of histologic subtypes of diffuse lymphoma. Thorough staging showed extensive disease (stage IV) in 12 of these patients (86%). In 10 of these the metastatic disease was unsuspected clinically. Seven patients achieved complete remissions after treatment was combination chemotherapy alone (two patients), irradiation alone (one patient), surgery alone (one patient), and both chemotherapy and irradiation (three patients) and are alive and free of disease 11 + to 70 + months after diagnosis. The other seven patients did not achieve complete remission status and have all died. Although lymphomas presenting in bone may occasionally be localized, careful staging in this series frequently showed extensive disease and altered the therapeutic approach.


[The relationship between the degree of dissemination of pharyngolaryngeal tumours and immunological changes (author's transl)]. An investigation was carried out on 34 patients with malignant pharyngolaryngeal tumours which had been operated on, microscopic changes in the regional ganglia (sinusal histocytosis, hypertrophy of the germinal centres, the paracortical area, the number of pyroninophilic plasmocytes, the behaviour of the mastocytes) and into certain cell immunity tests (the cytological formula of the inflammatory reaction in the cutaneous window, intracutaneous reaction to tuberculin, the time taken to reject normal skin homografts). The results were correlated with the presence or absence of ganglionic metastases. A relative correlation was found between the absence of metastasis, and manifest sinusal histiocytosis, the hypertrophied paracortical zone, the considerable number of young mastocytes, early mobilisation of macrophages, a normal amount of time taken to reject the cutaneous homograft. These tests enable certain prognostic conclusions to be drawn and draw attention to the need, in some cases, to build up the low level of immunity.


Serum fibrinogen/fibrin degradation products in patients with ovarian carcinoma. Fibrinogen/fibrin degradation products (FDP) in the serum of 50 patients with ovarian carcinoma was examined by Nyléhn's immunochemical method. FDP were rarely found in early but frequently in advanced stages of ovarian tumours. With successful treatment, FDP decreased; otherwise persistently high FDP concentrations were observed in the serum. The determination serum FDP might be a valuable aid in assessing the effect of treatment.


Predominance of extreme geographical proximity of the spouses of heirs to independent farms in a mountain valley in Norway between 1600 and 1850. The marriages contracted between 1600 and 1850 in the parishes Vang and Slidre in the mountain valley of Valdres in Norway were investigated, using the information in the genealogical and local history of the parishes and in various public archives. The parishes functioned as a marriage isolate, in spite of regular communication with neighbouring districts. Only 54 of 4334 marriages were with residents outside the parishes, and marriages with a non-farming class (clergy) were as rare (47); 1130 marriages were probably between offspring of crofters and independent farmers. The further analysis concerns 3103 marriages contracted by the eldest sons and other heirs to 463 of the 493 farms, with members of the farming class within the parishes. Because of the linear settlement with clusters of same-named farms along both sides of the river, marital distance was measured by counting the number of farm-clusters (neighbourhood steps) between places of birth. In comparison with expectation when the marriage partner is chosen at random, marriages within the cluster occurred 13 times more frequently than expected, with an adjoining cluster 8 times more frequently and with a neighbour 1-2 clusters away 6 times as frequently as expected. One-third of the 3103 marriages were contracted within a distance of two clusters or less, and 60% eight clusters or less apart. A marital distance of 15 clusters (= 7 km) included 74% of the marriages. The predominance of a marriage pattern based on such geographical proximity must necessarily imply similarity in genetic structure of the descendants. Close consanguineous mating was apparently consciously avoided. This extreme geographical proximity of the spouses of heirs to the independent farms is probably explained by the function of a marriage as a contract to benefit the farm: promoting good neighbourliness and preventing quarrels and lawsuits related to the already very complicated ownership of cultivated land.


[Comparative study of the physicochemical properties of the surface of Escherichia, their sensitivity to ampicillin and tetracycline and their capacity to absorb tetracycline]. Development of resistance to ampicillin and tetracycline in Escherichia resulted in an increase in the electrokinetic potential and a decrease in the level of hydration and isoelectric values of pH. The changes in the hydration level mainly depended on the accompanying dissociation. Studies on 3H-tetracycline binding revealed a low accumulation capacity of the resistant mutants. The rate of 3H-tetracycline binding did not depend on the changes in the physico-chemical parameters of the cell surface due to resistance and dissociation.


[Effect of amphotericin B on the enzyme system of Candida albicans]. The mechanism of amphotericin B action was studied with the aid of cytochemical methods providing determination of the activity of the 4 main enzymes characterizing the cell energetics, i. e. succinate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase and glucose-6-phosphate dehydrogenase inside the cell. With an increase in the concentration of amphotericin B in the medium the activity of all the 4 enzymes decreased, the percentage of the inactive cells being regularly increased. Changes in the fermentative activity of C. albicans as dependent on the incubation time with the antibiotic were studied. Only the respiration activity decreased in 2 hours. As a result of a 4-hour exposure to the polyen in the cells of C. albicans the activity of the lactic acid fermentation, respiration through succinate dehydrogenase and activity of the pentose shunt decreased 1.5--2 times. In 24 hours of incubation the activity of the above decreased 80--90 per cent as compared to the activity of the initial culture.


[Action of various surface-active substances on the genetic transmission of R-plasmids in E. coli]. The effect of 4 groups of surface active-substances (SAS) on conjugation and transduction transfer of plasmid RIdrd from the donor of E. coli J 5-3 to the recipient of E. coli C600 was studied. It was shown that the anionic SAS (8 compounds) had the highest inhibitory effect. They completely inhibited both the conjugation and the transduction transfer of R-plasmids. The amphoteric SAS, i. e. tego-51 and ampholan had the same effect only on the transduction R-transfer. The conjugation R-transfer was inhibited by the above compounds to a significant extent but not completely, i. e. by 70.8 and 361.9 times respectively. The effect of the non-ionogenic preparations, i. e. sintanol DT-7 was even less (the inhibition coefficients of 54.8 and 22.8 on conjuction and transduction respectively). The cationic SAS, i. e. catamine AB and HIPC-200 had no effect on the genetic R-transfer. It was shown that the anionic SAS had a phagocytic effect on phage Plks. It is of interest to note that the anionic SAS, i. e. sintanol NP-3 effectively suppressed the conjugation transfer even in a concentration of 100 gamma/ml which was 1000 times lower than the subbacteriostatic one. The effectiveness of the anionic SAS did not depend on the length of the dydrocarbon chain and was the same in separate homologues and their mixtures. The high inhibitory activity of most of the SAS and especially the anionic ones with respect to both the conjugation and the transduction R-transfer was of interest.


[Effect of the cultivation conditions of Candida species yeast-like fungi on their sensitivity to levorin]. The effect of levorin on yeast-like fungi under (different) cultivation conditions was studied. It was shown that the medium composition and incubation temperature affected the results of determination of the test-culture sensitivity to levorin. There was correlation between the time of the population lag-phase and the critical time of the zone formation and these values depended on the temperature of the test-microbe vegetation. Strain 037 of C. utilis was more sensitive to levorin and had a longer lag-phase as compared to the other species of the yeast-like fungi, which provided favourable conditions for formation of the growth inhibition zones.


[Sensitivity of Proteus hauseri bacteria to chemotherapeutic preparations depending on the cultivation conditions and on the composition of the nutrient medium]. Sensitivity of 227 Proteus strains isolated from patients was studied comparatively using the agar-diffusion method (disks) and the method of serial dilutions. Marked differences in the numbers of the strains resistant to benzylpenicillin and chloramphenicol were found with the above methods. It was shown that the ingredients of Ploskirev's medium significantly (by 2.8--13.5 times) inhibited the antibacterial activity of streptomycin, neomycin, monomycin, kanamycin, ampicillin and nalidixic acid and had practically no effect on the activity of benzylpenicillin, chloramphenicol and furazolidone. The values of the MIC of the drugs used in the experiment with liquid media correlated with those obtained with Sabouro's medium, which provided recommendation of the latter for determination of Proteus sensitivity by the method of serial dilutions in the solid medium, Cultivation of Proteus at a temperature of 40 degrees C resulted in a decrease of the resistance to most of the drugs tested by (by 3--12.4 times).


[Action of tetracyclines on the pseudotuberculosis microbe in vitro experiments and their effectiveness in experimental pseudotuberculosis in white mice]. 227 out of 228 strains of pseudotuberculosis microbes studied in vitro proved to be sensitive to tetracyclines. The MIC of tetracycline and morphocycline ranged within 0.25--25 gamma/ml. The MIC of chlortetracycline and oxytetracycline was somewhat lower, i. e. 1--50 gamma/ml. When administered intramuscularly all the tetracyclines had pronounced therapeutic effect in experiments with albino mice infected with the antibiotic sensitive strains of J. pseudotuberculosis. Chlortetracycline proved to be the most active drug in treatment of albino mice per os.


Amoxicillin therapy of acute urinary infections in adults. Fifty-two patients, 48 females and 4 males, with suspected urinary infection were treated with amoxicillin. Twenty-two females with presumed bladder infection were treated with amoxicillin, 250 mg three times a day for 7 days; 26 females and 4 males with presumed renal infection were treated with amoxicillin, 500 mg three times a day for 14 days. Five patients were immediate treatment failures, with positive urine cultures during therapy. All five patients had been infected with amoxicillin-resistant urinary pathogens. Three patients, treated as for bladder infections, reinfected during 6 weeks of follow-up, and only one relapsed. Two patients, treated as for renal infections, reinfected, whereas four relapsed. During therapy, amoxicillin-susceptible gram-negative rods were eradicated from the periurethral area in all but one patient. Of 28 patients studied, 19 acquired a predominant growth of either resistant aerobic gram-negative rods or Candida albicans from periurethral cultures. Our findings suggest that these two regimens of amoxicillin achieve satisfactory cure rates in urinary infection, but both regimens significantly alter the normal periurethral flora.


Antimicrobial therapy of experimental group B streptococcal infection in mice. Group B beta-hemolytic streptococci (GB-BHS) frequently cause severe infection in newborns. Previous in vitro studies showed accelerated killing of GB-BHS by ampicillin plus gentamicin as compared with ampicillin alone. To extend the in vitro observations, mice were infected experimentally with GB-BHS and treated with gentamicin plus ampicillin or ampicillin alone. Untreated mice died within 10 to 48 h. Compared with treatment with ampicillin alone, ampicillin-and-gentamicin therapy resulted in improved survival when the antibiotics were given in established infection or as a single dose at the time of infection. Ampicillin and gentamicin accelerated the clearing of bacteremia as compared with treatment with ampicillin alone. In view of these findings, the therapy of GB-BHS infection in newborns and other patients should be reconsidered in that a combination of ampicillin or penicillin G plus gentamicin might be superior to the use of ampicillin or penicillin G alone.


Energy coupling factor as target of colicin K: characterization of a colicin K-insensitive ecf mutant of Escherichia coli. We isolated a colicin K-insensitive energy uncoupled mutant of Escherichia coli. This mutant was presumed to be an ecf mutant as evidenced by its similarity to a known ecf mutant (M. A. Lieberman and J.-S. Hong, 1974) with respect to the mutational site, reversion pattern, and defects in transport and growth. The mutation conferring the colicin K-insensitivity resided in the ecf gene as the majority of the secondary mutations overcoming the ecf phenotype reverted the colicin K-insensitive phenotype to colicin K-sensitive. The insensitivity of the mutant to colicin K was not due to either a defect in adsorption or to a lack of the energized membrane state. The defect was most probably due to the inability of colicin K molecules to interact with their target. Our previous studies concerning the role of the ecf gene product in energy coupling to active transport and oxidative phosphorylation support the contention that the ECF protein is itself the direct target of colicin K.


Semiautomated turbidimetric bioassay for the ionophore A23187. The inhibitory effect of A23187 against Staphylococcus aureus was used to quantitate the activity of this ionophore in fermentation samples and in isolation and crystallization samples. The assay was shown to be rapid and reproducible.


Double-osmotic-shock procedure to prepare gentamicin adenine mononucleotide transferase for the enzymatic assay of gentamicin. The release of gentamicin adenine mononucleotide transferase during single, cold, osmotic-shock treatment of Escherichia coli K-12 W677/HJR66 is not always maximal. The quantity of gentamicin adenine mononucleotide transferase in osmotic extracts could be significantly increased when a double-shock procedure was performed.


Beta-lactamase-directed barrier for penicillins of Escherichia coli carrying R plasmids. Strains of Escherichia coli and Salmonella typhimurium carrying R plasmids, which were obtained from ampicillin-resistant clinical isolates of E. coli and Klebsiella spp. and specified either the type IIIa (TEM-type) or type Va (oxacillin-hydrolyzing) beta-lactamase, are resistant not only to ampicillin but also to carbenicillin and sulbenicillin. The latter two derivatives, however, are poorly hydrolyzed in vitro by the beta-lactamases. Although values of K(m) of the enzymes are lower for sulbenicillin and carbenicillin than for ampicillin, the ratios of V(max) to K(m) for sulbenicillin and carbenicillin are not high enough to explain the high resistance in E. coli bearing the R plasmid. Two mutants of the plasmids conferring a temperature-sensitive ampicillin resistance were induced by nitrosoguanidine treatment. It was confirmed that E. coli CSH2, harboring the mutant plasmid, produces a temperature-sensitive beta-lactamase and is resistant only at low temperatures (below 33 degrees C), but not at 42 degrees C, to ampicillin, sulbenicillin, and carbenicillin simultaneously. It is thus concluded that beta-lactamase itself is responsible for the mechanism of resistance not only to ampicillin but also to sulbenicillin and carbenicillin, even though the enzyme as determined in cell-free extracts hydrolyzes the latter two drugs poorly. An unknown barrier for sulbenicillin and carbenicillin directed by beta-lactamase in E. coli strains carrying R (bla) plasmids is postulated.


Inhibition of amino acid transport in Escherichia coli by some beta-lactam antibiotics. Among 10 antibiotics tested, cephaloridine and cephalothin showed the greatest inhibition of proline active transport. Ethylenediaminetetraacetate pretreatment of the cells did not enhance inhibition by any of these 10 antibiotics. The inhibition of active transport of 10 additional amino acids by cephaloridine and cephalothin was studied. Both antibiotics inhibited transport of three amino acids which, like proline, have transport systems resistant to osmotic shock; neither antibiotic inhibited transport of the remaining amino acids, including three with shock-resistant and four with shock-sensitive systems.


Altered surface properties of Escherichia coli associated with a specific amino acid change in the S12 ribosomal protein of streptomycin-resistant mutants. Escherichia coli mutants resistant to streptomycin exhibited differences in countercurrent distribution from the parental strains. The degree of difference from the parental strain correlated with the degree of restriction of translation and thus the particular strA allele. The changes in countercurrent distribution in the phase systems used probably resulted predominantly from surface charge alterations. The differences in countercurrent distribution in these and other mutants may be a useful selective technique to obtain different types of mutants for which specific selective techniques may not be available. In addition, it appears that the surface properties of cells, which determine their position in countercurrent distribution, are a function of the translational efficiency and fidelity, and that the surface of cells consists of a mosaic that is an expression of this translational fidelity.


Destruction of coliforms in water and sewage water by dye-sensitized photooxidation. A new approach to disinfection of water and sewage water, by oxidative destruction of microorganisms by photosensitization, is described. Samples of water and sewage water, to which an inoculum of fecal Escherichia coli had been added, were exposed to solar radiation in the presence of a dye sensitizer, under continuous aeration. The effects of the sensitizer methylene blue at concentrations of 0 to 10 mg/liter, different radiation times from 0 to 2 h, and sunlight intensities of 0, 68, and 2,030 muE/m2 per s were investigated. In laboratory-scale experiments, 1.3 X 10(9) coliforms in 100 ml of oxidation pond municipal sewage water containing 0.5 mg of methylene blue were destroyed in about 30 min. Similar results were obtained with nonchlorinated potable water. These results demonstrate the possibilities available for the disinfection of water and sewage water by this method.


Mercury resistance and R plasmids in Escherichia coli isolated from clinical lesions in Japan. The mercury and antibiotic resistance of 338 strains of Escherichia coli isolated from hospital patients was determined. Resistance to mercury was found in 58.6% of the isolates. The frequencies of resistance to streptomycin (Sm), tetracycline (Tc), chloramphenicol (Cm), kanamycin (Kan), cephaloridine (Cer), and gentamicin (Gm) were 66.3, 60.3, 56.5, 42.9, 32.1, and 1.5%, respectively. Among the above, 198 mercury- and antibiotic-resistant isolates were selected and tested for their ability to transfer the resistance to susceptible strains of E. coli K-12 and Klebsiella pneumoniae JK5. R plasmids carrying mercury resistance were demonstrated in 89.9% of the mercury-resistant strains of E. coli. Furthermore, R(Hg,Sm,Tc,Cm) plasmids were demonstrated most frequently, followed by R(Hg,Sm,Tc,Cm,Kan), R(Hg,Cm,Kan), and R(Hg,Sm,Tc,Cm,Kan,Cer) plasmids.


New microbial growth factor.

New microbial growth factor. A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a new microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight, and it has high specific activity. When added to the diets for a meadow vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.


Osmoregulation in symbiosis-independent mutants of Bdellovibrio bacteriovorus. Bdellovibrios capable of axenic growth grow in a cell-free medium at a rate considerably lower than that attainable in a two-membered culture with Escherichia coli. The axenic growth rate may be improved either by adjustment of the osmosity of the medium or by the addition of low concentrations of spermine.


Gentle lysis of Staphylococcus aureus at low temperature. A low-temperature lysis procedure for Staphylococcus aureus is described. It is simple and requires no special equipment.


Use of nuclepore filters for counting bacteria by fluorescence microscopy. Polycarbonate Nuclepore filters are better than cellulose filters for the direct counting of bacteria because they have uniform pore size and a flat surface that retains all of the bacteria on top of the filter. Although cellulose filters also retain all of the bacteria, many are trapped inside the filter where they cannot be counted. Before use, the Nuclepore filters must be dyed with irgalan black to eliminate autofluorescence. Direct counts of bacteria in lake and ocean waters are twice as high with Nuclepore filters as with cellulose filters.


Comparison of two direct-count techniques for enumerating aquatic bacteria. Planktonic bacteria from an estuary were concentrated on membrane filters and counted with both a scanning electron microscope and an epi-illuminated fluorescent microscope. Counts on 0.2 micron Nuclepore filters (polycarbonate) were significantly higher (P less than 0.001) than counts on 0.2-micron Sartorius filters (cellulose). In contrast, there was not a statistically significant difference between the two techniques when Nuclepore filters were used (0.5 less than P less than 0.9). The average cell volume from this study area was 0.047 micron3. The estimated number of bacteria ranged from 10(6) to 10(7) bacteria per ml, representing from 4 to 40 mg of C per m3.


Changes in lipid composition of Escherichia coli resulting from growth with organic solvents and with food additives. Cells of Escherichia coli contain an altered fatty acid and phospholipid composition when grown in the presence of sublethal concentrations of a variety of organic solvents and food additives. The diversity of compounds examined which caused these changes indicates that no single catabolic pathway is involved. Many of the observed changes are consistent with the hypothesis that cells adapt their membrane lipids to compensate for the presence of these compounds in the environment. Both sodium benzoate and calcium propionate caused the synthesis of unusual fatty acids.


Two-temperature membrane filter method for enumerating fecal coliform bacteria from chlorinated effluents. Reports indicate that the standard membrane filter (MF) technique for recovery of fecal coliform bacteria from chlorinated sewage effluents is less effective than the multiple-tube (or most-probable-number [MPN]) procedure. A modified MF method was developed that requires a preincubation period of 5 h at 35 degrees C followed by 18+/-1 h at 44.5 degrees C. This procedure was evaluated by using both laboratory- and plant-chlorinated primary and secondary effluents. Results obtained by the modified MF method compared favorably with those of the MPN technique for the enumeration of fecal coliforms from chlorinated effluent. Agreement between these two methods was greatest with samples from secondary treatment plants. The average recovery of fecal coliforms by the standard MF procedure was only 14% that of the MPN method, whereas with the modified technique recovery was increased to 68% of the MPN counts. Enhanced recovery resulting from a simple modification in the incubation schedule makes the MF method a valuable adjunct for enumerating fecal coliforms from chlorinated effluents.


Comparison of limulus amebocyte lysates and correlation with the United States Pharmacopeial pyrogen test. Six limulus amebocyte lysate (LAL) preparations obtained from five different suppliers were evaluated for sensitivity, dependability, cost, convenience of use, and correlation with the United States Pharmacopeial (USP) rabbit pyrogen test method. Endotoxins from various gram-negative microorganisms were used for the evaluation. Major differences among the LAL preparations lie in the area of sensitivity. Differences, up to 100-fold, exist in the sensitivity of the various LAL preparations to the same endotoxin. The LAL tests in general were 3 to 300 times more sensitive than was the USP rabbit pyrogen test method. The LAL and the USP rabbit pyrogen test data correlated well when the endotoxin in a relatively pure and undegraded form was examined. However, large discrepancies in correlation were found when partially degraded endotoxins were compared. One LAL preparation responded to both intact and degraded endotoxin, whereas others responded only to intact endotoxin; the latter closely correlated with the febrile response of the rabbit. Therefore, proper selection of an LAL preparation is important for its application in clinical, pharmaceutical, public health, and environmental areas.


Use of the Minitek system for characterizing lactobacilli. Incubation of inoculated substrates of the Minitek system in anaerobic GasPak jars provided a method that produced results comparable to those of conventional tubed media for characterizing species of Lactobacillus. The use of sterile mineral oil to overlay inoculated substrate disks was responsible for erroneous results.


Pemphigus vegetans of Hallopeau: immunofluorescent studies. Immunofluorescent techniques were used in the study of tissue from a patient with pemphigus vegetans of Hallopeau. The findings were typical of pemphigus, confirming the propriety of classifying this entity as a benign variant of pemphigus, rather than a disease of purely microbial etiology. The question is raised whether other types of vegetating pyodermas actually are separate diseases or represent a spectrum of pemphigus with the clinical appearance dependent on the patient's immunity to his disease. Immunofluorescent studies are proposed as a basis for classification.


Beclomethasone dipropionate aerosol in treatment of perennial allergic rhinitis in children. Forty-four children with perennial allergic rhinitis who had failed to respond to conventional therapy, including sodium cromoglycate insufflation and hyposensitization, were treated with beclomethasone aerosol given intranasally. The study was conducted in a double-blind manner, the patients being allocated active drug or placebo for a 3-week period, followed by a 1-week rest period. The treatments were then crossed over for a period of 3 weeks. After this all children were put on active drug and followed-up at monthly intervals for a period of 3 months. Results were graded as either success of failure, and success had to be an unequivocal vote for the active drug by the patient, parent, and doctor. An overall success rate of 77% was obtained and no untoward or toxic effect was noted in any child. Tetracosactrin tests in 5 children remained normal at the end of the study period. We found intranasal beclomethasone dipropionate to be the most effective drug we have used for treating perennial allergic rhinitis in children.


Intramuscular salbutamol in treatment of acute exacerbations of childhood asthma. Salbutamol was given by the intramuscular route to children aged 3 to 16 years with an attack of asthma. Results with a dose of 8 microgram/kg were favourable but suggested that a higher dose might be more so. 16 children thereafter were treated with 20 microgram/kg which produced a greater mean increase in peak expiratory flow rates (PEFR) without increase in side effects. This dose was then used in a double-blind crossover trial of salbutamol against a saline placebo. Half of 36 children treated with 20 microgram/kg showed rapid clinical improvement, the maximum rise in PEFR occurring within the first 5 minutes. A rise in pulse rate and occasionally a tremor were the only side effects noted. We conclude that intramuscular salbutamol 20 microgram/kg is a safe and useful initial medication in the management of the asthmatic child suffering an acute exacerbation.


Evaluation of Vickers-Trexler isolator in children undergoing bone marrow transplantation. Four children, 5 months to 15 years of age, underwent bone marrow transplantation in Vickers-Trexler isolator tents. Two grafts were elective. During 170 days of isolation no clinical infections due to exogenous micro-organisms developed despite severe immunodeficiency. The decontamination regimen and sterile procedures used, as well as the microbiological results, are described. This form of isolation in paediatric practice was found to be highly acceptable to both patients and staff.


Polymyalgia rheumatica. Abrupt and gradual withdrawal of prednisolone treatment, clinical and laboratory observations. Eighteen patients with polymyalgia rheumatica had corticosteroid treatment withdrawn abruptly under close observation. In each case polymyalgic symptoms reappeared but were controlled rapidly when prednisolone was reintroduced. Prednisolone withdrawal was then started by slow decrements of dose. In no patient was it possible to withdraw prednisolone treatment, after using either method, during the period of observation.


Double-blind study of erbium 169 injection (synoviorthesis) in rheumatoid digital joints. A double-blind study of erbium 169 injection into rheumatoid digital joints was carried out with saline as control. 201 joints in 36 patients were studied (137 metacarpophalalangeal, 64 proximal interphalangeal). Erbium 169 was injected into 121 joints and saline water into 80 joints. Local injection of corticosteroids was given to both groups. A definite improvement was observed in 55% to 58% of cases with erbium 169 (+prednisolone acetate) and in 26% to 28% of cases with saline (+prednisolone acetate). The difference was highly significant.


When should the third renal transplant rejection episode be treated? Recent reports cite better survival when repeatedly rejecting renal allografts are removed and patients returned to hemodialysis. However, the criteria for graft removal remain undefined; although some reports recommend removing all kidneys undergoing a third rejection. In our series (1968-1973) of 316 patients with technically successful first grafts followed 2(1/2)-8 years, graft survival was inversely related to the number of rejection episodes. One hundred per cent of kidneys without rejection are currently functioning or functioned at the time of death compared to 90% with one rejection, 67.4% with two and 21% with three. However, 40% of kidneys having three rejection episodes functioned longer than one year after treatment of the third rejection episode. In an attempt to determine the predictability of one year graft survival or failure following treatment of the third rejection, a formula was developed that correctly predicted in 33 of 38 (87%) patients. The formula was based on information available prior to treatment of the third rejection episode, and represents an index of baseline renal function (serum creatinine after second rejection episode) and two indices of the severity of rejection episodes (serum creatinine change between the first and second rejection episodes; rapidity of sequential rejection).Following its derivation, the formula was applied to a second group (1974) of 19 patients having had three rejection episodes. The formula correctly predicted one year allograft survival or failure following treatment of the third rejection episode in 68% of these patients. A striking finding of our review was a significant difference in current patient survival between those having no rejection episodes (89%) and those having one or more rejection episodes (65%) (p < .00001). There was no significantly greater long-term curtailment in survival if more than one rejection eipsode was treated. Patients having one rejection eipsode seemed to die from varying causes and at varying time periods. Patients dying after two or more rejection episodes had an increased incidence of deaths due to bacterial infection.


Fungus infections after liver transplantation. The problem of fungus infections after liver transplantation was studied. In 100 consecutive recipients of orthotopic liver homografts there were 10 and 8 examples, respectively, of localized and disseminated infections caused by Candida species. Candidemia was demonstrated in 8 of these 18 patients. One patient who had a localized Candida infection also had disseminated cryptococcosis. An additional 31 patients were infested in that Candida could be cultured from sites where it is not normally found, such as the blood (8 examples), urine (8), ascitic fluid (8), and wounds (22). This exorbitant incidence of monilial infections and infestations was associated with a high frequency of complications involving the homograft as well as the hosts' gastrointestinal tract during the post-transplantation period. The yeasts found in blood, urine, ascitic fluid and elsewhere were thought to have originated from the gut. Ten of the 100 patients had aspergillosis which was localized in 7 instances and disseminated in 3. The lung was the most frequently affected organ. The fungus infections played a contributory role in the downhill course of our patients but in the event of death more fundamental and more frequent causes of failure were technical complications involving the homografts, difficulties in controlling rejection with reasonable immunosuppressive doses and bacterial sepsis. Suggestions have been made for the better control of fungal infections in liver recipients.


Surgical treatment of pulmonary aspergilloma. Fourteen patients with aspergilloma (fungus ball) were reviewed. Hemoptysis was the major symptom (93%). Chest roentgenograms disclosed a "fungus ball" in every patient, and the mycelia of Aspergillus fumigatus were recovered from all resected specimens. One of three patients treated by pneumonectomy died post-operatively. A lobectomy was performed in ten patients, and segmental resection in one without mortality or significant morbidity. There has been no evidence of recurrence in a follow up of six months to ten years. On the basis of this experience and a review of the literature, excision of a solitary "fungus ball" is recommended when the diagnosis is made. Non-surgical therapy should be reserved for patients whose general medical status or pulmonary reserved prohibit resection.


Treatment of peptic ulcer disease in the renal transplant patient. This study reviews previous reports of peptic ulcer disease in kidney transplant recipients and includes our own experience. Between 1968-1976, 12 transplant centers reported on gastrointestinal complications occurring in 1853 renal transplant recipients. Among these are 52 patients in whom peptic ulcers developed before trnasplantation and 72 patients in whom peptic ulcers developed after transplantation. Included are 21 patients with peptic ulcer from 115 renal transplant recipients at VA Wadsworth Hospital. Patients who were operated upon for peptic ulcer before trnasplant were compared to patients with peptic ulcer before transplant but who were not operated upon. Ulcer recurrence was significantly lower in the operated group p less than .0003. Following transplantation 59 of 68 patients with peptic ulcer disease presented with bleeding or perforation. Mortality was high: 31 deaths in 72 patients (43%). Symptoms usually occurred early, 74% in 6 months, but 19% occurred after one year. The mortality from duodenal, gastric, combined gastric and duodenal and recurrent ulcers did not differ significantly. Elective surgery is indicated for peptic ulcer when demonstrated before or after kidney transplantation.


Pseudorejection: factors mimicking rejection in renal allograft recipients. Serum creatinine level is used as a major measure of post-transplant renal function at most centers. A significant elevation of creatinine level suggests allograft rejection. However, other factors affect renal function in the transplant recipient and each may cause an elevation in serum creatinine level, suggesting a rejection episode. It is important to make the correct diagnosis and not treat these episodes with anti-rejection therapy. We reviewed the course of patients transplanted between 1969 and 1974 to determine the pathogenesis of creatinine elevations retrospectively found to be due to causes other than rejection. Six distinct causes were found: hyperglycemia, ureteral obstruction, infection, lymphocele, arterial stenosis, and recurrence of the original disease. Each of these is discussed individually. In order to make the diagnosis of pseudorejection, a high index of suspicion is necessary.


Comparison of the fecal microflora of Seventh-Day Adventists with individuals consuming a general diet. Implications concerning colonic carcinoma. Qualitative and quantitative fecal microflora was studied in a double blind fashion in 28 subjects. Fourteen were Seventh-Day Adventists, who were strict vegetarians, while the remaining 14 subjects were individuals consuming a general western diet. No statistically significant differences were identified in the fecal microflora of the two groups. The bacteriologic analysis included total aerobes and total anaerobes as well as each of the major fecal aerobes and anaerobes. This study seems to indicate that the dietary intake of animal fat and protein does not significantly alter the fecal microflora, a possibility which has previously been suggested as being part of the explanation for the higher incidence of colonic carcinoma in those who consume meat compared with vegetarians. It does not, however, invalidate the concept that dietary animal fat does increase bile acid degradation within the gastrointestinal tract, a factor which has been related to colon cancer. Future studies should be directed at identifying the factors that may be present in the gastrointestinal tracts of vegetarians which modify the ability of their colonic microflora to degrade bile acids, an essential step in the production of intraluminal carcinogens or co-carcinogens.


Guilds, boards, and hobgoblins.

Guilds, boards, and hobgoblins. The American specialty board system is viewed in the historical perspective of a quest for quality assessment of surgical trainees. Beginning with the American Board for Ophthalmic Examinations in 1916, a system of 22 boards has developed which, by their training requirements and examinations, essentially dictate the length and content of all postgraduate educational programs. The time has come for the boards, as a powerful force in postgraduate education and in organized medicine, to reassess their position and to be sensitive to the responsibilities they have for the future. The events of history suggest six changes that might be profitable. (1) Recognize their purpose to be broader than the administration of certifying examinations. (2) Recognize that the certificate is now a license, and deal squarely with this issue. (3) Initiate and support needed medical reforms while the private sector can still do so. (4) Assume a leadership role in the shaping and future direction of graduate medical education. (5) Relinquish a degree of autonomy in order to strengthen the American Board of Medical Specialties. (6) Define their place in the medical scene and reorganize their board structures accordingly. The primary responsibility of the boards should be to make certain all aspects of resident training in approved programs are sound. Long-range goals should be the elimination of the certifying examination, and public recognition and approval of specialty status attainment.