A new technique for measuring protein turnover in the gut, liver and kidneys of lean and obese mice with [3H] glutamic acid. 1. We have measured the incorporation of an intraperitoneal injection of [3H] glutamate into the protein of the gut, liver and kidney of lean and obese siblings of the genetically obese mouse. 2. Recycling of the 3H was minimized by using glutamate labelled at the C-2 position. Loss of label from the amino acid pool by transamination and deamination was rapid, with a half-life of 4 h. 3. In tissue protein the amino acid showing the highest 3H radioactivity was glutamate. 4. The half-lives for protein synthesis and catabolism were calculated from the decay curves of both specific and total radioactivity of [3H] glutamate in tissue protein. No significant differences were found between kidney, liver and gut in lean and obese mice.


Effect of streptozotocin-diabetes on the local and general responses to injury in the rat. 1. The effects of streptozotocin-diabetes on the local and general responses to a 4 h period of bilateral hind-limb ischaemia in the rat have been investigated. The rats were injured 48 h after the intravenous injection of the streptozotocin. 2. Less fluid was lost from the circulation into the injured limbs after injury in the diabetic rats and this was directly related to the severity of the diabetes, but could not be explained by dehydration. However, when the diabetic and nondiabetic injured rats were considered together there was significant negative correlation between either plasma osmolality or plasma glucose concentration and water content in the injured hind limb. 3. The relationship between plasma glucose concentration and plasma osmolality was changed by injury such that, particularly in the injured diabetic rats, plasma osmolality at a given glucose concentration was higher than that predicted from the relationship betweeen these variables in the uninjured rat.


Effect of oophorectomy and calcium deprivation on bone mass in the rat. 1. The effects of a low calcium diet and of oophorectomy, separately and together, on cortical and trabecular bone mass, have been examined in mature female rats. 2. Calcium deprivation caused a significant decrease of weight, cortical cross-sectional area and ratio of cortical to total area in the femur, it significantly reduced the volume of trabecular bone and increased the percentage of osteoid surface in the tail vertebrae, and in addition increased the urinary excretion of phosphate and, initially, of hydroxyproline. 3. Oophorectomy caused similar though smaller changes in trabecular bone and urine, whereas the effects of oophorectomy on cortical bone were greater on a low calcium intake than on a normal intake. 4. The ash weight of the femora, expressed as a percentage of the total dry weight, was unaffected by calcium deprivation or oophorectomy alone but was significantly reduced when the two occurred together. 5. The percentage of resorption surfaces in the vertebrae tended to increase on the low calcium diet and after oophorectomy on the normal diet but decreased after oophorectomy on a low calcium diet. 6. It is concluded that oophorectomy and calcium deficiency each reduce bone mass in the adult rat but the greatest effect is seen when they are combined.


Circadian rhythmicity of delayed hypersensitivity to oxazolone in the rat. 1. A marked circadian rhythm was detected in the ear swelling of rats immunized and then challenged with oxazolone. 2. The peak response observed at 10.00 hours was over eight times the minimum at 16.00 hours. 3. As related tests are used frequently in man greater attention to clock time is necessary in clinical immunology.


Effect of chenodeoxycholic acid on serum and biliary lipids in patients with hyperlipoproteinaemia. 1. In order to study the effects of chenodeoxycholic acid on serum and biliary lipids in hyperlipoproteinaemia, chenodeoxycholic acid was administered to seven type IIa, eight type IIb and eight type IV patients in a daily dose of 750 mg (1.9 mmol) for 3 months. 2. The serum concentrations of cholesterol and triglycerides were determined at 4-week intervals: cholesterol remained unchanged whereas triglycerides decreased 15--20%. 3. In 17 patients, biliary lipids were studied. The proportion of chenodeoxycholic acid in the bile increased to about 70%; lithocholic acid and ursodeoxycholic acid increased significantly. 4. Bile saturation with cholesterol decreased and correlated negatively with the proportion of chenodeoxycholic acid in biliary bile acids but positively with serum triglycerides. 5. It is concluded that chenodeoxycholic acid treatment in hyperlipoproteinaemia is associated with parallel fall in serum triglycerides and biliary cholesterol and thus may prove to be a useful adjunct in hypolipidaemic treatment.


A computer program for parenthood diagnosis within a family. The knowledge of human polymorphism provides an efficient tool for parenthood diagnosis. This paper describes an algorithm to diagnose fatherhood within a family. In genetic research, the validation of human families is useful since at least 7% of the families have to be rejected from such studies. First, the algorithm verifies whether the phenotype of the presumed father is compatible with the genotypes of all children under the assumption of assured motherhood. An original index coding allows us to write simple algorithms: automatic creation of genetic elements, search of compatible genotypes of parentes and children. Finally, the algorithm calculates several indices used to estimate the likehood of the paternity of non-excluded man.


An approach for physiological signal processing by laboratory minicomputer. Physiological signal-processing instrumentation including the digital oscilloscope is becoming more dependent upon the microprocessor. Minicomputer software has been developed which demonstrates data-processing approaches that should be considered for incorporation into the firmware of digital oscilloscopes. This core-resident software called DATAC operates in an interpretive mode and provides such features as digital signal editing, filtering, and basic processing including differentiation and integration.


Computer analysis of rapid eye movements. Simulation of the saccadic eye movement mechanism and, more recently, diagnosis of neuromuscular disorders associated with saccades rely on accurate recording and analysis of saccade characteristics. Traditionally, eye movements are monitored objectively by registering a transduced voltage correlate of eye position on a pen or cathode ray oscillograph. Analysis of the record obtained is tedious and often inaccurate. The advent of small digital computers with analog-to-digital capability permits more efficient recording. However, computer programs reviewed are limited to the analysis of specific saccade parameters or partly depend on manual operations. The computer program described stores the entire saccadic event of each eye between pre-defined limits including the pre- and post-saccade intervals. Preliminary operations including artifact identification, location of onset, elimination of RC decay, DC offset and amplitude scaling prepare the data for display and subsequent analysis. The program also includes a subroutine to derive the mean and standard deviation of successive saccades.


A program to simulate drug elimination interactions: warfarin and BSP - an illustrative example. The kinetics of drug elimination of interactive drug systems is stimulated by a set of differential equations based on mass balances, the mass of organs and blood flow rates. Experimentally determined concentration profiles of the drugs in the plasma and bile are used to evaluate clearance rate parameters. An example is shown in which the clearance of the anticoagulant warfarin is reduced to less than 50% of its normal rate due to the interference by BSP.


Clinical application of a single compartment model to urea and creatinine kinetics in dialysis therapy. A single compartment mathematical model has been shown to accurately described changing serum concentrations of low molecular weight solutes (urea and creatinine) during dialysis. Clinical application of the model permits prediction of serum concentrations in response to changes in prescription of dialysis therapy. The programs presented here can be used to predict the effect of changes in treatment time and dialyzer clearance on serum concentrations. Sequential pre- and end-dialysis solute concentrations are displayed on a programmable pocket calculator. Dialyzer clearance during any individual dialysis can be calculated. These programs permit an evaluation of the efficacy of prescribed dialysis treatment schedules in advance of therapeutic trials.


NEW: an interactive data management system for monitoring ambulatory patients. Biobehavioral monitoring is a method of gathering daily biological and behavioral measurements from ambulatory patients so that hospital-based care can be extended to the home. Such data can also serve many other purposes such as peer review and assesing the outcome of treatment. To assist in handling the increased information about patients, NEW, a system of three interactive APL Plus computer program packages, has been developed. The program packages, NEWDATA, EVALUATION, and WARNINGS, form an interactive data management system to provide: a rapid means of entering and verifying each patient's data from either a single day or a group of days; a flexible and simple means of retrieving and analyzing the data for an individual patient or for groups of patients; and a means of reviewing, detecting, and signaling trends in the data that deviate from present clinical criteria.


Demodex canis: redescription and reevaluation. A brief review of the taxonomy of Demodex canis is followed by a complete redescription. Demodex canis is diagnosed with D. odocoilei of the white-tailed deer. In view of the continued speculation that dogs and man share the same demodicid, simple morphological characters are noted which distinguish D. canis from D. folliculorum and D. brevis in all stages of their life cycles.


Treatment of cystic ovarian disease in dairy cattle. Fourty-four Holstein Friesian cows diagnosed as having ovarian follicular cysts from rectal palpation of the ovaries and observation of estrous behavior were used for the present experiments. Of the 16 cows injected intramuscularly (i.m.) with 110 mg of depot-progestins containing 100 mg of 17alpha-hydroxyprogesterone caproate and 10 mg of progesterone in oil, 8 cows responded with conception with 103 +/- 53 days in average after the treatment. The 8 cows not responding to depot-progestins were injected i.m. with 6,000 MU of HCG on the 10th day after the treatment. As a result, 2 cows of them conceived within 72 days in average after the initial treatment. Of the other 16 cows injected i.m. with 100 mg of progesteron in oil, 3 cows conceived. Interval between the treatment and conception was 36 +/- 9 days in average. In the 11 cows which failed to respond to progesterone treatment, an intramuscular injection of 6,000 MU of HCG on the 5th day after treatment resulted in conception of 7 cows within 42 +/- 10 days in average after the first treatment. Of the remaining 12 cows which received an i.m. injection with 10,000 MU of HCG, 4 cows responded with conception with 64 +/- 51 days in average after treatment. No remarkable rise in serum progesterone levels was observed either 10 days after depot-progestins injection or 5 days after progesterone treatment. Serum progesteron levels increased distinctly after HCG injections. The combined treatment with 100 mg of progesterone and 6,000 MU of HCG at 5 days interval gave the most successful results and this treatment was effective even when performed long after calving. Thus this method of treatment of cystic ovarian disease may be recommended for practical application.


Gastrict carcinoma with pseudohyperparathyroidism in a horse. Pseudohyperparathyroidism was diagnosed in a mature stallion presented for anorexia, weight loss, pollakiuria and constipation. Laboratory findings included hypercalcemia, hypophosphatemia, anemia and isosthenuria. Thoracocentesis indicated an exfoliating squamous cell carcinoma. At necropsy, a squamous cell carcinoma of the stomach with metastases to the abdominal and thoracic cavities was diagnosed. No osseous metastases were found. No gross or microscopic renal lesions were noted. Bone tissue showed arrested resorption, and the parathyroid gland was atrophic.


Right ventricular heart failure of Montana cattle. Congestive right ventricular heart failure of Montana cattle is characterized clinically by an accumulation of edematous fluid in the brisket region and ventral portions of the body but not of the legs. A well developed jugular pulse is first observed followed by a watery diarrhea and usually by the accumulation of excessive fluid in the pleural and peritoneal cavities. As the case develops over a period of two to three weeks, the ventral edema becomes more marked (Fig. 1) and straw-colored fluid may accumulate in the body cavities until the abdomen is distended and breathing labored. Death may occur as a result of respiratory failure due to the large volume of pleural fluid or from general debilitation as a result of the right ventricular failure. The incidence of this type of heart failure in Montana cattle is highest on moist mountain valleys. Eighty-one of 113 cases observed over a seven year period occurred in cattle that were maintained at altitudes of 1525 m or below. This paper describes the conditions under which the disease occurs in Montana and compares the hemograms of clinically ill and healthy cattle.


A serologic method for the detection of Corynebacterium pseudotuberculosis infections in horses. A serologic technique useful for detecting antibodies formed in horses in response to infection with Corynebacterium pseudotuberculosis is described. The test relies on the ability of C. pseudotuberculosis toxin to produce a wide zone of hemolysis when applied to erythrocytes previously treated with a sterile filtrate of Corynebacterium equi broth culture. The synergistic hemolytic activity can be neutralized by anti-C. pseudotuberculosis serum. This test was used to analyze sera from 616 horses for the presence of C. pseudotuberculosis antitoxin. Of 177 animals (see Table 2) found positive, there were 34 horses with bacteriologically confirmed, active infections and 18 with active but unconfirmed infections. In addition, 13 animals had a history of having had the disease and 112 had no history or evidence of having had the infection. The other 439 horses had negative titers. Statistical treatments confirmed the value of the test as an epidemiological tool but precluded using only titers for the diagnosis of active clinical disease.


Neurologic signs and neuropathology associated with a case of equine infectious anemia. Neurologic signs and neuropathologic lesions associated with a case of equine infectious anemia in a 7 year old Quarter-horse mare were studied. Clinical signs included depression, disorientation, circling, knuckling at the fetlock and hypermetria. The neuropathologic lesions were characterized by a granulomatous ependymitis, subependymal encephalitis, choroiditis and hydrocephalus. These lesions were associated with signs of neurologic dysfunction which were the cause of the prominent clinical features.


Effect of tolazoline on persistent hypoxemia in neonatal respiratory distress. Twenty-seven infants with respiratory distress and hypoxemia of noncardiac etiology were treated with tolazoline. Thirteen infants had hyaline membrane disease and 14 had respiratory distress attributable to causes other than hyaline membrane disease. An immediate response to tolazoline, a rise in PaO2 of 15 torr or more within 15 min, was seen in 11 infants in the hyaline membrane disease group and in eight infants of the other group. Six infants in the hyaline membrane disease group and 11 infants in the second group survived. Tolazoline should be considered as a therapeutic adjunct in the management of hypoxemia which persists after optimal homeostatic and ventilatory support.


Pentobarbital therapy for intracranial hypertension in metabolic coma. Reye's syndrome. In severe Reye's syndrome, with nonspecific intensive supportive therapy, the mortality rate approaches 75%. In many instances, death is due to uncontrolled cerebral edema and elevated intracranial pressure. (ICP). Pentobarbital therapy, sufficient to maintain a blood barbiturate level between 2.5 mg% and 4.0 mg%, was used to control ICP in seven patients with metabolic coma complicated by intracranial hypertension (intracranial pressure greater than 30 mm Hg for 30 min). The nadir of their neurological function was characterized by no response to deep pain, absent or abnormal oculocephalic responses, bilaterally dilated, unreactive pupils, and markedly irregular or absent respirations. Before barbiturate administration hyperventilation, steroids, mannitol, and other supportive therapies commonly used in Reye's syndrome were begun. After institution of pentobarbital therapy, the daily mannitol dose required to maintain the intracranial pressure below 20 mm Hg was significantly reduced (p less than 0.001), from 3.7 +/- 0.3 to 0.5 +/- 0.2 g/kg/day. All the patients survived, and six have no obvious neurological sequelae. Pentobarbital is a useful adjunct for intracranial pressure control in advanced metabolic coma.


Membrane oxygenators: what role (if any) in acute ventilatory insufficiency? Extracorporeal membrane oxygenation has been suggested as an alternative means of support for the patient who is critically ill with acute ventilatory insufficiency. The determination of which patients should receive this therapy has not been clarified to date. Clinical data have revealed overall survival of 10 to 13%. Comparison of therapeutic results with those in which "conventional" therapy is employed has yielded little useful information. At present the overall impact of extracorporeal membrane oxygenation in reducing death from ventilatory insufficiency appears to be minimal. The technique requires major commitments of manpower, equipment, and money, and appears to be limited to a relatively small number of major institutions. A truly objective study, which defines patient entry criteria, specific therapy to be used, and end-points to be achieved has yet to be developed or implemented.


Hemodynamic pressure variables and stroke index. The relationships between right atrial mean, pulmonary artery diastolic, mean, and wedge pressures, and stroke index were studied in 100 patients. The various pressures correlated fairly well with one another, but poorly with stroke index. However, this correlation improved when the values of individual patients were analyzed. Infusion of calcium chloride modified the correlation of the various pressures with the stroke index over a short period of time. During anesthesia, when pulmonary vascular resistances, systemic resistances and myocardial contractility were stable, both pulmonary artery mean and wedge pressure correlated significantly with the stroke index.


Acquired right-to-left intracardiac shunts and severe hypoxemia. Critically ill hypoxemic patients without significant radiological changes on the chest x-ray present a diagnostic and therapeutic problem. Three patients with patent foramen ovale and a patient with a spontaneously closed congenital ventricular septal defect which reopened due to ischemic changes in the ventricular septum are presented. In reviewing the literature, we could not find this type of presentation. Their hypoxemia was associated with right-to-left intracardiac shunts demonstrated by dye dilution cardiac output curves. Because of the risk of systemic embolism associated with a right-to-left intracardiac shunt, air bubbles and particulate material in the intravenous infusion should be avoided. Use of anticoagulants may be beneficial. High inspired oxygen concentration may not correct the associated hypoxemia. The detection of these shunts is easily done at the bedside.


Persistent left superior vena cava complicating hemodynamic monitoring catheterization. Two cases of flow-directed, balloon-tipped catheterizations of the right heart via a persistent left superior vena cava are presented. In both cases, the monitoring catheters assumed similar, atypical configurations on plain chest roentgenograms. Recognition of the characteristic configuration of the course of transvenous catheters through the persistent left superior vena cava allows for plain film diagnosis of this anomaly.


Psychological reactions to acute medical illness and critical care. The psychological stresses evoked by acute critical illness and intensive care in both patient and physician are examined and certain approaches proposed which, in our experience, can alleviate these stresses. Admittedly, these psychological concepts may appear inconsequential at first glance. We have found, however, that such intervention may facilitate the physician's efforts to provide appropriate care for his critically ill patients, including those who must die, without experiencing the psychological reactions--the guilt, shame, anguish, and despair--these patients typically arouse.


Use of Doppler ultrasound in dissecting aortic aneurysm. Immediate intensive therapy is of major importance in the initial management of patients with dissecting aortic aneurysm. The Doppler ultrasound stethoscope is a noninvasive tool which may be used in the diagnosis and management of this disease. A case is presented in which this instrument was used to diagnose and follow the progress of a patient with acute aortic dissection. Further use of this device for similar disorders can be expected.


Artifacts in the measurement of pulmonary artery wedge pressure. Pulmonary artery wedge pressure (PAWP) will only reflect left atrial pressure (LAP) if continuity of fluid exists from the catheter tip to the left atrium. Either increased airway pressure or decreased hydrostatic pressure may lead to discontinuity of the fluid column and midinterpretation of PAWP. Simultaneous measurements of PAWP and LAP were made in 19 anesthetized dogs. Placement of the pulmonary artery wedge catheter above the left atrium (West Zone I) in combination with the incremental addition of 5 cm H2O of PEEP caused a 5 mm Hg gradient between PAWP and LAP in the normovolemic animal. Augmenting PEEP further or hypovolemia (i.e., decrease in LAP) increased the gradient. Hypervolemia (increase in LAP) diminished the gradient. Fluid continuity between the PAW catheter and LA is a prerequisite for monitoring LAP with the Swan-Ganz catheter. Increases in PEEP, placement of the catheter above the left atrium and hypovolemia may occlude the fluid column and cause artifacts in the PAWP obtained.


Fiberoptic bronchoscopic balloon occlusion and reexpansion of refractory unilateral atelectasis. A new method using the flexible fiberoptic bronchoscope is described for the reexpansion of refractory unilateral lung or lobar atelectasis. The technique is well adapted for the critically ill ICU patient.


The risk of positive cultures for Candida in the critically ill patient. It is frequently stated that a positive fungal culture is of little clinical significance unless the culture is obtained on repetitive blood specimens. We analyzed the mortality associated with a positive culture for Candida species in ICU patients from several locations over a 3-month period. Criteria for inclusion in this study were: (1) residence in the ICU for at least 4 days, (2) no GI tract alimentation during this period, and (3) administration of at least one antibiotic during this period. Forty-four patients fit these criteria; 23 had positive Candida cultures from at least one site and 12 (52%) died. Four of 21 patients (19%) who did not grow Candida died. Cultures of urine and sputum were most likely to be positive. Positive cultures from the urine, sputum, or wound were associated with at least a 50% mortality. This suggests that routine sputum and urine cultures may be of substantial clinical therapeutic and prognostic significance. Two patients had positive blood cultures and both died. No single class of antibiotics, surgical complications or underlying disease predisposed to these results. It is concluded that the presence of a single positive culture for Candida from any site in the critically ill surgical patient kept without GI alimentation and on any antibiotic is a grave prognostic sign which requires further attention.


Decay-induced incorporation of tritium into nucleosides in aqueous solutions. In view of environmental and biological implications, the decay-induced incorporation of tritium from T2 into nucleosides in aqueous solutions has been studied by chromatographic methods. It could be shown that at T2 concentrations of about 1 to 2 mCi/ml, labeling of thymidine or deoxyuridine mainly occurs via the 3HeT+ decay ion rather than via beta--radiolysis. In a saturated solution of thymidine, the number of thymidine molecules labeled per tritium decay (L-value) is only 8 X 10(-4), concomitantly 0.6 HTO molecules are also formed, together with CH3T (L = 0.2) and an unidentified organic product (L = 10(-3). Compared to identical concentrations of HT and HTO in aqueous deoxyuridine solutions, the labeling efficiency of T2 is an order of magnitude higher.


Red cell sodium concentration as an indicator of cellular injury in clinical shock. Red cell sodium concentration has been found to be elevated in shock. The significance of this change relative to survival and the possible sources for this increase were examined. Twenty patients in shock had red cell sodium levels compared to shock-related variables and to conditions known to increase red cell sodium levels in vitro. There was no difference noted in red cell sodium elevations between survivors and nonsurvivors. There was a highly significant correlation with transfusions of banked blood and a significant correlation with the administration of digitalis. There was no correlation with the type, duration, or severity of shock. Changes in the sodium gradients across red cell membranes in clinical shock are not good indicators of the general cellular injury of shock.


Study of the distribution and biological effects of 3H in the algae Acetabularia, Chlamydomonas and Porphyra. Freshwater and marine algae are particularly useful for studying the radioactive contamination of aquatic systems. Acetabularia, Chlamydomonas and Porphyra were used to investigate the uptake and eventual biological effects of tritium. When the Acetabularia are grown in the presence of tritiated water, a significant amount of 3H is incorporated in the total nucleic acids and protein fraction. Chloroplasts of Acetabularia were isolated from whole cells and their DNA purified by the agarose procedure, before radioactivity analysis: a significant amount of 3H was incorporated into the chloroplast genome. Chlamydomonas was grown on minimal medium containing increasing concentrations of tritiated water. The increase in cell number was checked by microscope counting. The generation time was 9.6 h and seemed not affected even by the highest 3H concentration. Parallel experiments have shown that an appreciable amount of 3H was incorporated into the total organic matter of the plants. In the case of Porphyra, it was found that a very low level of 3H was incorporated into the total DNA of the plant.


Local distribution of energy deposition in and around the follicles of a 125I contaminated thyroid. Iodine-125, which is used for the clinical diagnosis of the thyroid gland, has a high probability of decay by K-capture followed by the emission of low-energy electrons having ranges of up to 23 micrometer. Thus one has high local concentrations of energy deposition comparable in size to that of the smaller follicles. In this paper the local distribution of energy deposition inside and outside the follicles of the human thyroid gland is calculated for follicle sizes of 20--400 micrometer. Also the local dose rate at the position of the nuclei of the follicle cells is determined as a function of the follicle size. Possible dosimetric approaches to the problem of radiobiological effectiveness are discussed, at first in general and then for the example of the inactivation of follicle cells due to the incorporation of 125I.


Long-term radial artery cannulation: effects on subsequent vessel function. Radial artery function was studied in 114 consecutive patients by arteriography, Doppler ultrasound flow detection, and physical examination following prolonged (1-10 days) percutaneous cannulation with a single type of 20-gauge catheter. Cannulations lasting 1-3 days produced 11% arterial occlusion, whereas those lasting 4-10 days induced 29% incidence of occlusion (p less than 0.05). In addition, a significantly higher incidence of cannula dysfunction (38% versus 18%, p less than 0.05) and thrombus formation (0-3+ scale) was also observed in the group cannulated 4-10 days as compared with the group of shorter duration. The risk of vascular complications arising from percutaneous radial artery cannulation with 20-gauge catheters increases markedly after 3 days.


Biokinetic aspects of tissue-bound tritium in algae. For the estimate of the radiation exposure of man and for the calculation of the risk of artificial tritium from nuclear power plants, organic tissue-bound tritium is of decisive importance. In model experiments, a tritium incorporation of 61 to 71% was found from tritiated water (HTO) into organic matter of planctonic algae under under reproducible conditions and this was related to the theoretical value. In further experiments the tritium release from these high tritiated algae was of interest. Kept in darkness in tritium-free, non-sterile river water, so that autolytic processes and bacterial decomposition could occur, the concentration of HTO was measured over a period of three weeks. A relatively long half-life of tissue-bound tritium was found under various temperature conditions. Therefore it must be considered that a significant retention of tritium in biological matter has to be taken into account in a natural ecosystem. In streams into which the cooling water of a nuclear reactor is released all conditions are found already for a long turnover and cycling of artificial tritium in living organisms as well as the conditions for a favourable transport of tritium by food chains to man.


Chromosome aberrations in human lymphocytes exposed to tritiated water in vitro. The induction of chromosome aberrations in human peripheral blood lymphocytes by tritiated water or 180 kV X-rays in vitro was studied. Lymphocytes were exposed to various concentrations of HTO for 2 h or for 53 h. Chromosome and chromatid type aberrations were scored during the first mitotic division after stimulation with phytohaemagglutinin. For the analysis of the dose-response relationship the data were fitted by the method of least-squares to different models. After acute exposure to tritium beta-rays and X-rays, the dicentrics + centric rings and terminal + interstitial deletions gave the best fit to the linear-quadratic function. However, data for these types of aberrations after 53 h exposure to HTO gave equally good fit to the linear and linear-quadratic functions. The best description of the dose-response relationship for chromatid aberrations is given by the linear model. In the system studied the RBE of tritium beta-rays as compared to 180 KV X-rays was 1.17 +/- 0.02.


Comparative effects of tritiated water and thymidine on the preimplanted mouse embryo in vitro. Preimplanted mouse embryos were cultured in an in vitro-system from the two cell stage to blastocysts. In the control cultures about 92% of the incubated embryos developed to blastocysts. When tritiated compounds like tritiated water or tritiated thymidine were present in the incubation medium the number of blastocysts decreased with increased medium tritiated thymidine was about one thousand times more effective than tritiated water. Tritiated thymidine caused a more pronounced division delay than tritiated water which had a strong effect on the blastulation process. Further studies showed that the incorporation of tritiated thymidine into the DNA lead to high concentrations of tritium in the cell nucleus. Dose calculations are performed for the cell nucleus in the case of incubation with tritiated thymidine as well as with tritiated water. The different action of the tritiated compounds can apparently be explained by the specific incorporation of thymidine into the DNA.


Some effects of irradiation of mice in utero with tritiated compounds. Mice have been exposed continuously, in utero, to tritiated water (via the maternal drinking water) or to tritiated thymidine (infused continuously into the mother). In both cases the patterns of labeling and subsequent loss of tritium over an extended period have been studied. The technique of infusion in unrestrained mice and its application in the production of fully tritium-labeled offspring is described in some detail. These fully labeled mice are being used to study a number of early and late effects, in particular, gonad cell effects and carcinogenesis, following this form of internal irradiation. Some preliminary results are presented. Similar results produced a homogeneous irradiation from tritiated water are also reported.


The genetic and late somatic effects of chronic tritium ingestion in mice. The long term somatic and genetic effects of chronic tritium (3H) ingestion have been measured in mice. Second generation animals, who with their parents were maintained on drinking water containing 3 muCi/ml of HTO, have been bred and the number of dominant lethal mutations measured. The increase in dominant lethal mutations in treated animals as compared to tap water controls is significant at the 1% level. The stem cell content of the bone marrow has been measured throughout the lifetime of the animals. A slight reduction in colony forming units in the bone marrow of treated animals is evident beginning after approximately 12 weeks, increasing in severity throughout the lifetime of the animals. The distribution of tritium in tissue water protein fractions was determined, and the relative contribution to tissue dose calculated. The differential incorporation into protein fractions was not found to be significant.


Comparative incorporation of tritium from tritiated water versus tritiated thymidine, uridine or leucine. Whereas the radiotoxicity of tritium has been extensively studied, comparatively little information exists on its long-term effects as a potential environmental pollutant, particularly at small dosage. This investigation was primarily aimed at assessing comparatively a possible carcinogenic potency of tritiated water versus radioactive precursors of DNA, RNA and proteins, namely tritiated thymidine, uridine and leucine in C57 Black mice. Tritium is largely released in the environment in the form of tritiated water. There are many uncertainties, however, as to how tritium is incorporated from tritiated water into cell constituents quantitively and qualitatively. In 1965, we reported on the carcinogenic effect of tritium in the form of tritiated thymidine on newborn C57 BL mice in the dose range of 0.3--1.5 muCi/g [Mewissen. 1965]. Hence the selection of tritiated water, and of tritiated precursors, in an attempt to evaluate their respective role in the tritium transfer process and to correlate their possible late effects with their specific patterns or sites of incorporation. This study deals with tritium incorporation from tritiated water and various precursors at the 1 or 10 muCi level. RSA values, i.e., the ratio of organically bound tritium per hydrogen content of dry tissue over aqueous tritium per hydrogen content of water, were estimated for newborn, juvenile and adult mice, at various time intervals (1, 8, 15, 22 and 29 days) following single administration of tritiated water, tritiated thymidine, uridine or leucine. The data available at this time show that administration of tritiated water (or precursors) result in a complex time dependent and age dependent residual activity dynamics both in the organic component and in the aqueous fraction of tissue. A few preliminary conclusions can be made. Following a single acute or brief exposure to tritiated water, values of activity become exceedingly small after a relatively short time period. In a steady state equilibrium, resulting from chronic exposure to tritiated drinking water, RSA values tend to stabilize. However, wide variations between various organs are to be expected, as suggested by their respective RSA values following a single exposure. In view of these observations, it would seem that a realistic estimate of the internal dose to the radiosensitive nucleus must take into consideration the age dependent incorporation of tritium from tritiated water, as well as the variation between organs. The carcinogenic risk has often been estimated from a uniform dose dependency model. The influence of time and space microdistribution of dose within tissues and more particularly at specific sites (such as DNA, RNA or protein) has received, as yet, little attention, as well as the relative contributions of the time sequence of dose absorption during the usually long latency period. Such factors, among others, may be critical in carcinogenesis from internal irradiation...


Distribution of tritiated compounds (tritiated thymidine and tritiated water) in the mother-fetus system and its consequences for the radiotoxic effect of tritium. The incorporation and distribution of tritiated thymidine (3H-TdR) and tritiated water (HTO) have been measured in newborn rats exposed to various levels of tritium by continuous infusion into pregnant rats from day 9 until term. In the animals exposed to HTO, the tritium activity was homogeneously distributed, while 3H-TdR led to accumulation of DNA-bound and homogeneously distributed tritium. The incorporated activity and the specific activity of DNA from ovaries which showed a reduction of total oocyte number by approximately 50% were used to estimate the dose absorbed by the ovarian cell nuclei in both systems. From the absorbed dose, a factor of 3.7 was calculated for the "internal relative biological effectiveness" of DNA-bound tritium as compared to homogeneously distributed 3H under the restrictive assumption that the static description of the system at birth reflects the situation during the time of dynamic development of the ovaries when the toxic effect occurs. The influence of these dynamic factors of changing nuclear size and tritium incorporation during the sensitive period is weighed against the possibility that the continuous 3H-TdR infusion during pregnancy might represent a model in which DNA-bound tritium shows a higher effectiveness than homogeneously distributed tritium.


Tritium retention in rat after administration of various doses of tritiated water. Hooded inbred rats were given subcutaneously HTO doses ranging from 1.8 muCi/g b.w. to 115 muCi/g b.w. Samples of liver, lung, kidney, skin muscle, small and large intestine were taken at 1, 3, and 5 days intervals within 21 days of the experiment. The concentrations of tritium in free water and bound in particular tissues have been determined, and the biological half-lifes (Tb) of tritium were calculated by means of least squares. The biological half-life of free-water tritium varied from 3.6 days in kidney to 4.8 days in muscle for the control group being slightly lower in the groups with higher HTO doses. The retention of tissue-bound tritium varied in each group of animals. Tb values varied from 10.3 days in the large intestine to 85.0 days in the muscle of the control group and were significantly lower at higher HTO doses. This result is opposite to the effect observed after external X-ray irradiation for the same radiation dose level.


The Auger cascade and therapeutic applications of 125I. The Auger cascade consists of low-energy electrons which are emitted instead of characteristic X-rays when a vacancy in an inner electronic shell is filled. Such atomic vacancies are produced by orbital electron capture, internal conversion, and the photoelectric absorption of photons. The relative abundance of Auger electrons and their decrease with increasing atomic charge (Z) is explained. For iodine (Z = 53), about 30% of the energy is carried by Auger electrons and thus is dissipated locally. As the concept of average dose cannot always be applied to electron capture decay in cellular components, microdosimetric parameters, applied separately to each of the distinct types of low energy radiations involved, seem more appropriate. The development and applications of the relevant microdosimetric concepts are reviewed briefly. The approach explains the high biological effectiveness of 125I in different and unrelated systems, such as DNA molecules and the thyroid gland. The effects of 125I on thyroids of humans and experimental animals were compared to those produced by 131I by the Glasgow and the Beilinson groups. The experience of these teams in applying therapeutic doses of 125I in order to control thyrotoxic patients is evaluated.


Distribution of tritium in the different organs of calves and pigs after ingestion of various tritiated feeds. A research programme on the transfer of tritium in the food chain has been in progress for several years on the experimental farm of the Nuclear Energy Research Center at Mol. The studies reported here are related to the distribution of tritium in the organs of farm animals contaminated in various ways. Two young male calves ingested tritiated milk; the daily intake of 3H-organic form was about 15 muCi for each calf and the total activity ingested until the sacrifice was 482 muCi. Three male pigs from the same litter and about 7 weeks old were used for each experiment on the administration of tritium under different forms: (a) single intraperitoneal injection of 39.3 mCi HTO (P2, P3, P4). (b) daily ingestion of 28.4 muCi HTO. The total activity ingested was respectively 569 muCi (P5) and 766.8 muCi (P6). (c) ingestion of tritiated potatoes. The total activity ingested was respectively 21 muCi (P8), 40.3 muCi (P9) and 48.1 muCi (P10). (d) ingestion of tritiated milk powder. The total activity ingested was respectively 60.6 muCi (P13), 110.4 muCi (P11) and 154.5 muCi (P12). After slaughtering of each animal various organs were removed and analyzed for the 3H content in the tissue water and in the organic matter. We could verify that the chemical form of 3H present in the food is of great importance for  the incorporation of 3H in the organic matter of the animal organs. The total incorporation increases by a factor 5.6 when 3H is ingested as tritiated milkpowder by pigs as compared to HTO and with a factor 15 for calves. When tritiated potatoes were ingested by pigs a factor 15.6 was found. The transfer of 3H from HTO and milk feed ingested in the organic fraction of organs is lower for pig than for calf. When we consider the 3H in the tissue water of organs the specific activity (SA) is a little lower than the SA of ingested HTO and after ingestion of tritiated milk feed the activity is very low and no difference due to the species is found. After fractionation of liver and spleen tissue following the technique of Schmidt--Thannhauser radioactivity was found in all liver and spleen constituent lipids--RNA--DNA and proteins, but after isolation and purification of DNA following the original methods, we have not been able to demonstrate that tritium is really incorporated into DNA molecules of a non-dividing organ such as the liver nor of an actively dividing organ such as the spleen.


Investigation of tritium incorporation of tritium incorporation by means of excreted metabolites. The commonly accepted urine analysis by liquid scintillation method was applied for whole body dose estimating. After the separation of metabolite fractions the organically bound tritium in urine could be measured. Urine samples from workers repeatedly exposed to tritium incorporation during the chemical processing of various labeled compounds have been collected and analyzed. The time dependence of tritium activity in certain metabolites was found to be characteristic, significantly differing from the 3H concentration curve of the native or treated urine sample.


Microlocalization of artificial radionuclides in radiological protection of the environment. Though environmental biological equilibrium seems to be safeguarded as long as the radiological protection of man is assumed, a number of problems raised by environmental protection are not fully solved. In particular, there occur both macroscopic processes of concentration at some levels of the biological chains, and microlocalization at the cellular, subcellular and molecular levels. The long-term consequences of the non-uniform distribution of the radionuclides should therefore be assessed even if the contamination levels of the physical environment are very low. These aspects are of particular significance with alpha-emitters (plutonium and transplutonium elements), beta-emitters (chiefly tritium) and activation products, some of which are radioisotopes of biologically significant elements. The incidence of these processes is discussed in the light of recent and future developments in nuclear energy. This approach might open new avenues for investigations in environmental radiological protection. The concept of a concentration factor between the environment and the total organism must be supplemented by the concept of a localization and concentration factor at the subcellular level. The significance of the physico-chemical forms of the radionuclides and the parameters likely to modify the characteristics of membranes should be emphasized. Finally, an indication is given on priority measures in the area of investigations of the long-term consequences of low doses on environmental organisms.


Biological toxicity of Auger emitters: molecular fragmentation versus electron irradiation. Two hypotheses have been advanced to explain the extreme biological toxicity of DNA associated 125I: (a) high local concentrations of radiation energy from low energy Auger electron; (b) charge-induced molecular fragmentations in the DNA. To distinguish between these two hypotheses an attempt was made to evaluate the molecular events associated with electron capture decay, to calculate the microdistribution of radiation energy after 125I decay, and to relate the microdosimetry data to the biological toxicity of 125I and 3H. The cellular damage produced by the two radionuclides was evaluated on synchronized Chinese hamster ovary cells (CHO) labeled with various doses of 3H-thymidine or 125I-iododeoxyuridine. As expected, 125I (LD50: 45 rad; D0: 74 rad) proved much more toxic to CHO cells than either 3H (LD50: 380 rad; D0: 250 rad) or external X-irradiation (LD50: 330 rad; D0: 230 rad). To evaluate the molecular mechanism of 125I toxicity, iododeoxyuridine labeled with both 125I and 14C was synthesized and the effect of 125I decay on the molecular structure of iododeoxyuridine was studied by monitoring the fate of 14C activity after 125I decay. The results of this experiment indicate that 125I decay does not cause molecular fragmentation in iododeoxyuridine, only deiodination. Moreover, microdosimetry calculations show that at least in small target spheres more radiation energy is deposited on the average by decaying 125I than by a high LET alpha-particle traversing a sphere of equal diameter. These findings greatly strengthen the hypothesis that the high LET-type damage produced by Auger emitters results from high local concentrations of radiation energy rather than from charge-induced fragmentation of the DNA.


Repair of the double-strand breaks produced by 125I disintegrations in the DNA of Micrococcus radiodurans. Wild-type M. radiodurans and two radiosensitive mutants were used to study the lethal effects of 125I disintegrations in their DNA. The relative sensitivities of these three strains to inactivation by gamma-radiation were reflected in their relative sensitivities to inactivation by 125I decay. The number of double-strand (ds) breaks in the DNA appeared to be similar at levels of gamma-radiation and of 125I decay that reduced survival to 10%. All three strains of M. radiodurans rapidly repaired ds breaks produced in their DNA by either gamma-radiation or 125I disintegrations. If one ds break per is a lethal event [Kirsch et al., 1975], cells of the three strains tested would die only when they had left unrepaired one ds break out of an initial 45,600 or 1800 ds breaks per single cell.


DNA strand breakage and repair in human kidney cells after exposure to incorporated iodine-125 and cobalt-60 gamma-rays. Biological effects of 125I incorporated into DNA exceed those to be expected from the absorbed radiation dose by a factor 3--30. The reason for this discrepancy suggests special mechanisms introduced by 125I transmutation, decays by K-capture leading to the emission of an average of 6 low energy electrons including Auger electrons and to a highly positively charged daughter nuclide. The effect of 125I decay on DNA strand breakage and subsequent repair was studied. Human kidney cells T in the deep frozen state (-196 degrees C) were exposed to incorporated 125I and 60Co gamma-rays. The number of DNA single strand breaks (ssb) was determined by DNA centrifugation in alkaline sucrose gradients. DNA repair was studied by incubating the cells after thawing at 37 degrees C. For 125I decay in frozen cells which were kept with or without dimethyl-sulfoxide, 4 and 6 ssb were measured per decay. The gamma-rays produced 1ssb per 26 eV absorbed energy. Most of this damage was repaired 30 to 40 min after onset of incubation. No repair of the damage caused by 125I was observed. The high efficiency of 125I decays for the production of unreparable ssb provides evidence for the high radiotoxicity of this isotope. The observed lack of repair may in part be due to the high numbers of at least 2,000 125I decays per cell nucleus necessary for the assay system. Damage from many 125I decays may interfere with enzymatic repair processes.


The tritium RBE at low-level exposure--variation with dose, dose rate, and exposure duration. Differing values have been reported for the relative biological effectiveness (RBE) of 3H beta-radiation compared with X- and gamma-rays; but the significance of these differences has not been adequately clarified. Because large quantities of tritium are involved in nuclear energy operations, it is essential to have precise knowledge of its effectiveness compared with a "standard" radiation such as gamma-rays. This is especially true for chronic, low-level exposure since available information on protracted irradiation derives mostly from gamma-ray studies. We have approached this problem experimentally by measuring effects of low-level exposures to HTO and gamma-rays on a very sensitive mammalian system. Microscopic enumeration of oocytes in ovaries of exposed and control mice provided measurements of in vivo cell killing by constant HTO levels in body water and, for comparison, by continuous 60Co gamma-irradiation. For protracted exposure from conception to 14 days after birth, the RBE was found to be greater than 1 and to vary inversely with exposure level. At effective gamma-ray doses of 50 rad, delivered at 3.5 rad/day, the RBE was 1.6. But for 25 rad, at 1.8 rad/day, it increased to 1.9. It continued to rise as dose decreased, reaching a value of 2.5. Corrected for scattered radiation, the RBE was 2.8, close to 2.9 reported previously, but below the maximum value of 3.75 predicted by microdosimetric measurements and the theory of dual radiation action. An RBE close to 3 at low doses was not suprising. But decrease at higher doses, due to downward curvilinearity of the gamma-ray dose-response curve, was unexpected for protracted exposure. It suggested that primary oocytes in the prepubertal mouse (the cells used in this study) have limited capacity for recovery. Survival-curves for constant gamma-ray dose rates of 1 rad/min and 0.002 rad/min were therefore determined. Curvilinearity was seen in both, with greater steepness for the higher dose rate, indicating that oocytes do have some ability to recover, but that even with a dose rate only 3.2 rad/day recovery is incomplete. This in turn suggests that the observed gradient in RBE is due partly to a dose-rate effect and partly to inverse variation with dose itself, as predicted by the theory of dual radiation action for acute exposure (or incomplete recovery). Comparing protracted and shorter, 5-day exposures revealed further contrasts. At 30 rad of gamma-rays the RBE in short exposures was only 1.4, while it was 2 for protracted ones. This could be due at least in part to dose rate; it may to some degree, however, reflect difference in microdistribution of tritium atoms, greater radiobiological effect in protracted exposures resulting from 3H incorporation into especially effective sites. These systematic variations of RBE with dose, dose rate, and exposure duration help to explain some of the existing lack of agreement regarding tritium's RBE and provide a more secure basis for hazard evaluation of chronic, low-level exposure.


Variation of hepatic mitochondrial nucleotides in rats contaminated with plutonium-239. Rats were given 239Pu citrate i.v. and the mitochondria of hepatocytes were studied. A reduction of oxygen consumption per mg protein with time was seen. We have investigated the nucleotides involved in nuclear phosphorylation. After mitochondrial extraction according to Schneider and Hogeboom, [1950], a new method was used for estimating CMP, NAD, 5' AMP, NADP, ADP and GTP. Flavine mononucleotide was not determined. The plutonium content was followed from day 0 to day 65 post injection. Mitochondrial nucleotides were studied on days 5 and 11. On day 5, all nucleotide levels were reduced by 20 to 70% except AMP which increased and GTP which remained constant. On day 11, all nucleotides had decreased by 70 to 100% except NAD which increased by 20 to 30%. The results suggest that plutonium citrate given intravenously has a time dependent effect on the energy metabolism of the liver.


Therapeutic application of iodine-125 labeled iododeoxyuridine in an early ascites tumour model. In its decay, iodine-125 emits cascades of Auger electrons with subcellular ranges and leaves a highly charged tellurium-125 product. When iodine-125 is incorporated into DNA as the thymidine analog 125I-UdR, the localized deposition of such energy has been shown to be extremely radiotoxic. This report presents the results of quantitative investigations into the therapeutic efficacy of 125I-UdR in an early ascites murine tumour model. An ovarian embryonal cell carcinoma has been maintained by serial intraperitoneal transplantation. Challenge doses of 10(4)-10(6) cells were used. Four divided doses of 125I-UdR were administered starting 24 h after tumour cell inoculation; the interval between doses was 4 or 12 h. Therapeutic efficacy was demonstrated by prolonged median and increased absolute survivals of treated animals. Divided doses were more effective than single doses, and antineoplastic activity was related to fractionation. The degree of cell killing with a given fractionation scheme was constant over the range of 10(4)-10(6) cells, and total doses of 50-100 muCi resulted in a 2-3 log killing of tumour cells (1-0.1% cell survival). Therapy with 125I-UdR affords a promising new approach to the treatment of cancer. The therapeutic potential of iodine-125 and other radionuclides whose decay results in a highly localized deposition of energy merits further investigation.


The form and interpretation of clearance curves for injected radioisotopes based on negative power laws, especially for 47Ca and estimating bone accretion rate. Many hundreds of clearance curves for plasma and urine after a single injection of tracer are well fitted by y = sigmari = Ai exp(-Bit), r = 2 or 3, based on models with homogeneous compartments. Reanalyzing such sums as in a plot of log y versus log t shows that many of the original curves would fit y = At-alpha or At-alpha exp(-betat) over wide ranges of time and specific acitivity. Results of such reanalyses for a complete published series for serum albumin 131I are given, and an outline of those for various compounds in the human body labeled by 3H. For radiocalcium two such power laws can be fitted in one curve, with a transition between about 1 and 3 days, so that much of the log y versus log t plot consists of two straight lines. These lines are used for starting a numerical analysis that splits the curve into 2 non-linear components, plus a third one that is neglibible after 5 min from injection. An outline of the iteration method is given. The components are interpreted physiologically and used to predict total bone activities by (de)convolution, and these are compared with observed ankle activities and with excretion rates. The bone accretion rate is obtained mainly from the middle component and comes to 2 to 3 g Ca/day, while return of 47Ca from bone to plasma begins at about 1/2 day. These results seem imcompatible with any based on compartments. The concept of biological half-life then needs to be reconsidered.


The bromine enhancement ratio in mammalian cells in vitro and experimental mouse tumours. Human kidney cells in culture and cells of mouse sarcoma-180 were allowed to incorporate bromine into their DNA. Cultured cells with and without incorporated BUdR were irradiated with electromagnetic radiations ranging in energy from 12 keV X-rays to 60Co gamma-rays to find out whether or not there exists any energy dependence of the bromine dose enhancement ratio BER. Such a dependence should show in the immediate neighbourhood of the K-absorption edge of bromine (13.5 keV). Any influence of the Auger effect triggered in bromine by external irradiation should show by a significant increase of the BER for energies rising from slightly below to slightly above the bromine K-edge. Values of D37, D0 and the extrapolation numbers of the cell survival curves served as biological endpoints. Measured values of BER ranged from 1.12-2.00 without any significant dependence energy. A weakly pronounced peak was found for 50 kV X-rays of 26 keV mean energy. Sarcoma-180 were irradiated with 14 kEV X-rays and 60C gamma-rays. BUdR was administered i.v., i.p. and directly into the tumours in quantities of up to 1 ml of a 10(-3) M solution. Tumour regression caused by the irradiations served as a measure of the radiation effects with and without incorporated BUdR. No significant dose enhancement effect of bromine was observed in this case. Within error limits, the combination of BUdR with 14 keV X-rays proved more effective than BUdR combined with 60Co gamma-rays.


Mohs' chemosurgery for the treatment of cutaneous gangrene. Mohs' chemosurgery provides a promising alternative to more conventional methods in the treatment of cutaneous gangrene. The method has low mortality and morbidity, and it may allow a more conservative removal of tissues, resulting in less permanent disability for the patient.


Topical therapy of leg ulcers with 20 percent benzoyl peroxide lotion. Preliminary clinical observations suggest that benzoyl peroxide lotion (20%) may be a useful topical treatment for various types of leg ulcers. Further studies utilizing patients as their own controls (treating half of the ulcer surface with 20% benzoyl peroxide) are now underway.


Pyoderma gangrenosum responsive to minocycline hydrochloride. Pyoderma gangrenosum (PG) is a characteristic ulcerative condition of unknown etiology. Four cases are reported of patients with PG who responded to minocycline hydrochloride therapy. Possible mechanisms for this apparently efficacious modality are discussed.


Telogen effluvium: a clinically useful concept, with traction alopecia as an example. Telogen effluvium is the excessive loss of normal club hairs. It can be diagnosed simply by microscopic examination of the hairs that are being shed. These hairs have uniform shaft diameter and normally shaped bulbs that contain no pigment. The causes of telogen effluvium are well known and easily distinguishable. They include parturition, febrile illness, surgical operations and anesthesia, anticoagulant drugs, psychi stress, crash diets, and traction. Traction alopecia often produces recognizable patterns of hair loss and can be diagnosed in many cases with reasonable certainty. It is usually not accompanied by inflammatory changes and the prognosis is excellent provided the causative styling practices-braids, rollers, ponytails, etc-are discontinued. Telogen conversion may be caused by interference with papillary blood flow. Since traction alopecia would seem to be reproducible, it may serve as a model for the study of telogen conversion.


Treatment of actinically damaged skin with a keratolytic gel. Rough-textured, actinically damaged skin of the extremities was treated with a keratolytic gel to restore the surface to a more normal appearance. The excellent improvement observed suggests that an abnormality of cell attachment may be the defect in some so-called dry skin states.


Interhemispheric subdural empyema: neuroradiological diagnosis. A case of subdural empyema situated in the interhemispheric subdural space is described. CT scan is useful in the diagnosis and follow-up of intracranial inflammatory pathology. Selective angiography was helpful in the compartmental localization of the abscess in the interhemispheric subdural space, adjacent to the falx and tentorium by virtue of the hypertrophied tentorial meningeal arteries and vascular displacement. CT scans are also useful in follow-up of cerebral abscess after micropaque barium has been injected into the cavity as in this patient.


Intraventricular chloramphenicol.

Intraventricular chloramphenicol. Very high intraventricular chloramphenicol levels can be obtained if the standard systemic dose is supplemented with a small intraventricular dose. Chloramphenicol sodium succinate can be hydrolyzed to the microbiologically active chloramphenicol in the ventricular fluid. Daily injections are ordinarily adequate to maintain a high concentration of antibiotic. Initial dosage should vary with ventricular volume. The brain does not tolerate repeated needle puncture and the use of a ventriculostomy reservoir is recommended.


Anterior cervical fusion after traumatic dislocation of the cervical spine in childhood and adolescence. 5 patients aged 11-16 years with traumatic lesions of the cervical spine are reported. 4 patients were treated by operative ventral fusion with good results. Regarding the preoperative history of these 4 patients and the history of another 1 treated by conservative means, the authors tend to relatively early operative ventral fusion.


Cricopharyngeal achalasia associated with Arnold-Chiari malformation in childhood. Six patients with myelomeningocele and the Arnold-Chiari malformation developed cricopharyngeal achalasia and lower cranial nerve deficits. Diagnosis is established by cine-esophagram. Distortion of the brain stem or cranial nerves secondary to the Arnold-Chiari malformation may produce the autonomic imbalance necessary for cricopharyngeal achalasia. Treatment is supportive and includes verification of cerebral spinal fluid shunt function. Suboccipital craniectomy may reverse progressive lower cranial nerve deficits and reduce cricopharyngeus spasm. Cricopharyngeal myotomy may be considered when the cranial nerve deficits and cricopharyngeal achalasia are fixed, irreversible, and continue to cause disability.


Cerebrospinal fluid antibiotic concentrations in ventricular shunt infections. The concentration of antibiotic in cerebrospinal fluid was measured during treatment of seven children with infected ventricular shunts. Antibiotics were administered via the ventricular shunt or through an external ventricular drain. 53 CSF samples were obtained 7-19 h after antibiotic administration. Wide variation in cerebrospinal fluid antibiotic concentration occurred from patient to patient following either route of administration. For optimal management of shunt infections, we recommend periodic assessment of antibiotic concentration or activity in ventricular fluid and determination of the minimum inhibitory concentration of antibiotic required for each pathogen.


Recurrent headaches in 100 children. Electroencephalographic abnormalities and response to phenytoin (Dilantin). The causes of chronic, recurrent headaches, the electroencephalographic findings and the response to phenytoin (Dilantin) and other medications have been evaluated in 100 children. A history of head injury was reported in 41% and convulsions had occurred in 15%. Electroencephalographic dysrhythmias were severe in 18 and moderate in 27%. Migraine was diagnosed in 42% and tension headaches in 18%; psychogenic factors complicated learning disabilities and minimal brain dysfunction in 21%. Phenytoin controlled migraine in 77% and headaches diagnosed as seizure equivalents in 40%; the response was unrelated to the degree of electroencephalographic abnormality. An abnormal electroencephalogram and response to phenytoin are insufficient criteria for a diagnosis of epilepsy in children with recurrent headaches.


[Total duodenopancreatectomy as a standard operation in pancreatic cancer]. Total pancreatectomy is recommended to improve the poor prognosis for patients with pancreatic cancer. Several factors support the use of this method as the best chance of cure: no cancer is left behind at the line of pancreatic resection, radical operation in case of multicentric or diffuse pancreatic carcinoma, more radical lymphadenectomy, no complications relative to the pancreaticojejunal anastomosis, and, primarily, longer survival rates. Operative treatment must be individual and depend on tumor stage. In case of localized operable pancreatic carcinoma, total pancreatectomy seems the best way of achieving more cures.


[Heatobiliary sequential scintigraphy. Value of this nuclear-medicine-diagnostic technic in the pre- and postoperative stages following hepato-biliary-tract injuries]. The increase in accidental abdominal trauma with liver injury and the wide spread of invasive gastroenterologic/radiologic procedures with the risk of liver or biliary tract damage necessitate diagnostic methods for detection and postoperative control of such lesions. Diagnostic procedures in acute liver damage are discussed. Hepato-biliary sequential scintigraphy proves reliable in detection of bile leakage into the peritoneal cavity. Because of the sensitivity, the method should be used before radiologic investigations, e.g., in diagnosis of postoperative biliary structures and in the examination of functional behavior of biliodigestive anastomoses. Intrahepatic bile stasis is recognized as the forerunner of cholangitis.


[Focal nodular hyperplasia of the liver and oral contraceptives]. Three cases of benign liver tumors in young women are reported in addition to 58 cases in the literature. Uncharacteristic pains in the upper abdomen and general weakness were the main symptoms. The most valuable diagnostic examination is selective angiography. Liver resection was successful in these cases. Elective surgery is advocated because massive bleeding with high lethality may occur. Histologically focal nodular hyperplasia was found and all three had taken oral contraceptives.


[Causes of vascular injuries in alloplastic hip replacement]. Vascular injuries were treated in 8 cases of total hip replacement. Acute and subacute arterial thrombosis, an AV fistula, and local thrombosis of pelvic veins were observed. These vascular complications of total hip replacement must be avoided by an effective local operative technique. Contact of bone cement with the vascular loge must also be avoided in order to prevent toxic or thermic irritation of arteries or veins.


[The typical wrist ganglion].

[The typical wrist ganglion]. Occurrence of ganglion on the wrist in the scaphoid region in connection with protuberance of the scaphoid bone is statistically of high significance. As ganglions result from mucoid degeneration of connective tissue following microtraumata, the scaphoid protuberance may cause ganglion to appear most frequently at a localization above the scaphoid bone on the wrist. We suggest that this localization be called 'loco typico'.


[Dilatation or sphincterotomy as the treatment of primary-chronic fissure in ano. Results of a random, clinical study after 2-3 years]. In a randomized clinical trial, 66 patients were treated for primary chronic fissure-in-ano by anal dilatation or sphincterotomy. Of the 64 patients still living, 57 (89.0%) could be submitted to a follow-up examination 26.7 +/- 4.6 months after the operation; 63 of them were surveyed on the basis of a questionnaire. Six patients who had reported functional lesions after operation at a six-month follow-up were reexamined: in two cases improvements were recorded, in the case of three patients the symptoms remained unchanged, and in one case a complete reduction was achieved. Though no significant difference (p less than 0.1) was noted with a recurrence rate of 20.5% (n = 7) after the dilatation versus 3.1% (n = 1) after the sphincterotomy, a definite trend was obvious. These findings support the sphincterotomy as being a definitive therapy for primary chronic fissure-in-ano.


[Modified bridle-plasty in recurrent luxation of the patella]. For local operative correction of slipping patella, we recommend a modified plasty of the patellar retinaculum apparatus. This simple operation can even be performed on adolescents with still open epiphyseal cartilages. The technique of our operation is described. The early results during the last 30 months are very good. None of our 20 patients noted a reluxation, and all have resumed their sports.


[Amputation of the knee joint in vascular diseases]. Reported are 97 extensive amputations in 87 patients from 1975 to 1977. Postoperative early mortality was 47% and depended on the disease and the various factors that made amputation necessary. Amputations in chronic occlusive vascular disease without septicemia had a far lower mortality, 10%. Amputations in patients with septicemia resulted in a mortality of 90%. According to Burgess, amputations of the lower leg, exarticulation in the knee joint, and myeloplastic and open amputation of the thigh should be considered in that order. Exarticulation in the knee joint is only feasible in the presence of an open, deep, femoral artery.


[Artificial embolization before septic amputation]. By artificial embolization before extensive septic amputation arrosion bleedings that are otherwise noncontrollable can be prevented. Resorbable gelatine (Gelforam) is suitable for embolization. For safety one can leave a balloon catheter above the embolized vessel segment for several days.


[Fibrin glue. A new treatment technic in persistent recurrent spontaneous pneumothorax]. The treatment of choice in idiopathic spontaneous pneumothorax is continuous suction drainage by chest tube for 8--10 days. If this method is not successful, i.e., in patients with a persistent or recurrent pneumothorax, an attempt can be made to produce local pleural adhesions by means of a special fibrin glue, especially in patients with poor general condition. This fibrin glue pleurodesis was performed successfully in seven patients, four of them having a persistent, two a recurrent, and one an iatrogenic pneumothorax. Six of them are now, 3--10 months after therapy, without a recurrence and free of discomfort. One patient died 6 days after treatment from a cerebral stroke. Autopsy showed fibrinous adhesions in the area of the upper lobe. Good tissue compatibility was confirmed histologically.


[Modification of postoperative glucose-tolerance disorders using bradykinin]. Glucose tolerance after abdominal operation was studied with and without infusion of bradykinin. With bradykinin a normalization of the postoperative decreased assimilation of glucose was found.


Complex and simple sequences in human repeated DNAs. Highly repeated human DNA sequences were isolated by isopycnic centrifugation, or were eluted from gels after restriction enzyme cleavage. High molecular weight DNA peaks separable from the bulk of the DNA in a variety of gradients were shown to consist of very simple sequences characteristic of simple satellite DNAs; DNA fingerprint studies indicated each of these peaks could consist of tandem repeats of a specific oligonucleotide sequence as low as 10 base pairs (bp) long. All the gradient peaks could be assigned to one of two sequence groups and several "different" buoyant density peaks revealed the same sequence.--Restriction fragment multimers did not share common sequences with the satellite DNAs as judged by hybridization data. They could not be separated by isopycnic centrifugation. Furthermore these highly repeated DNAs were more complex in sequence and more variable than the satellites. Even the smallest (50 bp) fragments by depurination and other direct sequencing methods were shown to be more complex than the high molecular weight satellite peaks.--The idea that subsets of repeated DNAs may be defined by sequence complexity, possibly with discrete or separable functions, is proposed.


Chromosomal localization of complex and simple repeated human DNAs. Complex repeating restriction multimers and a simple AT rich satellite isolated with Hoechst 33258 ( less than or equal to 0.5% of the human genome) were localized by in situ hybridization to human chromosomes. The complex repeats were clustered at the centromeres, consonant with their integration in tandem arrays at these loci; these sequences were very prominent on chromosomes 7, 10 and 19, sites not previously identified with any specific human repeated sequence. The Hoechst simple satellite labelled predominantly the long arms of the Y chromosome. Although this simple satellite and the complex restriction multimers did not hybridize with each other, and did not contain detectable ribosomal sequences, both isolates additionally labelled the nucleolus organizing regions (NORs) of acrocentric chromosomes.--The possible relationship of complex and simple repeated DNAs, and their assignment to specific chromosomal domains, is discussed.


The products of the "heat-shock" loci of Drosophila hydei. Correlation between locus 2-36A and the 70,000 MW "heat-shock" peptide. Antibody was raised against total Drosophila hydei embryonic cellular protein with a molecular weight between 65,000 and 70,000 dalton. This antiserum reacted with the 70,000 MW "heat-shock" peptide found in "S labelled cell extracts of "heat-shocked" D. hydei tissue culture cells or salivary glands.--The antibody was coupled to Sepharose 4B and this material was used to absorb polysomes obtained from tissue culture cells incubated at 37 degrees C in the presence of tritiated RNA precursors. The relative concentrations of various RNA species complementary to the "heat-shock" loci 2-32A, 2-36A, and 2-48C in either bound, non-bound, or total polysomal material was then determined by in situ hybridization. The RNA species complementary to locus 2-36A was found to be enriched in the bound polysomal material.


Co-replication of satellite DNA of Chironomus melanotus with mainband DNA during polytenization. The DNAs of five Chironomus species, C. plumosus, C. nuditarsis, C. thummi thummi, C. melanotus, and Camptochironomus pallidivittatus, were investigated in analytical neutral isopycnic CsCl density gradients. DNA was isolated both from larval brains ("diploid-DNA") and salivary glands ("polytene-DNA"). The buoyant densities of mainband DNAs were 1.692 g/cm3, with the exception of C. melanotus whose mainband had a density of 1.693 g/cm3. The densities correspond to a calculated GC content of 33% and 34% respectively. Only in C. melanotus was the DNA clearly resolved into mainband DNA and two distinct satellite shoulders: Satellite I, with a buoyant density of 1.684 g/cm3 (25% GC, calculated) and satellite II of 1.679 g/cm3 (19% GC, calculated). The two satellites comprise 15% of the total DNA in the "diploid-DNA"' and they also occur in the "polytene-DNA", where they make up 11%. The results are discussed in the general context of under- and overreplication in polyploid and polytene cells.


Adenocarcinoma of the prostate involving the rectum. Five cases of prostatic carcinoma invading the rectum were found on reviewing 161 prostatic carcinomas over a five-year period. A summary of the clinical and laboratory findings of these cases is given. A review of previous reports in the literature and discussion of the modality of presentation and methods of diagnosis of this entity are presented. The importance of differentiating a primary rectal carcinoma from a prostatic carcinoma involving the rectum is emphasized.


Synchronous primary adenocarcinomas of the colon and rectum. In a series of 1,002 cases of primary colorectal adenocarcinomas diagnosed during a ten-year period there were 62 (6.2%) patients who had two or more primary colorectal adenocarcinomas. Most of the tumors were more than 5 cm away from each other: 27 carcinomas were separated by 6-10 cm, 16 were separated by 11-20 cm, and 12 were separated by more than 20 cm. It is concluded that the incidence of synchronous carcinomas of the colon is sufficiently high to warrant a search by both surgeon and endoscopist for additional tumors some distance from the initial lesion.


Mental disorders in ulcerative colitis: suicide, divorce, psychosis, hospitalization for mental disease, alcoholism, and consumption of psychotropic drugs in 178 patients subjected to colectomy. The population in the Nordic countries is relatively homogenous. In 178 Norwegian patients subjected to colectomy for ulcerative colitis the frequencies of suicide, divorce, psychosis, and hospitalization for mental disorders, and consumption of psychotropic drugs, did not differ significantly from corresponding frequencies in the general population.


Tumor-host relationships in colorectal carcinoma. Eighty-seven colorectal carcinomas were studied histologically with special reference to grade of tumor, reactions of stromal tissue, and the morphology of regional lymph nodes. A special search was focused on the morphologic manifestations of possible host factors. The most interesting findings were: 1) nuclear grade of the tumor correlated with five-year survival; 2) the content of tumor-derived mucus was not a prognostic determinant; 3) the intensities of stromal lymphocyte and mast-cell reactions correlated with survival; 4) an active lymph-node paracortical area was almost incompatible with the appearance of nodal metastases.