Urinary metabolites characteristic of urea-cycle amino acid deficiency. Experiments with 45-75-g male rats gave conclusive evidence that the simultaneous absence from the diet of arginine, ornithine, or citrulline caused an immediate and persistent elevation of orotic and citric acids in the urine. The experiments also demonstrated that a deficiency of no other individual amino acid increased urinary citrate and orotate. Elevated urinary excretion of orotic and citric acid occurred independently of the form of nonessential nitrogen. Replacement of arginine isonitrogenously with ornithine or citrulline prevented the rise in urinary orotic acid, but had different effects on growth, urinary citrate, and urinary urea. These differences were probably due to differential uptake of arginine, ornithine, and citrulline by tissues; In the reported experiments employing L-amino acids as sources of dietary nitrogen, a deficiency of any amino acid indispensable for growth and nitrogen balance or a deficiency of arginine, ornithine, or citrulline retarded growth, increased urinary urea, and decreased urinary ammonia. It is concluded that the severe loss of orotic acid during urea-cycle amino acid deficiency arises from a decreased capacity of the urea cycle to detoxify ammonia, thereby causing increased shunting of intramitochondrial carbamyl phosphate into pyrimidine synthesis. The similarities in metabolism during arginine deficiency and ammonia intoxication are discussed. The evidence shows that urinary orotic acid may be a valuable measure of arginine nutrition in mammals.


Hepatic steatosis and the elevated plasma insulin level in patients with endogenous hypertriglyceridemia. Among 31 nonobese or obese patients with endogenous hypertriglyceridemia, hepatic steatosis was found by histologic examination of the biopsied specimen in 17 patients, and it was severe in six patients, They had no history of excessive alcohol intake. Chemical analysis revealed that the lipid accumulated in the liver was triglyceride. The hypertriglyceridemic patients, with or without histologic steatosis, showed significantly increased responses of both plasma insulin and blood glucose to oral glucose load compared with control subjects. The responses were more exaggerated in the hypertriglyceridemic patients with steatosis than in the hypertriglyceridemic patients without steatosis. Analysis of correlations between five variables (liver triglyceride, plasma insulin, blood glucose, body weight index, and serum triglyceride) was done on 15 subjects whose liver triglyceride values were quantified, and highly significant correlations were found between liver triglyceride and plasma insulin, blood glucose, or body weight index. A step wise multiple regression analysis performed on the five variables with liver triglyceride as the dependent variable revealed that the plasma insulin level was the most closely related variable, and the blood glucose level the next. The prediction equation for liver triglyceride as a function of plasma insulin and blood glucose levels (r = 0.91, p greater than 0.001) accounted for 84 percent of the total variance of liver triglyceride. It was shown that the decay of intravenously injected insulin in plasma was not delayed in the hypertriglyceridemic patients with steatosis, while the insulin sensitivity examined after intravenous insulin injection significantly decreased in the hypertriglyceridemic patients with or without steatosis, thus suggesting that the hyperinsulinemia in the hypertriglyceridemic patients was due to an increased insulin secretion associated with the decrease in the insulin sensitivity. Therefore, the elevated plasma insulin and blood glucose levels--or the insulin insensitivity by itself--might be the essential abnormalities in patients with endogenous hypertriglyceridemia, which, in extreme cases, might lead to massive triglyceride accumulation in the liver.


Regional adipose tissue cellularity in relation to metabolism in young and middle-aged women. Body composition and total number of fat cells were investigated in 31 randomly selected women 52 yr of age and in 13 young women (mean age 22 yr) whose body weights were within plus or minus 10% of the ideal weight. Two of the 52-year-old women were obviously obese and excluded. Regional determinations of adipose tissue thickness, fat cell size, and number were also determined. Middle-aged women had more body fat (BF) but a lower body cell mass (BCM) than the younger group. The increased BF in the middle-aged women was exclusively explained by larger fat cells, since the younger women had a significantly higher total number of fat cells. This increase was also found when differences in height, body weight, and body fat were matched out. Local fat cell number was also increased in the younger group. Local fat cell size was increased in all regions investigated in the middle-aged women, but the increase was particularly pronounced in the abdominal region. The highest degrees of correlation between fat cell sizes of different regions were found between the epigastric and hypogastric regions and between femoral and gluteal regions. Furthermore, the plasma insulin levels correlated with the fat cell sizes of the abdominal region but not with those of the femoral or gluteal regions. In conclusion, the data might indicate that the fat cells of the abdominal region are more sensitive to nutritional and/or hormonal factors than those of other regions. This may in turn indicate the existence of different fat cell populations.


Labile methyl balances for normal humans on various dietary regimens. Normal young adult male and female subjects were maintained on fixed dietary regimens which were either essentially normal or were semisynthetic and curtailed in methionine and choline intakes and virtually free of cystine. The subjects maintained stable weights and remained in positive nitrogen balance or within the zone of sulfur equilibrium. Choline intakes were calculated, and urinary excretions of creatinine, creatine, and sacrosine were measured. Creatinine excretions of male subjects on essentially normal diets outweighed the total intakes of labile methyl groups. Taking into account the excretions of additional methylated compounds, as judged from published values, it appears that methyl neogenesis must normally play a role in both males and females. When labile methyl intake is curtailed, de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties. On the normal diets used in these experiments, the average homocysteinyl moiety in males cycled between methionine and homocysteine at least 1.9 times before being converted to cystathionine. For females, the average number of cycles was at least 1.5. When labile methyl intake was curtailed, the average number of cycles rose to 3.9 for males and 3.0 for females under the conditions employed.


Glycogen metabolism in muscle: its circadian and seasonal variations. The glycogen content of mice diaphragm and 14-C-glucose incorporation into glycogen was studied around the clock at 4-hr intervals. It was found that glycogen content presents a circadian rhythm with a peak value around 4 hr; this rhythm was reproduced in four different months, but with changes both in the absolute values and in the range of oscillation around the 24-hr mean value. Although labeled glucose incorporation exhibited a circadian variation as well, it peak value was 180 degrees out of phase compared with the glycogen rhythm. When the animals were submitted to a 29-hr fasting, the glycogen-24 hr-variation was still present, with similar oscillation around the mean. However, the absolute glycogen values were one-third as high as the ones obtained in the control animals. Our results suggest that the rhythm of glycogen content is due, at least partly, to the circadian variation of its synthesis. Furthermore, food intake is not the main factor responsible for the above mentioned rhythm.


Skeletal turnover and total body elemental composition during extended calcitonin treatment of Paget's disease. Twenty patients with generalized symptomatic Paget's disease had serial measurements of radiocalcium turnover and/or total body elemental composition by in vivo neutron activation analysis during long-term calcitonin therapy. Despite maintained clinical improvement, seven of 15 patients showed partial or total loss of the initial decelerating effect of calcitonin on skeletal turnover, whereas the remaining eight patients maintained the calcitonin-induced deceleration. The changes in skeletal turnover were roughly proportional to the induced changes in serum alkaline phosphatase and urinary hydroxyproline. However, disparities in the magnitude of the changes among the three parameters were not uncommon. Total body calcium was increased by a mean of 22% above predicted prior to calcitonin and decreased significantly by 4% during long-term calcitonin treatment. Total body phosphorus, nitrogen, and sodium also decreased. The phosphorus and sodium losses appeared to be mostly from the skeleton. These data confirm histologic evidence of the disappearance of pagetic bone, resumption of normal lamelar bone formation, and radiographic evidence of a decrease in bone volume during calcitonin treatment and incidate the relative magnitude of this effect. The action of calcitonin in this regard possibly represents a specific effect on Paget's disease beyond its general skeletal effect of reduce cellular activity.


Unususpected meningioma in a patient with pituitary gigantism. Case report with autopsy findings. A unique example of a clinically unsuspected large parasellar meningioma is described in a 36-yr-old pituitary giant who had been treated initially with conventional irradiation, subsequently by surgical excision of an acidophil adenoma, and ultimately with medroxyprogesterone acetate (MPA) prior to his demise. The patient died of increased intracranial pressure resulting from a combined mass effect of the meningioma and recurrent tumor. The relationship between radiation and the development of the meningioma is discussed, as well as the fine ultrastructure of a highly functioning acidophil adenoma.


An instrument for the rapid determination of L-lactate in biological fluids. An analyzer for lactate has been developed based upon an electrochemical-enzymatic method. It allows the determination of lactate within 2 to 3 minutes after sample collection. The instrument is capable of performing up to 20 measurements per hour. A minimum sample volume of 50 mul is needed. Except for the injection of the sample, all steps of the measurement are automated. The instrument is easy to operate and can also be used by nontechnical staff.


Approximate identification and digital simulation of the respiration--heart-rate system. This paper considers the problem of determining a digital computer model for the heart-rate system that includes nonrespiratory as well as respiratory effects on the heart rate. A sampled-data model is shown to be exact in certain cases and can be used with some errors for other cases. Several methods are developed for finding the model transfer function parameters as well as the parameters of a signal added to the system output. Linear and nonlinear models are considered.


Temperature-dependent characteristics of Teflon membranes used in mass spectrometry. In vitro information is provided on the gas partial pressure/temperature relationship and on the membrane permeability/temperature relationship, when a special type of Teflon membrane is used with a mass spectrometer. Monitored pressures of oxygen, nitrogen, and carbon dioxide in an equilibrating gas mixture decreased with stepwise decreases in temperature from 37 to 18 degrees C. Permeability of membranes to all gases also decreased with decreasing temperature. Observed partial pressure changes were apparently due to temperature-induced changes in Teflon membrane permeability characteristics.


A simulator for teaching electrical safety procedures in the hospital. The dangers of accidental electrocution in the hospital, especially in the intensive care and coronary care units, have recently received much attention. The most important step in reducing such dangers is the proper training of hospital personnel in appropriate safety procedures. As a teaching aid for the training of V.A. personnel, a Simulator of Assorted Hazardous Malfunctions in Electrical Equipment (SAHMEE) was developed. With this simulator, safety hazards that might exist in a hospital environment can be shown, as well as the effects of electrical shock on a patient, and the effectiveness of various safety measures.


Automated system for measurement of mechanics of breathing. We describe a complete automated system for measurement of total respiratory resistance and compliance, and of pulmonary resistance and compliance in humans and anesthetized animals. The device for testing the chest-lung system consists of a sinusoidal pump with a stroke adjustable from 20 ml to 600 ml over a cycling frequency of 0.3 to 30 Hz. Pressure and flow or volume are inputted into an analog network for wave shaping, then to an arithmetic unit composed of sample-and-hold amplifiers, peak, minimum and zero detecting circuits, an analog division circuit, and a digital logic processor. The computer takes the peak-to-peak amplitude of one of two sinusoidal inputs at 0.3 to 10 Hz and the corresponding amplitude of the other input in the presence of a.c. noise and d.c. shifts, divides one into the other, and displays an answer on a digital voltmeter. In addition, the analog output is displayed on the cathode-ray tube of a storage oscilloscope. Plots of total resistance and pulmonary resistance are recorded as a function of lung volume in both humans inspiring voluntarily as well as anesthetized dogs inflated by positive pressure from the test apparatus. Total and pulmonary dynamic compliance, as a function of breathing frequency, can only be measured by the computer if a symmetrical waveform is presented to it. This cannot be achieved in spontaneously breathing subjects but is accomplished in apneic animals by producing sinusoidal oscillations from the test apparatus. Our on-line method for measurement of total respiratory resistance is now used in the Clinical Pulmonary Laboratory for experimental work, and we are in the process of obtaining values in normal subjects.


An on-line system for measurement of opacity pulse propagation times in atraumatic screening of patients for occlusive vascular disease. Measurement of opacity pulse propagation times to internal and external carotid vascular beds of the face and to upper extremities on either side of the body is a useful atraumatic method of screening patients for extracranial cerebrovascular disease. We describe a system for rapid measurement and on-line presentation of pulse propagation times that improves upon factors of measurement accuracy and time required to perform the procedure that had previously limited the clinical application of the method. Pulse propagation measurements evaluating common carotid, internal carotid, external carotid, and subclavian arteries can be carried out and results obtained in 10 to 15 minutes using this system. Correlations of data obtained with the system with results of four vessel angiography in patients are presented.


Dispersion-casting thin and ultrathin fabric-reinforced silicone rubber membrane for use in the membrane lung. Pinholes in thin silicone rubber membrane have previously been traced to undispersed silica filer aggregates within the silicone rubber. This was overcome by centrifuging the dispersion to remove the aggregates prior to membrane fabrication. Thin (less than 75 mu) and ultra-thin (less than 25 mum) membrane could then be dispersion-cast. To facilitate handling and to increase mixing of blood in the membrane lung, it is often desirable to reinforce the silicone rubber membrane with fabric. Unfortunately, this process frequently introduces pinholes of its own. We have found than pinhole-free fabric-reinforced silicone rubber membrane can consistently be produced by the double-layer casting technique. First, the dispersion is cast onto aluminum foil, solvent evaporated, and partially cured. A second layer is next cast on top of it, followed by fabric. After solvent evaporation, final cure is under nitrogen using organic peroxide catalysts. This technique has permitted us to consistently cast strong pinhole-free membranes as thin as 9 mu.


Nondestructive measurements of the properties of healing burn scars. A testing protocol and the requisite instrumentation have been developed to nondestructively monitor the temporal and mechanical properties of maturing scar. The maturing scar can become progressively and unpredictably adherent or contractured, producing varying degrees of functional impairment. By plotting these mechanical changes as a temporal function of limb motion history, more accurate prediction and control of the ultimate scarring may result. These same techniques could also be used to study normal skin aging. Extrapolation could be made to connective tissue scars in tendons, ligaments, and other structural elements. Scar contractures may develop slowly along lines of tension or areas of maximum skin defect in large maturing scars once the patient has recovered sufficiently to exercise the underlying joints. Since the present endeavor to monitor potential contractures requires measurement of the "in-plane" stresses and strains, we have chosen to utilize an in situ strip biaxial test configuration.


The coiled envelope-a disposable insert for coil dialysis. The coiled envelope, a disposable pre-sterilized insert for coil dialysis, and its associated hardware were developed. In vitro and in vivo characterizations of the dialyzer were carried out and clinical dialyses performed. Clinical studies show the efficacy of the device and indicate advantages in its design. The dialyzer can be assembled in less than 5 minutes. The blood fluid path materials are replaceable in the coiled envelope kidney and can be certified sterile and pyrogen-free for each dialysis. This is a distinct advantage over the reuse of commercial dialyzers which can not be certified after their initial use. The disposable insert could be made available for patient use at a cost about one-half that of present commercial dialyzers.


A method for the in vitro measurement of tensions of blood gases with a mass spectrometer. A specially designed cuvette with an in vivo catheter allows the in vitro measurement of gas tensions in heparinized samples of blood with a mass spectrometer. Approximately 1.5 cc of blood is required, half of which is used to clear the dead space of the cuvette. The partial pressures of oxygen (P-o2) and of carbon dioxide (Pco2) of arterial and venous samples obtained from the catheterized femoral arteries and veins of 10 mongrel dogs were measured with the mass spectometer and with a conventional pH/gass analyzer. Good agreement was obtained between the two methods. The range of validation for P-o2 was between 35 and 100 mmHg; for P-co2 it was between 20 and 88 mmHg. Depletion, temperature control, flow dependency, and calibration problems are discussed.


Standards-their impact upon the economics of instrumentation development. The potential impact of the medical device amendments bill pending before Congress is analyzed in terms of its possible effects on 27 specific biomedical instrumentation and equipment markets. Characteristics, business opportunities, and growth potentials are evaluated for three tiers of device manufacturers, resulting in the development of several scenarios. The "most likely" scenario, according to the author, will result in strong growth for biomedical equipment and device markets but an uneven effect upon market participants.


Rationalization of standards for medical devices-Part 1. Current practices for preparing standards in general-and standards for medical devices, instruments, and products in particular-are too slow, too expensive, and too cumbersome. There is a need, therefore, for establishing administrative mechanisms to expedite standards preparation. This paper addresses some administrative, conceptual, and methodological aspects of standards preparation and suggests actions that might contribute to improvements in the effectiveness of standards and in the methods of their preparation.


Human snake bite victims: the successful detection of circulating snake venom by radiommunoassay,. A new solid-phase radioimmunoassay has been developed which allows positive identification of the type of snake venom in human tissue and fluids and its accurate quantitation. Tiger snake venom at a level of 210 ng/ml was detected post mortem in the serum of a child, and brown snake venom was detected in two adults bitten by unidentified snakes. Apart from forensic applications, the assay will be useful in studying clinical aspects of envenomation and the use of antivenenes.


Treatment of snake bite in Australia. Some observations and recommendations. Amongst snake bite deaths in Australia there are a number which could be considered as avoidable. Prompt and adequate administration of the appropriate antivenene, when indicated, combined with a more intensive surveillance of snake bite victims, would decrease the number of fatalities.


The effect of chest physiotherapy upon the FEV1 in chronic bronchitis. Chest physiotherapy, including posturing the patient head downwards while the chest is percussed and vibrated, was used in the treatment of patients with an exacerbation of chronic bronchitis. In seven patients the mean FEV declined from 1.38 litres plus or minus 0.39 to 1.25 litres plus or minus 0.37 after postural drainage and percussion (P less than 0.001). Twenty minutes later the FEV rose to 1.37 litres plus or minus 0.33. The mean decline in the FEV1 was prevented by prior administration of salbutamol. The fall in the FEV1 did not occur in 10 patients who received the postural tipping without chest percussion. Also it was not induced by coughing every two minutes during posturing. It was considered that the fall in FEV1 after chest physiotherapy was due to bronchoconstriction caused by the chest percussion or vibration, particularly in patients with bronchoconstriction under basal conditions. The induced bronchoconstriction counter-balanced any improvement of the FEV due to freeing the airways of sputum, but in two patients with moderate to copious sputum an improvement of the FEV1 was repeatedly obtained in measurements made 20 minutes after the physiotherapy when the bronchoconstriction had presumably subsided. Although the immediate decline in FEV1 was not large, it is considered inadvisable to employ chest percussion and vibration in sick patients unless a bronchodilator is administered previously.


Unusual chromosomal changes in polycythaemia vera. Of 13 cases of polycythaemia vera in which direct bone marrow culture was carried out for chromosome analysis, a consistent count of 48 chromosomes was found in two on admission to the hospital. Neither patient showed evidence of blastic transformation.


Tuberculous meningitis in childhood.

Tuberculous meningitis in childhood. The 43 cases of tuberculous meningitis treated at the Royal Children's Hospital, Melbourne, over the 15-year period from January, 1954, to December, 1969, are reviewed in detail. With "triple drug" antituberculosis therapy, 19 patients made a full recovery and seven died. Of the other 17, 11 had major permanent sequelae. There was a strong correlation between the patient's state of consciousness at the time antituberculosis therapy was commenced and the ultimate result. Suggestions are made on how the mortality and morbidity can be reduced.


Starch peritonitis--a hazard of surgical glove powder. Starch peritonitis, a granulomatous reacton to surgical glove powder, is reported in four patients. The condition presents as a well defined clinical syndrome, and should perferably be diagnosed clinically to avoid reoperation and the risk of introduction of more starch. Studies show that a mean of 107 mg of starch per pair is present on the outside of Austrailn-made surgical gloves. It is suggested that gloves be rinsed and dried before operation and it is recommended that a warning to this effect be printed on glove packets.


Acute interstitial nephritis following ampicillin hypersensitivity. A case of acute anuric renal failure following hypersensitivity to ampicillin is presented. Renal biopsy showed severe interstitial nephritis. Treatment with prednisolone and heparin, together with supportive measures and peritoneal dialysis, was followed by rapid recovery of renal function. It is concluded that hypersensitivity to ampicillin can cause acute interstitial nephritis, analogous to that seen with penicillin and methicillin.


Geochemistry and multiple sclerosis: a hypothesis. A hypothesis is presented and evidence is adduced to show that high-risk areas of multiple sclerosis are related to the ability of the soils of the locality to obtain and fix molybdenum perferentially to copper. Soil conditons capable of such partition are known to be present characteristically in cool temperate zones and are significantly present in acid podsols of these regions. On the other hand, under tropical and subtropical conditions, molybdenum is normally highly mobile and leached from the environment. Copper may also be leached but can accumulate in caliche deposits. This hypothesis is notopposed to the theory of a viral aetology of multiple sclerosis, but rather seeks to show that certain individuals, if exposed to trace element imbalance at a critical period in life, may be rendered susceptible to a slow virus infection.


[Interaction between alcohol and drugs (author's transl)]. The interaction of ethanol with drugs becomes more and more important because of a constant increase of the consumption of both. While most of the commonly used drugs  do not alter the elimination of alcohol there exist a number of drugs which influence the degradation of ethanol by inhibition of the acetaldehyddehydrogenase. In combination with alcohol these drugs lead to an antabus-like reaction. In respect to the influence of ethanol on the metabolic degradation of drugs it must be destinguished between acute and chronic effects of alcohol. Upon acute influence of ethanol we observe an increased efficiency of many drugs. Chronical influence of ethanol on the other hand leads to a reduced action of drugs by enzyme inhibition. Besides the interaction on the level of biotransformation the interaction on the receptor-level is important. This mechanism especially leads to an increased efficiency of drugs which influence the central-nervous system.


[1000 selective coronary angiographies (method of Sones) (author's transl)]. Complications during and after performance of selective coronary angiography are reported from the first 1000 patients examined in Frankfurt. All examinations were done according to the method of Sones after preparation of the right brachial artery. There was no lethal complication. The following serious complications were observed: infarction 2, oedema of the lung 6, ventricular fibrillation 13, severe bradycardia and temporary cardiac arrest 29, incompatibility of contrast medium 8. Complications concerning the used peripheral artery were very rare. Quantitative measurement of the blood flow in the forearm of patients did not show any decrease in maximal blood flow under exercise after arteriotomy in relation to the flow in the other arm of the patients. In about 98% of all cases the selective angiography of both the right and the left coronary artery was successful. The conclusion is that selective coronary arteriography with the Sones-technic is a reliable way of examining the coronary arteries with a very low complication rate if it is performed by two well trained cardiologists with experience and knowledge about the method and its possible complications.


Studies on the immunochemistry of Staphylococcus aureus cell wall: antigenicity of pentaglycine bridges. The specific antigenicity of pentaglycine bridges in cell walls of S. aureus was investigated. The antistaphylococcal sera (against 11 Oeding strains of S. aureus) were found to contain antibodies of two different specificities against polyglycyl peptides; one type reacted with polyglycyl peptides with a free amino terminus and the other with polyglycyl peptides with a free carboxyl terminus. These antibodies were assayed by passive hemagglutination with tanned sheep red cells sensitized with N-polyglycyl-BSA (containing polyglycyl peptides with a free amino terminus) or with C-poe antibodies against N-polyglycyl peptides were absorbed by S. aureus strains and by S. epidermidis. Heterologous bacterial species failed to absorb antibodies of either specificity. Antibodies against polyglycyl peptides were used to confirm the mechanism of action of penicillin on S. aureus cell wall.


Production of potent salmonella H antisera by immunization with flagellae, isolated by immunosorption. For serotyping Salmonella H sera should exhibit a high H titer and preferably a low O titer which does not interfere with the H slide agglutination at the working dilution of the serum. By conventional immunization with motile bacteria OH sera are always produced. We isolated flagellae from highly motile Salmonella cultures, which were detached from the bacterial cells by a waring blendor, with an immunosorbent, i.e. cyanobromide-activated Sepharose to which the respective anti H antibody was coupled. The desorption of the flagella from the immunosorbent was done by lowering the pH to 2.3 with glycine-HC1 buffer. 4.2 mg of flagellar protein were recovered from 20 agar swarm plates. 10 mug of the antigen incorporated into complete Freund adjuvant was found to immunize a rabbit successfully. The H titers varied from 10,000-160,000 and the majority of the O titers did not exceed 160. Only one immunosorbent was necessary to isolate a group of related H antigens (i.e., lv, lw, lz13, lz28). After regeneration the immunosorbent can be reused many times.


Absolute kilovoltage calibration of a diagnostic x-ray generator. A method for absolute calibration of diagnostic x-ray generators is presented and discussed. The method employs a Ge(Li) detector and relies on the direct observation of the onset of fluorescence radiation from scattering foils placed in the primary beam.


Remote measurement of fluid volume by x-ray fluorescence. A technique utilizing x-ray fluorescence has been used to measure remotely the volume and, thereby, the hydrostatic pressure of a cesium nitrate solution in vitro. The excitation radiation source was 99m-Tc, and the x-ray spectra were measured with a sodium iodide spectrometry system. This technique may be applicable to long term in vivo measurements of intracranial pressure for conditions such as hydrocephalus.


Hidden-part suppression on three-dimensional plots. The conceptual and mathematical description of a method to draw a three-dimensional histographic surface in oblique projection, with the drawing of hidden parts suppressed, is given.


Treatment planning with a graphics tablet. A graphics-tablet treatment planning system is described. The cost effectiveness of this approach is especially attractive where time-sharing use of a central computer facility is available.


Penetration quality measurement for standardization of radiographic image quality. Interchange or transfer of radiographic techniques through measurement of penetration quality is discussed. The usefulness of this achievement is verified using an aluminum step wedge. Also, the procedure described provides a method for performance evaluation of kVp compensation on diagnostic x-ray installations.


Edge sharpness and enhancement of electron radiographs (ERGs) produced with powder cloud development. Much renewed interest has developed in electrostatic imaging systems. This is partly because of their use of relatively inexpensive materials and their potential for improved diagnostic accuracy--a novel combination of image latitude with great detail contrast. All such systems can exhibit these image characteristics when developed by the generally used "powder cloud" technique or some similar partial development system. We have measured edge sharpness and enhancement of electron radiographs (ERGs) produced with the powder cloud technique. Edge sharpness can be excellent at low image-density levels, but deteriorates with increasing density. Edge enhancement is also appreciable; it appears to decrease somewhat with increasing image density, but no simple relationship has yet been shown.


Computerized therapy registry: the Mayo Clinic experience. Establishing a computerized tumor registry involves careful consideration of a number of factors. Included in this consideration are the cost of both software and hardware, the type and selection of data needed, and the ongoing cost of the program. A representative listing of the data to be collected for the radiotherapy tumor registry is included.


The interaction of histones with native and denatured DNA. A description is provided for the effects of various concentrations of NaCl, MgC12, and urea on the precipitation of native and denatured DNA by histones. The solubility of complexes between total histones and fractions F1, F2a, F2b, and F3 with denatured and partially denatured DNA was greater than that of the complexes between histones and native DNA. The complexes formed between histones and denatured DNA were soluble in excess histones, unlike those formed between histones and native DNA. Electrophoresis of the individual histone fractions through a polyacrylamide gel layer containing DNA led to the determination of the amount of histones bound to native and denatured DNA under conditions of saturation (0.04 ionic strength). It was established that 1 mug of native DNA binds 2.4, 2.8, and 2.5 mug of histones F1, F2a, F2b and F3, respectively. The denatured DNA binds 1.4-1.5 times less of each histone fraction than does native DNA, but the binding seems stronger. It has been demonstrated that the histones inhibit to a lesser extent the template activity of denatured and partially denatured (about 5% disruption of hydrogen bonds) DNA in comparison with native DNA in an RNA polymerase system. It has been suggested that the properties of the complexes formed between histones and denatured or partially denatured DNA, may underlie the control mechanism for genome activity in the cells of higher organisms.


Renaturation of DNA from ultrasonically fragmented chromatin. The rates of renaturation of ultrasonically treated DNA, isolated from fragments of rat liver chromatin, were compared. Chromatographic fractionation on hydroxylapatite was used to fractionate the denatured and renatured DNAs. It was shown that DNA fraction 1 renatures considerably faster than fraction 2. The results are compared with previously published data on the specificity coefficient of DNA, the content of basic amino acids and alkali-labile phosphorus of the protein in the corresponding fragments of the chromatin. The possible functional role of these fragments in the genome is discussed.


The structure of hydrophobic cores of globins. The contacts between bulky hydrophobic side chains (Val, Leu, Ile, Met, Phe, Tyr, and Trp) were studied in five globins with known three-dimensional structures. It is shown that a large majority of these side chains participate in such contacts, where most often one side chain makes contact with two to four nearby side chains. The "recognition element" of a helical region is most often a pair of bulky hydrophobic side chains belinging to neighboring turns of an alpha-helix. Such pairs most often make contact with bulky hydrophobic side chains brought in from the outside. An analysis is made of contacts between the hydrophobic side chains common to all five globins. It is shown that as a rule the most intense contacts in each globin are also common to the five globins. The role of these invariant contacts in the formation of the tertiary structure of globin molecules is considered. A suggestion is made that the apoglobin molecule consists of independently self-organizing halves, the internal structure of which is less subject to fluctuation than their mutual arrangement.


The formation of a complex between the membrane structures of the mitochondria and DNA of nonmitochondrial origin. The ability of decomposed rat liver mitochondria, stripped of their outer membrane (fracton C) to bind 14C-DNA of phage T4 was demonstrated. The bound phage DNA is 10-15% resistant to treatment of fraction C with DNAase I. Treatment of fraction C with sarcosyl (final concentration 0.1%) and centrifugation in a linear sucrose gradient (20-50%) permits the detection of a label in the Mt-DNA-membrane complex, isolated at 35% sucrose. Further fractionation of the membrane complex on sepharose 4 B promotes the detection of the label in "elementary particles of transcription" [1], structural units of the inner membrane, containing specific centers for binding to DNA. The centers of binding of the elementary particles of transcription possess greatest affinity for Mt-DNA; however, they are also capable of binding DNA of various origin (both the DNA of eucaryotes and that of procaryotes). The significance of fixation of DNA of nonmitochondrial origin by the membrane structures of the mitochondria is discussed.


The presence of an endonuclease acting on UV-irradiated and depurinized DNA in cells of Micrococcus lysodeikticus. Enzymatic activity, hydrolyzing DNA treated with beta-isopropyl-bis-beta-chloroethylamine (HN2-DNA), HN2-DNA exposed at 50 degrees for 1 h, and DNA treated with acid, to acid-soluble fragments was found in extracts from cells of M. lysodeikticus. The endonucleolytic component ofthe indicated activity manifests chromatographic properties on DEAE- and CM-cellulose, close to those for UV-endonuclease. Activity is manifested by UV-irradiated DNA, proflavin, and cyanide. Two electrophoretically homogeneous fractions of UV-endonuclease (after chromatography on DEAE- and CM-cellulose), with molecular weights about 13,000 and 15,000 daltons, exhibit endonucleolytic activity with respect to HN2-DNA, exposed at 50 degrees for 1 h, and with respect to "acid" DNA, treated for 6 min at 70 degrees in citrate buffer, pH 3.5. The activity with respect to the latter substrate is competitively suppressed by UV-irradiated DNA. The most probable substrate of UV-endonuclease, in addition to cyclobutane dimers, is the depurinized region of DNA.


A study of the mechanism of action of phosphorylase B using isotope-labelled substrates. We have measured the alpha-deuterium and alpha-tritium secondary kinetic isotope effects on the synthesis and phosphorolysis of glycogen catalyzed by glycogen phosphorylase B (EC 2.4.1.1). The isotope-labeled substrates glucose-1T-1-phosphate and 1C14-glucose-1D-1-phosphate were used in the experiments, together with 6T-glucose-1-phosphate and C14-glucose-1-phosphate as controls. Measurement by the double label technique showed that both effects studied were equal to zero within the limits of experimental error. The possible mechanism of action of phosphorylase B is discussed.


Bouyant density of the DNA of sea urchin embryos at different stages of development. Preparations of high-molecular nuclear DNA were obtained from embroys of the sea urchin Strongylocentrotus droebachiensis at the stages of early and late blastula, gastrula, and pluteus. In an equilibrium cesium chloride density gradient, these preparations exhibit a single narrow symmetrical band at 1.695-1.703 g/cm3 with a maximum at l.699 plus or minus 0.001 g/cm3 and do not contain satellite components. Nuclear DNA of embroys at the stage of 128 blastomeres (morula), which has a molecular weight of 10-6, exhibits a single broad symmetrical band at 1.690-1.710 g/cm3 with a maximum at 1.699 g/cm3 in a density gradient. Fragments of blastula and pluteus DNA obtained as a result of treatment with ultrasound give an analogous distribution. Preparations of total DNA of unfertilized ovicells, total DNA of spermatozoids, and cytoplasmic DNA of the morula contain satellite components with buoyant densities of 1.717-1.725 g/cm3 side by side with the main band.


A study of the interaction of oligonucleotides with polynucleotides by the method of equilibrium gel filtration. The effect of magnesium ions and the composition of the oligonucleotides on the stability of the complex. The interaction of the oligonucleotides ApApA, ApApU and ApApC with polyribouridylic acid and of hexariboinosinic acid with and without phosphate near the 3'-end with polyribocytidylic acid was studied by the method of equilibrium gel filtration through Sephadexes. The free energy, the energy and entropy of the complexing were calculated from isotherms of the adsorption of the oligonucleotides on the polynucleotides in relation to the composition of the oligonucleotides and the concentration of magnesium ions in the buffer. It was shown that in the case of the interaction of ApApA and ApApC with poly(U) a perfect triple complex is formed, while in the case of the interaction of ApApU with poly(U) the noncomplementary base is partially displaced from the complex. The free energy of the interaction of neighboring oligonucleotides in a complex with polynucleotides is from --1000 to --3000 cal/mole depending on the type of the complex. It was shown that after the interaction of hexainosinic acid with poly(C) a double complex is formed. The free energy of the interaction of neighboring oligonucleotides in this complex is formed. The free energy of the interaction of neighboring oligonucleotides in this complex is about --1200 cal/mole. Magnesium ions have a different effect on the formation of triple and double complexes in the interaction of oligonucleotides with polynucleotides.


Dependence of noncovalent interactions of benzene and adenine rings on distance between them in adenylyl-(5' yields N)-omega-arylalkylamines. A series of adenylyl-(5' yields N)-omega-arylalkylamines, containing from one to six methylene groups in the amino component, was studied by methods of nuclear magnetic resonance and circular dichroism. It was shown that independently of the length of the aliphatic chain of the amine convergence of the adenine and benzene rings and a hydrophobic interaction between them occur. The plane of the benzene ring is inclined toward the adenine ring, which has an anticonformation relative to the ribose. The structure of the intramolecular complex and the energy of the interaction of the aromatic systems of the amine and nucleotide depend on the number of methylene groups in the amino component. Maximum interaction occurs in the presence of two methylene groups; weakening of the interaction occurs with an increase in the chain to four links, which does not change upon further lengthening of the chain. The conformation of adenylyl-(5' yields N)-benzylamine differs from the structure of the other compounds of the series investigated.


Diffuse scattering of x rays by polypeptides and proteins in solution. III. Analysis of scattering curve of sperm whale myoglobin. X-ray scattering curves for the sperm whale myoglobin molecule and a model which includes only the helical regions of the polypeptide chain are calculated. The portion of the scattering curve associated with the packing of the helices inside the protein globule is analyzed. The model of the myoglobin molecule is used to investigate the sensitivity of the scattering curve to changes in the mutual packing of the helical regions.


The action of staphylococcal nuclease (EC-number 3. 1. 4. 7.) on thymus nucleohistone (TNH) and on some nucleoprotamines. The biphasic nature of the time course of the action of staphylococcal nuclease on thymus nucleohistone was confirmed by studying the hydrolysis of this nucleoprotein at various enzyme concentrations. The transition from the rapid first to the sluggish second phase of the time course was particularly distinct at the highest enzyme concentrations. The rapid initial phase of the hydrolysis curve leveled off sharply when between 60 and 65 per cent of the total TNH phosphorus had been converted to acid-soluble phosphorus compounds. The insoluble complexes of TNH with protamines were found to be very resistant against the action of staphylococcal nuclease. The time course of the action of staphylococcal nuclease on a commercial nucleoprotamine of salmon testicles was found to become very sluggish when between 35 and 40 per cent of its total phosphorus had been converted to acid-soluble phosphorus compounds. When nucleoprotamines prepared in the laboratory from the secreted sperm cell suspension of Brown Brook Trout were digested with staphylococcal nuclease, only between 15 and 20 per cent of the total phosphorus were cleaved to acid-soluble phosphorus compounds during the rapid phase of the nuclease action. The respective values for the phosphorus fractions available for magnesium-binding and those susceptible to the rapid cleavage by staphylococcal nuclease were found to be very similar.


Protein composition of nuclear 14 S ribonucleoprotein particles containing poly (A). Nuclear 14 S RNP particles containing poly (A) from Ehrlich ascites carcinoma cells and rat liver were purified by re-sedimentation in sucrose gradients, by Cs2SO4 density gradient centrifugation and by affinity chromatography on a poly (dT)-Sepharose column. Proteins of these RNP particles were electrophoresed in urea and SDS-polyacrylamide gels. RNP particles of ascites carcinoma cells contain two main bands having molecular weights of 51 000 and 69 000 daltons, respectively, and two or three minor components.


The separation of rat liver endoplasmic reticulum membrane proteins by two dimensional polyacrylamide gel electrophoresis. The separation of rat liver endoplasmic reticulum membrane proteins by two dimensional polyacrylamide gel electrophoresis is described. By this method, the proteins of the rough membrane ribosomes could be separated from the other rough membrane proteins. Both rough and smooth membrane fractions contain at least 30 defined membranal proteins. The electro-phoretic patterns of rough and smooth membrane proteins are clearly different.


Buoyant density centrifugation of sea urchin embryo chromatin on sucrose-glucose gradient. Unsheared chromatin isolated from sea urchin embryos was submitted to buoyant density centrifugation in sucrose-glucose gradients. The main peak of blastula chromatin was at a density position of 1.299 plus or minus 0.028 plus or minus 0.009 g ml -minus 1 whereas at gastrula stage a shift to a lower bouoyant density position of (1.276 plus or minus 0.021 plus or minus 0.007 g ml minus 1) was observed. Besides the main peak, a small band with a density of 1.18 g ml minus 1 was noticed. The lighter fraction differed from the heavy one in a higher histone to DNA ratio, a lower proportion of the F-1 histone, and a lower nonhistone to DNA ratio. The most pronounced developmental alterations of proteins were observed at the level of nonhistone protein patterns of the light fractions.


Different sensitivities of avian- and mammalian-haemoglobin synthesis to elevated temperatures. Avian- and mammalian-haemoglobin synthesis show different sensitivities to elevated temperatures. Temperature-dependent, reversible polyribosome disaggregation in avian cells occurs only at 45 degrees C, which is 3 degrees higher than the temperature for mammalian cells, and seems to be due to a block in the initiation of new polypeptide chains. The implications of these findings are discussed.


The in vitro reconstitution of a functional rough membrane active in protein synthesis. Rough endoplasmic reticulum was reconstituted from free polyribosomes and rough membrane stripped from its ribosomes by KCl and puromycin. The reconstituted rough membrane resembled the native rough membrane in the following aspects: RNA/protein ratio, buoyant density in a continuous sucrose gradient, amino acid incorporation capacity and sensitivity towards protein synthesis inhibitors. When the reconstitution was done with double labelled polyribosomes ([32-P] polyribosomes, [3-H] leucine labelling of nascent peptide chain before or after the attachment of the polyribosomes to the membrane) both labels banded together with the reconstituted rough membrane band. Hybrid rough membrane could be formed from rat liver stripped rough membrane and wheat germ ribosomes. This hybrid membrane could translate globin mRNA.


[Investigations on the Heredity of the Nephrotic Syndrome (author's transl)]. The familial nephrotic syndrome has a frequency of 3%. There are 2  types of manifestation. A malignant form with probably autosomal recessive inheritance and bad prognosis, and a benign form with the histology of mimal change disease, complete recovery and a multifactorial inheritance. According to the literature and our own calculations there is in the BRD a yearly frequency of 9--14.4 families with a familial nephrotic syndrome, based on the assumption of 300--480 new cases of nephrotic syndrome per year.


[Long-Term Results of Surgical Treatment of Spinal Tumours in Children and Adolescents]. Catamneses of children up to the age of 16, operated on spinal tumours, are reported. Spinal tumours of this age account for about 15% of the total (all ages). There are about 50% intradural and 50% extradural tumours. The most frequent extradural tumours are sarcomas, followed by lipomas and dysontogenetic tumours like teratomas. Intradural tumours consist of intramedullary and extramedullary ones, about 50% each. Intramedullary tumours are gliomas, extramedullary ones may be neurinomas, meningeomas and vascular tumours. Time from onset of first diffuse symptoms up to clinical diagnosis depends on growth tendency of the tumour as well as on its localization. Hence, case history in cases of intramedullary gliomas usually covers two years, of sarcomas only a couple of months. In half of the cases, pain was the first symptom, followed by disturbed motor function. In more than 50% of the cases, complete restoration or significant improvement could be achieved by surgery. In the remaining half, there was either no change or even deterioration of the disturbed function.  It seems justified to replace the former pessimistic attitude towards therapy of spinal tumours in childhood by a discret optimism. If in addition other spinal diseases like disk herniation are taken into account, prognosis is even more favourable.


[Correlation of obstetrical and clinical data with nevi flammei in the newborn (author's transl)]. Nevus flammeus (teleangiectaticus) is the most common variety of congenital nevus. Among 3961 infants checked at the ages of 3--7 days and again at 6 weeks 42% showed nevi flammei mediales in the nape and/or in the eyelids and glabella. The mothers of the infants presenting with n.fl. tended to be overweight, to have circulatory distrubances and prolonged duration of laor. The infants with n.fl. frequently had concomittant edema, navel hernia and minor degenerative stigmata. However malformations did not occur more commonly. This investigation suggests that exogenous factors such as diseases during pregnancy, intake of drugs and difficulties in delivery do not influence the genesis of n.fl. Only constitutional factors could be correlated with the incidence of n.fl. Since there was a higher frequency in female than in male infants and a lower frequency in premature than in term newborns it may be that hormonal inffluences increase the incidence of n.fl., too. These results were obtained from the prospective study: Schwanger-schaftsverlauf und Kindesentwickling (DFG).


[A new classification of urinary tract infection in children (author's transl)]. A classification of urinary tract infection based on severity of infection is presented. It is based primarily on the presence or absence of symptoms of urinary tract infection. The symptomatic infections are subdivided according to results of certain blood tests indicating general infection or not. Grade 1 covers asymptomatic bacteriuria, and grade 2 symptomatic infections with no signs of general infections. Grade 3 comprises symptomatic urinary tract infections with changes indicative of general infection. Elevated ESR and leucocytosis of the blood were regarded as criteria of general infection.


[Fatigue fracture of the tibia and fibroma non ossificans in a girl (author's transl)]. Stress, fatigue or march fractures rarely occur in children. Usually the bones do not show any other pathological alterations. The authors observed a 10 year old girl with stress fracture of the tibia, and additional skeletal alterations like "fibroma non ossificans" which probably are not connected with the main disease.


[Epidemiology of Tuberculosis in Children from 1968 til 1973 in Schleswig-Holstein (author's transl)]. In Schleswig-Holstein 271 children (131 boys, 140 girls) were treated for tuberculosis between january 1968 and June 1973; 84% were aged 5--14 years, 14% between 1--4 years and 29% between 0--1 year. Each year, nearly the same number of infections occurred in the various districts of the country. In 246 children a primary form of tuberculosis was diagnosed (in 11 cases with pleurisy). 11 patients tuberculous meningitis, 3 patients miliary tuberculosis and 5 patients another form of the disease, 18 of 271 patients (7%) had been vaccinated against tuberculosis as newborns; in 4 of these children tubercle bacilli could be isolated. BCG vaccination had been done 8--12 years before disease in 11 cases and 1--5 years before disease in 7 cases. None of these vaccinated children had a hematogenous tuberculosis or died. Of the non-vaccinated children two patients had meninogencephalitis and died. The other children were cured by chemotherapy, 12 children by additional surgery. The morbidity of tuberculosis in Schleswig-Holstein was 7--10 per 100000 children. Therefore, further BCG vaccination, chemoprophylaxis or preventive chemotherapy seems necessary. Early recognition of tuberculosis in old persons may be of practical value to prevent infections in children.


Non-equivalence of YEPD and synthetic complete media in yeast reversion studies. In yeast reversion studies, assay of the total number of cells is made by plating irradiated cells on agar plates containing yeast extract, peptone and dextrose (YEPD) medium. The number of revertants are scored by plating cells on synthetic complete (SC) medium deficient in the particular nutrient for which the reversion is tested. In this procedure equivalence for cell survival between the YEPD and the SC media is always assumed. However it is shown in this paper that this assumption is valid only up to dose levels where cell killing is not significant. At high doses, survivals on the two media differ significantly from each other for both high and low LET radiations. This difference influences the slope of the reversion frequency curve at high doses. Since the reversion frequency is expressed with reference to the number of survivors after a given radiation dose, it is essential to see that the same chance of survival is offered to the reverted and unreverted cells. Even though reversion is reported to vary linearly with dose, it is found that this linearity is restricted only to dose levels where cell killing is not significant. At higher doses, the reversion frequency varies in a very complex manner with dose for both high and low LET radiations. The complexity depends further on the reference medium chosen.


Mutation and nuclear stage in Schizosaccharomyces pombe. I. An experimental approach to the role of recombination in mutation induction. A reverse mutation system using G1 and G2 cells of Schizosaccharomyces pombe is described. In order to enable the system to deal with the problem of mutation dependence on recombination, tests were performed on (i) the homogeneity of cell populations with respect to nuclear stage;(ii) the fate of cells during post-irradiation incubation;(iii) the colony-forming ability of G1 and G2 revertants, and (iv) cell viability on the mutation plates. On the basis of the results, it is thought that, using this system, information can be obtained on the role of recombinational events in the process of mutation induction.


Mutation and nuclear stage in Schizosaccharomyces pombe. II. Reverse mutations induced by x-rays in the absence of recombination. Induction of mutations by X-rays in Schizosaccharomyces pombe cells in which sister-strand recombination appears to be excluded is offered as evidence against a requirement for recombination in radiation-induced mutagenesis.


Analysis of the dominance effect of a spontaneous recessive lethal in the mouse on homozygous and heterozygous genetic background. A spontaneous lethal (l-15) without detectable dominant phenotypical effects has been studied in F-4 offspring on a homozygous (CBA/CBA) or a heterozygous (CBA/Ajax) genetic background. No significant dominance effect resulting in increased intra-uterine death or decreased mating ability was found irrespective of the genetic background.


Chromosomal rearrangements induced in mouse spermatogonia by 14.5-MeV neutrons. Inbred CBA male mice were irradiated with 14.5MeV neutrons. Three acute doses, 75, 150 and 250 rad, and one chronic dose, 250 rad, were given. The percentages of affected spermatocytes as counted from reciprocal translocation which had been induced in spermatogonia were 0.7, 0.8 and 1.6 respectively for acute series and  2.2 after chronic exposure. The data could be fitted to a linear or concave curvilinear regression line. There seemed to be a slight increase of damage with dose, even if the percentages were generally lower than those reported earlier for fast neutrons with energies around 1 MeV. The existence of dose-relat effects is discussed, and the conclusion drawn so far is that there seems to be no such effect either for 1-MeV fast neutrons or 14.5-MeV high energy neutrons. The term "reversed dose-rate effect" as used earlier, relates to another phenomenon. The difference between the point estimates for the chronic and acute 250 rad series is not significant. The effectiveness of neutrons with energies around 14MeV versus neutrons with energies around 1 MeV is discussed.


The yield of chromosomal aberrations in rabbit lymphocytes after irradiation in vitro and in vivo. The culture time of rabbit lymphocytes (41-42h) that provides cells in their first post-stimulation mitosis, was estimated on the basis of the mitotic index, dicentric yield and presence of the cells with these aberrations unaccompanied by acentric fragments, studied as a function of culture duration. The cells obtained in metaphase from cultures terminated at this time displayed no donor-to-donor variation where induction of dicentrics by x-rays was concerned. Rabbit venous blood was irradiated in vitro with a range of X-and gamma-ray doses, and dose-effect curves were obtained by regression analysis. Sixteen rabbits were irradiated in vivo (uniform whole-body irradiation), and blood was sampled 10 min, 6, 24, and 48 h after exposure. The frequency of dicentrics in the lymphocytes cultured did not change significantly over the first 24 h after irradiation. Dose-effect relationships in vivo fell within one standard error confidence limits of the respective curves in vitro. The authors conclude that the latter may be used for estimation of dose in vivo under conditions of homogeneous whole-body irradiation.


The effect of methylxanthines on chromosomes of human lyphocytes in culture. The effect of caffeine (I,3,7-trimethylxanthine), theophylline (I,3-dimethylxanthine), theobromine (3,7-dimethylxanthine), paraxanthine (I,7-dimethylxanthine) I-methylxanthine, 3-methylxanthine, and 7-methylxanthine added at the 48th h on the chromosomes of human lymphocytes in 72-h cultures has been investigated. Caffeine and the dimethylxanthines cause breakage at 750 mug/ml, with caffeine the most, and paraxanthine the least clastogenic. I-Methylxanthine and dimethylxanthines with a methyl group in the I-position are the most effective in depressing mitotic indices. No chromosome damage was exhibited by the monomethylxanthines.


N-nitrosomorpholine and N-nitrosobutylamine-stimulated DNA synthesis in BHK-21/C13 cells. Non-semiconservative DNA synthesis was examined in BHK-21/C13 cells after treatment with the aliphatic N-nitrosobutylamine (NB) and the heterocyclic N-nitrosomorpholine (NM). The extent of repair synthesis after alkylation was compared quentitatively and calculations were made of the amount of DNA damage per cell and number of bases inserted per damaged site. Of the chromosome aberrations caused by NM the most predominant were dicentrics. Other aberrations included fragments, gaps, breaks and exchanges of both the chromatid and chromosome type. Unlike NM, NB elicted a higher frequency of chromatid breaks.


Work activity and coronary heart mortality. To appraise the role of physical activity in reducing coronary mortality among longshoremen, 6351 men, 35 to 74 years old upon entry, were followed for 22 years or to death or to the age of 75. Their longshoring experience was computed in terms of work-years according to categories of high, medium and low caloric output. Individual work assignments were reclassified annually to allow for effect of job transfers. The age-adjusted coronary death rate for the high-activity category was 26.9 per 10,000 work-years, and the medium and low catgories had rates of 46.3 and 49.0 which were little different from each other. This protective "threshold" effect was seen especially for the sudden-death syndrome, in which the death rate for heavy workers was 5.6, as contrasted with 19.9 for moderate and 15.7 for light workers. We conclude that repeated bursts of high energy output established a plateau of protection against coronary mortality, and that several different mechanisms may explain this finding.


Hemolytic uremic syndrome in families.

Hemolytic uremic syndrome in families. The occurrence of the hemolytic uremic syndrome in three siblings prompted us to study this illness in families. Two groups of patients could be identified when 83 siblings with the syndrome in 41 families were examined. Siblings whose onset occurred within a short time of each other had a relatively good prognosis (19 per cent mortality); those whose onset was more than a year apart had a poorer prognosis (68 per cent mortality). We speculate that an environmental agent may have caused the syndrome in the first group, and that genetic factors may have been important in the second.


Successful application of prenatal diagnosis in a pregnancy at risk for homozygous beta-thalassemia. A Sicilian couple whose first child had homozygous beta-+-thalassemia requiring monthly transfusion requested prenatal diagnosis during the second pregnancy. Fully informed consent was obtained. The placenta was localized by ultra-sound at the 20th week of gestation, and was aspirated with a 20-gauge needle. Samples containing fetal red cells were obtained, and studies of globinchain synthesis showed a normal beta/gamma synthesis ratio for this gestational age. The conclusion that the child was not affected by beta-thalassemia was confirmed when an infant not affected with homozygous of heterozygous beta-thalassemia was born at term. Although more experience with this approach is necessary, this study demonstrates that prenatal diagnosis or exclusion of beta-thalassemia and sickle-cell anemia is feasible.


Indwelling arterial catheters as a source of nosocomial bacteremia. An outbreak caused by Flavobacterium Species. Between mid-May and mid-October, 1973, 49 blood cultures from 14 patients in an intensive care unit were positive for flavobacterium species, Group II-b. We conducted an investigation to determine how patients were being infected with this unusual organism. Comparison of the 14 infected patients with 37 controls associated indwelling arterial catheters with subsequent flavobacterium bacteremia (p = 0.005). Risk of infection was greatest during the period in which blood gas determinations were done most frequently (the first three days of catheterization) and in which infected patients had more blood gas determinations than control patients with arterial catheters (p less than 0.05). Flavobacterium species was cultured from in-use arterial catheters, from stopcocks, and from ice in the intensive-care unit's ice machine; the catheters were probably contaminated by syringes that were cooled in ice before being used to obtain arterial specimens for blood gas determination. This outbreak calls attention to arterial monitoring systems as a potential source of nosocomial infection.


Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. Although morphine depresses respiration the mechanism of this depression remains unknown. Accordingly, ventilatory responses to hypoxia and to hypercapnia were measured before and after administration of 7.5 mg of morphine sulfate subcutaneously in six normal subjects. This procedure produced resting hypoventilation manifested as a peak rise in alveolar carbon dioxide tension from 42.9 plus or minus 1.7 to 45.4 plus or minus 1.5 mm Hg (plus or minus S.E.M.) at 30 minutes ( greater than 0.01). Hypoxic ventilatory drive, measured by an index of the relation between ventilation and hypoxia (parameter A), decreased from a control of 108 plus or minus 17.6 to 42.8 plus or minus 5.3 at 60 minutes after morphine (p greater than 0.01); Hypercapnic ventilatory drive, measured as the slope of the ventilatory response to hypercapnia, also decreased from 1.69 plus or minus 0.24 to 0;98 plus or minus 0.20 (p greater than 0.01) 75 minutes after morphine. Decreased responsiveness to the chemical stimuli to breathing may contribute to the ventilatory depression frequently seen after administration of morphine.


Development of an intravenous bile acid tolerance test. Plasma disappearance of cholylglycine in health. To develop an intravenous bile acid tolerance test that might be useful for detecting impaired liver function or liver injury, the plasma disappearance of intravenously injected cholyglycine was characterized in healthy man by a radiommunoassay, specific for conjugates of cholic acid, on serial samples of venous blood. Cholylglycine disappearance was rapid (mean half-life plus or minus S.E. equals 2.6 plus or minus 0.1 minutes) and of first-order kinetics; the rate of disappearance was independent of dose between 2 and 15 mumoles per kilogram of body weight. A dose of 5 mumoles per kilogram was selected as an optimal dose, and its clearance was defined in 45 healthy subjects. After intravenous injection of this dose, conjugates of cholic acid increased 10-fold, but in all subjects the concentration of these bile acids had returned to 1 muM (the upper limit of normal, fasting state) by 10 minutes. No side effects were observed.


Validity and sensitivity of an intravenous bile acid tolerance test in patients with liver disease. A bile acid tolerance test, which measures the plasma disappearance rate of injected cholyglycine by radioimmunoassay, was studied in 36 patients with biopsy-proved chronic liver disease and compared to fasting-state levels of conjugated cholic acid and other conventional liver tests. In 25 patients in whom one or more of the conventional tests for liver disease showed abnormal results, fasting-state levels of conjugated cholic acid were increased in 20, but plasma disappearance of cholyglycine was delayed in all. Of the 11 other patients in whom conventional tests were within normal limits, fasting-state levels of conjugated cholic acid were increased in three of 10, but cholyglycine disappearance was dealyed in nine of 11. The bile acid tolerance test indicated liver disease more sensitively than the fasting-state level of conjugated cholic acid, which, in turn, was more sensitive than other conventional liver tests.


Failure of association of premature rupture of membranes with respiratory-distress syndrome. Records on 16,458 consecutive births were examined to determine associations between the respiratory-distress syndrome of the newborn and cesarean section, maternal diabetes, ante-partum hemorrhage, toxemia of pregnancy, low one-minute Apgar scores and prolonged rupture of fetal membranes. Groups of infants were compared by four-week gestational age blocks. One-minute Apgar scores of less than 5 and of less than 8 were associated with a significant ( less than 0.05) increase in the incidence of respiratory-distress syndrome at gestational ages beyond 30 weeks. Cesarean section was associated with a significant increase after 34 weeks of gestation. There was no association between the syndrome and toxemia of pregnancy, ante-partum hemorrhage or prolonged rupture of fetal membranes. These data do not support the hypothesis that there is a lower incidence of the respiratory-distress syndrome in infants born after prolonged rupture of fetal membranes.


Nonketotic hyperglycinemia. Glycine accumulation due to absence of glycerine cleavage in brain. Glycine concentrations were measured in plasma and cerebrospinal fluid of five patients in different types of hyperglycinemia to determine why severe neurologic deterioration is confined to the so-called nonketotic form of hyperglycinemia. Glycine content and glycine-cleavage enzyme activity were also determined in brain obtained in autopsy from three of these patients. Spinal-fluid glycine concentrations were 15 to 30 times above normal in patients with nonketotic hyperglycinemia, but were normal in those with hyperglycinemias of undetermined type who had comparable elevations of plasma glycine. Glycine content was two to four times above normal in several brain regions, and brain glycine cleavage enzyme activity was absent in two patients dying of nonketotic hyperglycinemia. By contrast, glycine content was normal and glycine cleavage activity present in the brain of an infant who died of hyperglycinemia of unknown cause. These results suggest that elevated glycine levels may be harmless in blood, but lethal in brain.


Time lapse between hypothesis and publication in the medical sciences. We studied a number of factors involved in the publication of 103 papers by Mayo Clinic authors. Basic-science and clinical-research articles averaged about four years from initiating the research idea until publishing; case reports averaged about two years, and literature reviews three years. Of this time, 75 per cent was spent contemplating the basic idea, performing the research, and writing the paper. The rest was required for processing, from institutional editing through publication. Most clinical workers wrote at home, and most basic researchers at the office. In a suprising 23 per cent of papers, about three fourths of the manuscript was written by someone other than the first author. Of references cited, between 10 per cent and 20 per cent were to the authors' own work or to that of co-workers. Half the papers were revised or rejected at least once, prolonging the journal handling time only in papers rejected or requiring more than one revision.


Heat-labile enzymes in skin fibroblasts from subjects with progeria. To characterize further the genetic basis of progeria, thermolability studies were performed on three genetically distinct enzymes in crude extracts of cultured skin fibroblasts derived from two subjects with that syndrome. At early passage the progeric fibroblasts, as compared to controls, contained a significantly higher percentage of heat-labile glucose-6-phosphate dehydrogenase (12.83 plus or minus 1.72 vs 1.11 plus or minus 0.44 [mean plus or minus S.E.M.], p smaller than 0.001), 6-phosphogluconate dehydrogenase (9.71 plus or minus 0.68 vs. 0.67 plus or minus 0.22, p smaller than 0.001), and hypoxanthine-guanine phosphoribosyltransferase (31.41 plus or minus 1.89 vs 7.67 plus or minus 1.71, p smaller than 0.001), and the differences were maintained throughout the in vitro life-span. These data, in conjunction with previous reports of defective HL-A antigens, indicate a widespread defect in genetic expression. The most likely cause appears to be an aberration in protein synthesis or degradation, or both, although multiple somatic mutations cannot be ruled out. Increased thermolability of enzymes in cultured cells may provide a screening test for persons predisposed to progeria and other disorders of premature aging.


Effect of oxandrolone treatment on the activity of lipoprotein lipase, hepatic lipase and phospholipase A1 of human postheparin plasma. The effect of a synthetic steroid, oxandrolone, on total postheparin plasma lipolytic activity, postherpain hepatic lipase activity, lipoprotein lipase and phospholipase A1 was studied in seven patients with hypertriglyceridemia. The mean total postheparin lipolytic activity increased 100 per cent during oxandrolone tratement (p smaller than 0.05). This change was caused mainly by postheparin hepatic lipase, whose activity increased on the average more than 2.5 times (p smaller than 0.001). The change in postheparin plasma-lipoprotein-lipase activity was insignificant. A highly significant correlation (r equals +0.87, p smaller than 0.01) was observed between the activities of postheparin hepatic lipase and phospholipase A1 before and during oxandrolone treatment. No relation was observed between serum triglyceride level and various postheparin lipase activities, or between the changes induced by oxandrolone in the level of serum lipids and the activities of postheparin lipases. We conclude that oxandrolone increases the activities of postheparin plasma hepatic lipase and phospholipase A1 but has little influence on lipoprotein lipase.


Serum insulin and growth hormone response patterns in monozygotic twin siblings of patients with juvenile-onset diabetes. To detect abnormalities in the secretion of insulin and growth hormone in monozygotic twin siblings of patients with juvenile-onset diabetes, their responses during oral, cortisone-primed oral, and intravenous, glucose tolerance tests and intravenous tolbutamide tests were compared to those of matched controls. The twins had higher mean serum insulin levels during all tests, but differences reached statistical significance (P less than 0.02) only in the cortisone-primed test. Growth hormone levels were higher in the twins (P less than 0.04) in the intravenous tolbutamide tolerance test. The frequency of abnormal oral glucose tolerance tests among controls, diabetic monozygotic twins and the offspring of two diabetic parents was also compared. Twins and controls had nearly the same frequency of normal tests; however, the diabetic offspring had a significantly higher (P less than 0.001) prevalence of abnormal tests. These data suggest that magnitudes of environmental and genetic factors operating in monozygotic "pre-diabetic" children of diabetic parents.


Detection and treatment of hypertension at the work site. A program linking detection to treatment was designed to improve blood-pressure control among adults with asymptomatic, uncomplicated hypertension. Key elements of this program were provision of all diagnostic and therapeutic services at work site, integration of delivery system with the administration of a labor union, adherence to rigid protocol, and continuous patient surveillance by nurses and paraprofessionals. At the first program site, Gimbels's principal New York City department store, 84 per cent of 1850 employees were screened, and 65 per cent of 186 with confirmed hypertension elected the treatment program. Of the 94 patients followed for one year, 97 per cent remained under therapy, with no untoward effect, and 81 per cent of patients had satisfactory blood-pressure reduction. This approach appears to be a safe, effective, and acceptable method for hypertension control in large numbers of patients.


[Aspergillus insulicola Sp. Nov].

[Aspergillus insulicola Sp. Nov]. A strain of Aspergillus sp. is described and proposed as a new species under the name "Aspergillus insulicola sp. nov." Montemayor & Santiago, 1973. This strain was isolated from soil samples taken in "Aves Island" during a scientific expedition.--Aves Island, situated at 15 degrees, 40 feet, 42 inches N and 63 degrees, 36 feet, 47 inches W, about 665 Km of the coast of Venezuela, has very special ecological conditions. Due to its smallness: 550 m long and 40 to 120 m across and to its low profile only 3 m over sea level, it is swept by the sea during the periodical storms and hurricanes in the area. It has thus a very interesting fauna and flora. We took a series of soil samples to study its mycological flora. Forty samples were inoculated by dilution method. In this first paper a species is described and proposed as a new species because of its macroscopic and microscopic characteristics, as well as by its biological properties, under the name "Aspergillus insulicola sp. nov.". In its study we have tried to follow as closely as possible the methods recommended by Kennet B. Raper & Dorothy Fenell, world authorities on the genera Aspergillus and Penicillium. The strain is being kept in USB under the number T1, and has been sent to ATCC & CBSC to be incorporated in their collections.


Carbohydrate composition of the isolated cell walls of dermatophytes. In an attempt to evaluate taxonomic character of sugar composition of dermatophytes, the purified cell walls from 13 species are analyzed on neutral sugar composition by gas liquid chromatography. The results were principally compatible with those obtained by conventional morphological examination. Neutral sugar components of dermatophytes cell walls were mannose and glucose in the ratio of 1:2.7 for Epidermophyton and 1:1.4 for Microsporum. There were two types in Trichophyton, in which the ratios of mannose to glucose were 1:1.6 and 1:3.8. The cases of Trichophyton ferrugineum and Trichophyton mentagrophytes were exceptional. The ratio of the former was 1:1.4, which implied the relation to Microsporum group, and the ratio of the latter was 1:2.3, which was supposed to be the intermediate of two types of Trichophyton group. Albino type cell wall of Epidermophyton floccosum was more rich in glucose than pigmented type one.


Experimentally induced mycetoma: species of Sporotrichum and Sporothrix. The potential pathogenicity of four saprophytic species of Sporotrichum, viz; S. carnis, S. cerebriforme, S. pruinosum and S. thermophile were compared to S. schenckii and all could survive in vivo and S. pruinosum may possess limited virulence. Thielavia thermophila and Sporothrix albicans were able to cause local mycetoma.


Single dose metyrapone test: 11 beta-hydroxylase inhibition by metyrapone and reduced metyrapone assayed by radioimmunoassay. To assess the effects of metyrapone and reduced metyrapone on 11 beta-hydroxylase inhibition, the plasma levels of cortisol, 11-deoxycortisol, and the inhibitors were measured by radioimmunoassays in 34 normal subjects 8 h after they received a single oral dose of metyrapone at midnight. The ratio of 11-deoxycortisol to cortisol, as an index of 11 beta-hydroxylase inhibition, was compared to plasma levels of metyrapone and reduced metyrapone. One subject received an infusion of metyrapone ditartrate in order to study the sequential conversion of metyrapone to reduced metyrapone. A new radioimmunoassay was developed for measurement of plasma concentrations of metyrapone and reduced metyrapone. Following intravenous administration of metyrapone, it is rapidly converted to an active metabolite, reduced metyrapone. At 8 h after a dose was given, the average reduced metyrapone level was 1.5 times higher than the average metyrapone level. Following oral administration of the drug, we found a high correlation when plasma levels of metyrapone were compared to reduced metyrapone and when the ratio of 11-deoxycortisol to cortisol was related to metyrapone or to total metyrapone levels. In conclusion, the conversion of metyrapone to reduced metyrapone is such that by 8 hours after a single oral dose, more than one-half of the inhibitory effect on 11 beta-hydroxylase appears to be produced by reduced metyrapone. The inhibitory action of metyrapone and reduced metyrapone on the enzyme system is reflected by their concentration  in plasma.


Modified nucleosides and bizarre 5'-termini in mouse myeloma mRNA. Messenger RNAs from mouse myeloma cells contain N-6-methyl adenosine and novel 5' termini having 7-methy-guanosine in a 5', 5' triphosphate linkage with ribose-methylated nucleosides. Ten common 5'-terminal sequences of the forms m-7-G-5'-PPP-5'-NmpNp and m-7-G-5'-ppp-5'-NmpNmpNp are reported. Structures like this may be a general feature of mRNA in eukaryotes.


Adequate dialysis.

Adequate dialysis. Regular haemodialysis with the Kiil dialyser for 8-10 h three times a week is the present standard of adequate dialysis. In 100 patients treated by this regime there was no positive correlation between plasma urea and creatinine before or after dialysis and any of the symptoms of which these patients still complained. There are no grounds for believing that a further increase in dialysis would relieve residual symptoms. However, any reduction in current standards of dialysis should be justified by prolonged clinical trial of large groups of patients before they are accepted as equivalent in view of the infrequency of some uraemic manifestations such as pericarditis. The implications of the middle molecular hypothesis are discussed.


The present status of radical prostatectomy for stages A and B prostatic cancer. The natural history of prostatic cancer is incompletely understood. Small cancers may have a very slow or rapid growthrate, and the majority are differentiated. Cells may leave the prostate by blood or lymph without penetrating capsule or invading the seminal vesicles. The predication of latency or of biologic activity in any givne case is impossible. Stage A cancer should be separated into A1 (focal) and A2 (diffuse). Stage A1 cancer that is low grade is best lfet alone. Stage A2 cancer and high grade cancer probably  should be treated by megavoltage radiation. Stage B includes many cancers that are microscopically stage C. If this stage is separated into clinical stage B1 (tumors grossly involving less than one lobe), and B2 (tumors involving one lobe or more) the underestimation of microscopic extent in B1 will be less than in 10 per cent of the cases. In clinical stage B2 cancer, 50 per cent are microscopically stage C. Radical prostatectomy for cure should be limited to clinical B1 cases without distant spread. It is not a cure-all, but it provides the best 15-year survival rate more completely, more quickly, less expensively, and with fewer discomforts than other methods. The alternative options are no treatment, endocrine treatment, and radiation. The first is risky in many instances and may allow an ac-ive cancer to get out of control. The second rarely destroys all of the cells in the total cell population and gives one a false sense of security. The last should be reserved for cases well beyond stage B1, but without distant metastases, where its usefulness exceeds that of radical excision.


Function of the kidney in adult patients with Cooley's disease. A preliminary report. The function of the kidney in adult subjects with Cooley's disease has been hitherto inadequately investigated. In 10 patients suffering from thalassemia major, glomerular filtration rate, renal plasma flow, renal blood flow have been studied, together with urine concentration capacity. The authors emphasize certain pathological changes, such as the increase in renal plasma flow and the failure of the urine concentration ability. On the basis of renal biopsies, two pathogenetic theories are discussed: the functional impairment of the coutercurrent system and fibrosis of the medullary tissue.


Glomerular-tubular balance for bicarbonate in man. We recently showed in dogs that there is a close relationship between bicarbonate reabsorption and glomerular filtration rate (GFR). The present studies were designed to confirm these findings in five normal men. Bicarbonate titrations were done after ingesting a low protein diet for one week and were repeated following elevation of GFR 11-29 per cent by high protein diet and dexamethazone ingestion. In every casetubular reabsorption of bicarbonate increased in proportion to the increases in GFR. We conclude that glomerular-tubular balance for bicarbonate reabsorption is a characteristic of human, as well as canine kidneys.


Measurement of intra-arterial blood pressure and cardiac output through the bovine artegraft. Hemodynamic measurements through the bovine artegraft. Serial hemodynamic studies have become increasingly important in hypertension research. These studies have been accomplished using the A-V shunt. The progressive decline in the number of A-V shunts in favor of the A-V fistula has limited the number of measure cardiac output, the intra-arterial blood pressure cannot be measured through it. The present paper describes a technique for measuring both the cardiac output and direct intra-arterial blood pressure using the bovine artegraft.


On the exudation of plasticizers from PVC haemodialysis tubings. Prompted by a series of hepatitis-like cases in patients on regular haemodialysis treatment, the sets of polyvinylchloride (PVC) test tubings used were submitted to perfusion experiments. The perfusates from four commercially available tubings were also investigated. Diethylphthalate (DEP) could be identified by by IR and PMR spectrometry in the perfusate from the test tubings. UV spectrometry proved the presence of other non-identified substances in the perfusate from both the test tubings and from some of the other tubings.


Aminonucleoside nephrosis in rats. Ultrastructural findings in the glomerulus by concomitant influence of indomethacin and aminonucleoside. The concomitant administration of Indomethacin reduced the biochemical signs of the nephrotic syndrome induced in rats by aminonucleoside; in the rats treated with both drugs a morphological picture suggesting activated function of podocytes was found at the electron microscopic examination of the renal glomerular structures, together with the lesions characteristic of the aminonucleoside nephrosis. The possibility is discussed that Indomethacin could modify the permeability of the glomerular capillary wall by stimulating the podocytes to synthesize basement membrane material.


Effect of prostaglandin a1 on acute renal failure in the rat. In an attempt to alter the natural course of glycerol and uranyl nitrate induced acute ranal failure in the rat, the vasodilator, prostaglandin A1 was adminstered systemically at varying times during the induction phase of renal failure.  According to the method used, no significant beneficial effect could be demonstrated in either experimental model.


Comparison of the role of testosterone and methyltestosterone in developing chloroform-induced renal tubular necrosis in mice. The presence of testosterone is a prerequisite for the development of chloroform-induced renal tubular necrosis in mice.  The purpose of this study was to check whether methyltestosterone exerts the same influence.  Castrated males and females were treated with one of these compounds: those treated with testosterone developed renal tubular necrosis after chloroform injection, those which received methyltestosterone were free of this lesion.


Ineffectiveness of hemodialysis in copper sulphate poisoning. A fatal case of severe copper sulphate poisoning is reported in whom hemodialysis was performed 13 h after ingestion.  At autopsy a significant amount of copper was found in the brain, heart, liver, kidney, spleen and adrenals.  This case indicates sopper is nondialysable and that hemodialysis is ineffective in the treatment of acute copper sulphate poisoning.


Prognosis of chronic renal failure.  III. Survival after one peritoneal dialysis. Survival after serum creatinine exceeded 10.0 mg/100 ml was increased if one peritoneal dialysis was performed.  After one peritoneal dialysis 'survival' of 62 patients to the present time, death or the next dialysis averaged 119 days; median survival was 28 days.  Characteristics of prolonged survivors were persistent reduction of serum creatinine below the predialysis concentration, tubulointerstitial diseases, i.e. polycystic kidneys, pyelonephritis or obstructive nephropathy, potentially reversibel complications such as urinary tract infection or extracellular volume depletion, and high urine volume, and low blood pressure.  Occasional pateints with survival exceeding 2 years suggest the possibility of prolonged benefit after a single dialysis at least in those wiht characteristics favoring longer survival.


[Evaluation of hepatic encephalopathy in portacaval shunts and mesenterico-caval bypass with the jugular vein]. Data relating to 30 patients subjected to side-to-side porta-cava anastomosis and 30 to mesenterico-cava by-pass with the internal jugular vein are presented. At follow-up after a period of over 1 yr, encephalopathy was observed in 40% and 21% of the two groups respectively. Angiography of the coeliac tripod and superior mesenteric showed the existence of a post-operative hepatopetal flow in 80% of porta-cava cases. This incidence was only 30% in the mesenterico-cava group. The relation between the clinical and angiographic data is briefly discussed and neuropsychiatric findings in patients with a picture of hepatic encephalopathy are also presented.


[Classification of congenital aortic stenosis]. Recent epidemiological data relating congenital stenosis of the aorta are cited. An anatomical criterion is used in the formation of three classification groups, each containing a number of different types. There are no clear-cut clinical pictures corresponding to these anatomical varieties, however, so that differential diagnosis is dependent on the haemodynamic and contrastographic data. There are, on the other hand, clinical signs that serve as pointers to the site of the stenosis.


[Our experience with peripheral arterial embolectomy]. 34 cases of acute peripheral ischaemia examined in recent years at the University of Messina General Surgery Clinic are presented. 16 were subjected to embolectomy according to Fogarty. The remaining 18 received protracted medical therapy. Some successes were obtained. In other cases, gangrene necessitated amputation of the affected limb. Satisfactory results were observed in 70% of the operated series. Success was more marked when only a short interval was left between the embolic episode, with progressively poorer results as the penalty for delay. The long-term results of embolectomy are related to the nature of the underlying disease and the treatment given after surgery.


[The association of local radiation therapy and systemic chemotherapy in the treatment of clinically localized Ewing's sarcoma]. The results obtained in 12 cases of still clinically localized Ewing's sarcoma by associating radiation therapy of the primary focus with intermittent systematic chemotherapy are reported. Two of these patients presented pulmonary and bone metastases 12 and 14 months respectively after bioptic diagnosis while the remaining ten were in good health and free from metastasis at between 6 and 28 months (average 16 months) after biopsy. Although it is considered necessary to make further observations before the association's validity is certain, it is considered that on this basis and on the basis of the few cases reported in the literature than the association of rationally conducted systematic chemotherapy with local radiation therapy will extend the onset time of metastasis and so increase average survival in Ewing's sarcoma.


[Measurement of the intradermal reaction to PPD in chronic hepatitis and in cirrhosis. Basic research]. Personal experience on the PPD-test in 154 patients with chronic liver disease is reported. The results show a frequent hyperergic response. The comparison with a similar group of patients previously studied in the same Clinic employing the old tubercolin shows the advantages of PPD in discriminating the differential degrees of reactivitty. The hyperergic response is important not only from a theoretical point of view, confirming the presence of an abnormal immunologic equilibrium in chronic liver diseases, but it may also be of therapeutic relevance particularly in the cases where the result of the test is strong exceedingly strong.


[Ice hockey accidents].

[Ice hockey accidents]. The present study is based on 2680 ice hockey accidents encountered in Switzerland over a period of 5 years: 1880 injuries during matches are compared with 800 that took place in training. Age: the athletes injuried during training were younger that 20 in 40% of cases; 38% of injuries in matches occurred to players aged between 20 and 24. 25% of accidents were caused by blows from the stick, particularly as a result of "high sticking"; 5% by skates; 17% by the puck (hard rubber); 17% by collisions; the remainder by crashing against the barrier, falls on the ice, body checking, etc. The most frequent injuries (42%) involved head and face: 740 dental injuries about of the 1460 facial injuries and 160 cases of concussion. The injuries affected: the legs in 21% of cases; the feet in 11%; the arms in 11%; the hands in 7% and the trunk in 8%. The commonest types of injuries were crushings and bruisings; during matches, 13% of the 1880 lesions involved fractures, a quarter of which were the result of collisions. Preventive measures would require all players to wear a helmet to protect their head, face and mouth; protective barriers should be sufficiently high; the game and rules should be taught from school age on and fair play should be instilled.


[Polygraphic changes in relation to active and passive upright position after myocardial infarct]. In 33 patients on the 15th day after the onset of myocardial infarct, without complications, the effects of active and passive gravitational stress on left ventricular efficiency were studied by measuring systolic intervals. It is concluded that the semivertical passive position means an unfavourable course for left ventricular dynamism wompared with thehorizontal position and that active rising, from this point of view, can be considered more physiological than passive rising.


[Lymphomas: clinical stages].

[Lymphomas: clinical stages]. The degree of diffusion and the histological type are the two main features of lymphoma that determine its course and prognosis, and influence its treatment programme. Recognition of the anatomoclinical stage is now made more certain by the adoption of diagnostic procedures to be applied to all patients in the pre-treatment phase in accordance with rational criteria of choice. Attention is directed to several of such methods: lymphography, photolymphoscintigraphy, scintiscanning with 67-Ga, bone biopsy and exploratory laparotomy with splenectomy. The advantages and limitations of each method are considered.


[Therapy of senile diabetes].

[Therapy of senile diabetes]. Changes in intermediate metabolism (amino acids, carbohydrates and plasma NEFA) noted in diabetes, obesity and old age are discussed.  Results obtained in a series of 1200 cases treated with sulphanylurea with or without biguanides are presented.  Metabolic compensation was obtained with the association in a larger number of obese and aged diabetics (about 15%).


[The association of diabetic disease with Friedreich's disease in members of the same family]. Friedreigh's disease is only rarely associated with diabetes mellitus and only few cases are to be found in the literature, especially as regards siblings.  Three cases of this association in members of two different families are reported.  Two of the patients died from cardiovascular complication; the third case is that of a 32-yr-old woman who was able to complete a pregnancy.  The pathogenesis of the association is discussed and a number of theories are put forward.  The most generally accepted genetic hypothesis makes it possible to explain under a common metabolic denominator neurological disturbances and those in other systems.  The association is not a purely casual event but is perhaps dependent on either two different genes or on a single gene with pleitropic effect.  Heart signs are frequent in Friedreich's disease and brief mention is made of these.


[Simple glaucoma and diabetic disease].

[Simple glaucoma and diabetic disease]. Blood sugar, blood insulin and the insulinogenic index after oral glucose were studied in 41 subjects with simple glaucoma.  Clinical diabetes was present in 9.76% and asymptomatic diabetes in 21.95%.  It is suggested that a high incidence of diabetes may be expected in simple glaucoma, probably as expressions of a common genetic disorder.


[Adriamycin in chemotherapy of solid tumors]. From one to eight, 7 or more day spaced, three-day 0,5 mg/kg/day cycles of adriamycin (an anthracycline antiblastic very similar to daunomycin) were administered to 50 adults with various solid tumour forms.  Toxic signs were constant and sometimes compelled abandonment.  The main residual signs were leucopenia, alopecia and stomatitis.  The drug also displayed a cardiotoxic effect, though this was less than observed with daunomycin.  It is felt that the theoretical interest aroused in adriamycin as an inhibitor nucleic acid systhesis, together with its marked anti-neoplastic efficacy in the experimental animal, have been betrayed by this performance in the management of solid tumors.


[Changes in some plasma parameters in the course of dextran 40]. Changes in certainplasma parameters (Hc, arterial and venous VP, creatinine clearance, potassium, PA and FC) induced by Dextran 40 perfusions (500 ml at 40 drops/min and 250 ml at 20 drops/min) were examined in 50 patients.  The expander effect was more intense, though less protracted when the larger quantity was used.  A rebound effect 24 hr after the test was also more frequent percentage-wise in this group.  Significant changes in Hc were not observed for 24 hr and 96 hr respectively with the higher and the lower dose.  The venous district was primarily concerned.  There were also increases in blood potassium, FC and max PA, while min PA and blood proteins fell.  No relation could be demonstrated between creatinine clearance and diuresis at the end of the test with respect to the amount of Dextran employed.  None of these latter modifications was significant.  There were no signs of intolerance.