Preliminary observations on the use of Corynebacterium parvum in patients with primary intracranial tumors: effect on intracranial pressure. It has been observed that patients with metastatic brain lesions developed neurologic symptoms when given Corynebacterium parvum. To obtain more information in patients with intracranial mass lesions, intracranial pressures (ICP) were measured or observed in six patients undergoing C. parvum therapy. All patients except two (one previously shunted, one recently operated) demonstrated a profound increase in ICP. It is presumed that either edema is formed within brain and tumor tissue (inasmuch as neurologic deterioration has not been observed in patients without an intracranial lesion) or transient increases in cerebral blood flow adversely alter an already compromised intracranial volume. Surgical decompression of tumor volume or use of Lasix may abort this response to C. parvum infusion.


Liver function tests after ligation of hepatic artery. Nine patients with unresectable primary and secondary malignancy of the liver underwent ligation of the hepatic artery (HAL) distal to the gastroduodenal artery as a therapeutic measure. Another patient had a similar operation for hepatic artery aneurysm. Their postoperative liver function tests are studied in detail, and the patterns of change are compared with three other patients who had extensive resection of tissues but without HAL. It appears that liver function tests rarely became abnormal after major operations, whereas HAL produced an immediate rise of lactic dehydrogenase and transaminase (up to 5--60 times normal value), and creatine phosphokinase (4--15 times normal). All elevated enzymes returned to preoperative levels within a week. Alkaline phosphatase and bilirubin rose mildly after HAL and returned to preoperative range in about one week. However, if the patient had repeated surgical stress, anoxic insult, or maximal loss of the hepatic parenchyma, serum enzymes rose only slightly after HAL.


Special problems in the evaluation of results in adjuvant trials of cancer treatment. Adjuvant trials in cancer treatment present special problems in statistical analysis. When the primary treatment modality results in a relatively high cure rate and additional methods of treatment are being inserted in an effort to raise the figures to even higher levels, therapeutic benefit can be obscured unless all features of the study are carefully considered. Biologic benefit may easily be masked by the sizable number of patients randomized to receive adjuvant treatment who have no residual tumor and therefore could not possibly benefit therefrom. For example, 50% of patients undergoing "curative" resection for colon cancer survive without evidence of disease beyond the five-year postoperative period; thus at least half the patients randomized to receive adjuvant treatment (chemotherapy, radiotherapy, immunotherapy) will be disease-free at the time of randomization and cannot benefit from adjuvant therapy. New methods of assessment of treatment must be developed; otherwise, substantial therapeutic effectiveness may go undetected.


Treatment of symptomatic metastatic cancer to the liver from primary colon and rectal cancer by the intraarterial administration of chemotherapy and radioactive isotopes. Sixty-five patients were referred for treatment with symptoms resulting from metastatic cancer to the liver from the GI tract. Two groups of patients were analyzed. The first group of 40 patients were subjected to a laparotomy and insertion of a catheter into the hepatic artery and a second group had the catheter inserted percutaneously and a bolus of cancer chemotherapeutic agents injected into the catheter. In both groups, chemotherapy in the form of 5-fluorouracil was supplemented by internal irradiation delivered from the intraarterial administration of Yttrium 90 microspheres. Forty percent of the patients who had an indwelling catheter performed at celiotomy manifested an objective response and in 60% a significant subjective improvement occurred. In the 25 patients whose catheter was inserted percutaneously, the response rate was roughly similar, in that 35% demonstrated an objective response and 65% demonstrated a subjective response.


"Localized" carcinoma of the mobile tongue and floor of the mouth--a lesion frequently misjudged and undertreated. A retrospective study of 74 cases of cancer of the mobile tongue and floor of the mouth, diagnosed between 1949 and 1975, with a two-year minimum follow-up was undertaken. The lesions were TNM staged, stages I and II  accounting for 56 cases (76%) and stages III and IV  accounting for 18 cases (24%). The analysis was restricted to the "localized" stage I  and stage II lesions. In this group failure occurred in 31 patients, or 55% of the group. Failure at the primary site accounted for 10 of the failures, failure at both primary and cervical lymph nodes accounted for 14, and failure at cervical lymph nodes only accounted for 7 of the failures. The treatment for these "localized" lesions was then analyzed for modality, adequacy, presence or absence of planning failure, and survival. The results indicate the lethal nature of this lesion when inadequately treated and strongly suggest more extensive use of prophylactic therapy to the cervical lymph nodes.


Urinary etiocholanolone and prognosis in early carcinoma of the breast. Etiocholanolone levels have been measured in both premastectomy and postoperative urines from 86 women with early breast cancer. Levels did not differ between patients subsequently surviving five years following mastectomy and those dying from recurrent disease within this period.


Three mice, two blind.

Three mice, two blind. In a closed colony of approximately one million mice which had been rigidly pedigreed (brother to sister) from a few original mice, three unusual mice have appeared. These three have obviously deviated from what would be expected according to the accepted laws of inbreeding geneity. Thus three unexpected incidences of increased variability have occurred three times in addition to the occasional appearance of new mutations (approximately one in 26,000 mice). The first mouse developed a sudden increase in susceptibility to spontaneous tumors of mammary origin. She became the mother of the well-known C family used extensively in cancer research. The second mouse clearly exhibited, among clear-cut altered biological characteristics, several somatic mutations, thus indicating an unstable genetic condition. The third mouse developed a highly significant capacity to regress and eliminate spontaneous tumor tissue. The conclusion is reached that unstable biological states arise occasionally during the process of inbreeding.


Understanding the adolescent patient.

Understanding the adolescent patient. The chapter has presented a frame of reference with which to approach adolescent patients with skin disease. To be most effective, the physician must understand the complexities of adolescent development and the various biological, social, and psychological circumstances and reactions with which young people must cope. Suggestions are made regarding approaches to the management of the adolescent skin patient, in the wish to maximize the usefulness of the physician--patient relationship as a resource for helping young people to health and happiness.


Senescence: a stochastic molecular control theory. A theoretical model of transcriptional control, in a preliminary form, is presented. The model has a critical boundary between a region of values in which the system is stable and essentially self-perpetuating and a region in which the essential macromolecules tend to disappear and not to be regenerated. The possibility of the transition results from cell division. Variation in the values of kinetic parameters or fluctuation in the partition of the macromolecules between the daughter cells of a division subject some cells in the population to the instability. Cells on the wrong side of the critical boundary may accumulate in G2, and will eventually die, at rates and frequencies depending on the specific peculiarities of various cell types (e.g., tissues). Such phenomena, in association with the characteristic division patterns predicted by the theory, have been observed in vitro and in vivo. "Programmed death" in morphogenesis may be an instance. Problems in the future development of the theory are outlined. The significance of clonal selection for atherogenesis and perhaps oncogenesis is noted. The theory is briefly contrasted with "damage" and "error" theories; and the eventual possibility of constructive intervention in ageing at the molecular level is suggested.


Tissue mosaics and clonal mechanisms of atherogenesis. It is known that atherosclerotic lesions arising in aortae of females heterozygous for the A and B variants of glucose-6-phosphate dehydrogenase are frequently though not invariably of one enzyme type. The occurrence of heterotypic lesions rules out single-cell origin. However, it is possible to analyze the results of such studies in terms of multicellular atherogenic foci. The variance in enzyme proportions in the normal tissue mosaic permits an assessment of clump or patch size. Then an application of geometrical probability permits the derivation of a relation between the proportion of monotypic lesions and the size and cell number of the original atherogenic focus. Comparison with suitable experimental data gives reasonable estimates of these cell numbers. The influence of selection in the cell population on such estimates is considered.


The waste-product theory of aging: waste dilution by cell division. When cells divide, the quantity of waste material per cell decreases because the wastes are "diluted" by apportionment between the daughters which result from the division. The quantity of waste present in a symmetrically or asymmetrically dividing population of cells is governed by a first-order non-linear differential equation. In the derivation of the equation, it is assumed (a) that waste is created at a rate which is either constant or proportional to the amount of waste already formed, (b) that waste is neither destroyed nor transported across cell walls, and (c) that the rate of cell division at large values of time is inversely proportional to the amount of waste per cell raised to a power. Relations among the parameters of the differential equation specify conditions under which its solutions rise to a critical value. If the amount of waste per cell given by a solution of the differential equation exceeds this value, it is assumed that deleterious effects become evident and that cell death follows. Decreases in the cell division rate leading to a cessation of population growth may occur at lower levels of waste accumulation.


Evidence that transcription changes in ageing cultures are terminal events occurring after the expression of a reduced replicative potential. There is a progressive decline in replicative capacity with increasing age as expressed in terms of percentage labelled nuclei with 3H-thymidine and altered saturation density at confluency. This expression of ageing in vitro is seen in three different lines of human embryo diploid fibroblasts, although the pattern and rate of decline is different in each case. Generalization about in vitro ageing from studies with one cell line should therefore be made with care or avoided. There was an increase in total cellular RNA content as cultures aged which was more pronounced as cells entered the senescent or terminal phase of their lifespan. This increase appeared to be accompanied by a slightly elevated uptake and incorporation of 3H-uridine per cell. Template activity of isolated nuclei was markedly reduced in very late passage or phase III cells, but did not show a progressive decline with increasing age. These studies show that there is a reduced replicative potential which is not accompanied by a detectable decline in transcription, and suggest that the altered template activity should be regarded as an effect of ageing in vitro.


Alteration of the activity and molecular from of thymidine kinase during development and aging in the mouse cerebellum. Protein, DNA and thymidine kinase levels were assayed during development and aging in the mouse cerebellum. A roughly parallel increase in protein and DNA content occurred from birth, reaching a plateau at 18 days; these adult levels increased by 30% in the 23 month-old cerebellum. Thymidine kinase activity reached a maximum at 6 postnatal days, then decreased steadily to reach, at 18 days, the low level that was maintained in the adult. The thymidine kinase synthesized in the aged cerebellum differed from that in the neonate by having (i) an increased specific activity, (ii) a faster migrating species upon electrophoresis, (iii) an inhibition by dCTP, and (iv) a lower affinity for the substrate thymidine (higher Km). Mathematical calculations indicated the appearance of a larger number of smaller sized cells in the aged cerebellum, when compared with the young adult. Histological analysis established that the newly synthesized cells were localized in the molecular layer of the old cerebellum. It appears that senescence in the mouse cerebellum may be associated with an increased synthesis of glial cells.


Development of the aging cell surface: concanavalin A-mediated intercellular binding and the distribution of binding sites with progressive subcultivation of human embryo fibroblasts. External surfaces of early and late passage human embryo fibroblasts were reacted with concanavalin A to determine whether quantitative and qualitative variations in receptor sites develop with increased serial subcultivation. Comparative analyses of direct con A binding to cell surfaces; lectin-mediated cell-to-cell binding and agglutination; and ultrastructural distribution of con A receptor sites were made on the surfaces of both cell groups. Subtle variations were observed in the patterns of intercellular binding between early and late passage cells as assayed by both agglutination and the binding of cells in suspension to substrate-attached monolayers. However, no major differences in the total number of binding sites per cell were expressed on the external surfaces of either group. Hemocyanin-labeled binding sites tended to be more clustered on membranes of late passage cells in contrast to more homogeneous patterns of distribution in early passage specimens. These observations suggest that variations in binding patterns are not the result of changes in numbers of binding sites but may be the result of alterations in the concerted actions of numerous factors which include cell surface topography (e.g. villous projections) and the relative distribution of lectin binding sites on the cell periphery.


Effects of cold stress on rats fed different levels of docosenoic acids. Male Sprague-Dawley rats, 4 weeks old, were subjected to an ambient temperature of 4 C for periods up to 24 days and fed a synthetic diet containing one of the following oils: peanut oil (PO), rapeseed oil (RO), low erucic acid rapeseed oil (LO), and partially hydrogenated marine oil (HO), each at 20% w/w. A parallel experiment using the same oils was performed at room temperature (23 C). During cold stress, animals on the RO diet showed higher mortality than all other groups; all 20 animals in this group died within 5 days. At room temperature, however, all animals survived. The lipid accumulation in the heart reached its peak in all groups after 3 days and then gradually declined. The accumulation was most pronounced in the RO animals and coincided with the high mortality at 4 C. The fatty acid composition of the cardiac triglycerides reflected that of the diet, while the composition of the cardiac lecithin was only marginally modified.


Liver and thymus lipid composition in AKR mice with and without lymphomas. Lipid composition of liver and thymus in controls, early stage lymphoma, and advanced stage lymphoma-bearing AKR mice was studied. There was a significant decrease in the liver total lipid content in mice with advanced lymphoma, whereas in the early stages, no quantitative change was seen. In livers of mice with advanced stage lymphoma, there was a significant decrease in the nonpolar fraction. The decrease was in triglyceride, whereas the cholesterol fractions were relatively increased though hig,ly variable. There was an increase in the polar lipid/nonpolar lipid ratio in the advanced lymphoma livers and a very large increase in the polar lipid/triglyceride ratio, indicating that the decrease in total lipid in these livers was largely in the triglyceride fraction. Similar changes were seen in the thymus, in which the lipid composition reflected the transformation from normal to malignant cells.


Lipogenesis in iron-deficient adult rats. Iron-deficient (5 ppm Fe) or control (307 ppm Fe) diets were fed ad libitum to female rats for 7 weeks, and then meal-fed for 4 weeks. Body weights, hemoglobin levels, and hematocrits were lower (p less than 0.01) in deficient group (184 +/- 7, 7.1 +/- 0.4, 32.7 +/- 0.6) than in the control group (220 +/- 10, 16.9 +/- 0.3, 51.8 +/- 0.8) at the end of the 11-week experiment. Animals were killed 4 hr after meal feeding, and liver slices, mesenteric adipose tissue, and segments of mid-jejunum were incubated in vitro with [U-14C] glucose or 3H2O. Adipose tissue from deficient rats had incorporation of [U-14C] glucose into triglycerides two to three times greater than control rats (p less than 0.01). Release of 14CO2 from glucose was greater in adipose tissue of deficient rats than controls (p less than 0.05). Incorporation of 3H2O into triglycerides was also two to three times greater in deficient adipose tissue than in controls (p less than 0.02). In liver slices, incorporation of glucose in polar lipids was slightly higher in deficient rats than in control rats (p less than 0.05). No significant differences were found in incorporation of 3H20 or [U-14C] glucose into lipids or CO2 in jejunum. Thus, iron- deficient adult rats have greater lipid synthesis from 3H2O and glucose in adipose tissue than rats fed adequate levels of iron.


The effects of clofibrate feeding on the metabolism of palmitate and erucate in isolated hepatocytes. The metabolism of palmitate and erucate has been investigated in hepatocytes isolated from control rats and from rats fed 0.3% clofibrate. Clofibrate increased the oxidation of [1-14C]palmitate 1.5 to 2-fold while the esterification was decreased. At a high concentration of palmitate (1.5 mM), the total rate of fatty acid metabolism was stimulated. Clofibrate stimulated both the oxidation (3.5 to 5-fold) and the esterfication (1.7-fold) of [14-14C]erucate. Erucate undergoes chain-shortening in isolated liver cells. This chain-shortening was stimulated at least 2-fold by clofibrate feedings. The isolated mitochondrial fraction from clofibrate-fed rats showed an increased capacity for oxidation of short-chain acylcarnitines (including acetylcarnitine), while the oxidation of palmitoyl- and erucoylcarnitine showed little change. It is suggested that erucate is shortened by the recently detected beta-oxidation system of peroxisomes.


Uropygial gland alkane diol diesters in the Kn mutation of the domestic chicken. Uropygial glands from chickens which are known to have the Kn gene secrete qualitatively the same types of alkane diol diesters as the normal domestic chicken. However, there are many significant differences in the mole percent of individual fatty acids and diols within the diester between the two genetic types of chickens. In general, the mutant chickens have lesser amounts of the shorter chain fatty acids and diols and greater amounts of the longer chain fatty acids and diols. There is also a gene dosage effect with two mutant genes having a greater effect in many cases than a single mutant gene.


Factors related to competitive stress among male youth sport participants. A study was conducted to determine intrapersonal and situational factors related to the stress experienced by 11 and 12 year old boys participating in competitive youth sports. Potential stress related factors were assessed at preseason, pregame, and postgame periods. The indicant of stress was state anxiety measured by the Spielberger State Anxiety Inventory for Children administered 30 minutes prior to and immediately following a competitive soccer game. Findings indicated that competitive trait anxiety, self esteem, basal state anxiety, and expectancies of self and team performance outcomes were significantly related to stress experienced when anticipating competition. As hypothesized, game win-loss was a highly significant predictor of post-game stress. Other predictors of postgame stress were the game win-loss x game closeness interaction, the amount of fun experienced during the game, basal state anxiety, and the perceived importance of a game win to the coach. The findings are discussed in terms of the child's actual and perceived response capabilities in meeting the performance demands of the highly evaluative sport competition process.


Recovery of muscular endurance following submaximal, isometric exercise. Each of 22 subjects squeezed a hand-gripping device for as long as possible at a tension of 50% of his maximum voluntary contraction. When the prescribed tension could no longer be maintained, the subject was given a predetermined rest period and at its conclusion again squeezed the hand dynamometer in a second all-out bout. The length of the interbout rest period was either 5, 10, 20, 40, 80, 160, 320, 640, 1280, or 2560 sec. Each subject experienced every rest period with the order of administration assigned at random. At least three days intervened between successive testing sessions. The mean time the subjects persisted during the first bout was 120.25 sec. The percentage of recovery, calculated by dividing the holding time of the first bout into the time of the second, ranged from 20.3% after 5 sec of rest to 86.8% following the 2,560-sec rest interval. An analysis of the percentages of recovery at the various time periods revealed that the pattern of submaximal isometric endurance recovery folowed a three-component exponential curve.


The effect of blood infusion upon endurance capacity and ratings of perceived exertion. The purpose of this investigation was to study the effect of blood infusion upon maximal endurance capacity and ratings of perceived exertaion (RPE). Sixteen long-distance runners, 13 of whom were marathoners, undertook four trials (T1-T4) of a treadmill run to exhaustion over a five week period. Criterion measures were time to exhaustion (TE) and RPE during each T. Data on Hb, Hct and RBCs were collected prior to each trial. Based on TE at T1, Ss were matched and assigned to either the experimental (E) or control (C) group. One week after T1, all Ss had 460 ml blood withdrawn. T2 was undertaken 2 weeks postwithdrawal. One week after T2, or 21 days postwithdrawal, the E group was infused with their own RBCs while the C group received 460 ml normal saline. T3 was taken 2 hours postinfusion and T4 one week later. The results of the factorial repeated measures ANOVA revealed no significant differences (p less than .05) between groups for either TE or RPE, even though the Hb level for the E group was significantly higher (P less than .01) than the C group at T3 and T4.


The effects of a collegiate wrestling season on body composition, cardiovascular fitness and muscular strength and endurance. The purposes of this investigation were: (1) to study the body composition, cardiovascular fitness and muscular strength and endurance of collegiate wrestlers during the course of a season; (2) to determine if selected regression equations used to predict minimal wrestling weight were accurate; (3) to determine if the wrestlers who participated in the study had an accurate perception of their ideal minimal wrestling weights. Body composition (body densitometry), aerobic power (Vo2 max), and muscular strength and endurance (isokinetic) were measured during pre, peak, and post-seasons. The fact that very few significant changes occurred in these measurements during the course of the study appears to be the result of year-round training on the part of the athletes studied. Their peak-season percent body fat (8.36%) was very similar to that reported in other studies involving mature wrestlers. Rapid weight loss through dehydration appeared to be the preferred method of weight reduction among these athletes.


Caloric cost of walking and running.

Caloric cost of walking and running. Twenty-four young adult male subjects were used to study the relationship between total caloric costs (exercise and recovery costs) incurred and speed of movement over a distance of 1 mile. Caloric costs were determined at walking speeds of 3, 4, and 5 mph and at running speeds of 5, 7, and 9 mph. Energy costs were assessed every 20 sec during the activity and during the recovery until the caloric cost returned to pre-established resting levels. The fitness level of the subjects was considered as a moderating variable. 3regression equations to predict caloric cost from body weight, speed of movement, and VO2 max were also developed. Conclusions for the given speeds were: (1) running is more costly than walking, (2) the cost of walking a mile increases with speed of movement, and (3) for running speeds, total caloric cost and VO2 max are inversely related. The independent variables for the regression equation for walking included body weight and speed squared times body weight (R2 = .86). The independent variables for the running equation were identical to the ones used in the walking equation with the addition of speed times VO2 max (R2 = .62).


Effects of arm training on retention of training effects derived from leg training. This study examined the effects of arm training on retention of training effects produced by leg training. Thirteen adult male subjects leg trained on bicycle ergometers for 8 weeks. During the subsequent 4 week control period group AT (N = 4) arm trained by cranking an ergometer, group DT (N = 4) discontinued training and group LT (N = 5) continued leg training. Metabolic response to maximal and submaximal (80% initial Vo2max) leg work was observed before (Test I) and after (Test II) the 8 week leg training program and at the conclusion of the control period (Test III). With the initial 8 weeks of leg training Vo2max and maximal Ve increased while Vo2, HR, Ve and blood lactate decreased during submaximal work (p less than .05). R was decreased during both maximal and submaximal work (p less than .05). Analysis of covariance of the Test III means (Test II as covariate) yielded significant (p less than .05)F-ratios for Vo2max and R at Vo2max. Post hoc testing indicated that Vo2max was greater in LT than in AT or DT but that there was no difference between AT and DT. R at Vo2max was greater in DT than in LT or AT. These data suggest that arm training does not significantly affect the deterioration in metabolic response to leg work which occurs with cessation of leg training.


Energy cost of circuit weight training.

Energy cost of circuit weight training. The metabolic cost of circuit weight training was determined in a group of 20 men and 20 women, 17 to 36 years of age, who volunteered to participate in this study. Performing 3 circuits (10 stations/circuit), using a work (30-sec) to rest (15-sec) ratio of 2:1, and a total exercise time of 22.5 min, the energy expenditure was found to be highly related to body weight (r = 0.84 and r = 0.67 for men and women respectively). The average gross energy expenditure was 539.7 and 367.5 kcal/hr. (9.0 and 6.1 kcal/min) for the men and women respectively, but was 7.0 and 6.0 kcal/kg-hr when expressed relative to body weight, and 8.1 and 8.2 kcal/kg(LBW)-min when expressed relative to lean body weight. Thus, when body composition was considered, there were essentially no differences in the energy expenditure for males and females.


Physiological alterations consequent to circuit weight training. The efficacy of a 10-week program of circuit weight training to elicit specific physiological alterations was evaluated in a group of men (n = 16) and a group of women (n = 12), with an additional group of men (n = 10) and a group of women (n = 11) serving as controls. The circuit consisted of 10 stations performed on a Universal Gym, 3 circuits per day (approximately 22.5 min/day), 3 days/week. The subjects exercised at 40-55% of 1-RM, executing as many repetitions as possible in 30 sec on each of the lifts, followed by a 15 sec rest as the subject moved to the next station. Following the training program, the experimental groups demonstrated significant increases in lean body weight, flexed biceps girth, treadmill endurance time, VEmax (women only), Vo2max in ml/kg-min (women only), flexibility and strength. Significant decreases were found in selected skinfold measurements, and in resting heart rate (control group showed similar decreases). No change was found in body weight or in relative or absolute body fat. Generally, the women exhibited equal or greater changes when compared to the men for all variables assessed, which could be a function of their lower initial starting levels, or a more intense training program. It was concluded that circuit weight training is a good general conditioning activity, i.e., attends to more than one component of fitness.


Muscle glycogen depletion and lactate concentration during downhill skiing. Skilled and unskilled skiers were studied during downhill skiing. Muscle glycogen and muscle lactate concentrations in the vastus lateralis muscle were determined following different skiing conditions. Heavy glycogen utilization was found in the groups studied during a day of skiing. The skilled and unskilled skiers differed with respect to selective glycogen depletion pattern and the skilled subjects demonstrated greater depletion of slow twitch fibers than the unskilled subjects. Lactate concentrations ranged from approximately 5-26 mmoles x kg-1 wet muscle after approximately one minute of maximal skiing. This wide range was not found to be related to the level of skiing proficiency. However, skiing with varyingly angled boots, resulting in different knee angles, did affect lactate concentration. Lactate concentration was positively correlated to individual muscle fiber composition expressed as a percent of fast twitch fibers. The results suggest more pronounced involvement of aerobic energy metabolism in skilled skiers than in unskilled skiers.


Performance and efficiency of intercollegiate cross-country skiers. Ten male intercollegiate cross-country skiers were studied to identify factors influencing competitive performance and to estimate the efficiency of energy expenditure in skiing. The variables examined were maximum oxygen intake, as determined by both uphill treadmill running and by maximal level skiing, physical characteristics, strength and experience in cross-country skiing and racing. Multiple regression analysis showed that racing experience, cardiorespiratory fitness, and body fat percentage were significant factors in racing success. The net mechanical efficiency at this level of competition was estimated at 21.3%.


Football fatalities in actuarial perspective. The relative risk of death among school and college varsity football players was calculated as a replication of a statistical exercise published a decade earlier. The purpose of the original exercise had been to demonstrate the epidemiological necessities and pitfalls in using fatality data to approach the hazardousness of sport. The purpose of this replication was to examine the stability of the findings of that exercise. In 1964, football was found not to constitute an additional risk of death to its participants compared to the overall mortality rate of young males adjusted for comparability by exposure to a football season. Further, compared to the automobile-related mortality rate of this population, football was much safer. In 1974 (and 1975), the frequency of football fatalities has declined, and the respective actuarial ratios consequently remained favorable to football. Fatality data, however, have limited utility in the search for preventive practices in sport. What is needed is continuous surveillance of all significant injuries and illnesses, using epidemiological principles.


Physical estimation and attraction scales: rationale and research. Rationale, development, and validation studies for the Physical Estimation and Attraction Scales (PEAS) are dicussed. A psychological model for physical activity participation is advanced which utilizes Estimation (self-perceptions of physical ability) and Attraction (measured interest in physical activity) as mediating variables in physical ability, physical activity participation, self-esteem relationships. Tests of the model have inferred physical ability from performance at motor fitness tests, participation from paper and pencil self-reports, and self-esteem from several of the more widely used measures of general self-esteem. Conclusions developed from studying these variables in male adolescent samples are presented.


[Resistance of medical equipment to exposure to molds]. When operating biomedical equipment and instruments in areas with tropical climate there arises danger of their microbiological damage. All pieces of equipment and instruments that have to meet requirements as to their resistance to the action of moulds are subjected to testing for mould-resistance. The paper sets forth the results of such tests and their analysis. The resistance of the equipment and instruments depends on the physical and chemical properties and on the technology of manufacture of their materials. The results of the analysis of the results obtained served as a background for recommendations as to the use of resistant materials and effecting measures raising their quality. Such measures include the choice of resistent components, biocides, additives and admixtures to materials and coatings.


[Foreign medical technology at the "Optika-77" exhibition]. An analytical review of technical means for medico-technical investigations exposed by foreign firms at the exhibition "Optika-77" in Moscow suggests the following trends in the development of technical means, viz. providing the researcher with a processes, readily comprehensible information; improving the macro- and microanalysis of morphological structure of the tissues; designing and construction of new analyzers of substances; automation of functional investigations and scrutiny of substances.


[Standardization of methods for testing the resistance of medical equipment to mechanical stress]. The existing methods and facilities for testing biomedical equipment for vibration resistence is adopted from technical standards prepared for manufactures of radio-industry and fail to take into consideration actual operation conditions and transportation of equipment and instruments of biomedical engineering. On the ground of experience gained by testing medical equipment proposals for elaborating rules and conditions for vibration resistance testing for medical equipment are offered.


[X-ray localizer for transthoracic puncture biopsy]. A spot-centring appliance whose purpose is to guide an instrument for transthoracic puncture biopsy with maximum precision into the spector of the thoracic cavity chosen during roentgenoscopy. The X-ray locator is made up of a centring device, depth gauge and a spotting device with roentgen-contrast orientation points which ensure all the spotting and centring manipulations. The transthoracic puncture biopsy is performed outside the range of the X-ray action.


[Determination of the permissible error of a photoelectric concentration meter for an automatic biochemical analyzer]. On the ground results derived from an analysis of metrological characteristics of the biochemical automatic unit systems and of their influence on the end-result with due regard for actual operating conditions a formula for the automatic unit error was deduced. The specificity of technical requirements to be met by automatic meters is shown and a new complex set of metrological characteristics of the concentration meter are given. At the same time permissible values for metrological characteristics of the meter satisfying medical requirements are defined. The new complex set of metrological characteristics for the biochemical automatic unit concentration meter allows it to make a change from the absolute photometric scale of the device to the one in relative units.


Inhibition of prolactin release by serotonin antagonists in hyperprolactinemic subjects. Metergoline (4 mg) and methysergide (3 mg), two serotonin antagonists known to inhibit prolactin secretion in normal subjects, and the dopaminergic agonist, bromocriptine (2.5 mg) were orally administered in hyperprolactinemic patients. Mean serum prolactin concentration was significantly decreased between 120 and 240 min following the ingestion of all three drugs in comparison with a placebo; a consistent reduction to below 50% of basal values occurred in 10 of 14 patients after metergoline, in 5 of 10 after methysergide, and in 11 of 14 after bromocriptine administration. These data indicate that serotonin antagonists may acutely lower serum prolactin levels in hyperprolactinemic patients similarly to bromocriptine, though their mechanism of action is most likely different.


Reticuloendothelial cell dysfunction in diabetes and hyperlipidemia. Using clearances of microaggregated iodinated human serum albumin in a serial 'stress test,' defective phagocytosis by the Kupffer cells has been demonstrated in diabetic patients with K.W. nephropathy and proliferative retinopathy. This indicates a disturbance of phagocytic cell function that has implications for the cellular pathology of microangiopathy. The effect is not due to uremia, but could be due to T3 deficiency or lipid deposition. In hypothyroidism, there is defective RES phagocytosis, and alcoholics with hyperlipidemia can have impaired clearances. Hence, patients with advanced diabetes, hypothyroidism, and some alcoholics are at risk from infection.


Pharmacologic profile of methyl 2-tetradecylglycidate (McN-3716)--an orally effective hypoglycemic agent. A specific inhibitor of fatty acid oxidation, methyl 2-tetradecylglycidate (McN-3716) has been found to produce a dose dependent hypoglycemic effect when administered orally to rats, mice, and dogs. In addition to being more potent than other inhibitors of fatty acid oxidation, McN-3716 was also found to be 15--20 times more potent than tolbutamide in lowering the blood glucose of fasting rats. Furthermore, evidence is presented that McN-3716 produces hypoglycemia by a mechanism which differs from that of other oral hypoglycemic agents, the biguanides and the sulfonylureas. As predicted by the Randle glucose-fatty acid cycle, McN-3716 lowered glucose concentrations only under conditions where fatty acids were being used as the major energy substrates (fasting, diabetes, and feeding of high fat diets) but not under conditions where energy was derived mainly from carbohydrate (fed state or following hypophysectomy). Administration of McN-3716 produced a remarkable lowering of the plasma glucose and the glycosuria of depancreatized dogs but did not result in complete normalization of glucose, especially the excursions of blood glucose following feeding. It did, however, produce virtually complete reversal of the ketoacidosis of alloxan diabetic rats and depancreatized dogs without worsening the plasma lipid profile. Thus, McN-3716 may have potential utility as an oral therapeutic agent for the treatment of ketosis-prone juvenile or maturity-onset diabetes.


Protein-free spreading technique for the electron microscopy of DNA and chromatin. A new protein-free technique of preparation of DNA molecules for electron microscopy is described. The technique is based on the phenomenon of formation of a thin liquid film of a high concentration buffer on the surface of the hypophase of the lower concentration buffer on depositing a droplet of the high concentration buffer on the hypophase. We found that under certain specific conditions most of all frequently used buffers form films of such a type. We have chosen an ammonium acetate buffer for the preparation of DNA molecules for electron microscopy. The diameter of the molecules prepared in compliance with the described technique ranges from 2.5 to 3 nm (according to shadow measurements made after one direction shadowing), this being in agreement with the actual diameter of DNA molecules. It is shown that for chromatin preparation Tris-HCl buffer can be used to advantage. Suitable buffers can be selected for different objects under investigation.


Improvements of the electrophoretic mobility test to measure lymphocyte sensitization. The Electrophoretic Mobility (EM)-test was performed in 316 children to examine their lymphocyte sensitization to a common antigen by measuring the mobility of special indicator cells. The results indicate that this test can serve as an additional help in differential diagnosis of malignant and non-malignant diseases. Measurements in the cytopherometer were facilitated by introducing several technical modifications: 1) The original method of timing with a stopwatch was replaced by two electric watches electrically combined with the cytopherometer. Thus individual faults were reduced. The next improvement of timing at the cytopherometer consisted in the construction of an electronic controller and stopwatch in combination with a minicomputer, data print out, and tape recorder in order to get more reliable results. 2) Further automatic recording of the data is time-sparing and useful for correct evaluation of the EM-test. That can be done now directly on-line in a calculator with a program developed in our laboratory. 3) By using a television monitor for the observation of the indicator particles an additional simplification is possible.


Acquired immunity to Mycoplasma pneumoniae. Pneumonia in hamsters. An inactivated Mycoplasma pneumoniae vaccine was prepared from a culture in a liquid medium supplemented with water extract of egg yolk. Vaccinated Syrian hamsters were exposed to virulent M. pneumoniae aerosol and were examined for the retention of mycoplasmas and for histopathological changes in the respiratory tracts. When a vaccine prepared with strain FH was administered intramuscularly or by inhalation in aerosol, no significant resistance was shown with respect to mycoplasma proliferation. An increased resistance, however, was observed when an aluminium phosphate-adsorbed vaccine, and when a plain vaccine (although to a lesser degree) prepared with hamster 24-passaged strain FH, was administered intramuscularly. Histopathologically, lung lesions were markedly suppressed in groups showing high resistance. A correlation between the serum antibody titer and the resistance to infection was observed. Hamsters which received a hyperimmune rabbit antiserum intracordally showed a high resistance to M. pneumoniae infection. The suppression of histopathological changes also coincided with high complement-fixing antibody titers of either actively or passively immunized hamster serum. The results suggest that humoral immunity plays an important role in resistance to M. pneumoniae pneumonia in hamsters.


Studies on the lipid components of endotoxin. II. Chemical analyses and biological properties of neutral, polar-I and polar-II subfractions. Lipid components obtained from Salmonella typhosa O-901 endotoxin by acid hydrolysis were separated into neutral, polar-I and polar-II lipid fractions by silica gel column chromatography. These lipids were further separated by silica gel column and/or thin-layer chromatography. The subfractions were analyzed by thin-layer chromatography, gas chromatography and infrared spectrophotometry. Seven subfractions obtained from the neutral lipid fraction contained lauric, myristic, palmitic, 3-OH-myristic acid, artificial products of 3-OH-myristic acid, or a small amount of two unidentified fatty acids. These fatty acids and glucosamine were commonly detected in six subfractions obtained from the polar-I lipid fraction. Fatty acids, glucosamine, and O-phosphorylethanolamine were detected in all of the 13 subfractions obtained from the polar-II lipid fraction. Chick embryo lethal activity, rabbit pyrogenicity and in vitro interferon inducing activity were found in three polar-I lipid subfractions and five polar-II lipid subfractions, but not in neutral lipids. The activities were highest in a polar-II lipid subfraction which contained smaller amounts of O-phosphorylethanolamine and glucosamine than the other subfractions. However, no particular chemical constituent(s) related to the biological activities could be found. Prolonged acid hydrolysis of the polar-II lipids gave rise to neutral and polar-I lipids. Chemical and biological aspects of the lipid constituents of endotoxin are discussed.


Dental caries induction in experimental animals by clinical strains of Streptococcus mutans isolated from Japanese children. Oral implantation and the cariogenic activity of clinical strains of Streptococcus mutans which had been isolated from Japanese children and labeled with streptomycin-resistance were examined in specific pathogen-free Sprague-Dawley rats. All the seven strains tested were easily implanted and persisted during the experimental period. Extensive carious lesions were produced in rats inoculated with clinical strains of S. mutans belonging to serotypes c, d, e, and f, and maintained on caries-inducing diet no. 2000. Noninfected rats did not develop dental caries when fed diet no. 2000. Type d S. mutans preferentially induced smooth surface caries in the rats. Strains of other serotypes primarily developed caries of pit and fissure origin. Caries also developed in rats inoculated with reference S. mutans strains BHTR and FAIR (type b) that had been maintained in the laboratories for many years. However, the cariogenicity of the laboratory strains was found to have decreased markedly. All three S. sanguis strains could be implanted, but only one strain induced definite fissure caries. Two S. salivarius strains could not be implanted well in the rats and therefore they were not cariogenic. Four different species of lactobacilli also failed to induce dental caries in rats subjected to similar caries test regimen on diet no. 200. S. mutans strain MT6R (type c) also induce caries in golden hamsters and ICR mice, but of variable degrees.


Effects of protamine sulfate on dengue type 1 viral activities. Protamine treatment of type 1 dengue-infected mouse brain suspension resulted in precipitation of several viral specific activities. Complement-fixation activity was almost completely precipitated by protamine. The complement-fixation components recovered in the precipitate were comparable to a non-precipitated reference dengue 1 antigen in their homologous and heterologous reactions. Dengue hemagglutinin was also precipitated by the same treatment. The precipitated hemagglutinin was resolved into three components by buoyant density centrifugation, whose densities were 1.236, 1.215, and 1.178 g/ml, respectively. Three similar HA components were detected in non-protamine treated virus preparations. In both instances the highest-titered HA fraction possessed a buoyant density of 1.21--1.22 g/ml. These HA components were tested in the hemagglutination-inhibition reaction and were proved to be virus-specific. Cesium chloride density gradient centrifugation was shown to be useful for removing possible inhibitor(s) of viral specific hemagglutinin.


[Sport and cardiac risk factors in middle age (author's transl)]. 1477 employees (868 males and 609 females) were examined for cardiac risk factors. The risk factor frequency was tested in relation to the amount of physical activity. Men and women active in sports are less subject to over-weight, diabetes, high blood pressure, and pathological ECG changes than are physically inactive; males who participate in sports also smoke less. On the other hand, a connection between risk factors and different levels of physical activity on the job could not be established. The mutual relations between risk factors, physical activity, weight, and social level imply that the lower number of risk factors in those who participate in sports is due largely to their consciously healthy way of living.


Advances in computer-based pharmacy systems. This paper summarizes recent advances in computer-based pharmacy information systems for both hospitalized and ambulatory patients. It discusses the clinical pharmacy applications of: pharmacokinetic modeling (which allows for the optimization of patient-specific dosage regimens); drug interaction and adverse drug therapy monitoring (to decrease therapeutic problems); intravenous additive and hyperalimentation programs (to aid in formulating complex solutions); drug usage review (to develop and utilize guidelines for appropriate prescribing); drug information services; and drug distribution systems. Administrative and management control systems are briefly described. Automated label preparation and identification of patient noncompliance with physician-directed therapy are also described. The advantages of a computerized integrated hospital information system are also discussed.


[Biochemical measures in cardiac patients: an analysis of change during rehabilitation (author's transl)]. 210 male patients hospitalized for cardiac rehabilitation have been studied. As a result of age matching the sample was reduced to 190 patients: 72 patients with myocardial infarction, 90 patients with functional cardiovascular diseases, and 28 patients with angina pectoris. At the beginning and at the end of the 4 to 6 week rehabilitation program total lipids, cholesterol, triglycerides, phosphatides, GOT, GPT, LDH, HBDH, cholinesterase, aldolase, blood sugar, creatinine, electrolytes, hemoglobin, erythrocytes, leukozytes, and catecholamines were measured. In addition to the statistical comparison of the three groups and their specific change patterns, effects of body weight reduction and improvement of physical fitness were analyzed. The decrease of lipids is especially associated with weight reduction, whereas the decrease of enzyme activity and electrolyte concentration is accompanied as well with weight reduction as with the improvement of physical fitness.


Medical information system, health records, and knowledge banks. A medical decision system with the capability to answer questions in an interactive mode to assist clinical decisions is described. The system consists of four modules: (a) clinical case history bank, (b) pooled clinical experience bank, (c) clinical knowledge band, and (d) biomedical research bank. At the human/machine interface, an encoder transforms input natural language into codes and retransforms output into natural language. If properly authorized, the physician can request his patient's files, ask for clinical experience in similar cases, ask for related textbook knowledge, or browse among related research findings or speculations. All four modules have been tested as prototypes. Multidisciplinary cooperation is needed for the implementation of a national medical information network and for the reorientation of clinical and academic medicine.


[Syncope on swallowing (author's transl)]. We studied a 71-year-old patient with sinusbradycardia due to ingestion of food. He had a history of two syncopes at lunch. Mechanical irritation of the esophagus close to the atrium as well as insufflation of air into the stomach caused bradycardia with a heart rate of 28 per minute. Bradycardia could be suppressed with atropin given intravenously. There were no abnormal roentgenographic and pathological findings regarding the esophagus and the stomach.


Computerized food service as a patient support system. This paper compares an operations support system with an information system in the area of clinical food service. The advantages of a computerized dietary system over a manual system are discussed. A flexible, data-independent information system facilitates inventory and production control and extends the benefits of nutritional analysis to more patients. Health professionals are freed from routine clerical duties, and labor costs are minimized through use of the system.


[Clinical experiences with holoxan within the framework of sequential combination therapy (author's transl)]. 153 patients with inoperable malignant tumors were treated by the so-called synchronization therapy with vincristine and ifosfamide. 13 complete remissions (8.5%) and 47 partial remissions (30.7%) were obtained. 5 times cessation of tumor growth occurred (3.3%). In 88 cases the therapy failed (57.5%), but in 11 cases a subjective improvement was noted. The most favourable results of treatment were obtained in cases of malignant lymphoma, small cell carcinoma of the lung and testicular carcinomas. Although the duration of remission was short in most cases, it could be demonstrated, that a targeted polychemotherapy is possible using the proliferation kinetic data in addition to the knowledge of the cell-phase-specific effect of cytostatic drugs. This therapy can succeed in causing a tumor regression even in metastatic carcinomas.


[Ureteral obstruction from metastases of a primary intestinal malignoma (author's transl)]. As of two own cases the authors refer about ureteral obstructions by paraureteral metastases of primary cancer within the intestinum. Diagnostic procedures within the digestive tract are strongly recommended, if within the urogenital region the etiology remains unclear. As often a causal therapy is not possible any more, recommendations for palliative urological procedures are given.


Method for respiratory sound analysis.

Method for respiratory sound analysis. A system is described for the analysis of respiratory sounds by means of a dual-channel sound envelope detector and a real-time spectrum analyzer. A three-dimensional spectral analyzer display for frequency, amplitude, and time has been utilized. Respiratory sounds have been observed with intensities up to 0.5 N/m2 and with normal frequencies in the range of 0 to 1.5 kHz. This system can extract useful information from the sounds of respiration, information which is not available by conventional auscultation.


Bovine coccidiosis. A review, including field safety studies with decoquinate for prevention. Decoquinate (Deccox: Hess  & Clark) has been demonstrated in in-house and university studies to be an active coccidiostat when fed daily at 0.5 mg/kg body weight during periods of oocyst exposure, or when experience indicates coccidiosis is likely to be a hazard. For prevention, feeding should be continued for at least 28 days. In 6 feedlot trials with 1993 cattle in 5 geographic areas, decoquinate fed at this level for 90-120 days had no adverse effects. In 5 of these trials, treated cattle had equal or slightly improved average daily gains and feed conversion by comparison with controls.


[Hospital acquired infections in children (author's transl)]. The incidence of hospital-accquired infections in children as given in the literature varies between 0.3%--25%. The most frequent infections are those of the urinary tract, respiratory tract, skin, wounds, gastrointestinal tract, or septicemia, and meningitis, caused by staphylococcus aureus, E. coli, klebsiella, enterobacter, pseudomonas, proteus, fungi or virus. Besides the identification of the type of infectious agent it is most important for the prevention and therapy of hospital-acquired infections to wash and desinfect hands, to isolate affected children, especially those with low resistance, employment of trained staff, improvement of special nursing techniques, repeated training and motivation of staff personal, and the critical use of antibiotics.


[On the calculation of the volume deficit in hypertonic dehydration (author's transl)]. It has been suggested in the literature than volume deficit in hypertonic dehydration can be calculated from actual osmolarity. But for an accurate estimation of volume deficit a number of factors must be given. The initial concentration and the loss of substance during the development of dehydration must be known, the distribution of the substance within the compartment must be homogeneous, and no shift between dissolved and undissolved compartments is allowed. For the osmotically active substances the second and the forth condition are not satisfied. Therefore, the calculation of volume deficit, based on actual osmolarity, can induce an error from 40 ml to as much as 100 ml per kg body weight.


[Intestinal lymphangiectasia in exudative enteropathy (author's transl)]. Clinical symptoms and diagnostic procedures in a 12 1/2 years old girl with protein-losing enteropathy due to intestinal lymphangiectasia are reported. The child had suffered from intestinal protein loss, hypoproteinemia, hypocalcemia and lymphocytopenia. Dietary fat reduction and medium chain triglyceride formula diet made all the symptoms disappear.


[The EEC-syndrome. Case report and some suggestions about its pathogenesis (author's transl)]. The clinical data of a boy with ectrodactyly, ectodermal dysplasia, and cleft lip and palate (EEC-syndrome) are presented. Until now about 80 case histories with this syndrome have been published, 30 of them having all 3 symptoms. The combination of defects in rather different organs of ectodermal as well as mesodermal origin is difficult to understand. Changes in ectodermal tissues may well be the key factor in explaining the pathogenesis of this syndrome. This is supported by evidence gained by ontogenetical research with animals.


Gamma-ray-induced dominant mutations that cause skeletal abnormalities in mice. II. Description of proved mutations. In a mutation-rate experiment described earlier, 31 dominant skeletal mutations were confirmed by breeding tests. Skeletal abnormalities were detected in the skeletons of some of the sons of irradiated males, and for 31 of these sons the study of skeletons in subsequent generations showed that they transmitted abnormalities. The detailed descriptions of these mutations, together with descriptions of 6 presumed mutations found in a later paper, provide the basis for determining which mutations cause effects that would, if they occurred in humans, cause a serious handicap. Such a determination is necessary before these data can be used to estimate genetic hazard to humans. Furthermore, these descriptions of syndromes caused by individual dominant mutations should be useful to clinicians interested in skeletal defects. The statistical analysis of the frequency of each abnormality in the mutant line versus an approximation of the frequency of the malformation in the absence of new mutations is essential to be sure that a mutation is indeed the cause of each abnormality. These analyses, together with analyses of the correlation of abnormalities caused by individual mutations, clearly demonstrate that dominant mutations exhibit low penetrance for many of their effects. A few of the mutations also cause the death of some heterozygotes. No externally visible effects have been detected in heterozygotes for most of these mutations. Externally visible effects found in some of the heterozygotes for a few of the mutations include hydrocephalus, circling behavior, increased nervous activity, gray coat color, webbing of digits, and small size. Two coat-color mutations were found that caused no detected skeletal abnormalities. The data suggest that a few of the mutations may be reciprocal translocations. In most of the mutant lines tested cytologically, however, there was no indication of chromosomal aberrations.


Mutation to ouabain-resistance in Chinese hamster cells: induction by ethyl methanesulphonate and lack of induction by ionising radiation. The spontaneous frequency of mutants resistant to growth inhibition by ouabain (OUAR mutants) was found to be about 5:10(-5) per viable cell in uncloned cultures of Chinese hamster V79-4 cells. In freshly-isolated clones or cultures started from a few cells this frequency was initially reduced to about 1.10(-6) in 1 mM ouabain. No increase in the frequency of OUAR mutants was found in cultures treated with gamma-rays despite exploration of such variables as radiation dose, ouabain concentration, post-treatment interval before selection, cell density in selective medium, and clonal state of the cells at the time of adding ouabain (in situ vs. respreading method). A similar negative result was found for accelerated helium ions, for which the mutagenic effectiveness per unit dose has been shown to be about 10 times higher than gamma-rays for the induction of thioguanine-resistant mutants in these cells. Some evidence was found for an interaction between cellular radiation damage and ouabain-resistance, which may lead to a reduction in the survival of OUAR mutants in irradiated populations, but this damage seemed insufficient to account for inability to detect radiation-induced OUAR mutants. Reproducibly large increases in the frequency of OUAR mutants were found in cultures treated with various concentrations of ethyl methanesulphonate (EMS) by respreading cells in 1 mM ouabain for up to 8 days after EMS treatment. The concentration-OUAR mutant induction curve was approximately linear with low EMS concentrations. Recent evidence is reviewed in support of the suggestion, made in earlier studies, that ionising radiation is unable to induce OUAR mutants because of the severity of the genetic damage it causes.


[Effect of pinocembrin on the course of experimental candida infections in mice]. Pinocembrin (5,7-dihydroxy-flavanon)--a component of the bee product propolis--was tested for its in vivo activity against Candida albicans in mice. It was shown that the intravenous infection of AB-Jena mice with 2.5 X 10(5) Candida albicans cells was a very suitable model. Despite of treatment with pinocembrin at daily doses of 100 mg/kg body weight the animals as well as the controls died between the 6th and 24th day after beginning. On the other hand the animals treated with 5 mg/kg amphotericin B survived the test-period of 30 days. The question of effectiveness of pinocembrin in vivo should be cleared up in further pharmacokinetic investigations.


[The formation of immunoglobulins A, G, M and E in dermatomycoses]. According to current concepts in the first place T-lymphocytes have an important part in the defense mechanism against dermatomycosis. This theory is strengthened by investigations in which we were not able to demonstrate an increase of the immunoglobulins A, G and M in 36 patients suffering from this disease. To gather further information we determined the values of the immunoglobulin E in 16 cases of dermatomycosis. Taking into account a larger variation of the normal value in healthy persons, we found in at least 3 cases an increased amount of IgE. As we observe now and then an immediate reaction of Type I (according to COOMBS and GELL) after intracutaneous injection of trichophytin, it appears that IgE plays a role in certain fungal infections of the skin.


The repetitive ventricular response in man. A predictor of sudden death. We examined the value of cardiac pacing for assessing ventricular electrical instability and for predicting ventricular tachycardia and sudden death in 50 patients with refractory symptomatic ventricular tachycardia, 12 normal patients, and 48 survivors of a recent myocardial infarction. The repetitive ventricular response (two or more ventricular premature beats produced by a single ventricular pacing stimulus during control of heart rate with atrial pacing) was absent in all 12 normal patients but was present in 44 of the 50 patients (88 per cent) with recurrent ventricular tachycardia (P less than 0.001). Of the 48 survivors of myocardial infarction, 19 had repetitive ventricular responses. During the next 12 months 15 of these patients (79 per cent) had symptomatic ventricular tachycardia or sudden death, or both, as compared with four of 29 patients (14 per cent) who did not have repetitive ventricular responses (P less than 0.001). The repetitive ventricular response identifies patients with life-threatening ventricular instability, but it is still an investigational technic that should be used only with due precautions.


Increased absenteeism from work after detection and labeling of hypertensive patients. A study of hypertension in an industrial setting allowed us to confirm and explore an earlier retrospective finding that the labeling of patients as hypertensive resulted in increased absenteeism from work. After screening and referral, we found that absenteeism rose (mean +/- 1 S.E.) 5.2 +/- 2.3 days per year (P less than 0.025); this 80 per cent increase greatly exceeded the 9 per cent rise in absenteeism in the general employee population during this period. The main factors associated with increased absenteeism were becoming aware of the condition (P less than 0.01) and low compliance with treatment (P less than 0.001). Subsequent absenteeism among patients unaware of their hypertension before screening was not related to the degree of hypertension, whether the worker was started on therapy, the degree of blood-pressure control achieved or exposure to attempts to promote compliance. These results have major implications for hypertension screening programs, especially since absenteeism rose among those previously unaware of their condition, regardless of whether antihypertensive therapy was begun.


Foreign medical graduates and the issue of substantial disruption of medical services. Provisions of the 1976 Health Professions Educational Assistance Act may result in a substantial disruption of medical services provided by foreign medical graduates in United States residency training programs. Estimates of the effect of the Act indicate that between one third and two thirds of foreign graduates receiving visas annually will not qualify for admission, under the new provisions. Results of a recent study show, furthermore, that foreign medical graduates constitute a majority of the residents in 23 per cent of the hospitals with residency programs. Transition to a decreased dependence on foreign graduates may be facilitated through the waiver of two provisions relating to exchange visitors. Projected numbers of United States medical graduates and citizens receiving medical education abroad will not be enough to fill the gap created by the ultimate reduction in alien physicians. United States residency programs will have to develop alternative sources of residents to continue operating at current levels.


The relation of product formulation to absorption of oral theophylline. To assess the potential for therapeutic problems related to the bioavailability of oral theophylline preparations, we examined the rate and extent of absorption for various formulations in adult volunteers. Absorption of theophylline from a solution or from uncoated tablets was rapid and complete. Three of six sustained-release formulations were more slowly, but still completely and consistently, absorbed. Absorption of the other three sustained-release formulations appeared to be more erratic and less complete. Serum concentration-time curves during multiple eight-hour dosing were simulated for the bioavailable preparations. With three sustained-release formulations it was predicted that fluctuations in serum theophylline concentrations between doses would decrease, as compared with uncoated tablets, to a clinically important extent, particularly in children, in whom elimination of theophylline is generally rapid.


Performance of United States citizens with foreign medical education on standardized medical examinations. To enter the mainstream of American medicine, United States students who enroll in foreign medical schools must either transfer to a United States medical school (usually after passing Part I of the NMBE examination) or complete their studies abroad and then pass FLEX and usually ECFMG examinations. Half those applying for transfer fail Part I. Although virtually all who succeed in transferring subsequently pass Parts II and III, their scores are below the mean of the reference group, and their relative performance progressively deteriorates. Sixty per cent of USFMG's fail the medical portion of the ECFMG examination as compared to an expected failure rate for United States medical students of only 2 to 3 per cent. Thirty-eight per cent of USFMG's who take both ECFMG and FLEX examinations fail the latter. The mean weighted score for USFMG's on FLEX is 75.8, while that for United States graduates is 80.1 and for FMG's 74.7. These preliminary data suggest that United States students who go abroad, regardless of where they complete their studies, do not perform as well on standard tests after they return home as do those who have had their entire education in United States schools. This question needs more systematic study.


Genetic mapping of the 21-hydroxylase-deficiency gene within the HLA linkage group. To document further the proposed genetic linkage between congenital adrenal hyperplasia due to 21-hydroxylase deficiency and HLA, 34 unrelated families from New York and Zurich, with a total of 48 patients, 48 siblings and their parents, were studied. All patients were HLA genotypically different from the healthy sibs; when two or more children were affected in the same sibship they were always HLA-B identical. The gene for 21-hydroxylase deficiency was separated by genetic recombination from the HLA-A locus and from the locus for glyoxalase I-polymorphism. No HLA-A, HLA-B or HLA-C antigen was selectively increased among the 34 unrelated patients. Lod-score analysis for HLA-B:21-hydroxylase deficiency gave a peak for theta approximately 0.00 at 5.20 for females and 4.30 for males, giving a total peak lod score of 9.5 at theta approximately 0.00 when male and female lod scores were combined. Close genetic linkage between HLA-B and 21-hydroxylase deficiency was thus established.


Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin. The clearance of endogenous creatinine in 20 burned patients, measured between the fourth and the 35th post-burn day, was a mean (+/- S.D.) of 172.1 p 48.4 ml per minute per 1.73 m2; in eight normal subjects the mean value was 125.4 g- 10.4 (P less than 0.02). Thirteen patients had values more than 2 S.D. above the normal mean. We confirmed this rise in glomerular filtration rate by measuring inulin or iothalamate clearance in nine patients. The pharmacokinetics of tobramycin were studied in 11 of the 20 patients and in eight normal subjects receiving continuous intravenous infusions of the drug. An inverse correlation was found between plasma half-life of the drug and creatinine clearance (r = 0.68, P less than 0.01). Increased creatinine clearances and shortened half-life of tobramycin occurred mainly in younger patients. Glomerular filtration rates in burned patients may rise to very high values and can be validly measured by creatinine clearance. The plasma half-lives of drugs with predominantly urinary excretion may decrease in patients with burns.


Transient hyperammonemia of the preterm infant. We report on five preterm infants (34 to 36 weeks' gestation) in whom an overwhelming illness developed within the first 48 hours of life. Each had mild respiratory distress that progressed within 48 hours to deep coma requiring ventilatory assistance. Ammonia concentrations in the plasma ranged from 844 to 7640 microgram per deciliter. Four received exchange transfusion and peritoneal dialysis; ammonia values returned to the normal range (less than 150 mug per deciliter) within 72 hours and remained there even after protein challenge. These four subsequently fed and developed normally. The fifth infant died without an attempt to lower plasma ammonia. In this infant (and two of the others) urea-cycle enzymes measured in liver tissue were in the normal range. Transient hyperammonemia of unknown cause may be a relatively common variety of neonatal hyperammonemia; it responds well to prompt diagnosis and aggressive therapy.


Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. To determine why many diagnostic tests have proved to be valueless after optimistic introduction into medical practice, we reviewed a series of investigations and identified two major problems that can cause erroneous statistical results for the "sensitivity" and "specificity" indexes of diagnostic efficacy. Unless an appropriately broad spectrum is chosen for the diseased and nondiseased patients who comprise the study population, the diagnostic test may receive falsely high values for its "rule-in" and "rule-out" performances. Unless the interpretation of the test and the establishment of the true diagnosis are done independently, bias may falsely elevate the test's efficacy. Avoidance of these problems might have prevented the early optimism and subsequent disillusionment with the diagnostic value of two selected examples: the carcinoembryonic antigen and nitro-blue tetrazolium tests.


Natural history of familial medullary thyroid carcinoma: effect of a program for early diagnosis. To detect familial medullary thyroid carcinoma in a premetastatic stage, we administered tests provocative of calcitonin secretion (infusion of calcium or pentagastrin or both) each year for seven years to members of a pedigree now numbering 107. Since 1970, 21 patients converted from normal to abnormal secretory responses (two separate tests in which calcitonin levels exceeded 0.58 ng per milliliter). Twenty of 21 glands removed showed C-cell hyperplasia, and eight of the 20 also showed foci of carcinoma. As compared to the 12 patients with tumors detected during the first year of screening, all of whom had bilateral carcinoma (seven of 12 with local metastases), later carcinomas were smaller (mean diameter of 0.2 vs. 0.8 cm), were unilateral (in all but two cases) and occurred in younger patients (mean age of 14.9 vs. 36.4 years), and none had detectable metastases.


[Study of the Sporothrix schenkii (yeast forms) extract. Electrophoretic and immunoelectrophoretic analyses: characterization of enzymatic activities]. An extract from living yeast forms of S. schenckii was prepared. The yeasts originated from a shake culture in B.H.I. broth (Difco) incubated for 3 days at 35 degrees C in darkness; they were harvested, washed and disrupted with glass beads in a model MSK Braun mechanical cell homogenizer; a freezing-thawing was added to improve the extract. After electrophoretic separation in agarose gel, the extract's components were characterized by their enzymic activity; with this technique, 30 bands were revealed. These enzymic activities were also investigated on the antigenic fractions of the extract revealed by a rabbit hyperimmunserum: 16 among 22 immunoprecipitates are identified by their catalytic properties. Study of the earliest precipitating antibodies (appearing-order and enzymic caracterization) in rabbits just immunized completes this work. How to ameliorate the quality of the extract by culture and extraction conditions is also specified.


Atypical strains of Microsporum canis.

Atypical strains of Microsporum canis. Four atypical isolates of Microsporum canis, three from humans and one from a cat, were obtained from North-West London. These and a further human isolate were compared with each other and with a typical isolate of the fungus. Immediately after isolation the atypical isolates were very labile, but were stabilised after a few subcultures from selected sectors. The stable forms differed from each other, but all had a tendency to brown rather than yellow pigmentation, to feathery submerged mycelium and to abnormal macroconidia. The macroscopic appearance and texture of the colonies depended on the density, orientation and branching pattern of the submerged mycelium. In recent years similar brown, feathery forms of M. canis have been reported from monkeys but not from cats. It is suggested that all such isolates may be culturally stable forms of a very unstable strains, probably feline in origin, which has yet to be described.


Red grain mycetoma of the scalp (Actinomadura pelletieri). A case report from India. A case of red grain mycetoma on the scalp is described. The disease, caused by Actinomadura pelletieri, is extremely rare in this part of the world, and from India this is perhaps the first case with scalp involvement. The lesion showed satisfactory response to partial excision followed by chemotherapy with streptomycin.


Epidemiologic study of dermatophyte infections in Nigeria (clinical survey and laboratory investigations). The commonest dermatophyte infection among the referred dermatology cases in Nigeria is tinea pedis, whereas among the surveyed population of school children, the commonest fungal infection was tinea capitis. It was found that the most ubiquitous causative organism for tinea pedis was E. fluccosum, that for tinea capitis was M. audouinii, while that for tinea corporis was T. soudanese. The source of infection of tinea capitis among the school children was found to be most likely the local barber who serviced the schools in all the villages, and this might explain the high incidence rate of T. soudanese in tinea capitis. Tinea pedis infection is believed to be highly favoured by the wearing of shoes among the senior students. Animals were not a major source of transmission of dermatophytes in Nigeria. No new species of dermatophytes has been identified among the cultured organisms.


Estimation of Absidia ramosa infection in the brain and kidneys of cortisone-treated mice by chitin assay. Chitin assay was used to measure Absidia ramosa infection in the brain and kidneys of cortisone-treated mice. Mice dying 3 days after challenge had brain and kidney infection but normal renal function as determined by measurement of blood urea levels. Mice dying 5 or 6 days after challenge had infection in the kidneys but not the brain and were uraemic.


[Effects of insulin, glucagon and secretin on intestinal resorption of glucose]. The authors describe a versatile experimental procedure for the study of intestinal digestion and resorption in animals. This procedure is based on the principle of the continuous perfusion of a completely isolated intestinal segment. The results from experiments on glucose absorption from the jejunum of the rabbit serve to demonstrate the great reproducibility of this in vitro technique. No hormonal influence on monosaccharide resorption could be detected by means of this procedure, even in case of unphysiologic dosage of insulin, glucagon and secretin.


[Biological value of wheat proteins as dependent on maturity of the wheat grain]. The authors studied the dependence of the change in biological protein value of the wheat grains upon the degree of maturity. The biological protein value (as calculated according to MITCHELL) decreases during the period of ripening and, at the time of full ripeness, it is significantly lower than in the initial stage. This decrease varies from 10.7 to 19.0%, according to wheat variety. In contrast to this, the essential amino-acid index changes but insignificantly with ripening. Virtually identical biological protein values were obtained with both methods from full-ripe wheat grains.


[Confirmatory reactions for the identification of patulin in apple juice by thin layer chromatography]. To avoid misinterpretations in identifying mycotoxins by means of thin-layer chromatography (silica gel), it is necessary to make use of a second method of identification. The reaction with phenylhydrazine and with 2,4-dinitrophenylhydrazine on the plate is suited for patulin. The thus obtained hydrazones are transferred to a second thin-layer chromatographic plate and separated using toluene/acetic acid ethyl ester/85% formic acid (50 + 40 + 10, v/v) or chloroform/acetone (68 + 32, v/v). This method of identification may be used, for example, for apple juices with a patulin content equal or greater than 500 microgram/l.


[Glucose-6-phosphate dehydrogenase activity in various organs of rats on high fat diets]. This paper deals with investigations on the activity of glucose-6-phosphat dehydrogenase (G6-P-GH), a key enzyme of HMP Shunt in erythrocytes, kidney, adrenal cortex, testes and adipose tissue of rats fed a high-fat diet (50% fat), in comparison with 3% fat diet as control animals. In erythrocytes, kidney and testes no significant differences of enzyme activity were observed. The number of erythrocytes and haematocrit value were also no different. The haemoglobin level was significantly elevated. In adrenal cortex and in mesenterial adipose tissue significantly lowered activity of G6P-DH is observed. These data are comparised with former studies in liver of high-fat diet rats and with literature data from adipose patients.


[Digestion and transport of carbohydrates and proteins]. Studies on the adaptive changes in the membrane hydrolysis and the carbohydrate and protein transport that occur when chickens are fed diets differing quantatively from each other with regard to their contents of major nutrients, yielded the following results: I. By increasing the protein content of the diet (up to 30%), the absorption of carbohydrates and proteins is inhibited. 2. A positive effect of a diet with increased fat content on the digestion of carbohydrates and proteins was observed solely with dietary lipids rich in unsaturated fatty acids (sunflower oil).


[Food substitution and consumption development]. Though being sometimes less in evidence, the food consumption of the population is undergoing a continuous change in course of time. It can be considered as a matual substitution of foods. In most cases, the increase in consumption of certain foods is correlated with the decrease in consumption of other foods. The author points to the contents, principles and examples of food substitutions that had been revealed by studies using a linear optimization model.


[Influence of a high fat diet on serum uric acid levels in rats]. In present paper the behaviour of uric acid is investigated in serum from rats fed with a 50% fat containing diet in comparison with 3% fat diet as control group. After feeding high-fat diet 5 resp. 52 weeks the level of uric acid is significantly elevated. In the same diet group heavier animals showed higher uric acid levels than lighter animals. In these experiments the age of animals is without influence of the uric acid level in serum.


[Mode of action and inhibition of polygalacturonase covalently bound to polysaccharide and glass carriers]. Endo-polygalacturonase (EC 3.2.1.15.) from Aspergillus spec. is much changed as far as its mode of action and the interaction with vegetable inhibitors of pectinase (from green beans and cucumbers) are concerned when it is covalently bound to insoluble carriers (Sepharose, cellulose powder, macroporous glass and nonporous ballotinis). Whereas a 2% degradation of substrate by the soluble enzyme caused a 50% decrease of viscosity of citrus pectic acid, the comparable degradation of substrate was increased to a level of about 10% with the investigated polygalacturonase carrier complexes apparently independent of the properties of the carriers and the kind of binding of the enzyme. In contrast to this the higher degradation of substrate of 15 and 20% respectively which was further stated at a 50% decrease of viscosity is unambiguously connected with the carriers and is in direct correlation with the specific activity of the polygalacturonase carrier complexes. Contrary to the soluble enzyme the covalently bound enzyme produces more lower oligomerous galacturonic acids by an exo-mechanism or by multiple attack already at the beginning of the hydrolysis of pectic acid. During the final stage there is an enrichment of trigalacturonic acid besides mono- and digalacturonic acids independent of the state of solution of the enzyme. It could further be stated that the strong inhibition of the soluble endo-polygalacturonase by selected pectinase inhibitors which was described earlier is reduced by degrees with the enzyme covalently bound to the insoluble carriers.


[Properties of adipocytes (diameter, volume, triglyceride content, cell number) of certain types of fatty tissue as a function of age in male Wistar rats]. The diameter, volume, triglyceride content and number of adipocytes were determined in male Wistar rats at the age of 6 weeks and 2, 3, 12 and 18 months, respectively. A standard diet and water were given ad libitum. The adipocytes were isolated by means of the method of RODBELL. The weight and fat content of the fatty tissues were determined gravimetrically. Age exerts no effect on the adipocyte parameter, nor on the weight and the fat content of the fatty tissue. In contrast to this, there are relationships between adipocyte diameter and the increases in body weight. In all age groups, the increase in size and number of the adipocytes was significantly greater in heavy animals than in light ones. Genetic, hormonal and dietarily-induced factors are discussed as a possible cause. The authors observed no difference in adipocyte size between epididymal and perirenal fatty tissues. As compared to this, the mesenteric adipocytes were smaller.


[Effect of a high fat diet on the behavior of the diameter, volume, triglyceride content and number of the adipocytes in different types of fatty tissues in male Wistar rats]. The effect of a high-fat diet on the diameter, volume, triglyceride content and number of the adipocytes was studied in male Wistar rats at the age of 9 weeks and 6 months, respectively. The adipocytes were isolated by means of the method of RODBELL. The adipocyte diameters were measured using the microscopic method. The weight and the fat content of the fatty tissue were determined gravimetrically. A diet containing 50% fat increases the diameter, volume and triglyceride content of the adipocytes and also the weight and the fat content of the different types of fatty tissue. The fat content of the diet and the duration of feeding are of importance. The high-fat diet exerts no effect on the adipocyte number. However, in both age groups, the adipocyte numbers were sometimes greater in heavy animals than in light ones fed the same diet. Genetic, hormonal, and dietarily-induced factors are considered as a possible cause.


[Sensitivity of marine bacteria to several disinfectants used in the fish processing industry. I. Homologous and heterologous resistance of Pseudomonas and Moraxella ssp]. It was shown that ability of developing resistance to QAC by Moraxella ssp. is limited, while marine strains of Pseudomonas sp. are able to develop both homological and heterological resistance to Sterinol and Laurosept. Five months storage in medium without QAC caused partial loss of resistance of strains which previously gained resistance to this compound. None of the tested marine bacteria strains was able to get resistance against Chloramina T. Strains with developed resistance to Laurosept and Sterinol became more sensitive to Chloramina T. On the other hand, as a result of contact of the same bacteria with sublethal doses of Chloramina T increase of sensitivity to QAC was observed.


The role of biogenic amines in foods.

The role of biogenic amines in foods. Biologically active amines are normal constituents of many foods for example cheese, plant foods and wines. These low molecular weight organic based do not represent any hazard to individuals, unless large quantities are ingested or natural mechanism of their catabolism are inhibited. Investigations were performed concerning the histamine and tyramine content of the Hungarian made cheese, domestic vegetables, fruits and some other foods. In this paper we should like to draw the attention to the problems of amines from the point of view of food hygiene and food-drug interactions.


[Effects of reduced diet and physical stress on liver lysosomes. Morphological and biochemical studies]. Groups of 15 rats each (I--non-reduced diet; II--non-reduced diet and physical stress; III--diet reduced by 40%; IV--reduced diet and physical stress) were examined after 20 and 140 days, respectively. The electron microscopic examination revealed that the most important changes had occurred in group III; there exists an excess of autophagolysosomes. The biochemical examinations show that the reduced diet (group III) also produces a considerable increase in activity of most of the lysosome enzymes in the liver. The occurrence of autophagy evidences that this is either physiologically induced or the manifestation of a beginning pathological process.


[Glyceride structure of fats. 11. Structure studies on selected nut fats using lipases]. Using pancreatic lipase of Geotrichum candidum, the authors determined the fatty acid pattern and the glyceride structure of peanut, filbert, walnut, Brazil nut and cashew-nut fats. Both the fatty acid pattern and the glyceride structure were comparable to those of other vegetable fats of corresponding total fatty acid composition.


[Residue determinations in milk following application of the fasciolicides rafoxanide and hexachloro-p-xylene]. The control of Fasciola hepatica in dairy cattle may lead to considerable residue problems in dairying. In the GDR, a hexachloro-p-xylene-based fasciolicide has been approved till recently, and another, rafoxanide-based fasciolicide has been on trial. The investigations have shown that the two active principles are excreted in the milk for a prolonged period, rafoxamide being found more suitable. Their marked lipophil behaviour leads to accumulation in the fat phase and, thus, in high-fat milk products.


[Dietary proteins and deiodination in the liver]. The authors studied in male Wistar rats the effects of diets containing 66 and 2% (w/w) of protein on the one hand, and 18% (w/w) of protein on the other hand, on the deiodination of L-thyroxine in liver homogenate supernatants. The deiodase activity in the liver protein increased in case of low-protein diet, and decreased in case of high-protein diet; these differences were statistically significant. When the body weights of the animals were taken into account, the deiodinating power of the whole liver was significantly reduced in case of low-protein diet, but not significantly reduced in case of high-protein diet. Consequently, the reference value adopted for the calculation of the degree of deiodination is of paramount importance to validity.


Three-dimensional reconstruction of the fibres of sickle cell haemoglobin. Three-dimensional reconstruction of electron micrographs of the 20-nm diameter fibres of HbS reveals an inner helical core of four strands surrounded by an outer helix of 10 strands to give a total of 14 strands. The strands are arranged with roughly hexagonal packing to produce an unusual helical structure which features a variety of intermolecular contacts and a non-circular cross section.


Scanning electron microscopy and the surface morphology of human lymphocytes. The surface of the human lymphocyte as seen by the scanning electron microscope shows variations which may reflect the functional state or environment of the cell. Preparative techniques and future developments in this area are reviewed.


Plasmid incompatibility: cloning analysis of an incFII determinant of R6-5. SalI and PstI restriction endonuclease-generated DNA fragments that specify an FII-type incompatibility function (incFII) of the low copy number antibiotic resistance plasmid R6-5 have been cloned in the high copy number pBR322 plasmid vector. A 1-kilobase DNA sequence that contains this incFII determinant has been identified and is shown to have coordinates of 95.5 and 96.5 kilobases on the R6-5 plasmid physical map. Expression of incompatibility by the cloned PstI fragment depends on its orientation within the vector molecule. The behaviour of pBR322-incFII hybrid plasmids suggests that plasmid replication control is not the only mechanism that can cause incompatibility between two plasmids.


Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. The nucleosome subunits of chromatin are assembled from histones and DNA by an acidic protein which binds histones. The nucleosome assembly protein has been identified and purified from eggs of Xenopus laevis.


A two-step fibrinogen--fibrin transition in blood coagulation. The kinetics of the thrombin-catalysed release of fibrino-peptides A and B from human fibrinogen have been investigated and a mechanism correlating the release of fibrinopeptides to fibrin formation is presented. The sequential release of fibrinopeptides results in sequential activation of two sets of polymerisation sites.


Nucleotide sequence homology at 12 intron--exon junctions in the chick ovalbumin gene. A short partial sequence homology is present at all intron-exon junctions, or splice points, in the chick ovalbumin gene; it is probably a signal for a splicing enzyme. The significance of the junction sequences for splicing is discussed. We find no evidence of strong Watson-Crick base pairing between adjacent junctions.


[Cancer, what do we know, what can de do?]. Some epidemiologic data on the frequency of cancer and etiologic factors that especially concern the formation of malignant tumors are reported. The role of prevention and prophylaxis is discussed as well as prophylactic precautions. Regarding therapy, not only the progress of local high-frequency hyperthermia combined with bacterial oncolysis is explained, but also that of cytostatic chemotherapy. Last but not least, attention is directed to the importance of basic oncologic research.


[Function of arginine in enzymes].

[Function of arginine in enzymes]. The average arginine content of proteins is 3.9%. Its frequency among the 20 amino acids of the proteins (13th position) is far lower than would be anticipated from the fact that 6 of the 61 codons for amino acids in the genetic code are arginine codons. Possible explanations for the relatively low frequency of arginine in proteins are discussed. The chemical and physicochemical properties of arginine, which are determined by the guanido group, and the method for chemical modification of arginine residues in proteins are described. The most important function of arginine residues in enzymes seems to be the recognition, binding, and orientation of anionic substrates and cofactors. This function is illustrated by numerous examples.


A single radial hemolysis technique for the measurement of influenza virus antibody in  swine serum. A single radial hemolysis technique was applied to the measurement of swine influenza virus antibody in swine serum. It was recognized to be useful for the detection of this antibody, although heating at 56 degrees C for 30 minutes was necessary to remove non--specific hemolysis from the test sample. The single radial hemolysis titer was correlative with the hemagglutination--inhibition titer in serum from pigs infected experimentally or naturally. This technique is simple, rapid and unaffected with non--specific inhibitors in swine serum. It does not require concentrated purified virus either. Therefore, it is applicable to the sero--epizootiologic surveillance of swine influenza on a large scale.


Development of tolerance to the analgesic effect of clonidine in rats. Cross-tolerance to morphine. The influence of chronic treatment with clonidine on analgesia produced by clonidine and morphine was studied in rats. Electrical stimuli were applied to the tail, and analgesia was measured as increase in the threshold voltage that elicited vocalisation. Twenty-two hours after the last of 14 injections of increasing doses of clonidine over 7 days, the acute analgesic effects of both clonidine and morphine were reduced, i.e. tolerance had developed. Pretest vocalisation thresholds (voltage) were unchanged by long-term treatment with clonidine, or, respectively, saline. Contrarywise, acute administration of clonidine enhanced the effect of morphine. The tolerance developed after long-term treatment with clonidine might be associated with changes in brain noradrenaline mechanisms.


The effect of thyroid hormone on serotonergic neurones: depletion of serotonin in discrete brain areas of developing hypothyroid rats. A single intraperitoneal injection of 131I in a dose of 200muCi in 1-day-old rats induced hypothyroidism and decreased the activity of tryptophan hydroxylase in mid-brain region. The levels of 5-hydroxytryptamine also were reduced in cerebellum, mid-brain and striatum by 22%, 29% and 31%, respectively. By contrast, the levels of its metabolite, 5-hydroxyindoleacetic acid, were significantly increased in cerebellum, mid-brain and striatal region. To ascertain whether changes induced by neonatal radiothyroidectomy were specific, the effect of replacement thyroid hormone therapy was studied on 5-hydroxytryptamine metabolism. Daily administration of L-triiodothyronine (10 microgram/100g s.c.) for 25 days beginning from five days after radio-iodine treatment enhanced tryptophan hydroxylase activity, tryptophan and 5-hydroxytryptamine levels to values seen in normal rats of the corresponding age group. The concentration of 5-hydroxyindoleacetic acid decreased following L-triiodothyronine treatment. Furthermore, when replacement therapy with L-triiodothyronine was postponed until adulthood, no significant effects could be seen on various parameters related to 5-hydroxytryptamine metabolism. Our data demonstrate that deficiency of thyroid hormone in early life disrupts the normal upsurge of 5-hydroxytryptamine metabolism in brain. A critical period exists in early life of rats during which thyroid hormone must be present for the optimal development of 5-hydroxytryptamine metabolizing systems in maturing brain.