Hepatic triglyceride lipase deficiency in liver disease.

The activity of post-heparin lipases in patients with alcoholic hepatitis and viral hepatitis was evaluated. Lipoprotein lipase and hepatic triglyceride lipase were differentiated by assay under high and low salt conditions and also by separation on heparin-agarose affinity chromatography columns. The mean activity of hepatic triglyceride lipase in the sera of liver disease patients was only 21-24% of the mean of controls, but lipoprotein lipase in patients' sera was not different from normal levels. Hepatic triglyceride lipase deficiency may partially account for the accumulation of a triglyceride-rich low density lipoprotein in liver disease.


Stimulation of hepatic lipogenesis by eicosa-5,8,11,14-tetraynoic acid in mice fed a high linoleate diet.

Liver slices, from mice fasted for one day and then refed for three days either a 15% corn oil diet or a 15% corn oil diet containing eicosa-5,8,11,14-tetraynoic acid (TYA), were incubated with [1-14C] acetate or [3H] H2O to determine lipogenic capacity. Dietary TYA produced a twofold stimulation in fatty acid and cholesterol synthesis. TYA also caused an increase in the relative proportion of linoleate (C18:2) and a decrease in that of arachidonate (C20:4) in liver. Thus, (a) despite high levels of C18:2, hepatic lipogenesis can be increased, and (b) even short term feeding of TYA can alter the hepatic fatty acid composition presumably by inhibition of arachidonate synthesis from linoleate.


[Intoxication with the pesticide IPO-1250 in rats].

Rats were administered porridge with pesticide IPO-1250 in doses 50, 200, 800 and 4000 ppm. The animals were killed and subjected to a selective examination. The mass of organs relative to the brain mass was determined and its segments were examined histopathologising. It has been concluded that IPO-1250 affect metabolic processes of rats, a decrease or increase of the inner organs mass. In the examined organs were observed non-specific and generally reversible pathomorphotic changes in the form of circulatory disturbances and regressive changes. The intensity of changes increased typically at the highest applied dose of pesticide = 4000 ppm. The observations allowed to establish the highest dose tolerated by rats which for the preparation IPO-1250 amounts to 800 ppm.


[Effect of carbon disulfide on the leukergic reaction in rabbits].

The leukergic reaction in rabbits exposed to carbon disulphide was studied. The investigations were carried out on 14 animals, where of 7 constituted the experimental group, the remainder the control group. The animals of the first group were subjected to CS2 action in a toxicological chamber over a varied period of time (from 16 to 103 days, 5 hrs daily), the CS2 concentration being 0,4 mg per litre of the flowing air. It was found that there was a significant increase in the agglutination test of leukocytes in animals of the experimental group (p less than 0,01). The several possibilities of interpreting the obtained results were discussed.


[Acute carbon tetrachloride poisoning].

The clinical course of acute poisoning with carbon tetrachloride in 13 patients is presented. The treatment with corticosteroids has been beneficial, particularly in cases with considerable damage of the liver. The extracorporal dialysis allowed to survive the period of heavy uraemia.


[Evaluation of tolerance of prolonged physical work as a function of the degree of endurance. I. Useflness of various tests determining physical endurance and the physiological cost of long-term physical exertion].

The physical capacity was determined in 23 men (aged from 19 to 27) using the following set of tests: Astrand and Ryhming's test, PWC170, PWC130, LPI, Crampton's test. The 70 min effort on the bicycle ergometer was considered as the model of prolonged work and the following parameters were accepted as standards of physiological cost of work; oxygen consumption, mechanical efficiency, heart rate during the work, stroke volume and cardiac output as well as the sum of systoles during recovery. The results of the correlation analysis point out that, at a given work intensity. the heart rate depends on results of PWC170 test and the systoles sum during recovery on the results of Crampton's tests. The capacity determined with used tests had no effect on the remaining indices of the cost of physical work.


[Effect of prolonged moderate physical work on psychomotor and mental performance].

The examinations were carried out in the group out in the group of 20 men aged from 19 to 27 with middle physical fitness level. The studied concerned the simple reaction time to auditory and visual stimuli, the Coordination Test performed with variable speed, the work output in Paule's Test and the learning and recalling of nonsense syllables. The positive effect of physical effort on the results obtained in the psychomotor task (Coordination Test) requiring a quick performance has been observed. The physical work had no significant effect on the duration of reaction time as well as on the work efficiency in the applied mental tests.


[Evaluation of the noise produced by mechanical saws used in forestry].

The noise level of 25-motor-saws used for felling and processing wood has been measured. There were found that the saws are the source of an intermittent noise, and the break periods of various duration occur irregularly. The sound pressure level ranges from 100 dBA to III dBA (N97-M108) and the daily noise exposure of a sawyer amounts to 77 minutes. Evaluating the noise produced by motor-saws by means of damage risk criteria for intermittent exposure, it was stated that the noise level exceeds slightly the allowable values. The statistical analysis showed correlations between noise level and type of the saw, speed of motor turns and degree of saw wear.


[Certification criteria in pre-employment interviews of candidates for operators of mechanical saws].

The work of the motor-saw operator is very hard and dangerous because of the exposure to noxious factors as vibration, noise, combustion gases and variable atmospheric conditions. The authors discuss the certification criteria including the medical contraindications and propose the range of the pre-employment examinations.


[Mobile soundproof booth for audiometric industrial testing].

The authors modified a caravan for the purpose of audiometric testing in the neighbourhood of industrial workplaces. The sound insulation of the caravan increased due to the use of double glasses in the windows, special tightening of the doors and covering the walls with sound absorbing material. The gained insluation enables the testing of the threshold of hearing in a surrounding where the ambient noise does not exceed foolowing octave-band noise levels: 49 dB--125 Hz, 59 dB--250 Hz, 57 dB--500 Hz, 74 dB--1000 Hz, 81 dB--2000 Hz, 91 dB--4000 Hz, and 100 dB--8000 Hz.


[Patch tests performed with Epidian in workers exposed to epoxy resins].

The patch tests according to the Jadassohn-Bloch's method were made with five Polish epoxy resins--"Epidian"--in 487 workers exposed to their action, and in 113 persons of the control group. The percentage of sensitized persons among 487 examined amounted to 22,8%, the results of test in the control group being negative. It has been found that particularly sensitizing action is produced by the non hardened resins (the percentage of persons sensitized in the group working at non hardened resins was 26,7, at hardening ones--2.6).


[Mass examination of women employed in the Lódź textile industry (with special reference to the genitalia)].

The complex examinations of the state of health of 468 women workers of the Central Laboratory of Textile Industry in Lodź were performed. In all women were performed physical and gynecological-biochemical examinations as well as hematological-biochemical ones of the selected blood parameters. It has been stated a high (61,8%) percentage of women with morbid changes or genital organs and lower values of examined blood parameters in spinners, comparing with workers of the finishing department and administration.


[Radioelectrocardiographic record in workers employed in railroad repair shops].

Cardiac response to the physical effort due to occupational work was studied in 33 workers employed in a railway repair shop by means of radioelectrocardiography. The HR ranges, HR mean values and r-ecg changes in different professional groups are described. Attention was paid to the pronounced sinus arrythmia observed in subjects performing hard work. The quantitative and qualitative changes of the obtained results were described and the difficulties in the evaluation of r-e.c.g. records obtained during dynamic examination were emphasized.


[Use of various accordance measures in the study of sick leave frequency distribution per man-year].

In the studies of a wide number of phenomena very often an attempt to describe their distributions with the help of certain theoretical distributions is undertaken. Pearson's  chi2 and Kolmogorovs lambda traditional tests, when applied to the evaluation of accordance between the empirical distribution and the distribution calculated on the basis of theoretical probability function, depend directly on the dimensions of population studied, and they are not useful in the case of big quantities. In the paper the author presents a great number of measures for two (empirical and theoretical) distributions accordance and their application to the study of sick-leave frequency distribution per man per year. On the basis of received results a high level of distributions accordance between the  sick leave cases distribution and the negative binomial distribution has been observed. The distribution of sick leave shows a high accordance with the logarithmically-normal distribution. In the light of the above mentioned distribution study, the imperfection of Pearson's chi2 and Kolmogorov's lambda tests can be ascertained. In the case of big quantities the evaluation of distributions accordance seems to require the application of the accordance measures based on relative quantities.


[Gas chromatography determination of trichloroethylene and tetrachloroethylene in the air].

Parameters of gas chromatographic separation and determination of trichloroethylene and tetrachlorethylene have been elaborated. The best separation has been achieved on column containing 7% OV-17 on Chromosorb W AW DMCS. For air samples collection, a method of absorption on charcoal and consequent desorption with carbon disulfide has been adapted. Stability of concentration of determined compounds in gas pipettes has been also evaluated. The investigations proved the concentration of compounds in gas pipettes to decrease in time. The magnitude of decrease was dependent on initial concentration and the boiling points of the compounds.


[Effect of machine modernization on the level of noise and its characteristics in the textile industry].

Results of noise measurements on work post before and after modernization are presented. In the majority of examined work areas noise levels were lowered by 2--20 dB(A) after machine modernization. Present noise level is there about 90 dB(A). On the other hand limit the noise level on work post of rewinders, trosiners and looms has not been changed. So far noise level on these areas has exceeded permissible level by 5--14 dB(A).


[Prolonged cardiologic and neurologic complications following electric shock].

Long-term cardiological and neurological observations of 8 patients struck with electric current are presented. It was found that electric shock causes chronic myocardiac lesions followed by the coronary heart disease, cardiac insufficiency and arrhythmia, occuring mostly as premature ventricular extrasystoles. In most of affected persons, symptoms of distonia vegetativa were present during several years. EEG changes and Marinesco-Radovici symptom suggest that in some cases the observed vegetative symptoms can depend on organic changes in the central nervous system.


[Effect of carbon disulfide on cholesterol content in rat tissue].

The effect of chronic intoxication of rats with CS2 on the level of cholesterol in the body tissues was studied. Prolonged exposure to CS2 vapour results in the increased level of cholesterol in serum. It was interesting to find out whether accumulation of cholesterol occurs subsequently in the body tissues. Studies were performed on male Wistar albino rats exposed to CS2 vapour at concentration 0.8--1 mg/1 during 13 months. The level of cholesterol in the blood, aorta wall, muscles, liver and adipose tissue was estimated after 4, 10 and 13 months of intoxication. Chronic exposure of rats to CS2 vapour causes: (a) loss of body weight about 30 per cent after 10 months of intoxication; (b) increase of concentration of free and esterified cholesterol in the aorta wall about 20 and 63 per cent, whereas in the skeletal muscles about 40 and 80 per cent, after 10 and 13 months of exposure respectively; (c) no changes of the level of cholesterol in the liver. On the base of the results obtained in this study it was concluded, that prolonged exposure to CS2 contributed to accumulation of cholesterol only in some tissues. Changes we found are probably the result of quantitative shift in the redistribution of cholesterol among the tissues.


[Effect of petroleum on the function and morphological picture of the liver].

The male rats of Wistar strain were exposed to the vapours of arabic petroleum Abu-Dhaki Zakun at concentration of 1500 mg/m3 during 12 weeks, 6 times weekly per 90 minutes daily. The biochemical examinations of blood serum (aminotransferase, alkaline phosphatase total protein level and its fractions, bilirubin level) and histopathological and histochemical examinations of the liver have revealed no deviations from the normal state.


[ECG picture in rats exposed to the action of petroleum].

The male rats of Wistar strain were exposed to the vapours of arabic petroleum Abu-Dhaki Zakun at concentration 1500 mg/m(3) during 16 weeks, 6 times weekly per 90 minutes daily. The ECG examinations revealed progressive bradycardia, increase of the percentage of conduction disturbances appearing as the bundle-right branch block, changes of the shape of P deflection, decrease of the angle of inclination of QRS vector, and increase of the percentage of nonspecific changes of ST-T syndrome. The obtained results can suggest a noxious effect of petroleum on the heart muscle when given by inhalation in a determined concentration.


[Non-specific immunity of persons exposed to contaminants emitted by nitrogen plants].

The examinations of methemoglobin and properdine levels as well as of the function of peripheral blood leukocytes in the tetranitrozolic blue reduction test (NBT) were performed in the exposed persons. The obtained results were compared with those of the control group, using statistical methods. It has been found that in persons exposed to the emitted contaminants occurs the increase of methemoglobin level, the decrease of peoperdine level and a disturbed phagocytes function. The recorded changes in the factors of nonspecific immunology, i.e. of properdine and phagocytes, can favour the development of inflammatory processes and of nonspecific diseases of the respiratory system.


Evidence for the early reduction of the 24,25 double bond in the conversion of lanosterol to cholesterol in cerebrotendinous xanthomatosis.

The metabolism of lanosterol and 24,25-dihydrolanosterol (DL) was examined in a patient with cerebrotendinous xanthomatosis after intravenous pulse labeling with a mixture of DL-2-14C and 3S,4S,3R,4R-(4-3H)mevalonate. Sterols were isolated from the feces and purified by silver nitrate thin-layer chromatography, and their identities were confirmed by gas-liquid chromatography and mass spectrometry. Their specific activities were then determined and plotted as a function of time. These isotope ratio measurements and specific activity decay curves were consistent with 24,25-dihydrolanosterol and delta7-cholestenol being intermediates in the synthesis of cholesterol from mevalonate and lanosterol, and they suggested that reduction of the lanosterol side chain may occur as an early step in the synthesis of cholesterol. These results are in contrast to the results reported after the administration of triparanol, a delta24-reductase inhibitor.


Comparison of clofibrate and chlorpropamide in vasopressin-responsive diabetes insipidus.

Six patients with vasopressin-responsive diabetes insipidus (DI) received clofibrate and chlorpropamide, singly and in combination. Decrease in urinary output averaged (mean +/- SEM): (1) clofibrate 2 g/day, 47% +/- 6%; (2) chlorpropamide 250 mg/day 59% +/- 5%; (3) clofibrate 2 g/day plus chlorpropamide 125 mg/day, 54% +/- 7%; (4) clofibrate 2 g/day plus chlorpropamide 250 mg/day 61% +/- 4%. Water deprivation tests before and during treatment showed significantly higher basal, final, and peak urinary osmolalities (Uosm) and lower free water clearance (CH20) on chlorpropamide, singly and in combination: clofibrate raised Uosm less but significantly decreased CH2O. Water load tests before and during treatment showed that chlorpropamide, singly and in combination, markedly decreased maximal urinary flow, maximal CH2O, percentage water load excreted, and increased minimal Uosm; clofibrate significantly decreased maximal urinary flow and CH2O only. One patient responded only to combination therapy. Chlorporpamide caused serious hypoglycemia in three of six patients. Clofibrate had no significant side effects.


Effect of caloric restriction on basal insulin levels and the in vivo lipogenesis and glycogen synthesis from glucose in the Koletsky obese rat.

Fasting plasma immunoreactive insulin levels increased with age in hyperinsulinemic Koletsky obese rats, being almost four times as high as in lean siblings at 3 mo (40 +/- 5 muU/ml) and rising steadily to 82 +/- 4 muU/ml at 6 mo (about seven times higher than lean siblings). Restricting the food intake of the obese rats markedly reduced but did not normalize the hyperinsulinemia, which in these rats was accompanied by normal plasma glucose concentrations. The incorporation in vivo of D-U-14C-glucose into tissue lipids and glycogen was measured 1 hr after the intravenous injection of 1 g glucose (containing 100 muDi D-U-14C-glucose) per kg body weight in obese rats eating ad libitum, obese rats after 3 mo on a restricted food intake, and lean siblings. All tissues (heart, diaphragm, skeletal muscle, and adipose tissues and liver) of obese rats exhibited a significantly greater lipogenesis from glucose than those of lean siblings. Dietary restriction of the obese rats reduced the 14C incorporation into lipid to levels not significantly different from lean controls in all tissues except skeletal muscle and liver, where, although greatly reduced, lipogenesis was still significantly higher than in lean rats. Glycogen synthesis tended to be greater in all tissues of obese rats than in lean animals. Dietary restriction of obese rats did not greatly affect glycogen synthesis.


Methods for separation of long-acting thyroid stimulator (LATS) from sera containing LATS and TSH.

Methods were devised for separation of long-acting thyroid-stimulator (LATS) from TSH in serum containing both thyroid stimulators by using Rivanol, concanavalin A (con A), or staphylococcal protein A. When 3-5 volumes of 0.5% Rivanol solution were mixed to serum containing TSH or LATS activity, LATS activity remained mainly with IgG in the supernatant fraction. On the contrary, TSH activity was precipitated. When 10 mg con A was added to 1 ml test serum, almost all TSH activity was precipitated, but LATS activity remained in the supernatant fraction, which consisted mainly of IgG and albumin. Almost all LATS activity and part of the TSH activity were precipitated by addition of more than 7.5% polyethylene glycol (PEG), which was therefore not useful for separation of the stimulators in serum. Affinity chromatography on staphylococcal protein A-Sepharose was also found to separate the two thyroid stimulators in serum. By this method LATS-immunoglobulin bound to the protein A column, but no binding of the biologic and immunologic activity of TSH was observed. The protein A method seems the most useful of these four methods for complete separation of both stimulators.


Effect of vasoactive intestinal polypeptide infused intrapancreatically on glucagon and insulin secretion.

Synthetic vasoactive intestinal polypeptide (VIP) was infused at a dose of 50 ng/kg/min for 10 min into the cranial pancreaticoduodenal artery in anesthetized dogs. Both mean blood flow and plasma glucagon concentration in the cranial pancreaticoduodenal vein were significantly enhanced during the infusion, indicating a great augmentation in glucagon output. The pancreatic venous plasma concentration of insulin was not significantly raised, but its output increased during the infusion, again due to the increase in plasma flow. Plasma concentration of glucagon in the femoral artery was not significantly augmented, whereas that of insulin was enhanced during VIP infusion. Mean arterial plasma glucose levels rose gradually during the infusion. Intrapancreatic pretreatment with propranolol failed to exert any significant inhibiting effect upon the VIP-induced enhancement in plasma glucose, pancreatic venous blood flow, or bihormonal output. These results suggest that the vasoactive polypeptide of intestinal origin may regulate the function of the endocrine pancreas and that this effect may not be mediated mainly via the beta-adrenergic receptor system.


A cytogeneticist's microscope.

It is demonstrated that there are a number of advantages in using a mechanised microscope for scoring a large number of metaphase cells from human blood lymphocyte preparations. Following the development of an automatic metaphase spread finding machine based upon a large motorised microscope and a synchronous closed circuit television camera and flashing light source, a much smaller machine which is more appropriate to the cytogenetics laboratory, but with a similar metaphase finding performance has been constructed. The new machine which consists of a Cambridge Instruments 1 micron stepping microscope stage, a linear diode array scanner and a computer is described in detail. Metaphase finding performance figures for various orcein stained human blood lymphocyte preparations are given.


Correlations between staff, peer and self assessments of fourth-year students in surgery.

Self, peer and staff assessments were made for 138 of 141 students, in two fourth-year surgery classes. Self assessments were significantly lower than peer assessments, which in turn were significantly lower than staff assessments. The highest correlation was between peer and staff assessments. Students with serious psychological problems identified themselves with failing self assessments. The study stimulated interest in assessment procedures amongst staff and students and the latter responded with an assessment of teachers and courses throughout the faculty.


Adaptation of museum specimens for use in anatomical teaching aids.

Colour transparencies are prepared of a re-colourized anatomical specimen after placing labels temporarily in position to indicate specific structures. The specimen is also radiographed to show skeletal and soft tissue structures and radio-opaque materials and letters may used to indicate certain parts. Having mounted the specimen it can then be placed in a teaching carrel together with the radiographs and a back-slide projector for viewing the colour transparencies. The student is guided through an examination of the specimen using a script or soundtape. Frequent cross-reference is made between the actual specimen, the colour transparencies on which certain parts of the specimen have been labelled, and also the radiographs. The examination is followed by self-assessment questions relevant to the specimen and these may include identification of structures on a photograph of the specimen and on duplicate radiographs. In the final section of the aid, the answers of the self-assessment questions are given.


An experimental comparison of three courses in history-taking skills for medical students.

Since clinical training often fails to equip medical students with essential history-taking skills, more effective teaching methods required to be developed. As previous work had suggested that training which included televised demonstrations of history-taking and practice with simulated patients might be superior to traditional methods, it was decided to evaluate this experimentally. Thirty students beginning the Oxford Clinical Course were randomly selected and allocated to a traditional or one of two experimental courses. Both experimental courses used television and simulation but differed in the way the history-taking demonstrations were presented. After completing these courses, each student was asked to take a history from a simulated patient. Rating of the videotapes of these interviews showed that the two experimental groups obtained much more information and used many more of the required skills than students assigned to the traditional course. The experimental students were also rated more favourably by the simulators and recorded more data in their case histories. It is concluded that these short courses were practical, very effective, and could be augmented by a self-teaching programme in history-taking skills.


A comparison of the performance of three multiple choice question papers in obstetrics and gynaecology over a period of three years administered at five London medical schools.

Four, and later five, of the medical schools in the one multiple choice question (MCQ) paper in Obstertrics and Gynaecology to their students at the end of the Obstetrics and Gynaecology courses. The paper was amended twice after intervals of approximately 12 months. The results showed differences in performance between the five schools on questions and alternatives within questions, which were common to all editions of the paper (the "short" paper). These differences were also shown in the first two editions of the full paper (the "long" paper), but were not apparent in the third. There was a significant improvement in performance from the first to the second paper edition of the long by approximately 11%, but this was reversed from the second to the third edition, where there was a significant decrease in performance by approximately 4%. We cannot here exclude the possibility that this decrease in the third edition has resulted from sample bias. The rank order of the schools may result from differences in methods of teaching. It seems that such relative performance between London medical schools in contributed to by the differences in course legnth and by the occurence of mid-course test. It appears also that student performance in any of the schools has not been uniform over the period of the study, there being a peak during the period when the second edition of the paper was used. Variations in student selection occuring between schools may effect some of these differences. There was also a marked difference in students' performance between Obstetrics and Gynaecology. The short papers appeared easier than the full papers. Whilst this may due to the greater clarity of phrasing for the questions of the short paper, we also believe the subject matter of the short paper may be more relevant. A distinct effect could also be shown, over the period, due to improvements in the wording of the questions. It is possible that students perform better at Obstetrics than at Gynaecology.


The Sheppe and Hain study revisited: professional students and their knowledge and attitudes about human sexuality.

The professions of law and medicine exert a profound influence on sexual attitudes and behaviour in our society. Previous reported studies of legal and medical students found no differences in sexual knowledge for entering first-year students. However, in this study, a sample of 160 medical and seventy-nine law students revealed significant differences in knowledge and attitudes about sexuality. The data indicate that a gender-linked double standard of acceptable behaviour is not present. Results further reinforce the necessity of medical sex education.


Verbal communication between students in multidisciplinary health teams.

The study reported here was connected with the influence of two variables--the context in which communication occurs, and the concept availability of various health professionals--upon the verbal interaction of various health professionals. Specifically, the verbal output of health professionals in groups consisting entirely of their own professional peers (i.e. all nurses, or all medical students) was compared with that of professionals in multidisciplinary health teams. The study, in attempting to delineate possible barriers to effective verbal interaction, has important implications for the functioning of multidisciplinary health teams.


Content analysis of drug-detailing by pharmaceutical representatives.

Drug detailing is important in drug prescribing. This report describes a study made on drug presentations to groups of doctors in Helsinki. The method was silent observation of presentations given by medical representatives. Analysis of the content of the presentations revealed that side-effects and contraindications were often neglected; the drug presented was always recommended as the drug of choice; other forms of treatment were seldom mentioned. References to Finnish doctors doing clinical trials with the drugs were often made. Even though this study was restricted, its results show that drug detailing and its significance in post-graduate education call for more attention.


Marking systems for multiple choice examinations.

This article discusses the advantages and disadvantages of no penalty and penalty marking systems. It also reviews ways in which examiners have attempted to correct for guessing by candidates, and the use of 'don't know' options and confidence-weighting for attempting to assess the degree of certainty that candidates attach to their answers.


Swimming pool immersion accidents: an analysis from the Brisbane drowning study.

An analysis of a consecutive series of 66 swimming pool immersion accidents is presented; 74% of these occurred in in-ground swimming pools. The estimated accident rate per pool is five times greater for in-ground pools compared with above-ground pools, where pools are inadequately fenced. Backyard swimming pools account for 74% of pool acidents. Motel and caravan park pools account for 9% of childhood immersion accidents, but the survival rate (17%) is very low. Fifty per cent of pool accidents occur in the family's own backyard pool, and 13.6% in a neighbour's pool; in the latter the survival rate is still low at only 33%. In only one of the 66 cases was there an adequate safety fence; in 76% of cases there was no fence or barrier whatsoever. Tables of swimming pool accidents by age, season, site and outcome are presented.


Acupuncture--effect on normal subjects.

The effect of acupuncture analgesia on pain threshold was assessed in a group of 60 healthy volunteers. On the average a 60% elevation of the pain threshold was achieved. This effect was seen bilaterally with unilateral acupuncture stimulation. There was no significant difference in the effect produced by three widely separate sites of acupuncture stimulation. The possibility of an additive effect when two sites were simultaneously stimulated was not confirmed in our limited study. Evidence is presented that sensory nerve fibre stimulation may be the basic primary requirement of successful acupuncture analgesia.


Pseudomonas maltophilia infection in an abattoir worker.

A case of infection with Pseudomonas maltophilia is described. The clinical record and bacteriological findings are reported, and the possible aetiology is discussed.


The management of febrile episodes in-neutropenic cancer.

The management of 33 febrile episodes in neutropenic patients suffering from acute leukaemia and other cancers is described. In 32 out of 33 episodes, the fever subsided. One patient died of cerebral haemorrhage while infected. The most common clinical sites of infection were, in order of frequency, the chest, the throat and the skin. Positive cultures were obtained in about half the episodes, the most common site being the throat followed by blood  and sputum. The most common organisms isolated were Gram negative. Eighty-four per cent of febrile episodes occurred with neutrophil counts of less than 500/mm3, and in the majority of these, less than 100 neutrophils per cubic millmetre. All patients were reverse barrier nursed and on becoming febrile were given 48 hours of parenteral antibiotic therapy. The most common antibiotic combination used was gentamicin and cephalothin. At 48 hours, granulocyte transfusion and a third antibiotic were added to the regimen of patients not responding. The percentage response to antibiotics alone, in this series, at 58% was similar to that of other series, but the mortality experienced was lower.


Filtration leukopheresis granulocyte support for infected neutropenic patients.

A pilot study of granulocyte support for neutropenic infected patients by means of white cells collected from the Aminco Celltrifuge at the Peter MacCallum Clinic showed acceptable side effects in donor and recipients, and an encouraging recovery occurred in two out of four patients treated. White cell filtration leukopheresis was introduced at the Alfred Hospital Haematology and Medical Oncology Unit in November, 1975, for supportive therapy of all patients with white cell counts below 500/mm3 who had sustained febrile episodes (temperatures greater than 38 degrees C for more than 48 hours) while receiving appropriate or empiric parenteral antibiotic therapy. A minimum of four or more daily transfusions was given from group and cross-matched compatible donors until fever lysis, recovery of the neutrophil count to over 500/mm3 or death. Of 13 patients given white cell support, 12 survived and were discharged from hospital. One patient died having received only one transfusion when he was moribund. We believe that white cell filtration leukopheresis cell support is useful when used with parenteral antibiotic therapy for infected neutropenic patients, and it has resulted in a high rate of recovery from life-threatening infection in patients at risk.


A comparative trial of haematinic supplements in pregnancy.

Four haematinic supplements--Slow-Fe, FGF, Ferro-Gradumet and Ferro-Grad tfolic--were prospectively studied in 103 healthy pregnant patients. Significant differences in the mean cell counts, haematocrit values, haemoglobin levels, iron-binding capacities and serum folate levels were noted. The changes paralleled the elemental iron present in the compount. In this series, side effects principally  vomiting and constipation, were more frequent in the lower dose iron group. Form both the haematological status aspect and the lack of side effects, Ferro-Grad Folic and Ferro-Gradumet were superior to both FGF  and Slow-Fe (old formulation).


Phaeochromocytoma in a footballer.

A young footballer with phaeochromocytoma showed classical exercise-induced symptoms. Noradrenergic clincial phenomena suggested an extra-adrenal site. The usefulness of urine metabolite estimation and of localizing procedures and the importance of preoperative alpha and beta blockade are stressed. Nitroprusside was used successfully to control hypertension during surgery. Unexplained fever after operation is reported.


Primary tuberculosis of the conjunctiva.

A five-year-old boy developed primary tuberculosis of the conjunctiva which spread to the preauricular and cervical lymph nodes, producing caseous lymphadenitis. Because conjunctival tuberculosis is rare, the correct diagnosis may be easily missed. When unilateral conjunctivitis is accompanied by lymph node enlargement and persists or progresses, tuberculosis should be suspected.


[Immunogenicity, efficacy and reactogenicity of a human diploid cell strain (HDCS) rabies vaccine in man; recommendations for pre- and post-exposure application (vaccination scheme) (author's transl)].

Since 1973 a total of 365 individuals between 4 and 74 years of age were vaccinated with the HDCS-rabies-vaccine produced by Mérieux/Lyon. Only minor local side reactions were observed in some patients. No adverse systemic reactions due to the vaccine occurred in any of the vaccinees. Seroconversion was observed in 100% of the vaccinated subjects. Neutralizing antibodies could be demonstrated in all 365 vaccinees in titers ranging from 1:10 to 1:2238 (0.35 to 72.5 I.U) employing 200 LD 50 of rabies virus in the mouse neutralization test. The persistence of antibodies has been followed up for 2 years. The efficacy of the HDCS-vaccine in post-exposure treatment proved to be reliable. Sixteen patients suffered bites, scratches, cuts und abrasions by proven rabid animals. Another 8 patients had come into close contact with saliva of confirmed rabid animals. None of these patients developed clinical rabies during an observation period now covering 1-3 years. The HDCS-rabies-vaccine, thus, proved to be well tolerated, innocuous and highly protective. Under those aspects, this vaccine must be considered superior to the duck-embryo-vaccine currently licensed in Germany and should be preferred for propylactic and post-exposure vaccination as well. The postexposure schedule elaborated in our laboratory has been adopted and recommended by a WHO expert group on rabies. The data presented here constitute the first report on post-exposure application of HDCS-rabies-vaccine in man.


[Little epidemic caused by Salmonella panama (author's transl)].

Between 8. 1. 1976 and 10. 8. 1976 16 new or premature born children got a gastroenteritis due to salmonella panama. All these children were together in one pediatric ward of the hospital. Most of them came directly for the labour ward or from the newborn-ward. They had antibiotic therapy due to the indication of the mother or the child. It was impossible to fine the source of the salmonella infection, therefore, finally the ward was closed. After radical desinfection new patients came to the ward. Again they were infected with salmonella panama. Now it became clear that contaminated milk (Humanan-Heilnahrung) was the source of infections. Most papers mention a mild benign course of the infections. In contrary we could see severe conditions dependent on the pre-damage of the child or his reduced immunity. The minimal number of germs of dietic food products needs to be examinated.


[Frequency and drug sensitivity of "Klebsiella oxytoca" in human clinical material (author's transl)].

962 Klebsiella strains were isolated from a total of 15422 clinical samples. 782 of these were characterized as the species Klebsiella pneumoniae, 170 as "Klebsiella oxytoca" and 10 as Klebsiella ozaenae. 95 of the Klebsiella oxytoca strains originated from samples of the respiratory tract, 13 from purulent materials, 1 from blood and 61 from urine samples. Among further biochemical criteria indole formation, lacking gas formation at 45 degrees C in lactose peptone water medium and delayed gelatine liquefaction were used to differentiate Klebsiella oxytoca from other enterobacteriaceae. In addition the drug resistance patterns were determined.


[Considerations to antibacterial chemo-therapy antecedent to the isolation of the causative agent and evaluation of the antibiogram (author's transl)].

The principles are discussed, which should serve as a basis for therapeutical decisions antecedent to the isolation of the causative agent and evaluation of the antibiogram. These concern the degree of urgency for chemotherapy, the frequency of the association of bacterial species with defined clinical pictures, the actual distribution of antibiotic resistance, the situation of the patient's immune defence system, and side effects of the drug. Possibilities of a "calculated" therapy in urinary tract infections, bronchitis, enteritis, septicaemia, and post-operative wound infection are explained. Considerations about the frequency of causative agents in certain bacterial infections and figures about the actual resistance distribution within bacteria species commonly connected with the disease in quesiton form the baseline for the choice of a chemotherapeutic until the antibiogram is performed.


[Thyroid cancer risk from iodine-131-treatment?  (author's transl)].

Six of 240 patients with thyroid carcinoma had a history of 131I treatment for a benign disease. All patients had underwent a total thyroidectomy. In this 2.5% of our cancer patients a tumor induction by radiation might be po-sible. The six cases are described in detail and the literature is revieved. A longer observation period than 30 years will be necessary to exclude an increase in prevalence of thyroid carcinomas after 131I treatment in the adult. The clinical importance of this possible increase will dubious; the thyroid carcinoma prevalence in a nonendemic goitre region has been estimated with 5--6%. On the other hand an increase in development of "benign" thyroid nodules has been seen after 131I treatment of thyrotoxicosis. Therefore not every younger hyperthyroid patient should be treated in this manner.


[The "alcohol-syndrome" from internal medical view (author's transl)].

A distict alcoholic withdrawal syndrome in chronic alcoholics cannot only be induced upon withdrawal of alcohol or dose reduction but also occurs upon continuous and long lasting consumption of larger quantities of alcohol. In the latter case we deal with an alcoholic predelirium which is characterized by simultaneous occurence of neurologic, vegetative and gastrointestinal disturbances as well as mental symptoms like anxiety, increased irritability and disturbance of sleep. In parallel to this alcoholic withdrawal syndrome from internal medical view a characteristic symptomatology can be observed in patients with chronic alcohol abuse. In most cases younger patients are concerned who, concomitantly with predelirant symptoms frequently display a labile hyperlipidemia and additional obesity, fatty liver, hyperlipidemia and often also hyperuricemia. Based on ten typical cases the combination of symptoms as described above is introduced. This combination can according to Feuerlein be defined as "alcohol-syndrome". The difficulties of diagnosis are shown because in many cases not the alcohol abuse but primarily vegetative and other functional disturbances dominate the clinical appearance. Additionally the pathogenetic connection between the described symptoms and alcohol abuse are discussed.


[Hemoperfusion with coated activated charcoal for treating acute poisoning by remedies, plant protectants, and fungi (author's transl)].

From the clinico-toxicological standpoint, the most important plant protectants are the insecticides (bipyridylium compounds). In vitro trials and investigations on poisoned patients have shown that it is fundamentally possible to eliminate such plant protectants from the blood by hemoperfusion with coated activated charcoal. With both the lipophilic alkyl phosphate, nitrostigmine (E605 forte), and by the two hydrophilic alkyl phosphates, demetone-S-methyl sulfoxide (Metasystox R) and dimethoate (Roxion), it was possible to measure hemoperfusion clearance values around 60 to 85 ml/min at a blood flow rate of 100 ml/min. Only the two hydrophilic alkyl phosphates were able to be eliminated by hemodialysis, the clearance values being, however, lower. Thus in severe alkyl phosphate intoxications the use of hemoperfusion may considered alongside the standard therapy. The bipyridylium compounds, paraquat (Gramoxone) and diquat (Reglone), are readily dialysed, but can be better eliminated from the blood by hemoperfusion. This therapeutic measure must be initiated as rapidly as possible independent of the clinical picture, for only when hemoperfusion is begun prior to the fixation of paraquat or diquat at tissue are there any prospects of success.


A new electronic transducer system for gastrointestinal pressure studies.

A new electronic transducer system has been developed for intraluminal pressure studies in the gastrointestinal tract. In contrast to other devices, inductance was used for the transformation of pressure into electrical signals. High sensitivity with a frequency response of 10(4) Hz guarantees accurate recording of sphincter as well as of peristaltic pressures. Pull-throughs can be carried out manually. Studies may be performed in the sitting as well as in the supine position since no hydraulic effects are present. No measurable temperature sensitivity was found; linearity is present in the physiological pressure range required. Small size, mechanical and electrical stability and simple handling make the PI-transducer system a suitable diagnostic tool for clinical as well as for investigatory purposes. By this method functional disorders of the esophagus, as in scleroderma, achalasia or hiatus hernia, of the pylorus and of the anal sphincter may be evaluated. The results of lower esophageal sphincter measurements in 30 asymptomatic volunteers and in 19 patients with symptomatic gastroesophageal reflux agree with the data obtained by conventional methods.


A hardware device for recognition of P and QRS waves.

A new hardware device has been constructed to detect QRS and P complexes for the purpose of automatic arrhythmia interpretation. This apparatus can operate in noisy conditions and provide synchronized pulses representative of P complex, QRS complex, wide QRS, and premature QRS to different output channels. P wave identification is achieved with a high degree of reliability through a specially designed bipolar electrode catheter. The device could minimize demands on central processor time and core storage computer.


A hybrid computer system for use in cardiology.

Recent upsurge in the use of physiologic data for medical diagnostic and treatment procedures has prompted the medical profession to use the computer to automate and reduce the time required for data processing. Although the digital computer has traditionally been used to perform these tasks, a hybrid computer (combined analog and digital) has been found to provide many advantages over the digital computer, especially where on-line data processing is concerned. As a result, the Bio-Medical Engineering Center has installed a centrally located hybrid computer system at Ohio State University. One of the applications of this system has been processing cardiac catheterization data. Data is transmitted between the hospital and computer via infrared optics. The data can be analyzed in real time, with the results immediately available to the physician.


Management of the severely injured animal.

Initial management of the seriously injured animal involves the immediate recognition of life-threatening abnormalities and prompt resuscitation based on priorities of care. Of equal importance to the ultimate survival of the animal is an aggressive approach to the diagnosis and control of the complications and sequelae of injury. This approach to patient care requires constant attention to details, but offers the most efficient management of these critically ill animals.


Protoplast fusion of Schizosaccharomyces pombe Auxotrophic mutants of identical mating-type.

Protoplasts of methionine- and lysine-requiring h- mutants isolated from the L972 h- strain of Schizosaccharomyces pombe were fused. The protoplasts were obtained from the cells with enzymes produced by Trichoderma viride. When a mixture of the protoplasts was treated with 30% PEG 4000 solution containing 10 mM CaCl2, cell fusion and complementation was attained with a frequency of 0.17%. Both fusion partners were recovered among the spores after crossing of the fusion products with  the strain M210 ade6 h+. Cytological and haploidization examinations showed that the fusion cells are not heterokaryons, and that the increased amount of genetic material is situated in one nucleus.


Early developmental subdivisions of the wing disk in Drosophila.

The properties of the mutation wingless discovered by Sharma are discussed. It appears that this mutation interferes with a step leading to normal wing-notum compartmentation of the wing disk. From the study of mutational mosaics in the wingless locus we conclude that mutations in this gene can be autonomous in mosaics.


Models for the active transport of cations...the steady-state analysis.

We summarise the progress that has been made in the analysis of active transport models, at the steady-state level. The two general classes of such model, counter-and co-transport, can be treated by a kinetic analysis which makes no assumptions as to the symmetry or asymmetry of the systems nor as to the presence of any particular rate-limiting steps. Precisely the same formalism is obeyed for primary active transport as for secondary active transport. Both are merely a generalisation of facilitated diffusion, in that they follow directly from accepted properties of carrier models. How affinities of such carriers for their substrates affect the efficiency of active transport is discussed and it is shown that in a number of cases, the affinity changes that the carrier demonstrates arise from inherent properties of the free carrier and not from any "high energy" properties of the chemical reactants. Methods of obtaining the kinetic parameters of the system from experimental data are reviewed, together with methods for testing and characterising the different transport models.


Renal uptake of lutropin. Studies based on electron microscopic autoradiography and nephrectomy.

Nephrectomy of mature rats was found to result in a significant increase in the circulatory half-life of tritiated ovine lutropin. The interaction of the glycoprotein hormone with the kidneys was studied in a more direct fashion using electron microscopic autoradiography. Evidence is presented showing the transfer of the hormone from microvilli into tubular epithelia (probably via vesicular transport), where radioactivity then becomes associated with lysosomes. This provides direct support for related results based on subcellular fractionation in which renal lysosomal catabolism  was suggested as being important in the degradation of tritiated lutropin (M. Ascoli, R. A. Liddle, and D. Puett, Molecular and Cellular Endocrinology 4, 297, 1976). These results add substantial weight to the growing evidence that the kidneys assume a major role in controlling the concentration of circulating macromolecules.


Preparation of poly (A)-binding proteins from endoplasmic reticulum-containing subfractions of rat liver cells and their use in mRNA purification.

Approximately 2% of the proteins solubilised from rat liver microsomes or rapidly sedimenting endoplasmic reticulum (RS-ER) adsorbed to poly(A)-Sepharose. The adsorption appeared to be selective for a few proteins, and proteins of different apparent molecular weights adsorbed from RS-ER and the microsomes. The proteins from RS-ER with affinity for poly(A) were coupled to Sepharose and used for the purification of mRNA from rabbit mammary glands. A portion of the RNA wihich did not adsorb to poly(U)-Sepharose adsorbed to protein-Sepharose and was active in a cell-free protein synthesis system.


Cell-mediated mutagenesis in cultured Chinese hamster cells by carcinogenic polycyclic hydrocarbons: nature and extent of the associated hydrocarbon-DNA reaction.

A system of cell-mediated mutagenesis is described for the study of compounds which require metabolic activation to exert their cytotoxic and mutagenic effects. This system combines BHK21 cells for metabolism of the compounds and V79 cells as targets for mutagenesis. Using the two polycyclic hydrocarbon carcinogens benzo(a)pyrene and 7-methylbenz(a)anthracene we have shown that the hydrocarbon-DNA reaction which accompanies mutagenesis in the target cell is indistinguishable from that reported to occur in vivo and in primary cell cultures. Our results also support the view that a diol epoxide metabolite is responsible for the biological activity of benzo(a)pyrene. The application of cell-mediated mutagenesis to the routine testing of suspect environmental chemicals for biological activity is discussed.


Effect of DNA repair on the cytotoxicity and mutagenicity of polycyclic hydrocarbon derivatives in normal and xeroderma pigmentosum human fibroblasts.

The cytotoxicity of the "K-region" epoxides as well as several other reactive metabolites or chemical derivatives of polycyclic hydrocarbons was compared in normally-repairing human diploid skin fibroblasts and in fibroblasts from a classical xeroderma pigmentosum (XP) patient (XP2BE) whose cells have been shown to carry out excision repair of damage induced in DNA by ultraviolet (UV) radiation at a rate approx. 20% that of normal cells. Each compound tested exhibited a 2- to 3-fold greater cytotoxicity in this XP strain than in the normal strain. To determine whether this difference in survival reflected a difference in the capacity of the strains to repair DNA damage caused by such hydrocarbon derivatives, we compared the cytotoxic effect of several "K-region" epoxides in two additional XP strains, each with a different capacity for repair of UV damage. The ratio of the slopes of the survival curves for each of the XP strains to that of the normal strain, following exposure to each epoxide, was very similar to that which we had previously determined for their respective UV curves, suggesting that human cells repair damage induced in DNA by exposure to hydrocarbon derivatives with the same system used for UV-induced lesions. To determine whether the deficiency in rate of excision repair in this classical XP strain (XP2BE) causes such cells to be abnormally susceptible to mutations induced by "K-region" epoxides of polycyclic hydrocarbons, we compared them with normal cells for the frequency of induced mutations to 8-azaguanine resistance. The XP cells were two to three times more susceptible to mutations induced by the "K-region" epoxide of benzo(a)pyrene (BP), 7,12-dimethyl-benz(a)anthracene (DMBA), and dibenz(a,h)anthracene (DBA). Evidence also was obtained that cells from an XP variant patient are abnormally susceptible to mutations induced by hydrocarbon epoxides and, as is the case following exposure to UV, are abnormally slow in converting low molecular weight DNA, synthesized from a template following exposure to hydrocarbon epoxides, into large-size DNA.


Excision of gamma-ray induced thymine lesions by preparations from ataxia telangiectasia fibroblasts.

The capacity of whole cell sonicates of skin fibroblasts of normal individuals and patients with the autosomal recessive disease Ataxia telangiectasia (AT) to remove aerobic gamma-ray products of the 5,6-dihydroxydihydrothymine type (tgamma02) from exogenous DNA substrates was investigated. All four AT strains (AT CRL 1312, AT CRL 1343, AT GM 367, AT 4BI) possessed normal capabilities to excise tgamma02 from irradiated bacteriophage DNA and irradiated chromatin isolated from normal and AT-skin fibroblasts.


Radiation-induced DNA single-strand scission and its rejoining in spermatogonia and spermatozoa of mouse.

Gamma-ray-induced DNA single-strand scissions and the ability to repair the scissions in spermatogonia from young mice and in spermatozoa from adult mice were studied quantitatively by an alkaline sucrose density-gradient centrifugation method. The average size of DNAs in non-irradiated spermatogonia was 2.6--3.0 X 10(8) daltons, similar to those of a spermatid-rich population, and the size of DNA in non-irradiated spermatozoa was 1.2 X 10(8) daltons. In spermatogonia, the radiosensitivity of DNA was 0.42 single-strand breaks/10(12) daltons of DNA/rad in oxic conditions and only 0.24 under anoxic conditions. In spermatozoa the break efficiency of DNA was 0.22 single-strand breaks/10(12) daltons of DNA/rad under oxic conditions and altered little under anoxic irradiation. The DNA scissions were efficiently repaired in spermatogonia within 10 min, whereas the breaks in spermatozoa were not rejoined at all even after two days of post-irradiation time. The radiosensitivities of DNA, repair capability and non- and/or slow-reparable DNA scissions were compared in spermatogonium-rich, spermatid-rich and spermatozoan-rich populations.


Individual susceptibility of mice to a mutagen in both germ and somatic cells.

Male Swiss mice received simultaneously, by gavage, 500 mg methylurea/kg body weight and 25 mg sodium nitrite/kg body weight, and in a further experiment 330 mg of methylurea/kg and 17 mg sodium nitrite/kg, for 5 consecutive days. This treatment resulted in a dose-dependent mutagenic effect in both the dominant-lethal and the micro-nucleus tests. Furthermore, in both mammalian tests, some animals were more susceptible to the mutagenic compounds than were others. However, the liver microsomal metabolizing system did not seem to be responsible for this variation of mutagenic induction.


gamma-Ray mutagenesis of cultured mammalian cells in vitro and in vivo.

The in vitro assay system used to study the reversion of L5178Y-Ala32 cells from an alanine requiring state to a non-requiring state has been modified in order to be of use in selected in vivo systems. Gamma-ray induced mutations were compared between cells cultured in vitro and those grown in vivo in the intraperitoneal cavity of mice. The expression time was chosen to be 2 days for cells grown in vitro and 5 days for those grown in vivo. The dose response curve can be described as cumulative for cells grown in vitro and linear for those grown in vivo. A dose-rate effect was observed in both systems. The cells grown in vivo were less sensitive to gamma-ray with respect to both  mutation rate per rad and cell killing as compared to cells grown in vitro. The delayed expression and reduced sensitivity of cells in vivo with respect to induced mutation may be due to factors such as hypoxia and/or reduced availability of essential nutrients. Sensitization in vitro by BUdR was detectable at a concentration as low as 10(-6) M, using an exposure time of 15 h. Under these conditions, BUdR alone did not induce any observable mutations.


The effect of dose fractionation on gamma-radiation induced mutations in mammalian cells.

The lethal and mutagenic effects of single and fractionated doses of gamma-radiation were studied in V79-4 Chinese hamster cells, as dose fractionation is of interest in radiation protection studies. The results show that the induction of 8-azaguanine resistant (Agr) mutants has a non-linear dose response curve following single doses of radiation. The lethal and mutagenic effects of fractionated doses were always less than if the radiation was given in a single dose. Any change in treatment which led to an increase in survival also led to a decrease in induced mutation frequency. There was a relationship between mutation and survival which was independent of the number of fractions in which the radiation was given. This could be of consequence in radiological protection.


Triethylenemelamine induced dominant lethals in mice--comparisons of oral versus intraperitoneal injection.

We have compared the relative effectiveness of oral and i.p. injections of triethylenemelamine (TEM) in inducing dominant lethality in male mice. The standard dominant lethal protocol was used in these experiments. TEM, when injected i.p. resulted in significant increased in fetal mortality during the first three weeks post-treatment. Decreases in the number of implants per pregnant female were noted during this same period, with only minor decreases in fertility. In contrast, oral injections of TEM resulted in only fluctuations in the percent of fetal mortality. In addition, oral injections of TEM did not result in significant differences in either total implants or percent fertility. Possible causes of the observed differences between these two routes of administration are discussed.


Induction of micronuclei in mouse and hamster bone-marrow by chemical carcinogens.

Four carcinogens, dimethylnitrosamine (DMN), acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and 3-methylcholanthrene (3-MC) were tested acutely and chronically in the micronucleus test in both mice and hamsters. In acute studies using mice, all compounds increased the relative frequency of micronuclei when compared to controls. There was a dose response which tended to tail off as bone-marrow suppression was observed. The order of activity appears to be DMN greater than AFB1 greater than or equal to 3-MC greater than AAF. In acute hamster studies, AFB1 was inactive at the highest dose tested (3 mg/kg). In the case of hamsters, all other compounds increased the incidence of micronuclei with DMN greater than 3-MC greater than AAF. Subacute studies with hamsters revealed that 3-MC was active at 1 week but not 8 weeks while DMN was active at both 1 and 8 weeks. AAF was active at 8 and 12 weeks and AFB1 was active at 12 weeks but not 8 weeks. The authors conclude that this test does not appear useful in chronic protocols and probably more reflects carcinogenicity of the test compounds than acute toxicity. Nevertheless, acute studies demonstrate that this test procedure is of value in the characterization of a compound's relative mutagenic potential.


Low-level DNA exchanges in normal human and xeroderma pigmentosum cells after UV irradiation.

We have used a T4 endonuclease V assay method for UV-induced pryrimidine dimers in cellular DNA in vivo to obtain evidence for recombinational DNA exhanges after UV irradiation of normal human and Xeroderma pigmentosum (XP) cells. Our data indicate that the endonuclease-sensitive sites in excision-defective XP cells are removed very slowly from the irradiated parental strands and appear concomitantly in daughter strands newly synthesized during post-UV incubation. In the defective XP cells, the extent of appearance of sensitive sites in daughter strands synthesized during a period of 24 h after 10 J/m2 appears to be small, probably less than 15% of the initial number of sensitive sites detected in cellular parental strands. Demonstration of such exchanges between normal-density parental and 5-bromodeoxyuridine-labeled daughter strands by alkaline CsCl isopycnic centrifugation was unsuccessful. Further, the extent is much lower in normal human cells because of their efficient excision repair of the dimers before and after exchanges than in the defective XP cells.


Gamma-radiation-induced chromosomal aberrations in human lymphocytes: dose-rate effects in stimulated and non-stimulated cells.

Stimulated and non-stimulated human peripheral blood lymphocytes were irradiated acutely and chronically, over 24 h. Dose-effect relationships for dicentric chromosomes were established and various models were fitted to the data. At prolonged irradiations the yield decreased in basic agreement with the linear-quadratic model of abberration induction. Dose-protraction experiments of PHA+ and PHA- lymphocytes, irradiated under various conditions of oxygenation and suspension (culture medium, whole blood) showed that the rejoining time increased from about 3 h in non-stimulated cells to about 10 h after PHA stimulation, and that this retarded rejoining was most likely due to blastic transformation itself and not to other conditions of irradiation.


The induction of chromosomal abnormalities by inhalational anaesthetics.

When Vicia faba root tips are exposed for 2 h to clinically useful concentrations of halothane or methoxyflurane in air, or to halothane in 80% nitrous oxide/20% oxygen, there is a transient increase in mitotic index and then abnormal interphase cells are produced in proportion to the anaesthetic concentrations. After exposure there is a period of mitotic inhibition during which the cells become partially synchronised. When colchicine-metaphase cells collected 28 h after exposure are compared with controls and with metaphases collected only 4 h after exposure, they show a significant increase in the incidence of aneuploidy, tetraploidy and the results of chromosome breakage. It is suggested that all the abnormalities seen can be accounted for by the effects of the anaesthetics on spindle movements, and that at the concentrations used the anaesthetics have no mutagenic effects on chromosomes in interphase.


Changes in circulating transcobalamin II after injection of cyanocobalamin.

Since transcobalamin II is the plasma binder of vitamin B12(cobalamin) that mediates delivery of cobalamin to tissues, we measured circulating levels of transcobalamin II after intravenous injection unlabeled cyanocobalamin in 12 control subjects and, because the liver is a major source of transcobalamin II, in eight patients with decompensated cirrhosis. Thirty minutes after injection of cyanocobalamin (200 ng per kilogram of body weight), total transcobalamin II (unsaturated plus cobalamin bound) declined in all 20 subjects to levels that averaged (+/- S.E.) 53.5 +/- 4.6 per cent of initial values. Subsequently, unsaturated transcobalamin II rapidly increased so that by eight hours, total transcobalamin II approached preinjection levels. Rates of regeneration of transcobalamin II were similar in control subjects and patients with liver disease. Unlike total transcobalamin II, total transcobalamin I was unaltered by injection of cyanocobalamin. Moreover, addition of cyanocobalamin to plasma in vitro did not alter measurements of total transcobalamin II. The rapid response of circulating transcobalamin II to cyanocobalamin injection strongly supports a dynamic role for this polypeptide during transport of a relatively large load of cobalamin.


Pulmonary embolism, pulmonary hemorrhage and pulmonary infarction.

We compared 41 patients with angiographic proof of pulmonary embolism and clinical signs of pulmonary infarction (as evidenced by an infiltrate on x-ray study and pleuritic pain in the area of the embolus) with 24 patients with pulmonary embolism but without infarction. Only 18 of the 41 patients with pulmonary infarction had associated heart disease. Pulmonary infarction was uncommon when emboli obstructed central arteries but frequent when distal arteries were occluded. Follow-up x-ray examination showed that the infiltrates resolved in the patients with pulmonary infarction without heart disease, but persisted when heart disease was present. We suggest that obstruction of distal arteries results in pulmonary hemorrhage owing to an influx of bronchial arterial blood at systemic pressure. Hemorrhage causes symptoms and x-ray changes usually attributed to pulmonary infarction. However, hemorrhage resolves without infarction in patients without, but progresses to infarction in those with, heart disease.


Accuracy of numerical coronary profile. Correlation of risk factors with arteriographically documented severity of atherosclerosis.

We compared a coronary risk profile (developed by the Framingham Study) based on age, sex, cigarette smoking, glucose intolerance, left ventricular hypertrophy, systolic blood pressure and serum cholesterol to angiographically determined severity of coronary-artery disease in 158 consecutive patients undergoing cardiac catheterization. A profile of 1.0 indicated average relative risk. Risk profiles for 105 patients with angiographically documented coronary-artery disease was 1.52 whereas it was 1.08 for the group without coronary disease (P less than 0.01). There was no difference between the patients with coronary disease with (1.44) and those without previous infarct (1.46). The coronary risk profile, however, increased with increasing severity of coronary disease. The high-risk coronary patient can be identified by seven easily measured risk factors, and the extent of coronary-artery disease increases with the number and severity coronary risk factors.


Science, society and the press.

Apprehension about federal support of and public involvement in research has prompted the biomedical community to adopt an accommodating--some would say, enlightened--attitude toward the press during the past several years. However, it is not uncommon for investigators to see reporters as a potential extension of themselves, whose job it is to "educate" the public so that it will appreciate and, therefore, support the scientific enterprise. With the distinction between "educating" and "informing" in mind, it is simply the duty of the press to inform the public about developments in science--particularly those that have implications for public health and safety--but not necessarily to speak for the biomedical community. As the recombinant-DNA controversy shows, the essence of the important issues between science and society will be that they have no obvious, easy answers, and that they cannot be resolved by a "scientific" analysis of the "facts."


Low-titer cold-hemagglutinin disease. Mechanism of hemolysis and response to corticosteroids.

We studied two patients with a low-titer cold-hemagglutinin disease syndrome to investigate the mechanism of hemolysis and the therapeutic response to corticosteroids. The antierythrocyte antibody was of the IgM class, had a high thermal amplitude and had enough activity of 37 degrees C to account for the hemolysis. The capacity of peripheral blood monocytes to increase the osmotic fragility of C3-coated erythrocytes suggests that macrophage interaction with C3-coated erythrocytes explains the observed in vivo spherocytosis. Both patients responded to high-dose corticosteroids. The data suggest that the steroid effect is probably due to alteration of macrophage complement-receptor function. These studies demonstrate the importance of antibody activity at body temperature in producing hemolysis, particularly in this variant of cold-hemagglutinin disease. The response to steroids suggests the efficacy of corticosteroid therapy in alleviating hemolysis due to macrophage recognition of erythrocytes coated with IgM and C3.


Theophylline disposition in patients with hepatic cirrhosis.

To determine the role of liver dysfunction in theophylline toxicity, we administered single intravenous doses of the drug to nine patients with cirrhosis and observed its disposition over a period of 24 to 48 hours. As compared to 19 normal subjects, these patients had a prolonged plasma half-life (mean, 25.6 vs. 6.7 hours) and a decreased plasma clearance (mean, 0.042 vs. 0.062 liter[kg-1]hr-1). Volumes of distribution of theophylline in the cirrhotic patients (central-compartment volume of 0.330, and steady-state volume of distribution of 0.785 liter per kilogram) did not substantially differ from normal (0.246 and 0.508 respectively). Plasma theophylline binding in three patients with cirrhosis averaged 36.8 per cent as compared to 52.6 per cent in four normal subjects. There was no correlation between any laboratory test of liver function and the plasma theophylline half-life, except for serum albumin (r = 0.92, P less than 0.001). The variable capacity to eliminate theophylline precludes the use of usual maintenance dose schedules for bronchodilation in cirrhosis.


Combined use of leg scanning and impedance plethysmography in suspected venous thrombosis. An alternative to venography.

Venography is the standard method for the diagnosis of venous thrombosis but is invasive and may cause discomfort. We evaluated the combination of impedance plethysmography and 125I-fibrinogen leg scanning as an alternative to venography in 200 symptomatic patients. One or both of these less invasive tests was positive in 81 of 86 patients with positive venograms (sensitivity of 94 per cent) and both were negative in 104 of 114 patients with negative venograms (specificity of 91 per cent). These two tests detected all 60 patients with popliteal or more proximal venous thrombosis and 21 of 26 patients with calf-vein thrombosis. In addition, this approach detected 21 of 22 patients with calf-vein thrombosis with symptoms for eight days or less. These results suggest that the combination of these two less invasive tests can be used as an alternative to venography in selected patients with clinically suspected venous thrombosis.


Association between hepatitis B virus and essential mixed cryoglobulinemia.

In view of a high frequency of liver involvement in patients with essential mixed cryoglubulinemia, we looked for evidence for hepatitis B virus infection in 25 serum specimens and 19 cryoprecipitates obtained from 30 patients. Three of the 25 serum specimens contained Hbs Ag, and 12 had antibody. The frequency of positive results was increased to six and 11 of 19 respectively when cryoprecipitates were examined, and 14 of 19 (74 per cent) of the cryoprecipitates were positive for either HBs Ag or its antibody. Electron microscopy of four cryoprecipitates showed structures resembling the 20-nm and 27-nm spheres, tubules, as well as the Dane particles characteristic of hepatitis B virus infection. Since such infection appears to be involved in the pathogenesis of the syndrome, the term "essential mixed cryoglobulinemia" should be replaced by "mixed cryoglobulinemia secondary to hepatitis B virus" or perhaps to other viral infections.


Azorean disease of the nervous system.

We studied a family of Portuguese ancestry from the Azores who suffered a progressive neurologic disease characterized by gait ataxia, features similar to Parkinson's disease in some patients, limitation of eye movements, widespread fasciculations of muscles, loss of reflexes in the lower limbs, followed by nystagmus, mild cerebellar tremor and extensor plantar responses. Two post-mortem examinations revealed loss of neurons and gliosis in the substantia nigra, nuclei pontis (and in the putamen in one case) as well as in the nuclei of the vestibular and other cranial nerves, columns of Clarke and anterior horns, in the spinal cord there were also loss of fibers in the fasciculi gracilis and mild changes in the pyramidal tracts. Comparison of the disease in this family with the findings reported in three families of similar ancestry, previously thought to have different disorders, suggests that they may all represent a single genetic entity with variable expression.


Long-term prognosis of mitral-valve prolapse.

We examined the natural history of mitral-valve prolapse in 53 patients who had had a midsystolic click or late systolic murmur (or both) documented phonocardiographically a mean of 13.7 years earlier. Thirty-eight patients were alive without serious complications, and seven had died of unrelated causes. In two patients prolapse was implicated in the cause of death. Other complications were ventricular fibrillation in one patient and bacterial endocarditis in three. Progressive mitral regurgitation developed in five patients, requiring valve replacement in two. These complications occurred in a total of eight patients (15 per cent), and were significantly (P = 0.15) associated with a late systolic murmur rather than an isolated midsystolic click. Thus it appears that the diagnosis of mitral-valve prolapse should not be regarded as ominous; however, patients in whom this diagnosis is associated with a late systolic murmur should be followed carefully.


The organization and structure of the national institutes of health.

In the assessment of domestic federal programs and the agencies responsible for them, few have been as frequently and highly praised as the National Institutes of Health (NIH). Contributing to that success in part is an unusual organization and structure. Based on a series of semiautonomous, disease-oriented program divisions supplemented by several support units with a co-ordinative function performed by the Director, NIH, a remarkable and essential combination of administrative stability and flexibility, as well as scientific and political acceptability, has emerged. The changing environment in which NIH now functions, however, suggests the need for a greater degree of intra-NIH and extra-NIH program integration and co-ordination. Concomitantly, there must be more consistent federal policies, a clearer definition and understanding of "technology transfer" and additional resources for the directors of NIH and the individual Institutes.


Hereditary hemochromatosis. Diagnosis in siblings and children.

We studied five patients with clinically manifest hemochromatosis and 19 of their siblings and children to define better the diagnostic criteria for stages of the disease. The earliest detectable abnormalities were an increase in hepatic-parenchymal-cell stainable iron, hepatic iron concentration, transferrin saturation and serum iron concentration. In contrast, urinary iron excretion after deferoxamine and serum ferritin concentration were usually normal in early iron loading. In either latent or clinically manifest disease, hepatic-parenchymal-cell stainable iron was Grade 3 or 4; hepatic iron concentration was greater than 250 microng per 100 mg; serum iron was greater than 170 microng per 100 ml; transferrin saturation was greater than 70 per cent; urinary iron excretion exceeded 2.2 mg per 24 hours; and serum ferritin usually exceeded 1000 ng per ml. Estimation of liver iron is the most sensitive method for detecting early disease. Urinary iron excretion and serum ferritin estimate the total body burden of iron in latent and clinically manifest disease.


Treatment results of 54 American patients with Burkitt's lymphoma are similar to the African experience.

Burkitt's lymphoma in Africa may be curable by chemotherapy alone; in nonendemic regions results are reportedly less favorable. Fifty-four Americans with Burkitt's lymphoma were treated with two sequential combined treatment regimens that incorporated therapeutic approaches from clinical trials in Africa. Four patients died during induction therapy, and 48 of the remaining 50 achieved complete remissions. Twenty-two relapsed at a median of three months from the start of therapy. The overall two-year actuarial survival was 54 percent: younger patients ( less than 12 years old) and patients with minimal tumor burden (stages A, B and AR) had significantly better survivals than older patients (P less than 0.02) and patients with advanced abdominal tumors (stages C and D) (P less than 0.01). No differences in survival were detected between patients treated at the National Institutes of Health and those treated in regional institutions on either protocol. Complete response rates, relapse frequency and survival in American patients are similar to results in Africa.


Syndrome of acquired factor X deficiency and systemic amyloidosis in vivo studies of the metabolic fate of factor X.

To determine the metabolic fate of factor X in primary amyloidosis associated with factor X deficiency, we examined the pathways of its catabolism in a man with this syndrome. Intravenous infusion of human or bovine 131I-labeled factor X established a triphasic plasma clearance pattern for factor X. About 85 per cent of the factor X disappeared, with a disappearance half-time of less than 30 seconds. A second and third phase showed a T1/2 of 90 minutes and nine hours respectively. 131I-labeles factor X in plasma did not appear to be rapidly modified or degraded. Relatively minor quantities of 131I were cleared into the urine. We observed a diffuse distribution of radioactivity over the body surface, with a concentration in the hepatic and splenic regions. These studies demonstrate than factor X deficiency associated with systemic amyloidosis is due to binding of factor X to body tissue, probably within the circulatory system.


Complete deficiency of adenine phosphoribosyltransferase. Report of a family.

We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both).


Biochemical profile or uremic breath.

We attempted to define the substances that contribute to the characteristic "uremic breath" of patients with end-stage renal disease. Breath samples from nine patients underwent direct analysis before and after hemodialysis with use of gas chromatography and confirmation by mass spectrometry, and indirectly assessment by an organoleptic panel. Concentrations of secondary and tertiary amines, dimethylamine and trimethylamine were increased, with subsequent reduction after hemodialysis (dimethylamine from 2.00 +/- 0.19 [S.E.M.] to 0.88 +/- 0.12 microng per 30 minutes, P less than 0.001, and trimethylamine from 0.79 +/- 0.22 to 0.44 +/- 0.15 microng per 30 minutes, P less than 0.003). Treatment with nonabsorbable antibiotics in two patients reduced both serum and breath amine levels without dialysis. Loss of nitrogen via the breath was not quantitatively important. We conclude that uremic breath reflects the systemic accumulation of potentially toxic volatile metabolites, among which dimethylamine and trimethylamine have been positively identified and correlated with the classic fishy odor.


Relief of uremic pruritus with ultraviolet phototherapy.

We studied the effect of ultraviolet-light phototherapy on severe persistent pruritus in 18 adult patients on hemodialysis. Patients were randomly assigned to one of two light sources. The experimental group received conventional sunburn-spectrum light in gradually increasing doses. The control group received time-matched exposures to long-wave ultraviolet light. All patients received eight exposures to the entire skin surface over a four-week treatment period. Nine of 10 patients in the sunburn-spectrum group reported marked decrease in pruritus as opposed to two of eight in the placebo group (P less than 0.01). of those responding to sunburn-spectrum light, improvement usually occurred two to three weeks into treatment. Mild sunburn, noted by some patients in this group, was the only side effect. The response to phototherapy was unaffected by the presence of secondary hyperparathyroidism. Ultraviolet phototherapy is a safe, convenient, inexpensive and effective treatment for uremic pruritus.


[Epidemic outbreak of tinea corporis due to Microsporum gypseum].

A small epidemic of tinea corporis due to M. gypseum is reported. There were 13 children affected, ages 1-15 years. These children belonged to 6 neighbouring families and all used a common "playground", an empty lot located nearby. Cultures were positive for M. gypseum in the 13 children and the agent was also isolated from 2 soils collected in the playing-ground. Soil isolates were classified as N. gypsea. Clinically, the lesions were circinated and had active borders, they were preferentially located in the trunk. Most children (8/13) had multiple lesions. These and other pertinent aspects are discussed in the text.


Effects of age on fresh weight, proteins, peroxidases, and other enzymes of the +, -, and crossed gymnothecial cultures of Nannizzia gypsea.

Cultures of the + (UAMH 1485) and - (UAMH 1486) mating types of Nannizzia gypsea and their crosses (1485 x 1486) were analyzed, after 1, 2, 3, and 4 weeks growth, for fresh weight, proteins, peroxidases, esterases, acid- and alkaline-phosphatases. The + type produced slightly more growth at all periods (90, 131, 131, and 129 mg/plate) than the - mating type (90, 123, 121, and 108 mg/plate). The growth of the crosses was much less (30, 88, 83, and 94 mg/plate). Total soluble proteins per gram fresh weight was greater for the crosses (51, 33, 48, and 63 mg) than for the + (19, 32, 34, and 32 mg) and - (20, 33, 33, and 33 mg) strains. Disc-gel electrophoretic analyses revealed 6-9 protein bands in each of the mating types, and 7-8 bands (protein) in crosses, several of which showed mobility and stain uptake differences. There were 1-2 peroxidase bands in the +, -, and crosses; their patterns were generally the same in 1-week-old cultures, but slight differences were found at the subsequent harvests. The number of esterases in the +, -, and crosses was 3-4 and 2-3, respectively, but their patterns were similar. Acid- and alkaline-phosphatases of the + and -, and crosses were quite similar to one another. For all the enzymes studied, the number of bands increased after the first harvest in crosses, but in the single strains there was no constant pattern.


[Lipid metabolism in Aspergillus versicolor (Vuill.) Tiragoschi. Relation to biogenesis of sterigmatocystin].

Aspergillus versicolor is cultivated in a synthetic medium for 22 days. Bioproduction of lipids and sterigmatocystin are compared. The fatty acids of the neutral lipid and polar lipids fractions are mainly: C 16:0, C 18:0, C 18:1, C 18:2, C 18:3. Maximal yields of dry weight, neutral lipids and sterigmatocystin occur, respectively, on the 4th, the 7th and the 20th days. These results and their comparison with other works emphasize that a fall of concentration in lipids precedes the phase of highest concentration in secondary metabolites of polyketide type; it appears that fats and particularly palmitic acid are present in biogenesis of these derivatives.


Isolation of Histoplasma capsulatum from the air in the Aguas Buenas Caves, Aguas Buenas, Puerto Rico.

White mice were used to isolate H. capsulatum from the air in the Aguas Buenas Caves, Puerto Rico. Based on the infection of mice, the ten test sites yielded positive results for the presence of the fungus. Air currents through this cave are believed to be the most important factor responsible for the even distribution of H. capsulatum. Cultural differences concerning spore concentrations were observed. Age and sex of the exposed mice do not seem to play a role in acquiring histoplasmosis.


Isolation of Histoplasma capsulatum from tissues of bats captured in the Aguas Buenas Caves, Aguas Buenos, Puerto Rico.

Of 30 bats belonging to four species, only one species, Brachyplylla cavernarum, yielded positive for Histoplasma capsulatum. Bats were collected at the Aguas Buenas Caves in Puerto Rico. The other species are: Artibeus jamaicensis, Monophyllus redmani portoricensis, and Erophylla bibombifrons; these resulted negative for the fungus.


Structure of RNA and RNA binding site in tobacco mosaic virus from 4-A map calculated from X-ray fibre diagrams.

The structure of tobacco mosaic virus has been solved to a resolution of 4 A using fibre diffraction methods. The general fold of the protein is clear, the conformation may be deduced in many places, and the conformation of the RNA and its interaction with the protein can be seen.


Transmembrane channel formation in rhodopsin-containing bilayer membranes.

Rhodopsin has been incorporated into planar lipid bilayer membranes. The effect of light is to increase the bilayer permeability in a pattern consistent with the formation of a transmembrane channel of about 10 A diameter. A model of visual excitation based on a light-activated and voltage-sensitive channel is presented.


[The deterioration of the aquatic ecosystem because of civilization].

The surface waters of northwestern Europe belong to the most heavily loaded waters of the world. Within the last decades, pollution by non-biogenic organic substances has often become more important than pollution by domestic sewage. Ecologic concepts aid in understanding the various modes of disturbance of aquatic ecosystems. Stream pollution control consists not only of waste treatment.


Immunosuppression and Carcinogenesis: effects of azathioprine on induction of sarcomas by 3-methylcholanthrene.

The effects of Azathioprine (AZA) on the carcinogenesis with 3-Methylcholanthrene (MC) are described. When AZA is given before MC, there is a shortened tumor latency period. When AZA treatment followed MC injection a lengthened latency period was observed. When AZA treatment is given both before and after MC injection, intermediate results were observed. It is concluded that the action of AZA treatment on tumor development depends on the time relationship between this treatment and the injection of the carcinogen. In particular, it is suggested that to obtain an enhancing effect on tumor development, probably by immunosuppression, AZA must be effective at the time or shortly after administration of the carcinogen. When AZA is administered later, an inhibition of tumor development, probably a cytostatic effect becomes prominent.


Dextramycine (the dextraisomer of chloramphenicol) as an inhibitor of the induction of lung adenomas in mice.

Dextramycine as well as leftrotating isomer (chloramphenicol--levomycetin) diminished the blastomogenic effect of urethane which is known to induce lung adenomas in mice.


Influence of stress and of endocrine imbalance on the experimental metastasis.

The influence of some stress agents applied during variable periods of time and under various modifications of the endocrine status was studied on the lymphotropic metastases of the 256 Walker carcinosarcoma, grafted intratesticulary in rats. Different reactivity of metastases, when compared to that of primary tumors was found in relation to the action of some compounds influencing the hormonal balance. Stress enhances the primary tumor development, while the metastatic growth is inhibited. However later on, sudden enhancement of the metastasis growth was observed. Adrenalectomy, as well as testosterone, thyroxine, of Stilbostat administration inhibit the metastasis, whereas cortisone, or antithyroid drug administration enhance the metastasis. The in vitro study of the tumor cell proliferation suggests some immunemorphological involvements in the development of this process.


Hamster apigmented melanoma as a model for screening of potential antineoplastic drugs.

The authors treated the apigmented melanoma IC-Sofia in hamster with various doses of the following cytostatics: Cyclophosphamide, 6-Mercaptopurine, Vinblastine and Actinomycin D for 7 consecutive days. Determination of the tumor growth inhibition on the 8th day (early test) on the basis of tumor weight in the animals treated and untreated with cytostatics indicates that the tumor used is more sensitive to the effect of Cyclophosphamide and 6-MP and less to Vinblastine and Actinomycin D. Nevertheless sensitivity to cytostatic action is high enough for each of the cytostatic agents, depending upon the applied dose. This gives grounds to the authors to assume that hamster apigmented melanoma IC-Sofia is an adequate model for testing and evaluation of antitumor drugs.


Serum immunoglobulin levels in cancer patients. III. Immunoglobulin levels and metastases of malignant tumors.

The levels of IgG, IgA and IgM were followed in 93 patients with metastases of various tumors in the liver, bones, lymph nodes, lungs and with the generalization of tumor in multiple organs. A significant increase of IgG was noted in those patients where liver, bones and lymph nodes were involved, compared to other tumor groups as well as with the values considered as normal range. A significant rise of the IgA class was observed in patients with liver metastases compared to cases with the generalization of tumor. In all groups the mean levels were scattered above the upper limit of normal values. The mean levels of IgM class did not exceed the upper normal limit, but in the group of bone metastases a significant rise was noted compared with the group of generalized tumors.


Serum immunoglobulin levels in cancer patients IV. The influence of therapy on the levels of IgG, IgA and IgM.

The levels of immunoglobulins (IgG, IgA, IgM) were measured in the blood serum of 232 patients with malignant diseases subjected to therapy with irradiation, cytostatic drugs, hormones and active immunotherapy. The values of two samples were compared before and after therapy. The local irradiation with usual doses and technique did not significantly influence the Ig levels. On the contrary, the levels of all three Ig classes decreased after chemotherapy, but only the IgG decrease was significant. A rise of Ig followed active immunotherapy and hormonal therapy but these changes were not significant.


Endocrine-metabolic criteria for distinguishing two pathogenetic types of breast cancer.

Hypothalamic threshold of sensitivity to homeostatic inhibition was studied by means of the dexamethasone test of inhibiting excretion of steroid hormones in 47 patients with the primary breast cancer of different age groups. Before the dexamethasone test and after it, blood specimens were taken for the following tests: daily variation of blood sugar or sensitivity to insulin action, cholesterol, lipoproteins, phospholipids, uric acid, growth hormone and insuline levels, and level of corticosteroids. On the base of the results obtained all the patients could be divided into two groups: 1. patients with signs of elevated threshold of hypothalamic sensitivity to inhibition and 2. patients without such signs. The breast cancer developing against the background of endocrine metabolic disturbances characteristic of advanced age is on the whole prognostically more favorable than tumors in women who have no disturbances of that kind. However, metabolic shifts characteristic of ageing obviously play an important role in creating a background that promotes higher incidence of mammary cancer in elderly subjects.


Chemotherapy and "second-look" procedure in the treatment of ovarian carcinoma.

A combination of chemotherapy with a "second-look" operation has its place in a long-tern treatment of ovarian cancer of stage III, though it will hardly improve the long-term results--the 5-year survival in this stage. Ocassionally, this combination may prove useful and even decisive for prolonging life and even bringing about recovery. This would apply to less advanced, better cases of stage III and to carcinomas with a lesser biological malignancy. "Second-look" operations may be indicated not only in an improvement of the local finding as has been reported up to now by several authors, but also if this local finding has not improved but the patients overall condition is satisfactory or has not deteriorated since the first laparotomy, especially if the latter had been performed at another hospital. The time for the second-look operation must be determined individually according to the clinical course.


Results of radiation therapy and a combination of radiation and surgery in the laryngeal cancer.

A total of 348 out of 349 patients with laryngeal cancer were treated over the period 1960-1970. Radiation therapy alone was used in 262 of them and surgical intervention with postoperative irradiation in 86. Results in the form of a five-year survival rate in the group treated solely by irradiation were superior by 12% in the case of glottic than in that of supraglottic carcinoma (48.8% and 36.8% respectively). In the group of patients operated upon and subsequently irradiated, relatively satisfactory results were obtained in the advanced, i. e. the III stage of supraglottic carcinoma (5-year survival in 61.4%). The overall 5-year survival rate in the patients operated upon and then irradiated proved to be better by 24.5% in supraglottic and by 4.1% in the glottic carcinoma, than in patients subjected solely to irradiation. Of 27 cases of relapses, 6 patients were successfully treated by laryngectomy. Post-irradiation complications involved most frequently minor cases of endolaryngeal edema; among the more serious ones were 2 cases of radiation myelitis. The discussion on the problem of radiation dosage in cancer of the larynx, the treatment of regional metastases and combined surgico-radiation therapy.


Different sensitivity to antibiotics of the established intermitent in vivo--in vitro tumor cell lines in comparison with the primary cultures.

From original strains of tumors growing only in vivo (I) new lines of strains (II) were obtained, the cells of which proliferated readily both in vitro and in vivo. Sensitivity in all the new strains (II) generally increased but in varying degrees as against individual cancerostatic drugs, as evident from the given ID50 values and sensitivity indices. In addition to an enhanced sensitivity of the strains to inhibitors, their ability to utilize precursors of the synthesis of nucleic acids and proteins in a linear dependence during the course of 24 hours has also been determined.


Effect of alterations of sodium intake in patients with hyporeninemic hypoaldosteronism.

The effect of changes of sodium intake on serum and urinary electrolytes, plasma renin activity (PRA) and plasma aldosterone concentration (PA) was studied in five hyperkalemic patients with the syndrome of hyporeninemic hypoaldosteronism (SHH). The patients were evaluated during 8 days on a 10-mEq sodium and 50-mEq potassium diet plus furosemide, followed by 8 days on a 150-mEq sodium and 50-mEq potassium diet. After sodium depletion, both PRA and PA were substantially higher than after a previous 4-day period of simple dietary sodium restriction and an increase in serum potassium concentration occurred in only one subject. Administration of a normal sodium intake induced small increases in serum chloride in all five subjects and a decrease in bicarbonate concentration in one patient. It is concluded that, at least in some patients with SHH, PRA and PA are volume-responsive and that considerable alterations of sodium intake have relatively little influence on serum electrolyte concentrations.